Dr. Kirchner completed her medical school, surgical residency and multi-organ transplant fellowship in adult and pediatric liver, pancreas, kidney transplantation and total pancreatectomy with islet auto-transplantation at the University of Minnesota. She underwent further training in living donor liver transplantation and hepatobiliary surgery at the Asan Medical Center, Seoul, South Korea. Her clinical practice involves living and deceased donor liver and kidney transplantation in adult and pediatric patients as well as total pancreatectomy with islet auto-transplantation for patients with chronic and acute recurrent pancreatitis. She currently serves as Surgical Director of the Islet Cell Auto-Transplant at Stanford Children’s and Associate Director of the Living Donor Liver Transplant Program at the Division of Abdominal Transplantation. Dr. Kirchner’s research focuses on the biology of aging, cellular and solid organ transplantation. Her specific interests are in auto-islet transplantation, iPSC-derived hepatocyte therapies and liver regeneration. Dr. Kirchner's research on the impact of donor age on generation of iPSC-derived hepatocyte-like cells is supported by the NIA K08 Faculty Development Award. She is an active member of the American Society of Transplant Surgeons and the International Liver Transplantation Society.
- Adult and Pediatric - Living and Deceased Donor Liver Transplantation
- Living Donor Hepatectomy
- Total Pancreatectomy with Islet Auto-Transplantation
- Adult and Pediatric Kidney Transplantation
- Living Donor Nephrectomy
- Hepatobiliary Surgery
- General Surgery
Associate Professor - University Medical Line, Surgery - Abdominal Transplantation
Associate Professor - University Medical Line (By courtesy), Pediatrics
Member, Stanford Maternal and Child Health Research Institute (2022 - Present)
Member, Stanford Diabetes Research Center (2022 - Present)
Associate Director of the Living Donor Liver Transplant Program, Stanford Healthcare (2022 - Present)
Surgical Director of the Islet Cell Auto-Transplant, Lucile Packard Children’s Hospital Stanford (2022 - Present)
Fellowship, (2016) Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, Living Donor Liver Transplantation and Hepatobiliary Surgery (2016)
Fellowship, (2013-2015) University of Minnesota Medical School, Minneapolis, MN, Multi-Organ Transplant Fellowship (liver, kidney, pancreas, total pancreatectomy islet auto-transplantation) (2015)
Board Certification: American Board of Surgery, General Surgery (2013)
Residencey, (2006-2013) University of Minnesota Medical School, Minneapolis, MN, General Surgery (2013)
Doctor of Medicine, (2002-2006) University of Minnesota Medical School, Minneapolis, MN, Medicine (2006)
A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment.
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
In total pancreatectomy with islet auto-transplantation, successful diabetes outcomes are limited by islet loss from the instant blood mediated inflammatory response. We hypothesized that blockade of the inflammatory response with either etanercept or alpha-1-antitrypsin would improve islet function and insulin independence.We randomized 43 participants to receive A1AT (90 mg/kg x 6 doses, n = 13), or etanercept (50 mg then 25 mg x 5 doses, n = 14), or standard care (n = 16), aiming to reduce detrimental effects of innate inflammation on early islet survival. Islet graft function was assessed using mixed meal tolerance testing, intravenous glucose tolerance testing, glucose-potentiated arginine-induced insulin secretion studies, HbA1c, and insulin dose 3 months and 1 year post-TPIAT.We observed the most robust acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) at 3 months after TPIAT in the etanercept-treated group (p ≤ 0.02), but no differences in other efficacy measures. The groups did not differ overall at 1 year but when adjusted by sex, there was a trend towards a sex-specific treatment effect in females (AIRglu p = 0.05, ACRglu p = 0.06), with insulin secretion measures highest in A1AT-treated females.Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment.This study was performed under an Investigational New Drug Application (IND #119828) from the Food and Drug Administration and was registered on clinicaltrials.gov (NCT#02713997).
View details for DOI 10.1016/j.pan.2022.11.006
View details for PubMedID 36443174
Orchialgia After Living Donor Nephrectomy: An Underreported Entity
2022; 8 (11): e1383
Laparoscopic donor nephrectomy (LDN) offers advantages to the donor. The reported incidence of testicular pain after LDN varies in the literature ranging from 3% to 55%.A survey was sent to 322 male LDN patients who donated from February 5, 2009, to February 5, 2019. The survey assessed if the donor had testicular pain or saw an additional medical professional after donation.Of the 322 surveyed, 147 (46%) responses were received. Of those who had a left nephrectomy, 39% had testicular pain; 23.8% of those patients had testicular swelling in addition. Of those who had pain, laterality of kidney donated did not impact if the patient had pain, pain onset, pain level, or pain duration. Of those who donated their right kidney, 35% had testicular pain, and 16.7% of those patients reported testicular swelling in addition. Twenty-seven symptomatic patients sought additional medical care for the testicular symptoms postdonation. Seven (25%) had hydroceles, 2 (7%) had testicular cysts, 1 had a urinary tract infection, and 16 (59%) had reassurance or no additional procedures provided.Our results suggest that orchialgia is not as uncommon as previously thought and may be one of the most common minor complications experienced by male donors.
View details for DOI 10.1097/TXD.0000000000001383
View details for Web of Science ID 000870824800003
View details for PubMedID 36299443
View details for PubMedCentralID PMC9592523
EXPLANT-BASED ANALYSIS OF RESPONSE TO LOCOREGIONAL THERAPIES IN PATIENTS WITH UNIFOCAL HEPATOCELLULAR CARCINOMA: A MULTICENTER STUDY
WILEY. 2022: S1435-S1436
View details for Web of Science ID 000870796604306
Has the Risk of Liver Re-Transplantation Improved Over the Two Decades? A UNOS Data Analysis
LIPPINCOTT WILLIAMS & WILKINS. 2022: S294
View details for Web of Science ID 000889117000441
COVID vaccination among liver transplant recipients: A EASL-ESOT/ELITA-ILTS multi society survey
ELSEVIER. 2022: S807-S808
View details for Web of Science ID 000826275104160
Low-dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
To investigate the effect of low-dose aspirin in primary adult liver transplantation LT on acute cellular rejection ACR as well as arterial patency rates.The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis HAT, although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after liver transplantation has a protective effect against ACR.This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up.In this cohort of 2,365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1,436 recipients 61%. One-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group HR 0.77, 95% CI 0.63-0.94, p=0.01. One-year primary arterial patency rates were 99% in the aspirin and 96% in the no-aspirin group with a HR of 0.23 95% CI: 0.13-0.40; p<0.001.Low-dose aspirin was associated with a lower risk of ACR and HAT after LT, especially in the first vulnerable year after transplantation. Therefore, low-dose aspirin use after primary LT should be evaluated to protect the liver graft from ACR and to maintain arterial patency.
View details for DOI 10.1002/lt.26534
View details for PubMedID 35735232
Proceedings of the 26th Annual Virtual Congress of the International Liver Transplantation Society.
After a 1-y absence due to the coronavirus disease 2019 pandemic, the 26th Annual Congress of the International Liver Transplantation Society was held from May 15 to 18, 2021, in a virtual format. Clinicians and researchers from all over the world came together to share their knowledge on all the aspects of liver transplantation (LT). Apart from a focus on LT in times of coronavirus disease 2019, featured topics of this year's conference included infectious diseases in LT, living donation, machine perfusion, oncology, predictive scoring systems and updates in anesthesia/critical care, immunology, radiology, pathology, and pediatrics. This report presents highlights from invited lectures and a review of the select abstracts. The aim of this report, generated by the Vanguard Committee of International Liver Transplantation Society, is to provide a summary of the most recent developments in clinical practice and research in LT.
View details for DOI 10.1097/TP.0000000000004183
View details for PubMedID 35676871
What is the optimal management of thromboprophylaxis after liver transplantation regarding prevention of bleeding, hepatic artery or portal vein thrombosis? A systematic review of the literature and expert panel recommendations.
A key tenet of clinical management of patients post liver transplantation (LT) is the prevention of thrombotic and bleeding complications. This systematic review investigated the optimal management of thromboprophylaxis after LT regarding portal vein thrombosis (PVT) or hepatic artery thrombosis (HAT) and prevention of bleeding.Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Seven databases were used to conduct extensive literature searches focusing on the use of anticoagulation in LT and its impact on the following outcomes: PVT, HAT, and bleeding. (CRD42021244288) RESULTS: Of the 2,478 articles/abstracts screened, 16 studies were included in the final review. All articles were critically appraised by a panel of independent reviewers. There was wide variation regarding the anticoagulation protocols used. Thromboprophylaxis with therapeutic doses of heparin/Vitamin K antagonist combination did not decrease the risk of de novo or the recurrence of PVT but was associated with an increased risk of bleeding in some studies. Only the use of aspirin resulted in a small but significant decrease in the incidence of HAT post-LT, yet it did not increase the risk of bleeding.Based on existing data and expert opinion, thromboprophylaxis at therapeutic or prophylactic dose is not recommended for prevention of de novo PVT following LT in patients not at high risk. Aspirin should be considered as the standard of care following LT to prevent HAT. Thromboprophylaxis should be strongly considered in recipients at risk of HAT and PVT following LT. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/ctr.14629
View details for PubMedID 35240723
Global impact of the first wave of COVID-19 on liver transplant centers: A multi-society survey (EASL-ESOT/ELITA-ILTS)
JOURNAL OF HEPATOLOGY
2022; 76 (2): 364-370
The global impact of SARS-CoV-2 on liver transplantation (LT) practices across the world is unknown. The goal of this survey was to assess the impact of the pandemic on global LT practices.A prospective web-based survey (available online from 7th September 2020 to 31st December 2020) was proposed to the active members of the EASL-ESOT/ELITA-ILTS in the Americas (including North, Central, and South America) (R1), Europe (R2), and the rest of the world (R3). The survey comprised 4 parts concerning transplant processes, therapy, living donors, and organ procurement.Of the 470 transplant centers reached, 128 answered each part of the survey, 29 centers (23%), 64 centers (50%), and 35 centers (27%) from R1, R2, and R3, respectively. When we compared the practices during the first 6 months of the pandemic in 2020 with those a year earlier in 2019, statistically significant differences were found in the number of patients added to the waiting list (WL), WL mortality, and the number of LTs performed. At the regional level, we found that in R2 the number of LTs was significantly higher in 2019 (p <0.01), while R3 had more patients listed, higher WL mortality, and more LTs performed before the pandemic. Countries severely affected by the pandemic ("hit" countries) had a lower number of WL patients (p = 0.009) and LTs (p = 0.002) during the pandemic. Interestingly, WL mortality was still higher in the "non-hit" countries in 2020 compared to 2019 (p = 0.022).The first wave of the pandemic differentially impacted LT practices across the world, especially with detrimental effects on the "hit" countries. Modifications to the policies of recipient and donor selection, organ retrieval, and postoperative recipient management were adopted at a regional or national level.The health emergency caused by the coronavirus pandemic has dramatically changed clinical practice during the pandemic. The first wave of the pandemic impacted liver transplantation differently across the world, with particularly detrimental effects on the countries badly hit by the virus. The resilience of the entire transplant network has enabled continued organ donation and transplantation, ultimately improving the lives of patients with end-stage liver disease.
View details for DOI 10.1016/j.jhep.2021.09.041
View details for Web of Science ID 000752560300014
View details for PubMedID 34653592
View details for PubMedCentralID PMC8511875
HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV
AMERICAN JOURNAL OF TRANSPLANTATION
2022; 22 (3): 853-864
Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.
