Clinical Focus


  • Liver Transplantation
  • General Surgery
  • Intestinal Transplantation
  • Pediatric LiverTransplantation
  • Liver cancer

Academic Appointments


Administrative Appointments


  • Director, Adult Liver Transplantation, Stanford University (1995 - 2023)
  • Chief, Division of Abdominal Transplantation, Stanford University (1998 - 2023)
  • Associate Director, Institute for Immunity, Transplantation and Infection, Stanford University (2004 - Present)
  • Director, Abdominal Transplant Fellowship, Stanford University (1998 - 2020)
  • Vice Chairman, Department of Surgery, Stanford University (1995 - 1997)
  • Surgical Director, Pediatric Liver Transplant Program, Stanford University (1995 - Present)

Honors & Awards


  • President, International Pediatric Transplant Association (May 2021 - 2023)
  • President Elect, International Pediatric Transplant Association (May 6, 2019)
  • Medical Staff Distinguished Service Award, Lucile Packard Children's Hospital at Stanford (April 16, 2015)
  • Francis Moore Excellence in Mentorship in the field of Transplantation Surgery Award, American Society of Transplant Surgeons (2015)
  • President, San Francisco Surgical Society (2010 - 2011)
  • Honoree 'Salute to Excellence', American Liver Foundation, Northern California Chapter (2003)
  • 1st Recipient "The Arnold and Barbara Chair in Pediatric Transplantation", Stanford University (1999)
  • Member, American Surgical Association (1997)
  • Premio a la Superacion (Honor al Merito) by Rafael A. Calderon F. Presidente de la Republica, Costa Rica (1991)
  • Fellow, American College of Surgeons (1990)
  • National Research Service Award, NIH (1980)

Professional Education


  • Residency: UC Davis Health Dept of Surgery (1984) CA
  • Internship: UC Davis Health Dept of Surgery (1978) CA
  • Board Certification: American Board of Surgery, General Surgery (1985)
  • Fellowship: University of Pittsburgh School of Medicine (1985) PA
  • Fellowship: University of Lund (1983) Sweden
  • Medical Education: University of Costa Rica School of Medicine (1975) Costa Rica
  • Fellowship, University of Pittsburgh, Transplantation (1985)
  • Residency, University of California, Davis, Surgery (1984)
  • Internship, University of California, Davis, Surgery (1978)
  • Ph.D., University of Lund, Sweden, Medicine (1983)
  • MD, University of Costa Rica, Medicine (1975)

Current Research and Scholarly Interests


My role in research is to bring clinical problems to the laboratory to find answers, which in turn, will improve patient care. Thus, my role is translational research in the field of liver and small bowel transplantation. As a senior clinical scientist, I provide leadership over many research projects conducted in the Division of Abdominal Transplantation laboratories. I have ensembled an outstanding research team lead by Olivia Martinez, Ph.D. and Sheri Krams, Ph.D. The investigators include undergraduate and post-graduate students, medical students, surgery residents and transplant fellows.
Research projects involve several models of transplantation of the liver, kidney, intestinal and heart transplantation in rodents. The goals of these research projects are to understand the molecular mechanisms of rejection and by manipulating those mechanisms, we are pursuing full acceptance of the transplanted organs, known as tolerance.

Clinical Trials


  • Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children Not Recruiting

    Solid organ transplantation is an important therapeutic option for children with a variety of end stage diseases. However, the same immunosuppressive medications that are required to prevent the child's immune system from attacking and rejecting the transplanted organ can predispose these individuals to developing a very serious cancer that is linked to Epstein-Barr virus (EBV).

    Stanford is currently not accepting patients for this trial. For more information, please contact Sheri Krams, PhD, 650-498-6246.

    View full details

  • Post-Traumatic Stress Symptoms (PTSS) in Transplant Recipients Not Recruiting

    This study is conducted to better understand Post-Traumatic Stress Symptoms (PTSS) in adolescent transplant recipients and their parent/guardian and to see if PTSS play a role in the way adolescent transplant recipients take their prescribed medicine. Target population: medically stable adolescent solid organ (e.g., heart, kidney, liver, lung, small bowel) transplant recipients and their parent(s)/guardian.

    Stanford is currently not accepting patients for this trial. For more information, please contact Gioia Zucchero, (650) 498 - 5689.

    View full details

  • Risk Factors and Molecular Genomics of U.S. Patients With Chronic Liver Disease and Hepatocellular Cancer Not Recruiting

    To identify risk factors for the development and diagnosis of hepatocellular CA in patients with chronic hepatitis C and to use the data to ultimately develop an effective screening program.

    Stanford is currently not accepting patients for this trial. For more information, please contact Andrea Linder, (650) 725 - 4047.

    View full details

2024-25 Courses


All Publications


  • Revisiting the Prognostic Influences of Donor-Recipient Size Mismatch in Deceased Donor Liver Transplantation. Transplantation direct Nakayama, T., Akabane, M., Imaoka, Y., Esquivel, C. O., Melcher, M. L., Sasaki, K. 2024; 10 (11): e1722

    Abstract

    Background: Liver transplantation (LT) outcomes are influenced by donor-recipient size mismatch. This study re-evaluated the impact on graft size discrepancies on survival outcomes.Methods: Data from 53389 adult LT recipients from the United Network for Organ Sharing database (2013-2022) were reviewed. The study population was divided by the body surface area index (BSAi), defined as the ratio of donor body surface area (BSA) to recipient BSA, into small-for-size (BSAi<0.78), normal-for-size (BSAi 0.78-1.24), and large-for-size (BSAi>1.24) grafts in deceased donor LT (SFSD, NFSD, and LFSD). Multivariate Cox regression and Kaplan-Meier survival analyses were conducted.Results: The frequency of size mismatch in deceased donor LT increased over the past 10 y. SFSD had significantly worse 90-d graft survival (P<0.01), and LFSD had inferior 1-y graft survival among 90-d survivors (P=0.01). SFSD was hazardous within 90 d post-LT because of vascular complications. Beyond 1 y, graft size did not affect graft survival. LFSD risk within the first year was mitigated with lower model for end-stage liver disease (MELD) 3.0 scores (<35) or shorter cold ischemia time (<8h).Conclusions: The negative impacts on donor-recipient size mismatch on survival outcomes are confined to the first year post-LT. SFSD is associated with a slight decrease in 90-d survival rates. LFSD should be utilized more frequently by minimizing cold ischemia time to <8h, particularly in patients with MELD 3.0 scores below 35. These findings could improve donor-recipient matching and enhance LT outcomes.

    View details for DOI 10.1097/TXD.0000000000001722

    View details for PubMedID 39440201

  • Does the introduction of acuity circle policy change split liver transplantation practice? Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Nakayama, T., Akabane, M., Imaoka, Y., Esquivel, C. O., Melcher, M. L., Sasaki, K. 2024

    Abstract

    With the Acuity Circles (AC) policy aiming to reduce disparities in liver transplantation (LT) access, the allocation of high-quality grafts has shifted, potentially affecting the use and outcomes of split LT. Data from the United Network for Organ Sharing (UNOS) database (February 4, 2016, to February 3, 2024) were analyzed, including 1,470 candidates who underwent deceased donor split LT, with 681 adult and 789 pediatric cases. The study periods were divided into pre-AC (February 4, 2016, to February 3, 2020) and post-AC (February 4, 2020, to February 3, 2024). The study assessed changes in split LT volumes and examined the impact of center practices. Both adult and pediatric split LTs decreased in the initial three years post-policy change, followed by an increase in the final year, with an overall 11.9% and 13.9% decrease between the eras. Adult female split LT cases remained consistent, ensuring access for smaller recipients. High-quality "splittable" livers were increasingly allocated to high MELD patients (MELD-Na ≥30). Despite the overall decrease in case volume, adult split LT volume increased in newly active LDLT centers, with six centers increasing LDLT volume by over 50.0%. Pediatric split LT volumes decreased despite additional priorities for pediatric candidates. The number of split LTs decreased in the initial period after the AC policy introduction, but there was a consistent need for small female candidates. In the adult population, LDLT and split LT demonstrated a synergistic effect in boosting center transplant volumes, potentially improving access for female candidates who need small grafts.

    View details for DOI 10.1097/LVT.0000000000000513

    View details for PubMedID 39412327

  • Beyond 75: Graft Allocation and Organ Utility Implications in Liver Transplantation. Transplantation direct Akabane, M., Kwong, A., Imaoka, Y., Esquivel, C. O., Kim, W. R., Melcher, M. L., Sasaki, K. 2024; 10 (10): e1661

    Abstract

    The global surge in aging has intensified debates on liver transplantation (LT) for candidates aged 75 y and older, given the prevalent donor scarcity. This study examined both the survival benefits and organ utility of LT for this age group.A total of 178 469 adult LT candidates from the United Network for Organ Sharing database (2003-2022) were analyzed, with 112 266 undergoing LT. Post-LT survival outcomes and waitlist dropout rates were monitored across varying age brackets. Multivariable Cox regression analysis determined prognostic indicators. The 5-y survival benefit was assessed by comparing LT recipients to waitlist candidates using hazard ratios. Organ utility was evaluated through a simulation model across various donor classifications.Among candidates aged 75 y and older, 343 received LT. The 90-d graft and patient survival rates for these patients were comparable with those in other age categories; however, differences emerged at 1 and 3 y. Age of 75 y or older was identified as a significant negative prognostic indicator for 3-y graft survival (hazard ratio: 1.72 [1.20-2.42], P < 0.01). Dropout rates for the 75 y and older age category were 12.0%, 24.1%, and 35.1% at 90 d, 1 y, and 3 y, respectively. The survival benefit of LT for the 75 y and older cohort was clear when comparing outcomes between LT recipients and those on waitlists. However, organ utility considerations did not favor allocating livers to this age group, regardless of donor type. Comparing 3-y patient survival between LT using donors aged 60 y and younger and older than 60 y showed no significant difference (P = 0.50) in the 75 y or older cohort.Although LT offers survival benefits to individuals aged 75 y and older, the system may need rethinking to optimize the use of scarce donor livers, perhaps by matching older donors with older recipients.

    View details for DOI 10.1097/TXD.0000000000001661

    View details for PubMedID 39359941

    View details for PubMedCentralID PMC11446594

  • Survival benefit of liver transplantation utilizing marginal donor organ according to ABO blood type. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Bekki, Y., Inaba, Y., Imaoka, Y., Esquivel, C. O., Kwong, A., Kim, W. R., Sasaki, K. 2024

    Abstract

    The current liver transplantation (LT) allocation policy focuses on the Model for End-Stage Liver Disease (MELD) scores, often overlooking factors like blood type and survival benefits. Understanding blood types' impact on survival benefits is crucial for optimizing the MELD 3.0 classification.This study used the United Network for Organ Sharing national registry database (2003-2020) to identify LT characteristics per ABO blood type and to determine the optimal MELD 3.0 scores for each blood type, based on survival benefits.The study included LT candidates aged 18 years or older listed for LT (total N=150,815; A:56,546, AB:5,841, B:18,500, O:69,928). Among these, 87,409 individuals (58.0%) underwent LT (A:32,156, AB:4,362, B:11,786, O:39,105). Higher transplantation rates were observed in AB and B groups, with lower median MELD 3.0 scores at transplantation (AB:21, B:24 vs. A/O:26, p<0.01) and shorter waiting times (AB:101 days, B:172 days vs. A:211 days, O:201 days, p<0.01). A preference for Donation after Cardiac Death (DCD) was seen in A and O recipients. Survival benefit analysis indicated that B blood type required higher MELD 3.0 scores for transplantation than A and O (Donation after Brain Death transplantation: ≥15 in B vs. ≥11 in A/O; DCD transplantation: ≥21 in B vs. ≥11 in A, ≥15 in O).The study suggests revising the allocation policy to consider blood type for improved post-LT survival. This calls for personalized LT policies, recommending higher MELD 3.0 thresholds, particularly for individuals with type B blood.

    View details for DOI 10.1097/LVT.0000000000000460

    View details for PubMedID 39287561

  • Pediatric to adult transition in solid organ transplant recipients: A systematic review of existing transition programs Yerigeri, S., Satariano, M., Pape, L., Johnson, J. N., Marks, S. D., Twombley, K. E., Doshi, K., Oh, J., McCulloch, M., Esquivel, C. O., Raina, R. LIPPINCOTT WILLIAMS & WILKINS. 2024: 413
  • Pediatric Combined Heart-liver Transplantation: A Single-center Long-term Experience. Transplantation direct Levitte, S., Nilkant, R., Chen, S., Beadles, A., Lee, J., Bonham, C. A., Rosenthal, D., Gallo, A., Hollander, S., Esquivel, C., Ma, M., Zhang, K. Y. 2024; 10 (9): e1696

    Abstract

    Combined heart liver transplant (CHLT) continues to gain attention as a surgical treatment for patients with end-stage heart and liver disease but remains rare. We present our institutional longitudinal experience with up to 14 y of follow-up, focused on long-term outcomes in CHLT recipients.We conducted a single-institutional, retrospective review from January 1, 2010, to December 31, 2023, including 7 patients ages 7-17 y who underwent CHLT.Most patients were surgically palliated via Fontan procedure pretransplant (n = 6), and all had evidence of advanced fibrosis or cirrhosis before transplant. The 30-d mortality was 14.3% (n = 1, multiorgan failure). During the follow-up period, 1 patient developed acute heart rejection which required treatment and 2 developed acute liver rejection. In all cases, rejection was successfully treated. Two patients developed acute heart rejection which did not require treatment (grade 1R). No patients developed chronic or refractory rejection. No patients developed allograft coronary artery vasculopathy.CHLT remains a rarely performed treatment for pediatric patients with end-stage heart and liver disease, but our long-term data suggest that this treatment strategy should be considered more frequently.

    View details for DOI 10.1097/TXD.0000000000001696

    View details for PubMedID 39165490

    View details for PubMedCentralID PMC11335332

  • Effect of transjugular intrahepatic portosystemic shunt insertion on waitlist mortality and access to liver transplantation in budd-chiari syndrome. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Imaoka, Y., Nakayama, T., Esquivel, C. O., Sasaki, K. 2024

    Abstract

    BACKGROUND: The impact of transjugular intrahepatic portosystemic shunt (TIPS) on waitlist mortality and liver transplantation (LT) urgency in Budd-Chiari Syndrome (BCS) patients remains unclear.METHOD: We analyzed BCS patients listed for LT in the UNOS database(2002-2024) to assess TIPS's impact on waitlist mortality and LT access via competing-risk analysis. We compared trends across two phases:Phase1(2002-2011) and Phase2(2012-2024).RESULTS: Of 815 BCS patients, 263(32.3%) received TIPS at listing. TIPS group had lower MELD-Na scores(20vs22,p<0.01), milder ascites(p=0.01), and fewer Status1 patients(those at risk of imminent death while awaiting LT)(2.7%vs8.3%,p<0.01) at listing compared to those without TIPS. TIPS patients had lower LT rates(43.3%vs56.5%,p<0.01) and longer waitlist times(350vs113d,p<0.01). TIPS use increased in Phase2(64.3%vs35.7%,p<0.01). Of 426 transplanted patients, 134(31.5%) received TIPS, showing lower MELD-Na scores(24vs27,p<0.01) and better medical conditions(Intensive care unit:14.9%vs21.9%,p<0.01) at LT. Status1 patients were fewer (3.7%vs12.3%,p<0.01), with longer waiting days(97vs26d,p<0.01) in TIPS group. TIPS use at listing increased from Phase1(25.6%) to Phase2(37.7%). From Phase1 to Phase2, ascites severity improved, re-LT cases decreased(Phase1:9.8%vsPhase2:2.2%,p<0.01), and cold ischemic time slightly decreased(Phase1:7.0vsPhase2:6.4 hours,p=0.14). Median donor body mass index significantly increased. No significant differences were identified in patient/graft survival at 1-/5-/10-year intervals between phases or TIPS/non-TIPS patients. While 90-day waitlist mortality showed no significant difference(p=0.11), TIPS trended towards lower mortality(subHazard ratio[sHR]:0.70[0.45-1.08]). Multivariable analysis indicated that TIPS was a significant factor in decreasing mortality(sHR:0.45[0.27-0.77],p<0.01). TIPS group also showed significantly lower LT access(sHR:0.65[0.53-0.81],p<0.01). Multivariable analysis showed that TIPS was a significant factor in decreasing access to LT(sHR:0.60[0.46-0.77],p<0.01). Sub-group analysis excluding Status1 or HCC showed similar trends.CONCLUSION: TIPS in BCS patients listed for LT reduces waitlist mortality and LT access, supporting its bridging role.

    View details for DOI 10.1097/LVT.0000000000000469

    View details for PubMedID 39177578

  • Interleukin-33 and liver natural killer cells: A novel perspective on antitumor activity in liver fibrosis. Hepatology research : the official journal of the Japan Society of Hepatology Imaoka, Y., Ohira, M., Imaoka, K., Bekki, T., Nakano, R., Yano, T., Tanaka, Y., Nakayama, T., Akabane, M., Tajima, T., Yokota, S., Krams, S. M., Martinez, O. M., Esquivel, C. O., Sasaki, K., Ohdan, H. 2024

    Abstract

    Liver fibrosis, heralding the potential progression to cirrhosis and hepatocellular carcinoma (HCC), compromises patient survival and augments post-hepatectomy recurrence. This study examined the detrimental effects of liver fibrosis on the antitumor functions of liver natural killer (NK) cells and the interleukin-33 (IL-33) signaling pathway.Our investigation, anchored in both human physiologies using living and deceased donor livers and the carbon tetrachloride (CCl4)-induced mouse fibrosis model, aimed to show a troubling interface between liver fibrosis and weakened hepatic immunity.The Fibrosis-4 (FIB-4) index emerged as a salient, non-invasive prognostic marker, and its elevation correlated with reduced survival and heightened recurrence after HCC surgery even after propensity matching (n = 385). We established a strong correlation between liver fibrosis and liver NK cell dysfunction by developing a method for extracting liver NK cells from the liver graft perfusate. Furthermore, liver fibrosis ostensibly disrupted chemokines and promoted IL-33 expression, impeding liver NK cell antitumor activities, as evidenced in mouse models. Intriguingly, our results implicated IL-33 in diminishing the antitumor responses of NK cells. This interrelation, consistent across both mouse and human studies, coincides with clinical data suggesting that liver fibrosis predisposes patients to an increased risk of HCC recurrence.Our study revealed a critical relationship between liver fibrosis and compromised tumor immunity, emphasizing the potential interference of IL-33 with NK cell function. These insights advocate for advanced immunostimulatory therapies targeting cytokines, such as IL-33, aiming to bolster the hepatic immune response against HCC in the context of liver fibrosis.

    View details for DOI 10.1111/hepr.14102

    View details for PubMedID 39134448

  • The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents. Pediatric transplantation Allen, U. D., L'Huillier, A. G., Bollard, C. M., Gross, T. G., Hayashi, R. J., Höcker, B., Maecker-Kolhoff, B., Marks, S. D., Mazariegos, G. V., Smets, F., Trappe, R. U., Visner, G., Chinnock, R. E., Comoli, P., Danziger-Isakov, L., Dulek, D. E., Dipchand, A. I., Ferry, J. A., Martinez, O. M., Metes, D. M., Michaels, M. G., Preiksaitis, J., Squires, J. E., Swerdlow, S. H., Wilkinson, J. D., Dharnidharka, V. R., Green, M., Webber, S. A., Esquivel, C. O. 2024; 28 (5): e14781

    Abstract

    The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.

    View details for DOI 10.1111/petr.14781

    View details for PubMedID 38808744

  • The Future Frontier of Liver Transplantation Exploring Young Donor Allocation Strategies for HCC Recipients. Transplantation direct Akabane, M., Esquivel, C. O., Kim, W. R., Sasaki, K. 2024; 10 (7): e1657

    Abstract

    The role of donor age in liver transplantation (LT) outcomes for hepatocellular carcinoma (HCC) is controversial. Given the significant risk of HCC recurrence post-LT, optimizing donor/recipient matching is crucial. This study reassesses the impact of young donors on LT outcomes in patients with HCC.A retrospective review of 11 704 LT cases from the United Network for Organ Sharing database (2012-2021) was conducted. The study focused on the effect of donor age on recurrence-free survival, using hazard associated with LT for HCC (HALT-HCC) and Metroticket 2.0 scores to evaluate post-LT survival in patients with HCC.Of 4706 cases with young donors, 11.0% had HCC recurrence or death within 2 y, and 18.3% within 5 y. These outcomes were comparable with those of non-young donors. A significant correlation between donor age and post-LT recurrence or mortality (P = 0.04) was observed, which became statistically insignificant after tumor-related adjustments (P = 0.32). The Kaplan-Meier curve showed that recipients with lower HALT-HCC scores (<9) and Metroticket 2.0 scores (<2.2) significantly benefited from young donors, unlike those exceeding these score thresholds. Cox regression analysis showed that donor age significantly influenced outcomes in recipients below certain score thresholds but was less impactful for higher scores.Young donors are particularly beneficial for LT recipients with less aggressive HCC, as indicated by their HALT-HCC and Metroticket 2.0 scores. These findings suggest strategically allocating young donors to recipients with less aggressive tumor profiles, which could foster more efficient use of the scarce donor supply and potentially enhance post-LT outcomes.

    View details for DOI 10.1097/TXD.0000000000001657

    View details for PubMedID 38881743

    View details for PubMedCentralID PMC11177833

  • The Spread Pattern of New Practice in Liver Transplantation in the United States. Clinical transplantation Akabane, M., Imaoka, Y., Esquivel, C. O., Kim, W. R., Sasaki, K. 2024; 38 (7): e15379

    Abstract

    Introducing new liver transplantation (LT) practices, like unconventional donor use, incurs higher costs, making evaluation of their prognostic justification crucial. This study reexamines the spread pattern of new LT practices and its prognosis across the United States.The study investigated the spread pattern of new practices using the UNOS database (2014-2023). Practices included LT for hepatitis B/C (HBV/HCV) nonviremic recipients with viremic donors, LT for COVID-19-positive recipients, and LT using onsite machine perfusion (OMP). One year post-LT patient and graft survival were also evaluated.LTs using HBV/HCV donors were common in the East, while LTs for COVID-19 recipients and those using OMP started predominantly in California, Arizona, Texas, and the Northeast. K-means cluster analysis identified three adoption groups: facilities with rapid, slow, and minimal adoption rates. Rapid adoption occurred mainly in high-volume centers, followed by a gradual increase in middle-volume centers, with little increase in low-volume centers. The current spread patterns did not significantly affect patient survival. Specifically, for LTs with HCV donors or COVID-19 recipients, patient and graft survivals in the rapid-increasing group was comparable to others. In LTs involving OMP, the rapid- or slow-increasing groups tended to have better patient survival (p = 0.05) and significantly improved graft survival rates (p = 0.02). Facilities adopting new practices often overlap across different practices.Our analysis revealed three distinct adoption groups across all practices, correlating the adoption aggressiveness with LT volume in centers. Aggressive adoption of new practices did not compromise patient and graft survivals, supporting the current strategy. Understanding historical trends could predict the rise in future LT cases with new practices, aiding in resource distribution.

    View details for DOI 10.1111/ctr.15379

    View details for PubMedID 38952196

  • The suggestion of mitigating disparity in the liver transplantation field among ABO blood type. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Akabane, M., Imaoka, Y., Esquivel, C. O., Kim, W. R., Sasaki, K. 2024

    Abstract

    Medical literature highlights differences in liver transplantation(LT) waitlist experiences among ABO blood types. Type AB candidates reportedly have higher LT rates and reduced mortality. Despite liver offer guidelines, ABO disparities persist. This study examines LT access discrepancies among blood types, focusing on type AB, and seeks equitable strategies. Using the UNOS database(2003-2022), 170,276 waitlist candidates were retrospectively analyzed. Dual predictive analyses(LT Opportunity&Survival Studies) evaluated 1-year recipient pool survival, considering waitlist and post-LT survival, alongside anticipated allocation value per recipient, under six scenarios. Of the cohort, 97,670 patients(57.2%) underwent LT. Type AB recipients had the highest LT rate(73.7vs55.2% for O), shortest median waiting time(90vs198days for A), and lowest waitlist mortality(12.9vs23.9% for O), with the lowest median MELD-Na score(20vs25 for A/O). The LT Opportunity Study revealed that reallocating type A(or A&O) donors-originally for AB recipients-to A recipients yielded the greatest reduction in disparities in anticipated value per recipient, from 0.19(before modification) to 0.08. Meanwhile, the Survival Study showed that ABO-identical LTs reduced disparity most(3.5% to 2.8%). Sensitivity analysis confirmed these findings were specific to the MELD-Na<30 population, indicating current LT allocation may favor certain blood types. Prioritizing ABO-identical LTs for MELD-Na<30 recipients could ensure uniform survival outcomes and mitigate disparities.

    View details for DOI 10.1016/j.ajt.2024.06.004

    View details for PubMedID 38866110

  • Landscape of donor cause of death and its impact on liver transplant outcomes: a ten-year analysis from the UNOS database. HPB : the official journal of the International Hepato Pancreato Biliary Association Akabane, M., Imaoka, Y., Esquivel, C. O., Sasaki, K. 2024

    Abstract

    Cause of death (COD) is a predictor of liver transplant (LT) outcomes independent of donor age, yet has not been recently reappraised.Analyzing UNOS database (2013-2022), the study explored COD trends and impacts on one-year post-LT graft survival (GS) and hazard ratios (HR) for graft failure.Of 80,282 brain-death donors, 55,413(69.0%) underwent initial LT. Anoxia became the predominant COD in 2015, increasing from 29.0% in 2013 to 45.1% in 2021, with notable increases in drug intoxication. Survival differences between anoxia and cerebrovascular accidents (CVA) recently became insignificant (P=0.95). Further analysis showed improved GS from intracranial hemorrhage/stroke (previously worse; P<0.01) (P=0.70). HRs for post-1-year graft failure showed reduced significance of CVA (vs.Anoxia) and intracranial hemorrhage/stroke (vs.any other COD) recently. Donors with intracranial hemorrhage/stroke, showing improved survival and HR, were allocated to recipients with lower MELD-Na, contrasting the trend for drug intoxication CODs.CVA, traditionally linked with poorer outcomes, shows improved GS and HRs (vs.Anoxia). This could be due to rising drug intoxication cases and the allocation of donors with drug intoxication to recipients with higher MELD-Na, and those with CVA to recipients with lower scores. While COD remains crucial in donor selection, proper matching can mitigate differences among CODs.

    View details for DOI 10.1016/j.hpb.2024.05.019

    View details for PubMedID 38879433

  • Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States. Pediatric transplantation Tajima, T., Martinez, O. M., Bernstein, D., Boyd, S. D., Gratzinger, D., Lum, G., Sasaki, K., Tan, B., Twist, C. J., Weinberg, K., Armstrong, B., Desai, D. M., Mazariegos, G. V., Chin, C., Fishbein, T. M., Tekin, A., Venick, R. S., Krams, S. M., Esquivel, C. O. 2024; 28 (4): e14763

    Abstract

    Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis.The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis.The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01).D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

    View details for DOI 10.1111/petr.14763

    View details for PubMedID 38682750

  • An updated analysis of retransplantation following living donor liver transplantation in the US: insights from the latest UNOS database. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Imaoka, Y., Esquivel, C. O., Sasaki, K. 2024

    Abstract

    BACKGROUND: There is no recent update on the clinical course of retransplantation(re-LT) after living-donor liver transplantation (LDLT) in the US using recent national data.METHOD: The UNOS database (2002-2023) was used to explore patient characteristics in initial LT, comparing deceased-donor liver transplantation (DDLT) and LDLT for graft survival (GS), reasons for graft failure, and GS after re-LT. It assesses waitlist dropout and re-LT likelihood, categorizing re-LT cohort based on time to re-listing as acute or chronic (≤ or >1mo).RESULTS: Of 132,323 DDLT and 5,955 LDLT initial transplants, 3,848 DDLT and 302 LDLT recipients underwent re-LT. Of the 302 re-LT following LDLT, 156 were acute and 146 chronic. Primary non-function (PNF) was more common in DDLT, although the difference was not statistically significant (17.4%vs14.8% for LDLT; p=0.52). Vascular complications were significantly higher in LDLT (12.5%vs8.3% for DDLT; p<0.01). Acute re-LT showed a larger difference in PNF between DDLT and LDLT (49.7%vs32.0%; p<0.01). Status 1 patients were more common in DDLT (51.3%vs34.0% in LDLT; p<0.01). In the acute cohort, Kaplan-Meier curves indicated superior GS post-re-LT for initial LDLT recipients in both short-term and long-term (p=0.02 and <0.01, respectively), with no significant difference in the chronic cohort. No significant differences in waitlist dropout were observed, but the initial LDLT group had a higher re-LT likelihood in the acute cohort (sHR 1.40, p<0.01). A sensitivity analysis focusing on the most recent 10-year cohort revealed trends consistent with the overall study findings.CONCLUSION: LDLT recipients had better GS in re-LT than DDLT. Despite a higher severity of illness, the DDLT cohort was less likely to undergo re-LT.

    View details for DOI 10.1097/LVT.0000000000000393

    View details for PubMedID 38727618

  • Enhancing the Usability of older DCD donors through strategic approaches in liver transplantation in the US. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Melcher, M. L., Esquivel, C. O., Imaoka, Y., Kim, W. R., Sasaki, K. 2024

    Abstract

    The use of older donors after circulatory death(DCD) for liver transplantation(LT) has increased over the past decade. This study examined whether outcomes of LT using older DCD(≥50 y) have improved with advancements in surgical/perioperative care and normothermic machine perfusion(NMP) technology.7,602 DCD LT cases from the UNOS database(2003-2022) were reviewed. The impact of older DCD donors on graft survival(GS) was assessed using Kaplan-Meier and hazard ratio(HR) analyses.1,447 LT cases(19.0%) involved older DCD donors. Although there was a decrease in their use from 2003-2014, a resurgence was noted post-2015 and reached 21.9% of all LT in the last four years(2019-2022). Initially, 90-day and one-year GS for older DCDs were worse than younger DCDs, but this difference decreased over time and there was no statistical difference after 2015. Similarly, HRs for graft loss in older DCD have recently become insignificant. In older DCD LT, NMP usage has increased recently, especially in cases with extended donor-recipient distances, while the median time from asystole to aortic cross-clamp has decreased. Multivariable Cox regression analyses revealed that in the early phase, asystole to cross-clamp time had the highest HR for graft loss in older DCD LT without NMP, while in the later phases, the CIT(>5.5 h) was a significant predictor.LT outcomes using older DCD donors have become comparable to those from young DCD donors, with recent HRs for graft loss becoming insignificant. The strategic approach in the recent period could mitigate risks, including managing CIT(≤5.5 h), reducing asystole to cross-clamp time, and adopting NMP for longer distances. Optimal use of older DCD donors may alleviate the donor shortage.

    View details for DOI 10.1097/LVT.0000000000000376

    View details for PubMedID 38625836

  • Impact of donor characteristics on hepatocellular carcinoma recurrence after liver transplantation. The British journal of surgery Akabane, M., Bekki, Y., Imaoka, Y., Inaba, Y., Esquivel, C. O., Melcher, M. L., Kwong, A., Sasaki, K. 2024; 111 (4)

    View details for DOI 10.1093/bjs/znae080

    View details for PubMedID 38630794

  • Three-dimensional Liver Model Application for Liver Transplantation. Transplantation Sanchez-Garcia, J., Lopez-Verdugo, F., Shorti, R., Krong, J., Kastenberg, Z. J., Walters, S., Gagnon, A., Paci, P., Zendejas, I., Alonso, D., Fujita, S., Contreras, A. G., Botha, J., Esquivel, C. O., Rodriguez-Davalos, M. I. 2024; 108 (2): 464-472

    Abstract

    BACKGROUND: Children are removed from the liver transplant waitlist because of death or progressive illness. Size mismatch accounts for 30% of organ refusal. This study aimed to demonstrate that 3-dimensional (3D) technology is a feasible and accurate adjunct to organ allocation and living donor selection process.METHODS: This prospective multicenter study included pediatric liver transplant candidates and living donors from January 2020 to February 2023. Patient-specific, 3D-printed liver models were used for anatomic planning, real-time evaluation during organ procurement, and surgical navigation. The primary outcome was to determine model accuracy. The secondary outcome was to determine the impact of outcomes in living donor hepatectomy. Study groups were analyzed using propensity score matching with a retrospective cohort.RESULTS: Twenty-eight recipients were included. The median percentage error was -0.6% for 3D models and had the highest correlation to the actual liver explant (Pearson's R=0.96, P<0.001) compared with other volume calculation methods. Patient and graft survival were comparable. From 41 living donors, the median percentage error of the allograft was 12.4%. The donor-matched study group had lower central line utilization (21.4% versus 75%, P=0.045), shorter length of stay (4 versus 7 d, P=0.003), and lower mean comprehensive complication index (3 versus 21, P=0.014).CONCLUSIONS: Three-dimensional volume is highly correlated with actual liver explant volume and may vary across different allografts for living donation. The addition of 3D-printed liver models during the transplant evaluation and organ procurement process is a feasible and safe adjunct to the perioperative decision-making process.

    View details for DOI 10.1097/TP.0000000000004730

    View details for PubMedID 38259179

  • Incidence and Outcomes of Simultaneous Thoracoabdominal Triple Organ Transplantation in the United States. Transplantation proceedings Adjei, M. A., Wisel, S. A., Steggerda, J. A., Mirocha, J., Mavis, A., Esquivel, C. O., Kim, I. K. 2024

    Abstract

    BACKGROUND: This study aims to evaluate patient outcomes of simultaneous triple organ transplants, which may provide insight into optimal donor allocation while maximizing recipient benefit.METHODS: Triple organ transplants and their corollary dual organ transplants were identified using the United Network for Organ Sharing database. Triple organ transplants evaluated included heart-lung-kidney (n=12) and heart-liver-kidney (n=37). Heart-lung-kidney recipients were compared with heart-lung (n=325), lung-kidney (n=91), and heart-kidney (n=2022) groups. Heart-liver-kidney recipients were compared with heart-liver (n=451), liver-kidney (n=10422), and heart-kidney (n=2517) recipients. Patient survival outcomes were calculated using the Kaplan-Meier method and compared using log-rank tests.RESULTS: Patients undergoing triple organ transplants showed similar 10-year survival as their corresponding dual organ transplant cohorts. Patient survival estimate at 10 years for the heart-lung-kidney group was 45%, with no statistically significant difference in survival when compared with dual organ groups (P=.16). Survival estimates at 10 years for the heart-liver-kidney group was 49%, with no statistically significant difference in survival when compared with dual organ groups (P=.06).CONCLUSION: Despite the surgical burden of adding a third organ transplant, heart-liver-kidney and heart-lung-kidney have similar survival outcomes to dual organ equivalents and represent a reasonable allocation option in well-selected patients.

    View details for DOI 10.1016/j.transproceed.2023.11.029

    View details for PubMedID 38195284

  • Antiviral Therapy Utilization and 10-Year Outcomes in Resected Hepatitis B Virus- and Hepatitis C Virus-Related Hepatocellular Carcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Huang, D. Q., Hoang, J. K., Kamal, R., Tsai, P. C., Toyoda, H., Yeh, M. L., Yasuda, S., Leong, J., Maeda, M., Huang, C. F., Won Jun, D., Ishigami, M., Tanaka, Y., Uojima, H., Ogawa, E., Abe, H., Hsu, Y. C., Tseng, C. H., Alsudaney, M., Yang, J. D., Yoshimaru, Y., Suzuki, T., Liu, J. K., Landis, C., Dai, C. Y., Huang, J. F., Chuang, W. L., Schwartz, M., Dan, Y. Y., Esquivel, C., Bonham, A., Yu, M. L., Nguyen, M. H. 2024: JCO2300757

    Abstract

    There are limited data on antiviral treatment utilization and its impact on long-term outcomes of hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after hepatic resection. We aimed to determine the utilization and impact of antivirals in HBV- and HCV-related HCC.This cohort study included 1,906 participants (1,054 HBV-related HCC and 852 HCV-related HCC) from 12 international sites. All participants had HBV- or HCV-related HCC and underwent curative surgical resection. The primary outcome was the utilization of antiviral therapy, and the secondary outcome was long-term overall survival (OS).The mean (±standard deviation [SD]) age was 62.1 (±11.3) years, 74% were male, and 84% were Asian. A total of 47% of the total cohort received antiviral therapy during a mean (±SD) follow-up of 5.0 (±4.3) years. The overall antiviral utilization for participants with HBV-related HCC was 57% and declined over time, from 65% before 2010, to 60% from 2010 to 2015, to 47% beyond 2015, P < .0001. The overall utilization of antivirals for HCV-related HCC was 35% and increased over time, from 24% before 2015 to 74% from 2015 and beyond, P < .0001. The 10-year OS was lower in untreated participants for both HBV (58% v 61%) and HCV participants (38% v 82%; both P < .0001). On multivariable Cox regression analysis adjusted for relevant confounders, antiviral therapy initiated before or within 6 months of HCC diagnosis was independently associated with lower mortality in both HBV- (adjusted hazard ratio [aHR], 0.60 [95% CI, 0.43 to 0.83]; P = .002) and HCV-related HCC (aHR, 0.18 [95% CI, 0.11 to 0.31]; P < .0001).Antiviral therapy is associated with long-term survival in people with HBV- or HCV-related HCC who undergo curative resection but is severely underutilized.

    View details for DOI 10.1200/JCO.23.00757

    View details for PubMedID 38175991

  • Evaluating Predictors of Quality in Liver NK Cells Among Deceased Donors CELL TRANSPLANTATION Imaoka, Y., Ohira, M., Nakayama, T., Akabane, M., Tajima, T., Yokota, S., Krams, S. M., Martinez, O. M., Esquivel, C. O., Sasaki, K., Ohdan, H. 2024; 33
  • Breaking distance barriers in liver transplantation: Risk factors and outcomes of long-distance liver grafts. Surgery Imaoka, Y., Bozhilov, K. K., Bekki, Y., Akabane, M., Kwong, A. J., Ohira, M., Ohdan, H., Esquivel, C. O., Melcher, M. L., Sasaki, K. 2023

    Abstract

    Long-distance-traveling liver grafts in liver transplantation present challenges due to prolonged cold ischemic time and increased risk of ischemia-reperfusion injury. We identified long-distance-traveling liver graft donor and recipient characteristics and risk factors associated with long-distance-traveling liver graft use.We conducted a retrospective analysis of data from donor liver transplantation patients registered from 2014 to 2020 in the United Network for Organ Sharing registry database. Donor, recipient, and transplant factors of graft survival were compared between short-travel grafts and long-distance-traveling liver grafts (traveled >500 miles).During the study period, 28,265 patients received a donation after brainstem death liver transplantation and 3,250 a donation after circulatory death liver transplantation. The long-distance-traveling liver graft rate was 6.2% in donation after brainstem death liver transplantation and 7.1% in donation after circulatory death liver transplantation. The 90-day graft survival rates were significantly worse for long-distance-traveling liver grafts (donation after brainstem death: 95.7% vs 94.5%, donation after circulatory death: 94.5% vs 93.9%). The 3-year graft survival rates were similar for long-distance-traveling liver grafts (donation after brainstem death: 85.5% vs 85.1%, donation after circulatory death: 81.0% vs 80.4%). Cubic spline regression analyses revealed that travel distance did not linearly worsen the prognosis of 3-year graft survival. On the other hand, younger donor age, lower donor body mass index, and shorter cold ischemic time mitigated the negative impact of 90-day graft survival in long-distance-traveling liver grafts.The use of long-distance-traveling liver grafts negatively impacts 90-day graft survival but not 3-year graft survival. Moreover, long-distance-traveling liver grafts are more feasible with appropriate donor and recipient factors offsetting the extended cold ischemic time. Mechanical perfusion can improve long-distance-traveling liver graft use. Enhanced collaboration between organ procurement organizations and transplant centers and optimized transportation systems are essential for increasing long-distance-traveling liver graft use, ultimately expanding the donor pool.

    View details for DOI 10.1016/j.surg.2023.09.052

    View details for PubMedID 37980203

  • Impact of Induction Therapy on Rejection in Pediatric Transplantation: A Multicenter Study in the US Tajima, T., Chin, C., Desai, D. M., Fishbein, T. M., Mazariegos, G. V., Tekin, A., Venick, R., Krams, S. M., Martinez, O. M., Esquivel, C. O. LIPPINCOTT WILLIAMS & WILKINS. 2023: S495
  • Alcohol Use in Liver Transplant Recipients With Alcohol-related Liver Disease: A Comparative Assessment of Relapse Prediction Models. Transplantation Sedki, M., Kwong, A., Bhargava, M., Ahmed, A., Daugherty, T., Kwo, P., Dronamraju, D., Kumari, R., Kim, W. R., Esquivel, C., Melcher, M., Bonham, C. A., Gallo, A., Nelson, A., Norwood, A., Hussain, F., Goel, A. 2023

    Abstract

    The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse.A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed. Risk factors associated with post-LT AR were evaluated and test characteristics of 3 prediction models were compared.Of 219 ALD LT recipients, 23 (11%) had AR during a median study follow-up of 37.5 mo. On multivariate analysis, comorbid psychiatric illness (odds ratio 5.22) and continued alcohol use after advice from a health care provider (odds ratio 3.8) were found to be significantly associated with post-LT AR. On sensitivity analysis, SIPAT of 30 was optimal on discriminating between ALD LT recipients with and without post-LT AR. SIPAT outperformed both the HRAR and SALT scores (c-statistic 0.67 versus 0.59 and 0.62, respectively) in identifying post-LT AR. However, all scores had poor positive predictive value (<25%).AR after LT is associated with comorbid psychiatric illness and lack of heeding health care provider advice to abstain from alcohol. Although SIPAT outperformed the HRAR and SALT scores in predicting AR, all are poor predictors. The current tools to predict post-LT AR should not be used to exclude LT candidacy.

    View details for DOI 10.1097/TP.0000000000004800

    View details for PubMedID 37899485

  • The short and long-term prognostic influences of liver grafts with high bilirubin levels at the time of organ recovery. Clinical transplantation Akabane, M., Bekki, Y., Imaoka, Y., Inaba, Y., Kwong, A. J., Esquivel, C. O., Melcher, M. L., Sasaki, K. 2023: e15155

    Abstract

    Donors with hyperbilirubinemia are often not utilized for liver transplantation (LT) due to concerns about potential liver dysfunction and graft survival. The potential to mitigate organ shortages using such donors remains unclear.This study analyzed adult deceased donor data from the United Network for Organ Sharing database (2002-2022). Hyperbilirubinemia was categorized as high total bilirubin (3.0-5.0 mg/dL) and very high bilirubin (≥5.0 mg/dL) in brain-dead donors. We assessed the impact of donor hyperbilirubinemia on 3-month and 3-year graft survival, comparing these outcomes to donors after circulatory death (DCD).Of 138 622 donors, 3452 (2.5%) had high bilirubin and 1999 (1.4%) had very high bilirubin levels. Utilization rates for normal, high, and very high bilirubin groups were 73.5%, 56.4%, and 29.2%, respectively. No significant differences were found in 3-month and 3-year graft survival between groups. Donors with high bilirubin had superior 3-year graft survival compared to DCD (hazard ratio .83, p = .02). Factors associated with inferior short-term graft survival included recipient medical condition in intensive care unit (ICU) and longer cold ischemic time; factors associated with inferior long-term graft survival included older donor age, recipient medical condition in ICU, older recipient age, and longer cold ischemic time. Donors with ≥10% macrosteatosis in the very high bilirubin group were also associated with worse 3-year graft survival (p = .04).The study suggests that despite many grafts with hyperbilirubinemia being non-utilized, acceptable post-LT outcomes can be achieved using donors with hyperbilirubinemia. Careful selection may increase utilization and expand the donor pool without negatively affecting graft outcome.

    View details for DOI 10.1111/ctr.15155

    View details for PubMedID 37812571

  • 311.2: Risk factors for Epstein-Barr virus DNAemia in pediatric transplantation: A multicenter study in the United States. Transplantation Tajima, T., Bernstein, D., Boyd, S. D., Gratzinger, D., Lum, G., Sasaki, K., Tan, B., Weinberg, K., Armstrong, B., Brown, M., Chin, C., Desai, D., Fishbein, T. M., Mazariegos, G., Robien, M. A., Tekin, A., Twist, C. J., Venick, R. S., Krams, S. M., Martinez, O. M., Esquivel, C. O. 2023; 107 (10S1): 71-72

    View details for DOI 10.1097/01.tp.0000993400.94644.c0

    View details for PubMedID 37845955

  • International Liver Transplantation Society Global Census: First Look at Pediatric Liver Transplantation Activity Around the World. Transplantation Rodriguez-Davalos, M. I., Lopez-Verdugo, F., Kasahara, M., Muiesan, P., Reddy, M. S., Flores-Huidobro Martinez, A., Xia, Q., Hong, J. C., Niemann, C. U., Seda-Neto, J., Miloh, T. A., Yi, N. J., Mazariegos, G. V., Ng, V. L., Esquivel, C. O., Lerut, J., Rela, M. 2023; 107 (10): 2087-2097

    Abstract

    Over 16 000 children under the age of 15 died worldwide in 2017 because of liver disease. Pediatric liver transplantation (PLT) is currently the standard of care for these patients. The aim of this study is to describe global PLT activity and identify variations between regions.A survey was conducted from May 2018 to August 2019 to determine the current state of PLT. Transplant centers were categorized into quintile categories according to the year they performed their first PLT. Countries were classified according to gross national income per capita.One hundred eight programs from 38 countries were included (68% response rate). 10 619 PLTs were performed within the last 5 y. High-income countries performed 4992 (46.4%) PLT, followed by upper-middle- (4704 [44·3%]) and lower-middle (993 [9·4%])-income countries. The most frequently used type of grafts worldwide are living donor grafts. A higher proportion of lower-middle-income countries (68·7%) performed ≥25 living donor liver transplants over the last 5 y compared to high-income countries (36%; P = 0.019). A greater proportion of programs from high-income countries have performed ≥25 whole liver transplants (52.4% versus 6.2%; P = 0.001) and ≥25 split/reduced liver transplants (53.2% versus 6.2%; P < 0.001) compared to lower-middle-income countries.This study represents, to our knowledge, the most geographically comprehensive report on PLT activity and a first step toward global collaboration and data sharing for the greater good of children with liver disease; it is imperative that these centers share the lead in PLT.

    View details for DOI 10.1097/TP.0000000000004644

    View details for PubMedID 37750781

  • Has the risk of liver re-transplantation improved over the two decades? Clinical transplantation Akabane, M., Bekki, Y., Imaoka, Y., Inaba, Y., Esquivel, C. O., Kwong, A., Melcher, M. L., Sasaki, K. 2023: e15127

    Abstract

    Despite advancements in liver transplantation (LT) over the past two decades, liver re-transplantation (re-LT) presents challenges. This study aimed to assess improvements in re-LT outcomes and contributing factors.Data from the United Network for Organ Sharing database (2002-2021) were analyzed, with recipients categorized into four-year intervals. Trends in re-LT characteristics and postoperative outcomes were evaluated.Of 128,462 LT patients, 7254 received re-LT. Graft survival (GS) for re-LT improved (91.3%, 82.1%, and 70.8% at 30 days, 1 year, and 3 years post-LT from 2018 to 2021). However, hazard ratios (HRs) for GS remained elevated compared to marginal donors including donors after circulatory death (DCD), although the difference in HRs decreased in long-term GS. Changes in re-LT causes included a reduction in hepatitis C recurrence and an increase in graft failure post-primary LT involving DCD. Trends identified included recent decreased cold ischemic time (CIT) and increased distance from donor hospital in re-LT group. Meanwhile, DCD cohort exhibited less significant increase in distance and more marked decrease in CIT. The shortest CIT was recorded in urgent re-LT group. The highest Model for End-Stage Liver Disease score was observed in urgent re-LT group, while the lowest was recorded in DCD group. Analysis revealed shorter time interval between previous LT and re-listing, leading to worse outcomes, and varying primary graft failure causes influencing overall survival post-re-LT.While short-term re-LT outcomes improved, challenges persist compared to DCD. Further enhancements are required, with ongoing research focusing on optimizing risk stratification models and allocation systems for better LT outcomes.

    View details for DOI 10.1111/ctr.15127

    View details for PubMedID 37772621

  • Technical Variant Liver Transplant Utilization for Pediatric Recipients: Equal Graft Survival to Whole Liver Transplants and Promotion of Timely Transplantation Only When Performed at High-volume Centers. Transplantation Stoltz, D. J., Gallo, A. E., Lum, G., Mendoza, J., Esquivel, C. O., Bonham, A. 2023

    Abstract

    Technical variant liver transplantation (TVLT) is a strategy to mitigate persistent pediatric waitlist mortality in the United States, although its implementation remains stagnant. This study investigated the relationship between TVLT utilization, transplant center volume, and graft survival.Pediatric liver transplant recipients from 2010 to 2020 (n = 5208) were analyzed using the Scientific Registry of Transplant Recipients database. Transplant centers were categorized according to the average number of pediatric liver transplants performed per year (high-volume, ≥5; low-volume, <5). Graft survival rates were compared using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models were used to identify predictors of graft failure.High-volume centers demonstrated equivalent whole liver transplant and TVLT graft survival (P = 0.057) and significantly improved TVLT graft survival compared with low-volume centers (P < 0.001). Transplantation at a low-volume center was significantly associated with graft failure (adjusted hazard ratio, 1.6; 95% confidence interval, 1.14-2.24; P = 0.007 in patients <12 y old and 1.8; 95% confidence interval, 1.13-2.87; P = 0.013 in patients ≥12 y old). A subset of high-volume centers with a significantly higher rate of TVLT use demonstrated a 23% reduction in waitlist mortality.Prompt transplantation with increased TVLT utilization at high-volume centers may reduce pediatric waitlist mortality without compromising graft survival.

    View details for DOI 10.1097/TP.0000000000004772

    View details for PubMedID 37635278

  • Overcoming the hurdles of steatotic grafts in liver transplantation: insights into survival and prognostic factors. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Imaoka, Y., Esquivel, C. O., Melcher, M. L., Kwong, A., Sasaki, K. 2023

    Abstract

    With increasing metabolic dysfunction associated steatotic liver disease (MASLD), the use of steatotic grafts in liver transplantation (LT) and their impact on postoperative graft survival (GS) needs further exploration.Analyzing adult LT recipient data (2002-2022) from the United Network for Organ Sharing database, outcomes of LT using steatotic (≥30% macrosteatosis) and non-steatotic donor livers, donors after circulatory death (DCD), and standard-risk older donors (age 45-50) were compared. GS predictors were evaluated using Kaplan-Meier and Cox regression analyses.Of the 35,345 LT donors, 8.9% (3,155) were fatty livers. Initial 30-day postoperative period revealed significant challenges with fatty livers, demonstrating inferior GS. However, the GS discrepancy between fatty and non-fatty livers subsided over time (p=0.10 at 5 y). Long-term GS outcomes showed comparable or even superior results in fatty livers relative to non-steatotic livers, conditional on surviving the initial 90 postoperative days (p=0.90 at 1 y) or 1 year (p=0.03 at 5 y). In the multivariable Cox regression analysis, high body surface area (BSA) ratio (≥1.1) (hazard ratio [HR] 1.42, p=0.02), calculated as donor BSA divided by recipient BSA, long cold ischemic time (≥6.5 hours) (HR 1.72, p<0.01), and recipient medical condition (ICU hospitalization) (HR 2.53, p<0.01) emerged as significant adverse prognostic factors. Young (<40 y) fatty donors showed a high BSA ratio, diabetes, and ICU hospitalization as significant indicators of worse prognosis (p<0.01).Our study emphasizes the initial postoperative 30-day survival challenge in LT using fatty livers. However, with careful donor-recipient matching, e.g. avoiding use of steatotic donors with long cold ischemic time and high BSA ratios for recipients in the ICU, it is possible to enhance immediate GS, and in a longer time, outcomes comparable to those using non-fatty livers, DCD livers, or standard-risk older donors, can be anticipated. These novel insights into decision-making criteria for steatotic liver use provide invaluable guidance for clinicians.

    View details for DOI 10.1097/LVT.0000000000000245

    View details for PubMedID 37616509

  • Highlights from the 12th congress of the international pediatric transplant association, Austin, Texas 2023. Pediatric transplantation Chinnakotla, S., Esquivel, C., Twombley, K., Posfay-Barbe, K., Krams, S. M. 2023: e14592

    Abstract

    The 12th Congress of the (IPTA) event in Austin, Texas, had over 400 attendees from 40 countries. The attendees included a diverse mix of pediatric transplant professionals from several specialties including physicians, surgeons, scientists, nurses, organ procurement personnel, advance transplant providers, pharmacists, administrators, fellows, residents, and students. The 4-day event featured nearly 200 abstracts, 90 oral presentations, 24 mini oral presentations, and more than 80 poster presentations. All of these presentations encouraged vibrant discussions and supported the exchange of new clinical and basic science information regarding clinical care management, basic science research, socioeconomic, and ethical and organ donation issues relevant to pediatric transplantation. We briefly describe here the highest scored presented abstracts at IPTA 2023 that are divided into two categories: clinical and basic sciences.

    View details for DOI 10.1111/petr.14592

    View details for PubMedID 37632202

  • High-dimensional profiling of pediatric immune responses to solid organ transplantation. Cell reports. Medicine Rao, M., Amouzgar, M., Harden, J. T., Lapasaran, M. G., Trickey, A., Armstrong, B., Odim, J., Debnam, T., Esquivel, C. O., Bendall, S. C., Martinez, O. M., Krams, S. M. 2023: 101147

    Abstract

    Solid organ transplant remains a life-saving therapy for children with end-stage heart, lung, liver, or kidney disease; however, ∼33% of allograft recipients experience acute rejection within the first year after transplant. Our ability to detect early rejection is hampered by an incomplete understanding of the immune changes associated with allograft health, particularly in the pediatric population. We performed detailed, multilineage, single-cell analysis of the peripheral blood immune composition in pediatric solid organ transplant recipients, with high-dimensional mass cytometry. Supervised and unsupervised analysis methods to study cell-type proportions indicate that the allograft type strongly influences the post-transplant immune profile. Further, when organ-specific differences are considered, graft health is associated with changes in the proportion of distinct T cell subpopulations. Together, these data form the basis for mechanistic studies into the pathobiology of rejection and allow for the development of new immunosuppressive agents with greater specificity.

    View details for DOI 10.1016/j.xcrm.2023.101147

    View details for PubMedID 37552988

  • Mesenchymal stem cell-derived exosomes for the treatment of acute rejection in pediatric and adult bowel transplant Zhang, K., Kumari, R., Lightner, A., Gallo, A., Bonham, C., Esquivel, C. LIPPINCOTT WILLIAMS & WILKINS. 2023: 38
  • The IPTA Nashville Consensus Conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: III - Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring. Pediatric transplantation Preiksaitis, J., Allen, U., Bollard, C. M., Dharnidharka, V. R., Dulek, D. E., Green, M., Martinez, O. M., Metes, D. M., Michaels, M. G., Smets, F., Chinnock, R. E., Comoli, P., Danziger-Isakov, L., Dipchand, A. I., Esquivel, C. O., Ferry, J. A., Gross, T. G., Hayashi, R. J., Höcker, B., L'Huillier, A. G., Marks, S. D., Mazariegos, G. V., Squires, J., Swerdlow, S. H., Trappe, R. U., Visner, G., Webber, S. A., Wilkinson, J. D., Maecker-Kolhoff, B. 2023: e14471

    Abstract

    The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.

