Kazunari Sasaki, MD

All Publications

• Hepatitis C-positive grafts for hepatitis C-negative recipients in liver transplantation: Buried treasure or depleting resource? Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Nakayama, T., Krist, D. T., Akabane, M., Imaoka, Y., Esquivel, C. O., Kwong, A. J., Kwo, P. Y., Melcher, M. L., Sasaki, K. 2024

  Abstract

  Long-term outcomes of using hepatitis C virus (HCV) positive donors in HCV-negative recipients in liver transplantation (LT) are not well established. Data from the United Network for Organ Sharing (UNOS) database between July 1, 2015, and December 31, 2023, were analyzed. The cohort included 44,447 HCV antibody-negative (Ab-) candidates who underwent deceased donor LT. Changes in case numbers and utilization rates of HCV-positive donors, divided into HCV-viremic (NAT+) or Ab+ nonviremic (Ab+/NAT-), were assessed. Kaplan-Meier analysis and propensity score matching were used to evaluate 5-year graft survival (GS). The number of HCV-viremic donation after brain death (DBD) donors and their use in LT for HCV Ab- recipients peaked at 640 donors in 2019 and 289 LTs in 2022. In contrast, Ab+ nonviremic DBD donations are rising, with 536 donors and 284 LTs in 2023. The utilization rate of viremic DBD grafts has continuously decreased despite increased willingness by waitlist candidates to accept them. HCV-positive donation after circulatory death (DCD) donors were seldom utilized in the study period. The 5-year GS rates for HCV-viremic, Ab+ nonviremic, and naïve donors were not significantly different in either DBD (p=0.56) or DCD (p=0.52). Furthermore, Ishak stage 2 or 3 fibrotic DBD grafts had similar 5-year GS to non-fibrotic grafts. The findings suggest that the long-term outcome of using HCV-viremic DBD or DCD grafts for HCV-negative recipients is comparable to that of other graft types, and that fibrotic grafts have the potential to expand the DBD donor pool.

  View details for DOI 10.1097/LVT.0000000000000557

  View details for PubMedID 39679922

• Combining a deep learning model with clinical data better predicts hepatocellular carcinoma behavior following surgery. Journal of pathology informatics Schmauch, B., Elsoukkary, S. S., Moro, A., Raj, R., Wehrle, C. J., Sasaki, K., Calderaro, J., Sin-Chan, P., Aucejo, F., Roberts, D. E. 2024; 15: 100360

  Abstract

  Hepatocellular carcinoma (HCC) is among the most common cancers worldwide, and tumor recurrence following liver resection or transplantation is one of the highest contributors to mortality in HCC patients after surgery. Using artificial intelligence (AI), we developed an interdisciplinary model to predict HCC recurrence and patient survival following surgery. We collected whole-slide H&E images, clinical variables, and follow-up data from 300 patients with HCC who underwent transplant and 169 patients who underwent resection at the Cleveland Clinic. A deep learning model was trained to predict recurrence-free survival (RFS) and disease-specific survival (DSS) from the H&E-stained slides. Repeated cross-validation splits were used to compute robust C-index estimates, and the results were compared to those obtained by fitting a Cox proportional hazard model using only clinical variables. While the deep learning model alone was predictive of recurrence and survival among patients in both cohorts, integrating the clinical and histologic models significantly increased the C-index in each cohort. In every subgroup analyzed, we found that a combined clinical and deep learning model better predicted post-surgical outcome in HCC patients compared to either approach independently.

  View details for DOI 10.1016/j.jpi.2023.100360

  View details for PubMedID 38292073

  View details for PubMedCentralID PMC10825615

• Recurrence Timing and Risk Following Curative Resection of Colorectal Liver Metastases: Insights From a Hazard Function Analysis. Journal of surgical oncology Kawashima, J., Akabane, M., Endo, Y., Woldesenbet, S., Altaf, A., Ruzzenente, A., Popescu, I., Kitago, M., Poultsides, G., Sasaki, K., Aucejo, F., Sahara, K., Endo, I., Pawlik, T. M. 2024

  Abstract

  INTRODUCTION: There is no consensus on the optimal surveillance interval for patients undergoing resection of colorectal liver metastases (CRLM). We sought to assess the timing and intensity of recurrence following curative-intent resection of CRLM utilizing a recurrence-free survival (RFS) hazard function analysis.METHODS: Patients with CRLM who underwent curative-intent resection were identified from a multi-institutional database. The RFS hazard function was used to plot hazard rates and identify the peak of recurrence over time.RESULTS: Among 1804 patients, the median RFS was 19.9 months. In the analytic cohort, the RFS hazard curve peaked at 5.9 months (peak hazard rate: 0.054) and gradually declined, indicative of early recurrence. In subgroup analyses, patients with high and medium tumor burden scores (TBS) had RFS hazard peaks at 4.9 months (peak hazard rate: 0.060) and 5.8 months (peak hazard rate: 0.054), respectively. In contrast, patients with low TBS had a later peak at 7.5 months, with the lowest peak hazard rate of 0.047.CONCLUSIONS: The recurrence peak for CRLM patients occurred approximately 6 months postsurgery, highlighting the need for intensified early postoperative surveillance. Patients with high TBS experienced earlier recurrence, underscoring the importance of close monitoring, particularly during the first 6 months after surgery.

  View details for DOI 10.1002/jso.28007

  View details for PubMedID 39574215

• ASO Visual Abstract: Evaluating Combinations of Biological and Clinicopathologic Factors Linked to Poor Outcomes in Resected Colorectal Liver Metastasis: An External Validation Study. Annals of surgical oncology Sasaki, K., Wang, J., Kamphues, C., Buettner, S., Gagniere, J., Ardilles, V., Imai, K., Wagner, D., Pozios, I., Papakonstantinou, D., Pikoulis, E., Antoniou, E., Morioka, D., Løes, I. M., Lønning, P. E., Kornprat, P., Aucejo, F. N., Baba, H., de Santibañes, E., Kaczirek, K., Burkhart, R., Endo, I., Beyer, K., Kreis, M. E., Pawlik, T. M., Margonis, G. A. 2024

  View details for DOI 10.1245/s10434-024-16436-w

  View details for PubMedID 39521737

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

  Abstract

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

  View details for DOI 10.1097/TXD.0000000000001722

  View details for PubMedID 39440201

• Abdominal aortic calcification among gastroenterological and transplant surgery. Annals of gastroenterological surgery Imaoka, Y., Ohira, M., Akabane, M., Sasaki, K., Ohdan, H. 2024; 8 (6): 987-998

  Abstract

  This review discusses the increasing global trend towards an aging population, which has resulted in a growing number of surgeries being performed on elderly patients, particularly those living with cancer. The focus was on the implications of abdominal aortic calcification (AAC), an indicator of systemic atherosclerosis, in these patients. This comprehensive review provided evidence detailing the complex processes of atherosclerosis and vascular calcification and various approaches to assess this condition. The prevalence of AAC is related to multiple factors, including cardiovascular disease, inflammation, frailty in various types of gastroenterological surgery. Additionally, notable links were found between AAC, postoperative complications, and patient survival following gastroenterological surgery. This study highlights how AAC could negatively impact the health status of elderly patients and undermine treatment efficacy, stressing the need for more research in this domain to improve patient outcomes.

  View details for DOI 10.1002/ags3.12816

  View details for PubMedID 39502733

  View details for PubMedCentralID PMC11533033

• ASO Author Reflections: Biological Contraindications to Surgery in Colorectal Liver Metastasis. Annals of surgical oncology Sasaki, K., Pawlik, T. M., Margonis, G. A. 2024

  View details for DOI 10.1245/s10434-024-16412-4

  View details for PubMedID 39441322

• Preoperative identification of early extrahepatic recurrence after hepatectomy for colorectal liver metastases: A machine learning approach. World journal of surgery Kawashima, J., Endo, Y., Woldesenbet, S., Chatzipanagiotou, O. P., Tsilimigras, D. I., Catalano, G., Khan, M. M., Rashid, Z., Khalil, M., Altaf, A., Munir, M. M., Guglielmi, A., Ruzzenente, A., Aldrighetti, L., Alexandrescu, S., Kitago, M., Poultsides, G., Sasaki, K., Aucejo, F., Endo, I., Pawlik, T. M. 2024

  Abstract

  Machine learning (ML) may provide novel insights into data patterns and improve model prediction accuracy. The current study sought to develop and validate an ML model to predict early extra-hepatic recurrence (EEHR) among patients undergoing resection of colorectal liver metastasis (CRLM).Patients with CRLM who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. An eXtreme gradient boosting (XGBoost) model was developed to estimate the risk of EEHR, defined as extrahepatic recurrence within 12 months after hepatectomy, using clinicopathological factors. The relative importance of factors was determined using Shapley additive explanations (SHAP) values.Among 1410 patients undergoing curative-intent resection, 131 (9.3%) patients experienced EEHR. Median OS among patients with and without EEHR was 35.4 months (interquartile range [IQR] 29.9-46.7) versus 120.5 months (IQR 97.2-134.0), respectively (p < 0.001). The ML predictive model had c-index values of 0.77 (95% CI, 0.72-0.81) and 0.77 (95% CI, 0.73-0.80) in the entire dataset and the validation data set with bootstrapping resamples, respectively. The SHAP algorithm demonstrated that T and N primary tumor categories, as well as tumor burden score were the three most important predictors of EEHR. An easy-to-use risk calculator for EEHR was developed and made available online at: https://junkawashima.shinyapps.io/EEHR/.An easy-to-use online calculator was developed using ML to help clinicians predict the chance of EEHR after curative-intent resection for CRLM. This tool may help clinicians in decision-making related to treatment strategies for patients with CRLM.

  View details for DOI 10.1002/wjs.12376

  View details for PubMedID 39425666

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

  Abstract

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

  View details for DOI 10.1097/LVT.0000000000000513

  View details for PubMedID 39412327

• Evaluating Combinations of Biological and Clinicopathologic Factors Linked to Poor Outcomes in Resected Colorectal Liver Metastasis: An External Validation Study. Annals of surgical oncology Sasaki, K., Wang, J., Kamphues, C., Buettner, S., Gagniere, J., Ardilles, V., Imai, K., Wagner, D., Pozios, I., Papakonstantinou, D., Pikoulis, E., Antoniou, E., Morioka, D., Loes, I. M., Lonning, P. E., Kornprat, P., Aucejo, F. N., Baba, H., de Santibanes, E., Kaczirek, K., Burkhart, R., Endo, I., Beyer, K., Kreis, M. E., Pawlik, T. M., Margonis, G. A. 2024

  Abstract

  BACKGROUND: Recent studies have suggested that certain combinations of KRAS or BRAF biomarkers with clinical factors are associated with poor outcomes and may indicate that surgery could be "biologically" futile in otherwise technically resectable colorectal liver metastasis (CRLM). However, these combinations have yet to be validated through external studies.PATIENTS AND METHODS: We conducted a systematic search to identify these studies. The overall survival (OS) of patients with these combinations was evaluated in a cohort of patients treated at 11 tertiary centers. Additionally, the study investigated whether using high-risk KRAS point mutations in these combinations could be associated with particularly poor outcomes.RESULTS: The recommendations of four studies were validated in 1661 patients. The first three studies utilized KRAS, and their validation showed the following median and 5-year OS: (1) 30 months and 16.9%, (2) 24.3 months and 21.6%, and (3) 46.8 months and 44.4%, respectively. When analyzing only patients with high-risk KRAS mutations, median and 5-year OS decreased to: (1) 26.2 months and 0%, (2) 22.3 months and 15.1%, and (3) not reached and 44.9%, respectively. The fourth study utilized BRAF, and its validation showed a median OS of 10.4 months, with no survivors beyond 21 months.CONCLUSION: The combinations of biomarkers and clinical factors proposed to render surgery for CRLM futile, as presented in studies 1 (KRAS high-risk mutations) and 4, appear justified. In these studies, there were no long-term survivors, and survival was similar to that of historic cohorts with similar mutational profiles that received systemic therapies alone for unresectable disease.

  View details for DOI 10.1245/s10434-024-16319-0

  View details for PubMedID 39377842

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

  Abstract

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

  View details for DOI 10.1097/TXD.0000000000001661

  View details for PubMedID 39359941

  View details for PubMedCentralID PMC11446594

• Innovative Strategies for Liver Transplantation: The Role of Mesenchymal Stem Cells and Their Cell-Free Derivatives. Cells Akabane, M., Imaoka, Y., Kawashima, J., Endo, Y., Schenk, A., Sasaki, K., Pawlik, T. M. 2024; 13 (19)

  Abstract

  Despite being the standard treatment for end-stage liver disease, liver transplantation has limitations like donor scarcity, high surgical costs, and immune rejection risks. Mesenchymal stem cells (MSCs) and their derivatives offer potential for liver regeneration and transplantation. MSCs, known for their multipotency, low immunogenicity, and ease of obtainability, can differentiate into hepatocyte-like cells and secrete bioactive factors that promote liver repair and reduce immune rejection. However, the clinical application of MSCs is limited by risks such as aberrant differentiation and low engraftment rates. As a safer alternative, MSC-derived secretomes and extracellular vesicles (EVs) offer promising therapeutic benefits, including enhanced graft survival, immunomodulation, and reduced ischemia-reperfusion injury. Current research highlights the efficacy of MSC-derived therapies in improving liver transplant outcomes, but further studies are necessary to standardize clinical applications. This review highlights the potential of MSCs and EVs to address key challenges in liver transplantation, paving the way for innovative therapeutic strategies.

  View details for DOI 10.3390/cells13191604

  View details for PubMedID 39404368

  View details for PubMedCentralID PMC11475694

• Evaluation of prognostic efficacy of liver immune status index in predicting postoperative outcomes in hepatocellular carcinoma patients: A multi-institutional retrospective study. Journal of hepato-biliary-pancreatic sciences Imaoka, Y., Ohira, M., Kobayashi, T., Honmyo, N., Hamaoka, M., Onoe, T., Takei, D., Oishi, K., Abe, T., Nakayama, T., Akabane, M., Sasaki, K., Ohdan, H. 2024

  Abstract

  Hepatocellular carcinoma (HCC) ranks third in cancer-related deaths globally. Despite treatment advances, high post-hepatectomy recurrence rates (RR), especially with liver fibrosis and hepatitis C virus infection, remain challenging. Key prognostic factors include vascular invasion and perioperative blood loss, impacting extrahepatic recurrence. Natural killer (NK) cells are crucial in countering circulating tumor cells through TRAIL-mediated pathways. The aim of this study was to validate the liver immune status index (LISI) as a predictive tool for liver NK cell antitumor efficiency, particularly in HCC patients with vascular invasion.A retrospective analysis of 1337 primary HCC hepatectomies was conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Clinicodemographic data were extracted from electronic medical records. Prognostic indices (FIB-4, ALBI, ALICE, GNRI, APRI, and LISI) were evaluated using area under the receiver operating characteristic curve values. Survival analyses employed Kaplan-Meier estimations and log-rank tests.LISI significantly correlated with other prognostic markers and stratified patients into risk groups with distinct overall survival (OS) and RR. It showed superior predictive performance for 2-year OS and RR, especially in patients with vascular invasion. Over longer periods, APRI and FIB-4 index reliabilities improved. The HISCO-HCC score, combining LISI, tumor burden score, and alpha-fetoprotein levels, enhanced prognostic accuracy.LISI outperformed existing models, particularly in HCC with vascular invasion. The HISCO-HCC score offers improved prognostic precision, guiding immunotherapeutic strategies and individualized patient care in HCC.

  View details for DOI 10.1002/jhbp.12070

  View details for PubMedID 39313837

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

  Abstract

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

  View details for DOI 10.1097/LVT.0000000000000460

  View details for PubMedID 39287561

• Advanced viability assessment in machine perfusion: what lies ahead? EBioMedicine Nakayama, T., Sasaki, K. 2024; 108: 105351

  View details for DOI 10.1016/j.ebiom.2024.105351

  View details for PubMedID 39278109

• Comment on "Age Matters: What Affects the Cumulative Lifespan of a Transplanted Liver?". Annals of surgery open : perspectives of surgical history, education, and clinical approaches Akabane, M., Imaoka, Y., Nakayama, T., Sasaki, K. 2024; 5 (3): e475

  View details for DOI 10.1097/AS9.0000000000000475

  View details for PubMedID 39310331

  View details for PubMedCentralID PMC11415112

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

  Abstract

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

  View details for DOI 10.1097/LVT.0000000000000469

  View details for PubMedID 39177578

• Reappraisal of tacrolimus levels post liver transplant for hepatocellular carcinoma: A multicenter study toward personalized immunosuppression regimen. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Kojima, L., Akabane, M., Murray, M., Fruscione, M., Soma, D., Snyder, A., McVey, J., Firl, D. J., Hernandez-Alejandro, R., Kubal, C. A., Markmann, J. F., Aucejo, F. N., Tomiyama, K., Kimura, S., Sasaki, K. 2024

  Abstract

  BACKGROUND: Post-liver transplant (LT) immunosuppression is necessary to prevent rejection; however, a major consequence of this is tumor recurrence. Although recurrence is a concern after LT for patients with hepatocellular carcinoma (HCC), the oncologically optimal tacrolimus (FK) regimen is still unknown.METHOD: This retrospective study included 1,406 LT patients with HCC (2002-2019) at four U.S. institutions utilizing variable post-LT immunosuppression regimens. ROC analyses were performed to investigate the influences of post-LT time-weighted average FK (TWA-FK) level on HCC recurrence. A competing risk analysis was employed to evaluate the prognostic influence of TWA-FK while adjusting for patient and tumor characteristics.RESULTS: The area under the curve (AUC) for TWA-FK was greatest at 2 weeks (0.68), followed by 1 week (0.64) post-LT. Importantly, this was consistently observed across the institutions despite immunosuppression regimen variability. Additionally, the TWA-FK at 2 weeks was not associated with rejection within 6 months of LT. A competing risk regression analysis showed that TWA-FK at 2 weeks post-LT is significantly associated with recurrence (HR: 1.31, 95% CI: 1.21-1.41 p<0.001). The TWA-FK effect on recurrence varied depending on the exposure level and the individual's risk of recurrence, including vascular invasion and tumor morphology.CONCLUSION: Although previous studies have explored the influence of FK levels at 1 to 3 months post-LT on HCC recurrence, this current study suggests that earlier time points and exposure levels must be evaluated. Each patient's oncological risk must also be considered in developing an individualized immunosuppression regimen.