View details for DOI 10.1111/ajt.16886
View details for Web of Science ID 000722279400001
View details for PubMedID 34741800
Portal Vein Thrombosis May Be More Strongly Associated With Islet Infusion Than Extreme Thrombocytosis After Total Pancreatectomy With Islet Autotransplantation
2021; 105 (11): 2499-2506
Total pancreatectomy with islet autotransplantation (TPIAT) involves pancreatectomy, splenectomy, and reinjection of the patient's pancreatic islets into the portal vein. This process triggers a local inflammatory reaction and increase in portal pressure, threatening islet survival and potentially causing portal vein thrombosis. Recent research has highlighted a high frequency of extreme thrombocytosis (platelets ≥1000 × 109/L) after TPIAT, but its cause and association with thrombotic risk remain unclear.This retrospective single-site study of a contemporary cohort of 409 pediatric and adult patients analyzed the frequency of thrombocytosis, risk factors for thrombosis, and antiplatelet and anticoagulation strategies.Of 409 patients, 67% developed extreme thrombocytosis, peaking around postoperative day 16. Extreme thrombocytosis was significantly associated with infused islet volumes. Thromboembolic events occurred in 12.2% of patients, with portal vein thromboses occurring significantly earlier than peripheral thromboses. Portal vein thromboses were associated with infused islet volumes and portal pressures but not platelet counts or other measures. Most thromboembolic events (82.7%) occurred before the postoperative day of maximum platelet count. Only 4 of 27 (14.8%) of portal vein thromboses occurred at platelet counts ≥500 × 109/L. Perioperative heparin was given to all patients. Treatment of reactive thrombocytosis using aspirin in adults and hydroxyurea in children was not associated with significantly decreased thromboembolic risk.These results suggest that post-TPIAT thrombocytosis and portal vein thromboses may be linked to the islet infusion inflammation, not directly to each other, and further reducing this inflammation may reduce thrombosis and thrombocytosis frequencies simultaneously.
View details for DOI 10.1097/TP.0000000000003624
View details for Web of Science ID 000711141800047
View details for PubMedID 33988346
Challenges, highlights, and opportunities in cellular transplantation: A white paper of the current landscape.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
2021; 21 (10): 3225-3238
Although cellular transplantation remains a relatively small field compared to solid organ transplantation, the prospects for advancement in basic science and clinical care remain bountiful. In this review, notable historical events and the current landscape of the field of cellular transplantation are reviewed with an emphasis on islets (allo- and xeno-), hepatocytes (including bioartificial liver), adoptive regulatory immunotherapy, and stem cells (SCs, specifically endogenous organ-specific and mesenchymal). Also, the nascent but rapidly evolving field of three-dimensional bioprinting is highlighted, including its major processing steps and latest achievements. To reach its full potential where cellular transplants are a more viable alternative than solid organ transplants, fundamental change in how the field is regulated and advanced is needed. Greater public and private investment in the development of cellular transplantation is required. Furthermore, consistent with the call of multiple national transplant societies for allo-islet transplants, the oversight of cellular transplants should mirror that of solid organ transplants and not be classified under the unsustainable, outdated model that requires licensing as a drug with the Food and Drug Administration. Cellular transplantation has the potential to bring profound benefit through progress in bioengineering and regenerative medicine, limiting immunosuppression-related toxicity, and providing markedly reduced surgical morbidity.
View details for DOI 10.1111/ajt.16740
View details for PubMedID 34212485
National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States
CLINICAL INFECTIOUS DISEASES
Organ transplantation from donors with HIV to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV+ donors is critical for safety.We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) testing within the HOPE in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262; NCT03500315; NCT03734393). We compared clinical characteristics in HIV+ versus FP donors. We measured CD4+ T cells, HIV viral load (VL), drug resistance mutations (DRMs), co-receptor tropism, and serum antiretroviral therapy (ART) detection using mass spectrometry in HIV+ donors.Between 03/2016-03/2020, 92 donors (58 HIV+, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidney, 46 liver). Each year the number of donors increased. Prevalence of hepatitis B (16% vs. 0%), syphilis (16% vs. 0%), and cytomegalovirus (91% vs. 58%) was higher in HIV+ versus FP donors; hepatitis C viremia was similar (2% vs. 6%). Most HIV+ donors (71%) had known HIV diagnosis, of whom 90% were prescribed ART and 68% had VL<400 copies/mL. Median CD4 count was 194 cells/uL (IQR=77-331); median CD4% was 27.0 (IQR=16.8-36.1). Major HIV DRMs were detected in 42%, including non-nucleoside reverse transcriptase inhibitors (33%), integrase strand transfer inhibitor (INSTI, 4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history.Utilization of HIV+ donor organs is increasing. HIV DRMs are common, yet resistance that would compromise INSTI-based regimens is rare, which is reassuring regarding safety.
View details for DOI 10.1093/cid/ciab743
View details for Web of Science ID 000756574300001
View details for PubMedID 34453519
Mental Health Support in the Transplantation Workforce: What Can We Learn From the COVID-19 Pandemic?
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation
2021; 19 (8): 763-770
Burnout (defined as a state of depersonalization, emotional exhaustion, and a sense of reduced achievement) is a risk to all health care workers. The transplantation workforce not only faces the same challenges but also many others linked to the unique work and setting in which they deliver health care. In the past, the mental health care of the transplantation workforce has been sidelined, rather than prioritized. The coronavirus disease 2019 pandemic has not only compromised the safe delivery of transplant organs worldwide but has magnified the challenges for the transplantation workforce. especially with the high mortality in transplant patients who are infected with SARS-CoV-2. This review addresses the challenges to the mental well-being and psychological health of health care providers, both generally and within the sphere of transplantation, and not only highlights some of the inadequacies but also proposes strategies to establish psychological interventions that could benefit health care professionals within transplantation.
View details for DOI 10.6002/ect.2020.0458
View details for PubMedID 33736587
The Association of Smoking and Alcohol Abuse on Anxiety and Depression in Patients With Recurrent Acute or Chronic Pancreatitis Undergoing Total Pancreatectomy and Islet Autotransplantation A Report From the Prospective Observational Study of TPIAT Cohort
2021; 50 (6): 852-858
Smoking and alcohol use are risk factors for acute and chronic pancreatitis, and their role on anxiety, depression, and opioid use in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT) is unknown.We included adults enrolled in the Prospective Observational Study of TPIAT (POST). Measured variables included smoking (never, former, current) and alcohol abuse or dependency history (yes vs no). Using univariable and multivariable analyses, we investigated the association of smoking and alcohol dependency history with anxiety and depression, opioid use, and postsurgical outcomes.Of 195 adults studied, 25 were current smokers and 77 former smokers, whereas 18 had a history of alcohol dependency (of whom 10 were current smokers). A diagnosis of anxiety was associated with current smoking (P = 0.005), and depression was associated with history of alcohol abuse/dependency (P = 0.0001). However, active symptoms of anxiety and depression at the time of TPIAT were not associated with smoking or alcohol status. Opioid use in the past 14 days was associated with being a former smoker (P = 0.005).Active smoking and alcohol abuse history were associated with a diagnosis of anxiety and depression, respectively; however, at the time of TPIAT, symptom scores suggested that they were being addressed.
View details for DOI 10.1097/MPA.0000000000001850
View details for Web of Science ID 000685052100016
View details for PubMedID 34347725
View details for PubMedCentralID PMC8373657
Circulating miRNA in Patients Undergoing Total Pancreatectomy and Islet Autotransplantation
2021; 30: 963689721999330
Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples (n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p (P = 0.03), hsa-miR-148a-3p (P = 0.04) and hsa-miR-221-3p (P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p (P = 0.04) and hsa-miR-7-5p (P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p (P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p (P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg (r = -0.20, P = 0.02). Also, hsa-miR-200c (r = 0.18, P = 0.03) and hsa-miR-221-3p (r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.
View details for DOI 10.1177/0963689721999330
View details for Web of Science ID 000755655300001
View details for PubMedID 33902338
View details for PubMedCentralID PMC8718159
Metabolic measures before surgery and long-term diabetes outcomes in recipients of total pancreatectomy and islet autotransplantation
AMERICAN JOURNAL OF TRANSPLANTATION
2021; 21 (10): 3411-3420
In this single-center, retrospective cohort study, we aimed to elucidate simple metabolic markers or surrogate indices of β-cell function that best predict long-term insulin independence and goal glycemic HbA1c control (HbA1c ≤ 6.5%) after total pancreatectomy with islet autotransplantation (TP-IAT). Patients who underwent TP-IAT (n = 371) were reviewed for metabolic measures before TP-IAT and for insulin independence and glycemic control at 1, 3, and 5 years after TP-IAT. Insulin independence and goal glycemic control were achieved in 33% and 68% at 1 year, respectively. Although the groups who were insulin independent and dependent overlap substantially on baseline measures, an individual who has abnormal glycemia (prediabetes HbA1c or fasting glucose) or estimated IEQs/kg < 2500 has a very high likelihood of remaining insulin dependent after surgery. In multivariate logistic regression modelling, metabolic measures correctly predicted insulin independence in about 70% of patients at 1, 3, and 5 years after TP-IAT. In conclusion, metabolic testing measures before surgery are highly associated with diabetes outcomes after TP-IAT at a population level and correctly predict outcomes in approximately two out of three patients. These findings may aid in prognostic counseling for chronic pancreatitis patients who are likely to eventually need TP-IAT.
View details for DOI 10.1111/ajt.16573
View details for Web of Science ID 000637417100001
View details for PubMedID 33754431
Safe use of right lobe living donor livers with moderate steatosis in adult-to-adult living donor liver transplantation: a retrospective study
2021; 34 (5): 872-881
Hepatic steatosis (HS) beyond a certain degree can jeopardize living donor (LD) safety, particularly in right lobe (RL) donors, making it a major obstacle for donor pool expansion in adult-to-adult living donor liver transplantation (ALDLT). From July 2004 to June 2016, 58 LDs donated their RLs despite having moderate HS (30%-50% steatosis) determined by intraoperative biopsy at a single center. We performed greedy matching to compare the outcomes of the donors and recipients of this group with those of LDs with no HS. The mean left lobe (LL) HS value in the 58 cases was 20.9 ± 12.4%, which was significantly lower than the mean RL HS value (38.8 ± 6.7%, P < 0.001). The mean ratio of the remnant LL to the total liver volume was 37.8 ± 2.2. No differences were observed in the postoperative liver function and donor and recipient morbidity and mortality rates. The liver regeneration rates in recipients and donors at 1 month, 6 months, and 1 year postoperatively did not differ significantly. The patient and graft survival rates of the recipients showed no differences. The use of well-selected RL grafts with moderate steatosis does not impair graft function, recipient outcomes, or donor safety.
View details for DOI 10.1111/tri.13859
View details for Web of Science ID 000634850300001
View details for PubMedID 33660330
Body Composition is Associated With Islet Function After Pancreatectomy and Islet Autotransplantation for Pancreatitis
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2021; 106 (2): E496-E506
Body composition in total pancreatectomy with islet autotransplantation (TPIAT) has never been studied.Determine whether presurgical body composition is associated with islet function and insulin sensitivity after TPIAT.In 88 adults undergoing TPIAT (median age 41.0 years, IQR 32.8-48.0), beta-cell function and insulin sensitivity were assessed using mixed meal tolerance test and frequent sample intravenous glucose tolerance test before surgery and 12 and 18 months afterward. Body composition was measured by dual x-ray absorptiometry. Analyses used linear and logistic regression.Before surgery, 8 individuals (9.1%) were underweight, 40 (45.5%) normal weight, 20 (22.7%) overweight, and 20 (22.7%) obese. Overweight/obese patients had higher area under the curve C-peptide and lower insulin sensitivity index. Baseline body weight was positively associated with first-phase insulin secretion (AIRg) at 12 months (average 38.5 [SE 17.1] mU/L/min higher per extra kg; P = 0.03) and 18 months (38.3 [18.5]; P = 0.04), while baseline lean mass was inversely associated with AIRg at 12 months (-0.05 [0.02] per extra kg; P = 0.01) and 18 months (-0.05 [0.02]; P = 0.03). Percent gynoid fat was inversely associated with disposition index at 18 months (-206.0 [97.2] per extra percent; P = 0.04). Percent body fat and percent gynoid fat were associated with glucose effectiveness index at 18 months (1.9 × 10-3 [0.9 × 10-3] per extra percent; P = 0.04 and -1.96 × 10-3 [0.8 × 10-3]; P = 0.02, respectively). Insulin independence was not significantly associated with body weight or composition.Half of these chronic pancreatitis patients were overweight/obese; underweight was uncommon. Preoperative body weight and composition were associated with islet function but not insulin independence after TPIAT.