    View details for DOI 10.1111/petr.14471

    View details for PubMedID 37294621

  • International Liver Transplantation Society Global Census: First Look at Pediatric Liver Transplantation Activity Around the World. Transplantation Rodriguez-Davalos, M. I., Lopez-Verdugo, F., Kasahara, M., Muiesan, P., Reddy, M. S., Flores-Huidobro Martinez, A., Xia, Q., Hong, J. C., Niemann, C. U., Seda-Neto, J., Miloh, T. A., Yi, N. J., Mazariegos, G. V., Ng, V. L., Esquivel, C. O., Lerut, J., Rela, M. 2023

    Abstract

    Over 16 000 children under the age of 15 died worldwide in 2017 because of liver disease. Pediatric liver transplantation (PLT) is currently the standard of care for these patients. The aim of this study is to describe global PLT activity and identify variations between regions.A survey was conducted from May 2018 to August 2019 to determine the current state of PLT. Transplant centers were categorized into quintile categories according to the year they performed their first PLT. Countries were classified according to gross national income per capita.One hundred eight programs from 38 countries were included (68% response rate). 10 619 PLTs were performed within the last 5 y. High-income countries performed 4992 (46.4%) PLT, followed by upper-middle- (4704 [44·3%]) and lower-middle (993 [9·4%])-income countries. The most frequently used type of grafts worldwide are living donor grafts. A higher proportion of lower-middle-income countries (68·7%) performed ≥25 living donor liver transplants over the last 5 y compared to high-income countries (36%; P = 0.019). A greater proportion of programs from high-income countries have performed ≥25 whole liver transplants (52.4% versus 6.2%; P = 0.001) and ≥25 split/reduced liver transplants (53.2% versus 6.2%; P < 0.001) compared to lower-middle-income countries.This study represents, to our knowledge, the most geographically comprehensive report on PLT activity and a first step toward global collaboration and data sharing for the greater good of children with liver disease; it is imperative that these centers share the lead in PLT.

    View details for DOI 10.1097/TP.0000000000004644

    View details for PubMedID 37289045

  • Outcomes after liver transplantation in MPV17 deficiency: A rebuttal. Pediatric transplantation Huang, A. C., Ebel, N. H., Romero, D., Enns, G. M., Esquivel, C. O., Bonham, C. 2023: e14472

    View details for DOI 10.1111/petr.14472

    View details for PubMedID 36872458

  • Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States Tajima, T., Bernstein, D., Boyd, S. D., Gratzinger, D., Lum, G., Sasaki, K., Tan, B., Twist, C. J., Weinberg, K., Robien, M. A., Brown, M., Armstrong, B., Desai, D., Mazariegos, G., Chin, C., Fishbein, T. M., Tekin, A., Venick, R. S., Martinez, O. M., Krams, S. M., Esquivel, C. O. WILEY. 2023
  • High-dimensional profiling of pediatric immune responses to solid organ transplantation Rao, M., Amouzgar, M., Harden, J. T., Lapasaran, M. G., Trickey, A., Armstrong, B., Odim, J., Debnam, T., Esquivel, C. O., Bendall, S. C., Martinez, O. M., Krams, S. M. WILEY. 2023
  • Pediatric Liver Transplant at Long-Distance High-Volume Centers Confers Improved Graft Survival Compared to Local Low-Volume Transplant Centers Bozhilov, K., Stotlz, D., Bonham, A., Kirchner, V., Lum, G., Esquivel, C., Gallo, A. WILEY. 2023
  • High-resolution natural killer cell phenotyping by mass cytometry in pediatric transplant recipients Zhang, W., Pena, J. K., Boonrat, P., Harden, J. T., Esquivel, C. O., Martinez, O. M., Krams, S. M. WILEY. 2023
  • Amplified inferior outcomes for infant pediatric liver transplant candidates and recipients at low volume centers Stoltz, D., Bozhilov, K., Gallo, A., Kirchner, V., Lum, G., Mendoza, J., Esquivel, C., Bonham, A. WILEY. 2023
  • Extracellular vesicle microRNAs are decreased in pediatric solid-organ transplant recipients during EBV plus post-transplant lymphoproliferative disorder Sen, A., Enriquez, J., Rao, M., Esquivel, C. O., Martinez, O. M., Krams, S. M. WILEY. 2023
  • Mutations In Latent Membrane Protein 1 of Epstein-Barr Virus are Associated with Increased Risk for Post-Transplant Lymphoproliferative Disorder in Children. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Martinez, O. M., Krams, S. M., Robien, M. A., Lapasaran, M. G., Arvedson, M. P., Reitsma, A., Balachandran, Y., Harris-Arnold, A., Weinberg, K., Boyd, S. D., Armstrong, B., Trickey, A., Twist, C. J., Gratzinger, D., Tan, B., Brown, M., Chin, C., Desai, D. M., Fishbein, T. M., Mazariegos, G. V., Tekin, A., Venick, R. S., Bernstein, D., Esquivel, C. O. 2023

    Abstract

    Epstein-Barr virus (EBV)+ post-transplant lymphoproliferative disorder (PTLD) results in significant morbidity and mortality in pediatric transplant recipients. Identifying individuals at increased risk of EBV+ PTLD could influence clinical management of immunosuppression and other therapies, improving post-transplant outcomes. A seven-center prospective, observational clinical trial of 872 pediatric transplant recipients evaluated the presence of mutations at position 212 and 366 of EBV latent membrane protein 1 (LMP1) as an indicator of risk for EBV+ PTLD (Clinical Trials: NCT02182986). DNA was isolated from peripheral blood of EBV+ PTLD cases and matched controls (1:2 nested case-control), and the cytoplasmic tail of LMP1 sequenced. Thirty-four participants reached the primary endpoint of biopsy-proven EBV+ PTLD. DNA was sequenced from 32 PTLD cases and 62 matched controls. Both LMP1 mutations were present in 31/32 PTLD cases (96.9%) and in 45/62 matched controls (72.6%) (p=0.005, OR=11.7, 95% CI 1.5, 92.6). The presence of both G212S and S366T carries a nearly 12-fold increased risk for development of EBV+ PTLD. Conversely, transplant recipients without both LMP1 mutations carry a very low risk of PTLD. Analysis of mutations at positions 212 and 366 of LMP1 can be informative in stratifying patients for risk of EBV+ PTLD.

    View details for DOI 10.1016/j.ajt.2023.02.014

    View details for PubMedID 36796762

  • IDENTIFYING NOVEL GENE TARGETS FOR DIAGNOSIS AND TREATEMENT OF HCC IN ASIAN AND CAUCASIAN POPULATIONS BASED ON WHOLE GENOME SEQUENCING Hong, S., Badshah, J., Aliwaisi, A., Sasaki, K., Pruett, T., Melcher, M., Bonham, C., Gallo, A., Martinez, O., Krams, S., Pham, K., Busque, S., Reitsma, A., Esquivel, C., Kirchner, V. ELSEVIER SCIENCE INC. 2023: S28
  • Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients. Hepatobiliary surgery and nutrition Huang, D. Q., Tran, A., Tan, E. X., Nerurkar, S. N., Teh, R., Teng, M. L., Yeo, E. J., Zou, B., Wong, C., Esquivel, C. O., Bonham, C. A., Nguyen, M. H. 2022; 11 (6): 848-860

    Abstract

    Guidelines recommend that hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and/or hepatic vein tumor thrombosis (HVTT) should undergo systemic therapy. However, recent data suggest that surgical resection may be beneficial in selected cases, but outcomes are heterogenous. We aimed to estimate pooled overall survival (OS), recurrence free survival (RFS) and complication rates in HCC patients with macrovascular invasion (MVI) following surgical resection.In this systematic review and meta-analysis, two investigators independently searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020, without language restrictions, for studies reporting outcomes of adult HCC patients with MVI who underwent liver resection with curative intent.We screened 8,598 articles and included 40 studies involving 8,218 patients. Among all patients with MVI, the pooled median OS was 14.39 months [95% confidence interval (CI): 10.99-18.84], 1-year OS was 54.47% (95% CI: 46.12-62.58%) and 3-year OS was 23.20% (95% CI: 16.61-31.42%). Overall, 1- and 3-year RFS were 27.70% (95% CI: 21.00-35.57%) and 10.06% (95% CI: 6.62-15.01%), respectively. Among patients with PVTT, median OS was 20.41 months in those with segmental/2nd order involvement compared to 12.91 months if 1st order branch was involved and 6.41 months if the main trunk was involved. The pooled rate of major complications was 6.17% (95% CI: 3.53-10.56%).Overall median survival was 14.39 months for HCC patients with MVI following resection. Median survival was higher in PVTT with segmental/2nd order involvement at 20.41 versus 6.41 months if the main trunk was involved.

    View details for DOI 10.21037/hbsn-21-419

    View details for PubMedID 36523924

    View details for PubMedCentralID PMC9745615

  • The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: I-Methodology for the development of consensus practice guidelines. Pediatric transplantation Wilkinson, J. D., Allen, U., Green, M., Dipchand, A. I., Dharnidharka, V. R., Esquivel, C. O., Maecker-Kolhoff, B., Preiksaitis, J., Swerdlow, S. H., Webber, S. A., IPTA Pediatric PTLD Consensus Guidelines Conference 2022: e14333

    Abstract

    The International Pediatric Transplant Association (IPTA) Consensus Conference on Practice Guidelines for the Diagnosis, Prevention, and Management of Post-Transplant Lymphoproliferative Disorders after Solid Organ Transplantation in Children took place on March 12-13, 2019, and the work of conference members continued until the end of December 2021. The goal was to produce evidence-based consensus guidelines on the definitions, diagnosis, prevention, and management of PTLD and related disorders based on the critical review of the literature and consensus of experts. This report describes the goals, organization, and methodology of the consensus conference and follow-up activities. The results of each working group (Definitions, Prevention, Management, and Epstein-Barr viral [EBV] load/Biomarker Monitoring) are presented in separate manuscripts within this volume of Pediatric Transplantation.

    View details for DOI 10.1111/petr.14333

    View details for PubMedID 36369733

  • The IPTA Nashville consensus conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: II-consensus guidelines for prevention. Pediatric transplantation Green, M., Squires, J. E., Chinnock, R. E., Comoli, P., Danziger-Isakov, L., Dulek, D. E., Esquivel, C. O., Hocker, B., L'Huillier, A. G., Mazariegos, G. V., Visner, G. A., Bollard, C. M., Dipchand, A. I., Ferry, J. A., Gross, T. G., Hayashi, R., Maecker-Kolhoff, B., Marks, S., Martinez, O. M., Metes, D. M., Michaels, M. G., Preiksaitis, J., Smets, F., Swerdlow, S. H., Trappe, R. U., Wilkinson, J. D., Allen, U., Webber, S. A., Dharnidharka, V. R. 2022: e14350

    Abstract

    The International Pediatric Transplant Association (IPTA) convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorder after solid organ transplantation in children. In this report from the Prevention Working Group, we reviewed the existing literature regarding immunoprophylaxis and chemoprophylaxis, and pre-emptive strategies. While the group made a strong recommendation for pre-emptive reduction of immunosuppression at the time of EBV DNAemia (low to moderate evidence), no recommendations for use could be made for any prophylactic strategy or alternate pre-emptive strategy, largely due to insufficient or conflicting evidence. Current gaps and future research priorities are highlighted.

    View details for DOI 10.1111/petr.14350

    View details for PubMedID 36369745

  • ANTIVIRAL THERAPY IS SEVERELY UNDERUTILIZED IN HEPATITIS B-AND HEPATITIS C-ASSOCIATED HEPATOCELLULAR CARCINOMA AFTER LIVER RESECTION: A REAL-HCC STUDY Huang, D., Kamal, R., Bonham, C., Tsai, P., Toyoda, H., Yeh, M., Yeh, M., Yasuda, S., Leong, J., Hoang, J., Maeda, M., Huang, C., Jun, D., Ishigami, M., Tanaka, Y., Uojima, H., Ogawa, E., Abe, H., Hsu, Y., Tseng, C., Yoshimaru, Y., Suzuki, T., Liu, J., Landis, C., Dai, C., Huang, J., Chuang, W., Schwartz, M. E., Dan, Y., Esquivel, C. O., Yu, M., Nguyen, M. H. WILEY. 2022: S1423-S1424
  • Exploring the Lower Weight Limit of Splitable Liver Grafts for Pediatric Recipients. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Stoltz, D. J., Esquivel, C. O., Gallo, A. E. 2022

    View details for DOI 10.1002/lt.26577

    View details for PubMedID 36168274

  • Has the Risk of Liver Re-Transplantation Improved Over the Two Decades? A UNOS Data Analysis Kim, M. H., Melcher, M. L., Kirchner, V. A., Gallo, A. E., Bonham, C. A., Esquivel, C., Sasaki, K. LIPPINCOTT WILLIAMS & WILKINS. 2022: S294
  • Evolution of Thromboelastography Parameters During Pediatric Liver Transplantation Damian, M. I., Tawfik, D., Mendoza, J., Gallo, A., Esquivel, C. LIPPINCOTT WILLIAMS & WILKINS. 2022: S452-S453
  • Utilization and outcomes of hepatitis B-positive grafts in orthotopic liver transplantation in the United States, 1999-2021. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Ali, S. E., Vutien, P., Bonham, C. A., Landis, C., Kwo, P., Esquivel, C., Nguyen, M. H. 2022

    Abstract

    The demand for orthotopic liver transplants (OLT) is projected to increase which indicates a need to expand the liver donor pool. We aimed to investigate the utilization of hepatitis B (HBV)-positive graft utilization and the outcomes of recipients undergoing orthotopic liver transplant (OLT) with HBV-positive grafts.We conducted a retrospective cohort study analyzing all deceased donors and OLT recipients in the Organ Procurement and Transplantation Network database from January 1999 through March 2021. Donor HBV status was positive if HBsAg was positive or HBV nucleic acid testing was detectable. Recipients of HBV-positive allografts were matched 1:5 to recipients of HBV-negative allografts based on recipient and donor age, transplant year, recipient gender, donation after circulatory death, recipient location, and MELD score at transplant.Among the 185,212 potential donors, 422(0.2%) were HBV-positive and 265(63%) of the HBV-positive grafts were transplanted (14 of 265[5.3%] in HBV-positive recipients). The overall discard rate for HBV-positive donors of 37.2% (157/422) remained significantly higher than the discard rate for HBV-negative donors of 26.5% (49,026/185,212) during the study period (p < 0.001). Recipients of HBV-positive (n = 209) had similar mortality (log-rank, p=0.47) and graft loss (log-rank, p=0.72) to matched recipients of HBV-negative allografts (n = 1,045). The 3-year graft survival was 77.9% for the HBV-positive group and 79.7% in the matched HBV-negative group.Based on this analysis, transplant recipients of HBV-positive liver allografts do not experience increased rates of mortality or graft loss. Utilizing these HBV-positive allografts is one strategy that may help expand the donor pool and lower the waiting-list mortality rate.

    View details for DOI 10.1002/lt.26543

    View details for PubMedID 35844046

  • Outcomes after liver transplantation in MPV17 deficiency (Navajo neurohepatopathy): A single-center case series. Pediatric transplantation Huang, A. C., Ebel, N. H., Romero, D., Martin, B., Jhun, I., Brown, M., Enns, G. M., Esquivel, C., Bonham, C. 2022: e14274

    Abstract

    BACKGROUND: MPV17-related mitochondrial DNA maintenance defect (MPV17 deficiency) is a rare, autosomal recessive mitochondrial DNA depletion syndrome with a high mortality rate in infancy and early childhood due to progression to liver failure. Liver transplantation for children with MPV17 deficiency has been considered controversial due to uncertainty about the potential progression of extrahepatic manifestations following liver transplantation.METHODS: We describe our institution's experience for two infants diagnosed with infantile MPV17 deficiency who presented in acute on chronic liver failure, but with normal development and normal neurological status who successfully underwent liver transplantation.RESULTS: Both patients underwent successful liver transplantation with normal development and neurological status at 3years and 16months post-transplant, respectively.CONCLUSIONS: In this rare disease population, we describe two infants with MPV17 deficiency who underwent liver transplantation for acute on chronic liver failure who continue to have normal development, without progression of neurological disease. MPV17 deficiency should not be considered a contraindication to liver transplantation.

    View details for DOI 10.1111/petr.14274

    View details for PubMedID 35466509

  • Human IL-10-producing B cells have diverse states that are induced from multiple B cell subsets. Cell reports Glass, M. C., Glass, D. R., Oliveria, J. P., Mbiribindi, B., Esquivel, C. O., Krams, S. M., Bendall, S. C., Martinez, O. M. 2022; 39 (3): 110728

    Abstract

    Regulatory B cells (Bregs) suppress immune responses through the secretion of interleukin-10 (IL-10). This immunomodulatory capacity holds therapeutic potential, yet a definitional immunophenotype for enumeration and prospective isolation of B cells capable of IL-10 production remains elusive. Here, we simultaneously quantify cytokine production and immunophenotype in human peripheral B cells across a range of stimulatory conditions and time points using mass cytometry. Our analysis shows that multiple functional B cell subsets produce IL-10 and that no phenotype uniquely identifies IL-10+ B cells. Further, a significant portion of IL-10+ B cells co-express the pro-inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNFα). Despite this heterogeneity, operationally tolerant liver transplant recipients have a unique enrichment of IL-10+, but not TNFα+ or IL-6+, B cells compared with transplant recipients receiving immunosuppression. Thus, human IL-10-producing B cells constitute an induced, transient state arising from a diversity of B cell subsets that may contribute to maintenance of immune homeostasis.

    View details for DOI 10.1016/j.celrep.2022.110728

    View details for PubMedID 35443184

  • Mutations in latent membrane protein 1 of Epstein Barr virus are associated with increased risk of post-transplant lymphoproliferative disorder Martinez, O. M., Krams, S. M., Robien, M., Lapasaran, M. M., Arvedson, M., Reitsma, A., Weinberg, K., Boyd, S., Armstrong, B., Twist, C., Gratzinger, D., Tan, B., Trickey, A., Sever, M., Brown, M., Bernstein, D., Esquivel, C., CTOC 06 Investigators WILEY. 2022
  • Quality improvement project to safely expedite liver biopsy in pediatric acute liver failure Mendoza, J., Ebel, N. H., Josephs, S., Wolke, O., Depper, J., Bonham, C. A., Damian, M. A., Esquivel, C. O., Gallo, A. WILEY. 2022
  • Re-transplantation in pediatric liver transplant: Indicators of intra-operative mortality Brubaker, A., Mendoza, J., Bonham, C. A., Damian, M. A., Esquivel, C. O., Gallo, A. E. WILEY. 2022
  • Underutilized technical variant liver grafts show equal graft survival to whole liver grafts in pediatric liver transplantation Stoltz, D., Bonham, A., Lum, G., Ebel, N., Mendoza, J., Esquivel, C., Gallo, A. WILEY. 2022
  • Towards identifying predictors of pediatric heart only versus combined heart liver transplantation Zhang, K., Chen, S., Syed, A., Gallo, A., Esquivel, C., Bonham, A., Hollander, S. A., Ma, M., Han, J., Ebel, N. H. WILEY. 2022
  • Advanced quantitative 3D modeling techniques provide accurate liver volume estimations for children on the waitlist Sanchez-Garcia, J., Lopez-Verdugo, F., Kastenberg, Z., Gagnon, A., Shorti, R., Krong, J., Fujita, S., Alonso, D., Zendejas, I., Esquivel, C. O., Rodriguez-Davalos, M. I. WILEY. 2022
  • Age at the time of liver transplant and its effect on quality of life, anxiety, and depression in adolescent patients Marshall, A., Mandac, C., Boothroyd, D., Qin, F., McKenzie, R., Esquivel, C. O., Nasr, A. WILEY. 2022
  • Neurologic complications in en bloc pediatric heart-liver transplants Pan, J., Bensen, R., Ebel, N., Mendoza, J., Ma, M., Hollander, S., Gallo, A., Esquivel, C. O., Bonham, A. WILEY. 2022
  • Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients HEPATOBILIARY SURGERY AND NUTRITION Huang, D. Q., Tran, A., Tan, E. X., Nerurkar, S. N., Teh, R., Teng, M. P., Yeo, E., Zou, B., Wong, C., Esquivel, C. O., Bonham, C., Nguyen, M. H. 2022
  • Global and regional long-term survival following resection for HCC in the recent decade: A meta-analysis of 110 studies. Hepatology communications Reveron-Thornton, R. F., Teng, M. L., Lee, E. Y., Tran, A., Vajanaphanich, S., Tan, E. X., Nerurkar, S. N., Ng, R. X., Teh, R., Tripathy, D. P., Ito, T., Tanaka, T., Miyake, N., Zou, B., Wong, C., Toyoda, H., Esquivel, C. O., Bonham, C. A., Nguyen, M. H., Huang, D. Q. 2022

    Abstract

    Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have improved over time. We aimed to estimate pooled overall survival (OS), recurrence-free survival (RFS), and complication rates in patients with hepatocellular carcinoma (HCC) following curative surgical resection and to compare outcomes by region and by time period. In this systematic review and meta-analysis, we searched Pubmed, Embase, and Cochrane databases from inception to May 15, 2020. We selected studies reporting OS, RFS, and complications in adult patients with HCC undergoing curative surgical resection. Two authors independently searched the literature and extracted the data. We screened 6983 articles and included 110 eligible studies with 82,392 patients, with study periods spanning from 1980-2017. The global pooled 1-year and 5-year survival rates were 88.9% (95% confidence interval [CI] 87.1-90.4) and 56.2% (95% CI 52.8-59.6) for OS and 71.1% (95% CI 67.6-74.3) and 35.2% (95% CI 32.5-38.0) for RFS, respectively. Five-year OS was higher in Asia (57.03%) than in other regions (Europe 48.3%; North America 48.0%; and South America 49.5%); p=0.002. Five-year RFS was higher in patients with hepatitis B virus versus patients with hepatitis C virus (34.8% vs. 24.1%; p=0.02). There was no significant improvement in 5-year OS and RFS over time. The pooled rate for complications was 27.6% (95% CI 23.4-32.3), with 9.7% (95% CI 6.3-14.7) classified as major. One-year OS after surgical resection for HCC is excellent (~90%). However, 5-year OS (~55%) and RFS (~35%) are still poor, suggesting that long-term care is suboptimal. Greater efforts are required to improve survival through enhanced surveillance and preventing recurrence through antiviral therapy.

    View details for DOI 10.1002/hep4.1923

    View details for PubMedID 35234371

  • Host microRNAs are decreased in pediatric solid-organ transplant recipients during EBV+ Post-transplant Lymphoproliferative Disorder. Frontiers in immunology Sen, A., Enriquez, J., Rao, M., Glass, M., Balachandran, Y., Syed, S., Twist, C. J., Weinberg, K., Boyd, S. D., Bernstein, D., Trickey, A. W., Gratzinger, D., Tan, B., Lapasaran, M. G., Robien, M. A., Brown, M., Armstrong, B., Desai, D., Mazariegos, G., Chin, C., Fishbein, T. M., Venick, R. S., Tekin, A., Zimmermann, H., Trappe, R. U., Anagnostopoulos, I., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2022; 13: 994552

    Abstract

    Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Predisposing factors include primary Epstein-Barr virus (EBV) infection, reactivation of EBV in recipient B cells, and decreased T cell immunity due to immunosuppression. In our previous studies EBV infection was demonstrated to markedly alter the expression of host B cell microRNA (miR). Specifically, miR-194 expression was uniquely suppressed in EBV+ B cell lines from PTLD patients and the 3'untranslated region of IL-10 was determined to be targeted by miR-194. Although EBV has been shown to regulate host miR expression in B cell lymphoma cell lines, the expression of miRs in the circulation of patients with EBV-associated PTLD has not been studied. The objective of this study was to determine if changes in miR expression are associated with EBV+ PTLD. In this study, we have shown that miR-194 is significantly decreased in EBV+PTLD tumors and that additional miRs, including miRs-17, 19 and 106a are also reduced in EBV+PTLD as compared to EBV-PTLD. We quantitated the levels of miRs-17, 19, 106a, 155, and 194 in the plasma and extracellular vesicles (EV; 50-70 nm as determined by nanoparticle tracking analysis) from pediatric recipients of solid organ transplants with EBV+ PTLD+ that were matched 1:2 with EBV+ PTLD- pediatric transplant recipients as part of the NIH-sponsored Clinical Trials in Organ Transplantation in Children, (CTOTC-06) study. Levels of miRs-17, 19, 106a, and 194 were reduced in the plasma and extracellular vesicles (EV) of EBV+ PTLD+ group compared to matched controls, with miRs-17 (p = 0.034; plasma), miRs-19 (p = 0.029; EV) and miR-106a (p = 0.007; plasma and EV) being significantly reduced. Similar levels of miR-155 were detected in the plasma and EV of all pediatric SOT recipients. Importantly, ~90% of the cell-free miR were contained within the EV supporting that EBV+ PTLD tumor miR are detected in the circulation and suggesting that EVs, containing miRs, may have the potential to target and regulate cells of the immune system. Further development of diagnostic, mechanistic and potential therapeutic uses of the miRs in PTLD is warranted.

    View details for DOI 10.3389/fimmu.2022.994552

    View details for PubMedID 36304469

  • Underutilized technical variant liver grafts show equal graft survival to whole liver grafts in pediatric liver transplantation Gallo, A., Brubaker, A., Lum, G., Esquivel, C., Bonham, A. WILEY. 2022: 89
  • Neurologic complications in en bloc pediatric heart-liver transplants Pan, J., Bensen, R., Ebel, N., Mendoza, J., Ma, M., Hollander, S., Gallo, A., Esquivel, C., Bonham, A. WILEY. 2022: 80
  • OVERALL (OS) AND RECURRENCE-FREE SURVIVAL (RFS) FOLLOWING SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA (HCC) WITH MACROVASCULAR INVASION (MVI): A META-ANALYSIS OF 40 STUDIES AND 8,218 PATIENTS Huang, D., Tran, A., Tan, X., Quek, S., Nerurkar, S., Teh, R., Teng, M., Yeo, E., Zou, B., Wong, C., Cheung, R. C., Esquivel, C. O., Bonham, A., Nguyen, M. H. WILEY. 2021: 861A
  • META-ANALYSIS: REGIONAL DIFFERENCES IN OUTCOMES OF SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA Teng, M., Reveron-Thornton, R., Lee, E. Y., Tran, A., Vajanaphanich, S., Tan, X., Nerurkar, S. N., Ng, R., Teh, R., Prasad, D., Ito, T., Tanaka, T., Miyake, N., Zou, B., Wong, C., Toyoda, H., Esquivel, C. O., Bonham, A., Nguyen, M. H., Huang, D. WILEY. 2021: 859A
  • LONG-TERM OVERALL AND RECURRENCE-FREE SURVIVAL FOLLOWING CURATIVE SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA IN THE RECENT DECADE: A META-ANALYSIS OF 110 STUDIES AND 82,392 PATIENTS Reveron-Thornton, R., Teng, M., Lee, E. Y., Tran, A., Vajanaphanich, S., Tan, X., Nerurkar, S. N., Ng, R., Teh, R., Prasad, D., Ito, T., Tanaka, T., Miyake, N., Zou, B., Wong, C., Toyoda, H., Esquivel, C. O., Bonham, A., Nguyen, M. H., Huang, D. WILEY. 2021: 655A-656A
  • UTILIZATION AND OUTCOMES OF HEPATITIS B-POSITIVE GRAFTS IN ORTHOTOPIC LIVER TRANSPLANTATION (OLT) IN THE UNITED STATES, 1987-2020 Ali, S., Vutien, P., Bonham, C., Landis, C., Kwo, P., Esquivel, C. O., Nguyen, M. H. WILEY. 2021: 919A-920A
  • Predictors of Outcomes of Patients Referred to a Transplant Center for Urgent Liver Transplantation Evaluation. Hepatology communications Alshuwaykh, O., Kwong, A., Goel, A., Cheung, A., Dhanasekaran, R., Ahmed, A., Daugherty, T., Dronamraju, D., Kumari, R., Kim, W. R., Nguyen, M. H., Esquivel, C. O., Concepcion, W., Melcher, M., Bonham, A., Pham, T., Gallo, A., Kwo, P. Y. 2021; 5 (3): 516-525

    Abstract

    Liver transplantation (LT) is definitive treatment for end-stage liver disease. This study evaluated factors predicting successful evaluation in patients transferred for urgent inpatient LT evaluation. Eighty-two patients with cirrhosis were transferred for urgent LT evaluation from January 2016 to December 2018. Alcohol-associated liver disease was the common etiology of liver disease (42/82). Of these 82 patients, 35 (43%) were declined for LT, 27 (33%) were wait-listed for LT, 5 (6%) improved, and 15 (18%) died. Psychosocial factors were the most common reasons for being declined for LT (49%). Predictors for listing and receiving LT on multivariate analysis included Hispanic race (odds ratio [OR], 1.89; P = 0.003), Asian race (OR, 1.52; P = 0.02), non-Hispanic ethnicity (OR, 1.49; P = 0.04), hyponatremia (OR, 1.38; P = 0.04), serum albumin (OR, 1.13; P = 0.01), and Model for End-Stage Liver Disease (MELD)-Na (OR, 1.02; P = 0.003). Public insurance (i.e., Medicaid) was a predictor of not being listed for LT on multivariate analysis (OR, 0.77; P = 0.02). Excluding patients declined for psychosocial reasons, predictors of being declined for LT on multivariate analysis included Chronic Liver Failure Consortium (CLIF-C) score >51.5 (OR, 1.26; P = 0.03), acute-on-chronic liver failure (ACLF) grade 3 (OR, 1.41; P = 0.01), hepatorenal syndrome (HRS) (OR, 1.38; P = 0.01), and respiratory failure (OR, 1.51; P = 0.01). Predictors of 3-month mortality included CLIF-C score >51.5 (hazard ratio [HR], 2.52; P = 0.04) and intensive care unit (HR, 8.25; P < 0.001). Conclusion: MELD-Na, albumin, hyponatremia, ACLF grade 3, HRS, respiratory failure, public insurance, Hispanic race, Asian race, and non-Hispanic ethnicity predicted liver transplant outcome. Lack of psychosocial support was a major reason for being declined for LT. The CLIF-C score predicted being declined for LT and mortality.

    View details for DOI 10.1002/hep4.1644

    View details for PubMedID 33681683

    View details for PubMedCentralID PMC7917272

  • High-resolution phenotyping of early acute rejection reveals a conserved alloimmune signature. Cell reports Harden, J. T., Wang, X. n., Toh, J. n., Sang, A. X., Brown, R. A., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2021; 34 (9): 108806

    Abstract

    Alloimmune responses in acute rejection are complex, involving multiple interacting cell types and pathways. Deep profiling of these cell types has been limited by technology that lacks the capacity to resolve this high dimensionality. Single-cell mass cytometry is used to characterize the alloimmune response in early acute rejection, measuring 37 parameters simultaneously, across multiple time points in two models: a murine cardiac and vascularized composite allotransplant (VCA). Semi-supervised hierarchical clustering is used to group related cell types defined by combinatorial expression of surface and intracellular proteins, along with markers of effector function and activation. This expression profile is mapped to visualize changes in antigen composition across cell types, revealing phenotypic signatures in alloimmune T cells, natural killer (NK) cells, and myeloid subsets that are conserved and that firmly distinguish rejecting from non-rejecting grafts. These data provide a comprehensive, high-dimensional profile of cellular rejection after allograft transplantation.

    View details for DOI 10.1016/j.celrep.2021.108806

    View details for PubMedID 33657374

  • Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation. Annals of surgery Turgeon, M. K., Shah, S. A., Delman, A. M., Tran, B. V., Agopian, V. G., Wedd, J. P., Magliocca, J. F., Kim, A., Cameron, A., Olyaei, A., Orloff, S. L., Anderson, M. P., Kubal, C. A., Cannon, R. M., Locke, J. E., Simpson, M. A., Akoad, M. E., Wongjirad, C. P., Emamaullee, J., Moro, A., Aucejo, F., Feizpour, C. A., Vagefi, P. A., Nguyen, M. H., Esquivel, C. O., Dhanireddy, K., Subramanian, V., Chavarriaga, A., Kazimi, M. M., Anderson, M. S., Sonnenday, C. J., Kim, S. C., Foley, D. P., Abdouljoud, M., Salgia, R. J., Moris, D., Sudan, D. L., Ganesh, S. R., Humar, A., Doyle, M., Chapman, W. C., Maithel, S. K. 2021; 274 (4): 613-620

    Abstract

    To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT).In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate.The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS).Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01).The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

    View details for DOI 10.1097/SLA.0000000000005070

    View details for PubMedID 34506316

  • Operative Technique of Donor Organ Procurement for En Bloc Heart-Liver Transplantation. Transplantation Elde, S. n., Brubaker, A. L., Than, P. A., Rinewalt, D. n., MacArthur, J. W., Alassar, A. n., Bonham, C. A., Esquivel, C. O., Shudo, Y. n., Concepcion, W. n., Woo, Y. J. 2021

    Abstract

    Combined heart-liver transplant is an emerging option for patients with indications for heart transplantation and otherwise prohibitive hepatic dysfunction. Heart-liver transplantation is particularly relevant for patients with single ventricle physiology who often develop Fontan-associated liver disease and fibrosis. While only performed at a limited number of centers, several approaches to combined heart-liver transplantation have been described. The en bloc technique offers several potential advantages over the traditional sequential technique. Specifically, en bloc heart-liver transplantation may allow improved hemodynamics, decreased bleeding, reduced liver allograft ischemic time, and may result in reduced rates of graft dysfunction. Here we describe our center's en bloc heart-liver procurement technique in detail, with the aim of allowing broader use and standardization of this technique. Supplemental Visual Abstract; http://links.lww.com/TP/C147.

    View details for DOI 10.1097/TP.0000000000003697

    View details for PubMedID 33606485

  • Predictors of Outcomes of Patients Referred to a Transplant Center for Urgent Liver Transplantation Evaluation HEPATOLOGY COMMUNICATIONS Alshuwaykh, O., Kwong, A., Goel, A., Cheung, A., Dhanasekaran, R., Ahmed, A., Daugherty, T., Dronamraju, D., Kumari, R., Kim, W., Esquivel, C. O., Concepcion, W., Melcher, M., Bonham, A., Pham, T., Gallo, A., Kwo, P. 2020

    View details for DOI 10.1002/hep4.1644

    View details for Web of Science ID 000602465100001

  • Epstein-Barr virus peptides derived from latent cycle proteins alter NKG2A+NK cell effector function. Scientific reports Mbiribindi, B., Pena, J. K., Arvedson, M. P., Moreno Romero, C., McCarthy, S. R., Hatton, O. L., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2020; 10 (1): 19973

    Abstract

    Natural killer (NK) cells control viral infection through the interaction between inhibitory receptors and human leukocyte antigen (HLA) ligands and bound peptide. NK cells expressing the inhibitory receptor NKG2A/CD94 recognize and respond to autologous B cells latently infected with Epstein-Barr virus (EBV). The mechanism is not yet understood, thus we investigated peptides derived from seven latent proteins of EBV in the interaction of NKG2A and its ligand HLA-E. Functional analysis demonstrated that EBV peptides can bind to HLA-E and block inhibition of NK cell effector function. Moreover, analysis of DNA from 79 subjects showed sequence variations in the latent protein, LMP1, which alters NK responses to EBV. We provide evidence that peptides derived from EBV latent cycle proteins can impair the recognition of NKG2A despite being presented by HLA-E, resulting in NK cell activation.

    View details for DOI 10.1038/s41598-020-76344-3

    View details for PubMedID 33203899

  • PERIOPERATIVE MANAGEMENT AND POST-LIVER TRANSPLANTATION OUTCOMES IN UREA CYCLE DISORDERS, MAPLE SYRUP URINE DISEASE AND ORGANIC ACIDEMIAS: 20 YEARS' EXPERIENCE Ebel, N., Vuong, P., Baker, C., Brubaker, A., Than, P., Enns, G., Esquivel, C. O. WILEY. 2020: 881A–882A
  • PERIOPERATIVE MANAGEMENT AND POST-LIVER TRANSPLANTATION OUTCOMES IN METHYLMALONIC ACIDEMIA, PROPIONIC ACIDEMIA AND UREA CYCLE DISORDERS: OUR 20 YEAR EXPERIENCE Vuong, P., Ebel, N., Baker, C. V., Brubaker, A., Than, P., Enns, G., Esquivel, C. O. LIPPINCOTT WILLIAMS & WILKINS. 2020: S547
  • The Emerging Need for Combined Heart and Liver Transplantation in Congenital Heart Disease CURRENT TRANSPLANTATION REPORTS Than, P. A., Brubaker, A. L., Ebel, N. H., Profita, E. L., Esquivel, C. O. 2020; 7 (3): 180-186
  • EXTRACORPOREAL PHOTOPHERESIS: TREATMENT FOR STEROID RESISTANT REJECTION IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS Depper, J., North, L., Mandac, C. A., Marshall, A. F., Schwartz, S., Mock, A., Sutherland, S., Esquivel, C. O., Bonham, C. LIPPINCOTT WILLIAMS & WILKINS. 2020: S550
  • LONG-TERM OUTCOMES OF PEDIATRIC LIVER TRANSPLANTATION FOR PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS Vuong, P., Lee, L., Brubaker, A., Than, P., Gallo, A., Esquivel, C., Bonham, C. LIPPINCOTT WILLIAMS & WILKINS. 2020: S557
  • Early Impact of COVID-19 on Solid Organ Transplantation in the United States. Transplantation Cholankeril, G., Podboy, A., Alshuwaykh, O. S., Kim, D., Kanwal, F., Esquivel, C. O., Ahmed, A. 2020

    Abstract

    BACKGROUND: The regional impact of COVID-19 on solid organ transplantation in the United States (US) has not been fully evaluated.METHODS: A retrospective analysis of month-to-month trends on waitlist additions, waitlist deaths, and transplant surgeries between all United Network for Organ Sharing (UNOS) regions was performed. A linear regression model trained on historical data was used to estimate anticipated transplantation volume.RESULTS: All UNOS Regions reported a decrease in total waitlist additions and transplant surgeries. The largest decreases in total transplants were identified in Regions 1,2,6 and 9; with Regions 2, 7, 8 and 9 noting the largest decrease in waitlist additions. Six of the 11 regions noted increases in waitlist deaths, with UNOS Regions 9, 1, and 2, all located within the Northeast, noting the highest percent increase in waitlist deaths at 170%, 89%, and 54%, respectively. The largest reductions in SOT and waitlist deaths were seen in kidney and lung transplantation. Current transplantation volume is significantly lower than the low range of the 95% CI derived from the linear regression model (2182 vs 3110, p<0.05) CONCLUSIONS:: Significant decreases in total waitlist additions and transplant surgeries with increases in waitlist deaths were noted in the majority of US transplant domains. The impact was especially prevalent in areas with high burden of COVID-19 infection. National and regional strategies aimed at minimizing disruptions in transplantation are needed.

    View details for DOI 10.1097/TP.0000000000003391

    View details for PubMedID 32675741

  • Eliminating International Normalized Ratio Threshold for Transfusion in Pediatric Patients with Acute Liver Failure. Clinical transplantation Lee, A., Mendoza, J., Brubaker, A. L., Stoltz, D. J., McKenzie, R., Bonham, C. A., Esquivel, C. O., Gallo, A. E. 2020

    Abstract

    INTRODUCTION: Transfusion protocols are not well-studied for pediatric patients with acute liver failure (ALF). This study evaluates the utility of an international normalized ratio (INR)-based transfusion threshold for these patients.METHODS: Forty-four ALF pediatric patients from 2009 to 2018 were reviewed and divided into two groups: (1) a threshold group including patients between 2009-2015 who were transfused for an INR above 3.0, per institutional policy (n=30), and (2) a post-threshold group including patients after 2015 through 2018 who were transfused based on clinical judgment (n=14). Preoperative INRs, preoperative transfusions, intraoperative transfusions, early reoperation, renal function, graft function and deaths were compared.RESULTS: Liver failure severity was similar between threshold and post-threshold groups. Threshold patients had a lower average INR prior to transplantation, 2.8 (range 1.8-3.8) versus 4.4 (range 2.1-9.0), respectively (p=0.01). Twenty-six threshold patients (87%) received preoperative FFP compared to seven post-threshold patients (50%, p=0.0088). Two threshold patients (7%) received preoperative cryoprecipitate compared to five post-threshold patients (36%, p=0.014). The incidence of pre-transplant bleeding, operative transfusions and one-year patient and graft survival did not differ significantly.CONCLUSION: Clinical judgment versus an INR-based threshold for transfusions did not increase perioperative complications in children with ALF.

    View details for DOI 10.1111/ctr.13819

    View details for PubMedID 32037570

  • Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Molecular genetics and metabolism Kripps, K. n., Nakayuenyongsuk, W. n., Shayota, B. J., Berquist, W. n., Gomez-Ospina, N. n., Esquivel, C. O., Concepcion, W. n., Sampson, J. B., Cristin, D. J., Jackson, W. E., Gilliland, S. n., Pomfret, E. A., Kueht, M. L., Pettit, R. W., Sherif, Y. A., Emrick, L. T., Elsea, S. H., Himes, R. n., Hirano, M. n., Van Hove, J. L., Scaglia, F. n., Enns, G. M., Larson, A. A. 2020

    Abstract

    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal disorder characterized by progressive gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, skeletal myopathy, ophthalmoparesis, and ptosis. MNGIE stems from deficient thymidine phosphorylase activity (TP) leading to toxic elevations of plasma thymidine. Hematopoietic stem cell transplant (HSCT) restores TP activity and halts disease progression but has high transplant-related morbidity and mortality. Liver transplant (LT) was reported to restore TP activity in two adult MNGIE patients. We report successful LT in four additional MNGIE patients, including a pediatric patient. Our patients were diagnosed between ages 14 months and 36 years with elevated thymidine levels and biallelic pathogenic variants in TYMP. Two patients presented with progressive gastrointestinal dysmotility, and three demonstrated progressive peripheral neuropathy with two suffering limitations in ambulation. Two patients, including the child, had liver dysfunction and cirrhosis. Following LT, thymidine levels nearly normalized in all four patients and remained low for the duration of follow-up. Disease symptoms stabilized in all patients, with some manifesting improvements, including intestinal function. No patient died, and LT appeared to have a more favorable safety profile than HSCT, especially when liver disease is present. Follow-up studies will need to document the long-term impact of this new approach on disease outcome. Take Home Message: Liver transplantation is effective in stabilizing symptoms and nearly normalizing thymidine levels in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and may have an improved safety profile over hematopoietic stem cell transplant.

    View details for DOI 10.1016/j.ymgme.2020.03.001

    View details for PubMedID 32173240

  • Eliminating INR Thresholds for Transfusion in Pediatric Patients with Fulminant Hepatic Failure Lee, A., Brubaker, A., Stoltz, D., McKenzie, R., Esquivel, C., Mendoza, J., Gallo, A. WILEY. 2020: 71–72
  • Pediatric Liver Retransplantation: 24 Years of Experience from a Single Center Lee, L., Vuong, P., Conlon, S., Esquivel, C. WILEY. 2020: 72
  • Establishment of Heterotopic Hind Limb Transplantation Model in the Mouse. Transplantation proceedings Wang, X. n., Harden, J. T., Sang, A. X., Esquivel, C. O., Martinez, O. n., Krams, S. M. 2020

    Abstract

    The mouse is the most widely used animal for establishing in vivo models in transplant research. However, because of the advanced microsurgical skills required for these operations, the vascularized composite transplantation model in mouse has proven to be technically challenging. The purpose of this report is to describe novel modifications in surgical techniques to establish a consistent and reliable mouse model of hind limb transplantation.Forty C57BL/6 male mice, half as donors and half as recipients, were used in this study. The donor hind limb was harvested and transplanted into the recipient's ipsilateral cervical region by anastomosing the donor femoral artery to the recipient common carotid artery with a modified sleeve technique. The donor femoral vein was mounted with a modified cuff and inserted into the recipient external jugular vein. The graft was evaluated at 2 weeks postoperatively.The modified cuff and modified sleeve technique facilitated anastomoses. The time spent on either of the donor operation and recipient operation was about 45 minutes. The graft survival rate was 80% (16 of 20) at 2 weeks after transplant. There was minimal blood loss and no infections were noted.Revised surgical techniques using a modified cuff proved to be a safe, reliable, and reproducible strategy in establishing a mouse model of hind limb heterotopic transplantation. The consistent graft survival in this syngeneic study demonstrates that this model can serve as a useful tool for further studies in vascularized composite transplantation.

    View details for DOI 10.1016/j.transproceed.2020.10.039

    View details for PubMedID 33341263

  • Genomic variations in EBNA3C of EBV associate with posttransplant lymphoproliferative disorder. JCI insight Maloney, E. M., Busque, V. A., Hui, S. T., Toh, J. n., Fernandez-Vina, M. n., Krams, S. M., Esquivel, C. O., Martinez, O. M. 2020; 5 (6)

    Abstract

    Epstein-Barr Virus (EBV) is a ubiquitous virus linked to a variety of lymphoid and epithelial malignancies. In solid organ and hematopoietic stem cell transplant recipients, EBV is causally associated with posttransplant lymphoproliferative disorder (PTLD), a group of heterogeneous lymphoid diseases. EBV+ B cell lymphomas that develop in the context of PTLD are generally attributed to the immunosuppression required to promote graft survival, but little is known regarding the role of EBV genome diversity in the development of malignancy. We deep-sequenced the EBV genome from the peripheral blood of 18 solid organ transplant recipients, including 6 PTLD patients. Sequences from 6 EBV+ spontaneous lymphoblastoid B cell lines (SLCL) were similarly analyzed. The EBV genome from PTLD patients had a significantly greater number of variations than EBV from transplant recipients without PTLD. Importantly, there were 15 nonsynonymous variations, including 8 in the latent cycle gene EBNA3C that were associated with the development of PTLD. One of the nonsynonymous variations in EBNA3C is located within a previously defined T cell epitope. These findings suggest that variations in the EBV genome can contribute to the pathogenesis of PTLD.

    View details for DOI 10.1172/jci.insight.131644

    View details for PubMedID 32213705

  • THE ROLE OF LOCOREGIONAL THERAPY (LRT), POST LRT IMAGING, AND EXPLANT PATHOLOGY AS PREDICTORS OF HEPATOCELLULAR CARCINOMA (HCC) RECURRENCE POST ORTHOTOPIC LIVER TRANSPLANT (OLT) Prabhakar, V., Dhanasekaran, R., Arjunan, V., Tulu, Z., Ahmed, A., Daugherty, T., Kumari, R., Patel, B., Kim, W., Goel, A., Esquivel, C. O., Concepcion, W., Melcher, M., Bonham, C., Gallo, A., Kwo, P. WILEY. 2019: 691A–692A
  • Are two operations better than one? The debate over combined versus sequential liver-kidney transplantation from a single live donor in the treatment of primary hyperoxaluria 1 PEDIATRIC TRANSPLANTATION Pham, T. A., Esquivel, C. 2019; 23 (4)

    View details for DOI 10.1111/petr.13457

    View details for Web of Science ID 000470844700016

  • Differential role of natural killer group 2D in recognition and cytotoxicity of hepatocyte-like cells derived from embryonic stem cells and induced pluripotent stem cells AMERICAN JOURNAL OF TRANSPLANTATION Cisneros, T., Dillard, D. W., Qu, X., Arredondo-Guerrero, J., Castro, M., Schaffert, S., Martin, R., Esquive, C. O., Krams, S. M., Martinez, O. M. 2019; 19 (6): 1652–62

    View details for DOI 10.1111/ajt.15217

    View details for Web of Science ID 000469275600010

  • Are two operations better than one? The debate over combined versus sequential liver-kidney transplantation from a single live donor in the treatment of primary hyperoxaluria 1. Pediatric transplantation Pham, T. A., Esquivel, C. 2019: e13457

    View details for PubMedID 31081215

  • Dual blockade of the PI3K/Akt/mTOR pathway inhibits posttransplant Epstein-Barr virus B cell lymphomas and promotes allograft survival AMERICAN JOURNAL OF TRANSPLANTATION Sang, A. X., McPherson, M. C., Ivison, G. T., Qu, X., Rigdon, J., Esquivel, C. O., Krams, S. M., Martinez, O. M. 2019; 19 (5): 1305–14

    View details for DOI 10.1111/ajt.15216

    View details for Web of Science ID 000471342300010

  • Genomic diversity of Epstein-Barr Virus in post-transplant lymphoproliferative disorder Martinez, O., Maloney, E., Busque, V., Hui, S., Esquivel, C. O., Krams, S. WILEY. 2019
  • Liver transplantation for acute liver failure in neonatal enteroviral sepsis Mandac, C., Schwartz, S. R., Concepcion, W., Gallo, A., Burgis, J., Berquist, W., Esquivel, C., Bonham, A. WILEY. 2019
  • The impact of intraoperative thromboelastography and blood product utilization during pediatric liver transplantation in a single center Ruiz, R., Lee, H., Mendoza, J., Burgis, J. C., Damian, M., Esquivel, C. O., Jeng, M. WILEY. 2019
  • LIVER TRANSPLANTATION IN MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALMYOPATHY (MNGIE) Kripps, K., Larson, A., Nakayuenyongsuk, W., Berquist, W., Ospina, N., Esquivel, C., Concepcion, W., Van Hove, J. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2019: 280–81
  • Differential role of natural killer group 2D in recognition and cytotoxicity of hepatocyte-like cells derived from embryonic stem cells and induced pluripotent stem cells. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Cisneros, T., Dillard, D. W., Qu, X., Arredondo-Guerrero, J., Castro, M., Schaffert, S., Martin, R., Esquivel, C. O., Krams, S. M., Martinez, O. M. 2018

    Abstract

    Stem cell-based approaches have the potential to address the organ shortage in transplantation. Whereas both embryonic stem cells and induced pluripotent stem cells have been utilized as cellular sources for differentiation and lineage specification, their relative ability to be recognized by immune effector cells is unclear. We determined the expression of immune recognition molecules on hepatocyte-like cells (HLC) generated from murine embryonic stem cells and induced pluripotent stem cells, compared to adult hepatocytes, and we evaluated the impact on recognition by NK cells. We report that HLC lack MHC class I expression, and that embryonic stem cell derived-HLC have higher expression of the NK cell activating ligands Rae1, H60, and Mult1 than induced pluripotent stem cell-derived HLC and adult hepatocytes. Moreover, the lack of MHC class I render embryonic stem cell derived-HLC, and induced pluripotent stem cell derived-HLC, susceptible to killing by syngeneic and allogeneic NK cells. Both embryonic stem cell derived-HLC, and induced pluripotent stem cell derived-HLC, are killed by NK cells at higher levels than adult hepatocytes. Finally, we demonstrate that the NK cell activation receptor, NKG2D, plays a key role in NK cell cytotoxicity of embryonic stem cell derived-HLC, but not induced pluripotent stem cell-derived HLC. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30549427

  • Dual blockade of the PI3K/Akt/mTOR pathway inhibits post-transplant Epstein-Barr virus B cell lymphomas and promotes allograft survival. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Sang, A. X., McPherson, M. C., Ivison, G. T., Qu, X., Rigdon, J., Esquivel, C. O., Krams, S. M., Martinez, O. M. 2018

    Abstract

    Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation that often manifests as Epstein-Barr virus (EBV)-associated B cell lymphomas. Current treatments for PTLD have limited efficacy and can be associated with graft rejection or systemic toxicities. The mTOR inhibitor, rapamycin, suppresses tumor growth of EBV+ B cell lymphoma cells in vitro and in vivo; however, the efficacy is limited and clinical benefits of mTOR inhibitors for PTLD are variable. Here, we show constitutive activation of multiple nodes within the PI3K/Akt/mTOR pathway in EBV+ PTLD-derived cell lines. Inhibition of either PI3K or Akt, with specific inhibitors CAL-101 and MK-2206, respectively, diminished growth of EBV+ B cell lines from PTLD patients in a dose-dependent manner. Importantly, rapamycin combined with CAL-101 or MK-2206 had a synergistic effect in suppressing cell growth as determined by IC50 isobolographic analysis and Loewe indices. Moreover, these combinations were significantly more effective than rapamycin alone in inhibiting tumor xenograft growth in NOD-SCID mice. Finally, both CAL-101 and MK-2206 also prolonged survival of heterotopic cardiac allografts in C57BL/6 mice. Thus, combination therapy with rapamycin and a PI3K inhibitor, or an Akt inhibitor, can be an efficacious treatment for EBV-associated PTLD, while simultaneously promoting allograft survival. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30549430

  • Orthotopic Liver Transplantation After Stereotactic Body Radiotherapy for Pediatric Hepatocellular Carcinoma with Central Biliary Obstruction and Nodal Involvement. Cureus Chen, E., Rangaswami, A., Esquivel, C. O., Concepcion, W., Lungren, M., Thakor, A. S., Yoo, C. H., Donaldson, S. S., Hiniker, S. M. 2018; 10 (10): e3499

    Abstract

    Here we describe the case of a 10-year-old boy with a history of chronic hepatitis B who was diagnosed with hepatocellular carcinoma (HCC) with a large central hepatic mass and metastatic disease in a celiac lymph node. His tumor wasunresectable, due to location and lack of clear margins, and he could not receive chemotherapy due to elevated bilirubin. He was treated with stereotactic body radiotherapy (SBRT) to the primary site and involved nodal region. After completing radiotherapy, his total bilirubin level fell below 1.0 mg/dL, allowing him to begin systemic therapy with cisplatinand doxorubicin.At threemonths after SBRT, his bilirubin was 0.1 mg/dL, alpha-fetoprotein (AFP) was 88 ng/mL, and imaging demonstrated a decrease in tumor size (total volume 28.7 cc), with no evidence of local or distant disease progression.He then developed distant disease within the liver, but his disease remained controlled at the primary site and nodes that had been treated with SBRT.He underwent orthotopic liver transplantation (OLT) with an uneventful operative course and remains with no evidence of disease at sevenmonths after OLT. This is one of the first reported cases of successful downstaging of pediatric HCC with nodal involvement to allow for OLT, and it argues for consideration of similar patients for OLT.

    View details for PubMedID 30648040

  • Improved Short-Term Survival in HCV Seropositive Kidney Transplant Recipients during the Daa Era in the United States Wong, K., Cholankeril, G., Gadiparthi, C., Somasundar, P., Busque, S., Esquivel, C. O., Ahmed, A. WILEY. 2018: 140A
  • Orthotopic Liver Transplantation After Stereotactic Body Radiotherapy for Pediatric Hepatocellular Carcinoma with Central Biliary obstruction and Nodal Involvement CUREUS Chen, E., Rangaswami, A., Esquivel, C., Concepcion, W., Lungren, M., Thakor, A. S., Yoo, C. H., Donaldson, S. S., Hiniker, S. M. 2018; 10 (10)
  • Prospective Analysis of EBV plus PTLD in a Multi-Center Study of Pediatric Transplant Recipients Martinez, O. M., Krams, S. M., Lapasaran, M., Boyd, S. D., Bernstein, D., Twist, C., Weinberg, K., Gratzinger, D., Tan, B., Armstrong, B., Ikle, D., Brown, M., Robien, M., Esquivel, C. O. LIPPINCOTT WILLIAMS & WILKINS. 2018: S319
  • Genomic Status of the Epstein Barr Virus and Virus-Associated PI3K/Akt/mTOR Pathway Dysregulation in Post-Transplant Lymphoproliferative Disorder McPherson, M., Balachandran, Y., Boyd, S. D., Zimmermann, H., Trappe, R. U., Esquivel, C. O., Krams, S. M., Martinez, O. M. LIPPINCOTT WILLIAMS & WILKINS. 2018: S95
  • Combined En-Bloc Heart Liver Transplantation in Children with Congenital Heart Disease Complicated by Cardiac Cirrhosis Conlon, S., Maeda, K., Reinhartz, O., Hollander, S., Rosenthal, D., Gallo, A., Concepcion, W., Esquivel, C., Bonham, A. LIPPINCOTT WILLIAMS & WILKINS. 2018: S295
  • Delineation of the Viral and Host Cell Genomic Alterations in EBV-positive PTLD Balachandran, Y., McPherson, M., Boyd, S. D., Esquivel, C. O., Krams, S., Martinez, O. M. LIPPINCOTT WILLIAMS & WILKINS. 2018: S319
  • Identifying shared patterns in the T cell receptor repertoire specific to IE-1 CMV Lucia Perez, M., Rubelt, F., Luque, S., Krams, S. M., Esquivel, C. O., Bestard, O., Martinez, O. M. LIPPINCOTT WILLIAMS & WILKINS. 2018: S141
  • Application of Mass Cytometry for Analysis of the Alloimmune Response in a Model of Vascularized Composite Allotransplantation Harden, J. T., Sang, A. X., Qu, X., Esquivel, C., Martinez, O. M., Krams, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2018: S198
  • Impact of the New Kidney Allocation System A2/A2B -> B Policy on Access to Transplantation among Minority Candidates Martins, P. N., Mustian, M., MacLennan, P. A., Ortiz, J. A., Akoad, M., Caicedo, J. C., Echeverri, G. J., Gray, S. H., Lopez-Soler, R. I., Gunasekaran, G., Kelly, B., Mobley, C. M., Black, S. M., Esquivel, C., Locke, J. E. LIPPINCOTT WILLIAMS & WILKINS. 2018: S412
  • Epstein-Barr Virus Genome Variation in Post-Transplant Lymphoproliferative Disorder Maloney, E., Busque, V. A., Hui, S., Krams, S. M., Esquivel, C. O., Martinez, O. M. LIPPINCOTT WILLIAMS & WILKINS. 2018: S95
  • Elucidation of the miRNome in EBV-positive and EBV-negative PTLD Balachandran, Y., Zimmermann, H., Esquivel, C. O., Krams, S., Trappe, R. U., Martinez, O. M. LIPPINCOTT WILLIAMS & WILKINS. 2018: S96
  • NK Cell Recognition of Peptides Encoded by EBV Latent Cycle Proteins Mbiribindi, B., Moreno, C., Esquivel, C. O., Martinez, O. M., Krams, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2018: S283
  • Temporal Trends in Disease Presentation and Survival of Patients With Hepatocellular Carcinoma: A Real-World Experience From 1998 to 2015 CANCER Kim, N. G., Nguyen, P. P., Dang, H., Kumari, R., Garcia, G., Esquivel, C. O., Nguyen, M. H. 2018; 124 (12): 2588–98

    View details for DOI 10.1002/cncr.31373

    View details for Web of Science ID 000434350700019

  • Transarterial chemoembolization in children to treat unresectable hepatocellular carcinoma PEDIATRIC TRANSPLANTATION Weiss, K. E., Sze, D. Y., Rangaswami, A. A., Esquivel, C. O., Concepcion, W., Lebowitz, E. A., Kothary, N., Lungren, M. P. 2018; 22 (4)

    View details for DOI 10.1111/petr.13187

    View details for Web of Science ID 000433590800016

  • Transarterial chemoembolization in children to treat unresectable hepatocellular carcinoma. Pediatric transplantation Weiss, K. E., Sze, D. Y., Rangaswami, A. A., Esquivel, C. O., Concepcion, W., Lebowitz, E. A., Kothary, N., Lungren, M. P. 2018: e13187

    Abstract

    Children with unresectable HCC have a dismal prognosis and few approved treatment options. TACE is an effective treatment option for adults with HCC, but experience in children is very limited. Retrospective analysis was performed of 8 patients aged 4-17years (4 male, mean 12.5years) who underwent TACE for unresectable HCC. Response to TACE was evaluated by change in AFP, RECIST and tumor volume, PRETEXT, and transplantation eligibility by UCSF and Milan criteria. Post-procedure mean follow-up was 8.2years. Mean overall change in tumor volume for the 8 patients was 51%. Percent change in AFP ranged from a decrease of 100% to an increase of 89.3%, with a mean change of -49.6%. Two patients did not undergo resection or transplantation and died of progressive disease. Six patients underwent orthotopic liver transplantation with mean first TACE-to-transplant interval of 141days (range 11-514). Following transplantation, 5 patients were alive at the end of the follow-up period and one died of recurrent disease. Based on our initial experience, TACE for children with unresectable HCC appears to be a safe and effective method for managing hepatic tumor burden and for downstaging and bridging to liver transplantation.