  View details for DOI 10.1097/LVT.0000000000000459

  View details for PubMedID 39172007

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

  Abstract

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

  View details for DOI 10.1111/hepr.14102

  View details for PubMedID 39134448

• Editorial: Clinical management of cholangiocarcinoma: surgical approaches and therapies. Frontiers in oncology Takahashi, H., Cohen, N. A., Sasaki, K., Gunasekaran, G. 2024; 14: 1456958

  View details for DOI 10.3389/fonc.2024.1456958

  View details for PubMedID 39135993

  View details for PubMedCentralID PMC11317458

• Preoperative and postoperative predictive models of early recurrence for colorectal liver metastases following chemotherapy and curative-intent one-stage hepatectomy. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology Kawashima, J., Chatzipanagiotou, O. P., Tsilimigras, D. I., Khan, M. M., Catalano, G., Rashid, Z., Khalil, M., Altaf, A., Munir, M. M., Endo, Y., Woldesenbet, S., Guglielmi, A., Ruzzenente, A., Aldrighetti, L., Alexandrescu, S., Kitago, M., Poultsides, G., Sasaki, K., Aucejo, F., Endo, I., Pawlik, T. M. 2024; 50 (9): 108532

  Abstract

  INTRODUCTION: Accurate prediction of patients at risk for early recurrence (ER) among patients with colorectal liver metastases (CRLM) following preoperative chemotherapy and hepatectomy remains limited.METHODS: Patients with CRLM who received chemotherapy prior to undergoing curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Multivariable Cox regression analysis was used to assess clinicopathological factors associated with ER, and an online calculator was developed and validated.RESULTS: Among 768 patients undergoing preoperative chemotherapy and curative-intent resection, 128 (16.7%) patients had ER. Multivariable Cox analysis demonstrated that Eastern Cooperative Oncology Group Performance status ≥1 (HR 2.09, 95%CI 1.46-2.98), rectal cancer (HR 1.95, 95%CI 1.35-2.83), lymph node metastases (HR 2.39, 95%CI 1.60-3.56), mutated Kirsten rat sarcoma oncogene status (HR 1.95, 95%CI 1.25-3.02), increase in tumor burden score during chemotherapy (HR 1.51, 95%CI 1.03-2.24), and bilateral metastases (HR 1.94, 95%CI 1.35-2.79) were independent predictors of ER in the preoperative setting. In the postoperative model, in addition to the aforementioned factors, tumor regression grade was associated with higher hazards of ER (HR 1.91, 95%CI 1.32-2.75), while receipt of adjuvant chemotherapy was associated with lower likelihood of ER (HR 0.44, 95%CI 0.30-0.63). The discriminative accuracy of the preoperative (training: c-index: 0.77, 95%CI 0.72-0.81; internal validation: c-index: 0.79, 95%CI 0.75-0.82) and postoperative (training: c-index: 0.79, 95%CI 0.75-0.83; internal validation: c-index: 0.81, 95%CI 0.77-0.84) models was favorable (https://junkawashima.shinyapps.io/CRLMfollwingchemotherapy/).CONCLUSIONS: Patient-, tumor- and treatment-related characteristics in the preoperative and postoperative setting were utilized to develop an online, easy-to-use risk calculator for ER following resection of CRLM.

  View details for DOI 10.1016/j.ejso.2024.108532

  View details for PubMedID 39004061

• Hepatectomy versus systemic therapy for liver-limited BRAF V600E-mutated colorectal liver metastases: multicentre retrospective study. The British journal of surgery Margonis, G. A., Wang, J. J., Boerner, T., Moretto, R., Buettner, S., Andreatos, N., Gagniere, J., Wagner, D., Loes, I. M., Bergamo, F., Pietrantonio, F., Scartozzi, M., Spallanzani, A., Vincenzi, B., Antoniou, E., Pikoulis, E., Sartore-Bianchi, A., Stasinos, G., Sasaki, K., Pawlik, T. M., Orlandi, A., Pella, N., Fitschek, F., Kaczirek, K., Dupre, A., Pozios, I., Beyer, K., Kornprat, P., Aucejo, F. N., Burkhart, R., Weiss, M. J., Lonning, P. E., Poultsides, G., Cremolini, C., Kreis, M. E., D'Angelica, M. 2024; 111 (7)

  Abstract

  BACKGROUND: To date, only two studies have compared the outcomes of patients with liver-limited BRAF V600E-mutated colorectal liver metastases (CRLMs) managed with resection versus systemic therapy alone, and these have reported contradictory findings.METHODS: In this observational, international, multicentre study, patients with liver-limited BRAF V600E-mutated CRLMs treated with resection or systemic therapy alone were identified from institutional databases. Patterns of recurrence/progression and overall survival were compared using multivariable analyses of the entire cohort and a propensity score-matched cohort.RESULTS: Of 170 patients included, 119 underwent hepatectomy and 51 received systemic treatment. Surgically treated patients had a more favourable pattern of recurrence with most recurrences limited to a single site, whereas diffuse progression was more common among patients who received systemic treatment (19 versus 44%; P = 0.002). Surgically treated patients had longer median overall survival (35 versus 20 months; P < 0.001). Hepatectomy was independently associated with better OS than systemic treatment alone (HR 0.37, 95% c.i. 0.21 to 0.65). In the propensity score-matched cohort, surgically treated patients had longer median overall survival (28 versus 20 months; P < 0.001); hepatectomy was independently associated with better overall survival (HR 0.47, 0.25 to 0.88).CONCLUSION: BRAF V600E mutation should not be considered a contraindication to surgery for patients with resectable, liver-only CRLMs.

  View details for DOI 10.1093/bjs/znae176

  View details for PubMedID 39051667

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

  Abstract

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

  View details for DOI 10.1097/TXD.0000000000001657

  View details for PubMedID 38881743

  View details for PubMedCentralID PMC11177833

• Chronological and Geographical Variations in the Incidence and Acceptance of COVID-19-Positive Donors and Outcomes Among Abdominal Transplant Patients. Clinical transplantation Yang, J., Endo, Y., Sasaki, K., Schenk, A., Pawlik, T. M. 2024; 38 (7): e15391

  Abstract

  Given the importance of understanding COVID-19-positive donor incidence and acceptance, we characterize chronological and geographic variations in COVID-19 incidence relative to COVID-19-positive donor acceptance.Data on deceased donors and recipients of liver and kidney transplants were obtained from the UNOS database between 2020 and 2023. Hierarchical cluster analysis was used to assess trends in COVID-19-positive donor incidence. Posttransplant graft and patient survival were assessed using Kaplan-Meier curves.From among 38 429 deceased donors, 1517 were COVID-19 positive. Fewer kidneys (72.4% vs. 76.5%, p < 0.001) and livers (56.4% vs. 62.0%, p < 0.001) were used from COVID-19-positive donors versus COVID-19-negative donors. Areas characterized by steadily increased COVID-19 donor incidence exhibit the highest transplantation acceptance rates (92.33%), followed by intermediate (84.62%) and rapidly increased (80.00%) COVID-19 incidence areas (p = 0.016). Posttransplant graft and patient survival was comparable among recipients, irrespective of donor COVID-19 status.Regions experiencing heightened rates of COVID-19-positive donors are associated with decreased acceptance of liver and kidney transplantation. Similar graft and patient survival is noted among recipients, irrespective of donor COVID-19 status. These findings emphasize the need for adaptive practices and unified medical consensus in navigating a dynamic pandemic.

  View details for DOI 10.1111/ctr.15391

  View details for PubMedID 38967586

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

  Abstract

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

  View details for DOI 10.1111/ctr.15379

  View details for PubMedID 38952196

• Letter to the Editor: Liver Machine Perfusion Technology in Liver Transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Akabane, M., Sasaki, K. 2024

  View details for DOI 10.1016/j.ajt.2024.05.022

  View details for PubMedID 38914282

• Continuous Risk Score Predicts Waitlist & Post-Transplant Outcomes in Hepatocellular Carcinoma Despite Exception Changes. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Akabane, M., McVey, J. C., Firl, D. J., Kwong, A. J., Melcher, M. L., Kim, W. R., Sasaki, K. 2024

  Abstract

  Continuous risk stratification of candidates and urgency-based prioritization have been utilized for liver transplantation (LT) in non-hepatocellular carcinoma (HCC) patients in the United States. Instead, for HCC patients, a dichotomous criterion with exception points is still used. This study evaluated the utility of the hazard associated with LT for HCC (HALT-HCC), an oncological continuous risk score, to stratify waitlist dropout and post-LT outcomes.A competing risk model was developed and validated using the UNOS database (2012-2021) through multiple policy changes. The primary outcome was to assess the discrimination ability of waitlist dropouts and LT outcomes. The study focused on the HALT-HCC score, compared to other HCC risk scores.Among 23,858 candidates, 14,646 (59.9%) underwent LT and 5,196 (21.8%) dropped out of the waitlist. Higher HALT-HCC scores correlated with increased dropout incidence and lower predicted five-year overall survival after LT. HALT-HCC demonstrated the highest AUC values for predicting dropout at various intervals post-listing (0.68 at six months, 0.66 at one year), with excellent calibration (R2=0.95 at six months, 0.88 at one year). Its accuracy remained stable across policy periods and locoregional therapy applications.This study highlights the predictive capability of the continuous oncological risk score to forecast waitlist dropout and post-LT outcomes in HCC patients, independent of policy changes. The study advocates integrating continuous scoring systems like HALT-HCC in liver allocation decisions, balancing urgency, organ utility, and survival benefit.

  View details for DOI 10.1016/j.cgh.2024.05.046

  View details for PubMedID 38908731

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

  Abstract

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

  View details for DOI 10.1016/j.ajt.2024.06.004

  View details for PubMedID 38866110

• Expanding Selection Criteria in Deceased Donor Liver Transplantation for Hepatocellular Carcinoma: Long-term Follow-up of a National Registry and 2 Transplant Centers. Transplantation Wehrle, C. J., Kusakabe, J., Akabane, M., Maspero, M., Zervos, B., Modaresi Esfeh, J., Whitsett Linganna, M., Imaoka, Y., Khalil, M., Pita, A., Kim, J., Diago-Uso, T., Fujiki, M., Eghtesad, B., Quintini, C., Kwon, C. D., Pinna, A., Aucejo, F., Miller, C., Mazzaferro, V., Schlegel, A., Sasaki, K., Hashimoto, K. 2024

  Abstract

  This study compares selection criteria for liver transplant (LT) for hepatocellular carcinoma (HCC) for inclusivity and predictive ability to identify the most permissive criteria that maintain patient outcomes.The Scientific Registry of Transplant Recipients (SRTR) database was queried for deceased donor LT's for HCC (2003-2020) with 3-y follow-up; these data were compared with a 2-center experience. Milan, University of California, San Francisco (UCSF), 5-5-500, Up-to-seven (U7), HALT-HCC, and Metroticket 2.0 scores were calculated.Nationally, 26 409 patients were included, and 547 at the 2 institutions. Median SRTR-follow-up was 6.8 y (interquartile range 3.9-10.1). Three criteria allowed the expansion of candidacy versus Milan: UCSF (7.7%, n = 1898), Metroticket 2.0 (4.2%, n = 1037), and U7 (3.5%, n = 828). The absolute difference in 3-y overall survival (OS) between scores was 1.5%. HALT-HCC (area under the curve [AUC] = 0.559, 0.551-0.567) best predicted 3-y OS although AUC was notably similar between criteria (0.506 < AUC < 0.527, Mila n = 0.513, UCSF = 0.506, 5-5-500 = 0.522, U7 = 0.511, HALT-HCC = 0.559, and Metroticket 2.0 = 0.520), as was Harrall's c-statistic (0.507 < c-statistic < 0.532). All scores predicted survival to P < 0.001 on competing risk analysis. Median follow-up in our enterprise was 9.8 y (interquartile range 7.1-13.3). U7 (13.0%, n = 58), UCSF (11.1%, n = 50), HALT-HCC (6.4%, n = 29), and Metroticket 2.0 (6.3%, n = 28) allowed candidate expansion. HALT-HCC (AUC = 0.768, 0.713-0.823) and Metroticket 2.0 (AUC = 0.739, 0.677-0.801) were the most predictive of recurrence. All scores predicted recurrence and survival to P < 0.001 using competing risk analysis.Less restrictive criteria such as Metroticket 2.0, UCSF, or U7 allow broader application of transplants for HCC without sacrificing outcomes. Thus, the criteria for Model for End-stage Liver Disease-exception points for HCC should be expanded to allow more patients to receive life-saving transplantation.

  View details for DOI 10.1097/TP.0000000000005097

  View details for PubMedID 38831488

• Abdominal aortic calcification among gastroenterological and transplant surgery ANNALS OF GASTROENTEROLOGICAL SURGERY Imaoka, Y., Ohira, M., Akabane, M., Sasaki, K., Ohdan, H. 2024

  View details for DOI 10.1002/ags3.12816

  View details for Web of Science ID 001239002000001

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

  Abstract

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

  View details for DOI 10.1016/j.hpb.2024.05.019

  View details for PubMedID 38879433

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

  Abstract

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

  View details for DOI 10.1111/petr.14763

  View details for PubMedID 38682750

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

  Abstract

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

  View details for DOI 10.1097/LVT.0000000000000393

  View details for PubMedID 38727618

• Where is the perfect triangle in the liver allocation system? The lancet. Healthy longevity Sasaki, K., Melcher, M. L. 2024; 5 (5): e310-e311

  View details for DOI 10.1016/S2666-7568(24)00064-3

  View details for PubMedID 38705149

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

  Abstract

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

  View details for DOI 10.1097/LVT.0000000000000376

  View details for PubMedID 38625836

• Impact of a Liver Immune Status Index among Living Liver Transplant Recipients with Hepatocellular Carcinoma. JMA journal Imaoka, Y., Ohira, M., Sato, S., Chogahara, I., Bekki, T., Imaoka, K., Nakano, R., Yano, T., Sakai, H., Kuroda, S., Tahara, H., Ide, K., Kobayashi, T., Tanaka, Y., Akabane, M., Sasaki, K., Ohdan, H. 2024; 7 (2): 232-239

  Abstract

  Hepatocellular carcinoma (HCC) is a major global health challenge, being the fifth most prevalent neoplasm and the third leading cause of cancer-related deaths worldwide. Liver transplantation offers a potentially curative approach for HCC, yet the risk of recurrence posttransplantation remains a significant concern. This study investigates the influence of a liver immune status index (LISI) on the prognosis of patients undergoing living-donor liver transplantation for HCC.In a single-center study spanning from 2001 to 2020, 113 patients undergoing living-donor liver transplantation for HCC were analyzed. LISI was calculated for each donor liver using body mass index, serum albumin levels, and the fibrosis-4 index. This study assessed the impact of donor LISI on short-term recurrence rates and survival, with special attention to its correlation with the antitumor activity of natural killer (NK) cells in the liver.The patients were divided into two grades (high donor LISI, >-1.23 [n = 43]; and low donor LISI, ≤-1.23 [n = 70]). After propensity matching to adjust the background of recipient factors, the survival rates at 1 and 3 years were 92.6% and 88.9% and 81.5% and 70.4% in the low and high donor LISI groups, respectively (p = 0.11). The 1- and 3-year recurrence-free survival were 88.9% and 85.2% and 74.1% and 55.1% in the low and high donor LISI groups, respectively (p = 0.02).This study underscores the potential of an LISI as a noninvasive biomarker for assessing liver NK cell antitumor capacity, with implications for living-donor liver transplantation for HCC. Donor LISI emerges as a significant predictor of early recurrence risk following living-donor liver transplantation for HCC, highlighting the role of the liver antitumor activity of liver NK cells in managing liver malignancies.

  View details for DOI 10.31662/jmaj.2023-0195

  View details for PubMedID 38721076

  View details for PubMedCentralID PMC11074505

• The impact of county-level food access on the mortality and post-transplant survival among patients with steatotic liver disease. Surgery Endo, Y., Tsilimigras, D. I., Khalil, M., Yang, J., Woldesenbet, S., Sasaki, K., Limkemann, A., Schenk, A., Pawlik, T. M. 2024

  Abstract

  The impact of county-level food access on mortality associated with steatotic liver disease, as well as post-liver transplant outcomes among individuals with steatotic liver disease, have not been characterized.Data on steatotic liver disease-related mortality and outcomes of liver transplant recipients with steatotic liver disease between 2010 and 2020 were obtained from the Centers for Disease Control Prevention mortality as well as the Scientific Registry of Transplant Recipients databases. These data were linked to the food desert score, defined as the proportion of the total population in each county characterized as having both low income and limited access to grocery stores.Among 2,710 counties included in the analytic cohort, median steatotic liver disease-related mortality was 27.3 per 100,000 population (interquartile range 24.9-32.1). Of note, patients residing in counties with high steatotic liver disease death rates were more likely to have higher food desert scores (low: 5.0, interquartile range 3.1-7.8 vs moderate: 6.1, interquartile range, 3.8-9.3 vs high: 7.6, interquartile range 4.1-11.7). Among 28,710 patients who did undergo liver transplantation, 5,310 (18.4%) individuals lived in counties with a high food desert score. Liver transplant recipients who resided in counties with the worst food access were more likely to have a higher body mass index (>35 kg/m2: low food desert score, 17.3% vs highest food desert score, 20.1%). After transplantation, there was no difference in 2-year graft survival relative to county-level food access (food desert score: low: 88.4% vs high: 88.6%; P = .77).Poor food access was associated with a higher incidence rate of steatotic liver disease-related death, as well as lower utilization of liver transplants. On the other hand, among patients who did receive a liver transplant, there was no difference in 2-year graft survival regardless of food access strata. Policy initiatives should target the expansion of transplantation services to vulnerable communities in which there is a high mortality of steatotic liver disease.

  View details for DOI 10.1016/j.surg.2024.02.034

  View details for PubMedID 38609786

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

  View details for DOI 10.1093/bjs/znae080

  View details for PubMedID 38630794

• Effect of the opioid crisis on the liver transplantation donor pool: A national analysis. Clinical transplantation Endo, Y., Sasaki, K., Munir, M. M., Woldesenbet, S., Tsilimigras, D. I., Katayama, E., Yang, J., Limkemann, A., Schenk, A., Washburn, K., Pawlik, T. M. 2024; 38 (4): e15290

  Abstract

  Over the last decade there has been a surge in overdose deaths due to the opioid crisis. We sought to characterize the temporal change in overdose donor (OD) use in liver transplantation (LT), as well as associated post-LT outcomes, relative to the COVID-19 era.LT candidates and donors listed between January 2016 and September 2022 were identified from the Scientific Registry of Transplant Recipients database. Trends in LT donors and changes related to OD were assessed pre- versus post-COVID-19 (February 2020).Between 2016 and 2022, most counties in the United States experienced an increase in overdose-related deaths (n = 1284, 92.3%) with many counties (n = 458, 32.9%) having more than a doubling in drug overdose deaths. Concurrently, there was an 11.2% increase in overall donors, including a 41.7% increase in the number of donors who died from drug overdose. In pre-COVID-19 overdose was the 4th top mechanism of donor death, while in the post-COVID-19 era, overdose was the 2nd most common cause of donor death. OD was younger (OD: 35 yrs, IQR 29-43 vs. non-OD: 43 yrs, IQR 31-56), had lower body mass index (≥35 kg/cm2, OD: 31.2% vs. non-OD: 33.5%), and was more likely to be HCV+ (OD: 28.9% vs. non-OD: 5.4%) with lower total bilirubin (≥1.1 mg/dL, OD: 12.9% vs. non-OD: 20.1%) (all p < .001). Receipt of an OD was not associated with worse graft survival (HR .94, 95% CI .88-1.01, p = .09).Opioid deaths markedly increased following the COVID-19 pandemic, substantially altering the LT donor pool in the United States.

  View details for DOI 10.1111/ctr.15290

  View details for PubMedID 38545890

• LightGBM outperforms other machine learning techniques in predicting graft failure after liver transplantation: Creation of a predictive model through large-scale analysis. Clinical transplantation Yanagawa, R., Iwadoh, K., Akabane, M., Imaoka, Y., Bozhilov, K. K., Melcher, M. L., Sasaki, K. 2024; 38 (4): e15316

  Abstract

  The incidence of graft failure following liver transplantation (LTx) is consistent. While traditional risk scores for LTx have limited accuracy, the potential of machine learning (ML) in this area remains uncertain, despite its promise in other transplant domains. This study aims to determine ML's predictive limitations in LTx by replicating methods used in previous heart transplant research.This study utilized the UNOS STAR database, selecting 64,384 adult patients who underwent LTx between 2010 and 2020. Gradient boosting models (XGBoost and LightGBM) were used to predict 14, 30, and 90-day graft failure compared to conventional logistic regression model. Models were evaluated using both shuffled and rolling cross-validation (CV) methodologies. Model performance was assessed using the AUC across validation iterations.In a study comparing predictive models for 14-day, 30-day and 90-day graft survival, LightGBM consistently outperformed other models, achieving the highest AUC of.740,.722, and.700 in shuffled CV methods. However, in rolling CV the accuracy of the model declined across every ML algorithm. The analysis revealed influential factors for graft survival prediction across all models, including total bilirubin, medical condition, recipient age, and donor AST, among others. Several features like donor age and recipient diabetes history were important in two out of three models.LightGBM enhances short-term graft survival predictions post-LTx. However, due to changing medical practices and selection criteria, continuous model evaluation is essential. Future studies should focus on temporal variations, clinical implications, and ensure model transparency for broader medical utility.