View details for DOI 10.1210/clinem/dgaa790
View details for Web of Science ID 000759115900025
View details for PubMedID 33124670
View details for PubMedCentralID PMC7823238
Preoperative ERCP has no impact on islet yield following total pancreatectomy and islet autotransplantation (TPIAT): Results from the Prospective Observational Study of TPIAT (POST) cohort
2021; 21 (1): 275-281
Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield.Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders.175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement.ERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.
View details for DOI 10.1016/j.pan.2020.11.008
View details for Web of Science ID 000612551100039
View details for PubMedID 33323311
View details for PubMedCentralID PMC7924984
Long-Term Outcome in 836 Kidney Transplant Recipients with 20 Years of Graft Function
International Journal of Medical Sciences
2021; 8 (451): 1-16
View details for DOI 10.15342/ijms.2021.451
Timing of native nephrectomy and kidney transplant outcomes in children
2021; 25 (5): e13952
No consensus exists on the optimal timing for native nephrectomy in pediatric kidney transplant recipients. Data comparing outcomes between recipients undergoing pretransplant nephrectomy (staged nephrectomy with subsequent transplant) and those undergoing nephrectomy simultaneously with the transplant are lacking.We studied 32 pediatric kidney transplant recipients who underwent native nephrectomy at a single center from 01/01/2011 to 12/31/2016. We divided recipients into two groups based on the nephrectomy timing (simultaneous nephrectomy/transplant and staged nephrectomy). We used Wilcoxon rank-sum test, Fisher's exact test, and Kaplan-Meier methods to compare outcomes.Of 32 recipients, 20 underwent simultaneous and 12 underwent staged nephrectomy. Simultaneous recipients were younger (median (years): 2.0 vs 7.0; P = .049). Staged recipients were more likely to have proteinuria/hypoalbuminemia, whereas simultaneous recipients were more likely to have hydronephrosis/vesicoureteral reflux/urinary infections as nephrectomy indications (P = .06). Median prenephrectomy albumin for patients with nephrotic syndrome was significantly lower in staged recipients (median g/dL: 1.9 vs 3.8; P = .02). Total number of hospital days (including both procedures) was higher for staged recipients compared with simultaneous (one procedure) recipients (median (days): 17.0 vs 11.5; P = .05). We observed no difference in 5-year graft survival between the groups (95.0% vs 91.7%, P = .73). Patient survival was 100% in both groups over a median follow-up of 44.2 months. Surgical complications were similar between the groups.Staged and simultaneous native nephrectomy in pediatric kidney transplant recipients are associated with comparable outcomes.
View details for DOI 10.1111/petr.13952
View details for Web of Science ID 000599079900001
View details for PubMedID 33326667
Early use of continuous glucose monitoring in children and adolescents after total pancreatectomy with islet autotransplantation
2021; 22 (3): 434-438
Children undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis require intensive insulin therapy early after TPIAT with narrow glycemic targets, which can a present significant care burden. Outpatient use of continuous glucose monitoring (CGM) systems by children and caregivers early after TPIAT is inadequately studied.In this open-label study, we randomized 14 children and adolescents (mean age 15.4 years) after hospital discharge for TPIAT to Dexcom G6 CGM (n = 7) or standard care with a glucometer (n = 7) to assess acceptability and glycemic control with use of CGM versus usual care (glucometer). Participants in the control arm also wore a blinded CGM for 1 week.Children randomized to real-time CGM had lower mean sensor glucose values compared with controls (p = 0.002), and high overall satisfaction with CGM.Our data indicate that CGM is a useful adjunct to diabetes management for children who have recently undergone TPIAT.
View details for DOI 10.1111/pedi.13168
View details for Web of Science ID 000597062300001
View details for PubMedID 33271633
Performance of modified Igls criteria to evaluate islet autograft function after total pancreatectomy with islet autotransplantation - a retrospective study
2021; 34 (1): 87-96
The Igls criteria assess islet function after islet allotransplant, based on C-peptide, insulin use, hemoglobin A1c, and severe hypoglycemia. However, these criteria as currently defined cannot be applied to total pancreatectomy islet autotransplant (TPIAT) patients. We tested modified criteria for assessing islet function in a large cohort of TPIAT patients (n = 379). Metabolic outcomes were assessed. We assigned Auto-Igls class to each patient as able and evaluated the utility, validity, and perioperative risk factors of Auto-Igls at 1-year post-IAT. We tested the association of Auto-Igls with independent measures of islet graft function, specifically continuous glucose monitoring (CGM) data or acute C-peptide response to glucose (ACRglu) from intravenous glucose tolerance tests. An Auto-Igls class was assigned to 264 patients (69%). Among patients who could not be classified, most were missing exact insulin dose. Seventy-three percent of TPIAT recipients were classified as optimal or good at 1 year. The only significant predictor of Auto-Igls class was islet mass transplanted (P < 0.0001). Auto-Igls class was associated with percent time in range (70-140 mg/dl) on CGM (P = 0.02) and ACRglu (P < 0.0001). Modified Igls classification for IAT permits simple, comprehensive assessment of metabolic outcomes after TPIAT and is associated with other islet functional measures.
View details for DOI 10.1111/tri.13762
View details for Web of Science ID 000583758200001
View details for PubMedID 33020957
View details for PubMedCentralID PMC7913469
Current status of liver transplantation in North America.
International journal of surgery (London, England)
2020; 82S: 9-13
Liver transplantation is continuing to grow and evolve in North America. Changes in organ availability, recipient selection, indications and progressive approaches to oncologic treatment have occurred in the last five years. Despite increased activity in deceased and living donation in North America, there continues to be a high mortality on the waitlist as the recipient indications have changed over time which has led to new approaches to help patients with end-stage liver disease.
View details for DOI 10.1016/j.ijsu.2020.05.059
View details for PubMedID 32473238
Predictors of Survival After Liver Transplantation in Patients With the Highest Acuity (MELD >= 40)
ANNALS OF SURGERY
2020; 272 (3): 458-466
To identify factors that accurately predict 1-year survival for liver transplant recipients with a MELD score ≥40.Although transplant is beneficial for patients with the highest acuity (MELD ≥40), mortality in this group is high. Predicting which patients are likely to survive for >1 year would be medically and economically helpful.The Scientific Registry of Transplant Recipients database was reviewed to identify adult liver transplant recipients from 2002 through 2016 with MELD score ≥40 at transplant. The relationships between 44 recipient and donor factors and 1-year patient survival were examined using random survival forests methods. Variable importance measures were used to identify the factors with the strongest influence on survival, and partial dependence plots were used to determine the dependence of survival on the target variable while adjusting for all other variables.We identified 5309 liver transplants that met our criteria. The overall 1-year survival of high-acuity patients improved from 69% in 2001 to 87% in 2016. The strongest predictors of death within 1 year of transplant were patient on mechanical ventilator before transplantation, prior liver transplant, older recipient age, older donor age, donation after cardiac death, and longer cold ischemia.Liver transplant outcomes continue to improve even for patients with high medical acuity. Applying ensemble learning methods to recipient and donor factors available before transplant can predict survival probabilities for future transplant cases. This information can be used to facilitate donor/recipient matching and to improve informed consent.
View details for DOI 10.1097/SLA.0000000000004211
View details for Web of Science ID 000589824900042
View details for PubMedID 32740239
View details for PubMedCentralID PMC7855276
Brief Report: Willingness to Accept HIV-Infected and Increased Infectious Risk Donor Organs Among Transplant Candidates Living With HIV
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
2020; 85 (1): 88-92
HIV-infected (HIV+) donor to HIV+ recipient (HIV D+/R+) transplantation might improve access to transplantation for people living with HIV. However, it remains unknown whether transplant candidates living with HIV will accept the currently unknown risks of HIV D+/R+ transplantation.We surveyed transplant candidates living with HIV from 9 US transplant centers regarding willingness to accept HIV+ donor organs.Among 116 participants, the median age was 55 years, 68% were men, and 78% were African American. Most were willing to accept HIV+ living donor organs (87%), HIV+ deceased donor organs (84%), and increased infectious risk donor organs (70%). Some (30%) were concerned about HIV superinfection; even among these respondents, 71% were willing to accept an HIV D+ organ. Respondents from centers that had already performed a transplant under an HIV D+/R+ transplantation research protocol were more willing to accept HIV+ deceased donor organs (89% vs. 71%, P = 0.04). Respondents who chose not to enroll in an HIV D+/R+ transplantation research protocol were less likely to believe that HIV D+/R+ transplantation was safe (45% vs. 77%, P = 0.02), and that HIV D+ organs would work similar to HIV D- organs (55% vs. 77%, P = 0.04), but more likely to believe they would receive an infection other than HIV from an HIV D+ organ (64% vs. 13%, P < 0.01).Willingness to accept HIV D+ organs among transplant candidates living with HIV does not seem to be a major barrier to HIV D+/R+ transplantation and may increase with growing HIV D+/R+ transplantation experience.
View details for DOI 10.1097/QAI.0000000000002405
View details for Web of Science ID 000571130000018
View details for PubMedID 32427721
View details for PubMedCentralID PMC7429320
Proceedings of the 25th Annual Congress of the International Liver Transplantation Society
2020; 104 (8): 1560-1565
View details for DOI 10.1097/TP.0000000000003160
View details for Web of Science ID 000562762000021
Combination of pancreas volume and HbA1c level predicts islet yield in patients undergoing total pancreatectomy and islet autotransplantation
2020; 34 (8): e14008
Islet yield is an important predictor of acceptable glucose control after total pancreatectomy with islet autotransplantation (TP-IAT). We assessed if pancreas volume calculated with preoperative MRI could assess islet yield and postoperative outcomes. We reviewed dynamic MRI studies from 154 adult TP-IAT patients (2009-2016), and associations between calculated volumes and digest islet equivalents (IEQs) were tested. In multivariate regression analysis, pancreas volume (P < .001) and preoperative HbA1c levels (P = .009) were independently associated with digest IEQs. The IEQ prediction formula was calculated according to each preoperative HbA1c level, (a) pancreas volume × 5800 for HbA1c ≥ 6.5, (b) pancreas volume × 10 000 for HbA1c ≥5.7/<6.5 and (iii) pancreas volume × 11 400 for HbA1c < 5.7. The formula was internally validated with 28 TP-IAT patients between 2017 and 2018 (r2 = .657 and r2 = .710 when restricted to 24 patients without prior pancreatectomy). An estimated IEQs/Body Weight (kg) ≥3700 predicted HbA1c ≤6.5 and insulin independence at 1 year after TP-IAT with 77% and 88% sensitivity and 55% and 43% specificity, respectively. The combination of pancreas volume and preoperative HbA1c levels may be useful to estimate islet yield. Estimated IEQs were reasonably sensitive to predict acceptable glucose control at 1 year.