    View details for PubMedID 29707868

  • Dynamics of Viral and Host Immune Cell MicroRNA Expression during Acute Infectious Mononucleosis FRONTIERS IN MICROBIOLOGY Kaul, V., Weinberg, K. I., Boyd, S. D., Bernstein, D., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2018; 8
  • Prenatal treatment of ornithine transcarbamylase deficiency. Molecular genetics and metabolism Wilnai, Y. n., Blumenfeld, Y. J., Cusmano, K. n., Hintz, S. R., Alcorn, D. n., Benitz, W. E., Berquist, W. E., Bernstein, J. A., Castillo, R. O., Concepcion, W. n., Cowan, T. M., Cox, K. L., Lyell, D. J., Esquivel, C. O., Homeyer, M. n., Hudgins, L. n., Hurwitz, M. n., Palma, J. P., Schelley, S. n., Akula, V. P., Summar, M. L., Enns, G. M. 2018

    Abstract

    Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul®) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor.Two heterozygote OTCD mothers carrying male fetuses with a prenatal diagnosis of OTCD received intravenous Ammonul, arginine and dextrose-containing fluids shortly before birth. Maintenance Ammonul and arginine infusions and high-caloric enteral nutrition were started immediately after birth. Ammonul metabolites were measured in umbilical cord blood and the blood of the newborn immediately after delivery. Serial ammonia and biochemical analyses were performed following delivery.Therapeutic concentrations of Ammonul metabolites were detected in umbilical cord and neonatal blood samples. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. Peak ammonia levels in the first 24-48h were 53mcmol/l and 62mcmol/l respectively. The boys did not experience neurological sequelae secondary to hyperammonemia and received liver transplantation at ages 3months and 5months. The patients show normal development at ages 7 and 3years.Prenatal treatment of mothers who harbor severe OTCD mutations and carry affected male fetuses with intravenous Ammonul and arginine, followed by immediate institution of maintenance infusions after delivery, results in therapeutic levels of benzoate and phenylacetate in the newborn at delivery and, in conjunction with high-caloric enteral nutrition, prevents acute hyperammonemia and neurological decompensation. Following initial medical management, early liver transplantation may improve developmental outcome.

    View details for PubMedID 29396029

  • The challenges of closing an ileostomy in patients with total intestinal aganglionosis after small bowel transplant PEDIATRIC SURGERY INTERNATIONAL Jazi, F., Sinclair, T. J., Thorson, C. M., Castillo, R., Bonham, A. C., Esquivel, C. O., Bruzoni, M. 2018; 34 (1): 113–16

    Abstract

    We present the case of a 14-year-old male with a history of small bowel transplantation for long segment Hirschsprung's disease who underwent Duhamel ileorectal pull-through procedure. In post-transplant, the patient had no restrictions and was not TPN-dependent. To improve his quality of life, he and his family were interested in closing the ileostomy and undergoing pull-through surgery. The complexity of the case includes the presence of an aganglionic rectal segment-a short root of the mesentery due to the small bowel transplant-and significant immunosuppression. At the moment, he is continent, doing well, and has not had any remarkable complications.

    View details for PubMedID 29170900

  • Temporal trends in disease presentation and survival of patients with hepatocellular carcinoma: A real-world experience from 1998 to 2015. Cancer Kim, N. G., Nguyen, P. P., Dang, H. n., Kumari, R. n., Garcia, G. n., Esquivel, C. O., Nguyen, M. H. 2018

    Abstract

    Hepatocellular carcinoma (HCC) is one of the few cancers whose incidence continues to increase. The goal of the current study was to investigate the presentation and survival trends of patients with HCC presenting to a university hospital between 1998 and 2015.Study data were ascertained by individual chart review with survival data also supplemented by National Death Index query up to December 31, 2015. Patients were divided into three 6-year groups by diagnosis date (1998-2003, 2004-2009, and 2010-2015).A total of 2106 consecutive patients with HCC were included. The majority of patients had either hepatitis C (56.7%) or hepatitis B (22.1%), but cases of nonalcoholic steatohepatitis HCC increased by 68% over the most recent time period. Screening/surveillance identified 61% of HCC cases, but only 31% of these patients underwent curative treatment, which did not increase significantly over time. The overall median survival was 29.8 months (2.48 years) and without improvement over time. On multivariable analysis, Asian or Hispanic ethnicity, meeting Milan criteria, and receiving any of the standard HCC treatments were found to be significantly associated with improved survival, but diagnosis time period and liver disease etiology were not.Over the last 18 years, the percentage of cases of nonalcoholic steatohepatitis HCC has increased but not overall survival. It is interesting to note that only 31% of patients with HCC identified via screening/surveillance received any curative treatment. Further research is needed to better understand the barriers to curative care for patients with HCC and the causes of the lack of improvement in survival in the more recent patient cohort. Cancer 2018. © 2018 American Cancer Society.

    View details for PubMedID 29624631

  • In MemoriamThe Legacy of Thomas E. Starzl, MD, PhD 3/11/1926-3/4/2017 PEDIATRIC TRANSPLANTATION Shapiro, R., Esquivel, C. O., Webber, S. A. 2017; 21 (6)

    View details for DOI 10.1111/petr.13028

    View details for Web of Science ID 000407930300028

  • Dynamics of Viral and Host Immune Cell MicroRNA Expression during Acute Infectious Mononucleosis. Frontiers in microbiology Kaul, V. n., Weinberg, K. I., Boyd, S. D., Bernstein, D. n., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2017; 8: 2666

    Abstract

    Epstein-Barr virus (EBV) is the etiological agent of acute infectious mononucleosis (IM). Since acute IM is a self-resolving disease with most patients regaining health in 1-3 weeks there have been few studies examining molecular signatures in early acute stages of the disease. MicroRNAs (miRNAs) have been shown, however, to influence immune cell function and consequently the generation of antibody responses in IM. In this study, we performed a comprehensive analysis of differentially expressed miRNAs in early stage uncomplicated acute IM. miRNAs were profiled from patient peripheral blood obtained at the time of IM diagnosis and at subsequent time points, and pathway analysis performed to identify important immune and cell signaling pathways. We identified 215 differentially regulated miRNAs at the most acute stage of infection when the patients initially sought medical help. The number of differentially expressed miRNAs decreased to 148 and 68 at 1 and 2 months post-primary infection, with no significantly changed miRNAs identified at 7 months post-infection. Interferon signaling, T and B cell signaling and antigen presentation were the top pathways influenced by the miRNAs associated with IM. Thus, a dynamic and regulated expression profile of miRNA accompanies the early acute immune response, and resolution of infection, in IM.

    View details for PubMedID 29379474

    View details for PubMedCentralID PMC5775229

  • Mass cytometry reveals a distinct immunoprofile of operational tolerance in pediatric liver transplantation. Pediatric transplantation Lau, A. H., Vitalone, M. J., Haas, K., Shawler, T., Esquivel, C. O., Berquist, W. E., Martinez, O. M., Castillo, R. O., Krams, S. M. 2016

    Abstract

    Long-term IS in transplant patients has significant morbidity, poorer quality of life, and substantial economic costs. TOL, defined as graft acceptance without functional impairment in the absence of IS, has been achieved in some pediatric LT recipients. Using mass cytometry, peripheral blood immunotyping was performed to characterize differences between tolerant patients and patients who are stable on single-agent IS. Single-cell mass cytometry was performed using blood samples from a single-center pediatric LT population of operationally tolerant patients to comprehensively characterize the immune cell populations in the tolerant state compared with patients on chronic low-dose IS. Specific T-cell populations of interest were confirmed by flow cytometry. This high-dimensional phenotypic analysis revealed distinct immunoprofiles between transplant populations as well as a CD4(+) TOT (CD4(+) CD5(+) CD25(+) CD38(-/lo) CD45RA) that correlates with tolerance in pediatric LT recipients. In TOL patients, the TOT was significantly increased as compared to patients stable on low levels of IS. This TOT cell was confirmed by flow cytometry and is distinct from classic Treg cells. These results demonstrate the power of mass cytometry to discover significant immune cell signatures that have diagnostic potential.

    View details for DOI 10.1111/petr.12795

    View details for PubMedID 27781378

  • The Use of HCV Positive Donors in HCV Negative Liver Transplant Recipients Cholankeril, G., Perumpail, R. B., Hu, M., Aggarwal, A., Liu, A., Kwong, A. J., Dhanasekaran, R., Bonham, C. A., Gonzalez, S. A., Kim, W., Esquivel, C. O., Ahmed, A. WILEY. 2016: 807A
  • Living donor liver transplantation for inborn errors of metabolism - An underutilized resource in the United States. Pediatric transplantation Pham, T. A., Enns, G. M., Esquivel, C. O. 2016; 20 (6): 770-773

    Abstract

    Inborn metabolic diseases of the liver can be life-threatening disorders that cause debilitating and permanent neurological damage. Symptoms may manifest as early as the neonatal period. Liver transplant replaces the enzymatically deficient liver, allowing for metabolism of toxic metabolites. LDLT for metabolic disorders is rarely performed in the United States as compared to countries such as Japan, where they report >2000 cases performed within the past two decades. Patient and graft survival is comparable to that of the United States, where most of the studies are based on deceased donors. No living donor complications were observed, suggesting that LDLT is as safe and effective as deceased donor transplants performed in the USA. Increased utilization of living donors in the USA will allow for early transplantation to prevent permanent neurological damage in those with severe disease. Pediatric transplant centers should consider utilizing living donors when feasible for children with metabolic disorders of the liver.

    View details for DOI 10.1111/petr.12746

    View details for PubMedID 27392539

  • Donor-specific antibodies are associated with rejection after intestinal transplant in pediatric patients Bonham, C., Thomas Pham, Lee, J., Castillo, R., Conlon, S., Concepcion, W., Esquivel, C. LIPPINCOTT WILLIAMS & WILKINS. 2016: S257
  • miRNA-181 promotes graft prolongation by plasmacytoid dendritic cells by decreasing marginal zone B cells and plasmablasts Lau, A. H., Vitalone, M., Qu, X., Shawler, T., Martinez, O., Esquivel, C. O., Krams, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2016: S362
  • MicroRNAs in EBV plus B cell lymphomas and secreted exosomes Kaul, V., Harris-Arnold, A., Esquivel, C., Martinez, O. M., Krams, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2016: S257
  • Generation of novel Cag-Luc-EGFP transgene-expressing murine embryonic stem cell derived hepatoblasts as a transplantable cell source Cisneros, T., Arredondo-Guerrero, J., Qu, X., Krams, S. M., Esquivel, C., Martinez, O. LIPPINCOTT WILLIAMS & WILKINS. 2016: S864
  • Inhibition of the constitutively active PI3K/Akt/mTOR signaling pathway in epstein-barr virus B cell lymphomas demonstrate both antitumor and antirejection properties Sang, A., Ivison, G. T., Qu, X., Esquivel, C. O., Krams, S. M., Martinez, O. M. LIPPINCOTT WILLIAMS & WILKINS. 2016: S258
  • Combined en-bloc heart-liver transplantation for patients with congenital heart disease complicated by cirrhosis Bonham, C., Lee, J., Thomas Pham, Concepcion, W., Conlon, S., Maeda, K., Hollander, S., Esquivel, C. LIPPINCOTT WILLIAMS & WILKINS. 2016: S35
  • Mass cytometry reveals NK cell and T cell subsets in pediatric liver transplant patients with acute rejection Lau, A., Haas, K., Shawler, T., Esquivel, C. O., Martinez, O. M., Castillo, R. O., Krams, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2016: S134
  • Epstein-Barr virus-associated lymphoepithelial carcinoma after pediatric liver transplant LIVER TRANSPLANTATION Sang, A. X., Harris-Arnold, A., Kambham, N., Martinez, O. M., Krams, S. M., Strichartz, D., Esquivel, C. O. 2016; 22 (6): 849–53

    View details for PubMedID 27065464

    View details for PubMedCentralID PMC4882240

  • Plasmacytic posttransplant lymphoproliferative disorder with hyperviscosity syndrome in a child after liver transplant. Hepatology Yang, C. H., Gombar, S., Twist, C. J., Gratzinger, D., Esquivel, C. O., Lau, A. H. 2016

    View details for DOI 10.1002/hep.28657

    View details for PubMedID 27227484

  • Liver microRNA Profile of Induced Allograft Tolerance. Transplantation Vitalone, M. J., Wei, L., Fujiki, M., Lau, A. H., Littau, E., Esquivel, C., Martinez, O. M., Krams, S. M. 2016; 100 (4): 781-790

    Abstract

    Although the liver is less immunogenic than other solid organs, most liver transplant recipients receive lifelong immunosuppression. In both experimental models and clinical transplantation, total lymphoid irradiation (TLI) has been shown to induce allograft tolerance. Our goal was to identify the microRNAs (miRNAs) expressed in tolerant liver allograft recipients in an experimental model of TLI-induced tolerance.To identify the miRNAs associated with TLI-induced tolerance, we examined syngeneic recipients (Lewis→Lewis) and allogeneic recipients (Dark Agouti→Lewis) of orthotropic liver transplants that received posttransplant TLI, allogeneic recipients that were not treated posttransplantation and experienced acute rejection, and native Dark Agouti livers. Quantitative-polymerase chain reaction miRNA array cards were used to profile liver grafts.We identified 12 miRNAs that were specifically and significantly increased during acute rejection. In early tolerance, 33 miRNAs were altered compared with syngeneic livers, with 80% of the miRNAs increased. In established tolerance, 42 miRNAs were altered. In addition, miR-142-5p and miR-181a demonstrated increased expression in tolerant livers (both early and established tolerance) as compared with syngeneic livers. A principal component analysis of all miRNAs assayed demonstrated a profile in established tolerance that was closely related to that seen in syngeneic livers.The miRNA profile of established tolerant allografts is very similar to syngeneic grafts, suggesting tolerance may be a return to an immunological state of quiescence.

    View details for DOI 10.1097/TP.0000000000001105

    View details for PubMedID 26950716

  • Trends in Liver Transplantation Multiple Listing Practices Associated With Disparities in Donor Availability: An Endless Pursuit to Implement the Final Rule. Gastroenterology Cholankeril, G. n., Perumpail, R. B., Tulu, Z. n., Jayasekera, C. R., Harrison, S. A., Hu, M. n., Esquivel, C. O., Ahmed, A. n. 2016; 151 (3): 382–86.e2

    View details for PubMedID 27456386

  • Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer JAMA SURGERY Pham, T. A., Gallo, A. M., Concepcion, W., Esquivel, C. O., Bonham, C. A. 2015; 150 (12): 1150-1158

    Abstract

    Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most common primary hepatic malignant neoplasms in childhood. Given the rarity of these childhood tumors and their propensity to present at advanced stages, updated long-term data are needed.To determine the efficacy of liver transplant in children with HBL or HCC.This single-institution retrospective medical record review and analysis spanned from January 1, 1997, through September 17, 2014, at Stanford University School of Medicine. A total of 40 patients younger than 18 years underwent liver transplant for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with follow-up until September 17, 2014. Patients who underwent transplant for HCC included those with tumors that were greater in size than what is proposed by the Milan (a single tumor measuring ≤5 cm or ≤3 nodules measuring ≤3 cm) and University of California, San Francisco (single tumor measuring ≤6.5 cm or ≤3 nodules measuring ≤4.5 cm and a total diameter of ≤8 cm), criteria.Disease-free and overall patient survival and graft survival.Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year disease-free survival after liver transplant was 93%, 82%, and 82%, respectively, for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients with HCC. Risk factors associated with HBL recurrence after transplant included having pretreatment extent of disease stage IV lesions and a longer waiting list time and being older at the time of the transplant. Recurrence was found in 2 of 7 patients with HBL and pretransplant metastases, which were not found to be an independent risk factor for recurrence. Patients with HCC larger than the proposed Milan and University of California, San Francisco, criteria experienced good 5-year disease-free (82%) and overall (78%) survival after transplant. Being older at the time of transplant (18 vs 11 years; P = .04) and the presence of metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor recurrence.Liver transplant combined with chemotherapy is an excellent treatment that provides long-term disease-free survival in children diagnosed with advanced HBL and HCC. Early addition to a waiting list and aggressive multimodal therapy provide excellent results. Transplant should still be considered in children with HCC larger than the Milan and University of California, San Francisco, criteria.

    View details for DOI 10.1001/jamasurg.2015.1847

    View details for Web of Science ID 000367990700010

  • Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer. JAMA surgery Pham, T. A., Gallo, A. M., Concepcion, W., Esquivel, C. O., Bonham, C. A. 2015; 150 (12): 1150-8

    Abstract

    Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most common primary hepatic malignant neoplasms in childhood. Given the rarity of these childhood tumors and their propensity to present at advanced stages, updated long-term data are needed.To determine the efficacy of liver transplant in children with HBL or HCC.This single-institution retrospective medical record review and analysis spanned from January 1, 1997, through September 17, 2014, at Stanford University School of Medicine. A total of 40 patients younger than 18 years underwent liver transplant for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with follow-up until September 17, 2014. Patients who underwent transplant for HCC included those with tumors that were greater in size than what is proposed by the Milan (a single tumor measuring ≤5 cm or ≤3 nodules measuring ≤3 cm) and University of California, San Francisco (single tumor measuring ≤6.5 cm or ≤3 nodules measuring ≤4.5 cm and a total diameter of ≤8 cm), criteria.Disease-free and overall patient survival and graft survival.Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year disease-free survival after liver transplant was 93%, 82%, and 82%, respectively, for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients with HCC. Risk factors associated with HBL recurrence after transplant included having pretreatment extent of disease stage IV lesions and a longer waiting list time and being older at the time of the transplant. Recurrence was found in 2 of 7 patients with HBL and pretransplant metastases, which were not found to be an independent risk factor for recurrence. Patients with HCC larger than the proposed Milan and University of California, San Francisco, criteria experienced good 5-year disease-free (82%) and overall (78%) survival after transplant. Being older at the time of transplant (18 vs 11 years; P = .04) and the presence of metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor recurrence.Liver transplant combined with chemotherapy is an excellent treatment that provides long-term disease-free survival in children diagnosed with advanced HBL and HCC. Early addition to a waiting list and aggressive multimodal therapy provide excellent results. Transplant should still be considered in children with HCC larger than the Milan and University of California, San Francisco, criteria.

    View details for DOI 10.1001/jamasurg.2015.1847

    View details for PubMedID 26308249

  • Epstein-Barr Virus Modulates Host Cell MicroRNA-194 to Promote IL-10 Production and B Lymphoma Cell Survival AMERICAN JOURNAL OF TRANSPLANTATION Harris-Arnold, A., Arnold, C. P., Schaffert, S., Hatton, O., Krams, S. M., Esquivel, C. O., Martinez, O. M. 2015; 15 (11): 2814-2824

    Abstract

    Epstein-Barr virus (EBV) is a γ-herpesvirus that is linked to the development of posttransplant lymphoproliferative disorder (PTLD) in solid organ recipients. We previously demonstrated that EBV(+) B cell lymphoma cell lines isolated from patients with PTLD produce human IL-10 as an autocrine growth factor. However, little is known regarding IL-10 regulation in B cells. Here we show that EBV infection markedly alters the expression of host B cell microRNA, a class of small noncoding RNA that is an important regulator of transcriptional and posttranscriptional gene expression. Gene arrays reveal unique microRNA profiles in EBV(+) B cell lymphoma lines from patients with PTLD, compared to normal B cells or in vitro generated EBV(+) lymphoblastoid cell lines. We show that microRNA-194 expression is uniquely suppressed in EBV(+) B cell lines from PTLD patients and that the 3'untranslated region of IL-10 is targeted by microRNA-194. Overexpression of microRNA-194 attenuates IL-10 production and increases apoptosis of EBV(+) B cell lymphoma lines. Together, these data indicate that EBV co-opts the host B cell microRNA network and specifically suppresses microRNA-194 to override control of IL-10 expression. Thus, modulation of microRNA-194 may constitute a novel approach to inhibiting proliferation of EBV(+) B cell lymphomas in PTLD.

    View details for DOI 10.1111/ajt.13375

    View details for Web of Science ID 000363264800006

    View details for PubMedID 26147452

  • Reduced Survival in Elderly Liver Transplant Recipients: How Old is Too Old? Heo, N., Mannalithara, A., Udompap, P., Kim, D., Concepcion, W., Esquivel, C. O., Kim, W. WILEY. 2015: 807A
  • Reduced Survival in Elderly Liver Transplant Recipients: How Old is Too Old? Heo, N., Mannalithara, A., Udompap, P., Kim, D., Concepcion, W., Esquivel, C. O., Kim, W. WILEY. 2015: 807A
  • Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation. journal of pediatrics Niemi, A., Kim, I. K., Krueger, C. E., Cowan, T. M., Baugh, N., Farrell, R., Bonham, C. A., Concepcion, W., Esquivel, C. O., Enns, G. M. 2015; 166 (6): 1455-61 e1

    Abstract

    To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA).A retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford.Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 ± 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantation was 1648 ± 1492 μmol/L (normal <0.3, range 99-4420). By 3 days, post-transplantation levels fell on average by 87% (mean 210 ± 154 μmol/L), and at 4 months, they were 83% below pre-transplantation levels (mean 305 ± 108 μmol/L). Developmental delay was present in 12 patients (86%) before transplantation. All patients maintained neurodevelopmental abilities or exhibited improvements in motor skills, learning abilities, and social functioning.LT or LKT for MMA eradicates episodes of hyperammonemia, results in excellent long-term survival, and suggests stabilization of neurocognitive development. Long-term follow-up is underway to evaluate whether patients who undergo early LT need kidney transplantation later in life.

    View details for DOI 10.1016/j.jpeds.2015.01.051

    View details for PubMedID 25771389

  • Donor Specific Antibodies Are Associated with Rejection After Small Bowel and Multi-Visceral Transplant in Children Pham, T., Castillo, R. O., Concepcion, W., Esquivel, C., Bonham, A. LIPPINCOTT WILLIAMS & WILKINS. 2015: S18
  • Treatment of Methylmalonic Acidemia by Liver or Combined Liver-Kidney Transplantation JOURNAL OF PEDIATRICS Niemi, A., Kim, I. K., Krueger, C. E., Cowan, T. M., Baugh, N., Farrell, R., Bonham, C. A., Concepcion, W., Esquivel, C. O., Enns, G. M. 2015; 166 (6): 1455-?

    Abstract

    To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA).A retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford.Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 ± 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantation was 1648 ± 1492 μmol/L (normal <0.3, range 99-4420). By 3 days, post-transplantation levels fell on average by 87% (mean 210 ± 154 μmol/L), and at 4 months, they were 83% below pre-transplantation levels (mean 305 ± 108 μmol/L). Developmental delay was present in 12 patients (86%) before transplantation. All patients maintained neurodevelopmental abilities or exhibited improvements in motor skills, learning abilities, and social functioning.LT or LKT for MMA eradicates episodes of hyperammonemia, results in excellent long-term survival, and suggests stabilization of neurocognitive development. Long-term follow-up is underway to evaluate whether patients who undergo early LT need kidney transplantation later in life.

    View details for DOI 10.1016/j.jpeds.2015.01.051

    View details for Web of Science ID 000355018200025

    View details for PubMedID 25771389

  • Employment After Liver Transplantation: A Review TRANSPLANTATION PROCEEDINGS Huda, A., Newcomer, R., Harrington, C., Keeffe, E. B., Esquivel, C. O. 2015; 47 (2): 233-239

    Abstract

    Return to productive employment is often an important milestone in the recovery and rehabilitation process after liver transplantation (OLT). This literature review identifies factors associated with employment in patients who underwent OLT.We searched PubMed for articles that addressed the various factors affecting employment after OLT.The studies demonstrated improvement in the quality of life and examined factors that predicted whether patients would return to work after OLT. Demographic variable associated with posttransplant employment included young age, male sex, college degree, Caucasian race, and pretransplant employment. Patients with alcohol-related liver disease had a significantly lower rate of employment than did those with other etiologies of liver disease. Recipients who were employed after transplantation had a significantly better posttransplant functional status than did those who were not employed.Economic pressures are increasing the expectation that patients who undergo successful OLT will return to work. Thus, transplant teams need to have a better understanding of posttransplant work outcomes for this vulnerable population, and greater attention must be paid to the full social rehabilitation of transplant recipients. Specific interventions for OLT recipients should be designed to evaluate and change their health perceptions and encourage their return to work.

    View details for DOI 10.1016/j.transproceed.2014.10.022

    View details for Web of Science ID 000351480600001

    View details for PubMedID 25769555

  • Recurrent Hepatocellular Carcinoma and Poorer Overall Survival in Patients Undergoing Left-sided Compared With Right-sided Partial Hepatectomy. Journal of clinical gastroenterology Valenzuela, A., Ha, N. B., Gallo, A., Bonham, C., Ahmed, A., Melcher, M., Kim, L. H., Esquivel, C., Concepcion, W., Ayoub, W. S., Lutchman, G. A., Daugherty, T., Nguyen, M. H. 2015; 49 (2): 158-164

    Abstract

    We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy.Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed.This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC.The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection.HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.

    View details for DOI 10.1097/MCG.0000000000000144

    View details for PubMedID 24804988

  • Improved Long Term Survival Following Liver Transplantation for Childhood Primary Hepatic Malignancy Pham, T., Gallo, A., Concepcion, W., Esquivel, C., Bonham, C. WILEY-BLACKWELL. 2015: 99–100
  • Pediatric Malignancy-What to do? Esquivel, C. O. WILEY-BLACKWELL. 2015: 44
  • Complications Following Liver Transplantation for Progressive Familial Intrahepatic Cholestasis DIGESTIVE DISEASES AND SCIENCES Berumen, J., Feinberg, E., Todo, T., Bonham, C. A., Concepcion, W., Esquivel, C. 2014; 59 (11): 2649-2652
  • Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure. Pediatric transplantation McKenzie, R. B., Berquist, W. E., Nadeau, K. C., Louie, C. Y., Chen, S. F., Sibley, R. K., Glader, B. E., Wong, W. B., Hofmann, L. V., Esquivel, C. O., Cox, K. L. 2014; 18 (5): 503-509

    Abstract

    In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy.

    View details for DOI 10.1111/petr.12296

    View details for PubMedID 24930635

  • Improved survival outcomes in patients with non-alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002-2012 United Network for Organ Sharing data. Clinical transplantation Wong, R. J., Chou, C., Bonham, C. A., Concepcion, W., Esquivel, C. O., Ahmed, A. 2014; 28 (6): 713-721

    Abstract

    There is an increasing trend of patients with hepatocellular carcinoma (HCC) and non-alcoholic fatty liver disease undergoing liver transplantation in the U.S. Our study utilized data from the 2002-2012 United Network for Organ Sharing registry to evaluate MELD era trends in U.S. liver transplantations focused on patients with non-alcoholic steatohepatitis (NASH), hepatitis C (HCV), alcoholic liver disease, and HCC. Survival outcomes were stratified by liver disease etiology and compared across time periods using Kaplan Meier and Cox proportional hazards models. Patients with NASH were more likely to be women, had higher body mass index, and higher prevalence of diabetes and cardiac disease. However, overall long term survival was significantly higher in NASH and alcoholic liver disease patients (p < 0.001). Compared to HCV, NASH patients had significantly higher post-transplantation survival (HR 0.69, 95% CI 0.63-0.77), and lower risk of graft failure (HR 0.76, 95% CI 0.69-0.83). Despite having higher body mass index and higher prevalence of diabetes and cardiac disease, NASH patients had better post-liver transplantation survival compared to patients with HCV or HCC. Patients with alcoholic liver disease also had superior survival outcomes. However, these survival differences were limited to patients without HCC that underwent liver transplantation. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/ctr.12364

    View details for PubMedID 24654688

  • Etiology of Liver Disease Affects Post-Liver Transplantation Survival Among Hepatocellular Carcinoma Patients. Wong, R. J., Ahmed, A., Concepcion, W., Esquivel, C. WILEY-BLACKWELL. 2014: S276
  • Late hepatic artery thrombosis in pediatric liver transplantation: an incomplete story. Liver transplantation Gallo, A., Esquivel, C. O. 2014; 20 (5): 512-513

    View details for DOI 10.1002/lt.23886

    View details for PubMedID 24711444

  • Primary surgical resection versus liver transplantation for transplant-eligible hepatocellular carcinoma patients. Digestive diseases and sciences Wong, R. J., Wantuck, J., Valenzuela, A., Ahmed, A., Bonham, C., Gallo, A., Melcher, M. L., Lutchman, G., Concepcion, W., Esquivel, C., Garcia, G., Daugherty, T., Nguyen, M. H. 2014; 59 (1): 183-191

    Abstract

    Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting.The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT.The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio.The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95 % CI, 1.08-6.86).Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.

    View details for DOI 10.1007/s10620-013-2947-8

    View details for PubMedID 24282054

  • Hepatocellular Carcinoma is associated with Lower Survival following Living Donor Liver Transplantation in the U.S Perumpail, R. B., Wong, R., Su, A. M., Bonham, C. A., Esquivel, C. O., Ahmed, A. WILEY-BLACKWELL. 2014: 511A
  • Higher MELD scores at time of transplant are not associated with lower survival following living donor liver transplantation among patients with MELD < 25 Perumpail, R. B., Wong, R., Su, A. M., Bonham, C. A., Esquivel, C. O., Ahmed, A. WILEY-BLACKWELL. 2014: 287A–288A
  • Resolution of Acute Kidney Injury after Liver Transplantation: Single Center Experience Todo, T., Gallo, A., Beruman, J., Feinberg, E., Melcher, M., Bonham, C., Busque, S., Concepcion, W., Esquivel, C. WILEY-BLACKWELL. 2014: 101
  • PI3K Inhibition Augments the Efficacy of Rapamycin in Suppressing Proliferation of Epstein-Barr Virus (EBV) plus B Cell Lymphomas AMERICAN JOURNAL OF TRANSPLANTATION Furukawa, S., Wei, L., Krams, S. M., Esquivel, C. O., Martinez, O. M. 2013; 13 (8): 2035-2043

    Abstract

    Posttransplant lymphoproliferative disorder (PTLD) continues to be a devastating and potentially life-threatening complication in organ transplant recipients. PTLD is associated with EBV infection and can result in malignant B cell lymphomas. Here we demonstrate that the PI3K/Akt/mTOR pathway is highly activated in EBV+ B cell lymphoma lines derived from patients with PTLD. Treatment with the mTORC1 inhibitor Rapamycin (RAPA) partially inhibited the proliferation of EBV+ B cell lines. Resistance to RAPA treatment correlated with high levels of Akt phosphorylation. An mTORC1/2 inhibitor and a PI3K/mTOR dual inhibitor suppressed Akt phosphorylation and showed a greater anti-proliferative effect on EBV+ B lymphoma lines compared to RAPA. EBV+ B cell lymphoma lines expressed high levels of PI3Kδ. We demonstrate that PI3Kδ is responsible for Akt activation in EBV+ B cell lymphomas, and that selective inhibition of PI3Kδ by either siRNA, or a small molecule inhibitor, augmented the anti-proliferative effect of RAPA on EBV+ B cell lymphomas. These results suggest that PI3Kδ is a novel, potential therapeutic target for the treatment of EBV-associated PTLD and that combined blockade of PI3Kδ and mTOR provides increased efficacy in inhibiting proliferation of EBV+ B cell lymphomas.

    View details for DOI 10.1111/ajt.12328

    View details for Web of Science ID 000322330000013

    View details for PubMedID 23841834

  • USE OF A NOVEL PROTOCOL TO SUCCESSFULLY CHARACTERIZE AND TREAT IMMUNE-MEDIATED ACUTE HEPATITIS AND LIVER FAILURE IN CHILDREN McKenzie, R. B., Berquist, W., Esquivel, C., Nadeau, K., Chen, S., Sibley, R., Cox, K. WILEY-BLACKWELL. 2013: 52
  • T cell responses to Epstein Barr Virus infections in pediatric organ transplant recipients Lin, D., Piard-Ruster, K., Esquivel, C., Martinez, O., Maecker, H. AMER ASSOC IMMUNOLOGISTS. 2013
  • Syk-Induced Phosphatidylinositol-3-Kinase Activation in EpsteinBarr Virus Posttransplant Lymphoproliferative Disorder AMERICAN JOURNAL OF TRANSPLANTATION Hatton, O., Lambert, S. L., Phillips, L. K., Vaysberg, M., Natkunam, Y., Esquivel, C. O., Krams, S. M., Martinez, O. M. 2013; 13 (4): 883-890

    Abstract

    Posttransplant lymphoproliferative disorder (PTLD)-associated Epstein-Barr virus (EBV)+ B cell lymphomas are serious complications of solid organ and bone marrow transplantation. The EBV protein LMP2a, a B cell receptor (BCR) mimic, provides survival signals to virally infected cells through Syk tyrosine kinase. Therefore, we explored whether Syk inhibition is a viable therapeutic strategy for EBV-associated PTLD. We have shown that R406, the active metabolite of the Syk inhibitor fostamatinib, induces apoptosis and cell cycle arrest while decreasing downstream phosphatidylinositol-3'-kinase (PI3K)/Akt signaling in EBV+ B cell lymphoma PTLD lines in vitro. However, Syk inhibition did not inhibit or delay the in vivo growth of solid tumors established from EBV-infected B cell lines. Instead, we observed tumor growth in adjacent inguinal lymph nodes exclusively in fostamatinib-treated animals. In contrast, direct inhibition of PI3K/Akt significantly reduced tumor burden in a xenogeneic mouse model of PTLD without evidence of tumor growth in adjacent inguinal lymph nodes. Taken together, our data indicate that Syk activates PI3K/Akt signaling which is required for survival of EBV+ B cell lymphomas. PI3K/Akt signaling may be a promising therapeutic target for PTLD, and other EBV-associated malignancies.

    View details for DOI 10.1111/ajt.12137

    View details for Web of Science ID 000316911900011

    View details for PubMedID 23398911

  • PI3K delta Inhibition Augments the Efficacy of mTOR Inhibitor Rapamycin on the Proliferation of Epstein-Barr Virus (EBV) plus B Cell Lymphomas. 13th American Transplant Congress (ATC) Furukawa, S., Hatton, O., Krams, S., Esquivel, C., Martinez, O. WILEY-BLACKWELL. 2013: 96–97
  • Liver transplantation for urea cycle disorders in pediatric patients: A single-center experience PEDIATRIC TRANSPLANTATION Kim, I. K., Niemi, A., Krueger, C., Bonham, C. A., Concepcion, W., Cowan, T. M., Enns, G. M., Esquivel, C. O. 2013; 17 (2): 158-167

    Abstract

    LT has emerged as a surgical treatment for UCDs. We hypothesize that LT can be safely and broadly utilized in the pediatric population to effectively prevent hyperammonemic crises and potentially improve neurocognitive outcomes. To determine the long-term outcomes of LT for UCDs, charts of children with UCD who underwent LT were retrospectively reviewed at an academic institution between July 2001 and May 2012. A total of 23 patients with UCD underwent LT at a mean age of 3.4 yr. Fifteen (65%) patients received a whole-liver graft, seven patients (30%) received a reduced-size graft, and one patient received a living donor graft. Mean five-yr patient survival was 100%, and allograft survival was 96%. Mean peak blood ammonia (NH(3) ) at presentation was 772 μmol/L (median 500, range 178-2969, normal <30-50). After transplantation, there were no episodes of hyperammonemia. Eleven patients were diagnosed with some degree of developmental delay before transplantation, which remained stable or improved after transplantation. Patients without developmental delay before transplantation maintained their cognitive abilities at long-term follow-up. LT was associated with the eradication of hyperammonemia, removal of dietary restrictions, and potentially improved neurocognitive development. Long-term follow-up is underway to evaluate whether LT at an early age (<1 yr) will attain improved neurodevelopmental outcomes.

    View details for DOI 10.1111/petr.12041

    View details for PubMedID 23347504

  • Current options for management of biliary atresia PEDIATRIC TRANSPLANTATION Gallo, A., Esquivel, C. O. 2013; 17 (2): 95-98

    Abstract

    It is encouraging that we are improving the technical aspects of treatment modalities for biliary atresia. However, it is clear that more needs to be done to best develop new treatment plans while applying the modalities we have (porto-enterostomy or liver transplantation or both) in a way that will afford the best survival and quality-of-life. This review article will discuss a number of points that are vital to improving care and illustrates the need to further scrutinize treatment decisions.

    View details for DOI 10.1111/petr.12040

    View details for Web of Science ID 000315467000009

    View details for PubMedID 23347466

  • Geographical Rural Status and Health Outcomes in Pediatric Liver Transplantation: An Analysis of 6 Years of National United Network of Organ Sharing Data JOURNAL OF PEDIATRICS Park, K. T., Bensen, R., Lu, B., Nanda, P., Esquivel, C., Cox, K. 2013; 162 (2): 313-?

    Abstract

    To determine whether children in rural areas have worse health than children in urban areas after liver transplantation (LT).We used urban influence codes published by the US Department of Agriculture to categorize 3307 pediatric patients undergoing LT in the United Network of Organ Sharing database between 2004 and 2009 as urban or rural. Allograft rejection, patient death, and graft failure were used as primary outcome measures of post-LT health. Pediatric end-stage liver disease/model of end-stage liver disease scores >20 was used to measure worse pre-LT health.In a multivariate analysis, we found greater rates of allograft rejection within 6 months of LT (OR 1.27; 95% CI 1.05-1.53) and a lower occurrence of posttransplantation lymphoproliferative disorder (OR 0.64; 95% CI 0.41-0.99) in patients in rural areas. The difference in allograft rejection was eliminated at 1 year of LT (OR 1.18; 95% CI 0.98-1.42). Rural location did not impact other outcome measures.We conclude that rural location makes a negative impact on patient health within the first 6 months of LT by increasing the risk for allograft rejection, although patients in rural areas may have lower rates of developing posttransplantation lymphoproliferative disorder. Long-term adverse health effects were not seen.

    View details for DOI 10.1016/j.jpeds.2012.07.015

    View details for Web of Science ID 000313579900021

    View details for PubMedID 22914224

  • Reoperation in Pediatric Liver Transplantation: A Five Year Review 13th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) Held in Conjunction with the NATCO Symposium for Advanced Transplant Professionals Feinberg, E. J., Beruman, J. A., Campos, B. D., Lodhia, N., Gallo, A. E., Melcher, M., Bonham, C. A., Concepcion, W., Esquivel, C. O. WILEY-BLACKWELL. 2013: 84–84
  • The impact of hepatic portoenterostomy on liver transplantation for the treatment of biliary atresia: Early failure adversely affects outcome PEDIATRIC TRANSPLANTATION Alexopoulos, S. P., Merrill, M., Kin, C., Matsuoka, L., Dorey, F., Concepcion, W., Esquivel, C., Bonham, A. 2012; 16 (4): 373-378

    Abstract

    The most common indication for pediatric LTx is biliary atresia with failed HPE, yet the effect of previous HPE on the outcome after LTx has not been well characterized. We retrospectively reviewed a single-center experience with 134 consecutive pediatric liver transplants for the treatment of biliary atresia from 1 May 1995 to 28 April 2008. Of 134 patients, 22 underwent LTx without prior HPE (NPE), while 112 patients underwent HPE first. HPE patients were grouped into EF, defined as need for LTx within the first year of life, and LF, defined as need for LTx beyond the first year of life. NPE and EF groups differed significantly from the LF group in age, weight, PELD, and ICU status (p < 0.05) with NPE having the highest PELD and ICU status. Patients who underwent salvage LTx after EF following HPE had a significantly higher incidence of post-operative bacteremia and septicemia (p < 0.05), and subsequently lower survival rates. One-year patient survival and graft survival were as follows: NPE 100%, EF 81%, and LF 96% (p < 0.05); and NPE 96%, EF 79%, and LF 96% (p < 0.05). Further investigation into the optimal treatment of biliary atresia should focus on identifying patients at high risk of EF who may benefit from proceeding directly to LTx given the increased risk of post-LTx bacteremia, sepsis, and death after failed HPE.

    View details for DOI 10.1111/j.1399-3046.2012.01677.x

    View details for Web of Science ID 000303998800021

    View details for PubMedID 22463739

  • Grafts too big or too small: Business as usual in pediatric liver transplantation PEDIATRIC TRANSPLANTATION Reding, R., Dhawan, A., Esquivel, C. O. 2012; 16 (3): 212-213
  • Differentiation of Murine Embryonic Stem Cells to Definitive Endoderm for Treatment of Liver Disease. Hill, A. L., Esquivel, C. O., Martinez, O. M. WILEY-BLACKWELL. 2012: S147
  • The Roles of microRNAs in Transplantation. Wei, L., Qu, X., Martinez, O. M., Esquivel, C. O., Krams, S. M. WILEY-BLACKWELL. 2012: S146–S147
  • Emerging therapeutic strategies for Epstein-Barr virus+ post-transplant lymphoproliferative disorder PEDIATRIC TRANSPLANTATION Hatton, O., Martinez, O. M., Esquivel, C. O. 2012; 16 (3): 220-229

    Abstract

    De novo malignancies represent an increasing concern in the transplant population, particularly as long-term graft and patient survival improves. EBV-associated B-cell lymphoma in the setting of PTLD is the leading malignancy in children following solid organ transplantation. Therapeutic strategies can be categorized as pharmacologic, biologic, and cell-based but the variable efficacy of these approaches and the complexity of PTLD suggest that new treatment options are warranted. Here, we review current therapeutic strategies for treatment of PTLD. We also describe the life cycle of EBV, addressing the viral mechanisms that contribute to the genesis and persistence of EBV+ B-cell lymphomas. Specifically, we focus on the oncogenic signaling pathways activated by the EBV LMP1 and LMP2a to understand the underlying mechanisms and mediators of lymphomagenesis with the goal of identifying novel, rational therapeutic targets for the treatment of EBV-associated malignancies.

    View details for DOI 10.1111/j.1399-3046.2012.01656.x

    View details for Web of Science ID 000302619500013

    View details for PubMedID 22353174

  • A Common Peripheral Blood Gene Set for Diagnosis of Operational Tolerance in Pediatric and Adult Liver Transplantation AMERICAN JOURNAL OF TRANSPLANTATION Li, L., Wozniak, L. J., RODDER, S., Heish, S., Talisetti, A., Wang, Q., Esquivel, C., Cox, K., Chen, R., McDiarmid, S. V., Sarwal, M. M. 2012; 12 (5): 1218-1228

    Abstract

    To identify biomarkers of operational tolerance in pediatric and adult liver transplant recipients, transcriptional profiles were examined from 300 samples by microarrays and Q-PCR measurements of blood specimens from pediatric and adult liver transplant recipients and normal tissues. Tolerance-specific genes were validated in independent samples across two different transplant programs and validated by Q-PCR. A minimal set of 13 unique genes, highly expressed in natural killer cells (p = 0.03), were significantly expressed in both pediatric and adult liver tolerance, irrespective of different clinical and demographic confounders. The performance of this gene set by microarray in independent samples was 100% sensitivity and 83% specificity and the AUC was 0.988 for only three genes by Q-PCR. 26% of adults and 64% of children with excellent liver allograft function, on minimal or dual immunosuppression, showed high prediction scores for tolerance. Novel peripheral transcriptional profiles can be identified in operational tolerance in pediatric and adult recipients of liver allografts, suggesting a high incidence of a pro-tolerogenic phenotype in stable patients on chronic immunosuppression. Given the high incidence of viral infections and malignancies in liver transplant recipients, this gene set provides an important monitoring tool that can move the field toward personalized and predictive medicine in organ transplantation.

    View details for DOI 10.1111/j.1600-6143.2011.03928.x

    View details for Web of Science ID 000303235100020

    View details for PubMedID 22300520

  • Changes in natural killer cell subsets in pediatric liver transplant recipients PEDIATRIC TRANSPLANTATION Pham, B., Piard-Ruster, K., Silva, R., Gallo, A., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2012; 16 (2): 176-182

    Abstract

    NK cells are important in the immune response against tumors and virally infected cells. A balance between inhibitory and activating receptors controls the effector functions of NK cells. We examined the fate of circulating NK cells and the expression of the NK cell-activating receptors in pediatric liver transplant recipients. Blood specimens were collected from 38 pediatric liver transplant recipients before transplant, and at one wk, one, three, six, and nine months, and one yr post-transplant. PBMCs were isolated and analyzed for the levels of NK cell activation receptors NKp30, NKp46, and NKG2D in the CD56(dim) CD16(+) and CD56(bright) CD16(+/-) subsets of NK cells. We demonstrated that there is a significant decrease in the percentage of circulating NK cells post-transplant (pretransplant 7.69 ± 1.54 vs. one wk post-transplant 1.73 ± 0.44) in pediatric liver transplant recipients. Interestingly, NKp30 expression is significantly increased, while NKp46 and NKG2D levels remain stable on the NK cells that persist at one wk post-transplant. These data indicate that the numbers and subsets of circulating NK cells are altered in children after liver transplantation.

    View details for DOI 10.1111/j.1399-3046.2012.01653.x

    View details for Web of Science ID 000300709600017

    View details for PubMedID 22360401

    View details for PubMedCentralID PMC3306774

  • In memoriam: Emmet B. Keeffe, M.D. LIVER TRANSPLANTATION Ahmed, A., Esquivel, C. O. 2011; 17 (12): 1371–73

    View details for DOI 10.1002/lt.22448

    View details for Web of Science ID 000298040600001

  • In Memoriam: Emmet B. Keeffe, M.D. DIGESTIVE DISEASES AND SCIENCES Ahmed, A., Esquivel, C. O. 2011; 56 (11): 3103–5
  • In Memoriam: Emmet B. Keeffe, MD HEPATOLOGY Ahmed, A., Esquivel, C. O. 2011; 54 (5): 1493–95

    View details for DOI 10.1002/hep.24687

    View details for Web of Science ID 000296443100001

  • Emmet B. Keeffe, MD In Memoriam GASTROENTEROLOGY Ahmed, A., Esquivel, C. O. 2011; 141 (5): 1537–38
  • Emmet B. Keeffe, MD IN MEMORIAM GASTROINTESTINAL ENDOSCOPY Ahmed, A., Esquivel, C. O. 2011; 74 (5): 959–60
  • Incidence and Predictors of Recurrent Hepatocellular Carcinoma (HCC) Following Partial Hepatectomy 76th Annual Scientific Meeting of the American-College-of-Gastroenterology Vergara, A. M., Gallo, A., Nghiem Ha, N., Bonham, C., Esquivel, C., Concepcion, W., Melcher, M., Daugherty, T., Ayoub, W., Lutchman, G., Ahmed, A., Mindie Nguyen, M. NATURE PUBLISHING GROUP. 2011: S103–S104
  • Liver Transplantation With Donation After Cardiac Death A Treacherous Field! ARCHIVES OF SURGERY Esquivel, C. O. 2011; 146 (9): 1023-1023

    View details for Web of Science ID 000295002900007

    View details for PubMedID 22029064

  • HIGH DOSES OF CALCINEURIN INHIBITORS ARE ASSOCIATED WITH LOW LEVELS OF T REGULATORY CELLS IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS. Piard-Ruster, K. S., Silva, R., Berquist, W., Pham, B., Gallo, A., Krams, S. M., Esquivel, C. O., Martinez, O. M. WILEY-BLACKWELL. 2011: 57–57
  • RURALITY AND HEALTH OUTCOMES IN PEDIATRIC LIVER TRANSPLANTATION Park, K. T., Bensen, R., Nanda, P., Esquivel, C., Cox, K. WILEY-BLACKWELL. 2011: 135–135
  • COMBINED HEART plus LIVER TRANSPLANTS (CH+LTx) IN CHILDREN: TECHNICAL AND IMMUNOSUPPRESSIVE STRATEGY TO ENSURE A GOOD OUTCOME Hwang, C. S., Gallo, A., Kim, I., Chin, C., Bonham, C. A., Concepcion, W., Esquivel, C. O. WILEY-BLACKWELL. 2011: 77–77
  • Effects of rural status on health outcomes in pediatric liver transplantation: A single center analysis of 388 patients PEDIATRIC TRANSPLANTATION Park, K. T., Nanda, P., Bensen, R., Strichartz, D., Esquivel, C., Cox, K. 2011; 15 (3): 300-305

    Abstract

    Rural status of patients may impact health before and after pediatric LT. We used UI codes published by the USDA to stratify patients as urban or rural depending county residence. A total of 388 patients who had LT and who met criteria were included. Rejection, PTLD, and survival were used as primary outcome measures of post-LT health. UNOS Status 1 and PELD/MELD scores >20 were used as secondary outcome measures of poorer pre-LT health. Logistic regression models were run to determine associations. We did not find any statistically significant differences in pre- or post-LT outcomes with respect to rurality. Among rural patients, there was a general trend for decreased incidence of rejection (25.0% vs. 33.4%; OR 0.64, 95% CI 0.29-1.44), increased risk of PTLD (5.6% vs. 3.4%; OR 1.86, 95% CI 0.36-3.31), and decreased survival (OR 0.85, 95% CI 0.34-2.13) after LT. Rural patients also tended to be sicker at the time of LT than patients from urban areas, with increased proportion of Status 1 (OR 1.17, 95% CI 0.51-2.70) and PELD/MELD scores >20 (OR 1.20, 95% CI 0.59-2.45). From a single center experience, we conclude that rurality did not significantly affect health outcomes after LT, although a larger study may validate the general trends that rural patients may have decreased rejection, increased PTLD, and mortality, and be in poorer health at the time of LT.

    View details for DOI 10.1111/j.1399-3046.2010.01452.x

    View details for Web of Science ID 000289628100018

    View details for PubMedID 21450010

  • Successful Cavoatrial Anastamosis in Technically Challenging Liver Transplant Recipients American Transplant Congress Hwang, C. S., Gallo, A. E., Lightner, A., Bonham, C. A., Concepcion, W., Esquivel, C. O. WILEY-BLACKWELL. 2011: 332–332
  • Targeting Akt for Treatment of Post-Transplant Lymphoproliferative Disorder (PTLD) American Transplant Congress Hatton, O., Lambert, S., Krams, S. M., Esquivel, C. O., Martinez, O. M. WILEY-BLACKWELL. 2011: 137–137
  • Rejection of Small Intestinal Allografts Associates with a Unique Signature of microRNAs American Transplant Congress Krams, S. M., Wei, L., Pham, B., Harris, A., Castillo, R. O., Esquivel, C. O., Martinez, O. WILEY-BLACKWELL. 2011: 133–133
  • Toll-Like Receptor 4 Contributes to Small Intestine Allograft Rejection TRANSPLANTATION Krams, S. M., Wang, M., Castillo, R. O., Ito, T., Phillips, L., Higgins, J., Kambham, N., Esquivel, C. O., Martinez, O. M. 2010; 90 (12): 1272-1277

    Abstract

    Although outcomes for small intestine transplantation (SIT) have improved in recent years, allograft rejection rates remain among the highest of solid organ grafts. The high load of commensal bacteria in the small intestine may contribute through activation of the toll-like receptor (TLR) pathway. In this study, we examine the participation of TLR4 in acute allograft rejection in an orthotopic mouse model of SIT.Wild-type C57Bl/6 (H-2b) or TLR49(-/-) (H-2b) mice were transplanted with syngeneic (C57Bl/6), allogeneic (BALB/c; H-2d), or F1 (BALB/cxC57Bl/6; H-2d/b) vascularized, orthotopic small intestine grafts. Graft recipients were killed on days 2 to 6 posttransplant. Serum cytokines were measured by Luminex, and tissue was obtained for histology and quantitative real-time polymerase chain reaction.BALB/c grafts transplanted into C57Bl/6 recipients exhibited mixed inflammatory infiltrates, destruction of the mucosa, and significant apoptosis. TLR2 and TLR4 transcripts were modestly increased in syngeneic grafts on days 2 and 6 compared with native bowel, whereas TLR2 and TLR4 were significantly increased on days 2 and 6 in allogeneic grafts. Although fully mismatched and F1 grafts were rejected by C57Bl/6 recipients (mean survival time=8.2 and 9.3 days, respectively), graft survival was significantly prolonged in TLR4(-/-) recipients (mean survival time=10.6 and 14.3 days, respectively). Proinflammatory cytokines were markedly reduced in TLR4(-/-) graft recipients.Small intestine graft survival is prolonged in the absence of TLR4, suggesting that gut flora associated with the graft may augment alloimmune responses through TLR4. Thus, the TLR pathway may be a novel therapeutic target for improving SIT allograft survival.

    View details for DOI 10.1097/TP.0b013e3181fdda0d

    View details for Web of Science ID 000285377100006

    View details for PubMedID 21197709

    View details for PubMedCentralID PMC3799863

  • Analysis of clinical variables associated with tolerance in pediatric liver transplant recipients PEDIATRIC TRANSPLANTATION Talisetti, A., Hurwitz, M., Sarwal, M., Berquist, W., Castillo, R., Bass, D., Concepcion, W., Esquivel, C. O., Cox, K. 2010; 14 (8): 976-979

    Abstract

    Tolerance has been defined as stable graft function off IMS. We reviewed the data of 369 pediatric liver transplant patients to examine demographic differences that may have a PV of pediatric LT tolerance. Of the 369 patients, 280 patients were stable with detectable blood levels of IMS agents and with good graft function without biopsy proven REJ > 1 yr posttransplantation, 18 patients were noted to be TOL off IMS, 27 patients were taking MIS with drug levels below detectable range by standard laboratory parameters, and 44 patients developed one or more episodes of biopsy proven acute or chronic REJ > 1 yr post-transplantation. Variables, including percentage of biliary atresia, type of transplanted organ, history of EBV infection, patient and donor gender, and ABO blood type mismatch between recipient and donor did not have PV of tolerance. Average age in years was 1.37 ± 1.53 (0.3-4.9) for TOL, 1.14 ± 0.89 (0.4-3.1) for MIS and 3.35 ± 4.45 (0.3-16) for REJ. Age difference of TOL/MIS vs. REJ was significant (p =0.002) and TOL vs. REJ was significant (0.01). Age at the time of transplantation is an important predictor in the development of pediatric LT tolerance.