  View details for DOI 10.1111/ctr.15316

  View details for PubMedID 38607291

• Correction to "Liquid Biopsy by ctDNA in Liver Transplantation for Colorectal Cancer Liver Metastasis" [J Gastrointest Surg.2023;27(7):1498-509]. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Wehrle, C. J., Raj, R., Aykun, N., Orabi, D., Estfan, B., Kamath, S., Krishnamurthi, S., Fujiki, M., Hashimoto, K., Quintini, C., Kwon, D. C., Diago-Uso, T., Sasaki, K., Aucejo, F. N. 2024; 28 (3): 336

  View details for DOI 10.1016/j.gassur.2024.01.029

  View details for PubMedID 38445929

• Early Onset Intrahepatic Cholangiocarcinoma: Clinical Characteristics, Oncological Outcomes, and Genomic/Transcriptomic Features. Annals of surgical oncology Tsilimigras, D. I., Han, X., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Chaucy, F., Koerkamp, B. G., Endo, I., Sasaki, K., Aucejo, F., Zhang, X. F., Zhu, H., Pawlik, T. M. 2024

  Abstract

  Data on clinical characteristics and disease-specific prognosis among patients with early onset intrahepatic cholangiocarcinoma (ICC) are currently limited.Patients undergoing hepatectomy for ICC between 2000 and 2020 were identified by using a multi-institutional database. The association of early (≤50 years) versus typical onset (>50 years) ICC with recurrence-free (RFS) and disease-specific survival (DSS) was assessed in the multi-institutional database and validated in an external cohort. The genomic and transcriptomic profiles of early versus late onset ICC were analyzed by using the Total Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center databases.Among 971 patients undergoing resection for ICC, 22.7% (n = 220) had early-onset ICC. Patients with early-onset ICC had worse 5-year RFS (24.1% vs. 29.7%, p < 0.05) and DSS (36.5% vs. 48.9%, p = 0.03) compared with patients with typical onset ICC despite having earlier T-stage tumors and lower rates of microvascular invasion. In the validation cohort, patients with early-onset ICC had worse 5-year RFS (7.4% vs. 20.5%, p = 0.002) compared with individuals with typical onset ICC. Using the TCGA cohort, 652 and 266 genes were found to be upregulated (including ATP8A2) and downregulated (including UTY and KDM5D) in early versus typical onset ICC, respectively. Genes frequently implicated as oncogenic drivers, including CDKN2A, IDH1, BRAF, and FGFR2 were infrequently mutated in the early-onset ICC patients.Early-onset ICC has distinct clinical and genomic/transcriptomic features. Morphologic and clinicopathologic characteristics were unable to fully explain differences in outcomes among early versus typical onset ICC patients. The current study offers a preliminary landscape of the molecular features of early-onset ICC.

  View details for DOI 10.1245/s10434-024-15013-5

  View details for PubMedID 38347332

  View details for PubMedCentralID 10358209

• Overexpression of Senescence-Associated Genes, SFN and CDC6, Correlates with Poor Survival in Patients with Stage II Hepatocellular Carcinoma (HCC) Badshah, J., Subramanian, S., Melcher, M., Sasaki, K., Visser, B., Delitto, D., Pruett, T., Niedernhofer, L., Kirchner, V. ELSEVIER SCIENCE INC. 2024: S64

  View details for Web of Science ID 001162078700140

• Evaluating Predictors of Quality in Liver NK Cells Among Deceased Donors CELL TRANSPLANTATION Imaoka, Y., Ohira, M., Nakayama, T., Akabane, M., Tajima, T., Yokota, S., Krams, S. M., Martinez, O. M., Esquivel, C. O., Sasaki, K., Ohdan, H. 2024; 33

  View details for DOI 10.1177/09636897241283289

  View details for Web of Science ID 001328777900001

• The impact of colonic allograft inclusion on intestinal transplantation outcomes: Results from UNOS/OPTN database analysis. Clinical transplantation Matsushima, H., Sasaki, K., Nair, A., Tajima, T., Soyama, A., Eguchi, S., Hashimoto, K., Fujiki, M. 2023: e15213

  Abstract

  Outcomes of intestinal transplantation with colon allograft (ICTx) remain controversial. We aimed to assess the outcomes of ICTx in comparison to intestinal transplantation without colon (ITx) using the UNOS/OPTN registry database.We retrospectively reviewed 2612 patients who received primary intestinal transplants from 1998 to 2020. The rates of acute rejection (AR) within 6 months after transplant were compared between ICTx and ITx. Risk factors of 6-month AR were examined using logistic regression model by era. Furthermore, conditional graft survival was analyzed to determine long-term outcomes of ICTx.Of 2612 recipients, 506 (19.4%) received ICTx. Graft and patient survival in ICTx recipients were comparable to those in ITx recipients. White ICTx recipients had a higher incidence of AR within 6 months compared to ITx during the entire study period (p = .002), colonic inclusion did not increase the risk of 6-month AR in the past decade. ICTx recipients who experienced 6-month AR had worse graft and patient survival compared to those who did not (p <.001 and p = .004, respectively). Among patients who did not develop 6-month AR, Cox proportional hazard model analysis revealed that colonic inclusion was independently associated with improved conditional graft survival.In the recent transplant era, colonic inclusion is no longer associated with a heightened risk of 6-month AR and may provide better long-term survival compared to ITx when AR is absent. Risk adjustment for rejection and proper immunosuppressive therapy are crucial to maximize the benefits of colonic inclusion.

  View details for DOI 10.1111/ctr.15213

  View details for PubMedID 38064299

• Postoperative morbidity after simultaneous versus staged resection of synchronous colorectal liver metastases: Impact of hepatic tumor burden. Surgery Endo, Y., Alaimo, L., Moazzam, Z., Woldesenbet, S., Lima, H. A., Munir, M. M., Shaikh, C. F., Yang, J., Azap, L., Katayama, E., Guglielmi, A., Ruzzenente, A., Aldrighetti, L., Alexandrescu, S., Kitago, M., Poultsides, G., Sasaki, K., Aucejo, F., Pawlik, T. M. 2023

  Abstract

  We sought to characterize the risk of postoperative complications relative to the surgical approach and overall synchronous colorectal liver metastases tumor burden score.Patients with synchronous colorectal liver metastases who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Propensity score matching was employed to control for heterogeneity between the 2 groups. A virtual twins analysis was performed to identify potential subgroups of patients who might benefit more from staged versus simultaneous resection.Among 976 patients who underwent liver resection for synchronous colorectal liver metastases, 589 patients (60.3%) had a staged approach, whereas 387 (39.7%) patients underwent simultaneous resection of the primary tumor and synchronous colorectal liver metastases. After propensity score matching, 295 patients who underwent each surgical approach were analyzed. Overall, the incidence of postoperative complications was 34.1% (n = 201). Among patients with high tumor burden scores, the surgical approach was associated with a higher incidence of postoperative complications; in contrast, among patients with low or medium tumor burden scores, the likelihood of complications did not differ based on the surgical approach. Virtual twins analysis demonstrated that preoperative tumor burden score was important to identify which subgroup of patients benefited most from staged versus simultaneous resection. Simultaneous resection was associated with better outcomes among patients with a tumor burden score <9 and a node-negative right-sided primary tumor; in contrast, staged resection was associated with better outcomes among patients with node-positive left-sided primary tumors and higher tumor burden score.Among patients with high tumor burden scores, simultaneous resection of the primary tumor and liver metastases was associated with an increased incidence of postoperative complications.

  View details for DOI 10.1016/j.surg.2023.10.019

  View details for PubMedID 38001013

• Update to 'A Contemporary Systematic Review on Liver Transplantation for Unresectable Liver Metastasis of Colorectal Cancer'. Annals of surgical oncology Wehrle, C. J., Fujiki, M., Schlegel, A., Whitsett Linganna, M., Pita, A., Kim, J. K., Kwon, D. C., Miller, C., Hashimoto, K., Dueland, S., Sasaki, K., Sapisochin, G., Line, P. D., Hernandez-Alejandro, R., Aucejo, F. 2023

  Abstract

  Colorectal cancer is the second most common cause of cancer-related death worldwide, and half of patients present with colorectal liver metastasis (CRLM). Liver transplant (LT) has emerged as a treatment modality for otherwise unresectable CRLM. Since the publication of the Lebeck-Lee systematic review in 2022, additional evidence has come to light supporting LT for CRLM in highly selected patients. This includes reports of >10-year follow-up with over 80% survival rates in low-risk patients. As these updated reports have significantly changed our collective knowledge, this article is intended to serve as an update to the 2022 systematic review to include the most up-to-date evidence on the subject.

  View details for DOI 10.1245/s10434-023-14611-z

  View details for PubMedID 37996635

  View details for PubMedCentralID 3481888

• Reappraisal of Donor Age in Liver Transplantation: NASH as a Potential Target to Safely Utilize Old Liver Grafts. Transplantation Kusakabe, J., Kozato, A., Tajima, T., Bekki, Y., Fujiki, M., Tomiyama, K., Nakamura, T., Matsushima, H., Hashimoto, K., Sasaki, K. 2023

  Abstract

  BACKGROUND: With the chronic shortage of donated organs, expanding the indications for liver transplantation (LT) from older donors is critical. Nonalcoholic steatohepatitis (NASH) stands out because of its unique systemic pathogenesis and high recurrence rate, both of which might make donor selection less decisive. The present study aims to investigate the usefulness of old donors in LT for NASH patients.METHODS: The retrospective cohort study was conducted using the Scientific Registry Transplant Recipient database. The cohort was divided into 3 categories according to donor age: young (aged 16-35), middle-aged (36-59), and old donors (60-). Multivariable and Kaplan-Meier analyses were performed to compare the risk of donor age on graft survival (GS).RESULTS: A total of 67 973 primary adult donation-after-brain-death LTs (2002-2016) were eligible for analysis. The multivariable analysis showed a reduced impact of donor age on GS for the NASH cohort (adjusted hazard ratio = 1.13, 95% confidence interval, 1.00-1.27), comparing old to middle-aged donors. If the cohort was limited to NASH recipients plus 1 of the following, recipient age ≥60, body mass index <30, or Model of End Stage Liver Disease score <30, adjusted hazard ratios were even smaller (0.99 [0.84-1.15], 0.92 [0.75-1.13], or 1.04 [0.91-1.19], respectively). Kaplan-Meier analysis revealed no significant differences in overall GS between old- and middle-aged donors in these subgroups (P = 0.86, 0.28, and 0.11, respectively).CONCLUSIONS: Donor age was less influential for overall GS in NASH cohort. Remarkably, old donors were equivalent to middle-aged donors in subgroups of recipient age ≥60, recipient body mass index <30, or Model of End Stage Liver Disease score <30.

  View details for DOI 10.1097/TP.0000000000004865

  View details for PubMedID 37990355

• Breaking distance barriers in liver transplantation: Risk factors and outcomes of long-distance liver grafts. Surgery Imaoka, Y., Bozhilov, K. K., Bekki, Y., Akabane, M., Kwong, A. J., Ohira, M., Ohdan, H., Esquivel, C. O., Melcher, M. L., Sasaki, K. 2023

  Abstract

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

  View details for DOI 10.1016/j.surg.2023.09.052

  View details for PubMedID 37980203

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

  Abstract

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

  View details for DOI 10.1111/ctr.15155

  View details for PubMedID 37812571

• Reply: ChatGPT and unknown clinical questions about liver transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Iwadoh, K., Melcher, M. L., Sasaki, K. 2023

  View details for DOI 10.1097/LVT.0000000000000282

  View details for PubMedID 37801561

• Using the win ratio to compare laparoscopic versus open liver resection for colorectal cancer liver metastases. Hepatobiliary surgery and nutrition Paro, A., Hyer, J. M., Avery, B. S., Tsilimigras, D. I., Bagante, F., Guglielmi, A., Ruzzenente, A., Alexandrescu, S., Poultsides, G., Sasaki, K., Aucejo, F., Pawlik, T. M. 2023; 12 (5): 692-703

  Abstract

  We sought to assess the overall benefit of laparoscopic versus open hepatectomy for treatment of colorectal liver metastases (CRLMs) using the win ratio, a novel methodological approach.CRLM patients undergoing curative-intent resection in 2001-2018 were identified from an international multi-institutional database. Patients were paired and matched based on age, number and size of lesions, lymph node status and receipt of preoperative chemotherapy. The win ratio was calculated based on margin status, severity of postoperative complications, 90-day mortality, time to recurrence, and time to death.Among 962 patients, the majority underwent open hepatectomy (n=832, 86.5%), while a minority underwent laparoscopic hepatectomy (n=130, 13.5%). Among matched patient-to-patient pairs, the odds of the patient undergoing laparoscopic resection "winning" were 1.77 [WR: 1.77, 95% confidence interval (CI): 1.42-2.34]. The win ratio favored laparoscopic hepatectomy independent of low (WR: 2.94, 95% CI: 1.20-6.39), medium (WR: 1.56, 95% CI: 1.16-2.10) or high (WR: 7.25, 95% CI: 1.13-32.0) tumor burden, as well as unilobar (WR: 1.71, 95% CI: 1.25-2.31) or bilobar (WR: 4.57, 95% CI: 2.36-8.64) disease. The odds of "winning" were particularly pronounced relative to short-term outcomes (i.e., 90-day mortality and severity of postoperative complications) (WR: 4.06, 95% CI: 2.33-7.78).Patients undergoing laparoscopic hepatectomy had 77% increased odds of "winning". Laparoscopic liver resection should be strongly considered as a preferred approach to resection in CRLM patients.

  View details for DOI 10.21037/hbsn-22-36

  View details for PubMedID 37886182

  View details for PubMedCentralID PMC10598303

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

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

  View details for PubMedID 37845955

• Preserving Liver Natural Killer Cell Activity: Developing Novel Culture Techniques for "Off-the-Shelf" Cell Immunotherapy Imaoka, Y., Akabane, M., Ohira, M., Ohdan, H., Sasaki, K. LIPPINCOTT WILLIAMS & WILKINS. 2023: 169

  View details for DOI 10.1097/01.tp.0000994700.79816.86

  View details for Web of Science ID 001089038800244

• Identifying high TRAIL-expressing liver NK cells from deceased and living donors for effective immunotherapy Imaoka, Y., Akabane, M., Ohira, M., Ohdan, H., Sasaki, K. LIPPINCOTT WILLIAMS & WILKINS. 2023: 48-49

  View details for DOI 10.1097/01.tp.0000993992.73475.a0

  View details for Web of Science ID 001089038800068

• SURVIVAL OF PATIENTS WITH DECOMPENSATED PRIMARY BILIARY CHOLANGITIS IN THE ERA OF OBETICHOLIC ACID AND MELD 3.0 Sedki, M., Chung, N. L., Goel, A., Montano-Loza, A. J., Kwong, A. J., Sasaki, K., Kim, W., Mannalithara, A. LIPPINCOTT WILLIAMS & WILKINS. 2023: S2075-S2076

  View details for Web of Science ID 001094865405118

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

  Abstract

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

  View details for DOI 10.1111/ctr.15127

  View details for PubMedID 37772621

• Optimal policy tree to assist in adjuvant therapy decision-making after resection of colorectal liver metastases. Surgery Endo, Y., Alaimo, L., Moazzam, Z., Woldesenbet, S., Lima, H. A., Yang, J., Munir, M. M., Shaikh, C. F., Azap, L., Katayama, E., Rueda, B. O., Guglielmi, A., Ruzzenente, A., Aldrighetti, L., Alexandrescu, S., Kitago, M., Poultsides, G., Sasaki, K., Aucejo, F., Pawlik, T. M. 2023

  Abstract

  Although systemic postoperative therapy after surgery for colorectal liver metastases is generally recommended, the benefit of adjuvant chemotherapy has been debated. We used machine learning to develop a decision tree and define which patients may benefit from adjuvant chemotherapy after hepatectomy for colorectal liver metastases.Patients who underwent curative-intent resection for colorectal liver metastases between 2000 and 2020 were identified from an international multi-institutional database. An optimal policy tree analysis was used to determine the optimal assignment of the adjuvant chemotherapy to subgroups of patients for overall survival and recurrence-free survival.Among 1,358 patients who underwent curative-intent resection of colorectal liver metastases, 1,032 (76.0%) received adjuvant chemotherapy. After a median follow-up of 28.7 months (interquartile range 13.7-52.0), 5-year overall survival was 67.5%, and 3-year recurrence-free survival was 52.6%, respectively. Adjuvant chemotherapy was associated with better recurrence-free survival (3-year recurrence-free survival: adjuvant chemotherapy, 54.4% vs no adjuvant chemotherapy, 46.8%; P < .001) but no overall survival significant improvement (5-year overall survival: adjuvant chemotherapy, 68.1% vs no adjuvant chemotherapy, 65.7%; P = .15). Patients were randomly allocated into 2 cohorts (training data set, n = 679, testing data set, n = 679). The random forest model demonstrated good performance in predicting counterfactual probabilities of death and recurrence relative to receipt of adjuvant chemotherapy. According to the optimal policy tree, patient demographics, secondary tumor characteristics, and primary tumor characteristics defined the subpopulation that would benefit from adjuvant chemotherapy.A novel artificial intelligence methodology based on patient, primary tumor, and treatment characteristics may help clinicians tailor adjuvant chemotherapy recommendations after colorectal liver metastases resection.

  View details for DOI 10.1016/j.surg.2023.06.045

  View details for PubMedID 37778970

• Liver transplantation access and outcomes: Impact of variations in liver-specific specialty care. Surgery Endo, Y., Sasaki, K., Moazzam, Z., Woldesenbet, S., Lima, H. A., Alaimo, L., Munir, M. M., Shaikh, C. F., Yang, J., Azap, L., Katayama, E., Kitago, M., Schenk, A., Washburn, K., Pawlik, T. M. 2023

  Abstract

  We sought to characterize the impact access to gastroenterologists/hepatologists has on liver transplantation listing, as well as time on the liver transplantation waitlist and post-transplant outcomes.Liver transplantation registrants aged >18 years between January 1, 2004 and December 31, 2019 were identified from the Scientific Registry of Transplant Recipients Standard Analytic Files. The liver transplantation registration ratio was defined as the ratio of liver transplant waitlist registrations in a given county per 1,000 liver-related deaths.A total of 150,679 liver transplantation registrants were included. Access to liver transplantation centers and liver-specific specialty physicians varied markedly throughout the United States. Of note, the liver transplantation registration ratio was lower in counties with poor access to liver-specific care versus counties with adequate access (poor access 137.2, interquartile range 117.8-163.2 vs adequate access 157.6, interquartile range 127.3-192.2, P < .001). Among patients referred for liver transplantation, the cumulative incidence of waitlist mortality and post-transplant graft survival was comparable among patients with poor versus adequate access to liver-specific care (both P > .05). Among liver transplantation recipients living in areas with poor access, after controlling for recipient and donor characteristics, cold ischemic time, and model for end-stage liver disease score, the area deprivation index predicted graft survival (referent, low area deprivation index; medium area deprivation index, hazard ratio 1.52, 95% confidence interval 1.03-12.23; high area deprivation index, 1.45, 95% confidence interval 1.01-12.09, both P < .05).Poor access to liver-specific care was associated with a reduction in liver transplantation registration, and individuals residing in counties with high social deprivation had worse graft survival among patients living in counties with poor access to liver-specific care.