View details for DOI 10.1111/ctr.14008
View details for Web of Science ID 000545125100001
View details for PubMedID 32530540
Alterations in Enteroendocrine Hormones After Total Pancreatectomy With Islet Autotransplantation
2020; 49 (6): 806-811
When total pancreatectomy with islet autotransplantation (TPIAT) is performed for chronic pancreatitis, the pancreas and most of the duodenum are removed, with Roux-en-Y reconstruction of the gastrointestinal tract. Enteroendocrine cells in the intestines and pancreas secrete hormones coordinating digestion and motility, but anatomic reconstruction alters transit of nutrients to these cells. We hypothesized that TPIAT leads to changes in enteroendocrine hormones.Glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and pancreatic polypeptide (PP) were measured from mixed-meal tolerance tests of 34 clinical trial participants before and 18 months after TPIAT. Area under the curve of GLP-1 and PYY-stimulated responses were calculated by trapezoidal method, and the PP response was measured as the stimulated max minus baseline (ΔPP).Area under the curve of GLP-1 and PYY increased significantly after TPIAT (GLP-1 average +553.1 pg/mL per minute, P = 0.004; PYY average +4647.9 pg/mL per minute, P = 0.02). ΔPP trended toward lower after TPIAT (average, -52.2 pg/mL, P = 0.06).In this novel study of enteroendocrine hormones in TPIAT patients, stimulated levels of GLP-1 and PYY were significantly higher after versus before TPIAT. ΔPP was lower after TPIAT, but not significantly. These hormone changes have potential clinical implications that warrant further research.
View details for DOI 10.1097/MPA.0000000000001582
View details for Web of Science ID 000549975300021
View details for PubMedID 32541637
View details for PubMedCentralID PMC7321866
Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells
2020; 9 (6)
Human liver-derived stem cells (hLD-SCs) have been proposed as a possible resource for stem cell therapy in patients with irreversible liver diseases. However, it is not known whether liver resident hLD-SCs can differentiate toward a hepatic fate better than mesenchymal stem cells (MSCs) obtained from other origins. In this study, we compared the differentiation ability and regeneration potency of hLD-SCs with those of human umbilical cord matrix-derived stem cells (hUC-MSCs) by inducing hepatic differentiation. Undifferentiated hLD-SCs expressed relatively high levels of endoderm-related markers (GATA4 and FOXA1). During directed hepatic differentiation supported by two small molecules (Fasudil and 5-azacytidine), hLD-SCs presented more advanced mitochondrial respiration compared to hUC-MSCs. Moreover, hLD-SCs featured higher numbers of hepatic progenitor cell markers on day 14 of differentiation (CPM and CD133) and matured into hepatocyte-like cells by day 7 through 21 with increased hepatocyte markers (ALB, HNF4A, and AFP). During in vivo cell transplantation, hLD-SCs migrated into the liver of ischemia-reperfusion injury-induced mice within 2 h and relieved liver injury. In the thioacetamide (TAA)-induced liver injury mouse model, transplanted hLD-SCs trafficked into the liver and spontaneously matured into hepatocyte-like cells within 14 days. These results collectively suggest that hLD-SCs hold greater hepatogenic potential, and hepatic differentiation-induced hLD-SCs may be a promising source of stem cells for liver regeneration.
View details for DOI 10.3390/cells9061521
View details for Web of Science ID 000550035400001
View details for PubMedID 32580448
View details for PubMedCentralID PMC7348751
Laparoscopic-assisted versus open total pancreatectomy and islet autotransplantation: A case-matched study of pediatric patients
JOURNAL OF PEDIATRIC SURGERY
2020; 55 (3): 558-563
Total Pancreatectomy and Islet Autotransplantation (TPIAT) are a potential treatment for children with severe, refractory chronic pancreatitis. A laparoscopic-assisted approach provides a smaller incision and excellent visualization of the distal pancreas and spleen during resection. A minimally-invasive approach has proven advantageous for other pediatric procedures, but its value is unknown for this rare operation. This retrospective review compares outcomes between patients undergoing laparoscopic-assisted versus open TPIAT.Children (n = 21) receiving laparoscopic-assisted TPIAT from 2013 to 2015 and children (n = 21) receiving open TPIAT from 2011 to 2015 were matched based on age, gender, symptom duration, previous interventions, and pancreatic fibrosis scores. Data reviewed included postoperative complications, operative time, estimated blood loss (EBL), intraoperative blood transfusions, number of islet equivalents (IEQ)/kg transplanted, hospital length-of-stay, graft function, narcotic use, and Patient Scar Assessment Questionnaire scores. Between-group differences were compared using Fisher's exact, Chi-square, and T-tests.Surgical complications were similar between surgical groups (p = 0.35) and included wound complications (n = 11), chyle leak (n = 7), bowel obstruction (n = 5), bile leak (n = 3), gastrointestinal bleed (n = 2), and pneumonia (n = 1). There were no significant differences in operative time (p = 0.18), EBL (p = 0.96), blood transfusions (p = 0.34), IEQ/kg transplanted (p = 0.15), and hospital length-of-stay (p = 0.66). Insulin and opioid use was similar except for a slightly higher use of opioids (n = 4) at 2 years in the laparoscopic group. Patient surgical scar satisfaction was similar between groups (p = 0.26).Outcomes for laparoscopic-assisted TPIAT appear comparable to open TPIAT. In children, a minimally-invasive approach does not compromise safety, effectiveness, or operative efficiency and may be used based on surgeon and patient preference.
View details for DOI 10.1016/j.jpedsurg.2019.10.007
View details for Web of Science ID 000522662800035
View details for PubMedID 31727387
The evolving microenvironment of the human hepatocyte: Healthy vs. cirrhotic liver vs. isolated cells
TISSUE & CELL
2020; 62: 101310
The study of the liver microenvironment and hepatocyte's response to this environment in the setting of healthy liver, cirrhotic liver or cultured primary human hepatocytes (PHHs) addresses key questions for the development of novel liver therapies and predicts relevance of ex vivo PHHs models in liver biology. This study compared quantitative gene and protein expression of the inflammatory profile, oxidative stress response, angiogenesis and homing mechanisms in the biopsies of healthy and cirrhotic human livers and isolated PHHs. These profiles were correlated with the metabolic health of liver and PHHs defined by albumin production. The analysis demonstrated that cirrhotic liver and PHHs exhibited a distinct upregulation of the pro-inflammatory, oxidative stress and homing mechanism markers when compared to normal liver. The upregulation of the oxidative stress markers in PHHs inversely correlated with the albumin production. PHHs had diverse secretion of matrix metalloproteinases and their inhibitors, reflective of the cellular response to non-physiological culture conditions. The current study suggests that ex vivo PHHs manifest adaptive behavior by upregulating stress mechanisms (similar to the cirrhotic liver), downregulating normal metabolic function and upregulating matrix turnover. The ex vivo profile of PHHs may limit their therapeutic functionality and metabolic capacity to serve as in vitro metabolism and toxicology models.
View details for DOI 10.1016/j.tice.2019.101310
View details for Web of Science ID 000508892200007
View details for PubMedID 32433018
- Reprogramming of Human Hepatic Non-Parenchymal Cells: Step-by-Step Protocol Current protocols in stem cell biology 2020; 53 (1)
Failure of everolimus in the management of Kaposi’s sarcoma in HOPE Act recipient following simultaneous liver and kidney transplantation
Trends in Transplant
2020; 13 (1)
View details for DOI 10.15761/TiT.1000269
HIF-1 alpha regulates A2B adenosine receptor expression in liver cancer cells
EXPERIMENTAL AND THERAPEUTIC MEDICINE
2019; 18 (6): 4231-4240
Liver cancer exhibits the fourth most common cause of cancer-associated mortality worldwide. Due to the rapid growth, solid tumors undergo severe hypoxia and produce high levels of extracellular adenosine to maintain homeostasis. A previous study indicated that the hypoxic condition in liver cancer increased hepatic adenosine, which is known to facilitate cancer survival and proliferation. Extracellular adenosine has been revealed to regulate pathological and physiological processes in cells and tissues. However, its pathophysiological role in liver cancer remains undetermined. Emerging evidence has indicated that the adenosine A2B receptor promotes the progression of liver cancer. Therefore, it was hypothesized that HIF-1α is a transcriptional regulator of A2B in human liver cancer. The current study determined A2B expression of a number of liver cancer cell lines and performed functional studies of HIF-1α as a master transcriptional regulator of hepatic A2B signaling during hypoxic conditions. The current study aimed to identify the promoter region of A2B, which has a hypoxia response element, by performing luciferase assays. The present study demonstrated that reduced HIF-1α expression is associated with low expression of A2B, and HIF-1α overexpression is associated with A2B induction. Furthermore, the siRNA-mediated downregulation of A2B inhibited the growth and proliferation of HepG2, which is a liver cancer cell line. The relationship between HIF-1α and A2B expression was also identified in human liver cancer specimens. In conclusion, the current study indicated that A2B is induced by the HIF-1α transcriptional regulator during hypoxia, and it may be a potential pharmacologic and therapeutic target for the treatment of patients with liver cancer.
View details for DOI 10.3892/etm.2019.8081
View details for Web of Science ID 000505222900006
View details for PubMedID 31772626
View details for PubMedCentralID PMC6862085
A Study on the Effect of Patient Characteristics, Geographical Utilization, and Patient Outcomes for Total Pancreatectomy Alone and Total Pancreatectomy With Islet Autotransplantation in Patients With Pancreatitis in the United States
2019; 48 (9): 1204-1211
A selective therapy for pancreatitis is total pancreatectomy and islet autotransplantation. Outcomes and geographical variability of patients who had total pancreatectomy (TP) alone or total pancreatectomy with islet autotransplantation (TPIAT) were assessed.Data were obtained from the Healthcare Cost and Utilization Project National Inpatient Sample database. Weighed univariate and multivariate analyses were performed to determine the effect of measured variables on outcomes.Between 2002 and 2013, there were 1006 TP and 825 TPIAT in patients with a diagnosis of chronic pancreatitis, and 1705 TP and 830 TPIAT for any diagnosis of pancreatitis. The majority of the TP and TPIAT were performed in larger urban hospitals. Costs were similar for TP and TPIAT for chronic pancreatitis but were lower for TPIAT compared with TP for any type of pancreatitis. The trend for TP and TPIAT was significant in all geographical areas during the study period.There is an increasing trend of both TP and TPIAT. Certain groups are more likely to be offered TPIAT compared with TP alone. More data are needed to understand disparities and barriers to TPIAT, and long-term outcomes of TPIAT such as pain control and glucose intolerance need further study.
View details for DOI 10.1097/MPA.0000000000001405
View details for Web of Science ID 000505802000013
View details for PubMedID 31593020
View details for PubMedCentralID PMC7952005
Risk Factors Associated With Progression Toward Endocrine Insufficiency in Chronic Pancreatitis
2019; 48 (9): 1160-1166
Little data exist describing the change over time in islet function and glycemic control in patients with chronic pancreatitis (CP).In 325 CP patients who underwent 2 mixed meal tolerance tests and/or glycated hemoglobin (HbA1c) levels, we estimated the rate of change in metabolic measures per 6 months and assessed the association between potential risk factors for diabetes and rate of change using multivariate regression models.Per 6-month time, HbA1c increased by 0.062% with a standard error of 0.029% (P = 0.037) and the ratio (area under the curve (AUC) C-peptide to AUC glucose from mixed meal tolerance testing) decreased by 0.0028 with a standard error of 0.0011 (P = 0.014). We observed more rapid decline in smokers (AUC C-peptide, P = 0.043) and patients with surgical drainage (AUC glucose, P = 0.001; ratio, P = 0.03) or with calcific pancreatitis (HbA1c, P = 0.003). In multivariate models, AUC C-peptide and ratio declined at a greater rate in smokers and HbA1c in those with pancreatic calcifications (both P < 0.05).We observed a measurable decline in β-cell function and glycemic control in patients with CP. Patients with a history of tobacco smoking, surgical drainage, or pancreatic calcification may be at highest risk.