    View details for DOI 10.1111/j.1399-3046.2010.01360.x

    View details for Web of Science ID 000285229500007

    View details for PubMedID 21108705

  • A review of abdominal organ transplantation in cystic fibrosis PEDIATRIC TRANSPLANTATION Lu, B. R., Esquivel, C. O. 2010; 14 (8): 954-960

    Abstract

    With advances in medical treatments, patients with CF are having improved quality of life and living longer. Although pulmonary disease is still the leading cause of morbidity and mortality, this longevity has allowed for the development of other organ dysfunction, mainly liver and pancreas. This review discusses the abdominal organ complications and the role of abdominal organ transplantation in CF. Liver failure and portal hypertension complications are the most common indicators for liver transplantation in CF, and five-yr survival for isolated liver transplantation is >80%. Deficiency of pancreatic enzymes is almost universal and up to 40% of patients with CF can develop insulin-dependent diabetes, although the role of pancreas transplantation is less clear and needs further research. Finally, the need for lung transplantation should always be assessed and considered in combination with liver transplantation on a case-by-case basis.

    View details for DOI 10.1111/j.1399-3046.2010.01412.x

    View details for Web of Science ID 000285229500004

    View details for PubMedID 20946451

  • Expression of Soluble HLA-G Identifies Favorable Outcomes in Liver Transplant Recipients TRANSPLANTATION Zarkhin, V., Talisetti, A., Li, L., Wozniak, L. J., McDiarmid, S. V., Cox, K., Esquivel, C., Sarwal, M. M. 2010; 90 (9): 1000-1005

    Abstract

    Human leukocyte antigen (HLA)-G displays immunotolerogenic properties toward the main effector cells involved in graft rejection through inhibition of natural killer cell- and cytotoxic T-lymphocyte-mediated cytolysis, and CD4 T-cell alloproliferation. An increase in serum and graft levels of HLA-G has been noted in transplant patients with improved allograft survival. However, the clinical relevance of soluble serum HLA-G molecules in tolerant pediatric and young adult liver transplant patients remains to be studied.We examined the serum HLA-G levels in 42 pediatric and young adult liver transplant patients with a mean age of 15 years; 13 patients had operational tolerance (TOL), with complete immunosuppression withdrawal for 2.3 to 13.2 years.Median HLA-G level in patients with acute rejection (AR) was similar to the level in pediatric healthy volunteers (9.9 vs. 4.2 U/mL, P=0.13). HLA-G was higher in patients with stable liver function on immunosuppression (54.6 U/mL) than in patients with AR (P=0.01) and healthy volunteers (P=0.003), but almost 6-fold lower than in TOL patients (325.4 U/mL). HLA-G did not correlate with clinical confounders or a history of posttransplant lymphoproliferative disease or Epstein-Barr virus; although levels in the TOL group were negatively correlated with time after immunosuppression withdrawal (r=-0.75, P=0.003). In rejectors, HLA-G levels trended to negatively correlate with a higher number (r=-0.58) and greater severity of AR episodes (r=-0.56) after 1 year posttransplantation.Increased serum HLA-G levels track with operational tolerance of liver grafts and support favorable outcomes in pediatric and young adult recipients.

    View details for DOI 10.1097/TP.0b013e3181f546af

    View details for Web of Science ID 000283650200011

    View details for PubMedID 20814356

  • Acute Rejection of Small Intestine Allografts Is Associated With Increased Expression of Toll-like Receptors TRANSPLANTATION PROCEEDINGS Castillo, R. O., Wang, M., Ito, T., Higgins, J., Esquivel, C. O., Krams, S. M., Martinez, O. M. 2010; 42 (7): 2676-2678

    Abstract

    Although outcomes after intestinal transplantation have steadily improved owing to advances in immunosuppressive therapy, operative techniques, and postoperative medical management, rejection of the intestinal allograft continues to be a major clinical problem and constitutes the primary reason for graft loss. Although the adaptive immune system has been the major focus of investigation regarding regulation of rejection of the intestinal allograft, the role of the innate immune system has recently become of increased interest. We hypothesized that microbial products of the microflora associated with the intestinal allograft may engage the Toll-like receptor pathway of the innate immune system to potentiate alloimmune responses and rejection of the allograft. To investigate this, we established a murine model for orthotopic intestinal transplantation and allograft rejection. Using this model, we show that the expression of Toll-like receptor 2 is increased 50-fold and the expression of Toll-like receptor 4 is increased 200-fold during rejection of the allograft. We then performed survival studies that showed increased survival of mice, which had the Toll-like receptor knocked out. These preliminary studies suggest an important role for in innate immune system in acute rejection of the small intestinal allografts, and as such represents an emerging and promising area of investigation.

    View details for DOI 10.1016/j.transproceed.2010.05.157

    View details for Web of Science ID 000281942200052

    View details for PubMedID 20832568

  • Complete immunosuppressive drug withdrawal from liver transplant recipients conditioned with total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) Annual Clinical Congress of American-College-of-Surgeons Gallo, A., Strober, S., Concepcion, W., Esquivel, C. ELSEVIER SCIENCE INC. 2010: S64–S64
  • Biliary Complications Following Liver Transplantation DIGESTIVE DISEASES AND SCIENCES Ayoub, W. S., Esquivel, C. O., Martin, P. 2010; 55 (6): 1540-1546

    Abstract

    The aphorism that reconstruction of the biliary anastomosis is the "Achilles heel" of liver transplantation remains valid as biliary complications following liver transplantation remain a major source of morbidity with an incidence of 5-32%. Biliary complications include biliary strictures, biliary leaks, and stones. Biliary strictures can be divided into anastomotic and non-anastomotic. The management of biliary complications previously relied on surgical intervention. However, advances in endoscopic and radiological interventions have resulted in less-invasive options. The management of biliary complications post-liver transplantation requires a multidisciplinary approach and continues to evolve. Biliary complications also reflect the continued expansion of the donor pool with extended, live, and non-heart beating donors.

    View details for DOI 10.1007/s10620-010-1217-2

    View details for Web of Science ID 000278578800008

    View details for PubMedID 20411422

  • Syk Inhibits Lymphoma Migration to the Lymph Node in a Xenotransplantaion Model of Epstein Barr Virus (EBV) plus Post-Transplant Lymphomproliferaive Disorder (PTLD) 10th American Transplant Congress Hatton, O., Lambert, S., Vaysberg, M., Krams, S. M., Esquivel, C. O., Martinez, O. M. WILEY-BLACKWELL. 2010: 62–62
  • NK Cells Promote Acceptance of Liver Allografts Ito, T., Wang, M., Wai, L., Esquivel, C. O., Martinez, O. M., Krams, S. M. WILEY-BLACKWELL PUBLISHING, INC. 2010: 467
  • The Role of NKG2D in Transplantation Wai, L., Wang, M., Ito, T., Piard-Ruster, K., Esquivel, C. O., Martinez, O. M., Krams, S. M. WILEY-BLACKWELL PUBLISHING, INC. 2010: 217
  • HLA-G: A Novel Serological Marker for Liver Transplant Tolerance Zarkhin, V., Talisetti, A., Cox, K., Hurwitz, M., Esquivel, C., Sarwal, M. WILEY-BLACKWELL PUBLISHING, INC. 2010: 178
  • Wealthy Patients Are More Likely To Be Listed at Multiple Transplant Centers and Be Transplanted. Melcher, M. L., Javaid, B., Esquivel, C. O. WILEY-BLACKWELL PUBLISHING, INC. 2010: 288
  • The Effect of Calcineurin Inhibitor Dose on T Regulatory Cell Levels in Pediatric Liver Transplant Recipients. Piard-Ruster, K., Silva, R., Berquist, W., Pham, B., Gallo, A., Krams, S. M., Esquivel, C. O., Martinez, O. M. WILEY-BLACKWELL PUBLISHING, INC. 2010: 486
  • Toll-Like Receptor 4 Contributes to Rejection of Small Intestine Allografts. 10th American Transplant Congress Krams, S. M., Wang, M., Castillo, R. O., Ito, T., Esquivel, C. O., Martinez, O. M. WILEY-BLACKWELL. 2010: 312–312
  • A Peripheral Blood 12 Gene-Set for Diagnosis of Pediatric Liver Allograft Tolerance 10th American Transplant Congress Li, L., Talisetti, A., Hsieh, S., Cox, K., Esquivel, C., Concepcion, W., Sarwal, M. WILEY-BLACKWELL. 2010: 290–290
  • Natural Killer Cell Activation Receptor Expression Is Increased Post-Transplant in Pediatric Liver Transplant Recipients. 10th American Transplant Congress Pham, B., Silva, R., Piard-Ruster, K., Gallo, A., Esquivel, C. O., Martinez, O. M., Krams, S. M. WILEY-BLACKWELL. 2010: 486–486
  • Excellent Outcome in All Patients with Combined Kidney and Liver Transplant for Primary Hyperoxaluria Type 1. 10th American Transplant Congress Hwang, C. S., Gallo, A. E., Sarwal, M. M., Concepcion, W., Esquivel, C. O. WILEY-BLACKWELL. 2010: 457–457
  • Long-term outcome following pediatric liver transplantation for metabolic disorders PEDIATRIC TRANSPLANTATION Stevenson, T., Millan, M. T., Wayman, K., Berquist, W. E., Sarwal, M., Johnston, E. E., Esquivel, C. O., Enns, G. M. 2010; 14 (2): 268-275

    Abstract

    In order to determine long-term outcome, including survival, growth and development, following liver transplantation in children with metabolic disorders, we retrospectively reviewed charts of 54 children with metabolic disorders evaluated from 1989-2005 for presenting symptoms, transplantation timing and indications, survival, metabolic parameters, growth, and development. Thirty-three patients underwent liver transplantation (12 received combined liver-kidney transplants) at a median age of 21 months. At a median follow-up of 3.6 yr, patient survival was 100%, and liver and kidney allograft survival was 92%, and 100%, respectively. For the group as a whole, weight Z scores improved and body mass index at follow-up was in the normal range. Two yr post-transplantation, psychomotor development improved significantly (p < 0.01), but mental skills did not; however, both indices were in the low-normal range of development. When compared to patients with biliary atresia, children with metabolic disorders showed significantly lower mental developmental scores at one and two yr post-transplantation (p < 0.05), but psychomotor developmental scores were not significantly different. We conclude that, in patients with metabolic disorders meeting indications for transplantation, liver transplantation or combined liver-kidney transplantation (for those with accompanying renal failure) is associated with excellent long-term survival, improved growth, and improved psychomotor development.

    View details for DOI 10.1111/j.1399-3046.2009.01228.x

    View details for PubMedID 19671092

  • Liver Transplantation: Where We Are and Where We Are Heading TRANSPLANTATION PROCEEDINGS Esquivel, C. O. 2010; 42 (2): 610-612

    Abstract

    Outcomes after liver transplantation are outstanding; however, the limiting factor is the shortage of organs. Recently, the utilization of donors after cardiac death has been encouraged; however, such transplants are associated with a high complication rate, mainly a high incidence of biliary complications, particularly ischemic cholangiopahty, a serious complication that often leads to retransplantation. The second problem is the morbidity associated with the use of immunosuppressive drugs. In this manuscript, the current status of clinical protocols for induction of tolerance is briefly discussed. Furthermore, the future of research in transplantation will involve basic scientists and clinical scholars working in concert as has been developed at Stanford School of Medicine with the creation of the Institute for Immunity, Transplantation and Infection.

    View details for DOI 10.1016/j.transproceed.2010.02.013

    View details for Web of Science ID 000276051400055

    View details for PubMedID 20304205

  • Induced Tolerance to Rat Liver Allografts Involves the Apoptosis of Intragraft T Cells and the Generation of CD4(+)CD25(+)FoxP3(+) T Regulatory Cells LIVER TRANSPLANTATION Fujiki, M., Esquivel, C. O., Martinez, O. M., Strober, S., Uemoto, S., Krams, S. M. 2010; 16 (2): 147-154

    Abstract

    Posttransplant total lymphoid irradiation is a nonmyeloablative regimen that has been extensively studied in rodent models for the induction of tolerance to bone marrow and solid organ allografts. Previous studies of experimental models and clinical transplantation have used total lymphoid irradiation in combination with anti-lymphocyte-depleting reagents and donor cell infusion to promote graft acceptance. In a rat model of orthotopic liver transplantation, we demonstrated that total lymphoid irradiation alone induced long-term graft survival. Apoptotic T cells were detected in markedly higher numbers in the livers of the total lymphoid irradiation-treated group in comparison with the control group of liver allograft recipients. Intragraft CD4(+)CD25(+)FoxP3(+) cells were increased in the total lymphoid irradiation group in the first week post-transplant and remained elevated in the graft and in the spleen. Importantly, the adoptive transfer of splenocytes from recipients that received posttransplant total lymphoid irradiation prolonged the survival of donor heart grafts, but not third-party heart grafts, whereas the depletion of CD4(+)CD25(+) cells from transferred splenocytes abrogated this prolongation. We conclude that posttransplant total lymphoid irradiation significantly increases the apoptosis of T cells in the liver graft and allows the accumulation of CD4(+)CD25(+)FoxP3(+) T regulatory cells, which facilitate the generation of donor-specific tolerance.

    View details for DOI 10.1002/lt.21963

    View details for Web of Science ID 000274437800005

    View details for PubMedID 20104482

    View details for PubMedCentralID PMC2937179

  • A Peripheral Blood 12 Gene-Set for Diagnosis of Pediatric Liver Allograft Tolerance American-Society-of-Transplantation Annual Scientific Exchange Li, L., Talisetti, A., Hsieh, S., Cox, K., Esquivel, C., Concepcion, W., Sarwal, M. WILEY-BLACKWELL PUBLISHING, INC. 2010: 11–11
  • Acute Liver Failure at 26 Weeks' Gestation in a Patient with Sickle Cell Disease LIVER TRANSPLANTATION Greenberg, M., Daugherty, T. J., Elihu, A., Sharaf, R., Concepcion, W., Druzin, M., Esquivel, C. O. 2009; 15 (10): 1236-1241

    Abstract

    Orthotopic liver transplantation (OLT) for acute liver failure (ALF) during pregnancy is an uncommon occurrence with variable outcomes. In pregnancy-related liver failure, prompt diagnosis and immediate delivery are essential for a reversal of the underlying process and for maternal and fetal survival. In rare cases, the reason for ALF during pregnancy is either unknown or irreversible, and thus OLT may be necessary. This case demonstrates the development of cryptogenic ALF during the 26th week of pregnancy in a woman with sickle cell disease. She underwent successful cesarean delivery of a healthy male fetus at 27 weeks with concurrent OLT. This report provides a literature review of OLT in pregnancy and examines the common causes of ALF in the pregnant patient. On the basis of the management and outcome of our case and the literature review, we present an algorithm for the suggested management of ALF in pregnancy.

    View details for DOI 10.1002/It.21820

    View details for Web of Science ID 000270931500014

    View details for PubMedID 19790148

  • Clinical models of tolerance induction in pediatric transplantation PEDIATRIC TRANSPLANTATION Esquivel, C. O., Benden, C. 2009; 13 (4): 397-399
  • Transarterial Chemoinfusion for Hepatocellular Carcinoma as Downstaging Therapy and a Bridge toward Liver Transplantation AMERICAN JOURNAL OF TRANSPLANTATION De Luna, W., Sze, D. Y., Ahmed, A., Ha, B. Y., Ayoub, W., Keeffe, E. B., Cooper, A., Esquivel, C., Nguyen, M. H. 2009; 9 (5): 1158-1168

    Abstract

    Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.

    View details for DOI 10.1111/j.1600-6143.2009.02576.x

    View details for Web of Science ID 000265222200023

    View details for PubMedID 19344435

  • Pediatric Transplantation: Ten years on PEDIATRIC TRANSPLANTATION Benden, C., Dipchand, A. I., Danziger-Isakov, L. A., Esquivel, C. O., Ringden, O., Wray, J., Marks, S. D. 2009; 13 (3): 272–77
  • Syk, a novel therapeutic target for PTLD, drives Epstein Barr Virus B cell lymphoma growth and survival through the PI3K/Akt pathway Hatton, O. L., Lambert, S., Vaysberg, M., Krams, S. M., Esquivel, C. O., Martinez, O. M. AMER ASSOC IMMUNOLOGISTS. 2009
  • Induced Tolerance to Liver Allografts Involves Apoptosis and the Generation of Regulatory T Cells Fujiki, M., Esquivel, C. O., Martinez, O. M., Strober, S., Krams, S. M. AMER ASSOC IMMUNOLOGISTS. 2009
  • Insights into the Mechanism Responsible for Spontaneous Acceptance of Liver Allografts Zhuo, M., Ito, T., Wang, M., Esquivel, C. O., Martinez, O. M., Krams, S. M. AMER ASSOC IMMUNOLOGISTS. 2009
  • Decreases in circulating CD4(+)CD25(hi)FOXP3(+) cells and increases in intragraft FOXP3(+) cells accompany allograft rejection in pediatric liver allograft recipients PEDIATRIC TRANSPLANTATION Stenard, F., Nguyen, C., Cox, K., Kambham, N., Umetsu, D. T., Krams, S. M., Esquivel, C. O., Martinez, O. M. 2009; 13 (1): 70-80

    Abstract

    We examined CD4(+)CD25(hi)FOXP3(+) cells Treg in children following liver transplantation and determined the relationship between Treg cell levels in the blood and in the graft. Peripheral blood was obtained from pediatric liver transplant patients at sequential time points: pre-transplant, one month, 3-4 months, 6-7 months, and 11-12 months post-transplant. PBMC were isolated, labeled for CD4, CD25 and FOXP3 expression and analyzed by flow cytometry for CD4(+)CD25(hi)FOXP3(+) cells. Sorted CD4(+)CD25(hi) cells were assessed for functional activity. Pretransplant blood levels of CD4(+)CD25(hi)FOXP3(+) Treg cells were not significantly different from post-transplant blood levels of CD4(+)CD25(hi)FOXP3(+) Treg cells. However, the blood levels of CD4(+)CD25(hi)FOXP3(+) Treg cells were significantly decreased during acute rejection compared with levels when graft function was stable. Immunohistochemistry revealed that FOXP3(+) cells were increased in the portal region of livers with histopathologic evidence of acute graft rejection compared with livers without evidence of rejection and were localized primarily within the inflammatory infiltrate. These data indicate that Treg cells are found at the site of allograft rejection and may play a role in regulation of alloreactivity. Moreover, monitoring peripheral CD4(+)CD25(hi)FOXP3(+) Treg cell levels may be useful in improving the post-transplant management of pediatric liver allograft recipients.

    View details for DOI 10.1111/j.1399-3046.2008.00917.x

    View details for PubMedID 18331536

  • Multicenter Analysis of Liver Transplantation (LT) for Metastatic Neuroendocrine Tumor (NET): Is a MELD Exception Justified? Wecsler, J., Mateo, R., Levi, D., Schwartz, M., Marsh, W., Miller, C., Dickson, R., Rudich, S., Esquivel, C., Mulligan, D., Shaked, A., Genyk, Y., Solomon, H., Fisher, R., Hong, J., Pruett, T., Selby, R., Sher, L. WILEY-BLACKWELL PUBLISHING, INC. 2009: 286
  • Induced Tolerance to Liver Allografts Involves Apoptosis of Intragraft T Cells and the Generation of CD4+CD25+FoxP3+T Regulatory Cells. Fujiki, M., Esquivel, C. O., Martinez, O. M., Strober, S., Krams, S. M. WILEY-BLACKWELL PUBLISHING, INC. 2009: 662
  • Insights into the Mechanism Responsible for Spontaneous Acceptance of Rat Liver Allografts. Ito, T., Wang, M., Zhuo, M., Esquivel, C. O., Martinez, O. M., Krams, S. WILEY-BLACKWELL PUBLISHING, INC. 2009: 631
  • Induced Tolerance to Liver Allografts Involves Apoptosis and the Generation of Regulatory T Cells Fujiki, M., Strober, S., Martinez, O., Esquivel, C., Krams, S. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2009: S76
  • SIR 2008 annual meeting film panel case: Alagille syndrome JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Sze, D. Y., Esquivel, C. O. 2008; 19 (9): 1278-1280

    View details for DOI 10.1016/j.jvir.2008.04.016

    View details for Web of Science ID 000259054900003

    View details for PubMedID 18725089

  • Predictors of long term outcome following transjugular intrahepatic portosystemic shunt (TIPS) Larsen, M., Reynolds, J., Kamal, A., Mattix, B., Keeffe, E., Esquivel, C., Sze, D., Ahmed, A. NATURE PUBLISHING GROUP. 2008: S162
  • Factors affecting survival to intestinal transplantation in the very young pediatric patient 10th International Symposium on Small Bowel Transplantation Mian, S. I., Dutta, S., Le, B., Esquivel, C. O., Davis, K., Castillo, R. O. LIPPINCOTT WILLIAMS & WILKINS. 2008: 1287–89

    Abstract

    Very young pediatric patients awaiting intestinal transplantation have a high mortality rate due to long waiting times, scarcity of appropriate size donor organs, and mortality due to sepsis and liver failure. To investigate specific risk factors impacting survival to intestinal transplantation, we performed a 4-year institutional retrospective study comparing children who received grafts by age 18 months with children 18 months or younger who died while on the waiting list.Twelve children comprised the transplanted group and had the underlying diagnoses: necrotizing enterocolitis, gastroschisis, Hirschsprung's disease, and omphalocele. Ten children comprised the deceased group and had the underlying diagnoses: intestinal atresia, necrotizing enterocolitis, gastroschisis, and midgut volvulus. Multiple risk factors were assessed in these groups.No differences in residual small bowel length, presence of the colon, number of line infections, or number of central lines were found. The average body weight of the transplanted group trended higher, whereas the deceased group had more impairment of hepatic function. Intestinal atresia was the most common diagnosis in the deceased group while none of the transplanted group carried this diagnosis. Ileocecal valve was retained in 80% of the deceased group and in none of the transplanted group.In children younger than 18 months, risk factors affecting survival to intestinal transplantation include small body size and advanced liver disease. A primary diagnosis of intestinal atresia and the presence of the ileocecal valve may confer additional risk to these very young children.

    View details for DOI 10.1097/TP.0b013e31816dd236

    View details for Web of Science ID 000255904400012

    View details for PubMedID 18475185

  • Syk drives Epstein Barr virus-infected B cell lymphoma growth and survival through activation of the PI3K/Akt pathway 8th American Transplant Congress Hatton, O., Lambert, S., Vaysberg, M., Sharman, J., Krams, S. M., Esquivel, C. O., Martinez, O. M. WILEY-BLACKWELL. 2008: 477–477
  • Tolerance to rat liver allografts after total lymphoid irradiation is mediated by CD4+CD25+FOXP3+T cells Fujiki, M., Esquivel, C. O., Martinez, O. M., Strober, S., Krams, S. M. BLACKWELL PUBLISHING. 2008: 484
  • cFLIP inhibits death receptor-induced apoptosis of EBV-infected B cells from PTLD patients Lambert, S. L., Vaysberg, M., Snow, A. L., Krams, S. M., Esquivel, C. O., Martinez, O. M. BLACKWELL PUBLISHING. 2008: 620
  • Tolerance to rat liver allograft after total lymphoid irradiation is mediated by CD4+CD25+regulatory T cells Fujiki, M., Esquivel, C. O., Martinez, O. M., Strober, S., Krams, S. M. FEDERATION AMER SOC EXP BIOL. 2008
  • Non-adherence to post-transplant care: Prevalence, risk factors and outcomes in adolescent liver transplant recipients PEDIATRIC TRANSPLANTATION Berquist, R. K., Berquist, W. E., Esquivel, C. O., Cox, K. L., Wayman, K. I., Litt, I. F. 2008; 12 (2): 194-200

    Abstract

    This study examined the prevalence, demographic variables and adverse outcomes associated with non-adherence to post-transplant care in adolescent liver transplant recipients. We conducted a retrospective chart review of 111 adolescent patients (age 12-21 yr) greater than six months post-transplantation and defined non-adherence as not taking the immunosuppressive(s) or not attending any clinic visit in 2005. Fifty subjects (45.0%) were non-adherent and 61 (55.0%) were adherent. Twenty percent of the subjects did not attend clinic and 10.9% did not complete laboratory tests. Non-adherence was significantly associated with fewer completed laboratory tests (p < 0.0001), single parent status (p < 0.0186), and older age and greater years post-transplantation by both univariate and multivariate analyses (p < 0.008, p < 0.0141 and p < 0.0012, p < 0.0174, respectively). Non-adherence to medication was significantly associated with a rejection episode in 31 patients (p < 0.0069) but not in the subgroup of seven patients who stopped their immunosuppression completely. Non-adherence to post-transplant care is a prevalent problem in adolescents particularly of an older age and greater years post-transplantation. Rejection was a significant consequence of medication non-adherence except in a subgroup with presumed graft tolerance who discontinued their immunosuppression. These results emphasize the need for strict monitoring of adherence to post-transplant care to improve long-term survival and quality of life in adolescent transplant patients.

    View details for DOI 10.1111/j.1399-3046.2007.00809.x

    View details for Web of Science ID 000253637400013

    View details for PubMedID 18307668

  • Alloimmunization to red blood cell antigens affects clinical outcomes in liver transplant patients LIVER TRANSPLANTATION Boyd, S. D., Stenard, F., Lee, D. K., Goodnough, L. T., Esquivel, C. O., Fontaine, M. J. 2007; 13 (12): 1654-1661

    Abstract

    Transfusion therapy of liver transplant patients remains a challenge. High volumes of intraoperative blood transfusion have been shown to increase the risk of poor graft or patient survival. We conducted a retrospective study of 209 consecutive liver transplant cases at our institution. Only patients receiving their first liver transplant, with no other simultaneous organ transplants, were included. Cox proportional hazard modeling was used to identify clinical variables correlated with postoperative patient mortality. Statistically significant variables for poor patient survival were the number of red blood cell and plasma units transfused, a history of red blood cell alloantibodies, and the immunosuppressive regimen used. History of pregnancy also approached statistical significance but was less robust than the other 3 variables. Our findings suggest that blood transfusion and immune modulation greatly affect the survival of patients after liver transplantation.

    View details for DOI 10.1002/It.21241

    View details for PubMedID 18044783

  • Mutations to bid cleavage sites protect hepatocytes from apoptosis after ischemia/reperfusion injury TRANSPLANTATION Riddle-Taylor, E., Nagasaki, K., Lopez, J., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2007; 84 (6): 778-785

    Abstract

    Apoptosis of hepatocytes contributes to many forms of liver pathology and can compromise liver function. Hepatocytes have been shown to require mitochondrial disruption to execute apoptosis, a process that is controlled by members of the Bcl-2 family. Bid is a proapoptotic Bcl-2 family member that is cleaved to its active form, tBid, by caspase 8 and granzyme B. Studies in the Bid-deficient mouse have established that hepatocytes require Bid to undergo apoptosis.We generated aspartic acid to glutamic acid mutations in the rat Bid protein, at the caspase 8 and granzyme B cleavage sites, and utilized recombinant adenoviruses to express this protein in hepatoma cells and in the livers of rats.Cells transduced with recombinant adenoviruses encoding Bid containing mutations to the caspase 8 and granzyme B cleavage sites are significantly protected from both tumor necrosis factor-alpha-induced and cell-mediated apoptosis. Protection occurs through a mechanism that includes decreased Bid cleavage, caspase activation, and mitochondrial membrane damage. Further, after warm ischemia/reperfusion injury, we show that rats expressing cleavage-resistant Bid in the liver display significantly less hepatocyte apoptosis as compared to control rat livers and this results in improved liver function and survival.Our results suggest that reagents that prevent the cleavage of Bid would be an effective strategy to inhibit hepatocyte apoptosis and decrease liver injury.

    View details for DOI 10.1097/01.tp.0000281555.18782.2b

    View details for Web of Science ID 000249841700017

    View details for PubMedID 17893612

  • Liver allografts are toleragenic in rats conditioned with posttransplant total lymphoid irradiation TRANSPLANTATION Nagasaki, K., Obara, H., Xiong, A., Kambham, N., Strober, S., Esquivel, C. O., Millan, M. T. 2007; 84 (5): 619-628

    Abstract

    Posttransplant total lymphoid irradiation (TLI) treatment has been applied to tolerance induction protocols in heart and kidney transplantation models.We examined the efficacy and mechanism of posttransplant TLI treatment in the induction and maintenance of tolerance in a rat orthotopic liver transplantation model.Posttransplant TLI prolonged ACI (RT1(a)) liver allograft survival in Lewis (RT1(b)) hosts, with 50% long-term engraftment without immunosuppression and without evidence of chronic rejection. Injection of donor-type liver mononuclear cells (LMCs) facilitated the prolongation of graft survival, with more than 70% of grafts in LMC recipients surviving more than 100 days without chronic rejection. Recipients with long-term liver allograft survival accepted ACI but not PVG skin grafts. In TLI-conditioned recipients with accepted grafts, apoptosis occurred predominantly in graft-infiltrating leukocytes. In contrast, there were few apoptotic leukocytes in rejecting grafts. Recipients with long-term graft acceptance (>100 days of survival) demonstrated evidence of immune deviation; mixed lymphocyte reaction to ACI stimulator cells was vigorous, but secretion of interferon-gamma and interleukin-2 was reduced. In tolerant recipients, the number of Foxp3(+) CD25(+) CD4(+) regulatory T cells was increased in the liver allograft as well as in the peripheral blood.We conclude that posttransplant TLI induces tolerance to liver allografts via a mechanism involving apoptotic cell-deletion and immunoregulation.

    View details for DOI 10.1097/01.tp.0000278104.15002.64

    View details for Web of Science ID 000249574900009

    View details for PubMedID 17876275

  • Outcomes of transplantation in children with primary hepatic malignancy PEDIATRIC TRANSPLANTATION Beaunoyer, M., Vanatta, J. M., Oyihara, M., Strichartz, D., Dahl, G., Berquist, W. E., Castillo, R. O., Cox, K. L., Esquivel, C. O. 2007; 11 (6): 655-660

    Abstract

    HBL and HCC are the most common hepatic malignancies in children. The role of OLT in children with HCC is still a matter of debate. The aim of this study was to review our experience of OLT for HCC. Medical records of patients (<18 yr) who underwent OLT for HCC were reviewed and compared to children who underwent OLT for HBL and for indications other than malignancy. There were 25 patients: HCC (10 cases) and HBL (15 cases). The actuarial patient survival for HCC at one and five yr was 100% and 83.3%, for the HBL group the survival was 86.7% at both one and five yr, and for indications (n=377) other than malignancy the patient survival for pediatric OLT at our center was 87.7% and 84.7% at one and five yr, respectively. The actuarial recurrence free survival at five yr was 83.3% for HCC and 66.8% for HBL. In conclusion, OLT is a good therapeutic modality for children with HCC and HBL.

    View details for DOI 10.1111/j.1399-3046.2007.00751.x

    View details for Web of Science ID 000249004000015

    View details for PubMedID 17663690

  • Sirolimus as maintenance immunosuppression in pediatric intestinal transplantation. Safta, A. M., Castillo, R. O., Cox, K., Esquivel, C. O. WILEY-BLACKWELL. 2007: 78–78
  • Should Milan criteria be applied to children with hepatocellular carcinom (HCC)? Beaunoyer, M., Vanatta, J., Ogihara, M., Strichartz, D., Cox, K., Esquivel, C. BLACKWELL PUBLISHING. 2007: 65–66
  • Mutations to Bid cleavage sites protect hepatocytes from apoptosis following ischemia/reperfusion injury Krams, S. M., Nagasaki, K., Esquivel, C. O., Martinez, O. M., Riddle, E. AMER ASSOC IMMUNOLOGISTS. 2007
  • Status of liver transplantation in infants < 5 kg PEDIATRIC TRANSPLANTATION Vanatta, J. M., Esquivel, C. O. 2007; 11 (1): 5–9
  • EBV can protect latently infected B cell lymphomas from death receptor-induced apoptosis JOURNAL OF IMMUNOLOGY Snow, A. L., Lambert, S. L., Natkunam, Y., Esquivel, C. O., Krams, S. M., Martinez, O. M. 2006; 177 (5): 3283-3293

    Abstract

    The relationship between EBV infection and sensitivity to death receptor (DR)-induced apoptosis is poorly understood. Using EBV- and EBV+ BJAB cells, we provide the first evidence that EBV can protect latently infected B cell lymphomas from apoptosis triggered through Fas or TRAIL receptors. Caspase 8 activation was impaired and cellular FLIP recruitment was enriched in death-inducing signaling complexes formed in EBV-infected BJAB cells relative to parent BJAB cells. Furthermore, latent membrane protein 1 expression alone could reduce caspase activation and confer partial resistance to DR apoptosis in BJAB cells. This protective effect was dependent on C-terminal activating region 2-driven NF-kappaB activation, which in turn up-regulated cellular FLIP expression in latent membrane protein 1+ BJAB cells. Thus, the ability of latent EBV to block DR apoptosis may help to ensure the survival of host cells during B cell differentiation, and contribute to the development of B cell lymphomas, especially in immunocompromised individuals.

    View details for Web of Science ID 000240002800065

    View details for PubMedID 16920969

  • Pediatric intestinal transplantation at Packard children's hospital/Stanford University medical center: Report of a four-year experience 9th International Symposium on Small Bowel Transplantation Castillo, R. O., Zarge, R., Cox, K., Strichartz, D., Berquist, W., Bonham, C. A., Esquivel, C. O. ELSEVIER SCIENCE INC. 2006: 1716–17

    Abstract

    We report a 4-year experience of a new program in pediatric intestinal transplantation. Among 50 children referred for evaluation, 27 were listed for transplantation. Two children originally listed for combined liver/small bowel transplant were changed to isolated intestinal transplant as rehabilitation efforts resulted in full recovery of hepatic function. Eighteen children received 18 grafts: 12 liver/intestine, 5 isolated intestine, and 1 multivisceral. Mean age at transplant was 3.6 year with 75% of patients aged 0 to 2 years. Five listed children died while waiting and four were still on the list. Immunotherapy included antithymocyte globulin induction and tacrolimus, sirolimus, and prednisone maintenance. At 1 year, patient and graft survivals were 75% and 67%, respectively. For isolated intestine, 1 year survivals were 100% and 75%, while for combined liver/intestine, they were 71% for both. Enteral autonomy is 100% with total parenteral nutrition stopping by 35.8 days (mean). We had two patients develop posttransplant lymphoproliferative disorder and three, exfoliative rejection, one of whom recovered completely. In conclusion, our program in pediatric intestinal transplantation has become well established with a high proportion of smaller/younger children receiving grafts. Outcomes achieved levels expected based on The Intestinal Transplant Registry and UNOS criteria, which were better than expected for isolated intestinal transplants and achievement of enteral autonomy.

    View details for DOI 10.1016/j.transproceed.2006.05.038

    View details for Web of Science ID 000240051700022

    View details for PubMedID 16908259

  • Adolescent non-adherence: Prevalence and consequences in liver transplant recipients PEDIATRIC TRANSPLANTATION Berquist, R. K., Berquist, W. E., Esquivel, C. O., Cox, K. L., Wayman, K. I., Litt, I. F. 2006; 10 (3): 304-310

    Abstract

    Few studies have examined the prevalence, demographic variables and adverse consequences associated with non-adherence to immunosuppressive therapy in the adolescent liver transplant population. Our hypothesis is that a significant proportion of adolescent liver transplant recipients exhibit non-adherence to medical regimens and that certain demographic and medical condition-related characteristics can be identified as potential predictors of non-adherent behavior. Furthermore, non-adherence leads to a greater incidence of morbidity and mortality in this population as compared with the adherent subset of adolescent patients. We reviewed the charts of 97 patients from 1987 to 2002 who by December of 2002 had survived at least 1 yr post-transplant and were followed by the Pediatric Liver Transplant Service at any point during their adolescent period (ages of 12-21). Non-adherence was defined as documentation of a report of non-adherence by a patient, parent or healthcare provider that was recorded in the patient's legal medical record. Descriptive statistics were used to determine the prevalence, demographic variables and adverse outcomes associated with non-adherence to immunosuppressive therapy. Categorical variables were analyzed using the chi-square test or the Fisher exact probability test. The unpaired Student's t-test was used to analyze the continuous variable of age at transplant. Using the inclusion criteria, a total of 97 patients represented the study sample of whom 37 subjects (38.1%) were defined as non-adherent and 60 (61.8%) were adherent. Non-adherent subjects were more likely to be female, older (>18 yr) and from a single-parent household. There was no significant difference in immunosuppressive regimen between non-adherent and adherent patients. Non-adherence was significantly (p<0.025) associated with lower socioeconomic status (SES), older age at transplant (p<0.005, 95% CI: -5.5 to -.99, Student's t-test) and episodes of late acute rejection (p<.001). Non-adherence was also significantly associated with re-transplantation and death secondary to chronic rejection by the Fisher exact test (p<0.006 and p<0.05, respectively). Non-adherence to immunosuppressive therapy is a prevalent problem that is correlated with certain demographic and medical condition-related risk factors and more frequent adverse consequences in the adolescent liver transplant population. The greater incidence of late acute rejection, death and re-transplantation owing to chronic rejection in non-adherent patients suggests that non-adherence is significantly associated with an increased risk of morbidity and mortality. Further investigation to identify patients at greatest risk for non-adherence is necessary to design the most effective intervention to increase patient survival and well being.

    View details for DOI 10.1111/j.1399-3046.2005.00451.x

    View details for Web of Science ID 000237096700007

    View details for PubMedID 16677353

  • Improved pain management in pediatric postoperative liver transplant patients using parental education and non-pharmacologic interventions PEDIATRIC TRANSPLANTATION Sharek, P. J., Wayman, K., Lin, E., Strichartz, D., Sentivany-Collins, S., Good, J., Esquivel, C., Brown, M., Cox, K. 2006; 10 (2): 172-177

    Abstract

    A pain management intervention, consisting of pretransplant parental education and support, pre- and postoperative behavioral pediatrics consultation, postoperative physical and occupational therapy consultation, and implementation of non-pharmacologic pain management strategies, was introduced to all pediatrics patients receiving liver transplants at Lucile Packard Children's Hospital beginning August 2001. Children receiving transplants pre-intervention (May, 2000 to February, 2001) and post-intervention (August, 2001 to March, 2002) were compared using pain scores, parent perception of pain ratings, length of stay, ventilator days, total cost, and opioid use. A total of 27 children were evaluated (13 historical control, 14 intervention). The two populations did not differ on age at transplant (mean age 53.8 vs. 63.6 months), sex (46.1% vs. 50% male), ethnicity (53.8% vs. 57.1% white, non-Hispanic) weight at transplant (17.5 vs. 24.7 kg), percent with biliary atresia as the primary reason for transplant (42.9% vs. 69.2%), percent with status 1 transplant listing score (38.5% vs. 50.0%), or public insurance status (30.8 vs. 57.2% with Medicaid). No differences were found in mean pediatric intensive care unit (PICU) postoperative length of stay (6.7 vs. 5.3 days), total postoperative length of stay (17.5 vs. 17.5 days), total inpatient length of stay (27.0 vs. 24.4 days), time to extubation (30 vs. 24.3 h), total cost (dollar 147,983 vs. dollar 157,882) or opioid use through postoperative day (POD) 6 (0.24 vs. 0.25 mg/kg/day morphine equivalent). A decrease in mean pain score between POD 0 and 6 (2.82 vs. 2.12; p = 0.047), a decrease in mean parental pain perception score (3.1 vs. 2.1; p = 0.001), and an increase in number of pain assessments per 12 h shift (3.43 vs. 6.79; p < 0.005) were seen. A comprehensive non-pharmacologic postoperative pain management program in children receiving a liver transplant was associated with decreased pain scores, improved parent perception of pain, and an increased number of pain assessments per 12 h shift. No increases in lengths of stay (PICU, postoperative, total), time to extubation, or total cost were found.

    View details for DOI 10.1111/j.1399-3046.2005.00438.x

    View details for PubMedID 16573603

  • Keratins as susceptibility genes for end-stage liver disease GASTROENTEROLOGY Ku, N. O., Lim, J. K., Krams, S. M., Esquivel, C. O., Keeffe, E. B., Wright, T. L., Parry, D. A., Omary, M. B. 2005; 129 (3): 885-893

    Abstract

    Keratins 8 and 18 protect the liver from stress. Keratin 8 and 18 variants in 17 of 467 liver disease explants and 2 of 349 blood bank controls were previously reported in 5 analyzed exonic regions. We asked whether mutations were present in the remaining 10 exons of keratins 8 and 18.Exonic regions were polymerase chain reaction-amplified from genomic DNA, isolated from the above-mentioned 2 cohorts, and analyzed for the presence of mutations. Mutant keratins were also studied biochemically.We identified 10 novel keratin 8 and 18 heterozygous variants in 44 of 467 explants and 11 of 349 controls: keratin 18 deletion (delta64-71), a keratin 8 frameshift that truncates the last 14 amino acids; 8 missense keratin 8 and 18 alterations; and several new polymorphisms. The most common variant, keratin 8 R340H, at the highly conserved R340 was found in 30 of 467 explants and 10 of 349 controls (P = .02) and was confirmed in the diseased livers by generation of an R340H-specific antibody. Germline transmission and variant protein expression were verified. The mutations involved a variety of liver diseases, and some variants had an ethnic background preponderance. Mutations that introduced disulfide bonds (keratin 8 G61C or R453C) decreased keratin solubility, particularly after oxidative stress, whereas others decreased keratin 8 phosphorylation (keratin 8 G433S).The overall frequency of keratin 8 and 18 variants was 12.4% in 467 liver disease explants and 3.7% in 349 blood bank controls (P < .0001). Variants can alter keratin solubility or phosphorylation and may render individuals susceptible to end-stage liver disease, depending on their genetic background and exposure to other insults, such as alcohol or viral infection.

    View details for DOI 10.1053/j.gastro.2005.06.065

    View details for Web of Science ID 000231816500016

    View details for PubMedID 16143128

  • IFN-gamma, produced by NK cells that infiltrate liver allografts early after transplantation, links the innate and adaptive immune responses AMERICAN JOURNAL OF TRANSPLANTATION Obara, H., Nagasaki, K., Hsieh, C. L., Ogura, Y., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2005; 5 (9): 2094-2103

    Abstract

    The role of NK cells following solid organ transplantation remains unclear. We examined NK cells in acute allograft rejection using a high responder model (DA-->Lewis) of rat orthotopic liver transplantation. Recipient-derived NK cells infiltrated liver allografts early after transplantation. Since chemokines are important in the trafficking of cells to areas of inflammation, we determined the intragraft expression of chemokines known to attract NK cells. CCL3 was significantly increased in allografts at 6 h post-transplant as compared to syngeneic grafts whereas CCL2 and CXCL10 were elevated in both syngeneic and allogeneic grafts. CXCL10 and CX3CL1 were significantly upregulated in allografts by day 3 post-transplant as compared to syngeneic grafts suggesting a role for these chemokines in the recruitment of effector cells to allografts. Graft-infiltrating NK cells were shown to be a major source of IFN-gamma, and IFN-gamma levels in the serum were markedly increased, specifically in allograft recipients, by day 3 post-transplant. Accordingly, in the absence of NK cells the levels of IFN-gamma were significantly decreased. Furthermore, graft survival was significantly prolonged. These data suggest that IFN-gamma-producing NK cells are an important link between the innate and adaptive immune responses early after transplantation.

    View details for DOI 10.1111/j.1600-6143.2005.00995.x

    View details for Web of Science ID 000231023700003

    View details for PubMedID 16095488

    View details for PubMedCentralID PMC1473982

  • Complete immunosuppressive withdrawal as a uniform approach to post-transplant lymphoproliferative disease in pediatric liver transplantation 4th Annual Meeting of the American-Transplant-Congress Hurwitz, M., Desai, D. M., Cox, K. L., Berquist, W. E., Esquivel, C. O., Millan, M. T. WILEY-BLACKWELL PUBLISHING, INC. 2004: 267–72

    Abstract

    Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients is associated with a high mortality (up to 60%) and the younger age groups, who are predominantly EBV-naïve, are at highest risk for development of this disease. The aim of this study is to assess, in this high-risk group, patient outcome and graft loss to rejection when complete withdrawal of immunosuppressive agents (IMS) is instituted as the mainstay of treatment in addition to the use of standard therapy. A retrospective analysis of 335 pediatric patients whose liver transplants were performed by our team between September 1988 and September 2002, was carried out through review of computer records, database and patient charts. Fifty patients developed either EBV or PTLD; 80% were < or =2 yr of age. Of these 50 patients, 19 had a positive tissue diagnosis for PTLD and 31 were diagnosed with EBV infection, 14 of whom had positive tissue for EBV. Fifty-eight percent of patients who developed PTLD and 51.6% of patients with EBV received antibody for induction or treatment of rejection prior to onset of disease. Forty-six patients (92%) received post-transplant antiviral prophylaxis with ganciclovir or acyclovir. Antiviral treatment included ganciclovir in 76%, acyclovir in 20% and Cytogam (in addition to one of the former agents) in 44%. In those with PTLD, treatment included chemotherapy (n = 1), Rituximab (n = 2), and ocular radiation (n = 1). IMS was stopped in all patients with PTLD and in 19 with EBV infection and was held as long as there was no allograft rejection. Eight patients have remained off IMS for a mean of 1535.5 +/- 623 days. Of the 21 patients who were restarted on IMS for acute rejection, 18 responded to steroids and/or reinstitution of low-dose calcineurin inhibitors. The mean time to rejection while off IMS in this group was 107.43 +/- 140 days (range: 7-476). Two patients were re-transplanted for chronic rejection; one had chronic rejection that existed prior to discontinuing IMS. The mortality rate in our series was 31.6% in those with PTLD and 6% in those with EBV disease. The cause of death was related to PTLD or sepsis in all cases; no deaths were due to graft loss from acute or chronic rejection. PTLD is associated with high mortality in the pediatric population. Based on this report, we advocate aggressive management of PTLD that is composed of early cessation of IMS, the use of antiviral therapy, and chemotherapy when indicated. Episodes of rejection that occur after stopping IMS can be successfully treated with standard therapy without graft loss to acute rejection.

    View details for Web of Science ID 000221693200014

    View details for PubMedID 15176965

  • Our new president - Emmet B Keeffe, MD GASTROENTEROLOGY Omary, M. B., Esquivel, C. O. 2004; 126 (5): 1454-1460

    View details for DOI 10.1053/j.gastro.2004.03.031

    View details for Web of Science ID 000221217100026

    View details for PubMedID 15131805

  • One hundred percent patient and kidney allograft survival with simultaneous liver and kidney transplantation in infants with primary hyperoxaluria: A single-center experience TRANSPLANTATION Millan, M. T., Berquist, W. E., So, S. K., Sarwal, M. M., Wayman, K. I., Cox, K. L., Filler, G., Salvatierra, O., Esquivel, C. O. 2003; 76 (10): 1458-1463

    Abstract

    Combined liver-kidney transplantation is the definitive treatment for end-stage renal disease caused by primary hyperoxaluria type I (PH1). The infantile form is characterized by renal failure early in life, advanced systemic oxalosis, and a formidable mortality rate. Although others have reported on overall results of transplantation for PH1 covering a wide age spectrum, none has specifically addressed the high-risk infantile form of the disease.Six infants with PH1 underwent simultaneous liver-kidney transplantation at our center between May 1994 and August 1998. Diagnosis was made at 5.2+/-3.3 months of age, they were on dialysis for 11.8+/-2.3 months, and they underwent transplantation at 14.8+/-3.0 months of age when they weighed 10.6+/-1.7 kg.At a mean follow-up of 6.4+/-1.7 years (range, 3.9-8.1 years), we report 100% patient and kidney allograft survival. There were no cases of acute tubular necrosis. Long-term kidney allograft function remained stable in all patients, with serum creatinine values of less than 1.1 mg/dL and a mean creatinine clearance of 99 mL/min/1.73 m2 at follow-up. Those who received combined hemodialysis and peritoneal dialysis pretransplant had lower posttransplant urinary oxalate values than those receiving peritoneal dialysis alone. There was improvement in growth and psychomotor and mental developmental scores after transplantation.Combined liver-kidney transplantation for the infantile presentation of PH1 is associated with excellent outcome when the approach includes early diagnosis and early combined transplantation, aggressive pretransplant dialysis, and avoidance of posttransplant renal dysfunction.

    View details for DOI 10.1097/01.TP.0000084203.76110.AC

    View details for Web of Science ID 000186833400014

    View details for PubMedID 14657686

  • Keratin 8 and 18 mutations are risk factors for developing liver disease of multiple etiologies PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ku, N. O., Darling, J. M., Krams, S. M., Esquivel, C. O., Keeffe, E. B., Sibley, R. K., Lee, Y. M., Wright, T. L., Omary, M. B. 2003; 100 (10): 6063-6068

    Abstract

    Keratin 8 and 18 (K8K18) mutations are found in patients with cryptogenic cirrhosis, but the role of keratin mutations in noncryptogenic cirrhosis and the incidence of keratin mutations in the general population are not known. We screened for K8K18 mutations in genomic DNA isolated from 314 liver explants of patients who primarily had noncryptogenic cirrhosis, and from 349 blood bank volunteers. Seven unique K8K18 mutations were found in 11 independent patients with biliary atresia, hepatitis BC, alcohol, primary biliary cirrhosis, and fulminant hepatitis. Seven of the 11 patients had mutations previously described in patients with cryptogenic cirrhosis: K8 Tyr-53 --> His, K8 Gly-61 --> Cys, and K18 His-127 --> Leu. The four remaining patients had mutations at one K8 and three other K18 new sites. Of the 349 blood bank control samples, only one contained the Tyr-53 --> His and one the Gly-61 --> Cys K8 mutations (P < 0.004 when comparing cirrhosis versus control groups). Two additional mutations were found in both the liver disease and blood bank groups and, hence, likely represent polymorphisms. Livers with keratin mutations had cytoplasmic filamentous deposits that were less frequent in livers without the mutations (P = 0.03). Therefore, K8K18 are likely susceptibility genes for developing cryptogenic and noncryptogenic forms of liver disease.

    View details for DOI 10.1073/pnas.0936165100

    View details for Web of Science ID 000182939400089

    View details for PubMedID 12724528

    View details for PubMedCentralID PMC156326

  • Is liver transplantation justified for the treatment of HCC in Child's A patients? Not always. LIVER TRANSPLANTATION Esquivel, C. O. 2003; 9 (5): 521–22

    View details for DOI 10.1053/jlts.2003.50112

    View details for Web of Science ID 000182640900012

    View details for PubMedID 12740797

  • A patient with hepatitis C-related liver cirrhosis and hepatocellular carcinoma who was cured with an orthotopic liver transplantation and interferon therapy JOURNAL OF GASTROENTEROLOGY Shibata, M., Yanaga, K., Morizane, T., Yanagawa, T., Hirakawa, M., Ueno, Y., Esquivel, C. O., Mitamura, K. 2003; 38 (6): 598-602

    Abstract

    A patient with hepatitis C virus (HCV)-related liver cirrhosis and hepatocellular carcinoma (HCC) was treated successfully with an orthotopic liver transplantation (OLT) followed by interferon therapy. The 36-year-old Japanese man was diagnosed as having liver cirrhosis in 1983. HCC was detected in 1991, and by 1994, jaundice and ascites had developed. The patient underwent OLT in June 1995, after which hepatitis C recurred, with elevated aminotransferases. His liver biopsy specimen showed chronic active hepatitis. He was given interferon-alpha three times weekly for 24 weeks in 1999. Six months after the end of the interferon treatment, the patient's serum HCV RNA became negative, with normalization of aminotransferases, and his liver histology exhibited amelioration of fibrosis and inflammation. At the present time, he remains free of HCC (more than 6.5 years after the OLT) and free of HCV RNA (more than 2.5 years since interferon therapy was completed). This is the first Japanese patient whose HCC was cured by OLT and HCV was eradicated by interferon therapy.

    View details for DOI 10.1007/s00535-002-1111-6

    View details for Web of Science ID 000183774700013

    View details for PubMedID 12858850

  • Identification of Epstein-Barr virus-specific CD8(+) T lymphocytes in the circulation of pediatric transplant recipients TRANSPLANTATION Falco, D. A., Nepomuceno, R. R., Krams, S. M., Lee, P. P., DAVIS, M. M., Salvatierra, O., Alexander, S. R., Esquivel, C. O., Cox, K. L., Frankel, L. R., Martinez, O. M. 2002; 74 (4): 501-510

    Abstract

    Pediatric transplant recipients are at increased risk for Epstein Barr virus (EBV)-related B cell lymphomas. In healthy individuals, the expansion of EBV-infected B cells is controlled by CD8+ cytotoxic T cells. However, immunosuppressive therapy may compromise antiviral immunity. We identified and determined the frequency of EBV-specific T cells in the peripheral blood of pediatric transplant recipients.HLA-B*0801 and HLA-A*0201 tetramers folded with immunodominant EBV peptides were used to detect EBV-specific CD8+ T cells by flow cytometry in peripheral blood mononuclear cells from 24 pediatric liver and kidney transplant recipients. The expression of CD38 and CD45RO on EBV-specific, tetramer-binding cells was also examined in a subset of patients by immunofluorescent staining and flow cytometry.Tetramer-binding CD8+ T cells were identified in 21 of 24 transplant recipients. EBV-specific CD8+ T cells were detected as early as 4 weeks after transplant in EBV seronegative patients receiving an organ from an EBV seropositive donor. The frequencies (expressed as a percentage of the CD8+ T cells) of the tetramer-binding cells were HLA-B8-RAKFKQLL (BZLF1 lytic antigen peptide) tetramer, range=0.96 to 3.94%; HLA-B8-FLRGRAYGL (EBNA3A latent antigen peptide) tetramer, range=0.03 to 0.59%; and HLA-A2-GLCTLVAML (BMLF1 lytic antigen peptide) tetramer, range=0.06 to 0.76%. The majority of tetramer reactive cells displayed an activated/memory phenotype.Pediatric transplant recipients receiving immunosuppression can generate EBV-specific CD8+ T cells. Phenotypic and functional analysis of tetramer cells may prove useful in defining and monitoring EBV infection in the posttransplant patient.

    View details for PubMedID 12352909

  • Thirteen years' experience in pediatric liver transplantation: Differences between tacrolimus and cyclosporine 2nd International Congress on Immunosuppression Zajicek, A., Esquivel, C., MILLAN, M., Cox, K., Berquist, R., Berquist, W. ELSEVIER SCIENCE INC. 2002: 1976–78

    View details for Web of Science ID 000177369700254

    View details for PubMedID 12176653

  • Liver transplantation for fulminant hepatitis at Stanford University 86th Annual Congress of the Japanese-Society-of-Gastroenterology Lu, A., Monge, H., Drazan, K., MILLAN, M., Esquivel, C. O. SPRINGER TOKYO. 2002: 82–87

    Abstract

    To review the clinical characteristics and outcomes of 26 patients evaluated for liver transplantation for fulminant hepatic failure at Stanford University and Lucile Packard Children's Hospital in an attempt to identify risk factors and prognostic predictors of survival.A retrospective review of the records of 26 consecutive patients who were evaluated for possible liver transplantation for acute liver failure from May 1, 1995, to January 1, 2000. Pretransplant patient demographics and clinical characteristics were collected, and the data were analyzed by univariate and multivariate analysis.Clinical assessment of encephalopathy did not predict outcome. Patients with abnormal computed tomography (CT) of the brain had a twofold increase in mortality compared with those patients with normal studies (p = 0.03). Patients requiring mechanical ventilation and continuous venovenous hemofiltration (CVVH) also had a poor prognosis.Predictors of poor outcome after fulminant hepatic failure include abnormal CT scan, mechanical ventilation, and requirement for hemofiltration.