  View details for DOI 10.1016/j.surg.2023.06.043

  View details for PubMedID 37743104

• An attempt to establish and apply global benchmarks for liver resection of malignant hepatic tumors. Surgery Alaimo, L., Moazzam, Z., Lima, H. A., Endo, Y., Ruzzenente, A., Guglielmi, A., Ratti, F., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Popescu, I., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Cauchy, F., Koerkamp, B. G., Endo, I., Kitago, M., Aucejo, F., Sasaki, K., Fields, R. C., Hugh, T., Lam, V., Pawlik, T. M. 2023

  Abstract

  Benchmarking is a process of continuous self-evaluation and comparison with best-in-class hospitals to guide quality improvement initiatives. We sought to define global benchmarks relative to liver resection for malignancy and to assess their achievement in hospitals in the United States.Patients who underwent curative-intent liver resection for hepatocellular carcinoma, intrahepatic cholangiocarcinoma, or colorectal or neuroendocrine liver metastases between 2000 and 2019 were identified from an international multi-institutional database. Propensity score matching was conducted to balance baseline characteristics between open and minimally invasive approaches. Best-in-class hospitals were defined relative to the achievement rate of textbook oncologic outcomes and case volume. Benchmark values were established relative to best-in-class institutions. The achievement of benchmark values among hospitals in the National Cancer Database was then assessed.Among 2,624 patients treated at 20 centers, a majority underwent liver resection for hepatocellular carcinoma (n = 1,609, 61.3%), followed by colorectal liver metastases (n = 650, 24.8%), intrahepatic cholangiocarcinoma (n = 299, 11.4%), and neuroendocrine liver metastases (n = 66, 2.5%). Notably, 1,947 (74.2%) patients achieved a textbook oncologic outcome. After propensity score matching, 6 best-in-class hospitals with the highest textbook oncologic outcome rates (≥75.0%) were identified. Benchmark values were calculated for margin positivity (≤11.7%), 30-day readmission (≤4.1%), 30-day mortality (≤1.6%), minor postoperative complications (≤24.7%), severe complications (≤12.4%), and failure to achieve the textbook oncologic outcome (≤22.8%). Among the National Cancer Database hospitals, global benchmarks for margin positivity, 30-day readmission, 30-day mortality, severe complications, and textbook oncologic outcome failure were achieved in 62.9%, 27.1%, 12.1%, 7.1%, and 29.3% of centers, respectively.These global benchmarks may help identify hospitals that may benefit from quality improvement initiatives, aiming to improve patient safety and surgical oncologic outcomes.

  View details for DOI 10.1016/j.surg.2023.08.024

  View details for PubMedID 37741777

• Survival Benefit Relative to Treatment Modalities Among Patients with Very Early Intrahepatic Cholangiocarcinoma: an Analysis of the National Cancer Database. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Endo, Y., Sasaki, K., Munir, M. M., Woldesenbet, S., Resende, V., Rawicz-Pruszyński, K., Waqar, U., Mavani, P., Katayama, E., Yang, J., Khalil, M., Khan, M. M., Kitago, M., Pawlik, T. M. 2023

  Abstract

  Liver transplantation (LT) has been considered a potential curative treatment for patients with very early intrahepatic cholangiocarcinoma (ICC) and cirrhosis, yet the survival benefit of LT has not been well defined. This study aimed to compare the long-term survival outcomes of patients who underwent LT with that of individuals who received resection and non-curative intent treatment (non-CIT).Patients who underwent LT, hepatectomy, and non-CIT between 2004 and 2018 were included in the National Cancer Database. Survival benefits of LT over resection and non-CIT were analyzed relative to overall survival (OS).Among 863 patients, 54 (6.3%) underwent LT, while 342 (39.6%) underwent surgical resection, and 467 (54.1%) received non-CIT, respectively. While the rates of non-CIT increased over time, the percentages of LT remained consistent during the study period. LT patients had similar 5-year OS to individuals who underwent resection (referent, resection: LT, HR 0.95, 95%CI 0.84-1.58, p=0.84). In contrast, 5-year OS was better among patients who underwent LT versus individuals who had non-CIT after controlling other variables using propensity score overlapping weighting (5-year OS, LT 57.1% vs. LR 25.8%, p<0.001).The outcomes of very early ICC patients who underwent LT were similar to individuals who underwent hepatectomy, but better than patients treated with non-CIT. LT should be may be a consideration as a treatment option for patients with early stage ICC who are unsuitable candidates for resection.

  View details for DOI 10.1007/s11605-023-05821-7

  View details for PubMedID 37674099

  View details for PubMedCentralID 3804834

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

  Abstract

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

  View details for DOI 10.1097/LVT.0000000000000245

  View details for PubMedID 37616509

• Exploring the potential of ChatGPT in generating unknown clinical questions about liver transplantation: a feasibility study. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Iwadoh, K., Melcher, M. L., Sasaki, K. 2023

  View details for DOI 10.1097/LVT.0000000000000246

  View details for PubMedID 37616504

• Decreased Utilization Rate of Grafts for Liver Transplantation After Implementation of Acuity Circle-based Allocation. Transplantation Bekki, Y., Myers, B., Tomiyama, K., Imaoka, Y., Akabane, M., Kwong, A. J., Melcher, M. L., Sasaki, K. 2023

  Abstract

  The allocation system for livers began using acuity circles (AC) in 2020. In this study, we sought to evaluate the impact of AC policy on the utilization rate for liver transplantation (LT).Using the US national registry data between 2018 and 2022, LTs were equally divided into 2 eras: pre-AC (before February 4, 2020) and post-AC (February 4, 2020, and after). Deceased potential liver donors were defined as deceased donors from whom at least 1 organ was procured.The annual number of deceased potential liver donors increased post-AC (from 10 423 to 12 259), approaching equal to that of new waitlist registrations for LT (n = 12 801). Although the discard risk index of liver grafts was comparable between the pre- and post-AC eras, liver utilization rates in donation after brain death (DBD) and donation after circulatory death (DCD) donors were lower post-AC (P < 0.01; 79.8% versus 83.4% and 23.7% versus 26.0%, respectively). Recipient factors, ie, no recipient located, recipient determined unsuitable, or time constraints, were more likely to be reasons for nonutilization after implementation of the AC allocation system compared to the pre-AC era (20.0% versus 12.3% for DBD donors and 50.1% versus 40.8% for DCD donors). Among non-high-volume centers, centers with lower utilization of marginal DBD donors or DCD donors were more likely to decrease LT volume post-AC.Although the number of deceased potential liver donors has increased, overall liver utilization among deceased donors has decreased in the post-AC era. To maximize the donor pool for LT, future efforts should target specific reasons for liver nonutilization.

  View details for DOI 10.1097/TP.0000000000004751

  View details for PubMedID 37585345

• Debating the indication: re-transplant for patients whose initial transplant indication was hepatocellular carcinoma. HPB : the official journal of the International Hepato Pancreato Biliary Association Akabane, M., Melcher, M. L., Sasaki, K. 2023

  View details for DOI 10.1016/j.hpb.2023.08.003

  View details for PubMedID 37633744

• Liver transplantation for elderly patients with early-stage hepatocellular carcinoma. The British journal of surgery Endo, Y., Sasaki, K., Moazzam, Z., Lima, H. A., Alaimo, L., Munir, M. M., Shaikh, C. F., Schenk, A., Kitago, M., Pawlik, T. M. 2023

  Abstract

  Although liver resection is a viable option for patients with early-stage hepatocellular carcinoma (HCC), liver transplantation is the optimal treatment. The aim of this study was to identify characteristics of liver transplantation for elderly patients, and to assess the therapeutic benefit derived from liver transplantation over liver resection.This was a population-based study of patients undergoing liver transplantation for HCC in the USA between 2004 and 2018. Data were retrieved from the National Cancer Database. Elderly patients were defined as individuals aged 70 years and over. Propensity score overlap weighting was used to control for heterogeneity between the liver resection and liver transplantation cohorts.Among 4909 liver transplant recipients, 215 patients (4.1 per cent) were classified as elderly. Among 5922 patients who underwent liver resection, 1907 (32.2 per cent) were elderly. Elderly patients who underwent liver transplantation did not have a higher hazard of dying during the first 5 years after transplantation than non-elderly recipients. After propensity score weighting, liver transplantation was associated with a lower risk of death than liver resection. Other factors associated with overall survival included diagnosis during 2016-2018, non-white/non-African American race, and α-fetoprotein level over 20 ng/dl.Elderly patients with HCC should not be excluded from liver transplantation based on age only. Transplantation leads to favourable survival compared with liver resection.

  View details for DOI 10.1093/bjs/znad243

  View details for PubMedID 37548041

• Living Donor Liver Transplantation (LDLT) for Hepatocellular Carcinoma (HCC) within and Outside Traditional Selection Criteria: A Multicentric North American Experience. Annals of surgery Ivanics, T., Claasen, M. P., Samstein, B., Emond, J. C., Fox, A. N., Pomfret, E., Pomposelli, J., Tabrizian, P., Florman, S. S., Mehta, N., Roberts, J. P., Emamaullee, J. A., Genyk, Y., Hernandez-Alejandro, R., Tomiyama, K., Sasaki, K., Quintini, C., Nagai, S., Abouljoud, M., Olthoff, K. M., Hoteit, M. A., Heimbach, J., Taner, T., Liapakis, A. H., Mulligan, D. C., Sapisochin, G., Halazun, K. J. 2023

  Abstract

  OBJECTIVE: We evaluated long-term oncologic outcomes of patients post-LDLT within and outside standard transplant selection criteria and the added value of the incorporation of the New York-California (NYCA) score.SUMMARY BACKGROUND DATA: LDLT offers an opportunity to decrease the liver transplant waitlist, reduce waitlist mortality and expand selection criteria for patients with HCC.METHODS: Primary adult LDLT recipients between Oct-1999 and Aug-2019 were identified from a multicenter cohort of twelve North American centers. Post-transplant and recurrence-free survival were evaluated using the Kaplan-Meier method.RESULTS: Three-hundred-and-sixty LDLTs were identified. Patients within Milan criteria (MC) at transplant had a 1-,5-, and 10-year post-transplant survival of 90.9%,78.5%, and 64.1% vs. outside MC 90.4%,68.6%, and 57.7%(P=0.20). For patients within the UCSF criteria, respective post-transplant survival was 90.6%,77.8%, and 65.0%, vs. outside UCSF 92.1%,63.8%, and 45.8%(P=0.08). Fifty-three (83%) patients classified as outside MC at transplant would have been classified as either low- or acceptable risk with the NYCA score. These patients had a 5-year OS of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplant would have been classified as low- or acceptable risk with a 5-year OS of 65.3%.CONCLUSIONS: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-years rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

  View details for DOI 10.1097/SLA.0000000000006049

  View details for PubMedID 37522174

• Left Lobe First with Purely Laparoscopic Approach: A Novel Strategy to Maximize Donor Safety in Adult Living Donor Liver Transplantation. Annals of surgery Fujiki, M., Pita, A., Kusakabe, J., Sasaki, K., You, T., Tuul, M., Aucejo, F. N., Quintini, C., Eghtesad, B., Pinna, A., Miller, C., Hashimoto, K., Kwon, C. H. 2023

  Abstract

  A left-lobe graft (LLG) first approach and a purely laparoscopic donor hemihepatectomy (PLDH) are two methods to reduce surgical stress for donors in adult living donor liver transplantation (LDLT). We herein report our strategy to minimize donor risk by applying LLG first combined with PLDH.From 2012-2023, 186 adult LDLTs were performed with hemiliver grafts, procured by open surgery in 95 and PLDH in 91 cases. LLGs were considered first when graft-to-recipient weight ratio ≥0.6%. Following a four-month adoption process, all donor hepatectomies since December 2019 were performed laparoscopically.There was one intra-operative conversion to open (1%). Mean operative times were similar in laparoscopic and open cases (366 vs. 371 minutes). PLDH provided shorter hospital stay, lower blood loss, and lower peak AST. Peak bilirubin was lower in LLG donors compared to RLG donors (1.4 mg/dL vs. 2.4 mg/dL, P<0.01), and PLDH further improved the bilirubin levels in LLG donors (1.2 vs. 1.6 mg/dL, P<0.01). PLDH also afforded a low rate of early complications (Clavien-Dindo grade ≥ II, 8% vs. 22%, P=0.007) and late complications including incisional hernia (0% vs. 13.7%, P<0.001) compared to open cases. LLG was more likely to have a single duct than RLG (89% vs. 60%, P<0.01). Importantly, with the aggressive use of LLG in 47% of adult LDLT, favorable graft survival was achieved without any differences between type of graft or surgical approach.The LLG first with PLDH approach minimizes surgical stress for donors in adult LDLT without compromising recipient outcomes. This strategy can lighten the burden for living donors, which could help expand the donor pool.

  View details for DOI 10.1097/SLA.0000000000005988

  View details for PubMedID 37436876

• The Impact of Colonic Allograft on Intestinal Transplantation Outcomes: Results from UNOS/OPTN Database Matsushima, H., Sasaki, K., Soyama, A., Eguchi, S., Hashimoto, K., Fujiki, M. LIPPINCOTT WILLIAMS & WILKINS. 2023: 17

  View details for DOI 10.1097/01.tp.0000945580.31330.0d

  View details for Web of Science ID 001023645700027

• Liquid Biopsy by ctDNA in Liver Transplantation for Colorectal Cancer Liver Metastasis. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Wehrle, C. J., Raj, R., Aykun, N., Orabi, D., Estfan, B., Kamath, S., Krishnamurthi, S., Fujiki, M., Hashimoto, K., Quintini, C., Kwon, D. C., Diago-Uso, T., Sasaki, K., Aucejo, F. N. 2023

  Abstract

  Colorectal cancer is a leading cause of cancer-related death worldwide. Metastatic liver disease develops in 50% of cases and drives patient outcomes. Although the ideal treatment for colorectal cancer liver metastases (CRLM) is resection, only a third of patients are suitable for this approach. Reports of liver transplantation in selected patients with unresectable CRLM have shown encouraging results compared to conventional forms of therapy. No study to date has examined the utility of liquid biopsy circulating tumor DNA (ctDNA) for evaluation of residual disease in this cohort of patients. We report a small series of liver transplantation in patients with CRLM in whom ctDNA was assessed peri-operatively.Five patients underwent liver transplantation for unresectable CRLM or liver failure following CRLM treatment from 2018 to 2022. Clinical data, cross-sectional imaging, and serum biomarkers including peri-operative ctDNA were reviewed from electronic medical records.All patients are alive without radiologic evidence of disease at time of this publication. Median time of follow-up was 32 months (IQR 6.6-40 months). ctDNA was assessed before (4 patients) and after transplant (6 patients). One patient experienced a pulmonary recurrence that was resected, for whom pre-recurrence ctDNA was not available; the remaining patients have not experienced recurrence. Four patients are without evidence of ctDNA following transplant, and two demonstrate persistent ctDNA positivity post-transplant. Three of four patients with positive pre-transplant ctDNA remain ctDNA-negative post-transplant.Liver transplantation for liver-confined unresectable CRLM is emerging as a valid surgical option in selected patients. The significance of liquid biopsy in this population remains elusive due to lack of data. The clearance of ctDNA after transplant in these patients with metastatic disease and despite their immunosuppression is notable. The significance and usefulness of liquid biopsy in patient selection, surveillance, and as an indication for treatment warrant further investigation.

  View details for DOI 10.1007/s11605-023-05723-8

  View details for PubMedID 37273078

  View details for PubMedCentralID 5769309

• Quality of ChatGPT Responses to Questions Related To Liver Transplantation. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Endo, Y., Sasaki, K., Moazzam, Z., Lima, H. A., Schenk, A., Limkemann, A., Washburn, K., Pawlik, T. M. 2023

  View details for DOI 10.1007/s11605-023-05714-9

  View details for PubMedID 37254022

• The impact of recurrence timing and tumor burden score on overall survival among patients undergoing repeat hepatectomy for colorectal liver metastases. Journal of surgical oncology Endo, Y., Rueda, B. O., Woldesenbet, S., Munir, M. M., Lima, H. A., Katayama, E. S., Shaikh, C. F., Guglielmi, A., Ruzzenente, A., Aldrighetti, L., Alexandrescu, S., Kitago, M., Poultsides, G., Sasaki, K., Aucejo, F., Pawlik, T. M. 2023

  Abstract

  Approximately 15% of patients experience a resectable intrahepatic recurrence after an index curative-intent hepatectomy for colorectal liver metastases (CRLM). We sought to investigate the impact of recurrence timing and tumor burden score (TBS) at the time of recurrence on overall survival among patients undergoing repeat hepatectomy.Patients with CRLM who experienced recurrent intrahepatic disease after initial hepatectomy between 2000 and 2020 were identified from an international multi-institutional database. The impact of time-TBS, defined as TBS divided by the time interval of recurrence, was assessed relative to overall survival.Among 220 patients, the median age was 60.9 years (interquartile range [IQR]: 53.0-69.0), and 144 (65.5%) patients were male. Most patients experienced multiple recurrences (n = 120, 54.5%) within 12 months after the initial hepatectomy (n = 139, 63.2%). The median tumor size of the recurrent CRLM was 2.2 cm (IQR: 1.5-3.0 cm) with a median TBS of 3.5 (2.3-4.9) at the time of recurrence. Overall, 121 (55.0%) patients underwent repeat hepatectomy, whereas 99 (45.0%) individuals were treated with systemic chemotherapy or other nonsurgical treatments; repeat hepatectomy was associated with better postrecurrence survival (PRS) (p < 0.001). Three-year PRS incrementally worsened (low time-TBS: 71.7%, 95% confidence interval [CI], 57.9-88.8 vs. medium: 63.6%, 95% CI, 47.7-84.8 vs. high: 49.2%, 95% CI, 31.1-77.7, p = 0.02) as time-TBS values increased. Each unit increase in time-TBS score was independently associated with a 41% higher possibility of death (hazard ratio: 1.41; 95% CI, 1.04-1.90, p = 0.03).Time-TBS was associated with long-term outcomes after repeat hepatectomy for recurrent CRLM. Time-TBS may be an easy tool to help select patients who may benefit the most from repeat hepatic resection of recurrent CRLM.