View details for DOI 10.1097/MPA.0000000000001394
View details for Web of Science ID 000505802000007
View details for PubMedID 31593013
View details for PubMedCentralID PMC6791757
Upregulation of Carbonyl Reductase 1 by Nrf2 as a Potential Therapeutic Intervention for Ischemia/Reperfusion Injury during Liver Transplantation
MOLECULES AND CELLS
2019; 42 (9): 672-685
Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygenglucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.
View details for DOI 10.14348/molcells.2019.0003
View details for Web of Science ID 000488204700006
View details for PubMedID 31486328
View details for PubMedCentralID PMC6776159
Clinical utility of postoperative phosphate recovery profiles to predict liver insufficiency after living donor hepatectomy.
American journal of surgery
2019; 218 (2): 374-379
Living donor hepatectomy (LDH) is associated with significant postoperative hypophosphatemia.From January 1997 through July 2017, we performed 176 LDH and compared donors who developed liver insufficiency (LI) to those that did not within 30 days of LDH. Using smoothing splines, we constructed a mixed-effects model and assessed receiver operating characteristic curves.Of the 176 donors, 161 were included in our study and 10 (6.2%) developed LI. The cohorts differed in minimum observed phosphate levels (1.77 mg/dL, LI cohort; 2.01 mg/dL No LI cohort) at a median nadir of 1.6 days (38 h) postoperatively (p = 0.003). In the ROC analysis, intraoperative time and postoperative phosphate levels best predicted LI (sensitivity, 90%; specificity, 55.6%).Mean postoperative phosphate profiles differ significantly between those patients who develop LI and those who do not in the first 38 h after LDH.
View details for DOI 10.1016/j.amjsurg.2019.01.006
View details for PubMedID 30660322
How Durable Is Total Pancreatectomy and Intraportal Islet Cell Transplantation for Treatment of Chronic Pancreatitis?
ELSEVIER SCIENCE INC. 2019: 329-339
A total pancreatectomy and intraportal islet cell autotransplant (TPIAT) is increasingly being offered to patients with chronic pancreatitis (CP). The benefits include removal of the root cause of pain and amelioration of diabetes. However, the long-term durability of this operation remains unclear.Of the 742 patients who have undergone a TPIAT at our center, 215 who did so between 1998 and 2008 now have at least 10 years of follow-up time and were eligible for this single-center observational study. Our outcomes measures included abdominal pain relief, narcotic use, islet graft function (subdivided into 3 groups: insulin independence; partial graft function, defined by C-peptide level > 0.6 mg/dL; and no function, defined by C-peptide level < 0.6 mg/dL), and health-related quality of life.The 10-year actuarial survival rate was 72%. A BMI > 30 kg/m2 (p = 0.04) predicted 10-year mortality. The rates of pain relief were 82% at 10 years and 90% at 15 years. Narcotic use declined with time: the rates were 50% at 5 years and 37% at 10 years. At 10 years, the rate of insulin independence was 20%; the rate of partial graft function, 32%. Transplantation of islet equivalents/kg > 4,000 was the strongest predictor of islet graft function at 10 years. Pediatric patients were more likely to have islet function than adults (p = 0.01). Health-related quality of life continued to improve at 10 years, even in patients on narcotics.This represents the first and largest series to examine long-term outcomes (10 years or more) in TPIAT patients. In our series, this dual procedure produced durable pain relief and sustained islet graft function, even past 10 years postoperatively.
View details for DOI 10.1016/j.jamcollsurg.2018.12.019
View details for Web of Science ID 000461357100002
View details for PubMedID 30630085
View details for PubMedCentralID PMC8579321
Report of the 24th Annual Congress of the International Liver Transplantation Society.
2019; 103 (3): 465-469
The 24th Joint Annual Congress of the International Liver Transplantation Society in association with European Liver and Intestine Transplant Association and Liver Intensive Care Group of Europe was held in Lisbon, Portugal from May 23 to 26, 2018. More than 1200 participants from over 60 countries including surgeons, hepatologists, anesthesiologists and critical care intensivists, radiologists, pathologists, organ procurement personnel, and research scientists came together with the common aim of improving care and outcomes for liver transplant recipients. Over 600 scientific abstracts were presented. The principal themes were living donation, use of marginal liver donors, machine preservation, disease-specific immunosuppressive regimen, malignancies, and advances in pediatric liver transplantation and liver transplant anesthesia. This report presents excerpts from invited lectures and select abstracts from scientific sessions, which add to current knowledge, and will drive clinical practice and future research.
View details for DOI 10.1097/TP.0000000000002549
View details for PubMedID 30461723
Pre-emptive Treatment of HCV after Living Donor Liver Transplantation with Direct-Acting Antiviral Agents
JOURNAL OF GASTROINTESTINAL SURGERY
2018; 22 (8): 1334-1342
Hepatitis C virus (HCV) universally recurs after liver transplantation (LT). Although the introduction of direct-acting antiviral agents (DAAs) has revolutionized the treatment of HCV infection, no optimal treatment for HCV recurrence after LT has been developed.This study retrospectively evaluated the efficacy of DAAs as a pre-emptive treatment for recurrent HCV infection after living donor liver transplantation (LDLT). From January 2010 to December 2016, 70 patients received pegylated interferon (PegIFN) and 35 patients were treated with DAA-based regimens to treat recurrent HCV after LDLT. All antiviral treatments were pre-emptive.Genotype 1b was the most common HCV type (61.9%). Twenty-two recipients in the DAA group were treated with ledipasvir/sofosbuvir, nine received daclatasvir plus asunaprevir, three received sofosbuvir, and one received sofosbuvir plus daclatasvir. All 35 patients (100%) in the DAA group achieved a sustained virologic response (SVR), a percentage significantly higher than that (71.4%) in the PegIFN group (p < 0.001). In the PegIFN group, the 1-, 3-, and 5-year graft survival rates were 85.7, 73.9, and 70.7%, respectively, whereas those in the DAA group were 100, 100, and 100%, respectively (p = 0.008).DAA-based regimens are an effective treatment for HCV recurrence after LDLT, resulting in an improved SVR and better graft survival than PegIFN.
View details for DOI 10.1007/s11605-018-3779-9
View details for Web of Science ID 000440295800003
View details for PubMedID 29679347
Complications after Living Donor Hepatectomy: Analysis of 176 Cases at a Single Center
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
2018; 227 (1): 24-36
Living liver donation is one of the most selfless and humane acts a person can perform. Few single-center reports have been published specifically evaluating complications and quality of life post-donation.We conducted a retrospective analysis of outcomes of 176 living liver donors at our center to determine the incidence, type, and Clavien grade of complications, as well as long-term quality of life.Of 176 living donors, 154 underwent right hepatectomy, 4 underwent left hepatectomy lobectomy, and 18 underwent left lateral segmentectomy. Mean follow-up time was 4.8 years. Complications were more frequent among right-lobe donors than left-lateral segmentectomy and left-lobe donors (p = 0.003). Of note, 82% of complications were Clavien grade 1 or 2. Of the 154 right-lobe donors, 3 had Clavien grade 3a complications, 9 had grade 3b complications (4 had bile leaks, 3 had intra-abdominal bleeding, and 2 had pleural effusions). No donor had complications that were Clavien grade 4 or higher. Per multivariate regression, resected graft volume (p = 0.0498) and post-donation international normalized ratio >2 (p = 0.00499) were significantly associated with a higher risk of Clavien grade 3 complications; however, sex, age, previous abdominal operation, post-donation bilirubin >6 mg/dL, and aspartate transaminase >650 IU/L were not. Per our 36-item Short-Form Health Survey results, donors (mean 8.3 years post-donation) reported above-average quality of life compared with standard US population. In a liver donation survey sent between 1 and 15 years post-donation, the most frequently reported problems were incisional discomfort and intolerance to fatty meals.In our single-center study, early complication rates were comparable with those of multicenter reports. Most complications (82%) were Clavien grade 1 or 2. During a long follow-up period, our donors continue to have improved quality of life.
View details for DOI 10.1016/j.jamcollsurg.2018.03.007
View details for Web of Science ID 000436646700006
View details for PubMedID 29555562
Outcome of ABO-incompatible adult living-donor liver transplantation for patients with hepatocellular carcinoma
JOURNAL OF HEPATOLOGY
2018; 68 (6): 1153-1162
Living-donor liver transplantation (LDLT) can simultaneously cure hepatocellular carcinoma (HCC) and underlying liver cirrhosis, improving long-term results in patients with HCC. ABO-incompatible LDLT could expand the living-donor pool, reduce waiting times for deceased-donor liver transplantation, and improve long-term survival for some patients with HCC.We retrospectively reviewed the medical records of patients undergoing LDLT for HCC from November 2008 to December 2015 at a single institution in Korea. In total, 165 patients underwent ABO-incompatible and 753 patients underwent ABO-compatible LDLT for HCC. ABO-incompatible recipients underwent desensitization to overcome the ABO blood group barrier, including pretransplant plasma exchange and rituximab administration (300-375 mg/m2 /body surface area).We performed 1:1 propensity score matching and included 165 patients in each group. 82.4% of ABO-incompatible and 83.0% of -compatible LDLT groups had HCC within conventional Milan criteria, respectively, and 92.1% and 92.7% of patients in each group had a Child-Pugh score of A or B. ABO-incompatible and -compatible LDLT groups were followed up for 48.0 and 48.7 months, respectively, with both groups showing comparable recurrence-free survival rates (hazard ratio [HR] 1.14; 95% CI 0.68-1.90; p = 0.630) and overall patient-survival outcomes (HR 1.10; 95% CI 0.60-2.00; p = 0.763).These findings suggested that ABO-incompatible liver transplantation is a feasible option for patients with HCC, especially for those with compensated cirrhosis with HCC within conventional Milan criteria.Despite hypothetical immunological concerns that the desensitization protocol for breaking through the ABO blood group barrier might have a negative impact on the recurrence of hepatocellular carcinoma, our experience demonstrated no significant differences in the long-term overall survival and recurrence-free survival rates between patients receiving ABO-compatible or ABO-incompatible liver transplantation. In conclusion, results from our institution indicated that ABO-incompatible living-donor liver transplantation constitutes a potentially feasible option for patients with hepatocellular carcinoma, especially those with compensated cirrhosis with hepatocellular carcinoma within conventional Milan criteria.
View details for DOI 10.1016/j.jhep.2018.02.002
View details for Web of Science ID 000432491000008
View details for PubMedID 29452208
A multicenter study of total pancreatectomy with islet autotransplantation (TPIAT): POST (Prospective Observational Study of TPIAT).
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
2018; 18 (3): 286-290
Total pancreatectomy with islet autotransplantation (TPIAT) is considered for managing chronic pancreatitis in selected patients when medical and endoscopic interventions have not provided adequate relief from debilitating pain. Although more centers are performing TPIAT, we lack large, multi-center studies to guide decisions about selecting candidates for and timing of TPIAT.Multiple centers across the United States (9 to date) performing TPIAT are prospectively enrolling patients undergoing TPIAT for chronic pancreatitis into the Prospective Observational Study of TPIAT (POST), a NIDDK funded study with a goal of accruing 450 TPIAT recipients. Baseline data include participant phenotype, pancreatitis history, and medical/psychological comorbidities from medical records, participant interview, and participant self-report (Medical Outcomes Survey Short Form-12, EQ-5D, andPROMIS inventories for pain interference, depression, and anxiety). Outcome measures are collected to at least 1 year after TPIAT, including the same participant questionnaires, visual analog pain scale, pain interference scores, opioid requirements, insulin requirements, islet graft function, and hemoglobin A1c. Health resource utilization data are collected for a cost-effectiveness analysis. Biorepository specimens including urine, serum/plasma, genetic material (saliva and blood), and pancreas tissue are collected for future study.This ongoing multicenter research study will enroll and follow TPIAT recipients, aiming to evaluate patient selection and timing for TPIAT to optimize pain relief, quality of life, and diabetes outcomes, and to measure the procedure's cost-effectiveness. A biorepository is also established for future ancillary studies.