    View details for Web of Science ID 000176596300017

    View details for PubMedID 12109673

  • Epstein-Barr virus infection is associated with endothelial bcl-2 expression in transplant liver allografts TRANSPLANTATION Millan, M. T., Natkunam, Y., Clarke-Katzenberg, R., Desai, D., Prapong, W., So, S. K., Esquivel, C. O., Sibley, R., Ferran, C., Martinez, O. M. 2002; 73 (3): 465-469

    Abstract

    In liver transplant recipients with Epstein-Barr virus (EBV) disease, we reported a low rate of acute rejection after stopping or markedly lowering immunosuppression. This observation led to the hypothesis that EBV, as a means of viral persistence, induces expression of antiapoptotic factors and these factors, in turn, confer protection to the transplanted organ. Bcl-2, an antiapoptotic factor induced by EBV in various host cells, is not normally expressed in the liver. We questioned whether bcl-2 is expressed in the transplanted liver and whether its expression is modified by EBV.Retrospective liver biopsy specimen from liver transplant patients diagnosed with EBV (n=12) were examined for the presence of bcl-2 by immunohistochemistry and compared with EBV (-) transplant (n=15), and nontransplant (n=13) livers.The most significant finding was the presence of endothelial bcl-2 expression in the majority of EBV (+) transplant samples examined (67%) and its relative absence in the other two groups (P<0.005). There was also bcl-2 expression in the hepatocytes and lymphocytes of the majority of transplant liver samples, irrespective of EBV status.We have identified a strong association between EBV infection and endothelial bcl-2 expression in transplant livers. We also found that transplantation, in itself, was associated with bcl-2 expression in the hepatocytes and lymphocytes of liver allografts.

    View details for Web of Science ID 000174115400023

    View details for PubMedID 11884946

  • The role of interventional radiology in a pediatric liver transplant program PEDIATRIC TRANSPLANTATION Sze, D. Y., Esquivel, C. O. 2002; 6 (1): 1-4

    View details for Web of Science ID 000174799300001

    View details for PubMedID 11906633

  • Resistance to Fas-mediated apoptosis in EBV-infected B cell lymphomas is due to defects in the proximal Fas signaling pathway JOURNAL OF IMMUNOLOGY Snow, A. L., Chen, L. J., Nepomuceno, R. R., Krams, S. M., Esquivel, C. O., Martinez, O. M. 2001; 167 (9): 5404-5411

    Abstract

    Post-transplant lymphoproliferative disorder is characterized by the outgrowth of EBV-infected B cell lymphomas in immunosuppressed transplant recipients. Using a panel of EBV-infected spontaneous lymphoblastoid cell lines (SLCL) derived from post-transplant lymphoproliferative disorder patients, we assessed the sensitivity of such lymphomas to Fas-mediated cell death. Treatment with either an agonist anti-Fas mAb or Fas ligand-expressing cells identifies two subsets of SLCL based on their sensitivity or resistance to Fas-driven apoptosis. Fas resistance in these cells cannot be attributed to reduced Fas expression or to mutations in the Fas molecule itself. In addition, all SLCL are sensitive to staurosporine-induced cell death, indicating that there is no global defect in apoptosis. Although all SLCL express comparable levels of Fas signaling molecules including Fas-associated death domain protein, caspase 8, and caspase 3, Fas-resistant SLCL exhibit a block in Fas-signaling before caspase 3 activation. In two SLCL, this block results in impaired assembly of the death-inducing signaling complex, resulting in reduced caspase 8 activation. In a third Fas-resistant SLCL, caspase 3 activation is hindered despite intact death-inducing signaling complex formation and caspase 8 activation. Whereas multiple mechanisms exist by which tumor cells can evade Fas-mediated apoptosis, these studies suggest that the proximal Fas-signaling pathway is impeded in Fas-resistant post-transplant lymphoproliferative disorder-associated EBV(+) B cell lymphomas.

    View details for Web of Science ID 000171858500080

    View details for PubMedID 11673559

  • Apoptosis and allograft rejection in the absence of CD8(+) T cells TRANSPLANTATION Ogura, Y., Martinez, O. M., Villanueva, J. C., Tait, J. F., Strauss, H. W., Higgins, J. P., Tanaka, K., Esquivel, C. O., Blankenberg, F. G., Krams, S. M. 2001; 71 (12): 1827-1834

    Abstract

    The requirement for cytotoxic T lymphocytes during allograft rejection is controversial. We previously demonstrated that CD8+ T cells are not necessary for allograft rejection or for the induction of apoptosis in rat small intestinal transplantation. In this study, we examined the mechanisms of apoptosis and rejection after liver transplantation in the absence of CD8+ T cells.Either Lewis or dark agouti rat liver grafts were transplanted into Lewis recipients to create syngeneic and allogeneic combinations. CD8+ T cells were depleted in an additional allogeneic group by treatment with OX-8 mAb on day -1 and day 1 after liver transplant.Apoptosis and rejection were observed in both the CD8+ T cell-depleted allogeneic and allogeneic grafts by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, and radiolabeled-annexin V in vivo imaging. Granzyme B and FasL were expressed in all allogeneic transplants, including those depleted of CD8+ T cells, indicating that a mononuclear cell other than a CD8+ T cell can be the source of these molecules during allograft rejection. Activation of the caspase cascade was detected in all rejecting allografts. Caspases 3, 8, and 9 were activated at similar significantly elevated levels in both allogeneic and CD8+ T cell-depleted liver grafts.These data indicate that in the absence of CD8+ T cells an alternative pathway, associated with granzyme B and FasL expression and activation of the caspase cascade, can mediate apoptosis and graft rejection.

    View details for Web of Science ID 000169753800020

    View details for PubMedID 11455265

  • Mortality rate correlated with the number of pediatric liver transplants performed at a center 18th World Congress of the Transplantation-Society Cox, K., Rodriguez-Baez, N., Nasr, A., Esquivel, C. ELSEVIER SCIENCE INC. 2001: 1512–13

    View details for Web of Science ID 000167629900707

    View details for PubMedID 11267400

  • Center experience in liver transplantation for hepatocellular carcinoma associated with cirrhosis 18th World Congress of the Transplantation-Society Lai, K. M., MILLAN, M., Razavi, M., Keeffe, E. B., Prapong, W., Fisher, G. A., Esquivel, C. O., So, S. K. ELSEVIER SCIENCE INC. 2001: 1490–91

    View details for Web of Science ID 000167629900694

    View details for PubMedID 11267387

  • Liver transplantation for hepatocellular carcinoma and the role of preoperative chemoembolization. Millan, M. T., Lai, K. M., Keeffe, E. B., Fisher, G. A., Razavi, M. K., Prapong, W., Barry, C. T., Esquivel, C. O., So, S. K. LIPPINCOTT WILLIAMS & WILKINS. 2000: S215–S215
  • Orthotopic liver transplantation for carcinoid tumour metastatic to the liver: anesthetic management CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE Claure, R. E., Drover, D. D., Haddow, G. R., Esquivel, C. O., Angst, M. S. 2000; 47 (4): 334-337

    Abstract

    To report the anesthetic management of a patient with carcinoid tumour metastatic to the liver who presented for orthotopic liver transplantation. Anesthetic implications of metastatic carcinoid tumour on liver transplantation and the use of octreotide are discussed.A 51-yr-old woman with intestinal carcinoid tumour metastatic to the liver presented for orthotopic liver transplantation, a recent treatment option for patients with extensive hepatic carcinoid metastases and disabling symptoms unresponsive to conventional therapy. Despite continuous administration of the somatostatin analogue octreotide via a hepatic artery infusate pump, the patient suffered from daily break through symptoms, which included flushing, palpitations, paroxysmal hypertension, and dyspnea. The patient presented to the operating room with sinus tachycardia and severe arterial hypertension. Octreotide and phentolamine were used to prevent further mediator release and to control the paroxysmal hypertension. Midazolam, fentanyl, thiopental, succinylcholine, vecuronium, and isoflurane were used to induce and maintain anesthesia safely. An intravenous octreotide infusion was initiated after induction and continued throughout the case. Infrequent and non-threatening peaks in arterial blood pressure were readily treated with small intravenous doses of vasoactive drugs and octreotide. No other manifestations of the carcinoid syndrome occurred. The patient had an uneventful recovery and was discharged on postoperative day #6.The patient safely underwent orthotopic liver transplantation for treatment of symptomatic carcinoid tumour metastatic to the liver. The anesthetic management followed recent recommendations favouring the use of octreotide to prevent patients from becoming symptomatic. Outlined dosing regimen for octreotide provided satisfactory hemodynamic stability.

    View details for PubMedID 10764178

  • Radiolabeled annexin V imaging: Diagnosis of allograft rejection in an experimental rodent model of liver transplantation RADIOLOGY Ogura, Y., Krams, S. M., Martinez, O. M., Kopiwoda, S., Higgins, J. P., Esquivel, C. O., Strauss, H. W., Tait, J. F., Blankenberg, F. G. 2000; 214 (3): 795-800

    Abstract

    To assess the value of imaging rejection-induced apoptosis with technetium 99m and annexin V, a human protein-based radiopharmaceutical used in the diagnosis of acute rejection of a liver transplant, in a well-characterized rodent model of orthotopic liver transplantation.99mTc-radiolabeled annexin V was intravenously administered to six allografted (immunologically mismatched) and five isografted (immunologically matched) recipient rats on days 2, 4, and 7 after orthotopic liver transplantation. Animals were imaged 1 hour after injection of 0.2-2.0 mCi (8.0-74.0 MBq) of radiolabeled annexin V by use of clinical nuclear scintigraphic equipment.All animals in the allografted group demonstrated marked increases of 55% and 97% above the activity in the isografted group in hepatic uptake of annexin V on days 4 and 7, respectively. Severe acute rejection was histologically detected in all allografted livers on day 7. There was no histologic evidence of acute rejection in isografted animals. Dynamic hepatobiliary imaging with 99mTc and mebrofenin, an iminodiacetic acid derivative, demonstrated no correlation with the presence or absence of acute rejection or with annexin V uptake.Noninvasive imaging with radiolabeled annexin V is more sensitive and specific than imaging with 99mTc-mebrofenin in the diagnosis of acute rejection of a liver transplant.

    View details for Web of Science ID 000085478800029

    View details for PubMedID 10715048

  • Significance of detecting Epstein-Barr-Specific sequences in the peripheral blood of asymptomatic pediatric liver transplant recipients 3rd International Congress on Pediatric Transplantation Krieger, N. R., Martinez, O. M., Krams, S. M., Cox, K., So, S., Esquivel, C. O. JOHN WILEY & SONS INC. 2000: 62–66

    Abstract

    Pediatric allograft recipients are at increased risk for Epstein-Barr virus (EBV)-associated illnesses. The early identification and diagnosis of EBV-associated disorders is critical because disease progression can often be curtailed by modification of immunosuppression. We have previously shown that detection of EBV-specific sequences in the circulation by polymerase chain reaction (PCR) correlated well with the clinical symptoms of EBV infection. The purpose of the current study is to determine the significance of detecting EBV-specific sequences by PCR in asymptomatic pediatric liver transplant recipients. Peripheral-blood DNA was analyzed for the EBV genes, coding from the nuclear antigen 1 (EBNA-1) and the viral capsid antigen (gp220) by PCR. Samples from asymptomatic pediatric liver transplant recipients were analyzed from the immediate postoperative period and at 2- to 4-month intervals thereafter. We followed up 13 of these asymptomatic recipients who tested positive for EBV compared with 7 asymptomatic recipients who tested negative for EBV during the early posttransplantation period. Follow-up ranged from 1.5 to 4 years posttransplantation. Nine patients (69%) initially positive for EBV and asymptomatic ultimately developed symptoms of EBV infection, including fever, lymphadenopathy, rash, respiratory and gastrointestinal symptoms, and/or hepatitis. Five of these patients (56%) went on to develop posttransplant lymphoproliferative disorder based on histological examination of biopsied tissue and immunohistochemical identification of the EBV antigen/DNA in tissue. This is the first report suggesting that detection of EBV-specific sequences in the absence of symptoms may herald impending EBV-associated disorders. Thus, routine monitoring for circulating EBV sequences in asymptomatic recipients may be useful in the early identification of those at risk for developing EBV-associated disease and its ultimate prevention.

    View details for Web of Science ID 000085673100008

    View details for PubMedID 10648579

  • CD81 gene expression is lost in hepatocellular carcinoma. Drazan, K. E., Higgins, J., Fisher, G. A., Keefe, E., Barry, C. T., So, S. S., Wieczorek, A., Keeffe, E., Levy, S., Esquivel, C. O. WILEY-BLACKWELL. 1999: 248A–248A
  • Major hepatic resection without blood transfusion: Experience with total vascular exclusion 1st University-of-California-San-Francisco/Stanford Asia Liver Symposium So, S. K., Monge, H., Esquivel, C. O. WILEY-BLACKWELL PUBLISHING, INC. 1999: S28–S31

    Abstract

    Thirty consecutive, major liver resections performed with total vascular exclusion in both non-cirrhotic and cirrhotic patients were analysed retrospectively. The patients' ages ranged from 6 months to 80 years. Ten were Asians and five had cirrhosis associated with chronic hepatitis B or C. There was no perioperative death and the mean hospital stay was 6 days for adults and 9.2 days for children. The average vascular exclusion or warm ischaemia time was 25 min (range 10-55 min) and the average intraoperative blood volume given was 275 mL (range 0-3000 mL) packed red blood cells. Sixty per cent required no intraoperative blood transfusion. The mean total bilirubin and aspartate aminotransferase were 1.0 mg/dL (range 0.3-2.3 mg/dL) and 84 IU/L (range 14-306 IU/L) when measured prior to discharge at postoperative day 4-7. In our experience, total vascular exclusion is invaluable in major or difficult liver resections, especially lesions adjacent to the hepatic veins and vena cava. It is associated with a low blood transfusion requirement and a low incidence of complications. It further obviates the need for dissection of the porta hepatis and its associated risks. Total vascular exclusion time of 30 min appears to be well tolerated, even in patients with compensated cirrhosis.

    View details for Web of Science ID 000081033600007

    View details for PubMedID 10382635

  • Does Asian race affect hepatitis B virus recurrence or survival following liver transplantation for hepatitis B cirrhosis? 1st University-of-California-San-Francisco/Stanford Asia Liver Symposium So, S. K., Esquivel, C. O., Imperial, J. C., Garcia, G., Monge, H., Keeffe, E. B. WILEY-BLACKWELL PUBLISHING, INC. 1999: S48–S52

    Abstract

    To assess whether Asian race is an independent variable affecting survival and hepatitis B virus (HBV) recurrence after liver transplantation, the results of 27 consecutive liver transplants performed between June 1994 and April 1997 for HBV cirrhosis were analysed. In the group of 13 Asians, 38% had associated hepatocellular carcinoma and 62% had positive hepatitis B virus early antigen (HBeAg) or elevated HBV-DNA before transplant. Prophylactic hepatitis B immunoglobulin (HBIG) was administered perioperatively and long term at 4-6 weekly interval. Four patients with elevated HBV-DNA received lamivudine before transplantation. The 3 year actuarial patient survival rate was 100% in both Asian and non-Asian patients. Twenty-six patients remained seronegative for hepatitis B virus surface antigen after transplantation. The incidence of post-transplant HBV recurrence was similar: 0% in Asians compared with 7% in non-Asians. There was no recurrence in the group of 12 patients who were HBV-DNA or HBeAg negative pretransplant.

    View details for Web of Science ID 000081033600011

    View details for PubMedID 10382639

  • Resection versus transplantation for hepatocellular carcinoma 1st University-of-California-San-Francisco/Stanford Asia Liver Symposium Esquivel, C. O., Keeffe, E. B., Garcia, G., Imperial, J. C., Millan, M. T., Monge, H., So, S. K. WILEY-BLACKWELL PUBLISHING, INC. 1999: S37–S41

    Abstract

    Hepatocellular carcinoma is responsible for more than 1 million deaths per year worldwide and thus remains a challenging medical problem. It causes few or no symptoms and the tumour frequently reaches an enormous size by the time of diagnosis in countries where screening is seldom used. It is generally resistant to commercially available anti-neoplastic agents and radiation therapy. The principal treatment continues to be resection, either partial or complete, with liver transplantation. However, less than one-third of patients are surgical candidates for either resection or transplantation at the time of clinical presentation. This review will address the results observed following resection or transplantation for hepatocellular carcinoma.

    View details for Web of Science ID 000081033600009

    View details for PubMedID 10382637

  • Long-term outcomes in pediatric liver recipients: comparison between cyclosporin A and tacrolimus. Pediatric transplantation Cao, S., Cox, K. L., Berquist, W., Hayashi, M., Concepcion, W., Hammes, G. B., Ojogho, O. K., So, S. K., Frerker, M., Castillo, R. O., Monge, H., Esquivel, C. O. 1999; 3 (1): 22-26

    Abstract

    In recent years, tacrolimus (FK506, TAC) has been increasingly utilized in liver transplantation. However, long-term risks and benefits as compared with conventional cyclosporin A (CsA) have not been fully elucidated. This retrospective study examined the potential outcome differences between TAC- and CsA-based immunosuppressive therapy in pediatric liver transplant recipients. From March 1988 to December 1996, 218 children (aged 0.1-17 yr) underwent 238 orthotopic liver transplantations; 58.7% (128/218) were under 2 yr of age at time of transplant. Initially, the maintenance immunosuppressive regimen consisted of CsA and prednisone, with antilymphocytic preparations (MALG, ATGAM, and OKT3) as induction therapy. Subsequently, TAC was used first as rescue therapy for steroid refractory rejection in CsA patients and then as maintenance immunosuppression. Fifty-seven out of the 147 CsA patients were converted to TAC for various reasons while 71 patients were placed on TAC as primary maintenance immunosuppression. 62.6 per cent (92/147) of liver recipients on CsA experienced at least one biopsy-proven acute rejection episode as compared to 50.7% (36/71) for TAC patients (p = 0.09); likewise, 34% (50/147) of CsA patients had more than one episode of rejection vs. 18.3% (13/71) for patients on TAC (p < 0.02). Rejection was the reason for conversion from CsA to TAC in 29 of 57 patients. Conversely, 19.0% (28/147) of CsA patients had to be switched to TAC for reasons not related to rejection (i.e. side-effects). The overall incidence of histologically proven chronic rejection was 7.8% (17/218). 10.9 per cent (16/147) of the children who were on CsA initially developed chronic rejection, which was significantly higher compared with one of 71 TAC recipients (p < 0.02). Of these 16 CsA patients with chronic rejection, 50.0% (8/16) underwent retransplantation for graft failure (mean interval from time of diagnosis of chronic rejection to re-transplant, 4.0 months; range 1-8 months), whereas the TAC patient has remained clinically stable with normal liver function tests after 23 months of follow-up. One year after liver transplantation, 72.8% (107/147) of CsA patients were still on steroids (mean dosage 0.20 mg/kg/d), as compared to 42.3% (30/71) of the TAC patients (mean dosage 0.14 mg/kg/d). The incidence of post-transplant lymphoproliferative disorder (PTLD) in Epstein-Barr virus (EBV)-infected patients was 2.2% (2/90), 7.0% (5/71) and 12.3% (7/57) for CsA, primary and TAC-converted groups, respectively. The overall incidence of PTLD was 6.9% (15/218). In summary, pediatric liver transplant recipients treated with TAC as primary maintenance immunosuppressive medication experienced significantly fewer episodes of rejection; especially chronic rejection, which lead to graft loss. However, the trade-off is a potential increased incidence of EBV-related PTLD in these patients.

    View details for PubMedID 10359027

  • Effect of intraoperative blood transfusion on patient outcome in hepatic transplantation ARCHIVES OF SURGERY Cacciarelli, T. V., Keeffe, E. B., Moore, D. H., BURNS, W., Busque, S., Concepcion, W., So, S. K., Esquivel, C. O. 1999; 134 (1): 25-29

    Abstract

    To evaluate the effect of intraoperative transfusion of red blood cells (RBCs) on patient and graft survival.A retrospective study.A tertiary care referral center.Between January 1, 1992, and December 31, 1994, medical records from 225 adult patients who underwent primary liver transplantations were analyzed.Overall patient survival was 90% at 1 year and 86% at 3 years, while graft survival was 89% at 1 year and 85% at 3 years. The following factors were associated with patient and graft survival: age, sex, medical condition at the time of transplantation, and intraoperative transfusion of RBCs. When these factors were subjected to a multivariate analysis, all were independently associated with survival. Fifty-four recipients (24%) underwent transplantation without intraoperative transfusion of RBCs, while 171 recipients (76%) received at least 1 U of RBCs intraoperatively. Recipients who did not receive transfusion of RBCs had higher patient and graft survival rates than patients who did receive RBCs. By multivariate analysis, transplantation without intraoperative transfusion of RBCs no longer remained statistically significant, and only sex and the patient's medical condition were independently associated with patient and graft survival. Patient and graft survival decreased if 5 or more U were transfused, but transfusion of 5 or more U was not independently associated with survival by multivariate analysis.Increased transfusion requirement for RBCs was independently associated with patient and graft survival. While transplantation without transfusion of intraoperative RBCs was associated with superior patient and graft survival, these effects were overridden by patient sex and medical condition at the time of transplantation.

    View details for Web of Science ID 000078053500006

    View details for PubMedID 9927126

  • Increased dosage requirement and rejection after neoral conversion in pediatric liver transplant patients TRANSPLANTATION PROCEEDINGS Cao, S., Cox, K. L., Berquist, W., So, S., Concepcion, W., Monge, H., Esquivel, C. O. 1998; 30 (8): 4322-4324

    View details for Web of Science ID 000077593000129

    View details for PubMedID 9865373

  • Posttransplant lymphoproliferative disorders and gastrointestinal manifestations of Epstein-Barr virus infection in children following liver transplantation TRANSPLANTATION Cao, S., Cox, K., Esquivel, C. O., Berquist, W., Concepcion, W., Ojogho, O., Monge, H., Krams, S., Martinez, O., So, S. 1998; 66 (7): 851-856

    Abstract

    Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD).This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506).After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD.In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.

    View details for Web of Science ID 000076585400007

    View details for PubMedID 9798693

  • Combined viral prophylactic and immunosuppressive strategy in liver transplantation (OLT) for HBV cirrhosis So, S. K., Esquivel, C. O., Imperial, J. C., Garcia, G., Keeffe, E. B. WILEY-BLACKWELL. 1998: 346A–346A
  • Liver transplantation in the first three months of life TRANSPLANTATION Woodle, E. S., Millis, J. M., So, S. K., McDiarmid, S. V., Busuttil, R. W., Esquivel, C. O., Whitington, P. F., Thistlethwaite, J. R. 1998; 66 (5): 606-609

    Abstract

    Pediatric liver transplant recipients have traditionally been grouped according to age. Age-based classification schemes are useful in identifying clinical problems in selected age groups and also for developing solutions to these problems. Although infants in the first 3 months of life have not traditionally been considered a distinct age group, several features of these infants may distinguish them from other pediatric liver transplant recipients.The experience with liver transplantation in infants during the first 3 months of life in three large pediatric liver transplant programs (University of Chicago, Stanford University, and UCLA) was analyzed in order to characterize this group.A total of 23 liver transplants were performed at these three centers in children younger than 3 months of age. This group of patients comprised approximately 37% of the U.S. experience between 1988 and 1994 according to United Network for Organ Sharing statistics. Age distribution at the time of transplantation included the following: <1 month, 28%; 1-2 months, 35%; and 2-3 months, 36%. Median age at the time of transplantation was 37 days (range, 7-90 days), and mean age was 57+/-30 days. Mean weight at the time of transplantation was 3.8+/-1.0 kg. Etiology of liver disease included idiopathic hepatitis, 52%; iron storage disease, 17%; and other causes, 31%. Types of liver allografts used included cadaveric, 85% (reduced size, 60%, and full-size, 25%); living donor, 15%; ABO-identical, 65%; and ABO-compatible, 35%. Actuarial patient and graft survival rates were 60% and 60% at 1 year and 60% and 42% at 2 years, respectively. Median follow-up was 1.5 years. Rejection occurred in 42% of patients, with a median time to first rejection of 13 days. Of these patients, 28% required steroids only and 14% required OKT3. Three patients (14%) were retransplanted at a median time to retransplantation of 1.6 years. Vascular thrombosis occurred in three patients (14%).Liver transplantation performed in infants younger than 3 months of age (1) provides acceptable short- and long-term patient and graft survival, (2) is associated with significant rates of rejection, and (3) is not associated with excessive rates of vascular thrombosis. The etiology of end-stage liver disease occurring in the first 3 months of life is distinct from that in other pediatric liver transplant recipient age groups. These infants should be referred promptly for liver transplantation as reasonable survival can be expected.

    View details for Web of Science ID 000075996500010

    View details for PubMedID 9753340

  • CD30 expression identifies a functional alloreactive human T-lymphocyte subset TRANSPLANTATION Martinez, O. M., Villanueva, J., Abtahi, S., Beatty, P. R., Esquivel, C. O., Krams, S. M. 1998; 65 (9): 1240-1247

    Abstract

    CD30 is a member of the tumor necrosis factor/nerve growth factor receptor family and has been proposed as a marker of specific cytokine-producing subsets in humans. Previous studies have examined the expression of CD30 on established T helper type 1 and T helper type 2 cell clones and the function of CD30+ cells after mitogenic stimulation. In this study, we examined the development and function of CD30+ T cells generated in response to alloantigen.Primary one-way mixed lymphocyte reactions were established, and the expression of CD30 on T lymphocytes was determined by immunofluorescence and flow cytometry. Fluorescence-activated cell sorting was utilized to define the cytokine profile of alloactivated CD30+ cells after restimulation with anti-CD3 monoclonal antibodies or alloantigen. The effect of cyclosporine on the development of CD30+ cells, and on cytokines produced by CD30+ T lymphocytes, in response to alloantigen was determined.CD30+ T lymphocytes could be detected on day 2 of mixed lymphocyte reactions and continued to increase in number and proportion through day 6. Both CD4 and CD8 T cells expressed CD30 after primary alloantigenic stimulation. CD30+ T cells are a subset of alloactivated T cells and are the major source of interferon-gamma and interleukin-5 produced in response to alloantigen. Cyclosporine partially, but not completely, inhibits the development of CD30+ cells, and has a greater effect on interferon-gamma production than on interleukin-5 production.CD30+ T lymphocytes may constitute an important immunoregulatory subset in human allograft rejection.

    View details for Web of Science ID 000073676600016

    View details for PubMedID 9603174

  • Effect of cyclosporine and tacrolimus on the growth of Epstein-Barr virus-transformed B-cell lines 16th Annual Meeting of the American-Society-of-Transplant-Physicians Beatty, P. R., Krams, S. M., Esquivel, C. O., Martinez, O. M. LIPPINCOTT WILLIAMS & WILKINS. 1998: 1248–55

    Abstract

    Transplant patients receiving immunosuppressive drugs are at increased risk for Epstein-Barr virus (EBV)-associated disorders including posttransplant lymphoproliferative disorder. The function of T lymphocytes, which are critical to preventing the expansion of EBV-infected B cells, is inhibited by immunosuppressive drugs. The purpose of this study was to determine whether immunosuppressive drugs have direct effects on EBV-infected B cells.The growth and proliferation of EBV-infected spontaneous lymphoblastoid cell lines (SLCLs), cultured in the presence or absence of cyclosporine (CsA) and tacrolimus (TAC), were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and [3H]thymidine incorporation assays. The effect of CsA and TAC on the viability of SLCLs was determined by cell counts with trypan blue. Apoptosis of SLCLs was induced with an anti-Fas agonist monoclonal antibody in the presence or absence of CsA and TAC and measured by flow cytometry after terminal deoxynucleotidyl transferase end-labeling and propidium iodide staining.CsA and TAC, but not sirolimus, increased the growth of SLCLs. The increased growth in the presence of CsA and TAC was attributable to enhanced cell viability and not increased cell division of SLCLs. In addition, CsA and TAC inhibited Fas-mediated apoptosis of SLCLs.CsA and TAC enhance the survival of EBV-transformed B-cell lines. CsA and TAC promote or augment SLCL growth through protection from cell death but do not affect cell division. The inhibition of cell death by CsA and TAC may contribute to the expansion of EBV-infected cells in immunosuppressed individuals.

    View details for Web of Science ID 000073676600017

    View details for PubMedID 9603175

  • Allograft rejection after liver transplantation for autoimmune liver diseases LIVER TRANSPLANTATION AND SURGERY Hayashi, M., Keeffe, E. B., Krams, S. M., Martinez, O. M., Ojogho, O. N., So, S. K., Garcia, G., Imperial, J. C., Esquivel, C. O. 1998; 4 (3): 208-214

    Abstract

    Autoimmune liver diseases (AILD) may progress to liver failure, requiring liver transplantation as definitive therapy, and these immune-mediated disorders may predispose the patient to more frequent graft rejection. The objective of this study was to determine the effect of preexisting AILD on the incidence of allograft rejection after liver transplantation. Sixty-three patients who underwent liver transplantation between March 1988 and December 1994 for AILDs that included autoimmune hepatitis (AIH; n = 33) and primary biliary cirrhosis (PBC; n = 30) were retrospectively compared with 47 patients who underwent liver transplantation for alcoholic cirrhosis during the same time period. There was a lower incidence of acute allograft rejection in patients with AILD who received tacrolimus-based compared with cyclosporine-based immunosuppression (50% v 85.5%; P = .02). However, patients with AILDs overall had a higher incidence of acute rejection than patients with alcoholic cirrhosis (81% v 46.8%; P < .001), regardless of the type of immunosuppression. In addition, steroid-resistant rejection occurred more frequently in patients with AILDs than in patients with alcoholic cirrhosis (38.1% v 12.8%; P = .003). There was also a trend toward a higher incidence of chronic rejection in patients with AILDs compared with patients with alcoholic cirrhosis (11.1% v 2.1%), but this difference did not reach statistical significance. Patient and graft survivals at 1 and 3 years were similar between patients with AILDs and alcoholic liver disease. Compared with alcoholic cirrhosis, preexisting AILDs are associated with a higher incidence of acute allograft rejection and a trend toward more frequent chronic rejection.

    View details for Web of Science ID 000077183800004

    View details for PubMedID 9563959

  • CD8(+) cells are not necessary for allograft rejection or the induction of apoptosis in an experimental model of small intestinal transplantation JOURNAL OF IMMUNOLOGY Krams, S. M., Hayashi, M., Fox, C. K., Villanueva, J. C., Whitmer, K. J., BURNS, W., Esquivel, C. O., Martinez, O. M. 1998; 160 (8): 3673-3680

    Abstract

    Allospecific CTL can function as cellular effectors of solid organ graft rejection; however, the specific mechanisms of cell damage remain undetermined. In this study we examined the role of CD8+ T cells in apoptosis and rejection of small intestinal allografts. ACI rat intestinal grafts transplanted into Lewis rat recipients showed apoptosis of epithelial crypt cells on day 3 posttransplant as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining. By day 7 numerous apoptotic crypt cells were detected in allografts, but were rarely observed in FK506-treated allograft recipients, isografts, or native intestine of allograft recipients. To further investigate the mechanism of rejection, recipient rats were depleted of CD8+ cells by treatment with OX-8 mAbs the day before and the day after transplantation of rat small intestinal allografts. Depletion of CD8+ cells from allograft recipients did not alter the tempo or the histologic features of rejection compared with those in the control (IgG-treated) group. Moreover, there was no difference in the number of apoptotic crypt epithelial cells in the grafts of control and CD8-depleted rats. Reverse transcriptase-PCR analyses determined there were similar levels of transcripts for Fas, Fas ligand, perforin, and granzyme B in control and CD8-depleted allograft recipients. By Western blot it was determined that the levels of Fas ligand protein were increased in the CD8-depleted group compared with those in control and FK506-treated allograft recipients. These data suggest that CD8 cells are not required for tissue injury or apoptotic cell death in small intestine allograft rejection.

    View details for Web of Science ID 000072970400008

    View details for PubMedID 9558067

  • Human hepatocytes produce an isoform of Fas that inhibits apoptosis TRANSPLANTATION Krams, S. M., Fox, C. K., Beatty, P. R., Cao, S., Villanueva, J. C., Esquivel, C. O., Martinez, O. M. 1998; 65 (5): 713-721

    Abstract

    Fas (Apo-1/CD95), a member of the tumor necrosis factor receptor family, can mediate apoptosis when engaged by its ligand or by anti-Fas antibody. Fas is expressed by cells of the immune system and by some nonlymphoid tissues. Numerous studies have suggested that the Fas pathway may play a role in the rejection of allografts. Functional, soluble forms of the Fas receptor are produced by activated peripheral blood mononuclear cells and some transformed cell lines. The purpose of this study was to determine if soluble variants of Fas are produced in the liver and to determine if blockade of the Fas pathway, by liver-derived soluble Fas, inhibits Fas-mediated apoptosis.Liver and purified hepatocyte specimens were analyzed for Fas transcripts by reverse transcriptase-polymerase chain reaction with primers that span the transmembrane region of the molecule. Bile and cell lysates were analyzed for soluble Fas by specific enzyme-linked immunosorbent assay. Lysates were prepared from normal liver and hepatocytes and utilized to block Fas-mediated apoptosis of Jurkat cells as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and flow cytometry.A variant form of Fas is abundantly expressed in normal liver and purified hepatocytes. This variant form of Fas is expressed in all normal liver specimens but only in half of the liver specimens obtained during allograft rejection. The levels of soluble Fas diminish in patients undergoing liver allograft rejection in contrast to patients with stable grafts. Importantly, a soluble form of Fas is produced in the liver by hepatocytes and can specifically inhibit Fas-mediated apoptosis.These data raise the possibility that soluble Fas, produced by hepatocytes, may influence the immune response by blocking Fas-mediated apoptosis and, thus, may have a role in liver transplantation.

    View details for Web of Science ID 000072573800019

    View details for PubMedID 9521208

  • Current status of living-related liver transplantation. Pediatric transplantation Hayashi, M., Cao, S., Concepcion, W., Monge, H., Ojogho, O., So, S., Esquivel, C. O. 1998; 2 (1): 16-25

    Abstract

    Living-related liver transplantation has come of age. This manuscript addresses the most important facets of the living-related liver transplant procedure including selection of the donor, the recipient operation, immunosuppression and rejection as well as the most common surgical complications. It also describes the results in terms of patient and graft survival, retransplantation and quality of life. Although living-related liver transplantation has not solved the problem of organ shortage, it has provided many children with an opportunity to live and enjoy life.

    View details for PubMedID 10084755

  • Experience with the piggyback technique without caval occlusion in adult orthotopic liver transplantation TRANSPLANTATION Busque, S., Esquivel, C. O., Concepcion, W., So, S. K. 1998; 65 (1): 77-82

    Abstract

    To assess the feasibility and outcome of a piggyback technique without caval occlusion or veno-venous bypass (VB), we retrospectively reviewed 131 consecutive adult orthotopic liver transplantation (OLT) performed in 129 patients between May 1993 and February 1995. Six were second transplants, and six were combined liver-kidney transplants. The piggyback technique was attempted in all cases.We were able to perform the piggyback technique in 98 OLTs (75%). The remaining 33 OLTs (25%) were converted to the standard technique; of these, 20 (15%) required VB. The reasons for conversion to the standard technique were: anatomical (22 transplants), severe portal hypertension requiring VB (8 transplants), tumor (1 transplant), and other reasons (2 transplants). Six retransplantations were performed (four piggyback, two standard).There was no significant difference in age, United Network for Organ Sharing status, Child's classification, and diagnosis between the patients in whom piggyback was possible or not. The actuarial patient and graft survival at 1 year were similar between the piggyback group and the group of patients converted to standard technique (87/85% vs. 86/86%, respectively). No death was related to either technique. With piggyback, the average operative time was 8.6+/-1.9 hr, median amount of blood transfused intraoperatively was 2 U (33% did not require transfusion), and median intensive care unit and hospital stays were 3 and 11 days, respectively. With the piggyback technique, the mean preoperative and maximum postoperative serum creatinine levels were 1.4+/-1.0 and 1.8+/-1.5 mg/dl.The piggyback technique without caval occlusion is possible in the majority of patients. It is safe and has reduced the use of VB to 15% of our adult OLTs. The piggyback technique avoids retrocaval dissection, facilitates retransplantation, and is associated with a short anhepatic phase, low blood product usage, and short intensive care unit stay.

    View details for Web of Science ID 000071516900014

    View details for PubMedID 9448148

  • New approaches to supporting the failing liver ANNUAL REVIEW OF MEDICINE Cao, S., Esquivel, C. O., Keeffe, E. B. 1998; 49: 85-94

    Abstract

    With the continued, growing disparity between the numbers of organ donations and patients waiting for liver transplantation, various efforts have been made to optimize the allocation of organs, as well as to devise means to support the failing liver. Over the years, the development of bioartificial liver-assist devices has aimed at replacing the three main functions of hepatocytes, which are synthetic, metabolic, and excretory. The application of porcine hepatocytes in humans to carry out biotransformation, as well as other metabolic functions and refinement of the membrane separator, have yielded some promising results in supporting patients with acute liver failure. Further advances will need to be made before these bioartificial devices can be considered for routine application in clinical settings.

    View details for Web of Science ID 000073046600006

    View details for PubMedID 9509251

  • Liver transplantation at Stanford University Medical Center. Clinical transplants Millan, M. T., Keeffe, E. B., Berquist, W. E., Castillo, R. O., Cox, K. L., Garcia, G., Imperial, J. C., Monge, H., So, S. K., Esquivel, C. O. 1998: 287-296

    Abstract

    Because of the unique demographics of our patient population, we have had the opportunity to dedicate further studies of the management of hepatitis B and hepatitis C. We have experienced a very low HBV recurrence rate with the use of HBIG in patients transplanted for hepatitis B. Investigations, including the use of new antiviral agents, and the development of approaches to minimize or abrogate disease recurrence such as lower levels of immunosuppression are ongoing. Using a standardized approach to the proper evaluation and selection of patients for liver transplantation with alcoholic liver disease or other liver diseases with coexistent alcohol abuse, we report favorable long-term results in these patients. We have reviewed our results and our approach to the management of EBV and posttransplant lymphoproliferative disorder. There is a firm commitment in our laboratories and outpatient clinics to the investigation of disease prevention, reliable detection and screening methods, and treatment modalities for EBV-related disease. We have addressed specific technical considerations to pediatric liver transplant and have discussed unique aspects of postoperative management in these patients. One-third of the transplants performed at Stanford are in children, 42% of whom are less than one year old. Results with our pediatric transplant recipients compare favorably with those of our adult recipients with patient and graft survival rates approaching 90% at one year and exceeding 80% at 46 months for both groups. As a response to the limited organ supply, we have extended our criteria for suitable donors. Most notably, we have utilized older donors and grafts with significant microsteatosis and have observed good results with these grafts as long as ischemia time is minimized. We have also successfully used reduced size grafts for our pediatric patients with good results and are continuing to expand the use of living-related partial grafts and split allografts.

    View details for PubMedID 10503106

  • Cholic acid synthesis is reduced in pediatric liver recipients during graft dysfunction due to ischemic injury and allograft rejection Annual Meeting of the American-Society-of-Pediatrics / Society-of-Pediatric-Research Lang, T., Sendl, A. F., Esquivel, C. O., Berquist, W. E., Cox, K. L. LIPPINCOTT WILLIAMS & WILKINS. 1997: 1585–90

    Abstract

    Bile acids are synthesized and secreted by the liver. During liver failure and hepatic dysfunction, a marked reduction of bile acid synthesis has been shown. The purpose of this study was to determine whether the biliary bile acid pattern was affected by preservation injury and rejection and whether it was a reliable marker for graft function in pediatric liver recipients after liver transplantation.We prospectively measured the biliary bile acid pattern in 126 serial bile samples obtained from 15 consecutive pediatric liver recipients by reversed phase high pressure liquid chromatography and correlated our results with clinical findings: preservation injury, no rejection, rejection, or infection.There was a significant change of the bile acid pattern during the first 3 days after transplant. Total biliary bile acids, cholic acid (CA), and CA/chenodeoxycholic acid (CDCA) ratio increased in 12 of 15 patients with mild preservation injury. These changes of the bile acid pattern were markedly delayed in patients with severe preservation injury. During 16 rejection episodes, total biliary bile acid, CA, and CA/CDCA ratio decreased significantly, but returned to normal after successful treatment of rejection. Bacterial infection, observed in nine children, and cyclosporine toxicity, observed in three children, seemed to have no affect on the biliary bile acids.Liver cell damage as a result of preservation injury or rejection leads to a reduction of biliary CA, resulting in a decrease of total biliary bile acids and the CA/CDCA ratio in pediatric liver recipients. This might be caused by a diminished secretion of bile acids and by a decreased synthesis of bile acids.

    View details for Web of Science ID 000071034100014

    View details for PubMedID 9415561

  • Neurodevelopmental outcome of young children with extrahepatic biliary atresia 1 year after liver transplantation JOURNAL OF PEDIATRICS Wayman, K. I., Cox, K. L., Esquivel, C. O. 1997; 131 (6): 894-898

    Abstract

    Forty children < 2 years of age receiving extrahepatic liver transplantation were tested with the Bayley Scales of Infant Development before transplantation and again at 3 and 12 months after transplantation. Neurodevelopmental status 1 year after transplantation was organized by a descriptive statistic of normal, suspect, or delayed. Disease and transplantation variables were investigated for association with delayed neurodevelopmental outcome.Before transplantation mental development was in the low-average range (92 +/- 13.2) with psychomotor development 1 SD below the norm (82.5 +/- 13). Three months after transplantation both mental (80.1 +/- 12.6) and psychomotor (69 +/- 16.1) scores dropped 1 SD, but 1 year after transplantation mental and psychomotor scores recovered to the pretransplantation level of functioning. One year after transplantation 35% of the study group was diagnosed as developmentally delayed. Delayed development was associated with decreased weight (p < 0.04), low albumin (p < 0.02), length of hospital stay (p < 0.04), and age at transplantation (p < 0.05).Young children undergoing liver transplantation are at risk for developmental delay. Aggressive nutritional support before transplantation and timing of transplantation before malnutrition develops may reduce developmental delays.

    View details for Web of Science ID 000071165100021

    View details for PubMedID 9427896

  • Transjugular intrahepatic portosystemic shunt placement in a child complicated by perforated Roux-en-Y portoenterostomy JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Wang, J., Cox, K. L., Dake, M., Esquivel, C. O., So, S. K. 1997; 25 (4): 421-425

    View details for Web of Science ID A1997XY50500011

    View details for PubMedID 9327374

  • Current status and outcome of pediatric liver transplantation. Clinics in liver disease Esquivel, C. O. 1997; 1 (2): 397-?

    Abstract

    In this article the diagnostic indications for hepatic transplantation are addressed in detail. The outcome of liver transplantation is also examined, including the impact of the following factors on survival: age and weight at transplantation, type of liver disease, and size of liver allograft, including living related transplantation. Morbidity and quality of life after transplantation are other aspects reviewed in this chapter.

    View details for PubMedID 15562575

  • Factors affecting survival after orthotopic liver transplantation in infants TRANSPLANTATION Cacciarelli, T. V., Esquivel, C. O., Moore, D. H., Cox, K. L., Berquist, W. E., Concepcion, W., Hammer, G. B., So, S. K. 1997; 64 (2): 242-248

    Abstract

    The technical and medical management of small infants requiring orthotopic liver transplantation remains a challenge. The present study examined 117 orthotopic liver transplantations performed in 101 infants from <1 to 23 months of age between March 1988 and February 1995 to determine factors that influence patient and graft outcome. Factors analyzed included etiology of liver disease, recipient and donor age and weight, United Network for Organ Sharing (UNOS) status, retransplantation, ABO-compatibility, full-size (FS) versus reduced-size grafts, vascular thrombosis (VT), including hepatic artery and portal vein (PVT), and the presence of lymphoproliferative disease (LPD). UNOS status 1, fulminant hepatic failure, and the development of Epstein-Barr virus-associated LPD were each associated with 10-20% lower patient and graft survival rates. Of 101 infants, 11 (11%) developed LPD with an associated 36% mortality. VT occurred in 10 (9 hepatic artery and 1 portal vein) of 117 orthotopic liver transplantations (9%), all less than 1 year of age, and was associated with significantly poorer 1-year (50% vs. 85% no VT, P<0.01) and 5-year patient survival rates (50% vs. 83% no VT, P<0.01). One-year graft survival rates for FS grafts in recipients <12 months versus 12-23 months were 67% vs. 94% (P<0.01); the patient survival rate was also significantly lower in FS graft recipients <12 months (76% vs. 100%, P<0.05). Recipients <5 months of age had the worst survival rates: 1-year and 5-year patient survival rates were 65% and 46% for recipients 0-4 months (n=17) versus 82% and 82% for recipients 5-11 months (n=56), and 93% and 93% for recipients age 12-23 months (n=28; P<0.05). In summary, factors associated with reduced survival rates include recipient age <5 months, recipient age <12 months who received FS grafts, development of VT and donor weight <6 kg. There was a trend for UNOS status 1, fulminant hepatic failure, and presence of LPD to be associated with reduced survival rates.

    View details for PubMedID 9256181

  • Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation - A report of the US Multicenter Liver Study Group TRANSPLANTATION Sher, L. S., Cosenza, C. A., Michel, J., Makowka, L., Miller, C. M., Schwartz, M. E., Busuttil, R., McDiarmid, S., Burdick, J. F., Klein, A. S., Esquivel, C., Klintmalm, G., Levy, M., Roberts, J. P., Lake, J. R., Kalayoglu, M., DALESSANDRO, A. M., Gordon, R. D., Stieber, A. C., Shaw, B. W., Thistlethwaite, J. R., Whittington, P., Wiesner, R. H., Porayko, M., Bynon, J. S., Eckhoff, D. E., Freeman, R. B., Rohrer, R. J., Lewis, W. D., Marsh, J. W., Peters, M., Powelson, J., Cosimi, A. B. 1997; 64 (2): 258-263

    Abstract

    A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection.Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study.Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of < or = 10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin > 10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus < or = 90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted > 90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients.Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

    View details for Web of Science ID A1997XN86900014

    View details for PubMedID 9256184

  • Orthotopic liver transplantation from non-heart-beating donor rats: Effect of flushing with cold/warm UW/SLS preservation solutions XVI International Congress of the Transplantation-Society Tojimbara, T., Winston, W. N., So, S. K., Esquivel, C. O. ELSEVIER SCIENCE INC. 1997: 1371–73

    View details for Web of Science ID A1997WM12700610

    View details for PubMedID 9123344

  • Emergency transjugular intrahepatic portosystemic shunt (TIPS) in an infant: A case report JOURNAL OF PEDIATRIC SURGERY Cao, S., Monge, H., Semba, C., Cox, K. L., Berquist, W., Concepcion, W., So, S. K., Esquivel, C. O. 1997; 32 (1): 125-127

    Abstract

    Since the first successful report regarding the feasibility of transjugular intrahepatic portosystemic shunt (TIPS) as an alternative to surgical decompression of portal hypertension, this method has been used extensively as a temporizing measure in controlling refractory variceal bleeding before liver transplantation in adults with cirrhosis. There are few reports of TIPS in pediatric patients because variceal bleeding in most of these patients can often be managed conservatively without invasive intervention. Recently, successful use of TIPS to treat complications of portal hypertension has been described in two children ages 10 and 13. To our knowledge, there are no reports of TIPS used in infants under the age of 1 year. The authors report a case in which TIPS was used to successfully control variceal bleeding in a 10-month-old infant before consideration for hepatic transplantation.

    View details for Web of Science ID A1997WE27500040

    View details for PubMedID 9021592

  • Liver transplantation from non-heart beating donors in rats: influence of viscosity and temperature of initial flushing solutions on graft function. Liver transplantation and surgery Tojimbara, T., Wicomb, W. N., Garcia-Kennedy, R., BURNS, W., Hayashi, M., Collins, G., Esquivel, C. O. 1997; 3 (1): 39-45

    Abstract

    We evaluated the effect of warm (37 degrees C) versus cold (4 degrees C) solutions as the initial flush for liver preservation from non-heart beating donors in rats.An initial flush was performed just before donor hepatectomy with cold or warm University of Wisconsin solution (UW), UW without hydroxyethyl starch, sodium lactobionate sucrose solution, or lactated Ringer's solution as the control group. A separate group also used as control received no initial flushing. Liver transplantation was performed, and the graft function was determined by survival and assessment of enzyme release. The viscosity of each solution and the vascular resistance of the graft were measured.The 7-day survival rate was 83% and 100% in the warm and cold sodium lactobionate sucrose solution groups and 60% and 50% in the warm and cold lactated Ringer's solution groups, respectively. In the no-initial-flush group, rats did not survive. The 7-day survival rate was 67% and 0% in the warm and cold UW groups, respectively. Eliminating the hydroxyethyl starch from the cold UW improved the survival to 67%. Serum alanine aminotransferase levels 1 day after transplantation in the no-initial-flush and the cold UW groups were significantly higher than those of the remaining groups. At 4 degrees C the viscosity was higher in the UW (86.2 cp) compared to hydroxyethyl starch-free UW solution (30.9 cp), lactated Ringer's solution (24.5 cp), and sodium lactobionate sucrose solution (32.7 cp). The viscosity of UW at 37 degrees C was 34.7 cp. Vascular resistance correlated well with the viscosity. Livers flushed with solutions with a low viscosity showed lower vascular resistance than those flushed with cold UW and led to better survival.These data suggest that the viscosity of the initial flushing solution may play an important role in determining the outcome of organ procurement from non-heart beating donors.

    View details for PubMedID 9377757

  • Liver transplantation in Asian patients with chronic hepatitis B HEPATOLOGY HO, B. M., So, S. K., Esquivel, C. O., Keeffe, E. B. 1997; 25 (1): 223-225

    Abstract

    It has been suggested that Asian patients have reduced survival after liver transplantation because of greater recurrence of hepatitis B virus (HBV). We analyzed the outcome of Asian and non-Asian patients receiving transplants for chronic hepatitis B between May 1988 and March 1994. Baseline Child-Pugh score and United Network for Organ Sharing (UNOS) status, HBV recurrence, and survival were compared between the two groups. All but one patient received variable doses of hepatitis B immune globulin. Mean follow-up of surviving patients was 28 months (range, 3-71 months). Fifteen Asians and 20 non-Asians underwent transplantation. Six of 15 Asians (40%) and 4 of 20 non-Asians (20%) died during the study period. Although Asians had a lower 1-year survival than non-Asians (59% for Asians and 94% for non-Asians), the 5-year actuarial survival was not different (59% and 57% for Asians and non-Asians, respectively). The causes of death in 5 of 6 Asians were factors other than recurrent hepatitis B, and 4 of 5 deaths occurred within 60 days after transplantation. Eighty percent of Asian patients were Child-Pugh class C at referral, compared with 50% of non-Asians, and Asians were more likely to be status 1 at transplantation (40% vs. 10%; P < .05). By contrast, all four deaths in non-Asians occurred late and were secondary to recurrent HBV infection. Of patients surviving more than 60 days after transplantation, 7 of 11 Asians (64%) and 10 of 20 non-Asians (50%) developed recurrent HBV infection (NS). Late mortality attributable to HBV recurrence was lower but not significantly different in Asians (1 of 7 [14%]) than in non-Asians (4 of 10 [40%]). In summary, HBV recurrence and late HBV-related mortality in Asians and non-Asians is similar after liver transplantation for chronic hepatitis B. Late referral and more advanced chronic liver disease at the time of transplantation probably account for the lower 1-year survival of Asians after liver transplantation.

    View details for Web of Science ID A1997WA90200040

    View details for PubMedID 8985294

  • Rapid development of hepatocellular siderosis after liver transplantation for neonatal hemochromatosis TRANSPLANTATION Egawa, H., Berquist, W., GARCIAKENNEDY, R., Cox, K., Knisely, A. S., Esquivel, C. O. 1996; 62 (10): 1511-1513

    Abstract

    A male infant with neonatal iron storage disease, also known as neonatal hemochromatosis (NH), underwent orthotopic liver transplantation (OLT) at the age of 55 days. The native liver contained an incidental hepatocellular carcinoma. Scant iron accumulation was found in a biopsy specimen of the implanted liver on the seventh postoperative day (POD); successive biopsies showed increasing siderosis. On POD 62, the patient died of a cardiac arrhythmia. Autopsy showed siderosis at many sites, including the implanted liver. We discuss the possibility that hemochromatosis recurred in the liver allograft and review possible factors contributing to the siderosis.

    View details for Web of Science ID A1996VV54900023

    View details for PubMedID 8958282

  • Primary liver transplantation without transfusion of red blood cells 53rd Annual Meeting of the Central-Surgical-Association Cacciarelli, T. V., Keeffe, E. B., Moore, D. H., BURNS, W., Chuljian, P., Busque, S., Concepcion, W., So, S. K., Esquivel, C. O. MOSBY-ELSEVIER. 1996: 698–704

    Abstract

    This study examines factors associated with the performance of orthotopic liver transplantation (OLT) without red blood cell (RBC) transfusion.Between January 1992 and December 1994, 306 primary OLTs were performed with recipients divided into two groups: group 1 patients (61 recipients, 20% of total) underwent transplantation without packed RBCs, and group 2 patients (245 recipients, 80% of cases) received a transfusion of at least 1 unit of RBCs during operation.Recipients in group 1 compared with group 2 had less advanced liver disease (20% hospitalized and 48% Child's class C versus 58% hospitalized and 73% Child's class C, p < 0.01) and lower frequency of right upper quadrant surgery (13% versus 25%, p < 0.05). Group 1 recipients also had significantly higher preoperative hematocrits (38% versus 33%, p < 0.01), lower prothrombin times (15.4 versus 16.7 seconds, p < 0.001) and partial thromboplastin times (36.9 versus 42.2 seconds, p < 0.01), a greater proportion of patients transplanted by piggyback technique (87% versus 59%, p < 0.001), and shorter operative times (7.9 hours versus 9.2 hours, p < 0.001). Moreover, a greater percentage of patients underwent OLT without RBC transfusion in each successive year: 9% in 1992, 21% in 1993, and 31% in 1994 (p < 0.001). Logistic regression analysis showed the following factors to be independent predictors of OLT without RBC transfusion. Preoperative Hct, United Network of Organ Sharing status, piggyback technique, operative time, and year of transplantation.OLT can be performed without transfusion of RBCs in recipients with less advanced liver disease, and surgical technique, along with increased experience by the transplant team, are important factors.

    View details for Web of Science ID A1996VP42300036

    View details for PubMedID 8862380

  • Orthotopic liver transplantation for hepatocellular carcinoma - Factors affecting long-term patient survival 67th Annual Session of the Pacific-Coast-Surgical-Association Ojogho, O. N., So, S. K., Keeffe, E. B., Berquist, W., Concepcion, W., GARCIAKENNEDY, R., Imperial, J., Esquivel, C. O. AMER MEDICAL ASSOC. 1996: 935–39

    Abstract

    To determine the influence of several clinicopathologic factors on the 3-year actuarial survival of patients with nonfibrolamellar hepatocellular carcinoma (HCC) following orthotopic liver transplantation (OLT).A case series of 26 consecutive patients with HCC treated with OLT, with a maximum follow-up of 90 months.A tertiary care center.Between March 1988 and December 1993, 521 OLTs were performed in 480 patients, 27 of whom had HCC. One patient was excluded because of donor-transmitted melanoma. Of the remaining 26 patients, there were 18 adults and 8 children, with a mean age of 41 years (range, 0.2-67.4 years). Fourteen patients (54%) had either hepatitis B (n = 6) or hepatitis C (n = 8), while 15 (58%) had coincidental tumor.OLT was performed using standard techniques.The effect of several clinicopathologic factors on 3-year actuarial patient survival.The overall actuarial survival rates for the 26 patients with HCC were 73%, 65.4%, and 65.4%, at 1, 2, and 3 years, respectively. Sixteen patients (62%) were alive at the time of this report, with 14 (54%) free of disease. None of the clinicopathologic factors significantly affected the 3-year patient survival rate. However, the rate of recurrent HCC was significantly higher in nonincidental vs coincidental tumors and in solitary vs multiple tumors.Our results suggest that HCC should not contraindicate OLT, as long-term patient survival and cure can be achieved. While patient selection is important, survival in patients with HCC after OLT is not always predictable using the usual clinicopathologic prognostic factors.

    View details for Web of Science ID A1996VF46900009

    View details for PubMedID 8790178

  • Continuous venovenous hemofiltration with dialysis in combination with total hepatectomy and portocaval shunting - Bridge to liver transplantation TRANSPLANTATION Hammer, G. B., So, S. K., ALUZRI, A., Conley, S. B., Concepcion, W., Cox, K. L., Berquist, W. E., Esquivel, C. O. 1996; 62 (1): 130-132

    Abstract

    Children who experience acute liver failure following liver transplantation will have multiple organ failure and a high rate of mortality unless emergency retransplantation can be performed. Transplant hepatectomy with portocaval shunting has been described as a bridge to transplantation in the most severe cases, as well as in patients with fulminant hepatic failure at high risk for mortality who have not undergone liver transplantation. Patients with multiple organ failure who have undergone hepatectomy require renal replacement therapy. Continuous hemofiltration may be used in patients with fulminant hepatic failure to facilitate fluid removal and circulatory and metabolic balance. We used continuous venovenous hemofiltration with dialysis following hepatectomy with portocaval shunting in a patient who remained anhepatic for 66 hr in order to achieve circulatory and metabolic homeostasis as well as stable neurologic function prior to successful retransplantation.