  View details for DOI 10.1002/jso.27314

  View details for PubMedID 37195231

• Travel distance and social vulnerability index: Impact on liver-related mortality among patients with end-stage liver disease. Clinical transplantation Yang, J., Endo, Y., Moazzam, Z., Lima, H. A., Woldesenbet, S., Alaimo, L., Azap, L., Shaikh, C. F., Munir, M. M., Katayama, E., Sasaki, K., Pawlik, T. M. 2023: e15001

  Abstract

  The reasons for the geographic disparities in liver-related mortality across the US remain ill-defined. We sought to investigate the impact of travel distance to liver transplantation (LT) programs and social vulnerability on county differences in liver-related mortality.Data on LT registrants were obtained from the Scientific Registry of Transplant Recipients Standard Analytic Files (SRTR SAFs) between 2004 and 2019. Liver-related mortality data were obtained from the Center for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) platform. Spatial epidemiological clustering of county-level LT registration and liver-related mortality rates was determined using local Moran's I. Comparison analyses assessed social vulnerability index (SVI) and travel distance within various county clusters.Among 151 864 LT waitlist registrants who were diagnosed with liver disease due to hepatitis C virus (HCV) or hepatitis B virus (HBV) (n = 68 479, 45.1%), alcohol (n = 38 328, 25.2%), non-alcoholic steatohepatitis (NASH) (n = 17 485, 11.5%), liver tumors (n = 16 644, 11.0%), and other diseases (n = 10 928, 7.2%), median SVI was 59.3 (IQR, 40.1-83.4). SVI (76.2 vs. 24.3, p < .001) was greater in the highest versus lowest liver-related mortality quartiles. The travel distances to LT centers (143.1 miles vs. 107.2 miles, p < .001) was longer in the lowest versus highest LT registration quartiles. Counties with low LT registration rates and high liver-related mortality rates were associated with long travel distances and high SVI. In contrast, while counties with high LT registration rates and high liver-related mortality rates had comparable SVI, travel distance was relatively shorter.Counties with greater SVIs were associated with higher liver-related mortality, with the highest SVI  counties having the highest overall liver-related mortality. Longer travel distances were associated with higher liver-related mortality. These findings highlight the impact of social determinants of health (SDOH) on liver disease outcomes.

  View details for DOI 10.1111/ctr.15001

  View details for PubMedID 37126400

• Impact of donor sex on hepatocellular carcinoma recurrence in liver transplantation after brain death. Clinical transplantation Nakamura, T., Sasaki, K., Kojima, L., Teo, R., Inaba, Y., Yamamoto, T., Kimura, S., Dageforde, L. A., Yeh, H., Elias, N., Bozorgzadeh, A., Kawai, T., Markmann, J. F. 2023: e14989

  Abstract

  BACKGROUND: Hepatocellular carcinoma (HCC) is predominantly seen in males but has a better prognosis in females. No prior studies have investigated HCC recurrence based on sex combination following liver transplant donated after brain death (DBDLT). This study sought to elucidate the effects of donor and recipient sex on HCC recurrence rates.METHODS: 9232 adult recipients from the United Network for Organ Sharing (UNOS) database who underwent DBDLT for HCC from 2012 to 2018 were included. Donor-recipient pairs were divided into (1) female donor/female recipient (F-F) (n=1089); (2) male donor/female recipient (M-F) (n=975); (3) female donor/male recipient (F-M) (n=2691); (4) male donor/male recipient (M-M) (n=4477). The primary prognostic outcome was HCC recurrence. A multivariable competing risk regression analysis was used to assess prognostic influences.RESULTS: The median recipient age and model for end-stage liver disease (MELD) scores were similar among the four groups. Livers of male recipients demonstrated greater in size and number of HCC (both p-values were <.0001). There was also a higher rate of vascular invasion in male recipients compared to female (p<.0001). Competing risk analyses showed that the cumulative HCC recurrence rate was significantly lower in the M-F group (p=.013). After adjusting for tumor characteristics, liver grafts from male donors were associated with a lower HCC recurrence rate in female recipients (HR: .62 95%CI: .42-.93) (p=.021).CONCLUSION: In DBDLT, male donor to female recipient pairing exhibited lower HCC recurrence rates.SUMMARY: Lowest rates of HCC recurrence were confirmed among the female recipients of male donor grafts group in the deceased donor LT cohort. A competing risk multivariable regression analysis demonstrated that male donor sex was significantly associated with low HCC recurrence in female but not male recipients.

  View details for DOI 10.1111/ctr.14989

  View details for PubMedID 37039506

• Liver Transplantation for Colorectal Liver Metastases: Hazard Function Analysis of Data from the Organ Procurement and Transplantation Network. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Endo, Y., Alaimo, L., Sasaki, K., Moazzam, Z., Yang, J., Schenk, A., Pawlik, T. M. 2023

  View details for DOI 10.1007/s11605-023-05672-2

  View details for PubMedID 37012488

• The Impact of a Liver Transplant Program on the Outcomes of Hepatocellular Carcinoma. Annals of surgery Endo, Y., Sasaki, K., Moazzam, Z., Woldesenbet, S., Yang, J., Lima, H. A., Alaimo, L., Munir, M. M., Shaikh, C. F., Schenk, A., Kitago, M., Pawlik, T. M. 2023

  Abstract

  We sought to evaluate the impact of liver transplantation (LT) programs on the prognosis of hepatocellular carcinoma (HCC) patients who underwent liver resection (LR) and non-curative intent treatment.LT programs have an array of resources and services that would positively affect the prognosis of patients with HCC.Patients who underwent LT, LR, radiotherapy (RT), or chemotherapy (CTx) for HCC between 2004 to 2018 were included from the National Cancer Database. Institutions with LT programs were defined as those that performed one or more LT for at least 5 years. Centers were stratified by hospital volume. The impact of LT programs was assessed after propensity score matching to achieve covariate balance.A total of 71,735 patients were identified, of which 7,997 received LT (11.1%), 12,683 LR (17.7%), 15,675 RT (21.9%), and 35,380 CTx (49.3%). Among a total of 1,267 distinct institutions, 94 (7.4%) were categorized as LT programs. Designation as a LT program was also associated with a high-volume of LR and non-curative intent treatment (both P<0.001). After propensity score matching, LT programs were associated with better survival among LR and non-curative intent treatment patients. Although hospital volume was also associated with improved prognosis, LT programs were associated with additional survival benefit in non-curative intent treatment. On the other hand, no such benefit was noted in patients who underwent LR.The presence of an LT program was associated with a higher volume of LR and non-curative intent treatment. Furthermore, designation as a LT program has a "halo effect" on the prognosis of patients undergoing RT/ CTx that goes beyond the procedure-volume effect.

  View details for DOI 10.1097/SLA.0000000000005849

  View details for PubMedID 36994716

• Normothermic Regional Perfusion Can Improve Both Utilization and Outcomes in DCD Liver, Kidney, and Pancreas Transplantation. Transplantation direct Bekki, Y., Croome, K. P., Myers, B., Sasaki, K., Tomiyama, K. 2023; 9 (3): e1450

  Abstract

  Normothermic regional perfusion (NRP) has gained widespread adoption in multiple European countries. The aim of this study was to examine the influence of thoracoabdominal-NRP (TA-NRP) on the utilization and outcomes of liver, kidney, and pancreas transplantation in the United States.Methods: Using the US national registry data between 2020 and 2021, donation after circulatory death (DCD) donors were separated into 2 groups: DCD with TA-NRP and without TA-NRP. There were 5234 DCD donors; among them 34 donors were with TA-NRP. After 1:4 propensity score matching, the utilization rates were compared between DCD with and without TA-NRP.Results: Although the utilization rates of kidney and pancreas were comparable (P=0.71 and P=0.06, 94.1% versus 95.6% and 8.8% versus 2.2%, respectively), that of liver in DCD with TA-NRP was significantly higher (P<0.001; 70.6% versus 39.0%). Among 24 liver transplantations, 62 kidney transplantations, and 3 pancreas transplantations from DCD with TA-NRP, there were 2 liver grafts and 1 kidney graft that failed within 1 y after transplantation.Conclusions: TA-NRP in the United States significantly increased the utilization rate of abdominal organs from DCD donors with comparable outcomes after transplantation. Increasing use of NRP may expand the donor pool without compromising transplant outcomes.

  View details for DOI 10.1097/TXD.0000000000001450

  View details for PubMedID 36845854

• Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States Tajima, T., Bernstein, D., Boyd, S. D., Gratzinger, D., Lum, G., Sasaki, K., Tan, B., Twist, C. J., Weinberg, K., Robien, M. A., Brown, M., Armstrong, B., Desai, D., Mazariegos, G., Chin, C., Fishbein, T. M., Tekin, A., Venick, R. S., Martinez, O. M., Krams, S. M., Esquivel, C. O. WILEY. 2023

  View details for Web of Science ID 001002465500078

• Biliary complications following split liver transplantation in adult recipients: a matched pair analysis on single-center experience. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Matsushima, H., Fujiki, M., Sasaki, K., Raj, R., D'Amico, G., Simioni, A., Aucejo, F., Diago Uso, T., Kwon, C. H., Eghtesad, B., Miller, C., Quintini, C., Eguchi, S., Hashimoto, K. 2023; 29 (3): 279-289

  Abstract

  The utilization of split liver grafts can increase access to liver transplantation (LT) for adult patients, particularly when liver grafts are shared between 2 adult recipients. However, it is yet to be determined whether split liver transplantation (SLT) increases the risk of biliary complications (BCs) compared with whole liver transplantation (WLT) in adult recipients. This retrospective study enrolled 1441 adult patients who underwent deceased donor LT at a single-site between January 2004 and June 2018. Of those, 73 patients underwent SLTs. Graft type for SLT includes 27 right trisegment grafts, 16 left lobes, and 30 right lobes. A propensity score matching analysis selected 97 WLTs and 60 SLTs. Biliary leakage was more frequently seen in SLTs (13.3% vs. 0%; p <0.001), whereas the frequency of biliary anastomotic stricture was comparable between SLTs and WLTs (11.7% vs. 9.3%; p=0.63). Graft and patient survival rates of patients undergoing SLTs were comparable to those undergoing WLTs (p=0.42 and 0.57, respectively). In the analysis of the entire SLT cohort, BCs were seen in 15 patients (20.5%) including biliary leakage in 11 patients (15.1%) and biliary anastomotic stricture in 8 patients (11.0%) [both in 4 patients (5.5%)]. The survival rates of recipients who developed BCs were significantly inferior to those without BCs (p <0.01). By multivariate analysis, the split grafts without common bile duct increased the risk of BCs. In conclusion, SLT increases the risk of biliary leakage compared with WLT. Biliary leakage can still lead to fatal infection and thus should be managed appropriately in SLT.

  View details for DOI 10.1097/LVT.0000000000000058

  View details for PubMedID 36811877

• Evaluating the outcomes of donor-recipient age differences in young adults undergoing liver transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Snyder, A., Kojima, L., Imaoka, Y., Akabane, M., Kwong, A., Melcher, M. L., Sasaki, K. 2023

  Abstract

  BACKGROUND: The current liver allocation system may be disadvantaging younger adult recipients as it does not incorporate the donor-recipient age difference. Given the longer life expectancy of younger recipients, the influences of older donor grafts on their long-term prognosis should be elucidated. This study sought to reveal the long-term prognostic influence of the donor-recipient age difference in young adult recipients.METHODS: Adult patients who received initial liver transplants from deceased donors between 2002-2021 were identified from the UNOS database. Young recipients (patients ≤45 y.o) were categorized into 4 groups: donor age younger than the recipient, 0-9 years older, 10-19 years older, or ≥20 years older. Older recipients were defined as patients ≥65 y.o. To examine the influence of the age difference in long-term survivors, conditional graft survival (CGS) analysis was conducted on both younger and older recipients.RESULTS: Among 91,952 transplant recipients, 15,170 patients were ≤45 years old (16.5%); these were categorized into 6,114 (40.3%), 3,315 (21.9%), 2,970 (19.6%), and 2,771 (18.3%) for groups 1-4, respectively. Group 1 demonstrated the highest probability of survival followed by groups 2, 3, and 4 for the actual graft survival and CGS analyses. In younger recipients who survived at least 5 years post-transplant, inferior long-term survival was observed when there was an age difference of ≥10 years (86.9% vs. 80.6%, log-rank P<0.01) while there was no difference in older recipients (72.6% vs. 74.2%, log-rank P=0.89).CONCLUSION: In younger patients who are not in emergent need of a transplant, preferential allocation of younger aged donor offers would optimize organ utility by increasing postoperative graft survival time.

  View details for DOI 10.1097/LVT.0000000000000109

  View details for PubMedID 36847140

• ASO Visual Abstract: The Current State of Liver Transplantation for Colorectal Liver Metastases in the United States: A Call for Standardized Reporting. Annals of surgical oncology Sasaki, K., Ruffolo, L. I., Kim, M. H., Fujiki, M., Hashimoto, K., Imaoka, Y., Melcher, M. L., Aucejo, F. N., Tomiyama, K., Hernandez-Alejandro, R. 2023

  View details for DOI 10.1245/s10434-023-13234-8

  View details for PubMedID 36807717

• The impact of geographic location vs center practice on center volume in liver transplantation after acuity circle policy. Clinical transplantation Bekki, Y., Myers, B., Tomiyama, K., Melcher, M. L., Sasaki, K. 2023: e14932

  Abstract

  The allocation system for livers used the Acuity Circles (AC) beginning in 2020. In this study, we sought to evaluate the effect of the AC policy on center transplant volumes, from geographic and center practice perspectives.Using the US national registry data between 2018 and 2022, adult liver transplantations (LT) were separated into 2 eras: before AC and after AC.The number of LT for Model for End-Stage Liver Disease (MELD) scores ≥ 29 have significantly increased by 10%, and waitlist times for those patients have been significantly shorter after AC. These benefits were not found in patients with MELD scores < 29. The geographic distribution of transplant centers reveals that the majority of centers which increased their transplant volume (18 out of 25 centers) are located in high population states while there are 7 transplant centers in non-high population states. The centers in the non-high population states utilized more marginal donation after brain death (DBD) and donation after circulatory death (DCD) donors by 27% and 155%, respectively. MELD scores were significantly lower in the non-high population states compared with those in the high population states (p < 0.01).AC improved the LT access for patients with MELD scores ≥ 29, which benefited the high population states. However, aggressive center practice to utilize marginal DBD and DCD donors were able to increase transplant volume and lower median allocation MELD scores. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.14932

  View details for PubMedID 36756928

• The Current State of Liver Transplantation for Colorectal Liver Metastases in the United States: A Call for Standardized Reporting. Annals of surgical oncology Sasaki, K., Ruffolo, L. I., Kim, M. H., Fujiki, M., Hashimoto, K., Imaoka, Y., Melcher, M. L., Aucejo, F. N., Tomiyama, K., Hernandez-Alejandro, R. 2023

  Abstract

  BACKGROUND: Current success in transplant oncology for select liver tumors, such as hepatocellular carcinoma, has ignited international interest in liver transplantation (LT) as a therapeutic option for nonresectable colorectal liver metastases (CRLM). In the United States, the CRLM LT experience is limited to reports from a handful of centers. This study was designed to summarize donor, recipient, and transplant center characteristics and posttransplant outcomes for the indication of CRLM.METHODS: Adult, primary LT patients listed between December 2017 and March 2022 were identified by using United Network Organ Sharing database. LT for CRLM was identified from variables: "DIAG_OSTXT"; "DGN_OSTXT_TCR"; "DGN2_OSTXT_TCR"; and "MALIG_TY_OSTXT."RESULTS: During this study period, 64 patients were listed, and 46 received LT for CRLM in 15 centers. Of 46 patients who underwent LT for CRLM, 26 patients (56.5%) received LTs using living donor LT (LDLT), and 20 patients received LT using deceased donor (DDLT) (43.5%). The median laboratory MELD-Na score at the time of listing was statistically similar between the LDLT and DDLT groups (8 vs. 9, P = 0.14). This persisted at the time of LT (8 vs. 12, P = 0.06). The 1-, 2-, and 3-year, disease-free, survival rates were 75.1, 53.7, and 53.7%. Overall survival rates were 89.0, 60.4, and 60.4%, respectively.CONCLUSIONS: This first comprehensive U.S. analysis of LT for CRLM suggests a burgeoning interest in high-volume U.S. transplant centers. Strategies to optimize patient selection are limited by the scarce oncologic history provided in UNOS data, warranting a separate registry to study LT in CRLM.

  View details for DOI 10.1245/s10434-023-13147-6

  View details for PubMedID 36719568

• ASO Author Reflections: At the Crossroad-Liver Transplantation for Unresectable Colorectal Liver Metastases in the United States. Annals of surgical oncology Bozhilov, K., Melcher, M. L., Hernandez-Alejandro, R., Sasaki, K. 2023

  View details for DOI 10.1245/s10434-023-13169-0

  View details for PubMedID 36715859

• The high incidence of occult carcinoma in total hepatectomy specimens of patients treated for unresectable colorectal liver metastases with liver transplant. Annals of surgery Chavez-Villa, M., Ruffolo, L. I., Al-Judaibi, B. M., Fujiki, M., Hashimoto, K., Kallas, J., Kwon, C. H., Nair, A., Orloff, M. S., Pineda-Solis, K., Raj, R., Sasaki, K., Tomiyama, K., Aucejo, F., Hernandez-Alejandro, R. 2023

  Abstract

  OBJECTIVE: To describe the rate of missed carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM).BACKGROUND: Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection.METHODS: Retrospective review of 14 patients who underwent LT for CRLM, at two centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed.RESULTS: The median (IQR) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in five patients (35.7%); six (42.9%) underwent surgical resection and five (35.7%) received locoregional therapy. The indication for LT was unresectability in eight patients (57.1%) and liver failure secondary to oncologic treatment in the remaining six (42.9%). Before LT, seven patients (50%) demonstrated FDG-avid tumors and seven (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors prior to LT. Furthermore, four (57.1%) of the seven patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology.CONCLUSIONS: A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment option to prevent indolent disease progression from disappearing CRLM.