View details for DOI 10.1016/j.pan.2018.02.001
View details for PubMedID 29456124
View details for PubMedCentralID PMC5879010
Age and Disease Duration Impact Outcomes of Total Pancreatectomy and Islet Autotransplant for PRSS1 Hereditary Pancreatitis.
2018; 47 (4): 466-470
We investigated the impact of patient age and disease duration on islet isolation results, diabetes outcomes, and pain outcomes after total pancreatectomy with islet autotransplant (TPIAT) performed in 64 patients with hereditary pancreatitis due to PRSS1 gene mutation.We evaluated the association of patient age and disease duration on islet isolation results and opioid use at 1 year using logistic regression and on graft function using 1-way analysis of variance.Islet mass was negatively associated with increasing age and longer disease duration, with a 13% reduction (95% confidence interval [CI], 3%-22%) and 22% (95% CI, 14%-29%) reduction in islet equivalents per kilogram body weight (IEQ/kg) for each 5 years of age and disease duration, respectively. Full graft function was associated with younger age and shorter duration of disease (P < 0.01). Persistent opioid use (15% of patients at 1 year) increased with age (P = 0.05) and disease duration (P = 0.04).The TPIAT outcomes were adversely impacted by older age and prolonged disease. In particular, islet mass is lower and risk of diabetes high in older patients with prolonged disease. This should be considered when counseling this subgroup of TPIAT recipients on expected outcomes.
View details for DOI 10.1097/MPA.0000000000001028
View details for PubMedID 29517634
Dual-graft adult living donor liver transplantation with ABO-incompatible graft: short-term and long-term outcomes.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
2018; 18 (2): 424-433
ABO-incompatible (ABOi) dual-graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data are lacking on the short- and long-term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end-stage liver disease score was 12.2 ± 4.6. The 1-, 3-, and 5-year patient survival rate was 96.4% during the mean follow-up period of 57.0 ± 22.4 months. The 1-, 3-, and 5-year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO-compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.
View details for DOI 10.1111/ajt.14448
View details for PubMedID 28758336
Total Pancreatectomy With Islet Autotransplantation for Acute Recurrent and Chronic Pancreatitis.
Current treatment options in gastroenterology
2017; 15 (4): 548-561
The first total pancreatectomy and islet autotransplantation (TP-IAT) was performed for chronic pancreatitis in 1977 with the goal to ameliorate the pain and simultaneously preserve islet function. We reviewed the recent medical literature regarding indications, patient suitability, current outcomes, and challenges in TP-IAT.Current indications for TP-IAT include intractable pain secondary to chronic pancreatitis (CP) or acute recurrent pancreatitis (ARP) with failed medical and endoscopic/surgical management. Independent studies have shown that TP-IAT is associated with elimination or significant improvement in pain control and partial or full islet graft function in the majority of patients. In single-center cost analyses, TP-IAT has been suggested to be more cost-effective than medical management of chronic pancreatitis. While initially introduced as a surgical option for adults with long-standing chronic pancreatitis, TP-IAT is now often utilized in children with chronic pancreatitis and in children and adults with intractable acute recurrent pancreatitis. The surgical procedure has evolved over time with some centers offering minimally invasive operative options, although the open approach remains the standard. Despite many advances in TP-IAT, there is a need for further research and development in disease diagnosis, patient selection, optimization of surgical technique, islet isolation and quality assessment, postoperative patient management, and establishment of uniform metrics for data collection and multicenter studies. TP-IAT is an option for patients with otherwise intractable acute recurrent or chronic pancreatitis which presents potential for pain relief and improved quality of life, often with partial or complete diabetes remission.
View details for DOI 10.1007/s11938-017-0148-9
View details for PubMedID 28895017
Living Donor Liver Transplantation for Patients Older Than Age 70 Years: A Single-Center Experience.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
2017; 17 (11): 2890-2900
Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70-78 years) and investigated the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in-hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1- and 5-year patient survival rates were 84.0% and 69.8%, and the 1- and 5-year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.
View details for DOI 10.1111/ajt.14355
View details for PubMedID 28510341
Pure laparoscopic right anterior sectionectomy for hepatocellular carcinoma with great vascular exposure.
2017; 31 (8): 3349-3350
Laparoscopic hepatectomy is a common procedure that has been reported frequently [1-3]. However, laparoscopic resection of tumors located in hepatic segments 5 and/or 8 remains a technically difficult procedure as it requires two transection planes . Furthermore, there are a greater number of hepatic vein and glissonian pedicle branches that require a division as compared to other hepatectomy operations. In this report, we present a pure laparoscopic right anterior sectionectomy (RAS) for hepatocellular carcinoma (HCC).Preoperative imaging showed HCC (3 cm × 4 cm) in segment 5 . After selective anterior segment inflow occlusion, transection lines were demarcated. Complete Pringle maneuver was performed for 15 min intervals five times during hepatic parenchymal transection. The Cavitron Ultrasonic Surgical Aspirator was used for the transection of the hepatic tissue. Small hepatic vein branches along the middle and right hepatic veins and small glissonian pedicles were clipped, sealed and divided with EnSEAL (TM) (Ethicon). iDrive (TM) Ultra Powered Stapling device (Medtronic) was used for the division of tertiary glissonian pedicles. Hanging maneuver was performed for transection of remaining liver parenchyma after complete division of hepatic venous branches. The specimen was removed through the lower abdominal transverse incision using the endocatch bag. Jackson-Pratt drain was left in the operative field. All work was performed with IRB approval.Pure laparoscopic RAS for HCC was performed successfully without intraoperative complications or transfusions. The operation time was 300 min, and the estimated blood loss was <200 ml. On postoperative day 5, computed tomography scan showed well-perfused hepatic parenchyma. Pathology specimen confirmed 3.2 cm × 3 cm × 2.2 cm HCC without involvement of surgical resection margins. The patient was discharged on postoperative day 7 without complications.Pure laparoscopic RAS is a feasible operative procedure in patients with tumors located in hepatic segments 5/8.
View details for DOI 10.1007/s00464-016-5349-0
View details for PubMedID 27928672
The impact of using an intraoperative goal directed fluid therapy protocol on clinical outcomes in patients undergoing total pancreatectomy and islet cell autotransplantation.
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
2017; 17 (4): 586-591
Patients undergoing total pancreatectomy and islet cell autotransplant (TPIAT) for treatment of pancreatitis are at risk for complications of over and under resuscitation. We hypothesized that using a goal directed fluid therapy (GDFT) protocol might impact clinical outcomes.A consecutive series of adult patients undergoing TPIAT were managed intraoperatively using either standard fluid therapy (SFT, n = 44) or GDFT (n = 23) as part of a pilot study between January 2013 and May 2015. Patient characteristics, intraoperative, and postoperative data were recorded prospectively, then retrospectively analyzed for differences between the groups.The GDFT group had lower total fluid resuscitation (3,240 cc vs 5,173 cc, p < 0.0001) and transfusion requirements (1.0 cc/kg vs 3.3 cc/kg, p = 0.050) compared to the SFT group. The pre to postop nadir hemoglobin change was significantly less for GDFT (4.2 vs 5.1 gm/dl, p = 0.021) despite less transfusion.Compared to SFT, using an intraoperative GDFT protocol in TPIAT patients was associated with significantly decreased intraoperative fluid resuscitation, blood transfusion and less postoperative dilutional anemia, without any difference in complications of underresuscitation. This pilot study suggests that GDFT is likely safe and further investigation is warranted.
View details for DOI 10.1016/j.pan.2017.06.010
View details for PubMedID 28659243
Successful Renal Transplantation in Small Children With a Completely Thrombosed Inferior Vena Cava.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
2017; 17 (6): 1670-1673
In small children with end-stage renal disease, an adult-sized kidney transplant is the best option. However, in the face of a completely thrombosed inferior vena cava (IVC), such transplants can be challenging, given the difficulty of achieving adequate renal venous outflow and the risk of graft thrombosis. Using a new technique to anastomose the renal vein to the right hepatic vein/IVC junction, we successfully implanted an adult-sized graft in two small children (9.8 and 14 kg) who had end-stage renal disease and a completely thrombosed IVC. After mobilizing the right lobe of the liver and obtaining total vascular occlusion of the liver, we used a Fogarty catheter to dilate the retrohepatic IVC. In the right hepatic vein, we made a venotomy and extended it inferiorly onto the retrohepatic IVC. To that venotomy, we anastomosed the donor left renal vein, using continuous 7-0 Prolene sutures. Both patients attained excellent renal allograft function: One had a serum creatinine level of 0.30 mg/dL at 6 mo after transplant, and the other had a level of 0.29 mg/dL at 1 year. In these two small children with completely thrombosed IVC, our technique for transplanting an adult-sized kidney provided adequate venous outflow.
View details for DOI 10.1111/ajt.14213
View details for PubMedID 28133953
Pure laparoscopic right hepatectomy for giant hemangioma using anterior approach.
2017; 31 (5): 2338-2339
Laparoscopic major hepatectomy remains a challenging procedure [1, 2]. In the case of giant tumors in the right liver, conventional approach (complete mobilization of the right liver before parenchymal transection) could be dangerous during mobilization because of large volume and weight [3, 4]. We present the case of a pure laparoscopic right hepatectomy for a giant hemangioma using an anterior approach.We achieved the informed consent with this patient and approved by the Ethics Committee of the Asan Medical Center. Giant hemangioma (13 × 11 × 14 cm) was located in right liver. After glissonean approach , Pringle maneuver was performed during the hepatic parenchymal transection. For the transection, the Cavitron Ultrasonic Surgical Aspirator was used. Small hepatic vein branches along the middle hepatic vein and small glissonean pedicles were sealed and divided with a THUNDERBEATTM (Olympus), which is the device with integration of both bipolar and ultrasonic energies delivered simultaneously. iDriveTM Ultra Powered Stapling device (Medtronic) was used for division of right glissonean pedicle and large hepatic veins. Hemangioma was removed through the lower abdominal transverse incision using the endo-bag. This technique has the advantage of avoiding excessive bleeding caused by avulsion of the hepatic vein and caval branches, iatrogenic tumor rupture .By means of the anterior approach, pure laparoscopic right hepatectomy was performed successfully without intraoperative complications and transfusions. The operation time was 202 min, and the estimated blood loss was less than 150 ml. On postoperative day 3, computed tomographic scan showed no pathological findings. The patient was discharged on postoperative day 5 without complications. Laparoscopic approach has good results because of the view with magnification enabling meticulous hemostasis and the small wounds that give patients less pain [6, 7].The authors recommend that the laparoscopic anterior approach is safe and feasible for right hepatectomy, even for giant tumors.
View details for DOI 10.1007/s00464-016-5224-z
View details for PubMedID 27620909
Outcomes and Risk Factors for Graft Loss: Lessons Learned from 1,056 Pediatric Kidney Transplants at the University of Minnesota.