    View details for PubMedID 8693530

  • Cyclosporine and tacrolimus both suppress activation of kupffer cells in vitro 4th International Congress of the Asian-Transplantation-Society Tojimbara, T., Bermudez, L. E., Egawa, H., Hayashi, M., So, S. K., Esquivel, C. O. ELSEVIER SCIENCE INC. 1996: 1381–82

    View details for Web of Science ID A1996UR78100105

    View details for PubMedID 8658704

  • Liver transplantation CURRENT OPINION IN GASTROENTEROLOGY Keeffe, E. B., Esquivel, C. O. 1996; 12 (3): 290-299
  • Oral tacrolimus (FK506) induction therapy in pediatric orthotopic liver transplantation TRANSPLANTATION Cacciarelli, T. V., Esquivel, C. O., Cox, K. L., Hayashi, M., Berquist, W. E., Concepcion, W., So, S. K. 1996; 61 (8): 1188-1192

    Abstract

    We have adopted the use of an oral tacrolimus induction protocol in pediatric liver transplantation since the commercial release of tacrolimus in 1994. In this study we analyzed the efficacy of oral tacrolimus induction therapy in 17 consecutive transplants (15 patients) performed between 6/94 and 2/95 and 4 additional patients who were retransplanted between 11/93-5/94 and received compassionate oral tacrolimus induction. Sixteen transplants were treated with oral tacrolimus induction only; 5 transplants, oral tacrolimus + ATGAM/OKT3 induction. The protocol consisted of 0.2 mg/kg of tacrolimus orally on the first postoperative day with a corticosteroid taper. Oral tacrolimus was started at day 1-8 in the 5 patients receiving ATGAM/OKT3 induction. Dosages were adjusted over time to maintain a whole-blood trough level of 12-15 ng/ml at 0-1 month, 10-12 ng/ml at 1-3 months, and 5-10 ng/ml after 3 months. The incidence of acute rejection was 50% (8/16) in children on oral tacrolimus induction alone and 80% (4/5) in the tacrolimus + ATGAM/OKT3 group. Epstein-Barr virus infection occurred in 6 of 19 children (32%), with no child developing lymphoproliferative disorder. No adverse effect on renal function was noted. Serum fasting glucose was stable over time while a trend was noted in decreasing serum cholesterol levels at 6 months. Antihypertensive medication was required in 4 of 19 children (21%) posttransplantation. Corticosteroids were withdrawn in 11% (2/19) of patients. Actuarial 1-year patient and graft survivals were 95% and 86%, respectively. The use of oral tacrolimus induction therapy was associated with excellent survival and a low incidence of complications.

    View details for Web of Science ID A1996UJ00300012

    View details for PubMedID 8610416

  • Elevations in IFN-gamma, IL-5, and IL-10 in patients with the autoimmune disease, primary biliary cirrhosis. Association with autoantibodies and soluble CD30. Krams, S. M., Cao, S., Hayashi, M., Esquivel, C. O., Martinez, O. M. W B SAUNDERS CO-ELSEVIER INC. 1996: A1240–A1240
  • Suggested guidelines for the use of tacrolimus in pediatric liver transplant patients TRANSPLANTATION Esquivel, C. O., So, S. K., McDiarmid, S. V., Andrews, W. S., Colombani, P. M. 1996; 61 (5): 847-848

    View details for Web of Science ID A1996UA76800033

    View details for PubMedID 8607198

  • Ganciclovir treatment of hepatitis B virus infection in liver transplant recipients HEPATOLOGY Gish, R. G., Lau, J. Y., Brooks, L., Fang, J. W., Steady, S. L., Imperial, J. C., GARCIAKENNEDY, R., Esquivel, C. O., Keeffe, E. B. 1996; 23 (1): 1-7

    Abstract

    To determine the safety and efficacy of ganciclovir treatment of hepatitis B virus (HBV) infection after liver transplantation, nine patients (seven males, two females; mean age, 38 years) with posttransplant HBV infection were treated with ganciclovir for 3 to 10 months. Ganciclovir was administered intravenously at an initial dose of 5 mg/kg/d and then increased to 10 mg/kg/d. Immunosuppressive drug therapy was maintained at low levels. There were no major side effects of ganciclovir therapy. Serum HBV DNA levels decreased by a mean of 90% (range, 42% to 100%), and four of nine patients had no measurable HBV DNA at the completion of therapy. Mean serum alanine aminotransferase levels decreased by 83%. Hepatic expression of HBV antigens and HBV DNA was assessed before and after therapy in six patients and found to be reduced in three patients. The histology activity index was also stabilized or improved in all patients. After discontinuation of therapy, four of nine patients underwent retreatment for 4- to 12-fold elevation of serum HBV DNA and/or biochemical and clinical relapse, that was severe in one patient. This pilot study shows the safety and efficacy of ganciclovir therapy for reducing HBV replication in patients with HBV infection after liver transplantation.

    View details for Web of Science ID A1996TN80100001

    View details for PubMedID 8550028

  • Expression of cytokines and immune mediators during chronic liver allograft rejection 14th Annual Meeting of the American-Society-of-Transplant-Physicians Hayashi, M., Martinez, O. M., GARCIAKENNEDY, R., So, S., Esquivel, C. O., Krams, S. M. WILLIAMS & WILKINS. 1995: 1533–38

    Abstract

    To determine the immune processes involved in chronic liver allograft rejection (CR) we examined in situ cytokine production in tissue from 15 patients with both clinical and histopathological diagnoses of CR. Total RNA was isolated from liver samples, reverse-transcribed and analyzed by RT-PCR for the production of proinflammatory cytokines and immunoregulatory mediators. Transcripts for the Th1-like cytokines IL-2 and IFN-gamma were detected in 53.3% and 46.7% of CR grafts, while they were detected in only 16% and 0% of stable grafts, respectively. The cytotoxic T cell mediator granzyme B was expressed in the majority of liver grafts undergoing CR, but was expressed only in a minority of stable grafts (80% vs. 16%, P < 0.05). The T cell product IL-5 was also significantly upregulated in CR as compared with stable livers (80% vs. 16%, P < 0.01). Other Th2 cytokines--IL-4 and IL-10--and macrophage products--IL-1 beta, IL-6, IL-8, TGF-beta, and TNF-alpha--were not substantially upregulated in CR grafts as compared with stable grafts. PDGF-beta transcripts were detected in the majority of the CR grafts, but were not detected in stable liver grafts (73% vs. 0, P < 0.05). By immunohistochemical staining, we observed that CD3+CD4+, and CD3+CD4- T cells were detected in CR grafts along with CD20+ B cells and CD68+ macrophages. There was, however, a predominant infiltration of CD3+CD4+ lymphocytes. Taken together, these data suggest that infiltrating cells produce proinflammatory and immunoregulatory cytokines that have a role in mediating graft damage in CR.

    View details for Web of Science ID A1995TN23000027

    View details for PubMedID 8545886

  • Elevated biliary interleukin 5 as an indicator of liver allograft rejection. Transplant immunology Lang, T., Krams, S. M., Berquist, W., Cox, K. L., Esquivel, C. O., Martinez, O. M. 1995; 3 (4): 291-298

    Abstract

    Interleukin 5 (IL-5) is a T cell-derived cytokine that acts as a potent and specific eosinophil differentiation factor in humans. During liver allograft rejection, intragraft IL-5 mRNA and eosinophilia have been observed. The objective of this study was to correlate the levels of IL-5 in bile and serum with eosinophilia and allograft rejection in paediatric liver recipients. IL-5 levels were determined by ELISA (enzyme-linked immunosorbent assay) in bile (n = 85) and serum (n = 106) and obtained prospectively from 15 patients during the first 3 weeks post-transplantation. Biliary and serum IL-5 levels were significantly elevated during allograft rejection compared to IL-5 levels when no rejection was apparent or during infectious complications. The highest IL-5 levels were measured in the bile during the early rejection period (3 days prior to biopsy-proven rejection). Fifteen of 16 rejection episodes were marked by increases in IL-5 as revealed by analysis of sequential samples from individual patients. In all patients with rejection, elevations in serum IL-5 were associated with elevations in peripheral eosinophil counts. These results indicate that IL-5 is produced in the liver and may be a useful and specific marker of allograft rejection. Furthermore, these findings provide further evidence for a pathway of liver allograft rejection mediated by IL-5 activated eosinophils.

    View details for PubMedID 8665147

  • THE USE OF NON-HEART-BEATING CADAVER DONORS IN EXPERIMENTAL LIVER-TRANSPLANTATION TRANSPLANTATION Tojimbara, T., Kennedy, R. G., BURNS, W., Hayashi, M., Krams, S., Martinez, O., So, S., Esquivel, C. O. 1995; 60 (10): 1179-1180

    View details for Web of Science ID A1995TH32800020

    View details for PubMedID 7482728

  • THE IMPACT OF IMMUNOSUPPRESSIVE REGIMENS ON THE COST OF LIVER-TRANSPLANTATION - RESULTS FROM THE US FK506 MULTICENTER TRIAL TRANSPLANTATION Lake, J. R., Gorman, K. J., Esquivel, C. O., Wiesner, R. H., Klintmalm, G. B., Miller, C. M., Shaw, B. W., Gordon, J. A. 1995; 60 (10): 1089-1095

    Abstract

    In an effort to determine the total one-year cost of liver transplantation, the underlying drivers of that cost, and any cost differences between alternative immunosuppressive regimens, an analysis was performed comparing the average one-year posttransplant charges of 322 patients participating in the "U.S. Multi-center Prospective Randomized Trial Comparing FK-506 to Cyclosporine in Liver Transplantation." Total one-year inpatient charges including all readmissions were examined. Professional fees and outpatient charges were excluded. Costs for tacrolimus drug and blood assays were assumed to be equal to those in the CsA group. For patients completing the study, the tacrolimus group had an average length of stay and average one-year cost seven days (P = .06) and $19,290 (P = .05) lower than the CsA group. The difference in rejection profiles between the two arms seems to largely account for the lower costs. The tacrolimus arm consistently had fewer patients in the more severe rejection groups. Increased incidence and severity of rejection were directly related to higher average lengths of stay and costs of transplantation (P < .001). Tacrolimus immunosuppression during the first year after liver transplantation is more cost-effective than CsA in achieving similar patient and graft survival rates. Differing incidence and severity of rejection can dramatically affect the first-year cost of liver transplantation.

    View details for Web of Science ID A1995TH32800005

    View details for PubMedID 7482713

  • A REASSESSMENT OF ABO INCOMPATIBILITY IN PEDIATRIC LIVER-TRANSPLANTATION TRANSPLANTATION Cacciarelli, T. V., So, S. K., Lim, J., Concepcion, W., Cox, K., Esquivel, C. O. 1995; 60 (7): 757-760

    Abstract

    The present study examined 144 pediatric liver transplants to determine the impact of ABO matching on liver allograft outcome. Pediatric transplants were divided into 3 groups: ABO identical (ABO-Id; n = 108), ABO-compatible nonidentical (ABO-Comp; n = 22), and ABO incompatible (ABO-Inc; n = 14). A higher proportion of United Network for Organ Sharing status 4 recipients in the ABO-Comp group (50% vs. 22% and 36% for ABO-Id and ABO-Inc, P < 0.05) and less time spent on the waiting list for ABO-Inc recipients (46 +/- 12 vs. 87 +/- 11 and 61 +/- 20 days for ABO-Id and ABO-Comp, P < 0.01) were noted. OKT3 induction therapy was greater in ABO-Inc grafts (57% vs. 19% and 14% for ABO-Id and ABO-Comp, P < 0.05), as was incidence of acute cellular rejection (79% vs. 59% and 41% for ABO-Id and ABO-Comp, P = 0.08). One- and 3-year patient survival rates were 87% and 83% in the ABO-Id group, 95% and 88% in the ABO-Comp group, and 79% and 79% in the ABO-Inc group (P = NS). One- and 3-year graft survival rates were 83% and 78% in the ABO-Id group, 87% and 80% in the ABO-Comp group, and 71% and 71% in the ABO-Inc group (P = NS). ABO-Inc transplantations can be performed successfully in pediatric recipients and warrant a reassessment of the utilization of ABO-Inc livers.

    View details for Web of Science ID A1995RZ96800024

    View details for PubMedID 7570989

  • LIVER-TRANSPLANTATION IN A CHILD WITH SICKLE-CELL-ANEMIA TRANSPLANTATION Lang, T., Berquist, W. E., So, S. K., Cox, K. L., RICH, E. J., Vichinsky, E., Concepcion, W., Esquivel, C. O. 1995; 59 (10): 1490-1492

    View details for Web of Science ID A1995RB42900025

    View details for PubMedID 7770941

  • LIVER-TRANSPLANTATION CURRENT OPINION IN GASTROENTEROLOGY Keeffe, E. B., Esquivel, C. O. 1995; 11 (3): 213-218
  • EFFECTS OF PENTOXIFYLLINE PRETREATMENT ON KUPFFER CELLS IN RAT-LIVER TRANSPLANTATION HEPATOLOGY Kozaki, K., Egawa, H., Bermudez, L., Keefe, E. B., So, S. K., Esquivel, C. O. 1995; 21 (4): 1079-1082

    Abstract

    Previous research with pentoxifylline (PTX), a methylxanthine phosphodiesterase inhibitor, suggests that this drug may be capable of suppressing the activation of Kupffer cells and thereby help decrease liver injury after transplantation. To investigate this possibility, the current study sought to determine whether the release of O2- and tumor necrosis factor (TNF) from Kupffer cells in donor livers can be suppressed if the organs are exposed to PTX before preservation. In an in vitro experiment, rat livers were flushed with PTX (25 mg/kg body weight) in University of Washington (UW) solution or UW solution alone (control) and then and stored in UW solution for either 4 or 24 hours. Kupffer cells then were purified and their degree of activation determined by measuring O2- release and the production of TNF after lipopolysaccharide stimulation. In an in vivo experiment, a group of rats underwent orthotopic liver transplantation with grafts prepared in the same manner as in the in vitro study. TNF and aspartate transaminase (AST) were measured in blood samples taken 3 hours and 24 hours after transplantation. Compared with controls, the Kupffer cells from grafts pretreated with PTX produced significantly less O2- and TNF, and the recipients of PTX-pretreated grafts had lower levels of TNF and AST 3 hours after transplantation. The current data indicate that O2- and TNF production in liver grafts is suppressed by PTX pretreatment. Through its suppressive effect on Kupffer cells, PTX may help minimize preservation-reperfusion injury and improve graft survival.

    View details for Web of Science ID A1995RC07100028

    View details for PubMedID 7705782

  • HEPATIC-FAILURE DUE TO MASSIVE IRON INGESTION SUCCESSFULLY TREATED WITH LIVER-TRANSPLANTATION CLINICAL TRANSPLANTATION Kozaki, K., Egawa, H., GARCIAKENNEDY, R., Cox, K. L., Lindsay, J., Esquivel, C. O. 1995; 9 (2): 85-87

    Abstract

    A 3-year-old female had fulminant hepatic and renal failure due to massive iron ingestion, despite gastric lavage, deferoxamine administration, hemodialysis and continuous arteriovenous hemofiltration. She underwent a successful emergency liver transplantation on 5th day after ingestion and was discharged 25 days later with excellent liver and renal function.

    View details for Web of Science ID A1995QV67600004

    View details for PubMedID 7599407

  • ISOLATED ALKALINE PHOSPHATEMIA FOLLOWING PEDIATRIC LIVER-TRANSPLANTATION IN THE FK506 ERA TRANSPLANTATION Egawa, H., Berquist, W., So, S. K., Cox, K., Menegaux, F., Esquivel, C. O. 1995; 59 (5): 791-793

    View details for Web of Science ID A1995QM65600028

    View details for PubMedID 7533958

  • Liver transplantation for treatment of giant hepatocellular adenomas. Liver transplantation and surgery Mueller, J., Keeffe, E. B., Esquivel, C. O. 1995; 1 (2): 99-102

    Abstract

    Giant hepatocellular adenomas are associated with a high incidence of rupture with intra-abdominal hemorrhage and may also undergo malignant transformation. If resection is not technically feasible, liver transplantation should be a treatment option. The aim of this report is to describe the indications, feasibility, and outcome of liver transplantation for hepatocellular adenomas. A 66-year-old man with a 17-cm hepatocellular adenoma originating in the left lobe but involving nearly the entire liver and a 35-year-old woman with a 20-cm tumor involving the right lobe of the liver and compressing the left lobe underwent liver transplantation without complication. In both cases, a histological diagnosis was made by core needle biopsy preoperatively, and resection was technically not possible. Hepatocellular adenoma involving nearly all of the liver with no evidence of malignant change was confirmed in the explant liver from both cases. Giant hepatocellular adenomas may be unresectable and require liver transplantation for complete removal to prevent potential rupture with hemorrhage or malignant transformation.

    View details for PubMedID 9346548

  • SURVIVAL AFTER LIVER-TRANSPLANTATION FOR CHRONIC HEPATITIS-B USING REDUCED IMMUNOSUPPRESSION JOURNAL OF HEPATOLOGY Gish, R. G., Keeffe, E. B., Lim, J., Brooks, L. J., Esquivel, C. O. 1995; 22 (3): 257-262

    Abstract

    Recurrent hepatitis B virus infection after liver transplantation performed for chronic hepatitis B with cirrhosis is influenced by a number of factors, including coinfection with the hepatitis D virus, the level of HBV replication, and administration of hepatitis B immune globulin. Another potentially important factor in modulating HBV infection after liver transplantation is the degree of immunosuppression post-transplant. We reviewed an institutional experience with liver transplantation for chronic hepatitis B and analyzed the impact of using lower doses of corticosteroids on HBV reinfection, expression of recurrent HBV disease and patient survival.Of 17 patients undergoing liver transplantation for chronic hepatitis B, 16 patients received variable doses of hepatitis B immune globulin for up to 6 months.Fifteen of the 16 patients remained HBsAg-negative during hepatitis B immune globulin therapy, but ultimately 13 of the 17 patients had HBV reinfection, including 3 of 4 patients with hepatitis D virus coinfection. Long-term survival (82%) of the 17 chronic hepatitis B patients was not different from the survival (75%) of 195 patients transplanted for other indications. Three of 13 patients who were reinfected died from chronic hepatitis B with liver failure. Reinfection did not appear to be related to the pretransplant degree of viral replication. Compared to an age- and sex-matched control group, patients undergoing liver transplantation for chronic hepatitis B received less cumulative intravenous methylprednisolone and oral prednisone, but did not experience a higher rate of graft rejection.We postulate that use of lower doses of corticosteroids after liver transplantation for chronic hepatitis B is safe and not associated with a higher incidence of graft rejection. Moreover, low-dose maintenance prednisone therapy may modify the course of post-transplant HBV reinfection by leading to less viral replication, milder HBV-related liver disease and better patient survival.

    View details for Web of Science ID A1995RL11200001

    View details for PubMedID 7608474

  • AN INCREASED INCIDENCE OF EPSTEIN-BARR-VIRUS INFECTION AND LYMPHOPROLIFERATIVE DISORDER IN YOUNG-CHILDREN ON FK506 AFTER LIVER-TRANSPLANTATION 13th Annual Meeting of the American-Society-of-Transplant-Physicians Cox, K. L., LAWRENCEMIYASAKI, L. S., GARCIAKENNEDY, R., Lennette, E. T., Martinez, O. M., Krams, S. M., Berquist, W. E., So, S. K., Esquivel, C. O. WILLIAMS & WILKINS. 1995: 524–29

    Abstract

    The incidence of Epstein-Barr virus (EBV) infection and lymphoproliferative disorder (LPD) was determined in a pediatric liver transplant population consisting of 51 children treated with FK506 and 91 treated with cyclosporine. The incidence of symptomatic EBV infection was 21.9% (23 of 105 cases) in children < 5 yr old and 10.8% (4 of 37 cases) in children 5 to 17 yr old as compared with 2.7% (9 of 323 cases) in adults (P < 0.0001). In the under 5 yr old group on cyclosporine, the incidences of EBV infection and LPD were 9 of 68 (13.2%) and 2 of 68 children, (2.9%), respectively. In contrast, in children under 5 yr old group on FK506, the incidences of EBV infection and LPD in the FK506 group were 14 of 37 (37.8%) and 7 of 37 children (18.9%), respectively. The difference between these two groups was statistically significant (P < 0.02). There were no cases of LPD in the 5-17 yr-old children on either cyclosporine (n = 23) or FK506 (n = 14). The incidence of EBV infections in the 5 to 17 yr age group, 17.4% on cyclosporine and 0% on FK506, was less than for the younger children on FK506 (37.8%). A total of 39% (9 of 23) of children under 5 yr old who had symptomatic EBV infections developed LPD, and 44% (4 of 9) with LPD died. The higher incidence of EBV infections and LPD in the younger children treated with FK506 was probably related to a greater intensity of immunosuppression for patients on FK506 than those on cyclosporine.

    View details for Web of Science ID A1995QK22500015

    View details for PubMedID 7533344

  • FK506 (TACROLIMUS) COMPARED WITH CYCLOSPORINE FOR PRIMARY IMMUNOSUPPRESSION AFTER PEDIATRIC LIVER-TRANSPLANTATION - RESULTS FROM THE US MULTICENTER TRIAL 13th Annual Meeting of the American-Society-of-Transplant-Physicians McDiarmid, S. V., Busuttil, R. W., Ascher, N. L., Burdick, J., DALESSANDRO, A. M., Esquivel, C., Kalayoglu, M., Klein, A. S., Marsh, J. W., Miller, C. M., Schwartz, M. E., Shaw, B. W., So, S. K. WILLIAMS & WILKINS. 1995: 530–36

    Abstract

    We report on the efficacy and safety of FK506 (tacrolimus) compared with a cyclosporine (CsA)-based immunosuppressive regimen after 1 year of treatment in pediatric liver allograft recipients (< 12 years) participating in a multicenter U.S. randomized trial. Patients received either FK506 or CsA as primary immunosuppression following a first ABO-compatible liver transplant. Intravenous FK506 was initiated at 0.1 mg/kg per day, followed by oral FK506 beginning at 0.3 mg/kg per day. The dose was adjusted to maintain plasma trough levels of 0.5-2.0 ng/ml. The CsA group was treated according to each center's usual protocol. Both groups received the same initial doses of corticosteroids. All rejection episodes were biopsy-proven and a standardized algorithm was adopted for the treatment of rejection. Thirty patients were randomized to the FK506 group and 20 to the CsA group. After twelve months of follow-up 20 patients remained in the FK506 group and 13 in the CsA group. Patient survivals were 80% and graft survival 70% in the FK506 group compared with 81% and 71% respectively, in the CsA group. 48% of the FK506 group remained rejection-free compared with 21% of the CsA group, and 79% of FK506-treated patients did not require OKT3 compared with 68% of CsA treated patients. The cumulative corticosteroid dose was less at each time point throughout the first year in the FK506 group. The incidence of serious and minor infections was similar in both groups. Nephrotoxicity, neurotoxicity, and gastrointestinal disturbances were the major toxicities reported. Differences did not reach statistical significance between the two groups although major neurologic events, diarrhea and dyspepsia were more often reported in the FK506 group. There was no difference in mean serum creatinine at 12 months between the two groups. There was a tendency toward lower mean serum cholesterol in the FK506 group. There was no hirsuitism in the FK506 group compared with a 30% incidence in the CsA group. In conclusion, compared with CsA, there is a trend toward less rejection in FK506-treated pediatric allograft recipients, while both drugs have a similar spectrum of side effects.

    View details for Web of Science ID A1995QK22500016

    View details for PubMedID 7533345

  • DISTINCT PATTERNS OF TH2 CYTOKINE PRODUCTION DURING IMMUNE ACTIVATION IN PEDIATRIC LIVER ALLOGRAFT RECIPIENTS XVth World Congress of the Transplantation-Society Lang, T., Krams, S. M., Villanueva, J. C., Cox, K., So, S., Esquivel, C., Martinez, O. M. ELSEVIER SCIENCE INC. 1995: 1146–47

    View details for Web of Science ID A1995QJ19900456

    View details for PubMedID 7533367

  • IMPACT OF REDUCED-SIZE LIVER-TRANSPLANTATION ON REJECTION AND LIVER ALLOGRAFT OUTCOME IN THE PEDIATRIC POPULATION XVth World Congress of the Transplantation-Society Cacciarelli, T. V., So, S. K., Egawa, H., Cox, K., Esquivel, C. O. ELSEVIER SCIENCE INC. 1995: 1239–40

    View details for Web of Science ID A1995QJ19900497

    View details for PubMedID 7878864

  • LONG-TERM NONRESPONSIVENESS TO A LIVER ALLOGRAFT MAY BE CYTOKINE-MEDIATED XVth World Congress of the Transplantation-Society Egawa, H., Martinez, O. M., QUINN, M. B., Villanueva, J. C., So, S., Esquivel, C. O., Krams, S. M. ELSEVIER SCIENCE INC. 1995: 241–42

    View details for Web of Science ID A1995QJ19900085

    View details for PubMedID 7533390

  • CHARACTERIZATION OF CYTOKINE EXPRESSION IN AN ANIMAL-MODEL OF ACUTE LIVER ALLOGRAFT-REJECTION XVth World Congress of the Transplantation-Society Egawa, H., Martinez, O. M., QUINN, M. B., So, S., Esquivel, C. O., Krams, S. M. ELSEVIER SCIENCE INC. 1995: 505–6

    View details for Web of Science ID A1995QJ19900201

    View details for PubMedID 7879079

  • MOLECULAR MARKERS OF EPSTEIN-BARR-VIRUS INFECTION IN THE CIRCULATION OF TRANSPLANT RECIPIENTS XVth World Congress of the Transplantation-Society Martinez, O. M., Villanueva, J. C., LAWRENCEMIYASAKI, L., QUINN, M. B., Gish, R., Cox, K., So, S., Esquivel, C. O., Krams, S. M. ELSEVIER SCIENCE INC. 1995: 1211–12

    View details for Web of Science ID A1995QJ19900484

    View details for PubMedID 7533372

  • CIRCULATING INTERCELLULAR-ADHESION MOLECULE-1 AND VASCULAR CELL-ADHESION MOLECULE-1 IN PEDIATRIC LIVER RECIPIENTS XVth World Congress of the Transplantation-Society Lang, T., Krams, S. M., Villanueva, J. C., So, S. K., Berquist, W. E., Cox, K. L., Esquivel, C. O., Martinez, O. M. ELSEVIER SCIENCE INC. 1995: 1148–49

    View details for Web of Science ID A1995QJ19900457

    View details for PubMedID 7533368

  • ACUTE LIVER ALLOGRAFT-REJECTION IN THE RAT - AN ANALYSIS OF THE IMMUNE RESPONSE TRANSPLANTATION Egawa, H., Martinez, O. M., QUINN, M. B., Villanueva, J. C., So, S., Esquivel, C. O., Krams, S. M. 1995; 59 (1): 97-102

    Abstract

    Liver allografts are vigorously rejected in 9-12 days in Lewis recipients of fully histoincompatible DA livers. The purpose of this study was to examine the initial events in this cascade, specifically the role of CD4+ T helper cells. Lewis recipients of DA or Lewis livers were killed at days 1, 2, 3, 4, and 7 days after transplant. Indicators of acute liver rejection, including a marked inflammatory infiltrate and decreased liver function, progressed in untreated recipients of allografts. Splenocytes taken from allogeneic recipients on days 1-4 and 7 proliferated in response to donor and third-party stimulators, whereas graft-infiltrating cells did not respond to donor and third-party antigens until day 3 after transplant, but thereafter maintained a good response. To further characterize the host T helper cell response to liver allografts, cytokine expression was analyzed in graft tissue and in the periphery. IL-4 mRNA was present in both syngeneic and allogeneic liver grafts, while message for IL-10 was present early in all liver grafts but persisted only in allografts. In contrast, IL-2 and IFN-gamma transcripts were specific to rejecting allografts. Similar patterns of cytokine expression were observed in the spleen, indicating the immune response to the graft involves the peripheral lymphoid organs. Thus, the cytokine profile detected during liver allograft rejection is extremely similar to that observed in other experimental models of transplantation.

    View details for Web of Science ID A1995QB42700017

    View details for PubMedID 7839435

  • HEPATOCELLULAR-CARCINOMA AND LIVER-CELL DYSPLASIA IN CHILDREN WITH CHRONIC LIVER-DISEASE JOURNAL OF PEDIATRIC SURGERY Esquivel, C. O., Gutierrez, C., Cox, K. L., GARCIAKENNEDY, R., Berquist, W., Concepcion, W. 1994; 29 (11): 1465-1469

    Abstract

    The histology of 72 livers from 72 children who underwent liver transplantation was reviewed. Nine children (12.5%) had hepatocellular carcinoma (HCC) and/or liver cell dysplasia (LCD) in their native livers. Ages at the time of transplantation ranged from 2 months to 11 years. Primary liver diseases included tyrosinemia (3), biliary atresia (2), chronic active hepatitis B (1), chronic active non-A non-B non-C hepatitis (1), idiopathic neonatal hepatitis (1), and neonatal iron storage disease (1). Explanted livers showed large multifocal HCC in two cases, incidental HCC in three, and dysplastic nodules in four. LCD also was present in three cases in conjunction with HCC. All patients had cirrhosis. Alpha-fetoprotein was measured in six children and was elevated in all six (range, 300 to 1,770,000 ng/mL; normal, 0 to 15 ng/mL). Abdominal computed tomography, ultrasonography, and/or magnetic resonance imaging showed large masses in two cases, but did not detect the tumors of less than 2 cm or the dysplastic nodules in the other seven children. After a follow-up period of 2 months to 3 years (mean, 19.8 +/- 12.1 months), eight children are alive and have no evidence of recurrence. The patient with neonatal iron storage disease died 2 months after transplantation, without evidence of tumor recurrence. The authors conclude that children with end-stage liver disease of diverse causes referred for liver transplantation may have LCD and/or HCC. Serial determination of alpha-fetoprotein and images studies may detect early lesions curable by liver transplantation.

    View details for Web of Science ID A1994PQ67000016

    View details for PubMedID 7844722

  • EX-VIVO TECHNIQUE FOR RIGHT LOBECTOMY IN PEDIATRIC HEPATIC TRANSPLANTATION JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Wong, L., Concepcion, W., So, S. K., Egawa, H., Menegaux, F., Esquivel, C. O. 1994; 179 (5): 601-603

    View details for Web of Science ID A1994PQ16900016

    View details for PubMedID 7952466

  • IMPACT OF TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT ON ORTHOTOPIC LIVER-TRANSPLANTATION 35th World Congress of the International-Society-of-Surgery Menegaux, F., Baker, E., Keeffe, E. B., Monge, H., Egawa, H., Esquivel, C. O. SPRINGER. 1994: 866–71

    Abstract

    Transjugular intrahepatic portosystemic shunt (TIPS) is being increasingly utilized prior to liver transplantation for portal hypertensive bleeding refractory to sclerotherapy or as initial management of variceal bleeding. The impact of TIPS on subsequent orthotopic liver transplantation (OLT) is uncertain. The purpose of this study was to analyze the effect of TIPS on OLT in terms of operative transfusion requirements, operative time, length of hospital stay, and graft and patient survival. The results in 17 patients undergoing TIPS for control of initial or recurrent variceal bleeding prior to OLT between June 1991 and December 1992 were compared to two other groups undergoing transplantation: 32 control patients with a history of variceal bleeding not treated by TIPS and 11 patients with a previous surgical portosystemic shunt. Compared with control and surgical shunt patients, patients who underwent TIPS had less transfusion requirement for packed red blood cells and fresh frozen plasma during OLT. The operative time and hospital stay of the TIPS patients were slightly, but not significantly, less. In contrast to patients having TIPS, the patients with a history of a previous surgical shunt had an increased requirement for packed red blood cells, longer operative time, and longer stay in the intensive care unit and hospital. Two patients had recurrent variceal bleeding after TIPS; one patient was found to have an occluded stent, and the other patient (with a patent stent) responded to sclerotherapy. Of the 14 patients with ascites, 8 patients improved and 6 patients had complete resolution after TIPS. There were no major complications related to TIPS, although 3 patients had new or recurrent hepatic encephalopathy that was easily manageable.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1994PY17700011

    View details for PubMedID 7846910

  • A COMPARISON OF TACROLIMUS (FK-506) AND CYCLOSPORINE FOR IMMUNOSUPPRESSION IN LIVER-TRANSPLANTATION NEW ENGLAND JOURNAL OF MEDICINE Busuttil, R. W., McDiarmid, S., Klintmalm, G. B., Goldstein, R., Miller, C. M., Schwartz, M., Shaw, B. W., Roberts, J. P., Hebert, M. F., Esquivel, C. O., Nakazato, P., Wiesner, R. H., Krom, R. A., Kalayoglu, M., DALESSANDRO, A. M., Marsh, J. W., Peters, M. G., Burdick, J., Klein, A., Lewis, W. D., Jenkins, R., Thistlethwaite, J. R., Emond, J. C., Jusko, W. J., DAMBROSIO, R., Buell, D., Fitzsimmons, W. E. 1994; 331 (17): 1110-1115
  • TREATMENT OF HEPATIC-FAILURE SECONDARY TO ISONIAZID HEPATITIS WITH LIVER-TRANSPLANTATION DIGESTIVE DISEASES AND SCIENCES Farrell, F. J., Keeffe, E. B., Man, K. M., Imperial, J. C., Esquivel, C. O. 1994; 39 (10): 2255-2259

    Abstract

    Two patients with liver failure secondary to isoniazid hepatotoxicity were successfully treated with orthotopic liver transplantation. A 49-year-old man received isoniazid prophylaxis for a positive tuberculin test, and a 60-year-old woman was treated for active pulmonary tuberculosis with isoniazid, rifampin, and pyrazinamide. Both patients developed hepatic failure 4 and 1.5 months after initiation of antituberculous drug therapy, respectively. Liver transplantation was performed for progressive hepatic failure and was successful in both patients. The patient with active pulmonary tuberculosis was successfully treated with a modified antituberculous drug regimen while taking standard doses of immunosuppressive drugs after transplantation. In conclusion, liver transplantation is feasible and effective therapy for patients with isoniazid-induced hepatic failure, and active pulmonary tuberculosis may represent a relative rather than absolute contraindication to transplantation.

    View details for Web of Science ID A1994PL97200031

    View details for PubMedID 7924752

  • COMPARISON OF TRANSJUGULAR AND SURGICAL PORTOSYSTEMIC SHUNTS ON THE OUTCOME OF LIVER-TRANSPLANTATION ARCHIVES OF SURGERY Menegaux, F., Keeffe, E. B., Baker, E., Egawa, H., Concepcion, W., Russell, T. R., Esquivel, C. O. 1994; 129 (10): 1018-1024

    Abstract

    To analyze the effect of previous transjugular intrahepatic portosystemic shunt (TIPS) vs surgical portosystemic shunt (SPS) on the outcome of orthotopic liver transplantation (OLT).A case series of 38 patients who underwent OLT: 25 with a previous TIPS and 13 with a previous SPS.A liver transplant center and interventional radiology service in a private, tertiary referral medical center.Eighteen men and seven women who had a TIPS before OLT were compared with nine men and four women who had an SPS before OLT.Operative transfusion requirements, operative time, length of hospital stay, postoperative liver chemistry studies, and graft and patient survival.Compared with patients who had an SPS, patients who had a TIPS had significantly less median transfusion requirements for packed red blood cells (5 vs 12 U), fresh-frozen plasma (0 vs 8 U), and thrombocytes (0 vs 1 U). The median operative time (9 vs 13 hours), length of intensive care unit stay (3 vs 5 days), and length of hospital stay (12 vs 24 days) were also significantly less in patients who had a TIPS. The 2-year actuarial patient survival rate was 92% in both groups.In patients undergoing OLT, TIPS is associated with reduced operative transfusion requirements, operative time, and length of intensive care unit and hospital stays compared with SPS. In the potential liver transplant candidate with refractory complications of portal hypertension, TIPS is preferred to SPS.

    View details for Web of Science ID A1994PL49300006

    View details for PubMedID 7944930

  • LIVER-TRANSPLANTATION FOR UNCONTROLLABLE VARICEAL BLEEDING AMERICAN JOURNAL OF GASTROENTEROLOGY EWAGA, H., Keeffe, E. B., Dort, J., Concepcion, W., Esquivel, C. O. 1994; 89 (10): 1823-1826

    Abstract

    A small number of liver transplant candidates experience variceal bleeding that cannot be controlled by standard medical therapy. The objective of this study was to analyze the role of urgent liver transplantation for this subset of patients with acute, refractory, portal hypertensive bleeding.Retrospective review of data from 416 patients undergoing 449 liver transplantations between March, 1988 and February, 1993 revealed seven patients (1.7%) with endstage liver disease who underwent transplantation for uncontrollable variceal bleeding. All patients failed therapy with intravenous pitressin, endoscopic sclerotherapy, balloon tamponade, and/or transjugular intrahepatic portosystemic shunt and continued to bleed. Patients ranged in age from 6 months to 56 years. All patients were Child's class C. Two patients were listed for transplantation with the United Network for Organ Sharing as status 3, and five patients were listed as status 4.All patients underwent successful liver transplantation with immediate control of bleeding. One patient expired on the 26th postoperative day from multiple organ failure, and another patient expired with recurrent hepatocellular carcinoma on the 110th postoperative day. No patients experienced late rebleeding from varices after transplantation.Urgent liver transplantation is effective and feasible for the small subset of patients with uncontrollable variceal bleeding and endstage liver disease. Prompt and complete evaluation of the potential recipient and availability of a donor organ are critical to the success of this approach.

    View details for Web of Science ID A1994PK76700014

    View details for PubMedID 7942675

  • AORTIC-VALVE ENDOCARDITIS AFTER ORTHOTOPIC LIVER-TRANSPLANTATION TRANSPLANTATION Egawa, H., Woodley, S., Keeffe, E. B., Concepcion, W., WIVIOTT, L. D., Menegaux, F., Esquivel, C. O. 1994; 58 (6): 732-734

    View details for Web of Science ID A1994PK26700019

    View details for PubMedID 7940698

  • NEUROLOGICAL COMPLICATIONS OF LIVER-TRANSPLANTATION IN ADULT VERSUS PEDIATRIC-PATIENTS TRANSPLANTATION Menegaux, F., Keeffe, E. B., Andrews, B. T., Egawa, H., Monge, H., Concepcion, W., So, S. K., Esquivel, C. O. 1994; 58 (4): 447-450

    Abstract

    Neurological complications are important contributors to morbidity and mortality after liver transplantation. We reviewed 391 patients who underwent 427 consecutive orthotopic liver transplantations to analyze the clinical features of patients who experienced one or more neurological complication (74 patients [19%]) and to compare postoperative neurological problems in adults versus children. Neurological complications were more frequent in adults (64 of 273 patients [23%]) than children (10 of 118 patients [8%]) (P < 0.01). The most common neurological complication was encephalopathy (59%), which ranged widely in severity and occurred with similar frequency in adults and children. Other common neurological complications were seizures (12 patients), brachial plexus and peripheral nerve injuries (16 patients, 15 of whom were adults), stroke (5 patients), and central nervous system infections (5 patients). In 27 patients, drug toxicity was the primary cause of neurological complications, all of which reversed with dosage reduction or discontinuation of drug. Cyclosporine and FK506, primarily during intravenous administration for induction of immunosuppression, accounted for 25 of 27 drug-induced neurological complications, which included encephalopathy, seizures, severe tremor, and severe headache. Despite a higher rate of neurological complications in adults, those in children were more severe and associated with a higher mortality rate. When compared with liver transplant recipients without neurological complications, patients with neurological complications had a higher posttransplant mortality rate (14% vs. 5% for adults, and 50% vs. 7% for children). In conclusion, neurological complications after liver transplantation are more common in adults, more severe and associated with a higher mortality rate in children, and associated with a higher mortality rate in both children and adults when compared with transplant recipients without neurological complications.

    View details for Web of Science ID A1994PE12000010

    View details for PubMedID 8073514

  • OUTCOME OF LIVER-TRANSPLANTATION IN PATIENTS WITH HEMOCHROMATOSIS HEPATOLOGY Farrell, F. J., Nguyen, M., Woodley, S., Imperial, J. C., GARCIAKENNEDY, R., Man, K., Esquivel, C. O., Keeffe, E. B. 1994; 20 (2): 404-410

    Abstract

    Recent preliminary reports suggest a poor outcome of orthotopic liver transplantation for patients with hemochromatosis. We analyzed an institutional experience with orthotopic liver transplantation for hemochromatosis, focusing on factors contributing to increased morbidity and mortality. Between March 1988 and October 1992, nine of 249 adults (3.6%) undergoing orthotopic liver transplantation had hemochromatosis. Mean age was 53 yr (range, 42 to 62 yr), and eight of nine patients were men. The diagnosis of hemochromatosis was based on transferrin saturation > 62% and hepatic iron index > 2.0. Only two patients were known to have hemochromatosis before liver transplantation. All nine patients underwent standard cardiac evaluation before transplantation, and no patient had detectable pre-existing cardiac disease. One patient had a major operative cardiac complication as a result of pulmonary embolism and made a full recovery. Postoperatively, congestive heart failure developed in three patients and four patients had arrhythmias. One patient is undergoing phlebotomy for post-transplant cardiac complications from hemochromatosis. Two patients had primary hepatic tumors in the explant liver. There were four deaths caused by multiorgan failure with congestive heart failure (1), infection (2), and/or malignancy (2). Five patients are alive 3 to 25 mo post-transplant. The actuarial survival of the nine patients was 53% at 25 mo vs. 89% for 18 age- and sex-matched control transplant recipients (p = 0.1) and 81% for all other adult liver transplant recipients (p < 0.01). In five of seven patients, post-transplant liver biopsies revealed hepatic iron accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1994PA13000020

    View details for PubMedID 8045502

  • RESPIRATORY-DISTRESS FROM BENIGN LIVER-TUMORS - A REPORT OF 2 UNUSUAL CASES TREATED WITH HEPATIC TRANSPLANTATION JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Egawa, H., Berquist, W., GARCIAKENNEDY, R., Cox, K. L., Concepcion, W., So, S. K., Esquivel, C. O. 1994; 19 (1): 114-117

    View details for Web of Science ID A1994PA26400020

    View details for PubMedID 7965461

  • PULMONARY VARICES PRESENTING AS A SOLITARY LUNG MASS IN A PATIENT WITH END-STAGE LIVER-DISEASE CHEST Man, K. M., Keeffe, E. B., Brown, C. R., Egawa, H., Esquivel, C. O. 1994; 106 (1): 294-296

    Abstract

    A man undergoing evaluation for liver transplantation was found to have an asymptomatic chest mass, which further evaluation revealed to be pulmonary varices. The left hilar lesion was discovered on a screening chest x-ray film and confirmed by a computed tomographic scan of the thoracic cavity. Bronchoscopy was nondiagnostic, and a thoracotomy was required to diagnose the vascular lesion and exclude carcinoma. The pathophysiology of this pulmonary venous anomaly appeared to be related to portal hypertension, since esophagogastric and colonic varices also were present and the pulmonary varices resolved after liver transplantation. This is the first reported case of pulmonary varices caused by portal hypertension.

    View details for Web of Science ID A1994NX37200056

    View details for PubMedID 8020292

  • FK506 CONVERSION THERAPY IN PEDIATRIC LIVER-TRANSPLANTATION TRANSPLANTATION Egawa, H., Esquivel, C. O., So, S. K., Cox, K., Concepcion, W., Lawrence, L. 1994; 57 (8): 1169-1173

    Abstract

    The safety and efficacy of conversion to FK506 after failing immunosuppression with cyclosporine was prospectively evaluated in 31 pediatric liver transplant recipients between April 1991 and March 1993. The patients, who ranged in age from 40 days to 14 years, accounted for 28 primary transplantations and 3 retransplantations. The initial immunosuppression regimen consisted of cyclosporine in combination with prednisone. The indications for conversion were acute or chronic rejection refractory to OKT3, Minnesota antilymphocyte globulin, or steroids (13 patients); hypertension (8 patients); inability to reach a therapeutic level of cyclosporine (6 patients); hirsutism (3 patients); and growth retardation (1 patient). After an average follow-up of 10 months (range, 2 to 25 months), 27 (87%) of the patients are alive and have functioning grafts. Of the 13 patients who were converted for refractory rejection, 9 are alive. Six of these 9 patients experienced a complete biochemical reversal of the rejection process within 3 months of conversion; 2 had a partial response to conversion, and 1 patient failed but underwent successful retransplantation. Three of the 4 patients who died did so without showing any improvement. The remaining 18 patients who were converted for various other reasons are alive and have functioning grafts. Of the 8 patients who developed hypertension on cyclosporine and prednisone, 6 experienced a resolution of this problem within 3 months of conversion. Three of the 18 children who underwent rescue therapy for reasons other than refractory rejection experienced rejection episodes after conversion to FK506. Two of these 3 children achieved resolution with either steroid therapy or an increased dosage of FK506, while the third child developed chronic rejection. The side effects of FK506 were generally minor and resolved by lowering the dose. Lymphoproliferative disease developed in 2 patients (6%). The present study suggests that FK506 is a relatively safe and effective rescue therapy for pediatric liver transplant recipients who have failed immunosuppression with cyclosporine. Longer follow-up is needed to assess the effect of FK506 on growth.

    View details for Web of Science ID A1994NJ20800005

    View details for PubMedID 7513911

  • MODIFICATION OF REJECTION BY POLYETHYLENE-GLYCOL SMALL-BOWEL TRANSPLANTATION TRANSPLANTATION Itasaka, H., BURNS, W., Wicomb, W. N., Egawa, H., Collins, G., Esquivel, C. O. 1994; 57 (5): 645-648

    Abstract

    The use of polyethylene glycol (PEG) in preservation solutions has been associated with a decreased incidence of rejection in clinical and experimental organ transplantation. In this study, we examined the effect of PEG with different molecular configurations on rejection of small bowel allografts in the rat. Male ACI and LEW rats were used as donors and recipients, respectively. Orthotopic small bowel transplantation was performed using the following preservation solutions: lactated Ringer's solution (n = 7), University of Wisconsin solution (n = 7), University of Wisconsin solution without hydroxyethyl starch (sUW; n = 7), sUW with PEG20M (n = 9), sUW with PEG8000 (n = 6), and sUW with PEG20L (n = 7). No immunosuppression was given. In orthotopic small bowel transplantation, only groups with a high molecular weight PEG, PEG20M and PEG20L, demonstrated longer survival (P < 0.01 and P < 0.001, respectively) and delayed onset of unkempt appearance (P < 0.05 and P < 0.001, respectively). In heterotopic small bowel transplantation, sUW was compared with sUW with PEG20L. Rejection occurred later and its progression was slower in the sUW with PEG20L than in the sUW alone. Our observations suggest that the onset and progression of rejection after small bowel transplantation were influenced by the molecular weight and configuration of the PEG molecule. The mechanism is unclear, but high molecular weight PEG appears to reduce or change the immunogenicity of the small bowel allograft.

    View details for Web of Science ID A1994NC19000001

    View details for PubMedID 8140625

  • LIVER-TRANSPLANTATION IN PATIENTS WITH SEVERE OBESITY TRANSPLANTATION Keeffe, E. B., GETTYS, C., Esquivel, C. O. 1994; 57 (2): 309-311

    View details for Web of Science ID A1994MU93900034

    View details for PubMedID 8310529

  • Liver transplantation at California Pacific Medical Center, San Francisco, California. Clinical transplants Esquivel, C. O., Martinez, O., Krams, S., Lim, J., So, S. K., Concepcion, W., Cox, K. L., Keeffe, E. B. 1994: 163-171

    Abstract

    A number of modifications in patient selection, operative technique, and immunosuppressive management have greatly contributed to the success of the liver transplant program at CPMC. Graft rejection and the timely detection of EBV infection are ongoing problems in hepatic transplantation that are foci of active research in our field. To address these issues, our group is investigating the activity of cytokines and adhesion molecules using sophisticated molecular techniques, and we are developing a sensitive assay for EBV markers in blood. These and other projects currently in progress will continue when we move our liver transplant program to Stanford University Medical Center in January 1995.

    View details for PubMedID 7547535

  • COMPARATIVE EFFECTS OF BLOOD, COLLOID, AND RINGERS LACTATE TERMINAL ALLOGRAFT RINSE ON THE RESULTS OF ORTHOTOPIC LIVER-TRANSPLANTATION 2nd International Congress of the Society-for-Organ-Sharing Menegaux, F., Egawa, H., Keeffe, E. B., So, S. K., Concepcion, W., Collins, G. M., Esquivel, C. O. ELSEVIER SCIENCE INC. 1993: 3196–98

    View details for Web of Science ID A1993ML92400093

    View details for PubMedID 8266513

  • SIGNIFICANCE OF TERMINAL RINSE FOR RAT-LIVER PRESERVATION TRANSPLANTATION Egawa, H., Esquivel, C. O., Wicomb, W. N., Kennedy, R. G., Collins, G. M. 1993; 56 (6): 1344-1347

    Abstract

    A terminal rinse (TR) is standard practice in liver preservation with University of Wisconsin solution (UW) to avoid a potassium load. The fact that sodium lactobionate sucrose solution (SLS) is an effective organ preservation solution with a low potassium provided an opportunity to evaluate rat liver preservation without the TR step. Its importance was investigated in 122 rat liver preservation experiments. In study 1, UW and a hydroxyethyl starch-free, modified UW (UWm) were used for 20-hr liver preservation followed by either no TR or Ringer's lactate TR. The 1-week survival was: UW-TR, 2/14; UW-no TR, 1/6; UWm-TR, 0/6; UWm-no TR, 5/5 (P < 0.01). In study 2, livers were stored for 30 hr in SLS, UW, UWm, and UWm + chlorpromazine 5 mg/L, all without a TR. Nine of 11 rats survived 7 days after SLS, but there were no survivors in the other groups (P < 0.05). Study 3 compared no TR with TR with SLS, Ringer's lactate (RL), or a modified Carolina rinse (CRm) after 30-hr SLS preservation. Survival, serum aspartate aminotransferase and alanine aminotransferase, and histology were assessed. One-week survival of 9/11 rats in no TR was significantly better than in the other groups (3/14 in TR-SLS, 0/8 in TR-RL, and 0/14 in TR-CRm, P < 0.01). The values of aspartate aminotransferase (mean +/- SE) 3 hr after transplantation were 1862 +/- 439 U/L, 3334 +/- 817 U/L, 6591 +/- 1944 U/L, and 7028 +/- 1704 U/L, respectively, in no TR, TR-SLS, TR-RL, and TR-CRm. There were significant differences both in aspartate aminotransferase and alanine aminotransferase between no-TR and each of TR-RL and TR-CRm (P < 0.05). Liver specimens from rats killed 3 hr after OLT showed only mild injury in the no TR group and severe injury in the remaining groups. We conclude that a terminal rinse is harmful in rat liver preservation.

    View details for Web of Science ID A1993MQ05600011

    View details for PubMedID 8279001

  • SIGNIFICANCE OF TERMINAL RINSE FOR RAT-LIVER PRESERVATION 2nd International Congress of the Society-for-Organ-Sharing Egawa, H., Esquivel, C. O., Wicomb, W. N., Kennedy, R. G., Menegaux, F., Collins, G. M. ELSEVIER SCIENCE INC. 1993: 3220–21

    View details for Web of Science ID A1993ML92400103

    View details for PubMedID 8266521

  • PENTOXIFYLLINE INHIBITS PRODUCTION OF SUPEROXIDE ANION AND TUMOR-NECROSIS-FACTOR BY KUPFFER CELLS IN RAT-LIVER PRESERVATION 2nd International Congress of the Society-for-Organ-Sharing Kozaki, K., Egawa, H., BERMUDES, L., Feduska, N. J., So, S., Esquivel, C. O. ELSEVIER SCIENCE INC. 1993: 3025–26

    View details for Web of Science ID A1993ML92400017

    View details for PubMedID 8266439

  • PRIMARY SCLEROSING CHOLANGITIS AND HODGKINS-DISEASE HEPATOLOGY Man, K. M., Drejet, A., Keeffe, E. B., GARCIAKENNEDY, R., Imperial, J. C., Esquivel, C. O. 1993; 18 (5): 1127-1131

    Abstract

    Three patients with primary sclerosing cholangitis and Hodgkin's disease, a previously unrecognized association, are reported. All three patients were men, and one patient had Crohn's disease of the colon. Primary sclerosing cholangitis was diagnosed 2, 11 and 17 yr before diagnosis of Hodgkin's disease in the three patients, and all three had advanced biliary cirrhosis prompting referral for liver transplantation. The symptoms of Hodgkin's disease were often masked by similar manifestations of primary sclerosing cholangitis, particularly symptoms of recurrent biliary sepsis. Hodgkin's disease is another disorder that may occur in patients with primary sclerosing cholangitis, particularly in the setting of advanced disease, and may be masked by the underlying hepatobiliary disease.

    View details for Web of Science ID A1993ME76900017

    View details for PubMedID 8225218

  • CHARACTERIZATION OF CHOLECYSTOKININ RECEPTORS ON THE HUMAN SPHINCTER OF ODDI SURGERY Tokunaga, Y., Cox, K. L., Itasaka, H., Concepcion, W., Nakazato, P., Esquivel, C. O. 1993; 114 (5): 942-950

    Abstract

    The present in vitro study investigated the interaction between cholecystokinin (CCK) and receptors on human sphincter of Oddi tissue obtained from donated human livers that were being transplanted.Radiolabeled ligands with cholecystokinin receptor specificity, autoradiography, and crystal scintillation counting were used to directly characterize cholecystokinin receptors on tissue sections.The binding of 125I-BH-CCK-8 to the tissue was saturable, specific, and dependent on time, pH, and temperature. Saturable binding of 125I-BH-CCK-8 was localized on the smooth muscle layer, and binding was inhibited only by cholecystokinin-related peptides. Computer analysis of 125I-BH-CCK-8 binding indicated the presence of two classes of binding sites, one with a high affinity and the other with a low affinity for CCK-8. CCK-8 caused relaxation (half-maximal concentration, 6 nmol/L) and carbachol caused contraction (half-maximal concentration, 10 nmol/L) of circular, cross-sectional strips of the tissue. Longitudinal strips were less responsive. The relative 125I-BH-CCK-8 binding inhibition potency of CCK-8 agreed closely with its relative ability to cause sphincter relaxation. Tetrodotoxin (1 mumol/L) and atropine (1 mumol/L) caused a rightward shift of the dose-response curve for CCK-8-stimulated sphincter relaxation.The present results indicate that cholecystokinin receptors on the human sphincter of Oddi are sulfate dependent and mediate sphincter relaxation.

    View details for Web of Science ID A1993MF75400013

    View details for PubMedID 8236019

  • CONTROVERSIES IN PATIENT SELECTION FOR LIVER-TRANSPLANTATION WESTERN JOURNAL OF MEDICINE Keeffe, E. B., Esquivel, C. O. 1993; 159 (5): 586-593

    Abstract

    A variety of specific conditions often stimulate controversy regarding candidacy for liver transplantation. We review the published experience with liver transplantation for alcoholic liver disease, fulminant and chronic hepatitis B, and hepatocellular carcinoma and transplantation in older subjects. Liver transplantation for alcoholic liver disease and in subjects older than 60 years is becoming less controversial because recent data demonstrate that these patients have excellent survival and good quality of life after transplantation. Only 10% to 15% of persons with alcoholism return to drinking after transplantation, and most do so only transiently. Liver transplantation for patients with hepatitis B virus infection or primary liver cancer is more problematic because recurrent disease is common in both conditions. After transplantation for chronic hepatitis B, 80% to 90% of patients have reinfection of the allograft and long-term survival is 45% to 50%. Patients receiving transplants for hepatocellular carcinoma have only 20% to 30% long-term survival, but these survivors are cured of malignancy. Data are presented to support continued liver transplantation for chronic hepatitis B and hepatocellular carcinoma; however, patients must be selected based on factors that predict a favorable outcome, and experimental therapies should be employed to explore ways to improve the existing survival rates.