  View details for DOI 10.1097/SLA.0000000000005803

  View details for PubMedID 36692112

• Comparison of outcomes of normothermic regional perfusion and rapid-recovery DCD livers Nassar, A., Sellers, M., Bohorquez, H., Hobeika, M., Lee, D., Siddiqui, F., Alebrahim, M., Cannon, R., Neidlinger, N., Selvaggi, G., Abt, P., Sasaki, K., Montenovo, M. ELSEVIER SCIENCE INC. 2023: S18

  View details for Web of Science ID 000994636600016

• Heart transplantation for pediatric foreign nationals in the United States. Clinical transplantation Harano, T., Sheth, M., Sasaki, K., Yu, J., Wightman, S. C., Atay, S. M., Sainathan, S., Kim, A. W. 2023: e14900

  Abstract

  This study aimed to clarify survival outcomes, waitlist mortality, and waitlist days of heart transplantation of pediatric foreign nationals compared to pediatric United States (US) citizens. We retrieved data from March 2012 to June 2021 in the United Network Organ Sharing registry. Of 5,857 pediatric patients newly waitlisted, 133 (2.27%) patients were non-US citizen/non-US residents (NCNR). Patients with congenital heart disease were higher in the US citizen group than in the NCNR group (51.9% vs 22.6%, p < 0.001); 76.7% of patients in the NCNR group (102/133) had cardiomyopathy. Of the 133 NCNRs, 111 patients (83.5%) underwent heart transplantation, which was significantly higher than that in the US citizen group (68.6%, p < 0.001). The median waitlist time was 71 days (IQR, 22-172 days) in the NCNR group and 74 days (29-184 days) in the US citizen group (P = 0.48). Survival after heart transplant was significantly better in the NCNR group than in the US citizen group (n = 3,982; logrank test p = 0.015). Heart transplantation for pediatric foreign nationals was mostly indicated for cardiomyopathy, and their transplant rate was significantly higher than that in the US citizen group, with better survival outcomes. The better survival outcomes in the NCNR group compared to the US citizen group can likely be attributed to the differing diagnoses for which transplantation was performed. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.14900

  View details for PubMedID 36587308

• The future direction of liver transplantation for intrahepatic cholangiocarcinoma HEPATOMA RESEARCH Akabane, M., Imaoka, Y., Sasaki, K. 2023; 9

  View details for DOI 10.20517/2394-5079.2023.45

  View details for Web of Science ID 001065297000029

• IDENTIFYING NOVEL GENE TARGETS FOR DIAGNOSIS AND TREATEMENT OF HCC IN ASIAN AND CAUCASIAN POPULATIONS BASED ON WHOLE GENOME SEQUENCING Hong, S., Badshah, J., Aliwaisi, A., Sasaki, K., Pruett, T., Melcher, M., Bonham, C., Gallo, A., Martinez, O., Krams, S., Pham, K., Busque, S., Reitsma, A., Esquivel, C., Kirchner, V. ELSEVIER SCIENCE INC. 2023: S28

  View details for Web of Science ID 000994636600041

• Demystifying BRAF Mutation Status in Colorectal Liver Metastases: A Multi-institutional, Collaborative Approach to 6 Open Clinical Questions. Annals of surgery Margonis, G. A., Boerner, T., Bachet, J. B., Buettner, S., Moretto, R., Andreatos, N., Sartore-Bianchi, A., Wang, J., Kamphues, C., Gagniere, J., Lonardi, S., Løes, I. M., Wagner, D., Spallanzani, A., Sasaki, K., Burkhart, R., Pietrantonio, F., Pikoulis, E., Pawlik, T. M., Truant, S., Orlandi, A., Pikouli, A., Pella, N., Beyer, K., Poultsides, G., Seeliger, H., Aucejo, F. N., Kornprat, P., Kaczirek, K., Lønning, P. E., Kreis, M. E., Wolfgang, C. L., Weiss, M. J., Cremolini, C., Benoist, S., D'Angelica, M. 2022

  Abstract

  To investigate the clinical implications of BRAF mutated (mutBRAF) colorectal liver metastases (CRLM).The clinical implications of mutBRAF status in CRLM are largely unknown.Patients undergoing resection for mutBRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus nonV600E mutations, KRAS/BRAF co-mutation versus mutBRAF alone, MSS versus MSI status, upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy (RH) versus non-operative management.240 patients harboring BRAF-mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs. 144 mo, P=0.004), but not RFS compared to nonV600E mutations. KRAS/BRAF co-mutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs. 26 mo, P<0.001) but not OS (33.5 vs. 41 mo, P=0.3) compared to MSI-high tumors, while patients with resected converted disease had slightly worse RFS (8 vs. 11 mo, P=0.01) and similar OS (30 vs. 40 mo, P=0.4) compared to those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared to those with liver-limited disease (8.8 vs. 40 mo, P<0.001). RH following intrahepatic recurrence was associated with improved OS compared to non-operative management (41 vs. 18.7 mo, P=0.004). All results continued to hold true in the multivariable OS analysis.Although surgery may be futile in patients with BRAF-mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, repeat hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group with regard to RFS while patients with nonV600E mutations have excellent prognosis.

  View details for DOI 10.1097/SLA.0000000000005771

  View details for PubMedID 36453261

• Simultaneous versus staged resection for synchronous colorectal liver metastases: The win ratio approach. American journal of surgery Endo, Y., Alaimo, L., Araujo Lima, H., Tsilimigras, D. I., Hyer, J. M., Guglielmi, A., Ruzzenente, A., Alexandrescu, S., Poultsides, G., Sasaki, K., Aucejo, F., Pawlik, T. M. 2022

  Abstract

  INTRODUCTION: In order to investigate the optimal approach for synchronous colorectal liver metastases (sCRLM), we sought to use the "win ratio" (WR), a novel statistical approach, to assess the relative benefit of simultaneous versus staged surgical treatment.METHODS: Patients who underwent hepatectomy for sCRLM between 2008 and 2020 were identified from a multi-institutional database. The WR approach was utilized to compare composite outcomes of patients undergoing simultaneous versus staged resection.RESULTS: Among 1116 patients, 642 (57.5%) presented with sCRLM; 290 (45.2%) underwent simultaneous resection, while 352 (54.8%) underwent staged resection. In assessing the composite outcome, staged resection yielded a WR of 1.59 (95%CI 1.47-1.71) over the simultaneous approach for sCRLM. The highest WR occurred among patients requiring major hepatectomy (WR=1.93, 95%CI 1.77-2.10) compared with patients who required minor liver resection (WR=1.55, 95%CI 1.44-1.70).CONCLUSIONS: Staged resection was superior to simultaneous resection for sCRLM based on a WR assessment.

  View details for DOI 10.1016/j.amjsurg.2022.11.015

  View details for PubMedID 36435656

• Higher Tumor Burden Status Dictates the Impact of Surgical Margin Status on Overall Survival in Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma. Annals of surgical oncology Endo, Y., Sasaki, K., Moazzam, Z., Lima, H. A., Alaimo, L., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Kitago, M., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Cauchy, F., Koerkamp, B. G., Endo, I., Pawlik, T. M. 2022

  Abstract

  BACKGROUND: The present study aimed to examine the prognostic significance of margin status following hepatectomy of intrahepatic cholangiocarcinoma (ICC) relative to overall tumor burden and nodal status.METHOD: Patients who underwent curative-intent surgery for ICC between 1990 and 2017 were included from a multi-institutional database. The impact of margin status and width on overall survival (OS) was examined relative to TBS and preoperative nodal status.RESULTS: Among 1105 patients with ICC who underwent resection, median tumor burden score (TBS) was 6.1 (IQR 4.2-8.8) and 218 (19.7%) patients had N1 disease. More than one in eight patients had an R1 surgical margin (n = 154, 13.9%). Among patients with low or medium TBS, an increasing margin width was associated with an incrementally improved 5-year OS (R1 31.9% vs. 1-3 mm 38.5% vs. 3-10 mm 48.0% vs. ≥ 10 mm 52.3%). In contrast, among patients with a high TBS, margin width was not associated with better survival (R1 28.9% vs. 1-3 mm 22.8% vs. 3-10 mm 29.6% vs. ≥ 10 mm 13.7%). In addition, surgical margin status did not impact survival with cutoffs of TBS 7 or greater. Furthermore, patients with low or medium TBS and preoperative negative lymph nodes derived a survival benefit from an R0 resection (R1 resection, HR 2.15, 95% CI 1.35-3.44, p = 0.001). In contrast, margin status was not associated with prognosis among patients with a high TBS and preoperative positive/suspicious lymph nodes (R1 resection, HR 1.34, 95% CI 0.58-3.11, p = 0.50).CONCLUSION: R0 resection and wider margin resection resulted in improved outcomes in patients with low tumor burden; however, the survival benefit of negative margin status disappeared in patients with underlying poor tumor biology.

  View details for DOI 10.1245/s10434-022-12803-7

  View details for PubMedID 36396868

• Outcomes of Liver Transplantation in Patients with Preexisting Coronary Artery Disease. Transplantation Reznicek, E., Sasaki, K., Montane, B., Sims, A., Beard, J., Fares, M., Sharma, V., Cywinski, J., Quintini, C., Aucejo, F. N., Eghtesad, B., Miller, C. M., Menon, K. V. 2022

  Abstract

  Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT.Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59).During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P<0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone (P<0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD.Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.

  View details for DOI 10.1097/TP.0000000000004402

  View details for PubMedID 36397734

• Sequential hypothermic and normothermic perfusion preservation and transplantation of expanded criteria donor livers. Surgery Liu, Q., Del Prete, L., Ali, K., Grady, P., Bilancini, M., Etterling, J., D'Amico, G., Diago Uso, T., Hashimoto, K., Aucejo, F., Fujiki, M., Eghtesad, B., Sasaki, K., Kwon, C. H., Chaudhry, S., Doi, J., Pita, A., New, B., Bennett, A., Cywinski, J., Miller, C., Quintini, C. 2022

  Abstract

  The purpose of this study was to assess the safety and feasibility of sequential hypothermic oxygenated perfusion and normothermic machine perfusion and the potential benefits of graft viability preservation and assessment before liver transplantation.With the Food and Drug Administration and institutional review board approval, 17 expanded criteria donor livers underwent sequential hypothermic oxygenated perfusion and normothermic machine perfusion using our institutionally developed perfusion device.Expanded criteria donor livers were from older donors, donors after cardiac death, with steatosis, hypertransaminasemia, or calcified arteries. Perfusion duration ranged between 1 and 2 hours for the hypothermic oxygenated perfusion phase and between 4 and 9 hours for the normothermic machine perfusion phase. Three livers were judged to be untransplantable during normothermic machine perfusion based on perfusate lactate, bile production, and macro-appearance. One liver was not transplanted because of recipient issue after anesthesia induction and failed reallocation. Thirteen livers were transplanted, including 9 donors after cardiac death livers (donor warm ischemia time 16-25 minutes) and 4 from donors after brain death. All livers had the standardized lactate clearance >60% (perfusate lactate cleared to <4.0 mmol/L) within 3 hours of normothermic machine perfusion. Bile production rate was 0.2 to 10.7 mL/h for donors after brain death livers and 0.3 to 6.1 mL/h for donors after cardiac death livers. After transplantation, 5 cases had early allograft dysfunction (3 donors after cardiac death and 2 donors after brain death livers). No graft failure or patient death has occurred during follow-up time of 6 to 13 months. Two livers developed ischemic cholangiopathy. Compared with our previous normothermic machine perfusion study, the bile duct had fewer inflammatory cells in histology, but the post-transplant outcomes had no difference.Sequential hypothermic oxygenated perfusion and normothermic machine perfusion preservation is safe and feasible and has the potential benefits of preserving and evaluating expanded criteria donor livers.

  View details for DOI 10.1016/j.surg.2022.07.035

  View details for PubMedID 36302699

• Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC - Is it the exception to the rule? Surgical oncology Kamphues, C., Lefevre, J. H., Wang, J., Amini, N., Beaugerie, L., Kuehn, F., Park, S. H., Andreatos, N., Lauscher, J. C., Enea, D., Lehmann, K. S., Peru, N., Weixler, B., Kirchgesner, J., Degro, C. E., Pozios, I., van Beekum, C. J., Scholch, S., Zambonin, D., Schineis, C., Loch, F. N., Geka, D., Theoxari, M., Wu, B., Wang, P., Antoniou, E., Pikoulis, E., Moussata, D., Theodoropoulos, G., Ouaissi, M., Seeliger, H., Inaba, Y., Scaringi, S., ReiSSfelder, C., Vilz, T. O., Lin, C., Yang, S., Beyer, K., Renz, B. W., Sasaki, K., Margonis, G. A., Svrcek, M., Kreis, M. E. 2022; 45: 101874

  Abstract

  BACKGROUND: Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC.METHODS: All eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence-free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS.RESULTS: A total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p=0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p=0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p=0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p=0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p=0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p=0.98).CONCLUSIONS: In contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.

  View details for DOI 10.1016/j.suronc.2022.101874

  View details for PubMedID 36257179

• Reevaluating Liver Donor Risk in the Era of Improved Hepatitis C Virus Treatment. JAMA surgery Handley, T. J., Arnow, K., Sasaki, K., Kwong, A., Melcher, M. L. 2022

  Abstract

  This cohort study examines the risk of graft failure associated with donors with hepatitis C virus (HCV) infection before and after the introduction of direct-acting antiviral medications.

  View details for DOI 10.1001/jamasurg.2022.3922

  View details for PubMedID 36197654

• Has the Risk of Liver Re-Transplantation Improved Over the Two Decades? A UNOS Data Analysis Kim, M. H., Melcher, M. L., Kirchner, V. A., Gallo, A. E., Bonham, C. A., Esquivel, C., Sasaki, K. LIPPINCOTT WILLIAMS & WILKINS. 2022: S294

  View details for Web of Science ID 000889117000441

• Living Donor Liver Transplantation with Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts. Annals of surgery Fujiki, M., Hashimoto, K., Quintini, C., Aucejo, F., Kwon, C. H., Matsushima, H., Sasaki, K., Campos, L., Eghtesad, B., Diago, T., Iuppa, G., D'amico, G., Kumar, S., Liu, P., Miller, C., Pinna, A. 2022

  Abstract

  Living donor liver transplantation (LDLT) using small grafts, especially left-lobe grafts (LLG), continues to be a challenge due to small-for-size syndrome (SFSS). We herein demonstrate that with surgical modifications, outcomes with small grafts can be improved.Between 2012 and 2020, we performed 130 adult LDLT using 61 (47%) LLG in a single Enterprise. The median graft-to-recipient weight ratio (GRWR) was 0.84%, with GRWR <0.7% accounting for 22%. Splenectomy was performed in 72 (56%) patients for inflow modulation before (n=50) or after (n=22) graft reperfusion. In LLG-LDLT, venous outflow was achieved using all three recipient hepatic veins. In right-lobe graft (RLG)-LDLT, the augmented graft right hepatic vein was anastomosed to the recipient's cava with a large cavotomy. Outcome measures include SFSS, early allograft dysfunction (EAD), and survival.Graft survival rates at 1, 3, and 5 years were 94%, 90% and 83%, respectively, with no differences between LLG and RLG. Splenectomy significantly reduced portal flow without increasing the complication rate. Despite the aggressive use of small grafts, SFSS and EAD developed in only 1 (0.8%) and 18 (13.8%) patients, respectively. Multivariable logistic regression revealed MELD score and LLG as independent risk factors for EAD and splenectomy as a protective factor (OR 0.09; P=0.03). For LLG-LDLT, patients who underwent pre-reperfusion splenectomy tended to have better 1-year graft survival than those receiving post-reperfusion splenectomy.LLG are feasible in adult LDLT with excellent outcomes comparable to RLG. Venous outflow augmentation and splenectomy help lower the threshold of using small-for-size grafts without compromising graft survival.

  View details for DOI 10.1097/SLA.0000000000005630

  View details for PubMedID 35894443

• Impact of the donor hepatectomy time on short-term outcomes in liver transplantation using donation after circulatory death: A review of the US national registry. Clinical transplantation Bekki, Y., Kozato, A., Kusakabe, J., Tajima, T., Fujiki, M., Gallo, A., Melcher, M. L., Bonham, C. A., Sasaki, K. 2022: e14778

  Abstract

  BACKGROUND: During the donor hepatectomy time (dHT), defined as the time from the start of cold perfusion to the end of the hepatectomy, liver grafts have a suboptimal temperature. The aim of this study was to analyze the impact of prolonged dHT on outcomes in donation after circulatory death (DCD) liver transplantation (LT).METHODS: Using the US national registry data between 2012 and 2020, DCD LT patients were separated into 2 groups based on their dHT: standard dHT (<42 min) and prolonged dHT (≥42 min).RESULTS: There were 3810 DCD LTs during the study period. Median dHT was 32 min (IQR 25-41 min). Kaplan- Meier graft survival curves demonstrated inferior outcomes in the prolonged dHT group at 1-year after DCD LT compared to those in the standard dHT group (85.3% vs 89.9%; p < 0.01). Multivariate Cox proportional hazards models for 1-year graft survival identified that prolonged dHT [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.19 - 1.79], recipient age ≥ 64 years (HR 1.40, 95% CI 1.14 - 1.72), and MELD score ≥ 24 (HR 1.43, 95% CI 1.16 - 1.76) were significant predictors of 1-year graft loss. Spline analysis shows that the dHT effects on the risk for 1-year graft loss with an increase in the slope after median dHT of 32 min.CONCLUSION: Prolonged dHTs significantly reduced graft and patient survival after DCD LT. Because dHT is a modifiable factor, donor surgeons should take on cases with caution by setting the dHT target of < 32 min. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.14778

  View details for PubMedID 35866342

• New-Onset Atrial Fibrillation in Patients Undergoing Liver Transplantation: Retrospective Analysis of Risk Factors and Outcomes. Journal of cardiothoracic and vascular anesthesia Rivas, E., Sasaki, K., Liang, C., Wang, J., Quintini, C., Maheshwari, K., Turan, A., Fares, M., Cywinski, J. B. 2022

  Abstract

  The authors aimed to identify predictors of new-onset postoperative atrial fibrillation (POAF) during the initial 90 days following liver transplantation, and to assess the association between POAF in-hospital and 1-year mortality.A retrospective cohort study.At a university hospital between 2005 and 2017.Adults without a history of preoperative atrial fibrillation who underwent orthotopicliver transplantation.The authors assessed the univariate association between new-onset of POAF in the postoperative period and each potential factor through a logistic regression model. Moreover, they explored predictors for POAF through stepwise selection. Finally, the authors assessed the relationship between POAF and in-hospital and 1-year mortality using logistic regression models, and whether the duration of atrial fibrillation was associated with in-hospital and 1-year mortality. Among 857 patients, 89 (10.4%) developed POAF. Using only preoperative variables, pulmonary hypertension, age, Model for End-Stage Liver Disease (MELD) score, and White race were identified as the most important predictors. Model discrimination was 0.75 (95% CI: 0.69-0.80), and incorporating intraoperative variables was 0.77 (95% CI: 0.72-0.82). In-hospital mortality was observed in 7.2% (6/83) of patients with new-onset of POAF, and in 2.8% (22/768) without, with confounder-adjusted odds ratio (OR) 1.00 (97.5% CI: 0.29,3.45; p = 0.996). One-year mortality was 22.4% (20/89) in patients who developed POAF and 8.3% (64/768) in patients who did not, confounder-adjusted OR 2.64 (97.5% CI: 1.35-5.16; p = 0.001). The duration of POAF did not affect long-term postoperative mortality.Preoperative, mostly unmodifiable comorbidities are important risk factors for new-onset POAF after liver transplantation. The POAF was not associated with in-hospital mortality, but with increased 1-year mortality. Once developed, the duration of POAF did not affect long-term mortality after a liver transplant.

  View details for DOI 10.1053/j.jvca.2022.07.013

  View details for PubMedID 35999113

• Using Artificial Intelligence to Find the Optimal Margin Width in Hepatectomy for Colorectal Cancer Liver Metastases. JAMA surgery Bertsimas, D., Margonis, G. A., Sujichantararat, S., Boerner, T., Ma, Y., Wang, J., Kamphues, C., Sasaki, K., Tang, S., Gagniere, J., Dupre, A., Loes, I. M., Wagner, D., Stasinos, G., Macher-Beer, A., Burkhart, R., Morioka, D., Imai, K., Ardiles, V., O'Connor, J. M., Pawlik, T. M., Poultsides, G., Seeliger, H., Beyer, K., Kaczirek, K., Kornprat, P., Aucejo, F. N., de Santibanes, E., Baba, H., Endo, I., Lonning, P. E., Kreis, M. E., Weiss, M. J., Wolfgang, C. L., D'Angelica, M. 2022: e221819

  Abstract

  Importance: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width.Objective: To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics.Design, Setting, and Participants: The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charite-University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021.Exposures: Hepatectomy.Main Outcomes and Measures: Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence-based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory-based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values.Results: This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort.Conclusions and Relevance: This cohort study used artificial intelligence-based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.