Journal of the American College of Surgeons
2017; 224 (4): 473-486
Advances in immunosuppression, surgical techniques, and management of infections in children receiving kidney transplants have affected outcomes.We analyzed a prospectively maintained database of pediatric kidney transplantations.From June 1963 through October 2016, we performed 1,056 pediatric kidney transplantations. Of these, 129 were in children less than 2 years old. The most common indications for transplant were congenital anomalies (dysplastic kidneys), obstructive uropathy, and congenital nephrotic syndrome. Living donors constituted 721 (68%) of all donors. The graft and patient survival rates remarkably improved for both deceased and living donor recipients (p = 0.001). Currently, graft survival rates for deceased donor recipients are 92% at 1 year, 76% at 5 years, and 57% at 10 years post-transplant; for living donor recipients, 96% at 1 year, 85% at 5 years, and 78% at 10 years. The graft half-life was 19 years in deceased donor recipients, compared with 25 years in living donor recipients (p ≤ 0.001). Acute rejection was the most common cause of graft loss in the first year post-transplant. The following risk factors were associated with an increased risk of graft loss: deceased donor grafts (p = 0.0001), retransplant (p = 0.02), ages 11 to 18 years (p = 0.001) and pre-transplant urologic issues (p = 0.04). Living donor grafts (p ≤ 0.0001) and pre-emptive transplants (p = 0.02) were associated with decreased risks of graft loss.The success rates of pediatric kidney transplants have significantly improved. Pre-emptive kidney transplantation with a living donor graft continues to be superior and should be the choice in children with end-stage renal disease.
View details for DOI 10.1016/j.jamcollsurg.2016.12.027
View details for PubMedID 28254584
Protective role of hypoxia-inducible factor-1α-dependent CD39 and CD73 in fulminant acute liver failure.
Toxicology and applied pharmacology
2017; 314: 72-81
Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5'-nucleotidase, Ecto5'NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF. To test our hypothesis, liver biopsies were obtained and we found that CD39 and CD73 mRNA and proteins from human specimens were dramatically elevated in ALF. We investigated that induction of CD39 and CD73 in ALF-related with wild type mice. In contrast, deletion of cd39 and cd73 mice has severe ALF. In this study, we concluded that CD39 and CD73 are molecular targets for the development of drugs for ALF patients care.
View details for DOI 10.1016/j.taap.2016.11.016
View details for PubMedID 27899277
Resolution of Hepatic Venous Congestion Following Gradual Occlusion of Middle Hepatic Vein Interposition Graft in Living Donor Liver Transplantation.
Annals of transplantation
2016; 21: 619-625
BACKGROUND The middle hepatic vein (MHV) interposition vessel graft (IVG) is often occluded within a few months after living-donor liver transplantation (LDLT). We aimed to assess the mechanisms of resolving the hepatic venous congestion (HVC) that develops after gradual occlusion of the MHV-IVG. MATERIAL AND METHODS This study comprised two parts. Part I involved an assessment of the process of HVC resolution in the remnant right liver after donation of an extended left liver graft (n=100). Part II involved an evaluation of the timing and patterns of gradual MHV-IVG occlusion and HVC resolution in LDLT recipients (n=100). RESULTS In Part I, the analysis of 1-week dynamic computed tomography (CT) showed pre-existing collaterals in 8, appropriate compensation in 44, and HVC in 48 patients. In Part II, reconstruction of a segment V vein (V5) and a segment VIII vein (V8) was the most common reconstruction type (n=65). The patency rates of MHV-IVG were 90% at 3 months, 65% at 6 months, 37% at 12 months, and 18% at 24 months. The patency rate of V5 was inferior to that of V8. CT imaging analysis indicated that extrinsic compression of IVG, development of intrahepatic collaterals, and IVG shrinkage were the main mechanisms underlying late MHV-IVG occlusion. Moreover, the timing of MHV-IVG occlusion was well correlated with that of neo-collateralization. CONCLUSIONS MHV-IVG reconstruction effectively prevents HVC in LDLT. Although gradual MHV-IVG occlusion is well compensated by neo-collateralization, we believe that the patency of the IVG should be maintained for at least 6 months after LDLT.
View details for DOI 10.12659/aot.900170
View details for PubMedID 27713391
Evolution of Living Donor Nephrectomy at a Single Center: Long-term Outcomes With 4 Different Techniques in Greater Than 4000 Donors Over 50 Years.
2016; 100 (6): 1299-305
The development of minimally invasive surgical approaches to donor nephrectomy (DN) has been driven by the potential advantages for the donor, with questions remaining about long-term outcomes.All living DN performed from June 1963 through December 2014 at the University of Minnesota were reviewed. Outcomes were compared among 4 DN techniques.We performed 4286 DNs: 2759 open DN (ODNs), 1190 hand-assisted (HA) laparoscopic DNs (LDNs), 203 pure LDN (P-LDNs), and 97 robot-assisted-LDN. Laparoscopic DN was associated with an older (P < 0.001) and heavier (P < 0.001) donor population. Laparoscopic DN was associated with a higher probability of left kidney procurement (P < 0.001). All 3 LDN modalities required a longer operative time (P < 0.001); robot-assisted-LDN took significantly longer than HA-LDN or P-LDN. Laparoscopic DN decreased the need for intraoperative blood transfusion (P < 0.001) and reduced the incidence of intraoperative complications (P < 0.001) and hospital length of stay (P < 0.001). However, LDN led to a significantly higher rate of readmissions, both short-term (<30 day, P < 0.001) and long-term (>30 day, P < 0.001). Undergoing HA-LDN was associated with a higher rate of an incisional hernia compared with all other modalities (P < 0.001). For recipients, LDN seemed to be associated with lower rates of graft failure at 1 year compared with ODN (P = 0.002). The odds of delayed graft function increased for kidneys with multiple arteries procured via P-LDN compared with HA-LDN (OR 3 [1,10]) and ODN (OR 5 [2, 15]).In our experience, LDN was associated with decreased donor intraoperative complications and hospital length of stay but higher rates of readmission and long-term complications.
View details for DOI 10.1097/TP.0000000000001251
View details for PubMedID 27136265
Receiving the Unwanted Gift: Infection Transmission through Organ Transplantation.
2016; 17 (3): 318-22
Infections are common in the general U.S. population, so it is inevitable that some persons with a potentially transmissible disease will become organ donors. There are numerous reports of viral, parasitic, fungal, and bacterial transmission through transplantation. At the same time, immunosuppression increases the risk of infection in organ recipients, so attribution of infectious diseases to the transplanted organ is often difficult.Review of the English-language literature.The Organ Procurement and Transplantation Network states that all potential deceased organ donors must be assessed for conditions that may influence donor acceptance. The infections most often transmitted knowingly to organ recipients are cytomegalovirus and hepatitis C virus. There was a 43% increase in the number of potential donor-derived transmission events between 2012 and 2013, but this affected only 3% of transplants; and the patterns of unexpected infection transmissions have remained fairly constant. The 2013 recognition of a case of raccoon rabies in a kidney recipient brought the risk of untested pathogens back into the general discussion of disease transmission. Also, unexpected transmissions of parasitic infection have resulted in highly visible recipient deaths.Organ transplantation has been an enormous advance in the treatment of chronic diseases, but the risk of unanticipated disease transmission has been gaining attention. The task for the organ donation community is to assess risk of transmission of clinically relevant diseases accurately without substantially diminishing organ availability.
View details for DOI 10.1089/sur.2016.009
View details for PubMedID 27096745
Long-term Outcomes for Living Pancreas Donors in the Modern Era.
2016; 100 (6): 1322-8
Living donor segmental pancreas transplants (LDSPTx) have been performed selectively to offer a preemptive transplant option for simultaneous pancreas-kidney recipients and to perform a single operation decreasing the cost of pancreas after kidney transplant. For solitary pancreas transplants, this option historically provided a better immunologic match. Although short-term donor outcomes have been documented, there are no long-term studies.We studied postdonation outcomes in 46 segmental pancreas living donors. Surgical complications, risk factors (RF) for development of diabetes mellitus (DM) and quality of life were studied. A risk stratification model (RSM) for DM was created using predonation and postdonation RFs. Recipient outcomes were analyzed.Between January 1, 1994 and May 1, 2013, 46 LDSPTx were performed. Intraoperatively, 5 (11%) donors received transfusion. Overall, 9 (20%) donors underwent splenectomy. Postoperative complications included: 6 (13%) peripancreatic fluid collections and 2 (4%) pancreatitis episodes. Postdonation, DM requiring oral hypoglycemics was diagnosed in 7 (15%) donors and insulin-dependent DM in 5 (11%) donors. RSM with three predonation RFs (oral glucose tolerance test, basal insulin, fasting plasma glucose) and 1 postdonation RF, greater than 15% increase in body mass index from preoperative (Δ body mass index >15), predicted 12 (100%) donors that developed postdonation DM. Quality of life was not significantly affected by donation. Mean graft survival was 9.5 (±4.4) years from donors without and 9.6 (±5.4) years from donors with postdonation DM.LDSPTx can be performed with good recipient outcomes. The donation is associated with donor morbidity including impaired glucose control. Donor morbidity can be minimized by using RSM and predonation counseling on life style modifications postdonation.
View details for DOI 10.1097/TP.0000000000001250
View details for PubMedID 27203593
Genetic Traits in the Liver Anatomy Between Parents and Children: An Analysis of Liver Transplant Recipients and Living Donors.
2016; 48 (6): 2084-6
To date, no significant similarities in the anatomy of the hepatic vasculature have been observed between blood-related individuals. However, we have frequently encountered anatomic similarities between parents and their children; thus, we performed an analysis of the genetic traits in the anatomy of the liver.The study cohort was 330 adult cases of living-donor liver transplantation (LDLT), in which the donor-recipient relationship was child to parent. The subjects underwent LDLT from January 2013 to December 2014. Preoperative dynamic computerized tomographic scans were used to classify the anatomy of the hepatic vasculature.Portal vein (PV) anatomy was classified as typical and 2 variant types. PV anatomy combinations in donor and recipient were typical in 232 subjects, variant in 16, and typical-variant in 82. The PV concordance rate was 75.2%, and the contingency coefficient was 0.130 (P = .017). Hepatic artery (HA) anatomy was classified as typical and 4 variant types. HA anatomy combinations in donor and recipient were typical in 167 subjects, variant in 33, and typical-variant in 130. The HA concordance rate was 60.6%, and the contingency coefficient was 0.058 (P = .294). The sizable inferior right hepatic vein in donor and recipient was present in 44 subjects, absent in 160, and discordant in 126; its concordance rate was 61.8% and contingency coefficient 0.133 (P = .014).There may be a shared but weak genetic trait between parents and children regarding the anatomy of the PV and inferior hepatic vein. This information may be helpful when LDLT is performed between 1st-degree relatives.
View details for DOI 10.1016/j.transproceed.2016.04.013
View details for PubMedID 27569949
Beta-cell replacement therapy: current outcomes and future landscape.
Current opinion in organ transplantation
2015; 20 (6): 681-90
This article provides a summary of the current outcomes of β-cell replacement strategies, an algorithm for choosing a specific modality while highlighting associated advantages and disadvantages, and outlines remaining challenges and areas of active investigation in β-cell replacement therapy.The most recent reports of islet cell allotransplantation have shown improvements over previous eras and now rival some outcomes of pancreas alone transplantation. Active areas of investigation are focused on improving techniques for islet isolation, graft monitoring, and managing challenges posed by the innate and alloimmune systems.Patients with insulin-dependent diabetes who continue to experience life threatening hypoglycemia despite maximal medical management can benefit from β-cell replacement. Emerging nontransplant technologies have not provided a physiologic euglycemic state to the extent offered by transplantation. Islet transplantation eliminates hypoglycemic episodes/unawareness, facilitates normalization of hemoglobin A1c (HbA1c), decreases microvascular disease progression, and improves quality of life for patients with problematic diabetes. Mid- and long-term outcomes of islet transplantation performed at expert centers approximate those of registry reports of solitary pancreas transplant, whereas the complication profile is quite favorable.