    View details for Web of Science ID A1993MH22400006

    View details for PubMedID 8279156

    View details for PubMedCentralID PMC1022349

  • LIVER-TRANSPLANTATION FOR PATIENTS WITH ALCOHOLISM AND END-STAGE LIVER-DISEASE AMERICAN JOURNAL OF GASTROENTEROLOGY Gish, R. G., Lee, A. H., Keeffe, E. B., ROME, H., Concepcion, W., Esquivel, C. O. 1993; 88 (9): 1337-1342

    Abstract

    Liver transplantation for alcoholic cirrhosis remains controversial. In particular, criteria for the selection of patients who will remain recovered from alcoholism post-transplant require better definition. We analyzed the long-term predictive value of categorizing transplant referral patients with alcoholism and end-stage liver disease into risk groups for recidivism and noncompliance. Forty-seven patients with the diagnosis of alcoholism and advanced liver disease were evaluated and placed into predefined risk groups (low-, moderate-, and high-risk) for recidivism and noncompliance. No absolute period of abstinence from alcohol was required. All patients were asked to sign a contract not to drink alcohol and comply with a rehabilitation program before and after transplantation. Compliance with alcohol rehabilitation, abstinence, functional level, employment, and survival were assessed. Patients who were not compliant with the rehabilitation program or consumed alcohol were scored as failures. Thirty-one patients were ranked as low risk, and were accepted for liver transplantation; 27 patients were transplanted. Five of 31 patients (16%) drank alcohol. One patient drank before and four patients drank transiently after transplantation. Ten patients were categorized as moderate risk, and were deferred for transplantation; two patients underwent later transplantation. All 10 patients (100%) were noncompliant or drank alcohol, including two patients who drank after transplantation after a period of abstinence and rehabilitation. Six patients were ranked as high risk, and were denied liver transplantation. Five patients (83%) drank alcohol and were noncompliant. Minimum follow-up was 12 months (mean, 24 months; range, 12-41 months). The mean Karnofsky performance score was 34 before and 84 after liver transplantation. Actuarial survival of alcoholic patients undergoing transplantation was 93%. We conclude that categorization of transplant referral patients with alcoholism and liver failure into predefined risk groups for recidivism and noncompliance accurately predicts pre- and post-transplant behavior. As defined, only low-risk alcoholic patients are good candidates for liver transplantation.

    View details for Web of Science ID A1993LW16600006

    View details for PubMedID 8362826

  • REVASCULARIZATION TECHNIQUE FOR REDUCED-SIZE LIVER-TRANSPLANTATION FOR INFANTS WEIGHING LESS-THAN 10-KG JOURNAL OF PEDIATRIC SURGERY Nakazato, P. Z., Cox, K. L., Concepcion, W., Berquist, W. E., Esquivel, C. O. 1993; 28 (7): 923-926

    Abstract

    Reduced-size liver transplantation has been recognized as a powerful modality in alleviating the global donor shortage in pediatric liver transplantation. We describe, for the first time, a technique for revascularizing reduced-size grafts which has not been patterned after adult revascularization techniques. This revascularization method for reduced-size liver transplantation is particularly suitable for infants weighing < 10 kg. This technique differs from adult revascularization techniques in that the supraceliac aorta is always used as the origin for graft arterialization, and that the anastomoses are always performed in the following order: end-to-side donor celiac artery to supraceliac aorta anastomoses first, followed by the suprahepatic vena caval anastomoses, infrahepatic vena caval anastomoses, and then portal vein anastomoses. Hepatic artery thrombosis in infants weighing < 10 kg has occurred in 4 of 32 nonreduced versus 0 of 21 reduced transplantations (P = .05616, Z test, one tail). Adult revascularization was primarily used in the nonreduced group, whereas our proposed revascularization method was primarily used in the reduced group. We conclude that, for infants weighing < 10 kg receiving reduced grafts, this proposed technique should be used to decrease hepatic artery thrombosis.

    View details for Web of Science ID A1993LN64600014

    View details for PubMedID 8229570

  • VIRAL PROPHYLAXIS IN HEPATIC TRANSPLANTATION - PRELIMINARY-REPORT OF A RANDOMIZED TRIAL OF ACYCLOVIR AND GANCYCLOVIR TRANSPLANTATION PROCEEDINGS Nakazato, P. Z., BURNS, W., Moore, P., GARCIAKENNEDY, R., Cox, K., Esquivel, C. 1993; 25 (2): 1935-1937

    View details for Web of Science ID A1993KY21900104

    View details for PubMedID 7682357

  • THE INFLUENCE OF PORTOENTEROSTOMY WITH STOMA ON MORBIDITY IN PEDIATRIC-PATIENTS WITH BILIARY ATRESIA UNDERGOING ORTHOTOPIC LIVER-TRANSPLANTATION 23RD ANNUAL MEETING OF THE AMERICAN PEDIATRIC SURGICAL ASSOC Meister, R. K., Esquivel, C. O., Cox, K. L., Concepcion, W., Berquist, W., Nakazato, P., deVries, P. A. W B SAUNDERS CO-ELSEVIER INC. 1993: 387–90

    Abstract

    A portoenterostomy (PE) procedure for extrahepatic biliary atresia (EHBA) is sometimes performed with a stoma in an attempt to reduce the incidence of acute cholangitis. The purpose of this study was to determine if the presence of a stoma increased the complication rate of patients undergoing orthotopic liver transplantation (OLT) for EHBA. The medical records of 42 consecutive patients with EHBA who underwent primary OLT between October 1988 and October 1991 were retrospectively reviewed. Three patients were excluded, since their grafts were lost within 3 days of OLT. The remaining 39 patients were divided into three groups: no PE (n = 7), PE without stoma (n = 23), and PE with stoma (n = 9). The mean age of the whole group was 19.62 +/- 24.37 months, with a range of 5 to 132 months. Mean weight was 9.62 kg, with a range of 4.2 to 41 kg. Survival at 3 and 12 months as well as number of retransplantations were similar among the three groups. However, at the time of OLT increased morbidity was observed, consisting of increased operative time and number of reoperations, whether or not the stoma had been closed prior to OLT.

    View details for Web of Science ID A1993KR55100019

    View details for PubMedID 8468652

  • EFFECTS OF ABDOMINAL EN-BLOC PROCUREMENT AND OF A HIGH SODIUM PRESERVATION SOLUTION IN LIVER-TRANSPLANTATION JEAN HAMBURGER MEMORIAL CONGRESS / 14TH INTERNATIONAL CONGRESS OF THE TRANSPLANTATION SOC Nakazato, P. Z., Itasaka, H., Concepcion, W., Lim, J., Esquivel, C., Collins, G. ELSEVIER SCIENCE INC. 1993: 1604–6

    View details for Web of Science ID A1993KN62200314

    View details for PubMedID 8442207

  • USE OF PROGRAF (FK-506) AS RESCUE THERAPY FOR REFRACTORY REJECTION AFTER LIVER-TRANSPLANTATION JEAN HAMBURGER MEMORIAL CONGRESS / 14TH INTERNATIONAL CONGRESS OF THE TRANSPLANTATION SOC Klintmalm, G. B., Goldstein, R., Gonwa, T., Wiesner, R. H., Krom, R. A., Shaw, B. W., Stratta, R., Ascher, N. L., Roberts, J. W., Lake, J., Busuttil, R. W., McDiarmid, S., Esquivel, C. O., Nakazato, P., Marsh, J. W., Woodle, E. S., Kalayoglu, M., DALESSANDRO, A. M., Pirsch, J. D., Miller, C., Schwartz, M., Lewis, W. D., Monaco, A. P., Jenkins, R. L., Emond, J. C., Thistlethwaite, J. R., Whitington, P. F., Steinmuller, D. R., Fitzsimmons, W. E., Lawrence, I. ELSEVIER SCIENCE INC. 1993: 679–88
  • CHARACTERIZATION OF CHOLECYSTOKININ RECEPTORS ON THE HUMAN GALLBLADDER SURGERY Tokunaga, Y., Cox, K. L., Coleman, R., Concepcion, W., Nakazato, P., Esquivel, C. O. 1993; 113 (2): 155-162

    Abstract

    Several studies examined in vivo and in vitro biologic activity of the human gallbladder in response to cholecystokinin (CCK). However, few studies have demonstrated directly the interaction of CCK with receptors on the human gallbladder, which is responsible for this biologic activity.To characterize CCK receptors on human gallbladder tissue, gallbladders were removed from human donor grafts that were being used for liver transplantation. The gallbladders were rapidly frozen and sectioned for measurement of binding of 125I-Bolton-Hunter-labeled-CCK-8 and were cut into strips for in vitro bioassay.Binding of 125I-BH-CCK-8 to human gallbladder was saturable, specific, and dependent on time, pH, and temperature. The binding was inhibited only by cholecystokinin-related peptides including CCK-8 (IC50 10 +/- 1.0 nmol/L) (mean +/- SD), des(SO3) CCK-8 (IC50 0.9 +/- 0.2 mumol/L), and gastrin-17-I (IC50 9.0 +/- 2.0 mumol/L) or specific CCK receptor antagonist L-364,718. Computer analysis of binding of 125I-BH-CCK-8 to gallbladder tissue showed a single class of binding sites with high affinity for CCK-8. Autoradiography localized binding of 125I-BH-CCK-8 only to the smooth muscle layer of the gallbladder. In the bioassay des(SO3) CCK-8 (EC50 1.2 +/- 0.7 mumol/L) and gastrin-17-I (EC50 4.5 +/- 2.4 mumol/L) were 150- and 563-fold less potent than CCK-8 (EC50 8.0 +/- 2.2 nmol/L). The relative potencies of CCK agonists for inhibiting binding of 125I-BH-CCK-8 agreed closely with their relative potencies for causing gallbladder contraction. The dose-response curve for CCK-8 alone to induce gallbladder contraction was not significantly different from those caused by CCK-8 plus 1 mumol/L tetrodotoxin or 1 mumol/L atropine.These results characterized the CCK receptors on smooth muscle of human gallbladder as sulfate dependent and causing gallbladder contraction.

    View details for Web of Science ID A1993KL37600007

    View details for PubMedID 7679224

  • USE OF FK-506 FOR THE PREVENTION OF RECURRENT ALLOGRAFT-REJECTION AFTER SUCCESSFUL CONVERSION FROM CYCLOSPORINE FOR REFRACTORY REJECTION JEAN HAMBURGER MEMORIAL CONGRESS / 14TH INTERNATIONAL CONGRESS OF THE TRANSPLANTATION SOC Klintmalm, G. B., Goldstein, R., Gonwa, T., Wiesner, R. H., Krom, R. A., Shaw, B. W., Stratta, R., Ascher, N. L., Roberts, J. W., Lake, J., Busuttil, R. W., McDiarmid, S., Esquivel, C. O., Nakazato, P., Marsh, J. W., Woodle, E. S., Kalayoglu, M., DALESSANDRO, A. M., Pirsch, J. D., Miller, C., Schwartz, M., Lewis, W. D., Monaco, A. P., Jenkins, R. L., Emond, J. C., Thistlethwaite, J. R., Whitington, P. F., Steinmuller, D. R., Fitzsimmons, W. E., Lawrence, I. ELSEVIER SCIENCE INC. 1993: 635–37
  • PROGNOSTIC FACTORS FOR SUCCESSFUL CONVERSION FROM CYCLOSPORINE TO FK-506 - BASED IMMUNOSUPPRESSIVE THERAPY FOR REFRACTORY REJECTION AFTER LIVER-TRANSPLANTATION JEAN HAMBURGER MEMORIAL CONGRESS / 14TH INTERNATIONAL CONGRESS OF THE TRANSPLANTATION SOC Klintmalm, G. B., Goldstein, R., Gonwa, T., Wiesner, R. H., Krom, R. A., Shaw, B. W., Stratta, R., Ascher, N. L., Roberts, J. W., Lake, J., Busuttil, R. W., McDiarmid, S., Esquivel, C. O., Nakazato, P., Marsh, J. W., Woodle, E. S., Kalayoglu, M., DALESSANDRO, A. M., Pirsch, J. D., Miller, C., Schwartz, M., Lewis, W. D., Monaco, A. P., Jenkins, R. L., Emond, J. C., Thistlethwaite, J. R., Whitington, P. F., Steinmuller, D. R., Fitzsimmons, W. E., Lawrence, I. ELSEVIER SCIENCE INC. 1993: 641–43
  • TRANSIENT DETERIORATION OF INTRAPULMONARY SHUNTING AFTER PEDIATRIC LIVER-TRANSPLANTATION TRANSPLANTATION Itasaka, H., Hershon, J. J., Cox, K. L., Tokunaga, Y., Concepcion, W., Nakazato, P., Esquivel, C. O. 1993; 55 (1): 212-214

    View details for Web of Science ID A1993KH66000042

    View details for PubMedID 8420052

  • EFFECT OF POLYETHYLENE-GLYCOL ON RAT SMALL-BOWEL REJECTION TRANSPLANTATION PROCEEDINGS Itasaka, H., Wicomb, W. N., BURNS, W., Tokunaga, Y., Nakazato, P., Collins, G. M., Esquivel, C. O. 1992; 24 (3): 1179-1180

    View details for Web of Science ID A1992HY79500214

    View details for PubMedID 1604578

  • LIVER-TRANSPLANTATION FOR ARTERIOHEPATIC DYSPLASIA (ALAGILLES SYNDROME) TRANSPLANT INTERNATIONAL Marino, I. R., Chapchap, P., Esquivel, C. O., ZETTI, G., Carone, E., Borland, L., Tzakis, A. G., Todo, S., Rowe, M. I., Starzl, T. E. 1992; 5 (2): 61-64

    Abstract

    Thirteen out of 268 children (less than 18 years old) underwent hepatic transplantation (OLT) for end-stage liver disease (ESLD) associated with arteriohepatic dysplasia (AHD). Seven children are alive and well with normal liver function. Six children died, four within 11 days of the operation and the other two at 4 and 10 months after the OLT. Vascular complications with associated septicemia were responsible for the deaths of three children. Two died of heart failure and circulatory collapse, secondary to pulmonary hypertension and congenital heart disease. The remaining patient died of overwhelming sepsis not associated with technical complications. Seven patients had a portoenterostomy or portocholecystostomy early in life; five of these died after the OLT. Severe cardiovascular abnormalities in some of our patients suggest that complete hemodynamic monitoring with invasive studies should be performed in all patients with AHD, especially in cases of documented hypertrophy of the right ventricle. The improved quality of life in our surviving patients confirms the validity of OLT as a treatment of choice in cases of ESLD due to AHD.

    View details for Web of Science ID A1992HV82300001

    View details for PubMedID 1627241

    View details for PubMedCentralID PMC2967196

  • GRAFT INVOLVEMENT BY LEGIONELLA IN A LIVER-TRANSPLANT RECIPIENT ARCHIVES OF SURGERY Tokunaga, Y., Concepcion, W., Berquist, W. E., Cox, K. L., WIVIOTT, L. D., GARCIAKENNEDY, R., Itasaka, H., Nakazato, P., Esquivel, C. O. 1992; 127 (4): 475-477

    Abstract

    Legionella pneumophila, serogroup 1, was identified by direct immunofluorescence in the lung and liver graft from a 2 1/2-month-old infant who underwent orthotopic liver transplantation because of fulminant hepatic failure secondary to neonatal hepatitis. The patient died of respiratory failure owing to this infection 22 days after transplantation despite treatment with erythromycin lactobionate. To our knowledge, this represents the first reported case of hepatic infection with Legionella in liver transplant recipients.

    View details for Web of Science ID A1992HM46400020

    View details for PubMedID 1558502

  • CALCIUM-ANTAGONISTS IN SODIUM LACTOBIONATE SUCROSE SOLUTION FOR RAT-LIVER PRESERVATION TRANSPLANTATION Tokunaga, Y., Collins, G. M., Esquivel, C. O., Wicomb, W. N. 1992; 53 (4): 726-730

    Abstract

    The effects of the calcium antagonists, chlorpromazine (CPZ), nisoldipine (NIS), trifluoperazine (TFP), and nicardipine (NIC) were compared in rat livers following either 20- or 30-hr ice storage in sodium lactobionate sucrose solution (SLS). Survivals beyond 7 days after orthotopic liver transplantation following 20-hr cold storage were 1/14 in the University of Wisconsin solution, 4/14 in SLS, 4/8 in UW+CPZ, 7/8 in SLS+CPZ. Survivals beyond 7 days after OLT following 30-hr cold storage were 3/8 in SLS+CPZ, 3/8 in SLS+NIS, 2/8 in SLS+TFP, 0/8 in SLS+NIC, and 0/8 in SLS alone. Survival rates were significantly (P less than 0.05) better in both SLS+CPZ and SLS+NIS than in UW and SLS alone. The effluent lactate dehydrogenase (LDH) levels and pH changes were measured at the time of OLT. After 20 hr, LDH levels were 525 +/- 78 IU/L (mean +/- SEM) in UW, 492 +/- 44 in SLS, 322 +/- 35 in UW+CPZ, and 290 +/- 39 in SLS+CPZ. After 30 hr, LDH values were 416 +/- 40 in SLS+CPZ, 450 +/- 25 in SLS+NIS, 448 +/- 21 in SLS+TFP, 573 +/- 18 in SLS+NIC, and 614 +/- 68 in SLS. The LDH levels for SLS+CPZ and SLS+NIS were significantly lower than those of SLS and UW (P less than 0.01). The pH changes in the effluent were significantly less in both the CPZ and NIS groups (P less than 0.01). This study demonstrated improved liver preservation by the use of a simplified colloid-free lactobionate solution containing sodium as the principal cation. The addition of CPZ or NIS to the solution demonstrated the same potency for significant improvement in efficacy of this solution, while NIC was ineffective.

    View details for Web of Science ID A1992HP30600003

    View details for PubMedID 1566335

  • TOTAL ABDOMINAL EVISCERATION - AN EN-BLOC TECHNIQUE FOR ABDOMINAL ORGAN HARVESTING SURGERY Nakazato, P. Z., Concepcion, W., Bry, W., Limm, W., Tokunaga, Y., Itasaka, H., FEDUSKA, N., Esquivel, C. O., Collins, G. M. 1992; 111 (1): 37-47

    Abstract

    This paper describes an en bloc total abdominal evisceration (TAE) technique that has been used successfully in 81 consecutive multi-organ procurements in donors ranging from 2.5 to 85 kg. Preliminary dissection performed by the surgeon and physician's assistant averaged 30 to 45 minutes before aortic cross-clamping. Removal of all abdominal organs (liver, kidneys, pancreas, bowel) en bloc averaged 16 to 24 minutes after aortic cross-clamping, depending on the speed of the thoracic procurement. Organ grafts were preserved with the University of Wisconsin preservation solution. Total procurement time for the removal of the liver, pancreas, and kidneys averaged 1.5 to 2.25 hours. Because all vascular anomalies were easily recognized ex vivo, vascular reconstruction was possible, so that all donors could potentially provide for combined liver, pancreas, and kidney transplantation. In the TAE group, primary liver graft nonfunction was 1.2% (1/81 grafts), which is less than the non-TAE liver graft nonfunction rate of 7% (7/99 grafts); this is statistically significant (p less than 0.05). Also, the incidence of fresh frozen plasma support after liver transplantation in the TAE group (2/81 transplantations) was lower than the non-TAE group (9/99 transplantations) (p less than 0.05). The overall liver recipient survival rate was 87% (non-TAE; 78/94 recipients; TAE; 65/70 recipients). Kidney-graft initial function has been similar in both the TAE and non-TAE groups. All pancreas tissue was histologically normal, and extraction of viable islet cells (average, 3600 islets per gram pancreas) was possible with yields similar to standard pancreatic (average, 379 islets per gram pancreas) harvest techniques. Preliminary experience with combined liver and whole-organ pancreas transplantations has been encouraging, with immediate discontinuation of intraoperative insulin during transplantation.

    View details for Web of Science ID A1992GY46500006

    View details for PubMedID 1728073

  • EARLY EXPERIENCE WITH FK-506 INDUCTION IMMUNOSUPPRESSION - SUGGESTION FOR USING ORAL FK-506 INTERNATIONAL CONGRESS ON FK 506 Nakazato, P., Cox, K., Concepcion, W., Gish, R., Berquist, W., Imperial, J., Esquivel, C. ELSEVIER SCIENCE INC. 1991: 3019–20

    View details for Web of Science ID A1991GV17500096

    View details for PubMedID 1721345

  • LIVER-TRANSPLANTATION - EXPERIENCE WITH 100 CASES WESTERN JOURNAL OF MEDICINE Szpakowski, J. L., Cox, K., Nakazato, P., Concepcion, W., Levin, B., Esquivel, C. O. 1991; 155 (5): 494-499

    Abstract

    Between March 1988 and November 1989, 100 liver transplants were performed on 90 patients at Pacific Presbyterian (now California Pacific) Medical Center in San Francisco. The immunosuppressive regimen was a combination of prophylactic Minnesota antilymphocyte globulin, cyclosporine, and low-dose corticosteroids. Rejections were treated with OKT3, a monoclonal antibody, or corticosteroids. Of the 100 transplants, 32 were done on 30 children, 18 of whom weighed less than 10 kg and 9 of whom received livers that had been surgically reduced in size to fit the recipient. The overall patient survival at 2 years was 85%. Of 100 liver transplants, treatment was given for 80 (80%) for at least 1 episode of rejection. At least 1 episode of serious infection occurred in 34 of the 60 adult patients and 25 of the 30 children. Of the entire group, 2% had hepatic artery thrombosis, and 12% had biliary complications that necessitated reoperation. The quality of life has been good, with a follow-up from 1 to almost 3 years (mean = 22 months). Comparing these data with those of other published series shows a decreased incidence of surgical complications and a lower rate of fungal and viral infections. We attribute this to the reduction of steroid dosage during convalescence without jeopardizing patient or graft survival.

    View details for Web of Science ID A1991GP12600003

    View details for PubMedID 1815388

    View details for PubMedCentralID PMC1003060

  • THE IMPACT OF LIVER REDUCTIONS IN PEDIATRIC LIVER-TRANSPLANTATION 62ND ANNUAL SCIENTIFIC SESSION OF THE PACIFIC COAST SURGICAL ASSOC Esquivel, C. O., Nakazato, P., Cox, K., Concepcion, W., Berquist, W., Russell, T. R. AMER MEDICAL ASSOC. 1991: 1278–86

    Abstract

    Reduced-size liver transplantation (RSLT) in children was introduced to alleviate a shortage of small-organ donors. The impact of RSLT on the waiting time for an organ and on morbidity and mortality was investigated. Between March 25, 1988, and August 11, 1990, 61 hepatic transplantations were performed in 55 children at the Pacific Transplant Institute in San Francisco, Calif. Full-size liver transplantation was performed in 41 cases and RSLT in 20 cases. The overall 30-month actuarial patient and graft survival rates were 89% and 73%, respectively. A comparison between full-size liver transplantation and RSLT showed no difference in patient and graft survival, reoperations, infections, or rejection. Benefits of RSLT were an increase in the donor pool size, a decrease in waiting time for a suitable donor, and a decrease in the rate of arterial thrombosis. The main morbidity of RSLT was an increase in perioperative blood requirement. We conclude that RSLT offers small children with end-stage liver disease a chance for long-term survival.

    View details for Web of Science ID A1991GJ52400018

    View details for PubMedID 1929830

  • SUCCESSFUL 20-HOUR RAT-LIVER PRESERVATION WITH CHLORPROMAZINE IN SODIUM LACTOBIONATE SUCROSE SOLUTION SURGERY Tokunaga, Y., Wicomb, W. N., Concepcion, W., Nakazato, P., Collins, G. M., Esquivel, C. O. 1991; 110 (1): 80-86

    Abstract

    We investigated the effect of the addition of chlorpromazine to a new, simplified organ preservation solution, sodium lactobionate sucrose (SLS), for 20-hour hypothermic rat liver preservation. Survival beyond 7 days after orthotopic transplantation of the stored liver was eight of eight rats in control groups (immediate transplantation, less than 1-hour preservation), one of 14 rats with the University of Wisconsin (UW) solution, four of 14 rats with SLS, seven of eight rats with SLS + chlorpromazine, 1 mg/L, and seven of eight rats with SLS + chlorpromazine, 10 mg/L. The differences is survival between UW and SLS and between SLS and SLS + chlorpromazine were significant (p less than 0.05). Lactic dehydrogenase levels in the effluent after reflushing through the portal vein at the time of transplantation were 145 +/- 20 IU/L (mean +/- SEM) in the controls, 525 +/- 78 IU/L in UW, 492 +/- 44 IU/L in SLS, 290 +/- 39 IU/L in SLS + chlorpromazine, 1 mg/L, 290 +/- 11 IU/L in SLS + chlorpromazine, 10 mg/L. The values for the SLS + chlorpromazine were significantly lower than for SLS and UW (p less than 0.05). The pH of the effluent was 7.10 +/- 0.10 in controls, 6.42 +/- 0.12 in UW, 6.64 +/- 0.18 in SLS, and 7.07 +/- 0.02 in SLS + chlorpromazine, 1 mg/L and 10 mg/L. The pH drop was significantly greater in the groups without chlorpromazine (p less than 0.01). This study shows that superior rat liver preservation was achieved with a simplified lactobionate solution containing sodium as the principal cation, sucrose in place of raffinose, and omitting the colloid and several of the other UW components. The addition of low concentrations of chlorpromazine further enhanced the effectiveness of this solution, without the need for donor pretreatment.

    View details for Web of Science ID A1991FV58700011

    View details for PubMedID 1866698

  • PHENOTYPES OF APOLIPOPROTEIN-B AND APOLIPOPROTEIN-E AFTER LIVER-TRANSPLANTATION JOURNAL OF CLINICAL INVESTIGATION Linton, M. F., Gish, R., Hubl, S. T., Butler, E., Esquivel, C., BRY, W. I., BOYLES, J. K., Wardell, M. R., Young, S. G. 1991; 88 (1): 270-281

    Abstract

    Apolipoprotein (apo) E and the two B apolipoproteins, apoB48 and apoB100, are important proteins in human lipoprotein metabolism. Commonly occurring polymorphisms in the genes for apoE and apoB result in amino acid substitutions that produce readily detectable phenotypic differences in these proteins. We studied changes in apoE and apoB phenotypes before and after liver transplantation to gain new insights into apolipoprotein physiology. In all 29 patients that we studied, the postoperative serum apoE phenotype of the recipient, as assessed by isoelectric focusing, converted virtually completely to that of the donor, providing evidence that greater than 90% of the apoE in the plasma is synthesized by the liver. In contrast, the cerebrospinal fluid apoE phenotype did not change to the donor's phenotype after liver transplantation, indicating that most of the apoE in CSF cannot be derived from the plasma pool and therefore must be synthesized locally. The apoB100 phenotype (assessed with immunoassays using monoclonal antibody MB19, an antibody that detects a two-allele polymorphism in apoB) invariably converted to the phenotype of the donor. In four normolipidemic patients, we determined the MB19 phenotype of both the apoB100 and apoB48 in the "chylomicron fraction" isolated from plasma 3 h after a fat-rich meal. Interestingly, the apoB100 in the chylomicron fraction invariably had the phenotype of the donor, indicating that the vast majority of the large, triglyceride-rich apoB100-containing lipoproteins that appear in the plasma after a fat-rich meal are actually VLDL of hepatic origin. The MB19 phenotype of the apoB48 in the plasma chylomicron fraction did not change after liver transplantation, indicating that almost all of the apoB48 in plasma chylomicrons is derived from the intestine. These results were consistent with our immunocytochemical studies on intestinal biopsy specimens of organ donors; using apoB-specific monoclonal antibodies, we found evidence for apoB48, but not apoB100, in donor intestinal biopsy specimens.

    View details for Web of Science ID A1991FU44300036

    View details for PubMedID 2056122

    View details for PubMedCentralID PMC296029

  • IMPROVED RAT-LIVER PRESERVATION USING CHLORPROMAZINE IN A NEW SODIUM LACTOBIONATE SUCROSE SOLUTION 13TH INTERNATIONAL CONGRESS OF THE TRANSPLANTATION SOC Tokunaga, Y., Wicomb, W. N., Concepcion, W., Nakazato, P., Cox, K. L., Esquivel, C. O., Collins, G. M. ELSEVIER SCIENCE INC. 1991: 660–61

    View details for Web of Science ID A1991EV39000259

    View details for PubMedID 1990638

  • LIVER-TRANSPLANTATION IN LANGERHANS CELL HISTIOCYTOSIS (HISTIOCYTOSIS-X) SEMINARS IN ONCOLOGY Concepcion, W., Esquivel, C. O., Terry, A., Nakazato, P., GARCIAKENNEDY, R., Houssin, D., Cox, K. L. 1991; 18 (1): 24-28

    Abstract

    Two children with biopsy-proven LCH underwent successful hepatic transplantation for end-stage liver disease. These patients were thought not to have active LCH disease at the time of transplantation, although one had developed a new osteolytic lesion a few months before the operation and the other had suspicious osteolytic lesions at the time of transplantation. The histologic examination of the excised liver showed features consistent with primary sclerosing cholangitis. The two patients had an excellent recovery with no evidence of progression of LCH or recurrence of the underlying disease in the hepatic allograft at 1 and 3 years after organ transplantation.

    View details for Web of Science ID A1991EX24100005

    View details for PubMedID 1992520

  • LIVER-TRANSPLANTATION IN INFANTS WEIGHING LESS THAN 10-KILOGRAMS TRANSPLANTATION PROCEEDINGS Cox, K., Nakazato, P., Berquist, W., Concepcion, W., Tokunaga, Y., Esquivel, C. 1991; 23 (1): 1579-1580

    View details for Web of Science ID A1991EV39100273

    View details for PubMedID 1989298

  • ANALYSIS OF HEPATIC LYMPHOCYTE-T AND IMMUNOGLOBULIN DEPOSITS IN PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS HEPATOLOGY Krams, S. M., VANDEWATER, J., Coppel, R. L., Esquivel, C., Roberts, J., ANSARI, A., Gershwin, M. E. 1990; 12 (2): 306-313

    Abstract

    The histological findings in patients with primary biliary cirrhosis have been well-defined and are often used in the clinical staging of disease. However, it has only been with the development of reagents that phenotypically characterize the lymphoid infiltrate that attempts have been made to correlate pathophysiology with immune effector populations. Indeed, the inflammatory hepatic lesions in primary biliary cirrhosis have been described as containing CD4-positive and CD8-positive T cells. Less clear, however, have been the T cell receptors in these lesions. Further, the data on immunoglobulin deposits in hepatic lesions have been less well-defined; this deficit may be a result of the quality of polyspecific sera and difficulties in background. To address these issues, we have used a battery of well-defined monospecific and polyspecific reagents to phenotypically define the occurrence of lymphoid cells in the livers of patients undergoing transplantation. Furthermore, we have defined these same markers on T cell lines derived from liver, regional lymph node and peripheral blood. The predominant cell type in the mononuclear infiltrate is the CD3+, CD4+ T lymphocyte bearing the T cell receptor alpha beta. T cell lines from the same patients demonstrate similar findings. Of special importance, however, was the detection of CD20+ B cells and Ig+ cells in the lymphoid infiltrate. Indeed, we also readily demonstrated the presence of immunoglobulin on the surface of biliary epithelium. These data suggest that mechanisms involved in the pathophysiology of primary biliary cirrhosis may include both T cell and antibody mechanisms. The results also underscore the need to develop a functional, and not just a phenotypical, assay of the inflammatory infiltrate.

    View details for Web of Science ID A1990DW92100018

    View details for PubMedID 2202637

  • LIVER-TRANSPLANTATION FOR TYROSINEMIA - A REVIEW OF 10 CASES FROM THE UNIVERSITY-OF-PITTSBURGH DIGESTIVE DISEASES AND SCIENCES Mieles, L. A., Esquivel, C. O., VANTHIEL, D. H., Koneru, B., Makowka, L., Tzakis, A. G., Starzl, T. E. 1990; 35 (1): 153-157

    Abstract

    Results of liver transplantation in 10 patients with tyrosinemia are reviewed. The indications for transplantation were: hepatoma in three, acute liver failure in two, and progressive chronic liver disease in five. One patient died during surgery. Of the remaining nine who survived the operation, one died at six months as a result of bronchial aspiration and aspiration pneumonia, and a second transplanted for hepatoma died five months later with metastases. Seven patients are alive 6 months to 6 1/2 years following transplantation. Of these seven patients, six have normal liver function and a good performance status. One is awaiting retransplantation for chronic rejection. Hepatocellular carcinoma (HCC) was found either preoperatively or incidentally in five patients, all older than 2 years at the time of their transplant. Four of these are alive and well without evidence of tumor with follow-ups between 3 1/2 and 6 1/2. Four of the five patients less than 2 years of age had hepatocellular dysplasia without evidence of carcinoma on histologic examination of the resected liver. This experience suggests that liver transplantation should be considered seriously for children with hereditary tyrosinemia who are more than 2 years of age because beyond that age the incidence of hepatocellular carcinoma (HCC) increases substantially.

    View details for Web of Science ID A1990CJ75200024

    View details for PubMedID 2153069

    View details for PubMedCentralID PMC2974306

  • LYMPHOMA AND HYPERCALCEMIA IN A PEDIATRIC ORTHOTOPIC LIVER-TRANSPLANT PATIENT TRANSPLANTATION Nakazato, P., Esquivel, C. O., URBACH, A. H., Makowka, L., Scantlebury, V., Jaffe, R., Starzl, T. E. 1989; 48 (6): 1003-1006

    Abstract

    We present a case report of a pediatric orthotopic liver transplant recipient who developed lymphoma with hypercalcemia on cyclosporine and prednisone immunosuppression. This is the first reported posttransplant lymphoproliferative disorder complicated by hypercalcemia, with a finding of an elevated 1,25 dihydroxyl vitamin D state, suggesting that it has a role in the pathophysiology of this B cell lymphoma hypercalcemia. The clinical course and management of this disorder with a 31-month follow-up are described.

    View details for Web of Science ID A1989CL69800022

    View details for PubMedID 2595760

    View details for PubMedCentralID PMC2963945

  • MECHANISMS OF HYPERTENSION DURING AND AFTER ORTHOTOPIC LIVER-TRANSPLANTATION IN CHILDREN JOURNAL OF PEDIATRICS Lawless, S., Ellis, D., Thompson, A., Cook, D. R., Esquivel, C., Starzl, T. 1989; 115 (3): 372-379

    Abstract

    The aim of this study was to assess the hormonal alterations that may mediate the systemic hypertension that develops in patients during the perioperative period of orthotopic liver transplantation. We studied nine pediatric patients without previous hypertension or renal disease during six time points, starting before transplantation and ending at 48 hours after surgery. Hypertension developed in all patients in association with central venous pressures less than 10 mm Hg. Free water clearance was negative in all nine patients. Vasopressin levels increased intraoperatively but fell as hypertension developed. Atrial natriuretic factor levels increased as systemic blood pressure rose. A high level of plasma renin activity was observed in four patients with renal insufficiency. In six patients, postoperative 24-hour urinary norepinephrine excretion was within the normal age-adjusted range. These findings suggest that the combination of cyclosporine, corticosteroids, and, in some patients, an elevated plasma renin activity prevents the kidney from responding to the acute volume and salt overload with an appropriate diuresis and natriuresis, thus leading to systemic hypertension. The treatment of hypertension after liver transplantation may include salt restriction, diuretics, and, in those patients with a low creatinine excretion index, angiotensin coverting enzyme inhibitors.

    View details for Web of Science ID A1989AN88400006

    View details for PubMedID 2527974

    View details for PubMedCentralID PMC2965614

  • HEPATIC-ARTERY THROMBOSIS FOLLOWING PEDIATRIC LIVER-TRANSPLANTATION - ASSESSMENT OF BLOOD-FLOW MEASUREMENT IN ALLOGRAFTS CLINICAL TRANSPLANTATION Yanaga, K., Makowka, L., Shimada, M., Esquivel, C. O., Bowman, J. S., Todo, S., Tzakis, A. G., Starzl, T. E. 1989; 3 (4): 184-189

    Abstract

    The purpose of this study was to define parameters which could be predictive of hepatic artery thrombosis, which continues to be a major complicating factor in pediatric liver transplantation. The hepatic blood flow of 14 pediatric liver patients (15 grafts) who weighed less than 15 kg was measured electromagnetically during orthotopic liver transplantation. The results of blood flow determination and the clinical data in 7 patients (8 grafts) who developed hepatic artery thrombosis were compared with those of 7 control patients. All patients with a hepatic arterial flow of less than 60 ml/min developed hepatic artery thrombosis (4/8 vs. 0/7; p < 0.05), and the patients with hepatic artery thrombosis exhibited higher total hepatic and portal vein flow per 100 gram of liver tissue (262 vs. 136 ml/min; p < 0.001 and 222 vs. 80 ml/min; p < 0.025, respectively) as well as longer cold preservation time (384 vs. 326 min; p < 0.025). The results of our study suggest that hepatic arterial flows of less than 60 ml/min are critical for the development of hepatic artery thrombosis, and that portal venous overflow and increased preservation times may contribute to the development of hepatic artery thrombosis.

    View details for Web of Science ID A1989AN51200002

    View details for PubMedCentralID PMC3000218

  • LONG-TERM RESULTS OF ORTHOTOPIC LIVER-TRANSPLANTATION DURING THE CYCLOSPORINE ERA (1980-1984) - 393 ORTHOTOPIC LIVER-TRANSPLANTATIONS PERFORMED IN 313 CONSECUTIVE PATIENTS AT THE PITTSBURGH TRANSPLANTATION CENTER, UNIVERSITY-OF-PITTSBURGH HELVETICA CHIRURGICA ACTA Lerut, J., Stieber, A. C., Makowka, L., Esquivel, C. O., WATSUKI, S., Gordon, R. D., Starzl, T. E. 1989; 56 (3): 405-420

    Abstract

    During the cyclosporine era 1980-1984, 393 consecutive orthotopic liver transplantations (OLT) were performed in 313 patients at the University of Pittsburgh. This paper analyses the long-term results in this group of patients who have been followed-up for a minimum of three years. The results of OLT for different indications are discussed. The five-year survival rates after OLT for metabolic diseases, biliary atresia, primary biliary cirrhosis, posthepatic cirrhosis and primary hepatobiliary cancer are 75%, 68%, 60%, 58.9%, 53.2% and 23.8%, respectively. Recurrence of the primary disease after OLT is rare for benign diseases but rather frequent for malignant ones. The incidence of retransplantation for delayed rejection and for extrahepatic complications is discussed. The quality of life for most of the long-term survivors is good. Because of its good long-term results, OLT should become the therapy of choice in a lot of acute and chronic hepatopathies.

    View details for Web of Science ID A1989AN76600022

    View details for PubMedID 2807976

    View details for PubMedCentralID PMC3007095

  • HEPATIC-ARTERY THROMBOSIS AFTER PEDIATRIC LIVER-TRANSPLANTATION - A MEDICAL OR SURGICAL EVENT TRANSPLANTATION Mazzaferro, V., Esquivel, C. O., Makowka, L., Belle, S., Kahn, D., Koneru, B., Scantlebury, V. P., Stieber, A. C., Todo, S., Tzakis, A. G., Starzl, T. E. 1989; 47 (6): 971-977

    Abstract

    Hepatic artery thrombosis (HAT) is one of the most serious complications after orthotopic liver transplantation, and is associated with a high morbidity and mortality. This study retrospectively reviewed 66 liver transplants in children under the age of 10 years during a year-long period at a single institution. A total of 28 perioperative variables were analyzed to identify responsible factors of HAT. Of the 66 children, 18 (26%) developed HAT within 15 days after the transplant (HAT group); 29 (42%) had an uneventful postoperative course (control group). To avoid the possible influence of other complications 19 patients were excluded. Of the variables compared between the 2 study groups, three surgical factors (diameter of the hepatic artery--greater or less than 3 mm; type of arterial anastomosis--end-to-end versus the use of an iliac graft or aortic conduit; and number of times the anastomosis was redone--one versus more than one), were found to be significantly different (P less than .05) between HAT and control groups. Two medical factors also were significantly different: the use of intraoperative transfusion of fresh frozen plasma (FFP) and the administration of postoperative prophylactic anticoagulant treatment. A heparin and dextran-40 protocol appeared to be effective in preventing HAT (P less than .02). Moreover, after multivariate analysis, anticoagulation therapy was demonstrated to be the major independent variable influencing HAT. A better definition of factors responsible for the occurrence of HAT is required. This study should help in formulating effective methods to decrease the incidence of this dreaded complication after liver transplantation.

    View details for Web of Science ID A1989AB98900011

    View details for PubMedID 2472028

  • CAUSES OF DEATH AFTER LIVER-TRANSPLANTATION IN CHILDREN TREATED WITH CYCLOSPORINE AND STEROIDS CLINICAL TRANSPLANTATION Kahn, D., Esquivel, C. O., Makowka, L., MADRIGALTORRES, M., Yunis, E., Iwatsuki, S., Starzl, T. E. 1989; 3 (3): 150-155

    Abstract

    Two-hundred-and-twenty-seven children underwent orthotopic liver transplantation between March 1980 and March 1986. Seventy (31 %) patients died during the study period. Four patients who died within 24 hours of the initial liver transplant and 5 patients who died outside of our institution were excluded from the analysis. Liver failure, related to either thrombosis of the hepatic artery, primary non-function of the graft or rejection accounted for 25 of the remaining 61 deaths. In 21 patients death was related to overwhelming sepsis while 7 patients died from excessive bleeding. Eight of the deaths were due to a miscellaneous group of causes. Twenty percent of the 150 patients who received a single liver transplant died compared to a death rate of 50% in patients who underwent three transplants. Eighty-five percent of the deaths occurred within 6 months after the initial liver transplant. Liver failure was the cause in the majority of the early deaths whereas the later deaths were more likely to be due to sepsis. This detailed analysis of the causes of death after pediatric liver transplantation in a large group of patients has revealed that advances in certain areas could lead to even better results.

    View details for Web of Science ID A1989AD86600003

    View details for PubMedCentralID PMC3000227

  • MARKED TRANSIENT ALKALINE PHOSPHATEMIA FOLLOWING PEDIATRIC LIVER-TRANSPLANTATION AMERICAN JOURNAL OF DISEASES OF CHILDREN Koneru, B., Carone, E., Malatack, J. J., Esquivel, C. O., Starzl, T. E. 1989; 143 (6): 669-670

    Abstract

    An isolated marked transient rise in serum alkaline phosphatase levels in otherwise healthy children is a well-documented occurrence. However, in children undergoing liver transplantation, elevated alkaline phosphatase values raise the possibility of biliary obstruction, rejection, or both. During a 6-year period, 6 of 278 children undergoing liver transplantation exhibited a similar phenomenon as an isolated abnormality. None had rejection, biliary obstruction, or other allograft dysfunction during a long follow-up. Eventually and without intervention, the alkaline phosphatase levels returned to normal. These instructive cases suggest that caution be used in advocating invasive procedures if elevated alkaline phosphatase levels are an isolated abnormality, and close observation with noninvasive testing is recommended.

    View details for Web of Science ID A1989AA14500018

    View details for PubMedID 2658549

    View details for PubMedCentralID PMC2978519

  • INTRAOPERATIVE BLOOD-TRANSFUSIONS IN HIGHLY ALLOIMMUNIZED PATIENTS UNDERGOING ORTHOTOPIC LIVER-TRANSPLANTATION TRANSPLANTATION Weber, T., Marino, I. R., Kang, Y. G., ESQUIVEL, C. D., Starzl, T. E., Duquesnoy, R. J. 1989; 47 (5): 797-801

    Abstract

    Intraoperative blood requirements were analyzed in patients undergoing primary orthotopic liver transplantation and divided into two groups on the basis of panel reactive antibody of pretransplant serum measured by lymphocytotoxicity testing. One group of highly sensitized patients (n = 25) had PRA values of over 70% and the second group of patients (n = 26) had 0% PRA values and were considered nonsensitized. During the transplant procedure, the 70% PRA group received considerably greater quantities of blood products than the 0% PRA group--namely, red blood cells: 21.1 +/- 3.7 vs. 9.8 +/- 0.8 units (P = 0.002), and platelets: 17.7 +/- 3.2 vs. 7.5 +/- 1.5 units (P = 0.003). Similar differences were observed for fresh frozen plasma and cryoprecipitate. Despite the larger infusion of platelets, the blood platelet counts in the 70% PRA group were lower postoperatively than preoperatively. Twenty patients in the 70% PRA group received platelet transfusions, and their mean platelet count dropped from 95,050 +/- 11,537 preoperatively to 67,750 +/- 8,228 postoperatively (P = 0.028). In contrast, nearly identical preoperative (84,058 +/- 17,297) and postoperative (85,647 +/- 12,445) platelet counts were observed in the 17 0% PRA patients who were transfused intraoperatively with platelets. Prothrombin time, activated partial thromboplastin time, and fibrinogen levels showed no significant differences between both groups. These data demonstrate that lymphocytotoxic antibody screening of liver transplant candidates is useful in identifying patients with increased risk of bleeding problems and who will require large quantities of blood during the transplant operation.

    View details for Web of Science ID A1989U676800010

    View details for PubMedID 2655216

    View details for PubMedCentralID PMC3005203

  • TRANSPLANTATION OF MULTIPLE ABDOMINAL VISCERA JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Starzl, T. E., Rowe, M. I., Todo, S., Jaffe, R., Tzakis, A., Hoffman, A. L., Esquivel, C., Porter, K. A., Venkataramanan, R., Makowka, L., Duquesnoy, R. 1989; 261 (10): 1449-1457

    Abstract

    Two children with the short-gut syndrome and secondary liver failure were treated with evisceration and transplantation en bloc of the stomach, small intestine, colon, pancreas, and liver. The first patient died perioperatively, but the second lived for more than 6 months before dying of an Epstein-Barr virus-associated lymphoproliferative disorder that caused biliary obstruction and lethal sepsis. There was never evidence of graft rejection or of graft-vs-host disease in the long-surviving child. The constituent organs of the homograft functioned and maintained their morphological integrity throughout the 193 days of survival.

    View details for Web of Science ID A1989T487400021

    View details for PubMedID 2918640

    View details for PubMedCentralID PMC3005343

  • OBSTRUCTION TO HEPATIC VENOUS DRAINAGE AFTER LIVER-TRANSPLANTATION - TREATMENT WITH BALLOON ANGIOPLASTY RADIOLOGY Zajko, A. B., Claus, D., Clapuyt, P., Esquivel, C. O., Moulin, D., Starzl, T. E., DeGoyet, J. D., Otte, J. B. 1989; 170 (3): 763-765

    Abstract

    Stenosis of the suprahepatic inferior vena caval anastomosis is a rare but serious vascular complication after liver transplantation. It may cause significant obstruction to venous drainage from the allograft liver and result in the Budd-Chiari syndrome with massive ascites and pleural effusion causing respiratory compromise. The authors report two such cases in which percutaneous transluminal angioplasty (PTA) of the stenotic anastomosis was performed. This nonsurgical approach resulted in resolution of ascites, pleural effusion, and respiratory distress in both patients. They conclude that PTA is a therapeutic alternative with minimal risk compared with surgical repair or retransplantation and should be considered the initial treatment of choice in selected patients.

    View details for Web of Science ID A1989T273400031

    View details for PubMedID 2521735

    View details for PubMedCentralID PMC3091358

  • INSITU VERSUS BENCH RESECTION OF LIVER ALLOGRAFTS BEFORE ORTHOTOPIC LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS CRUCITTI, F., Marino, I. R., DeLuca, G., Celli, S., Santini, E., Cavicchioni, C., Negro, F., Frontera, D., DEFRANCISCI, G., Perrelli, L., Esquivel, C. O. 1989; 21 (1): 2364-2366

    View details for Web of Science ID A1989U152400460

    View details for PubMedID 2652769

  • PSEUDOANEURYSMS FOLLOWING ORTHOTOPIC LIVER-TRANSPLANTATION - CLINICAL AND RADIOLOGIC MANIFESTATIONS TRANSPLANTATION PROCEEDINGS Zajko, A. B., TOBBEN, P. J., Esquivel, C. O., Starzl, T. E. 1989; 21 (1): 2457-2459

    View details for Web of Science ID A1989U152400498

    View details for PubMedID 2652804

    View details for PubMedCentralID PMC2903847

  • HLA ALLOIMMUNIZATION AND BLOOD REQUIREMENTS IN ORTHOTOPIC LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Marino, I. R., Weber, T., Kang, Y. G., Esquivel, C. O., Starzl, T. E., Duquesnoy, R. 1989; 21 (1): 789-791

    View details for Web of Science ID A1989U152300336

    View details for PubMedID 2650271

    View details for PubMedCentralID PMC2967352

  • SIGNIFICANCE OF BLOOD-FLOW MEASUREMENT IN CLINICAL LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Yanaga, K., Shimada, M., Makowka, L., Esquivel, C. O., Tzakis, A. G., Starzl, T. E. 1989; 21 (1): 2330-2331

    View details for Web of Science ID A1989U152400445

    View details for PubMedID 2652755

    View details for PubMedCentralID PMC2978525

  • ANTIBODY MEDIATED REJECTION OF HUMAN-LIVER ALLOGRAFTS - TRANSPLANTATION ACROSS ABO BLOOD-GROUP BARRIERS TRANSPLANTATION PROCEEDINGS Demetris, A. J., Jaffe, R., Tzakis, A., Ramsey, G., Todo, S., Belle, S., Esquivel, C., Shapiro, R., ZJAKO, A., Markus, B., MOROZEC, E., VANTHIEL, D. H., Sysyn, G., Gordon, R., Makowka, L., Starzl, T. E. 1989; 21 (1): 2217-2220

    View details for Web of Science ID A1989U152400397

    View details for PubMedID 2652716

    View details for PubMedCentralID PMC3022483

  • INFECTIONS IN PEDIATRIC LIVER RECIPIENTS TREATED FOR ACUTE REJECTION TRANSPLANTATION PROCEEDINGS Koneru, B., Scantlebury, V. P., Makowka, L., Esquivel, C. O., Todo, S., Tzakis, A. G., Marsh, J. W., Iwatsuki, S., Douglas, L., Starzl, T. E. 1989; 21 (1): 2251-2252

    View details for Web of Science ID A1989U152400412

    View details for PubMedID 2652730

    View details for PubMedCentralID PMC2903875

  • LIVER-TRANSPLANTATION FOR HEREDITARY TYROSINEMIA IN THE PRESENCE OF HEPATOCELLULAR-CARCINOMA TRANSPLANTATION PROCEEDINGS Esquivel, C. O., Mieles, L., Marino, I. R., Todo, S., Makowka, L., Ambrosino, G., Nakazato, P., Starzl, T. E. 1989; 21 (1): 2445-2446

    View details for Web of Science ID A1989U152400491

    View details for PubMedID 2540570

    View details for PubMedCentralID PMC2903894

  • FACTORS RESPONSIBLE FOR HEPATIC-ARTERY THROMBOSIS AFTER PEDIATRIC LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Mazzaferro, V., Esquivel, C. O., Makowka, L., Kahn, D., Belle, S., Kahn, D., Scantlebury, V. P., Ferla, G., Koneru, B., SCOTTIFOGLIENI, C. L., Todo, S., Tzakis, A. G., Starzl, T. E. 1989; 21 (1): 2466-2467

    View details for Web of Science ID A1989U152400502

    View details for PubMedID 2652807

    View details for PubMedCentralID PMC2966154

  • DISTAL SPLENORENAL SHUNT FOR PORTAL-VEIN THROMBOSIS AFTER LIVER-TRANSPLANTATION AMERICAN JOURNAL OF GASTROENTEROLOGY Marino, I. R., Esquivel, C. O., Zajko, A. B., MALATACK, J., Scantlebury, V. P., Shaw, B. W., Starzl, T. E. 1989; 84 (1): 67-70

    Abstract

    A 17-yr-old female received a liver transplant for type I glycogen storage disease. A year later, when she experienced variceal gastrointestinal hemorrhage, an angiogram revealed thrombosis of the portal vein with hepatopetal collateral channels. A distal splenorenal shunt was performed because of failure of sclerotherapy to control subsequent bleeding episodes and the fact that the liver function was normal. This patient continues to have normal hepatic function with a patent splenorenal shunt 4 yr after the shunting procedure. This case illustrates the feasibility of a distal splenorenal shunt to alleviate portal hypertension in cases of thrombosis of the portal vein following hepatic transplantation if the liver function is normal.

    View details for Web of Science ID A1989R822000017

    View details for PubMedID 2643299

    View details for PubMedCentralID PMC2963577

  • INTRAOPERATIVE BLOOD-TRANSFUSION REQUIREMENTS AND DEFICIENT HEMOSTASIS IN HIGHLY ALLOIMMUNIZED PATIENTS UNDERGOING LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Marino, I. R., Weber, T., Esquivel, C. O., Kang, Y. G., Starzl, T. E., Duquesnoy, R. J. 1988; 20 (6): 1087-1089

    View details for Web of Science ID A1988R285300008

    View details for PubMedID 3059590

    View details for PubMedCentralID PMC3033038

  • TREATMENT OF HEPATIC EPITHELIOID HEMANGIOENDOTHELIOMA WITH LIVER-TRANSPLANTATION CANCER Marino, I. R., Todo, S., Tzakis, A. G., Klintmalm, G., Kelleher, M., Iwatsuki, S., Starzl, T. E., Esquivel, C. O. 1988; 62 (10): 2079-2084

    Abstract

    Ten patients received liver transplants for unresectable epithelioid hemangioendothelioma (EHE). At the time of transplantation, four patients had microscopic metastases to the hilar lymph nodes, and one of the four also had metastases to a rib. The fifth patient had metastases to the lung, pleura, and diaphragm. The remaining five patients were believed to be free of metastatic disease. Two of these five patients died of metastatic disease at 3 and 16 months, respectively, after transplantation. Interestingly, all five patients with metastatic involvement are currently alive 40.6 +/- 22 months (mean +/- standard error of mean [SEM]) after transplantation, although one of these patients currently has metastatic disease to the lungs and mediastinum. Thus, the projected 5-year actuarial survival rate is 76%, with two patients at risk after the third year. In conclusion, liver transplantation is a reasonable procedure for bulky, otherwise unresectable, EHE even in the presence of metastatic disease.

    View details for Web of Science ID A1988Q718400001

    View details for PubMedID 3052779

    View details for PubMedCentralID PMC2990224

  • PSEUDOANEURYSMS COMPLICATING ORGAN-TRANSPLANTATION - ROLES OF CT, DUPLEX SONOGRAPHY, AND ANGIOGRAPHY RADIOLOGY TOBBEN, P. J., Zajko, A. B., Sumkin, J. H., Bowen, A., Fuhrman, C. R., SKOLNICK, M. L., BRON, K. M., Esquivel, C. O., Starzl, T. E. 1988; 169 (1): 65-70

    Abstract

    In a retrospective study of proved pseudoaneurysms (PAs) in 15 patients with transplanted organs (11 liver, three kidney, one pancreas), the results of computed tomography (CT), duplex sonography, and angiography were reviewed. Of the 15 cases of PA, eight occurred at the arterial anastomosis and seven were nonanastomotic. Three of the eight anastomotic PAs were caused by infection. Of the seven nonanastomotic PAs, four were caused by percutaneous biopsy, two were caused by infection, and one was of undetermined cause. In nine (60%) of the 15 patients the PAs were incidentally detected at imaging studies performed for other reasons. Diagnosis requires a high degree of suspicion. CT was performed in nine cases and duplex sonography in ten. The diagnosis of PA was made with CT in six (67%) patients and with duplex sonography in five (50%). CT and duplex sonography could not enable diagnosis when the PA was small, when the arterial anastomosis was not included in the field of study, or when enhancement with intravenously administered contract material was suboptimal. Angiography depicted the PAs in all 15 patients. In three liver transplant recipients with gastrointestinal tract bleeding, the causative PAs were detected only with angiography.