  View details for DOI 10.1001/jamasurg.2022.1819

  View details for PubMedID 35648428

• KRAS alterations in colorectal liver metastases: shifting to exon, codon, and point mutations. The British journal of surgery Olthof, P. B., Buettner, S., Andreatos, N., Wang, J., Løes, I. M., Wagner, D., Sasaki, K., Macher-Beer, A., Kamphues, C., Pozios, I., Seeliger, H., Morioka, D., Imai, K., Kaczirek, K., Pawlik, T. M., Poultsides, G., Burkhart, R., Endo, I., Baba, H., Kornprat, P., Aucejo, F. N., Lønning, P. E., Beyer, K., Weiss, M. J., Wolfgang, C. L., Kreis, M. E., Margonis, G. A. 2022

  View details for DOI 10.1093/bjs/znac147

  View details for PubMedID 35595182

• Using the win ratio to compare laparoscopic versus open liver resection for colorectal cancer liver metastases HEPATOBILIARY SURGERY AND NUTRITION Paro, A., Hyer, J., Avery, B. S., Tsilimigras, D. I., Bagante, F., Guglielmi, A., Ruzzenente, A., Alexandrescu, S., Poultsides, G., Sasaki, K., Aucejo, F., Pawlik, T. M. 2022

  View details for DOI 10.21037/hbsn-22-36

  View details for Web of Science ID 000814161500001

• Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study. Clinical transplantation Sellers, M. T., Nassar, A., Alebrahim, M., Sasaki, K., Lee, D. D., Bohorquez, H., Cannon, R. M., Selvaggi, G., Neidlinger, N., McMaster, W. G., Hoffman, J. R., Shah, A. S., Montenovo, M. I. 2022: e14659

  Abstract

  Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from 8 organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal pre-sepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; 1 patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.14659

  View details for PubMedID 35362152

• Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases. JAMA surgery Hernandez-Alejandro, R., Ruffolo, L. I., Sasaki, K., Tomiyama, K., Orloff, M. S., Pineda-Solis, K., Nair, A., Errigo, J., Dokus, M. K., Cattral, M., McGilvray, I. D., Ghanekar, A., Gallinger, S., Selzner, N., Claasen, M. P., Burkes, R., Hashimoto, K., Fujiki, M., Quintini, C., Estfan, B. N., Kwon, C. H., Menon, K. V., Aucejo, F., Sapisochin, G. 2022

  Abstract

  Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic.To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs.This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021.Living-donor liver transplant.Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients.Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III).This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.

  View details for DOI 10.1001/jamasurg.2022.0300

  View details for PubMedID 35353121

• Nontumor related risk score: A new tool to improve prediction of prognosis after hepatectomy for colorectal liver metastases. Surgery Sasaki, K., Margonis, G. A., Moro, A., Wang, J., Wagner, D., Gagniere, J., Shin, J. K., D'Silva, M., Sahara, K., Miyata, T., Kusakabe, J., Beyer, K., Dupre, A., Kamphues, C., Imai, K., Baba, H., Endo, I., Taura, K., Cho, J. Y., Aucejo, F., Kornprat, P., Kreis, M. E., Kim, J. M., Burkhart, R., David Kwon, C. H., Pawlik, T. M. 2022

  Abstract

  BACKGROUND: Prognostic stratification of patients with colorectal cancer liver metastasis based solely on tumor-related factors has only moderate discriminatory ability. We hypothesized that the inclusion of nontumor related factors can improve prediction of long-term prognosis of patients with colorectal cancer liver metastasis.METHODS: Nontumor related laboratory markers were assessed utilizing a training cohort from 2 U.S. institutions (n= 1,205). Factors independently associated with prognosis were used to develop a nontumor related prognostic score. The discriminatory ability, assessed by Harrell's C-statistics (C-index) and net reclassification improvement, was validated and compared with 3 commonly used tumor-related clinical risk scores: Fong clinical risk scores, m-clinical risk scores, and Genetic and Morphological Evaluation (GAME) score in an external validation cohort from 5 Asian (n= 1,307) and 3 European (n= 1,058) institutions. The discriminatory ability of nontumor related prognostic score combined with each of these 3 tumor-related prognostic scores was also estimated.RESULTS: Alkaline phosphatase (hazard ratio 1.43; 95% confidence interval, 1.11-1.84), albumin (hazard ratio 0.71; 95% confidence interval, 0.57-0.89), and mean corpuscular volume (hazard ratio 19.0, per log unit; 95% confidence interval, 4.79-75.0) were each independently associated with increased risk of death after resection of colorectal cancer liver metastasis (all P < .05). In turn, alkaline phosphatase, albumin, and mean corpuscular volume were combined to form a nontumor related prognostic score (2.942* mean corpuscular volume+ 0.399* alkaline phosphatase-0.339* albumin-12)* 10 (median, 16; range, 1-30). The nontumor related prognostic score had good-to-modest discriminatory ability in the external cohort (C-index= 0.58), which was comparable to the 3 established tumor-related prognostic scores (C-index: Fong clinical risk scores, 0.53, m-clinical risk scores, 0.55, GAME, 0.58). The addition of the nontumor related prognostic score to the tumor-related prognostic scores enhanced the discriminatory ability in the entire study cohort (C-index: nontumor related score+Fong, 0.60, nontumor related score+m-clinical risk scores, 0.61, nontumor related score+GAME, 0.64), as well reclassification improvement (42.5, 42.7%, and 21.2%, respectively).CONCLUSION: Nontumor related prognostic information may help improve the prognostic stratification of patients after resection of colorectal cancer liver metastasis. The nontumor related prognostic score may be combined with tumor-related prognostic tools to enhance prognostic stratification of patients with colorectal cancer liver metastasis.

  View details for DOI 10.1016/j.surg.2022.01.030

  View details for PubMedID 35221105

• Is Laterality Prognostic in Resected KRAS-Mutated Colorectal Liver Metastases? A Systematic Review and Meta-Analysis. Cancers Belias, M., Sasaki, K., Wang, J., Andreatos, N., Kamphues, C., Kyriakos, G., Seeliger, H., Beyer, K., Kreis, M. E., Margonis, G. A. 2022; 14 (3)

  Abstract

  It is debated whether primary tumor laterality (PTL) is prognostic in all patients with colorectal liver metastases (CRLM) or only those with KRAS wild-type or KRAS-mutated tumors; Methods: We systematically reviewed PubMed for studies reporting on resected CRLM originating from left-sided (LS) versus right-sided (RS) colon cancer stratified by KRAS status. Individual participant data (IPD) were used if available. Given that there are two definitions of PTL, we performed two meta-analyses for KRAS-mutated and two for wild-type patients. To assess if an interaction underlies the possible difference between the effects of PTL in KRAS-mutated vs. wild-type CRLM, we similarly performed two meta-analyses of interaction terms; Results: The meta-analyses included eight studies and 7475 patients. PTL had a prognostic association with OS in patients with wild-type tumors (HR for LS: 0.71 [0.60-0.84]), but not in those with KRAS-mutated tumors (HR: 0.99 [0.82-1.19]). This difference stemmed from a truly variable effect of PTL for each KRAS status (mutated vs. wild-type) as the meta-analysis of interaction terms showed a significant interaction between them (HR:1.38 [1.24-1.53]). Similar results were obtained when the second definition of PTL (LS to not include the rectum) was used; Conclusions: KRAS status modifies the association of tumor site with survival. Right-sided tumors are associated with worse OS only in patients with wild-type CRLM.

  View details for DOI 10.3390/cancers14030799

  View details for PubMedID 35159066

• A chronological review of 500 minimally invasive liver resections in a North American institution: overcoming stagnation and toward consolidation. Surgical endoscopy Sasaki, K., Nair, A., Moro, A., Augustin, T., Quintini, C., Berber, E., Aucejo, F. N., Kwon, C. H. 2022

  Abstract

  Although interest in expanding the application of minimally invasive liver resection (MILR) is high the world over, most of the extensive experience in MILR has been reported from Far East Asia and Europe and its adoption in North America is limited. The aim of this study was to review the experience of MILR in a single North American institute over a 15-year period, highlighting both the obstacles encountered and strategies adopted to overcome the stagnation in its uptake.This study included 500 MILR cases between 2006 and 2020. Patient demographics, disease characteristics, surgical technique, and perioperative outcomes are summarized. The major hepatectomy rate and conversion rate were assessed according to case numbers (first 100, 101-300, and 301-500 cases) to assess chronological trends.Of 500, 402 MILRs were done by pure laparoscopic (80.4%), 67 were hand assisted (13.4%), and 31 were robotic (6.2%). The majority (64%) of cases were performed for malignancy (n = 320; 100 Hepatocellular carcinoma, 153 Colorectal metastases, 27 Intrahepatic cholangiocarcinoma, and others, 40, 64%). A total of 71 cases were converted to open (14.2%). The annual case number gradually increased over the first few years; however, case numbers stayed around 30 between 2009 and 2017. In this period, despite accumulating MILR experience, open conversion rates increased despite no change in major hepatectomy rate. After this period of long-term stagnation, we introduced crucial changes in team composition and laparoscopic instrumentation. Our MILR case number and major hepatectomy rate thereafter increased significantly without increasing conversion or complication rates.Our recovery from long-term stagnation by instituting key changes as detailed in this study could be used as a guidepost for programs that are contemplating transitioning their MILR program from minor to advanced resections. Establishing a formal MILR training model through proper mentorship/proctorship and building a dedicated MILR team would be imperative to this strategy.

  View details for DOI 10.1007/s00464-022-09182-1

  View details for PubMedID 35277772

• Transplantation of declined livers after normothermic perfusion. Surgery Quintini, C., Del Prete, L., Simioni, A., Del Angel, L., Diago Uso, T., D'Amico, G., Hashimoto, K., Aucejo, F., Fujiki, M., Eghtesad, B., Sasaki, K., Kwon, C. H., Cywinski, J., Bennett, A., Bilancini, M., Miller, C., Liu, Q. 2022

  Abstract

  The persistent shortage of liver allografts contributes to significant waitlist mortality despite efforts to increase organ donation. Normothermic machine perfusion holds the potential to enhance graft preservation, extend viability, and allow liver function evaluation in organs previously discarded because considered too high-risk for transplant.Discarded livers from other transplant centers were transplanted after assessment and reconditioning with our institutionally developed normothermic machine perfusion device. We report here our preliminary data.Twenty-one human livers declined for transplantation were enrolled for assessment with normothermic machine perfusion. Six livers (28.5%) were ultimately discarded after normothermic machine perfusion because of insufficient lactate clearance (>4.1 mmol/L after 4 hours), limited bile production (<0.5 mI/h), or moderate macrosteatosis, whereas 15 (71.5%) were considered suitable for transplantation. Normothermic machine perfusion duration was from 3 hours, 49 minutes to 10 hours, 29 minutes without technical problems or adverse events. No intraoperative or major early postoperative complications occurred in all transplanted recipients. No primary nonfunction occurred after transplantation. Seven livers had early allograft dysfunction with fast recovery, and 1 patient developed ischemic cholangiopathy after 4 months treated with biliary stents. All other patients had good liver function with a follow-up time of 8 weeks to 14 months.In total, 71.5% of discarded livers subjected to ex vivo normothermic machine perfusion were successfully transplanted after organ perfusion and assessment using an institutionally built device. This study challenges the current viability criteria reported in the literature and calls for a standardization of viability markers collection, an essential condition for the advancement of the field.

  View details for DOI 10.1016/j.surg.2021.10.056

  View details for PubMedID 35065791

• Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases: does the primary disease site matter? Journal of hepato-biliary-pancreatic sciences Amini, N., Andreatos, N., Margonis, G. A., Buettner, S., Wang, J., Galjart, B., Wagner, D., Sasaki, K., Angelou, A., Sun, J., Kamphues, C., Beer, A., Morioka, D., Marie Loes, I., Antoniou, E., Imai, K., Pikoulis, E., He, J., Kaczirek, K., Poultsides, G., Verhoef, C., Lonning, P. E., Endo, I., Baba, H., Kornprat, P., NAucejo, F., Kreis, M. E., Wolfgang, C. L., Weiss, M. J., Safar, B., Burkhart, R. A. 2021

  Abstract

  BACKGROUND: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown.METHODS: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed.RESULTS: A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio (HR): 1.58, 95%CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95%CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95%CI 1.22-1.99; codon 13, HR 2.10 95%CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy.CONCLUSIONS: While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.

  View details for DOI 10.1002/jhbp.1054

  View details for PubMedID 34614304

• Performance of two prognostic scores that incorporate genetic information to predict long-term outcomes following resection of colorectal cancer liver metastases: an external validation of the MD Anderson and JHH-MSK scores. Journal of hepato-biliary-pancreatic sciences Sasaki, K., Gagniere, J., Dupre, A., Ardiles, V., O Connor, J., Wang, J., Moro, A., Morioka, D., Buettner, S., Gau, L., Ribeiro, M., Wagner, D., Andreatos, N., Marie Loes, I., Fitschek, F., Kaczirek, K., Lonning, P., Kornprat, P., Poultsides, G., Kamphues, C., Imai, K., Baba, H., Endo, I., Kwon, C., Aucejo, F. N., Santibanes, E., Kreis, M. E., Margonis, G. 2021

  Abstract

  INTRODUCTION: Two novel clinical risk scores (CRS) that incorporate KRAS mutation status (modified CRS (mCRS) and GAME score) were developed. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS.METHODS: Patients undergoing hepatectomy for CRLM (2000-2018) in ten centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrel's C-index and Akaike's Information Criterion.RESULTS: In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14405, 14447, and 14319, respectively.CONCLUSION: In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS.

  View details for DOI 10.1002/jhbp.963

  View details for PubMedID 33797866

• Trends and outcomes of simultaneous versus staged resection of synchronous colorectal cancer and colorectal liver metastases. Surgery Tsilimigras, D. I., Sahara, K., Hyer, J. M., Diaz, A., Moris, D., Bagante, F., Guglielmi, A., Ruzzenente, A., Alexandrescu, S., Poultsides, G., Sasaki, K., Aucejo, F., Ejaz, A., Cloyd, J. M., Pawlik, T. M. 2021

  Abstract

  BACKGROUND: The objective of this study was to assess trends in the use as well as the outcomes of patients undergoing simultaneous versus staged resection for synchronous colorectal liver metastases.METHODS: Patients undergoing resection for colorectal liver metastases between 2008 and 2018 were identified using a multi-institutional database. Trends in use and outcomes of simultaneous resection of colorectal liver metastases were examined over time and compared with that of staged resection after propensity score matching.RESULTS: Among 1,116 patients undergoing resection for colorectal liver metastases, 690 (61.8%) patients had synchronous disease. Among them, 314 (45.5%) patients underwent simultaneous resection, while 376 (54.5%) had staged resection. The proportion of patients undergoing simultaneous resection for synchronous colorectal liver metastases increased over time (2008: 37.2% vs 2018: 47.4%; ptrend= 0.02). After propensity score matching (n= 201 per group), patients undergoing simultaneous resection for synchronous colorectal liver metastases had a higher incidence of overall (44.8% vs 34.3%; P= .03) and severe complications (Clavien-Dindo ≥III) (16.9% vs 7.0%; P= .002) yet comparable 90-day mortality (3.5% vs 1.0%; P= .09) compared with patients undergoing staged resection. The incidence of severe morbidity decreased over time (2008: 50% vs 2018: 11.1%; ptrend= 0.02). Survival was comparable among patients undergoing simultaneous versus staged resection of colorectal liver metastases (3-year overall survival: 66.1% vs 62.3%; P= .67). Following simultaneous resection, severe morbidity and mortality increased incrementally based on the extent of liver resection and complexity of colectomy.CONCLUSION: While simultaneous resection was associated with increased morbidity, the incidence of severe morbidity decreased over time. Long-term survival was comparable after simultaneous resection versus staged resection of colorectal liver metastases.

  View details for DOI 10.1016/j.surg.2021.01.041

  View details for PubMedID 33674128

• The optimal cut-off values for tumor size, number of lesions, and CEA levels in patients with surgically treated colorectal cancer liver metastases: An international, multi-institutional study. Journal of surgical oncology Kamphues, C., Andreatos, N., Kruppa, J., Buettner, S., Wang, J., Sasaki, K., Wagner, D., Morioka, D., Fitschek, F., Loes, I. M., Imai, K., Sun, J., Poultsides, G., Kaczirek, K., Lonning, P. E., Endo, I., Baba, H., Kornprat, P., Aucejo, F. N., Wolfgang, C. L., Kreis, M. E., Weiss, M. J., Margonis, G. A. 2021

  Abstract

  BACKGROUND AND OBJECTIVES: Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen(CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established.METHODS: Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature.RESULTS: A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95cm for tumor size, 1.5 for tumor number and 6.15ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs.CONCLUSION: The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.

  View details for DOI 10.1002/jso.26361

  View details for PubMedID 33400818

• Association of Early Bifurcation of Hepatic Artery with Arterial Injury in Right-Sided Living-Donor Hepatectomy: Retrospective Analysis of 500 Cases. Annals of surgery Kusakabe, J., Taura, K., Sasaki, K., Yagi, S., Doi, J., Ogiso, S., Hatano, E. 2021

  Abstract

  To explore the incidence of early bifurcation of the right hepatic artery (RHA) and the right posterior hepatic artery (RPHA), which is crucial in right lobe graft (RLG) and right posterior sector graft (RPSG) procurement for living-donor liver transplantation.Early bifurcation of the hepatic artery tends to induce oversight of one of the bifurcated arteries and its injury in RLG/RPSG procurement. Unrecognizable on conventional three-dimensional (3-D) images, its significance is underestimated.We enrolled 500 patients who underwent preoperative imaging for scheduled surgeries at two major transplant centers. All-in-one 3-D images consisting of the hepatic artery, portal vein, and bile duct were constructed. Early bifurcation of the RHA and the RPHA was defined as the arteries bifurcating proximal to the cutting line of the right hepatic duct and the right posterior duct, respectively.Early bifurcation of the RHA was seen in 11.3% of cases of an infra-portal RPHA and in 46.0% of cases of a supra-portal RPHA (P < 0.001). Early bifurcation of the RPHA was encountered in 35.3% of cases of an infra-portal RPHA, in no cases of a supra-portal RPHA, and in 100% of cases in which the arteries to segment 6/7 arose individually from the RHA. The overall incidence of early bifurcation was 19.9% for RHA and 43.6% for RPHA.Early bifurcation of the RHA and the RPHA is frequently encountered and requires caution for RLG/RPSG procurement. Special attention should be paid to supra-portal RPHA for RLG procurement.

  View details for DOI 10.1097/SLA.0000000000005335

  View details for PubMedID 34913890

• Should We Be Utilizing More Liver Grafts From Pediatric Donation After Circulatory Death Donors? A National Analysis of the SRTR from 2002 to 2017. Transplantation Sasaki, K., Nair, A., Firl, D. J., McVey, J. C., El-Gazzaz, G., Diago Uso, T., Fujiki, M., Aucejo, F. N., Quintini, C., Kwon, C. D., Hashimoto, K., Miller, C. M., Eghtesad, B. 2021; 105 (9): 1998-2006

  Abstract

  Rates of withdrawal of life-sustaining treatment are higher among critically ill pediatric patients compared to adults. Therefore, livers from pediatric donation after circulatory death (pDCD) could improve graft organ shortage and waiting time for listed patients. As knowledge on the utilization of pDCD is limited, this study used US national registry data (2002-2017) to estimate the prognostic impact of pDCD in both adult and pediatric liver transplant (LT).In adult LT, the short-term (1-year) and long-term (overall) graft survival (GS) between pDCD and adult donation after circulatory death (aDCD) grafts was compared. In pediatric LT, the short- and long-term prognostic outcomes of pDCD were compared with other type of grafts (brain dead, split, and living donor).Of 80 843 LTs in the study, 8967 (11.1%) were from pediatric donors. Among these, only 443 were pDCD, which were utilized mainly in adult recipients (91.9%). In adult recipients, short- and long-term GS did not differ significantly between pDCD and aDCD grafts (hazard ratio = 0.82 in short term and 0.73 in long term, both P > 0.05, respectively). Even "very young" (≤12 y) pDCD grafts had similar GS to aDCD grafts, although the rate of graft loss from vascular complications was higher in the former (14.0% versus 3.6%, P < 0.01). In pediatric recipients, pDCD grafts showed similar GS with other graft types whereas waiting time for DCD livers was significantly shorter (36.5 d versus 53.0 d, P < 0.01).Given the comparable survival seen to aDCDs, this data show that there is still much scope to improve the utilization of pDCD liver grafts.