View details for DOI 10.1097/MOT.0000000000000245
View details for PubMedID 26536431
- Infection and Cancer Screening in Potential Living Donors: Best Practices to Protect the Donor and Recipient Curr Transpl Rep. 2015; 2: 35-43
- Total Pancreatectomy with Islet Autotransplant Failure. Now What? Curr Transpl Rep 2015; 2: 144-148
Who's covering our loved ones: surprising barriers in the sign-out process.
American journal of surgery
2013; 205 (1): 77-84
The aims of this study were to characterize obstacles affecting current sign-out practices and to evaluate the potential impact of standardized sign-out guidelines.In June 2011, detailed guidelines for transitions of care were implemented, and a 29-item multiple-choice survey was developed to assess sign-out practices, attitudes, and barriers to effective communication. Surveys were administered to residents and nurses at 3 time points. Comparisons between time points were assessed using t tests and χ(2) tests (α = .05).Guideline implementation achieved nonsignificant improvements in satisfaction with sign-outs, perceptions of patient safety, adequacy of information provided in sign-out, and patient knowledge by on-call residents. On follow-up, concerns surfaced regarding less complete sign-out processes due to new duty-hour restrictions.Guideline implementation mildly improved perceptions of safety and adequacy of sign-out; however, persistent barriers to continuity of care remain. Sign-out standardization may not adequately ensure patient safety, and further efforts to improve handoff processes are in need.
View details for DOI 10.1016/j.amjsurg.2012.05.009
View details for PubMedID 22959413
Opioid Drug Abuse and Modulation of Immune Function: Consequences in the Susceptibility to Opportunistic Infections
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
2011; 6 (4): 442-465
Infection rate among intravenous drug users (IDU) is higher than the general public, and is the major cause of morbidity and hospitalization in the IDU population. Epidemiologic studies provide data on increased prevalence of opportunistic bacterial infections such as TB and pneumonia, and viral infections such as HIV-1 and hepatitis in the IDU population. An important component in the intravenous drug abuse population and in patients receiving medically indicated chronic opioid treatment is opioid withdrawal. Data on bacterial virulence in the context of opioid withdrawal suggest that mice undergoing withdrawal had shortened survival and increased bacterial load in response to Salmonella infection. As the body of evidence in support of opioid dependency and its immunosuppressive effects is growing, it is imperative to understand the mechanisms by which opioids exert these effects and identify the populations at risk that would benefit the most from the interventions to counteract opioid immunosuppressive effects. Thus, it is important to refine the existing animal model to closely match human conditions and to cross-validate these findings through carefully controlled human studies. Better understanding of the mechanisms will facilitate the search for new therapeutic modalities to counteract adverse effects including increased infection rates. This review will summarize the effects of morphine on innate and adaptive immunity, identify the role of the mu opioid receptor in these functions and the signal transduction activated in the process. The role of opioid withdrawal in immunosuppression and the clinical relevance of these findings will also be discussed.
View details for DOI 10.1007/s11481-011-9292-5
View details for Web of Science ID 000296651500003
View details for PubMedID 21789507
View details for PubMedCentralID PMC3601186
Surgical Protocol Involving the Infusion of Paramagnetic Microparticles for Preferential Incorporation Within Porcine Islets
23rd International Congress of the Transplantation-Society
ELSEVIER SCIENCE INC. 2010: 4209–12
Despite significant advances, widespread applicability of islet cell transplantation remains elusive. Refinement of current islet isolation protocols may improve transplant outcomes. Islet purification by magnetic separation has shown early promise. However, surgical protocols must be optimized to maximize the incorporation of paramagnetic microparticles (MP) within a greater number of islets. This study explores the impact of MP concentration and infusion method on optimizing MP incorporation within islets.Five porcine pancreata were procured from donors after cardiac death. Splenic lobes were isolated and infused with varying concentrations of MP (8, 16, and 32 × 10(8) MP/L of cold preservation solution) and using one of two delivery techniques (hanging bag versus hand-syringe). After procurement and infusion, pancreata were stored at 0°C to 4°C during transportation (less than 1 hour), fixed in 10% buffered formalin, and examined by standard magnetic resonance imaging (MRI) and histopathology.T2*-weighted MRI showed homogeneous distribution of MP in all experimental splenic lobes. In addition, histologic analysis confirmed that MP were primarily located within the microvasculature of islets (82% to 85%), with few MP present in acinar tissue (15% to 18%), with an average of five to seven MP per islet (within a 5-μm thick section). The highest MP incorporation was achieved at a concentration of 16 × 10(8) MP/L using the hand-syringe technique.This preliminary study suggests that optimization of a surgical protocol, MP concentrations, and applied infusion pressures may enable more uniform distribution of MP in the porcine pancreas and better control of MP incorporation within islets. These results may have implications in maximizing the efficacy of islet purification by magnetic separation.
View details for DOI 10.1016/j.transproceed.2010.09.138
View details for Web of Science ID 000285732200083
View details for PubMedID 21168666
View details for PubMedCentralID PMC3035915
Pancreas oxygen persufflation increases ATP levels as shown by nuclear magnetic resonance.
2010; 42 (6): 2011-5
Islet transplantation is a promising treatment for type 1 diabetes. Due to a shortage of suitable human pancreata, high cost, and the large dose of islets presently required for long-term diabetes reversal; it is important to maximize viable islet yield. Traditional methods of pancreas preservation have been identified as suboptimal due to insufficient oxygenation. Enhanced oxygen delivery is a key area of improvement. In this paper, we explored improved oxygen delivery by persufflation (PSF), ie, vascular gas perfusion.Human pancreata were obtained from brain-dead donors. Porcine pancreata were procured by en bloc viscerectomy from heparinized donation after cardiac death donors and were either preserved by either two-layer method (TLM) or PSF. Following procurement, organs were transported to a 1.5-T magnetic resonance (MR) system for (31)P nuclear magnetic resonance spectroscopy to investigate their bioenergetic status by measuring the ratio of adenosine triphosphate to inorganic phosphate (ATP:P(i)) and for assessing PSF homogeneity by MRI.Human and porcine pancreata can be effectively preserved by PSF. MRI showed that pancreatic tissue was homogeneously filled with gas. TLM can effectively raise ATP:P(i) levels in rat pancreata but not in larger porcine pancreata. ATP:P(i) levels were almost undetectable in porcine organs preserved with TLM. When human or porcine organs were preserved by PSF, ATP:P(i) was elevated to levels similar to those observed in rat pancreata.The methods developed for human and porcine pancreas PSF homogeneously deliver oxygen throughout the organ. This elevates ATP levels during preservation and may improve islet isolation outcomes while enabling the use of marginal donors, thus expanding the usable donor pool.
View details for DOI 10.1016/j.transproceed.2010.05.091
View details for PubMedID 20692395
View details for PubMedCentralID PMC2947552
Anti-CD25 antibody (daclizumab) maintenance therapy in pancreas transplantation.
2010; 42 (6): 2003-5
Calcineurin inhibitors (CNI) are the basis of contemporary immunosuppression in clinical pancreas transplantation (PT). Nevertheless, CNI toxicities, especially nephrotoxicity, have stimulated the search for CNI-sparing protocols. We performed a retrospective analysis of 25 PT patients with progressive CNI toxicities that were switched to a daclizumab (DAC)-based maintenance regimen.From 2003 to 2007, 25 PT patients with progressive CNI toxicity (predominantly nephrotoxicity) were identified and switched from CNI to monthly DAC maintenance therapy. The DAC group was compared with matched control subjects (1:1) by transplant type and number, age, year of transplant, and duct management.Results showed improved graft survival rates and decreased immunologic loss rates at 1, 3, and 5 years in the DAC group compared with the control group. There was no difference in patient survival rate between the 2 groups. Analysis demonstrates that DAC maintenance therapy is safe and effective for PT patients experiencing CNI toxicities. A randomized trial to compare DAC- and CNI-based regimens is needed in CNI-intolerant patients, with particular attention to the impact on renal function and patient morbidity (eg, infection rates).
View details for DOI 10.1016/j.transproceed.2010.05.083
View details for PubMedID 20692392
Continuous real-time viability assessment of kidneys based on oxygen consumption.
2010; 42 (6): 2020-3
Current ex vivo quality assessment of donor kidneys is limited to vascular resistance measurements and histological analysis. New techniques for the assessment of organ quality before transplantation may further improve clinical outcomes while expanding the depleted deceased-donor pool. We propose the measurement of whole organ oxygen consumption rate (WOOCR) as a method to assess the quality of kidneys in real time before transplantation.Five porcine kidneys were procured using a donation after cardiac death (DCD) model. The renal artery and renal vein were cannulated and the kidney connected to a custom-made hypothermic machine perfusion (HMP) system equipped with an inline oxygenator and fiber-optic oxygen sensors. Kidneys were perfused at 8 degrees C, and the perfusion parameters and partial oxygen pressures (pO(2)) were measured to calculate WOOCR.Without an inline oxygenator, the pO(2) of the perfusion solution at the arterial inlet and venous outlet diminished to near 0 within minutes. However, once adequate oxygenation was provided, a significant pO(2) difference was observed and used to calculate the WOOCR. The WOOCR was consistently measured from presumably healthy kidneys, and results suggest that it can be used to differentiate between healthy and purposely damaged organs.Custom-made HMP systems equipped with an oxygenator and inline oxygen sensors can be applied for WOOCR measurements. We suggest that WOOCR is a promising approach for the real-time quality assessment of kidneys and other organs during preservation before transplantation.
View details for DOI 10.1016/j.transproceed.2010.05.082
View details for PubMedID 20692397
View details for PubMedCentralID PMC2947551
Persufflation improves pancreas preservation when compared with the two-layer method.
2010; 42 (6): 2016-9
Islet transplantation is emerging as a promising treatment for patients with type 1 diabetes. It is important to maximize viable islet yield for each organ due to scarcity of suitable human donor pancreata, high cost, and the large dose of islets required for insulin independence. However, organ transport for 8 hours using the two-layer method (TLM) frequently results in low islet yields. Since efficient oxygenation of the core of larger organs (eg, pig, human) in TLM has recently come under question, we investigated oxygen persufflation as an alternative way to supply the pancreas with oxygen during preservation. Porcine pancreata were procured from donors after cardiac death and preserved by either TLM or persufflation for 24 hours and subsequently fixed. Biopsies collected from several regions of the pancreas were sectioned, stained with hematoxylin and eosin, and evaluated by a histologist. Persufflated tissues exhibited distended capillaries and significantly less autolysis/cell death relative to regions not exposed to persufflation or to tissues preserved with TLM. The histology presented here suggests that after 24 hours of preservation, persufflation dramatically improves tissue health when compared with TLM. These results indicate the potential for persufflation to improve viable islet yields and extend the duration of preservation, allowing more donor organs to be utilized.
View details for DOI 10.1016/j.transproceed.2010.05.092
View details for PubMedID 20692396
View details for PubMedCentralID PMC2956134
Enteric parasites in east African immigrants. Symptoms and duration of U.S. residence are not predictive.
2000; 83 (12): 25-8
The Minnesota Department of Health recommends a health assessment for all refugees within 1 to 3 months of arrival, including screening for enteric parasites. Little information exists, however, to help clinicians decide whether to screen asymptomatic persons who have lived in the United States for a year or more. We questioned 71 immigrants from East Africa now living in Minnesota's Twin Cities about gastrointestinal symptoms and duration of residence in the United States and asked for stool specimens for ova and parasite examination. Fifty-one patients (72%) returned specimens. The prevalence of symptoms was no different in the 14 patients with pathogenic parasites than in the 37 without (71% vs. 76%). Patients with pathogens were likely to have lived in the United States for less time than those without pathogens (median 17 months vs. 32 months), but the groups were not discrete. Clinical data did not identify a group unlikely to have parasites or need screening.
View details for PubMedID 11147284