    View details for Web of Science ID A1988Q109800013

    View details for PubMedID 3047790

    View details for PubMedCentralID PMC3022506

  • ANTIBODY-MEDIATED REJECTION OF HUMAN ORTHOTOPIC LIVER ALLOGRAFTS - A STUDY OF LIVER-TRANSPLANTATION ACROSS ABO BLOOD-GROUP BARRIERS AMERICAN JOURNAL OF PATHOLOGY Demetris, A. J., Jaffe, R., Tzakis, A., Ramsey, G., Todo, S., Belle, S., Esquivel, C., Shapiro, R., Markus, B., Mroczek, E., VANTHIEL, D. H., Sysyn, G., Gordon, R., Makowka, L., Starzl, T. 1988; 132 (3): 489-502

    Abstract

    A clinicopathologic analysis of liver transplantation across major ABO blood group barriers was carried out 1) to determine if antibody-mediated (humoral) rejection was a cause of graft failure and if humoral rejection can be identified, 2) to propose criteria for establishing the diagnosis, and 3) to describe the clinical and pathological features of humoral rejection. A total of 51 (24 primary) ABO-incompatible (ABO-I) liver grafts were transplanted into 49 recipients. There was a 46% graft failure rate during the first 30 days for primary ABO-I grafts compared with an 11% graft failure rate for primary ABO compatible (ABO-C), crossmatch negative, age, sex and priority-matched control patients (P less than 0.02). A similarly high early graft failure rate (60%) was seen for nonprimary ABO-I grafts during the first 30 days. Clinically, the patients experienced a relentless rise in serum transaminases, hepatic failure, and coagulopathy during the first weeks after transplant. Pathologic examination of ABO-I grafts that failed early demonstrated widespread areas of geographic hemorrhagic necrosis with diffuse intraorgan coagulation. Prominent arterial deposition of antibody and complement components was demonstrated by immunoflourescent staining. Elution studies confirmed the presence of tissue-bound, donor-specific isoagglutinins within the grafts. No such deposition was seen in control cases. These studies confirm that antibody mediated rejection of the liver occurs and allows for the development of criteria for establishing the diagnosis.

    View details for Web of Science ID A1988Q131200011

    View details for PubMedID 3046369

    View details for PubMedCentralID PMC1880751

  • APLASTIC-ANEMIA COMPLICATING ORTHOTOPIC LIVER-TRANSPLANTATION FOR NON-A, NON-B HEPATITIS NEW ENGLAND JOURNAL OF MEDICINE Tzakis, A. G., Arditi, M., Whitington, P. F., Yanaga, K., Esquivel, C., Andrews, W. A., Makowka, L., MALATAK, J., Freese, D. K., Stock, P. G., Ascher, N. L., Johnson, F. L., Broelsch, C. E., Starzl, T. E. 1988; 319 (7): 393-396

    Abstract

    Aplastic anemia developed in 9 of 32 patients (28 percent) undergoing orthotopic liver transplantation for acute non-A, non-B hepatitis, at one to seven weeks after the procedure. No patient previously had evidence of hematologic dysfunction or conditions known to be associated with aplastic anemia. No other cases of aplastic anemia were identified among 1463 patients undergoing liver transplantation for all other indications at the four centers participating in the study (chi-square = 415, P less than 0.001; 95 percent confidence interval for the incidence of aplastic anemia after transplantation for non-A, non-B hepatitis, 13 to 44 percent, vs. 0.00 to 0.13 percent for all other indications). The operative and postoperative treatment of these patients was not otherwise different, indicating that the aplastic anemia was a complication of the hepatitis, not of the transplantation procedure. Four of the nine patients died of complications due to infections. Three of the surviving patients have been followed for less than six months, one for one year, and one for two years. The two patients followed the longest have recovered marrow function to an appreciable degree, and two of the others have evidence of early recovery. We conclude that patients undergoing orthotopic liver transplantation for non-A, non-B hepatitis are at a high risk for the development of aplastic anemia.

    View details for Web of Science ID A1988P684200002

    View details for PubMedID 3135496

    View details for PubMedCentralID PMC3034374

  • EARLY DETECTION AND MANAGEMENT OF PORTAL-VEIN THROMBOSIS AFTER HEPATIC TRANSPLANTATION - A CASE-REPORT CLINICAL TRANSPLANTATION Koneru, B., Esquivel, C. O., Bowen, A. D., Zajko, A. B., Starzl, T. E. 1988; 2 (4): 214-215
  • PATHOLOGIC ANALYSIS OF LIVER-TRANSPLANTATION FOR PRIMARY BILIARY-CIRRHOSIS HEPATOLOGY Demetris, A. J., Markus, B. H., Esquivel, C., VANTHIEL, D. H., Saidman, S., Gordon, R., Makowka, L., Sysyn, G. D., Starzl, T. E. 1988; 8 (4): 939-947

    Abstract

    A retrospective histopathologic review of all pathologic specimens from 394 adult liver transplant patients was undertaken with clinical correlation to determine if primary biliary cirrhosis has affected the posttransplant course compared to all other indications for liver transplantation and if recurrent primary biliary cirrhosis has occurred after liver transplantation. We also compared the histopathologic features seen in native livers with primary biliary cirrhosis to failed allografts with chronic rejection. One hundred six of the 394 adult patients transplanted during this time (1981 to July, 1986) fulfilled clinicopathologic criteria for a diagnosis of primary biliary cirrhosis. Neither the incidence nor any qualitative pathologic feature of histologically documented acute cellular rejection differentiated subjects transplanted for primary biliary cirrhosis vs. other diseases. No correlation between the titers of antimitochondrial antibody and the presence of posttransplant hepatic dysfunction based on liver enzyme profiles or the development of chronic rejection was seen in patients transplanted for primary biliary cirrhosis. Minor differences noted in the posttransplant course of primary biliary cirrhosis patients as compared to other conditions (higher incidence of chronic rejection as a cause of graft failure) was seen, but this did not significantly affect graft or patient survival. Recurrent primary biliary cirrhosis could not be diagnosed with certainty in any patient. A comparison of failed chronically rejected allografts vs. native hepatectomies obtained from patients with primary biliary cirrhosis revealed the presence of chronic obliterative vasculopathy, centrilobular cholestasis, and lack of granulomas, cirrhosis, cholangiolar proliferation, copper-associated protein deposition and Mallory's hyalin in specimens with chronic rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1988P436300038

    View details for PubMedID 3292365

    View details for PubMedCentralID PMC2981803

  • TRANSPLANTATION FOR PRIMARY BILIARY-CIRRHOSIS GASTROENTEROLOGY Esquivel, C. O., VANTHIEL, D. H., Demetris, A. J., Bernardos, A., Iwatsuki, S., Markus, B., Gordon, R. D., Marsh, J. W., Makowka, L., Tzakis, A. G., Todo, S., GAVALER, J. S., Starzl, T. E. 1988; 94 (5): 1207-1216

    Abstract

    Primary biliary cirrhosis is a frequent indication for liver transplantation. The purpose of this report is to present our experience with liver transplantation for primary biliary cirrhosis. Attention is given to the causes of hepatic dysfunction seen in allografts. In addition, we review the postoperative problems encountered and the quality of life at time of last follow-up in patients with transplants for primary biliary cirrhosis. A total of 97 orthotopic liver transplant procedures were performed in 76 patients with advanced primary biliary cirrhosis at the University of Pittsburgh from March 1980 through September 1985. The transplant operation was relatively easy to perform. The most common technical complications experienced were fragmentation and intramural dissection of the recipient hepatic artery, which required an arterial graft in 20% of the cases. Most of the postoperative mortality occurred in the first 6 mo after transplantation, with an essentially flat actuarial life survival curve from that time point to a projected 5-yr survival of 66%. Common causes of death included rejection and primary graft nonfunction. Thirteen of the 76 patients had some hepatic dysfunction at the time of the last follow-up, although none were jaundiced. Recurrence of primary biliary cirrhosis could not be demonstrated in any of the patients. Antimitochondrial antibody was detected in the serum of almost all of the patients studied postoperatively for it. Most important, almost all of the 52 surviving patients have been rehabilitated socially and vocationally.

    View details for Web of Science ID A1988M938200014

    View details for PubMedID 3280389

    View details for PubMedCentralID PMC3095835

  • OCCURRENCE OF CYTOMEGALO-VIRUS HEPATITIS IN LIVER-TRANSPLANT PATIENTS JOURNAL OF MEDICAL VIROLOGY Bronsther, O., Makowka, L., Jaffe, R., Demetris, A. J., BREINIG, M. K., Ho, M., Esquivel, C. O., Gordon, R. D., Iwatsuki, S., Tzakis, A., Marsh, J. W., Mazzaferro, V., Vanthiel, D., Starzl, T. E. 1988; 24 (4): 423-434

    Abstract

    The differential diagnosis of liver dysfunction after orthotopic liver transplantation can be difficult. Cytomegalovirus (CMV) hepatitis is one possibility. This report reviews our experience with 17 cases of pathologically proven CMV hepatitis following liver transplantation and demonstrates the need for percutaneous liver biopsies to establish the diagnosis. There were seven pediatric patients (ages 2-11 years, five males, two females) and ten adult patients (ages 17-53 years, eight males, two females). The most common symptoms were prolonged fever (15 patients, with a mean duration of 22 +/- 5.5 days), elevation in total bilirubin (14 patients), and elevation in liver enzymes (15 patients); all symptoms were also found in rejection. Leukopenia and thrombocytopenia, reported to frequently occur with CMV infection, were found in only three and five patients, respectively. Twelve patients with the above symptoms underwent percutaneous biopsy on one or more occasions to differentiate CMV hepatitis from rejection. The diagnosis was made at retransplantation in five patients. CMV hepatitis followed treatment for acute rejection in 14 patients and occurred without additional immunosuppression in three patients. All patients were maintained on cyclosporine and prednisone. Acute rejection episodes were treated with a 5-day tapering dose of steroids (17 courses in 12 patients), OKT3 monoclonal antibody [Ortho (4 patients)] antithymocyte globulin [Upjohn (2 patients)], and azathioprine (1 patient). CMV was isolated from urine (nine patients), blood (nine patients), throat (seven patients), lungs (two patients), and other organs (two patients). CMV was cultured from the liver biopsy specimens in five of the seven attempts in pediatric patients. When the diagnosis was confirmed in the absence of rejection, immunosuppression was routinely lowered. When rejection occurred concomitantly with CMV hepatitis, therapy had to be individualized. Retrospectively, three patients treated for rejection were noted at retransplantation to have only CMV hepatitis, and all three patients died. A high index of suspicion and the judicious use of liver biopsies is essential in order to differentiate CMV hepatitis from other causes of posttransplant liver dysfunction.

    View details for Web of Science ID A1988M850200008

    View details for PubMedID 2835433

  • LIVER-TRANSPLANTATION FOR METABOLIC DISEASE OF THE LIVER GASTROENTEROLOGY CLINICS OF NORTH AMERICA Esquivel, C. O., Marino, I. R., FIORAVANTI, V., VANTHIEL, D. H. 1988; 17 (1): 167-175

    Abstract

    Hepatic transplantation for metabolic or genetic diseases of the liver produces a definite cure of the liver disease and also effectively cures the underlying metabolic abnormalities of the genetic disease in question. Liver transplantation is highly likely to become the current treatment of choice for a wide variety of metabolic disorders based predominantly in the liver. This is true not only for those that produce grossly evident hepatic disease with cirrhosis, but also for those that are free of obvious hepatocellular injury but are based either predominantly or exclusively within the liver.

    View details for Web of Science ID A1988N568500011

    View details for PubMedID 3292426

  • LIVER-TRANSPLANTATION FOR CHRONIC CHOLESTATIC LIVER-DISEASE IN ADULTS AND CHILDREN GASTROENTEROLOGY CLINICS OF NORTH AMERICA Esquivel, C. O., Marsh, J. W., VANTHIEL, D. H. 1988; 17 (1): 145-155

    Abstract

    Liver transplantation has provided individuals with cholestatic disorders a chance for long-term near-normal quality and quantity of survival. The experience at the University of Pittsburgh with hepatic transplantation for chronic cholestatic liver disease is presented in brief in this article.

    View details for Web of Science ID A1988N568500009

    View details for PubMedID 3292424

  • INFECTIONS AFTER LIVER-TRANSPLANTATION - AN ANALYSIS OF 101 CONSECUTIVE CASES MEDICINE Kusne, S., Dummer, J. S., Singh, N., Iwatsuki, S., Makowka, L., Esquivel, C., Tzakis, A. G., Starzl, T. E., Ho, M. 1988; 67 (2): 132-143

    Abstract

    We studied infections in 101 consecutive patients who underwent liver transplantation between July 1984 and September 1985. The mean length of follow-up was 394 days. Eighty-three percent of population had 1 or more episodes of infection and 67% of the population had severe infections. The overall mortality was 26/101 (26%) and 23 of 26 deaths (88%) were associated with infection. Seventy percent of severe infections occurred in the first 2 months after transplantation. The most frequent severe infections were abdominal abscess, bacterial pneumonia, invasive candidiasis, Pneumocystis pneumonia, and symptomatic cytomegalovirus infection. Patients with more than 12 hours of cumulative surgical time had a higher rate of severe infections (P less than 0.001), particularly fungal (P less than 0.001) and bacterial (P less than 0.01) infections. Also, the use of choledocho-jejunostomy was associated with a higher rate of infection in patients who had more than 1 transplant operation (P less than 0.02). No increase in infection was found in patients who received azathioprine, or more than the median number of steroid boluses or "recycles"; but patients who received OKT3 therapy had a higher rate of protozoal infections (P less than 0.05). A result similar to that of our previous studies was a strong relation between the number of severe fungal infections and prolonged courses of antibiotics after transplant operation (P less than 0.001). Pretransplant manifestations of severe liver disease such as ascites, encephalopathy, and gastrointestinal bleeding were not associated with higher rates of infection after transplantation, but high serum levels of ALT were. Patients with lower ratios of T-helper to T-suppressor lymphocytes had more severe viral (P less than 0.02) and fungal (P less than 0.01) infections after transplantation.

    View details for Web of Science ID A1988N035600006

    View details for PubMedID 3280944

    View details for PubMedCentralID PMC2979316

  • ORTHOTOPIC LIVER-TRANSPLANTATION OF LIVER GRAFTS PREVIOUSLY RESECTED INSITU TRANSPLANTATION PROCEEDINGS Marino, I. R., Esquivel, C. O., DeLuca, G., Santini, E., Celli, S., Napolitano, M. M., DIPIETRO, C., Frena, A., Bevilacqua, P., Cavicchioni, C., Mazzaferro, V., Markus, B. H., DEFRANCISCI, G., Falappa, P. G., Perrelli, L. 1988; 20 (1): 548-551

    View details for Web of Science ID A1988M463100167

    View details for PubMedID 3279647

  • EXPERIENCE WITH ORTHOCLONE OKT3 MONOCLONAL-ANTIBODY IN LIVER-TRANSPLANTATION AMERICAN JOURNAL OF KIDNEY DISEASES Gordon, R. D., Tzakis, A. G., Iwatsuki, S., Todo, S., Esquivel, C. O., Marsh, J. W., Stieber, A., Makowka, L., Starzl, T. E. 1988; 11 (2): 141-144

    Abstract

    Experience with the use of Orthoclone OKT3 monoclonal antibody for the treatment of acute cellular rejection in a series of 130 human orthotopic liver transplantations is reviewed. Treatment was highly effective in reversing rejection, in reducing the rate of retransplantation, and in lowering patient mortality. OKT3 was also useful for cyclosporine sparing in patients with poor renal function, hypertension, or CNS toxicity. There was a significant incidence of opportunistic infection associated with the use of OKT3.

    View details for Web of Science ID A1988M005600016

    View details for PubMedID 3124609

    View details for PubMedCentralID PMC2958668

  • EXPERIENCE IN 1,000 LIVER-TRANSPLANTS UNDER CYCLOSPORINE-STEROID THERAPY - A SURVIVAL REPORT TRANSPLANTATION PROCEEDINGS Iwatsuki, S., Starzl, T. E., Todo, S., Gordon, R. D., Esquivel, C. O., Tzakis, A. G., Makowka, L., Marsh, J. W., Koneru, B., Stieber, A., Klintmalm, G., Husberg, B. 1988; 20 (1): 498-504

    View details for Web of Science ID A1988M463100152

    View details for PubMedID 3279643

    View details for PubMedCentralID PMC2954652

  • AN UNUSUAL COMPLICATION OF CHOLEDOCHOCHOLEDOCHOSTOMY IN ORTHOTOPIC LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Stieber, A. C., Ambrosino, G., Kahn, D., Mieles, L., Makowka, L., Lerut, J., Iwatsuki, S., Todo, S., Marsh, J. W., Tzakis, A. G., Gordon, R. D., Esquivel, C. O., Starzl, T. E. 1988; 20 (1): 619-621
  • BILIARY COMPLICATIONS IN LIVER ALLOGRAFTS AFTER HEPATIC-ARTERY OCCLUSION - A 6-1/2-YEAR STUDY TRANSPLANTATION PROCEEDINGS Zajko, A. B., Campbell, W. L., LOGSDON, G. A., BRON, K. M., Tzakis, A., Esquivel, C. O., Starzl, T. E. 1988; 20 (1): 607-609
  • AN ANALYSIS OF THE CAUSES OF DEATH AFTER PEDIATRIC LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Kahn, D., Esquivel, C. O., MADRIGALTORRES, M., Todo, S., Yunis, E., Iwatsuki, S., Starzl, T. E. 1988; 20 (1): 613-615
  • FUNGAL-INFECTIONS AFTER LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Kusne, S., Dummer, J. S., Singh, N., Makowka, L., Esquivel, C., Starzl, T. E., Ho, M. 1988; 20 (1): 650-651
  • Progress in liver transplantation. Advances in surgery Gordon, R. D., Iwatsuki, S., Esquivel, C. O., Makowka, L., Todo, S., Tzakis, A. G., Marsh, J. W., Starzl, T. E. 1988; 21: 49-64

    View details for PubMedID 3120501

    View details for PubMedCentralID PMC3022381

  • INTRAHEPATIC BILE-DUCT STRICTURES AFTER HUMAN ORTHOTOPIC LIVER-TRANSPLANTATION - RECURRENCE OF PRIMARY SCLEROSING CHOLANGITIS OR UNUSUAL PRESENTATION OF ALLOGRAFT-REJECTION TRANSPLANT INTERNATIONAL Lerut, J., Demetris, A. J., Stieber, A. C., Marsh, J. W., Gordon, R. D., Esquivel, C. O., Iwatsuki, S., Starzl, T. E. 1988; 1 (3): 127-130

    Abstract

    One of 55 patients transplanted for sclerosing cholangitis during the cyclosporin-steroid era (March 1980-June 1986) developed intrahepatic biliary strictures in the absence of allograft rejection within the 1st year posttransplantation. Although many causes underlie biliary pathology in the postoperative period (i.e., arterial injury, ischemia, chronic rejection, cholangitis), recurrent disease remains a possibility.

    View details for Web of Science ID A1988R067500002

    View details for PubMedID 3075471

    View details for PubMedCentralID PMC2979302

  • ORTHOTOPIC LIVER-TRANSPLANTATION FOR PRIMARY SCLEROSING CHOLANGITIS ANNALS OF SURGERY Marsh, J. W., Iwatsuki, S., Makowka, L., Esquivel, C. O., Gordon, R. D., Todo, S., Tzakis, A., Miller, C., Vanthiel, D., Starzl, T. E. 1988; 207 (1): 21-25

    Abstract

    The incidence or diagnostic rate of sclerosing cholangitis is increasing. Because of the lack of effective medical or surgical therapy for patients with end-stage liver disease and sclerosing cholangitis, results with orthotopic liver transplantation were examined. The results of 55 consecutive liver replacements for this disease were reviewed. The 1- and 2-year actuarial survival rates are 71% and 57%, respectively. Orthotopic liver transplantation for end-stage liver disease from sclerosing cholangitis has emerged as the most effective therapy.

    View details for Web of Science ID A1988L633700005

    View details for PubMedID 2827593

    View details for PubMedCentralID PMC1493239

  • EXPERIENCE WITH PRIMARY LIVER-TRANSPLANTATION ACROSS ABO BLOOD-GROUPS TRANSPLANTATION PROCEEDINGS Gordon, R. D., Iwatsuki, S., Esquivel, C. O., Todo, S., Makowka, L., Tzakis, A., Marsh, J. W., Starzl, T. E. 1987; 19 (6): 4575-4579

    View details for Web of Science ID A1987L305600042

    View details for PubMedID 3321622

    View details for PubMedCentralID PMC2911142

  • INDICATIONS FOR PEDIATRIC LIVER-TRANSPLANTATION JOURNAL OF PEDIATRICS Esquivel, C. O., Iwatsuki, S., Gordon, R. D., Marsh, W. W., Koneru, B., Makowka, L., Tzakis, A. G., Todo, S., Starzl, T. E. 1987; 111 (6): 1039-1045

    Abstract

    Two hundred fifty pediatric (less than 18 years of age) patients underwent orthotopic liver transplantation because of end-stage liver disease and were given combination therapy with cyclosporine and prednisone. The most common indications for transplantation in decreasing order of frequency were biliary atresia, inborn errors of metabolism, and postnecrotic cirrhosis. The 5-year actuarial survival for the entire group was 69.2%. Age and diagnosis did not influence survival. Infections were the most common cause of death, followed by liver failure and cerebrovascular accident. The impact of retransplantation on survival depends on the indication. The survival is better when retransplantation is carried out after rejection than because of technical complications, and the latter has a better survival than does primary graft nonfunction. The difference in survival among these groups is statistically significant. The quality of life for 164 of 173 survivors is good to excellent; only nine children are currently experiencing medical problems. A persistent problem in pediatric transplantation is the scarcity of small donors.

    View details for Web of Science ID A1987L199500012

    View details for PubMedID 3316578

    View details for PubMedCentralID PMC3086407

  • Orthotopic liver transplantation for alpha-1-antitrypsin deficiency: an experience in 29 children and ten adults. Transplantation proceedings Esquivel, C. O., Vicente, E., Van Thiel, D., Gordon, R., Marsh, W., Makowka, L., Koneru, B., Iwatsuki, S., Madrigal, M., Delgado Millan, M. A. 1987; 19 (5): 3798-3802

    Abstract

    Thirty-nine patients (29 children and ten adults) underwent OLT for liver disease associated with A1AD from March 1980 to March 1986. Thirty of thirty-six patients (83%) with available data were homozygous phenotype PiZZ. The other six were Pi heterozygotes, being either PiMZ or PiSZ. The mean A1A activity in homozygous and heterozygous patients was 38.8 mg/dL and 114.3 mg/dL respectively. Eight patients died during the first 3 months after OLT (20%). The 5-year actuarial survival is 83% and 60% in pediatric and adult recipients respectively. Today 30 (76%) of the recipients are alive, with follow-ups of 8 to 64 months (average 27 months). The quality of life in the surviving patients is excellent.

    View details for PubMedID 3313926

  • PROLONGATION OF PIG-TO-DOG RENAL XENOGRAFT SURVIVAL BY MODIFICATION OF THE INFLAMMATORY MEDIATOR RESPONSE ANNALS OF SURGERY Makowka, L., Miller, C., Chapchap, P., Podesta, L., Pan, C., Pressley, D., Mazzaferro, V., Esquivel, C. O., Todo, S., Banner, B., Jaffe, R., Saunders, R., Starzl, T. E. 1987; 206 (4): 482-495

    Abstract

    The pathogenesis of hyperacute renal rejection consists of a nonspecific effector cascade that invokes most of the components of a typical acute inflammatory response. Platelet-activating factor (PAF) represents the most recent and perhaps the most significant mediator and promoting agent of this phenomenon. These studies evaluated SRI 63-441, a novel, synthetic, and the most potent PAF receptor antagonist available, alone and in combination with other prostanoids, for their ability to influence this response and to prolong renal xenograft survival and function in a model of pig-to-dog heterotransplantation. Inhibition of PAF by SRI 63-441 alone, at the dosage and schedule used in these experiments, did not significantly prolong xenograft survival or function. However, the combination of SRI 63-441 with either prostacyclin (PGI2) or prostaglandin E1 (PGE1) infusion demonstrated significant synergism, and resulted in a 6-9-fold increase in kidney survival and a 3-20-fold increase in urine output. Neither PGI2 nor PGE1 infusions alone significantly influenced this xenograft model. Electromagnetic flow studies demonstrated significantly delayed diminution in renal artery blood flow in the combination-treated animals. Serial and end-stage histologic examination of kidneys receiving combination therapy demonstrated a delayed onset of the pathologic deterioration and an overall amelioration of the entire process. These studies demonstrate that significant abrogation of a rapid and violent form of hyperacute rejection can be achieved solely by the pharmacologic manipulation of the inflammatory mediator response.

    View details for Web of Science ID A1987K399900009

    View details for PubMedID 3310931

    View details for PubMedCentralID PMC1493236

  • ORTHOTOPIC LIVER-TRANSPLANTATION FOR ALPHA-1-ANTITRYPSIN DEFICIENCY - AN EXPERIENCE IN 29 CHILDREN AND 10 ADULTS TRANSPLANTATION PROCEEDINGS Esquivel, C. O., Vicente, E., Vanthiel, D., Gordon, R., Marsh, W., Makowka, L., Koneru, B., Iwatsuki, S., Madrigal, M., Millan, M. A., Todo, S., Tzakis, A., Starzl, T. E. 1987; 19 (5): 3798-3802

    Abstract

    Thirty-nine patients (29 children and ten adults) underwent OLT for liver disease associated with A1AD from March 1980 to March 1986. Thirty of thirty-six patients (83%) with available data were homozygous phenotype PiZZ. The other six were Pi heterozygotes, being either PiMZ or PiSZ. The mean A1A activity in homozygous and heterozygous patients was 38.8 mg/dL and 114.3 mg/dL respectively. Eight patients died during the first 3 months after OLT (20%). The 5-year actuarial survival is 83% and 60% in pediatric and adult recipients respectively. Today 30 (76%) of the recipients are alive, with follow-ups of 8 to 64 months (average 27 months). The quality of life in the surviving patients is excellent.

    View details for Web of Science ID A1987K855800092

    View details for PubMedCentralID PMC2903897

  • CHOLANGIOGRAPHIC FINDINGS IN HEPATIC-ARTERY OCCLUSION AFTER LIVER-TRANSPLANTATION AMERICAN JOURNAL OF ROENTGENOLOGY Zajko, A. B., Campbell, W. L., LOGSDON, G. A., BRON, K. M., Tzakis, A., Esquivel, C. O., Starzl, T. E. 1987; 149 (3): 485-489

    Abstract

    Because the hepatic artery provides the only blood supply to the biliary tree of a liver allograft, posttransplantation arterial occlusion may result in a biliary complication. Cholangiograms were reviewed retrospectively in 31 transplant patients who had proved complete or partial occlusions of the hepatic artery (thrombosis in 29 and marked stenosis in two). Cholangiograms were abnormal in 26 (84%). The most common abnormality, seen in 16 patients, was nonanastomotic contrast leakage from the donor intra- or extrahepatic bile ducts. Strictures of the donor biliary tree occurred in 14 patients, four of whom also had a nonanastomotic bile leak. In 12 of the 14, the strictures were nonanastomotic. Other findings included poor filling of the intrahepatic bile ducts, generalized donor ductal dilatation and irregularity, and intraductal filling defects. Sixteen (89%) of 18 transplants with nonanastomotic contrast leakage had occlusions of the hepatic artery. Of 21 transplants with nonanastomotic strictures, 12 (57%) had occlusions of the hepatic artery. Only two (10%) of 20 transplants with biliary anastomotic strictures had arterial occlusion. We conclude that liver transplant recipients who exhibit nonanastomotic contrast leakage or nonanastomotic strictures on cholangiography should be evaluated for occlusion of the hepatic artery as the probable cause.

    View details for Web of Science ID A1987J751000007

    View details for PubMedID 3303874

    View details for PubMedCentralID PMC2965516

  • IS MULTIPLE ORGAN FAILURE A CONTRAINDICATION FOR LIVER-TRANSPLANTATION IN CHILDREN TRANSPLANTATION PROCEEDINGS Esquivel, C. O., Koneru, B., Todo, S., Iwatsuki, S., Gordon, R. D., Marsh, J. W., Makowka, L., Tzakis, A. G., Starzl, T. E. 1987; 19 (4): 47-48

    View details for Web of Science ID A1987J700500010

    View details for PubMedID 3303532

    View details for PubMedCentralID PMC2903843

  • PEDIATRIC LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Starzl, T. E., Esquivel, C., Gordon, R., Todo, S. 1987; 19 (4): 3230-3235

    Abstract

    Liver transplantation, which once was an experimental procedure of no practical interest, has become the preferred treatment for infants and children dying of almost all non-neoplastic end-stage liver diseases. Liver replacement is being provided by many well-trained teams on all of the continents, as is evident from the program today--the first international symposium on pediatric liver transplantation. I have been honored in giving the first paper in the process of introducing the remarkable work of a gifted younger generation of physicians and surgeons.

    View details for Web of Science ID A1987J615600002

    View details for PubMedID 3303488

    View details for PubMedCentralID PMC2903879

  • ADENOVIRAL INFECTIONS IN PEDIATRIC LIVER-TRANSPLANT RECIPIENTS JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Koneru, B., Jaffe, R., Esquivel, C. O., Kunz, R., Todo, S., Iwatsuki, S., Starzl, T. E. 1987; 258 (4): 489-492

    Abstract

    Over a 5 1/2-year period, 22 of 262 children receiving liver transplants developed adenoviral infections. Five had adenoviral hepatitis in the allograft, caused by serotype 5. All five were treated for rejection, either just before or at the time of infection. Liver biopsy specimens had characteristic histological appearance, and diagnosis of adenoviral infection was confirmed with monoclonal antiadenoviral antibodies, electron microscopy, and by culture of liver tissue. In the remaining 17 patients, adenovirus was isolated from urine, stool, throat secretions, and/or blood samples, but none had any detectable visceral infection. Serotypes 1 and 2 predominated, similar to children not receiving transplants during the same time period. Three of the patients with hepatitis are alive and well; two died of liver failure. Adenoviral hepatitis did not recur in the second allograft of a patient who underwent retransplantation for combined rejection and adenoviral hepatitis, and appears, therefore, not to be a contraindication to retransplantation when liver failure ensues.

    View details for Web of Science ID A1987J144500022

    View details for PubMedID 3037128

    View details for PubMedCentralID PMC2964055

  • LIVER REPLACEMENT AFTER MASSIVE HEPATIC-TRAUMA JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE Esquivel, C. O., Bernardos, A., Makowka, L., Iwatsuki, S., Gordon, R. D., Starzl, T. E. 1987; 27 (7): 800-802

    Abstract

    Two patients sustained massive hepatic injuries from blunt trauma in motor vehicle accidents. At the time of operation, nonreconstructable injuries to the porta hepatis were found in addition to destruction of the right lobe. Life-threatening hemorrhage was controlled, but both patients were left with nonfunctional or inadequate hepatic remnants. Liver transplantation was performed. Both patients recovered after liver replacement. One died 7 weeks later of cytomegalovirus infection. The other recipient is well 16 months later. Liver transplantation is a reasonable option in patients with lethal hepatic injuries or unreconstructable injuries to the porta hepatis.

    View details for Web of Science ID A1987J509700020

    View details for PubMedID 3302281

    View details for PubMedCentralID PMC3091379

  • ORTHOTOPIC LIVER-TRANSPLANTATION FOR ACUTE AND SUBACUTE HEPATIC-FAILURE IN ADULTS HEPATOLOGY Peleman, R. R., GAVALER, J. S., VANTHIEL, D. H., Esquivel, C., Gordon, R., Iwatsuki, S., Starzl, T. E. 1987; 7 (3): 484-489

    Abstract

    The role of liver transplantation in 29 patients with fulminant and subacute hepatic failure due to a variety of different causes was examined by comparing the outcome and a variety of "hospitalization" variables. Transplanted patients (n = 13) were more likely to survive (p less than 0.05), were younger (p less than 0.05) and spent more time in the hospital (p less than 0.025) than did those who were not transplanted (n = 16). Despite spending a much longer time in the hospital, transplanted patients spent less time in the intensive care unit (p less than 0.05) in coma (p less than 0.01) and on a respirator (p less than 0.01) than did those not transplanted. Most importantly, the survival rate for transplanted patients was significantly improved (p less than 0.05) as compared to those not transplanted. We conclude that liver transplantation can be applied successfully to the difficult clinical problem of fulminant and subacute hepatic failure.

    View details for Web of Science ID A1987H406200011

    View details for PubMedID 3552924

    View details for PubMedCentralID PMC3032406

  • LIVER-TRANSPLANTATION IN PATIENTS WITH PATENT SPLENORENAL SHUNTS SURGERY Esquivel, C. O., Klintmalm, G., Iwatsuki, S., MAKOWSKA, L., Gordon, R. D., Tzakis, A., Starzl, T. E. 1987; 101 (4): 430-432

    Abstract

    Patent distal splenorenal shunts (Warren shunt) have been reported to cause decreases in the portal perfusion pressure and the total hepatic blood flow. Such hemodynamic alterations could have adverse effects on the transplanted liver. The experience with hepatic replacement in four patients with patent Warren shunts is reported. Operative findings were phlebosclerotic portal veins of small size and diminished portal blood flows. Hepatofugal collateral channels created by the construction of the Warren shunt were eliminated by division of the shunt and splenectomy in three patients and splenectomy alone in the other. All patients recovered; thus the presence of a patent Warren shunt should not be a contraindication for hepatic transplantation.

    View details for Web of Science ID A1987G781100008

    View details for PubMedID 3551166

    View details for PubMedCentralID PMC2974321

  • LIVER-TRANSPLANTATION BEFORE 1 YEAR OF AGE JOURNAL OF PEDIATRICS Esquivel, C. O., Koneru, B., Karrer, F., Todo, S., Iwatsuki, S., Gordon, R. D., Makowka, L., Marsh, W. J., Starzl, T. E. 1987; 110 (4): 545-548

    Abstract

    Since 1981, 20 infants younger than 1 year of age received 26 orthotopic liver transplants. Immunosuppression was with cyclosporine and corticosteroids. Thirteen (65%) of the recipients were discharged from the hospital. To date, 12 (60%) of the 20 recipients are surviving, with follow-up of 1 to 56 months (average 14 months). The 5-year actuarial survival is 53.8%. The allograft liver function in the majority of surviving infants is excellent. The predominant causes of mortality were primary nonfunction of the allograft (three patients) and sepsis (three). Major morbidity was caused by hepatic artery thrombosis (five patients), gastrointestinal complications (six), biliary tract complications (five), and bacterial and viral infections (13). Six patients underwent retransplantation; three of these six survived. Results could be improved by prevention of hepatic artery thrombosis, by decreasing the incidence of sepsis, and by procurement of more and better suited pediatric donors.

    View details for Web of Science ID A1987G751100007

    View details for PubMedID 3550022

    View details for PubMedCentralID PMC2965445

  • IMPACT OF ORTHOCLONE-OKT3 ON LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Fung, J. J., Markus, B. H., Gordon, R. D., Esquivel, C. O., Makowka, L., Tzakis, A., Starzl, T. E. 1987; 19 (2): 37-44

    View details for Web of Science ID A1987G784800007

    View details for PubMedID 3105139

    View details for PubMedCentralID PMC2943668

  • COMPLICATIONS OF VENOUS RECONSTRUCTION IN HUMAN ORTHOTOPIC LIVER-TRANSPLANTATION ANNALS OF SURGERY Lerut, J., Tzakis, A. G., Bron, K., Gordon, R. D., Iwatsuki, S., Esquivel, C. O., Makowka, L., Todo, S., Starzl, T. E. 1987; 205 (4): 404-414

    Abstract

    In 313 consecutive recipients of 393 orthotopic liver grafts, there were 51 (16.3%) and nine (2.9%) patients who had pre-existing portal vein and inferior vena cava abnormalities, respectively. These abnormalities required adjustments in the transplant operation and were a source of morbidity and mortality. The incidence of thrombosis of the reconstructed portal vein was 1.8%. Only three (0.8%) vena caval thromboses were seen after 393 liver replacements. Venous stenoses or disruptions were rare. Six women with the Budd-Chiari syndrome had liver replacement. Although this disorder is a veno-occlusive disease, five of the recipients achieved prolonged survival, only one had recurrence of disease, and three are alive after 2-6 years.

    View details for Web of Science ID A1987G695700011

    View details for PubMedID 3551857

    View details for PubMedCentralID PMC1492747

  • CLINICAL CONSIDERATIONS IN ORTHOTOPIC LIVER-TRANSPLANTATION RADIOLOGIC CLINICS OF NORTH AMERICA Tzakis, A. G., Gordon, R. D., Makowka, L., Esquivel, C. O., Todo, S., Iwatsuki, S., Starzl, T. E. 1987; 25 (2): 289-297

    Abstract

    Progress in immunosuppression, surgical techniques, and perioperative care has promoted orthotopic liver transplantation from an experimental procedure to an accepted clinical treatment. Orthotopic liver transplantation, in turn, has changed the treatment of terminal liver disease from care that is largely treatment of symptoms and support to cure, but at the price of major surgery and life-long immunosuppression. This article reviews the current status of liver transplantation as practiced at the University of Pittsburgh.

    View details for Web of Science ID A1987G568700007

    View details for PubMedID 3547476

    View details for PubMedCentralID PMC2965559

  • HEPATIC-ARTERY IN LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Todo, S., Makowka, L., Tzakis, A. G., Marsh, J. W., Karrer, F. M., ARMANY, M., Miller, C., TALLENT, M. B., Esquivel, C. O., Gordon, R. D., Iwatsuki, S., Starzl, T. E. 1987; 19 (1): 2406-2411

    View details for Web of Science ID A1987G101500207

    View details for PubMedID 3547931

    View details for PubMedCentralID PMC2911136

  • OKT3 IN THE REVERSAL OF ACUTE HEPATIC ALLOGRAFT-REJECTION TRANSPLANTATION PROCEEDINGS Esquivel, C. O., Fung, J. J., Markus, B., Iwatsuki, S., Gordon, R. D., Makowka, L., Marsh, J. W., Tzakis, A. G., Todo, S., Starzl, T. E. 1987; 19 (1): 2443-2446

    Abstract

    OKT3 was an effective immunosuppressant agent in patients with acute cell-mediated allograft rejection that had not responded to initial steroid therapy. OKT3 was also valuable for treating patients with early hepatic graft dysfunction caused by other factors than rejection. In such recipients, the doses of CyA can be greatly reduced, allowing recovery of frequently damaged kidneys while maintaining effective immunosuppression.

    View details for Web of Science ID A1987G101500220

    View details for PubMedID 3103297

    View details for PubMedCentralID PMC2904687

  • ANALYSIS OF DONOR CRITERIA FOR THE PREDICTION OF OUTCOME IN CLINICAL LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Makowka, L., Gordon, R. D., Todo, S., Ohkohchi, N., Marsh, J. W., Tzakis, A. G., Yokoi, H., Ligush, J., Esquivel, C. O., Satake, M., Iwatsuki, S., Starzl, T. E. 1987; 19 (1): 2378-2382

    Abstract

    The results of 219 orthotopic human liver transplants performed during 1985 at the University of Pittsburgh were reviewed to determine whether donor parameters could be used to predict the quality of early graft function. Multivariate discriminant analysis demonstrated that traditional parameters of donor assessment are unreliable predictors of poor graft function. Furthermore, 56% of the donors considered poor by conservative selection criteria produced livers with good early posttransplant function. Survival of recipients of primary allografts from donors rated poor was no different than survival of recipients of allografts from donors rated good.

    View details for Web of Science ID A1987G101500197

    View details for PubMedID 3103296

    View details for PubMedCentralID PMC2903845

  • LATE MORTALITY AND MORBIDITY AFTER LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Iwatsuki, S., Starzl, T. E., Gordon, R. D., Esquivel, C. O., Todo, S., Tzakis, A. G., Makowka, L., Marsh, J. W., Miller, C. M. 1987; 19 (1): 2373-2377

    View details for Web of Science ID A1987G101500196

    View details for PubMedID 3547930

    View details for PubMedCentralID PMC2911151

  • BILIARY-TRACT COMPLICATIONS IN HUMAN ORTHOTOPIC LIVER-TRANSPLANTATION TRANSPLANTATION Lerut, J., Gordon, R. D., Iwatsuki, S., Esquivel, C. O., Todo, S., Tzakis, A., Starzl, T. E. 1987; 43 (1): 47-51

    Abstract

    The results of 393 consecutive orthotopic liver transplants in 313 patients were reviewed to determine the incidence of primary biliary tract complications. There were 52 biliary tract complications in 393 grafts (13.2%), and 5 directly related deaths. Choledochojejunostomy over an internal stent to a Roux-en-Y limb of proximal jejunum (RYCJ-S) was the most frequently used technique (175 cases) and the most successful with only 9 technical failures (5.2%). Choledochocholedochostomy over a T tube (CC-T) was used in 159 cases and was successful in all but 20 cases (12.6%). Other methods of reconstruction were associated with high failure rates or technical complexity that do not justify their use. Biliary leak and obstruction were the most common complications. Leakage after CC-T at the T tube exit site was usually directly repaired, but anastomotic leakage required conversion to RYCJ-S. Obstruction may be relieved by percutaneous balloon dilatation but definitive treatment also usually required conversion to RYCJ-S. The most common complication after RYCJ-S is functional obstruction by a retained stent, which has a low morbidity but may necessitate surgical removal. Anastomotic leaks, which occurred in 2 cases, were successfully managed by revision of the choledochojejunostomy.

    View details for Web of Science ID A1987F645400011

    View details for PubMedID 3541321

    View details for PubMedCentralID PMC2952476

  • MONOCLONAL-ANTIBODY THERAPY WITH CICLOSPORIN AND STEROIDS IN NONMATCHED CADAVERIC RENAL-TRANSPLANTS NEPHRON Gordon, R. D., Starzl, T. E., Fung, J. J., Iwatsuki, S., Esquivel, C. O., Tzakis, A., Todo, S. 1987; 46: 56-59

    Abstract

    Thirty-six ciclosporin-prednisone-treated recipients of nonmatched cadaver renal allografts were given a course of Orthoclone OKT3 monoclonal antibody for steroid-resistant cell-mediated rejection. Although side effects were common, only 2 patients had to be withdrawn from therapy and there were no deaths related to therapy. Twenty-three (63.9%) allografts were rescued with OKT3 therapy and 21 (58.3%) of the grafts have continued to function well. We conclude that OKT3 is an effective agent for the treatment of steroid-resistant cell-mediated rejection and that rebound rejection can be prevented in most patients if adequate therapy with ciclosporin-prednisone is maintained.

    View details for Web of Science ID A1987J437000009

    View details for PubMedID 3306426

    View details for PubMedCentralID PMC3005204

  • USE OF OKT3 WITH CICLOSPORIN AND STEROIDS FOR REVERSAL OF ACUTE KIDNEY AND LIVER ALLOGRAFT-REJECTION NEPHRON Fung, J. J., Demetris, A. J., Porter, K. A., Iwatsuki, S., Gordon, R. D., Esquivel, C. O., Jaffe, R., Tzakis, A., Shaw, B. W., Starzl, T. E. 1987; 46: 19-33

    Abstract

    OKT3 monoclonal antibody therapy was added to preexisting baseline immunosuppressive treatment with ciclosporin and steroids to treat rejection in 52 recipients of cadaveric livers and 10 recipients of cadaveric kidneys. Rejection was controlled in 75% of patients treated, often after high-dose steroid therapy had failed. Rejection recurred during the 17-month follow-up period, after completion of OKT3, in only 25% of the patients who had responded. The safety and effectiveness of this monoclonal therapy, added to ciclosporin and steroids, has been established in this study.

    View details for Web of Science ID A1987J437000004

    View details for PubMedID 3306422

    View details for PubMedCentralID PMC2994552

  • The Denver-Pittsburgh liver transplant series. Clinical transplants Gordon, R. D., Iwatsuki, S., Tzakis, A. G., Esquivel, C. O., Todo, S., Makowka, L., Starzl, T. E. 1987: 43-49

    Abstract

    Liver transplantation is now the preferred treatment for many diseases leading to end-stage liver disease. Transplantation for cancer has been disappointing and there is a significant recurrence rate after transplantation in hepatitis B-virus carriers. Additional strategies will have to be developed if we are to improve the results of transplantation for these patients. The role of immunological factors in liver transplantation continues to reveal significant differences from their role in renal transplantation and will continue to be an interesting area of study for years to come.

    View details for PubMedID 3154443

    View details for PubMedCentralID PMC2982704

  • CYCLOSPORINE TROUGH CONCENTRATION MONITORING IN LIVER-TRANSPLANT PATIENTS TRANSPLANTATION PROCEEDINGS Burckart, G. J., Ptachcinski, R. J., Venkataramanan, R., Iwatsuki, S., Esquivel, C., VANTHIEL, D. H., Starzl, T. E. 1986; 18 (6): 188-193

    Abstract

    Trough blood or plasma concentration measurements of CsA must be carefully interpreted in OLT patients in relation to hepatic function, sample timing, assay specificity, and concurrent drug therapy. The RIA:HPLC ratio of blood or plasma measurements will vary with the patient's liver function, the time of blood sampling in reference to the time of drug administration, the absolute CsA concentration, and concurrent use of drugs that may alter the metabolism of CsA. The RIA assay should be used in conjunction with HPLC for trough blood or plasma measurement during the first postoperative weeks, during periods of changing hepatic function, and during changing drug regimens. In the future, the specific measurement of active or toxic metabolites of CsA should improve trough CsA concentration monitoring in OLT patients.

    View details for Web of Science ID A1986F245100026

    View details for PubMedID 3538569

    View details for PubMedCentralID PMC2999908

  • EXCRETION OF CYCLOSPORINE AND ITS METABOLITES IN HUMAN BILE TRANSPLANTATION PROCEEDINGS Burckart, G. J., Starzl, T. E., Venkataramanan, R., Hashim, H., Wong, L., Wang, P., Makowka, L., Zeevi, A., Ptachcinski, R. J., Knapp, J. E., Iwatsuki, S., Esquivel, C., Sanghvi, A., VANTHIEL, D. H. 1986; 18 (6): 46-49

    Abstract

    Quantitative and qualitative studies of cyclosporine and its metabolites were performed on human bile from liver transplant and liver disease patients. The concentration of CsA in bile is higher in patients with normal liver function than in those with poor liver function but in neither case could account for more than 2% of an absorbed dose of CsA. Although concentrations of CsA plus metabolites in bile measured by RIA were 18 to 36 times higher than HPLC concentrations, they accounted for less than 50% of an absorbed CsA dose. By means of mass spectrometry and HPLC retention times of known metabolites, peaks equivalent to the previously isolated CsA M8, M13, M17, M1, M18, and M21 of Maurer et al were found in the ether extracts of bile. Future studies should not only concentrate on the pharmacologic and toxicologic effects of the metabolites but should also accurately quantitate these compounds in blood, plasma, urine, and bile.

    View details for Web of Science ID A1986F245100008

    View details for PubMedID 3538573

    View details for PubMedCentralID PMC2903880

  • LIVER RESECTION FOR METASTATIC COLORECTAL-CANCER SURGERY Iwatsuki, S., Esquivel, C. O., Gordon, R. D., Starzl, T. E. 1986; 100 (4): 804-810

    Abstract

    From 1975 to 1985, 60 patients with isolated hepatic metastases from colorectal cancer were treated by 17 right trisegmentectomies, five left trisegmentectomies, 20 right lobectomies, seven left lobectomies, eight left lateral segmentectomies, and three nonanatomic wedge resections. The 1-month operative mortality rate was 0%. One- to 5-year actuarial survival rates of the 60 patients were 95%, 72%, 53%, 45%, and 45%, respectively. The survival rate after liver resection was the same when solitary lesions were compared with multiple lesions. However, none of the seven patients with four or more lesions survived 3 years. The interval after colorectal resection did not influence the survival rate after liver resection, and survival rates did not differ statistically when synchronous metastases were compared with metachronous tumors. A significant survival advantage of patients with Dukes' B primary lesions was noted when compared with Dukes' C and D lesions. The pattern of tumor recurrence after liver resection appeared to be systemic rather than hepatic. The patients who received systemic chemotherapy before clinical evidence of tumor recurrence after liver resection survived longer than those who did not.

    View details for Web of Science ID A1986E313900029

    View details for PubMedID 3764701

    View details for PubMedCentralID PMC2975979

  • THE ANTIBODY CROSS-MATCH IN LIVER-TRANSPLANTATION SURGERY Gordon, R. D., Fung, J. J., Markus, B., Fox, I., Iwatsuki, S., Esquivel, C. O., Tzakis, A., Todo, S., Starzl, T. E. 1986; 100 (4): 705-715

    Abstract

    Six hundred sixty-seven first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of recipient panel-reactive antibody (PRA) and donor-recipient antibody crossmatch on 2-year patient and liver allograft survival rates. Neither a high panel-reactive antibody nor a positive crossmatch for donor-specific preformed antibody was associated with decreased patient or liver allograft survival for primary grafts or retransplants. Two patients have been given kidney transplants immediately after a liver allograft from a donor with whom each patient had an initial strongly positive donor-specific antibody crossmatch. The liver apparently removed or neutralized circulating anti-donor antibody, since the renal allografts functioned promptly and did not experience hyperacute rejection.

    View details for Web of Science ID A1986E313900017

    View details for PubMedID 3532391

    View details for PubMedCentralID PMC3095820

  • LIVER-TRANSPLANTATION ACROSS ABO BLOOD-GROUPS SURGERY Gordon, R. D., Iwatsuki, S., Esquivel, C. O., Tzakis, A., Todo, S., Starzl, T. E. 1986; 100 (2): 342-348

    Abstract

    Six hundred seventy-one first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of donor-recipient mismatches or incompatibilities for the ABO blood groups on graft survival. A significant advantage for ABO donor-recipient identity was found, especially in adults and for first grafts. However, a surprisingly large number of ABO incompatible grafts were successful. We recommend that nonidentical or incompatible grafts be limited to patients such as small children for whom the supply of available donors is severely limited or for patients in urgent need of transplantation or retransplantation.

    View details for Web of Science ID A1986D485300029

    View details for PubMedID 3526607

  • INDICATIONS FOR LIVER-TRANSPLANTATION IN THE CYCLOSPORINE ERA SURGICAL CLINICS OF NORTH AMERICA Gordon, R. D., Shaw, B. W., Iwatsuki, S., Esquivel, C. O., Starzl, T. E. 1986; 66 (3): 541-556

    Abstract

    One hundred seventy orthotopic liver transplants were performed under conventional immunosuppression with azathioprine and steroids with 1- and 5-year survivals of 32.9 per cent and 20.0 per cent, respectively. Since the introduction of cyclosporine-prednisone therapy in March 1980, 313 primary orthotopic liver transplants have been performed. Actuarial survivals at 1 and 5 years have improved to 69.7 per cent and 62.8 per cent, respectively. Biliary atresia is now the most common indication for liver replacement. In adults, primary biliary cirrhosis and sclerosing cholangitis have become more common indications for transplantation, and alcoholic cirrhosis and primary liver malignancy as indications have declined. Early enthusiasm for liver transplantation in patients with hepatic cancer has been tempered by the finding that recurrence is both common and rapid. An increasing number of patients with inborn errors of metabolism originating in the liver are receiving transplants, including patients with Wilson's disease, tyrosinemia, alpha-1-antitrypsin deficiency, glycogen storage disease, familial hypercholesterolemia, and hemochromatosis. Survival in this group of patients has been excellent (74.4 per cent at 1 and 5 years). A hemophiliac who received a transplant for postnecrotic cirrhosis has survived and may have been cured of his hemophilia. About 20 per cent of patients require retransplantation for rejection, technical failure, or primary graft failure. Only four of the patients receiving retransplants under conventional immunosuppression survived beyond 6 months, and all died within 14 months of retransplantation. Sixty-eight patients have received retransplants under cyclosporine-prednisone. Thirty-one patients are surviving, all for at least 1 year. Six of the twelve patients requiring a third transplant are alive 2 to 3 years after the primary operation. An aggressive approach to retransplantation in the patient with a failed graft is justified.

    View details for Web of Science ID A1986C707400012

    View details for PubMedID 3520895

  • LIVER-TRANSPLANTATION IN THE CICLOSPORIN ERA PROGRESS IN ALLERGY Starzl, T. E., Iwatsuki, S., Shaw, B. W., Gordon, R. D., Esquivel, C. 1986; 38: 366-394

    View details for Web of Science ID A1986D111900021

    View details for PubMedID 3088582

    View details for PubMedCentralID PMC2972621

  • Nephrotoxicity of cyclosporine in liver transplantation. Transplantation proceedings Iwatsuki, S., Esquivel, C. O., Klintmalm, G. B., Gordon, R. D., Shaw, B. W., Starzl, T. E. 1985; 17 (4): 191-195

    View details for PubMedID 3895661

    View details for PubMedCentralID PMC2921837

  • REFINEMENTS IN THE SURGICAL TECHNIQUE OF LIVER-TRANSPLANTATION SEMINARS IN LIVER DISEASE Starzl, T. E., Iwatsuki, S., Esquivel, C. O., Todo, S., Kam, I., Lynch, S., Gordon, R. D., Shaw, B. W. 1985; 5 (4): 349-356

    View details for Web of Science ID A1985AVM4600008

    View details for PubMedID 3909429

    View details for PubMedCentralID PMC3075625

  • IMMUNOSUPPRESSION AND OTHER NONSURGICAL FACTORS IN THE IMPROVED RESULTS OF LIVER-TRANSPLANTATION SEMINARS IN LIVER DISEASE Starzl, T. E., Iwatsuki, S., Shaw, B. W., Gordon, R. D., Esquivel, C. O. 1985; 5 (4): 334-343

    Abstract

    During the last 5 years, liver transplantation has become a service as opposed to an experimental operation. The most important factor in making this possible has been the introduction of cyclosporine-steroid therapy. At the same time, liver transplantation has been made more practical by improvements in diagnosing and managing other causes of postoperative hepatic dysfunction. Tissue typing and matching have played no role in improving the results of liver transplantation. With the demonstration that performed antibody states are irrelevant, even avoidance of positive cross-matches caused by cytotoxic antibodies and observance of ABO blood group barriers have become unnecessary if the recipient's needs are great. With the exceptions of malignancy and cirrhosis, the nature of the underlying hepatic disease has not profoundly influenced the results. Retransplantation has played an important role in improving survival, although the costs of retransplantation have been extremely high.

    View details for Web of Science ID A1985AVM4600006

    View details for PubMedID 3909427

    View details for PubMedCentralID PMC2975458

  • FACTORS IN THE DEVELOPMENT OF LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Starzl, T. E., Iwatsuki, S., Shaw, B. W., Gordon, R. D., Esquivel, C., Todo, S., Kam, I., Lynch, S. 1985; 17: 107-119
  • LIVER REJECTION AND ITS DIFFERENTIATION FROM OTHER CAUSES OF GRAFT DYSFUNCTION SEMINARS IN LIVER DISEASE Esquivel, C. O., Jaffe, R., Gordon, R. D., Iwatsuki, S., Shaw, B. W., Starzl, T. E. 1985; 5 (4): 369-374

    Abstract

    Numerous causes can lead to hepatic dysfunction following orthotopic liver transplantation. The most common cause is rejection, which is usually nonpreventable. The clinical presentation, time of onset, and even treatment are variable. Other causes, such as perioperative ischemic injury, vascular thrombosis, and complications of bile duct reconstruction may be preventable with good surgical technique. Infections can also be minimized by careful adjustment of immunotherapy, avoidance overimmunosuppression, and the judicious use of antibiotics. Hepatic dysfunction following orthotopic liver transplantation requires rapid assessment and proper treatment in order to prevent serious and possibly fatal complications.

    View details for Web of Science ID A1985AVM4600010

    View details for PubMedID 3001943

  • LIVER-TRANSPLANTATION FOR FULMINANT HEPATIC-FAILURE SEMINARS IN LIVER DISEASE Iwatsuki, S., Esquivel, C. O., Gordon, R. D., Shaw, B. W., Starzl, T. E., SHADE, R. R., VANTHIEL, D. H. 1985; 5 (4): 325-328

    View details for Web of Science ID A1985AVM4600004

    View details for PubMedID 3909425

    View details for PubMedCentralID PMC2975970

  • POSTOPERATIVE SMALL BOWEL INTUSSUSCEPTION WESTERN JOURNAL OF MEDICINE Esquivel, C. O., Bishop, P. J., Marr, C., Schwartz, M. Z. 1985; 143 (1): 108-110

    View details for Web of Science ID A1985AMK8500031

    View details for PubMedID 4036108

    View details for PubMedCentralID PMC1306252

  • NEPHROTOXICITY OF CYCLOSPORINE IN LIVER-TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Iwatsuki, S., Esquivel, C. O., Klintmalm, G. B., Gordon, R. D., Shaw, B. W., Starzl, T. E. 1984; 17 (4): 191-195