  View details for DOI 10.1097/TP.0000000000003458

  View details for PubMedID 32947583

• Is 0.6% Reasonable as the Minimum Requirement of the Graft-to-recipient Weight Ratio Regardless of Lobe Selection in Adult Living-donor Liver Transplantation? Transplantation Kusakabe, J., Yagi, S., Sasaki, K., Uozumi, R., Abe, H., Okamura, Y., Taura, K., Kaido, T., Uemoto, S. 2021; 105 (9): 2007-2017

  Abstract

  Several studies reported favorable outcomes of small-for-size grafts with graft-to-recipient weight ratio (GRWR) <0.8% in living-donor liver transplantation (LDLT). However, their indications should be carefully determined because they must have been indicated for low-risk cases over larger grafts with 0.8% ≤ GRWR. Furthermore, evidence for minimum requirements of GRWR remains inconclusive. We investigated the safety of small-for-size grafts against larger grafts by adjusting for confounding risk factors, and minimum requirement of graft volume in adult LDLT.We enrolled 417 cases of primary adult-to-adult LDLT in our center between 2006 and 2019. The outcomes of small grafts (0.6% ≤ GRWR < 0.8%, n = 113) and large grafts (0.8% ≤ GRWR, n = 289) were mainly compared using a multivariate analysis and Kaplan-Meier estimates.The multivariate analysis showed that small grafts were not a significant risk factor for overall graft survival (GS). In the Kaplan-Meier analysis, small grafts did not significantly affect overall GS regardless of lobe selection (versus large grafts). However, GRWR < 0.6% was associated with poor overall GS. Although there were no significant differences between the 2 groups, unadjusted Kaplan-Meier curves of small grafts were inferior to those of large grafts in subcohorts with ABO incompatibility, and donor age ≥50 years.Similar outcomes were observed for small and large graft use regardless of lobe selection. 0.6% in GRWR was reasonable as the minimum requirement of graft volume in LDLT. However, small grafts should be indicated carefully for high-risk cases.

  View details for DOI 10.1097/TP.0000000000003472

  View details for PubMedID 33031228

• Neuroendocrine liver metastases: The role of liver transplantation. Transplantation reviews (Orlando, Fla.) D'Amico, G., Uso, T. D., Del Prete, L., Hashimoto, K., Aucejo, F. N., Fujiki, M., Eghtesad, B., Sasaki, K., David Kwon, C. H., Miller, C. M., Quintini, C. 2021; 35 (2): 100595

  Abstract

  Neuroendocrine tumor (NET) metastasis localized to the liver is an accepted indication for liver transplantation as such tumors have a low biological aggressiveness in terms of malignancy and are slow growing.The long-term results are comparable with and in some cases even better than those of transplantations performed for primary liver cancer. However, compared with nonmalignant conditions, neuroendocrine liver metastasis (NELM) may result in an inferior outcome of transplantation. In the face of the scarcity of donated organs and recent improved results of non-surgical treatment for NELM, controversy over patient selection and timing for liver transplantation continues.In this review, we provide an overview of the diagnostic work-up and selection criteria of patients with NELM being considered for liver transplantation. Thereafter, we provide a critical analysis of the reported outcomes of OLT.

  View details for DOI 10.1016/j.trre.2021.100595

  View details for PubMedID 33548685

• Machine learning predicts unpredicted deaths with high accuracy following hepatopancreatic surgery. Hepatobiliary surgery and nutrition Sahara, K., Paredes, A. Z., Tsilimigras, D. I., Sasaki, K., Moro, A., Hyer, J. M., Mehta, R., Farooq, S. A., Wu, L., Endo, I., Pawlik, T. M. 2021; 10 (1): 20-30

  Abstract

  Machine learning to predict morbidity and mortality-especially in a population traditionally considered low risk-has not been previously examined. We sought to characterize the incidence of death among patients with a low estimated morbidity and mortality risk based on the National Surgical Quality Improvement Program (NSQIP) estimated probability (EP), as well as develop a machine learning model to identify individuals at risk for "unpredicted death" (UD) among patients undergoing hepatopancreatic (HP) procedures.The NSQIP database was used to identify patients who underwent elective HP surgery between 2012-2017. The risk of morbidity and mortality was stratified into three tiers (low, intermediate, or high estimated) using a k-means clustering method with bin sorting. A machine learning classification tree and multivariable regression analyses were used to predict 30-day mortality with a 10-fold cross validation. C statistics were used to compare model performance.Among 63,507 patients who underwent an HP procedure, median patient age was 63 (IQR: 54-71) years. Patients underwent either pancreatectomy (n=38,209, 60.2%) or hepatic resection (n=25,298, 39.8%). Patients were stratified into three tiers of predicted morbidity and mortality risk based on the NSQIP EP: low (n=36,923, 58.1%), intermediate (n=23,609, 37.2%) and high risk (n=2,975, 4.7%). Among 36,923 patients with low estimated risk of morbidity and mortality, 237 patients (0.6%) experienced a UD. According to the classification tree analysis, age was the most important factor to predict UD (importance 16.9) followed by preoperative albumin level (importance: 10.8), disseminated cancer (importance: 6.5), preoperative platelet count (importance: 6.5), and sex (importance 5.9). Among patients deemed to be low risk, the c-statistic for the machine learning derived prediction model was 0.807 compared with an AUC of only 0.662 for the NSQIP EP.A prognostic model derived using machine learning methodology performed better than the NSQIP EP in predicting 30-day UD among low risk patients undergoing HP surgery.

  View details for DOI 10.21037/hbsn.2019.11.30

  View details for PubMedID 33575287

  View details for PubMedCentralID PMC7867718

• Conditional probability of graft survival in liver transplantation using donation after circulatory death grafts - a retrospective study. Transplant international : official journal of the European Society for Organ Transplantation Sasaki, K., Nair, A., Firl, D. J., McVey, J. C., Moro, A., Diago Uso, T., Fujiki, M., Aucejo, F. N., Quintini, C., Kwon, C. D., Eghtesad, B., Miller, C. M., Hashimoto, K. 2021; 34 (8): 1433-1443

  Abstract

  The use of livers from donation after circulatory death (DCD) is historically characterized by increased rates of biliary complications and inferior short-term graft survival (GS) compared to donation after brain death (DBD) allografts. This study aimed to evaluate the dynamic prognostic impact of DCD livers to reveal whether they remain an adverse factor even after patients survive a certain period following liver transplant (LT). This study used 74 961 LT patients including 4065 DCD LT in the scientific registry of transplant recipients from 2002-2017. The actual, 1 and 3-year conditional hazard ratio (HR) of 1-year GS in DCD LT were calculated using a conditional version of Cox regression model. The actual 1-, 3-, and 5-year GS of DCD LT recipients were 83.3%, 73.3%, and 66.3%, which were significantly worse than those of DBD (all P < 0.01). Actual, 1-, and 3-year conditional HR of 1-year GS in DCD compared to DBD livers were 1.87, 1.49, and 1.39, respectively. Graft loss analyses showed that those lost to biliary related complications were significantly higher in the DCD group even 3 years after LT. National registry data demonstrate the protracted higher risks inherent to DCD liver grafts in comparison to their DBD counterparts, despite survival through the early period after LT. These findings underscore the importance of judicious DCD graft selection at individual center level to minimize the risk of long-term biliary complications.

  View details for DOI 10.1111/tri.13846

  View details for PubMedID 33599045

• Seamless Introduction of a Purely Laparoscopic Full-Lobe Living Donor Hepatectomy Program in a North American Center. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Sasaki, K., Aucejo, F. N., Nair, A., Fujiki, M., Diago Uso, T., Quintini, C., Miller, C. M., Hashimoto, K., Kwon, C. H. 2021; 27 (8): 1203-1206

  View details for DOI 10.1002/lt.26030

  View details for PubMedID 33629504

• A case of 18 years disease-free survival after combined pancreatoduodenectomy and hemicolectomy for carcinosarcoma of the transverse colon. Surgical case reports Ohwada, S., Moro, A., Amit, N., Sasaki, K., Sakurai, S., Takada-Owada, A., Izumi, M., Nakano, Y., Kashima, Y., Matsuyama, H. 2021; 7 (1): 76

  Abstract

  Ascertaining the origin of large tumors located in the region of the pancreas head and adjacent mesocolon can pose a challenge preoperatively. En bloc pancreatoduodenectomy with hemicolectomy is often required towards curative tumor resection (R0) of malignant tumors in this region.Herein we report a case of a 48-year-old man with two contiguous masses each 5 cm in size, located in the pancreatic head. The masses were detected incidentally by abdominal ultrasonography at an annual health check. Endoscopic biopsies revealed inflammation with no malignancy. Cross-sectional imaging showed the tumor direct invasion of the uncinate process of the pancreas, and the third portion of the duodenum. Based on imaging, a malignant submucosal tumor originating from mesenchymal cells in the mesentery of the transverse colon was made preoperatively. The mass required en bloc pancreatoduodenectomy, right hemicolectomy, and resection of the superior mesenteric vein. The final pathology was carcinosarcoma of the transverse colon. The patient survived 18 years after surgery without recurrence.Malignant tumors located in the region of the pancreas head should be considered for an en bloc curative tumor resection and adjuvant chemotherapy treatments offered that might be beneficial for carcinosarcoma.

  View details for DOI 10.1186/s40792-021-01159-x

  View details for PubMedID 33765265

  View details for PubMedCentralID PMC7994500

• Dynamic α-Fetoprotein Response and Outcomes After Liver Transplant for Hepatocellular Carcinoma. JAMA surgery Halazun, K. J., Rosenblatt, R. E., Mehta, N., Lai, Q., Hajifathalian, K., Gorgen, A., Brar, G., Sasaki, K., Doyle, M. B., Tabrizian, P., Agopian, V. G., Najjar, M., Ivanics, T., Samstein, B., Brown, R. S., Emond, J. C., Yao, F., Lerut, J., Rossi, M., Mennini, G., Iesari, S., Finkenstedt, A., Schaefer, B., Mittler, J., Hoppe-Lotichius, M., Quintini, C., Aucejo, F., Chapman, W., Sapisochin, G. 2021; 156 (6): 559-567

  Abstract

  Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured.To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated score with currently accepted HCC selection tools, namely, the Milan Criteria (MC), the French-AFP (F-AFP), and Metroticket 2.0 models.A retrospective, multicenter prognostic analysis of prospectively collected databases of 2236 adults undergoing liver transplant for HCC was conducted at 3 US, 1 Canadian, and 4 European centers from January 1, 2001, to December 31, 2013. The AFP-R was measured as the difference between maximum and final pre-liver transplant AFP level. Cox proportional hazards regression and competing risk regression analyses examined recurrence-free and overall survival. Receiver operating characteristic analyses and net reclassification index were used to compare NYCA with MC, F-AFP, and Metroticket 2.0. Data analysis was performed from June 2019 to April 2020.The primary study outcome was 5-year recurrence-free survival; overall survival was the secondary outcome.Of 2236 patients, 1808 (80.9%) were men; mean (SD) age was 58.3 (7.96) years. A total of 545 patients (24.4%) did not meet the MC. The NYCA score proved valid on competing risk regression analysis, accurately predicting recurrence-free and overall survival (5-year cumulative incidence of recurrence risk in NYCA risk categories was 9.5% for low-, 20.5%, for acceptable-, and 40.5% for high-risk categories; P < .001 for all). The NYCA also predicted recurrence-free survival on a center-specific level: 453 of 545 patients (83.1%) who did not meet MC, 213 of 308 (69.2%) who did not meet the French-AFP, 292 of 384 (76.1%) who did not meet Metroticket 2.0 would be recategorized into NYCA low- and acceptable-risk groups (>75% 5-year recurrence-free survival). The Harrell C statistic for the validated NYCA score was 0.66 compared with 0.59 for the MC and 0.57 for the F-AFP models (P < .001). The net reclassification index for NYCA was 8.1 vs MC, 12.9 vs F-AFP, and 10.1 vs Metroticket 2.0.This study appears to externally validate the importance of AFP-R in the selection of patients with HCC for liver transplant. The AFP-R represents one of the truly objective measures of biological characteristics available before transplantation. Incorporation of AFP-R into selection criteria allows safe expansion of MC and other models, offering liver transplant to patients with acceptable tumor biological characteristics who would otherwise be denied potential cure.

  View details for DOI 10.1001/jamasurg.2021.0954

  View details for PubMedID 33950167

  View details for PubMedCentralID PMC8100910

• Long term outcomes and complications of reno-portal anastomosis in liver transplantation: results from a propensity score-based outcome analysis. Transplant international : official journal of the European Society for Organ Transplantation D'Amico, G., Matsushima, H., Del Prete, L., Diago Uso, T., Armanyous, S. R., Hashimoto, K., Eghtesad, B., Fujiki, M., Aucejo, F., Sasaki, K., Kwon, C. H., Simioni, A., Miller, C., Quintini, C. 2021; 34 (10): 1938-1947

  Abstract

  Diffuse splanchnic vein thrombosis (DSVT) remains a serious challenge in liver transplantation (LT). Reno-portal anastomosis (RPA) has previously been reported as a valid option for management of patients with DSVT during LT. The aim of this study was to evaluate post-transplant renal function and surgical outcomes of patients with DSVT who underwent RPA during LT. Between January 2005 and December 2017, 1270 patients underwent LT at our institution, including 16 with DSVT managed with RPA (RPA group). We compared renal function and surgical outcomes in these patients to outcomes in 48 propensity score (PS)-matched patients without thrombosis (control group), using a 1:3 matching model. The two groups had similar rates of postoperative portal vein thrombosis (PVT), renal dysfunction as measured by estimated glomerular filtration rate (eGFR), and overall postoperative complications (Clavien grade III), although the RPA group had a higher incidence of postoperative upper gastrointestinal (GI) bleeding (31.3% vs 4.2%; P = 0.009) that had no clinical consequence. There were no significant differences in five-year graft and patient survival rates between the groups (P = 0.133 and P = 0.166, respectively). RPA is an established technique in the management of patients with DSVT during LT, with comparable outcomes to patients without thrombosis. Our report is the first to demonstrate similar surgical outcomes, including long-term renal function, in LT recipients with or without RPA.

  View details for DOI 10.1111/tri.13920

  View details for PubMedID 34008257

• Validation of the IWATE criteria as a laparoscopic liver resection difficulty score in a single North American cohort. Surgical endoscopy Barron, J. O., Orabi, D., Moro, A., Quintini, C., Berber, E., Aucejo, F. N., Sasaki, K., Kwon, C. D. 2021

  Abstract

  Laparoscopic liver resection (LLR) involves a difficult learning curve, for which multiple difficulty scores have been proposed to assist with safe adaptation. The IWATE Criteria is a 4-level difficulty score shown to correlate with conversion to open surgery, estimated blood loss (EBL), and operative time in Japanese and French cohorts. We set out to validate the IWATE Criteria in a North American cohort, describe the evolution of our LLR program, and analyze the IWATE Criteria's ability to predict conversion to open surgery.Patients that underwent LLR between January 2006 and December 2019 were selected from a prospectively maintained database. Difficulty outcomes, including conversion to open surgery, EBL, operative time, and post-operative complications were analyzed according to IWATE difficulty level, both overall and between chronological eras. The IWATE Criteria's ability to predict conversion to open surgery was assessed with a receiver operating characteristic (ROC) analysis.A total of 426 patients met inclusion criteria. Operative time, EBL, and conversion to open surgery increased in concordance with low to advanced IWATE difficulty. ROC analysis for conversion to open surgery demonstrated an overall area under the curve (AUC) of 0.694. Predictive performance was superior during the first two eras, with AUCs of 0.771 and 0.775; predictive value decreased as the LLR program gained experience, with AUCs of 0.708 and 0.551 for eras three and four.This study validated the IWATE Criteria in a North American population distinct from previous Japanese and French cohorts, based on its correlation with operative time, EBL, and conversion to open surgery. The IWATE Criteria may be of utility for identification of LLR cases appropriate for surgeon experience, as well as determination of laparoscopic feasibility. Interval difficulty score recalibration may be warranted as surgeon perception of difficulty evolves.

  View details for DOI 10.1007/s00464-021-08561-4

  View details for PubMedID 34031739

• The Prognostic Utility of Intraoperative Allograft Vascular Inflow Measurements in Donation After Circulatory Death Liver Transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Nair, A., Sasaki, K., Diago Uso, T., D'Amico, G., Eghtesad, B., Aucejo, F., Kwon, C. H., Fujiki, M., Miller, C., Hashimoto, K., Quintini, C. 2021

  Abstract

  Donation after circulatory death (DCD) liver transplantation improves deceased donor liver use and decreases waitlist burden, albeit at an increased risk of biliary complications and inferior graft survival. Employing liver vascular inflow measurements intraoperatively permits allograft prognostication. However, its use in DCD liver transplantation is hitherto largely unknown and further explored here. DCD liver transplantation patient records at a single center from 2005 to 2018 were retrospectively scrutinized. Intraoperative flow data and relevant donor parameters were analyzed against endpoints of biliary events and graft survival. A total of 138 cases were chosen. The incidence of cumulative biliary complications was 38%, the majority of which were anastomotic strictures and managed successfully by endoscopic means. The ischemic cholangiopathy rate was 6%. At median thresholds of a portal vein (PV) flow rate of <92 mL/minute/100 g and buffer capacity (BC) of >0.04, both variables were independently associated with risk of biliary events (P = 0.01 and 0.04, respectively). Graft survival was 90% at 12 months and 75% at 5 years. Cox regression analysis revealed a PV flow rate of <50 mL/minute/100 g as predictive of poorer graft survival (P = 0.01). Furthermore, 126 of these DCD livers were analyzed against a propensity-matched group of 378 contemporaneous donation after brain death liver allografts (1:3), revealing significantly higher rates (P < 0.001) of both early allograft dysfunction (70% versus 30%) and biliary complications (37% versus 20%) in the former group. Although flow data were comparable between both sets, PV flow and BC were predictive of biliary events only in the DCD cohort. Intraoperative inflow measurements therefore provide valuable prognostication on biliary/graft outcomes in DCD liver transplantation, can help inform graft surveillance, and its routine use is recommended.

  View details for DOI 10.1002/lt.26212

  View details for PubMedID 34133830

• Induction Therapy With Antithymocyte Globulin and Delayed Calcineurin Inhibitor Initiation for Renal Protection in Liver Transplantation: A Multicenter Randomized Controlled Phase II-B Trial. Transplantation Nair, A., Coromina Hernandez, L., Shah, S., Zervos, X., Zimmerman, M., Sasaki, K., Diago, T., Hashimoto, K., Fujiki, M., Aucejo, F., Bollinger, J., Kaiser, T. L., Miller, C. M., Quintini, C., Fung, J. J., Eghtesad, B. 2021

  Abstract

  Calcineurin inhibitor (CNI) based immunosuppression in liver transplantation (LTx) is associated with acute and chronic deterioration of kidney function. Delaying CNI initiation by using induction rabbit anti-thymocyte globulin (rATG) may provide kidneys with adequate time to recover from a perioperative insult reducing the risk of early post-LTx renal deterioration.This was an open-label, multicenter, randomized controlled clinical trial comparing use of induction rATG with delayed CNI initiation (day-10) against upfront CNI commencement (SOC; standard of care) in those patients deemed at standard risk of postoperative renal dysfunction following LTx. The primary end point was change in (delta) creatinine from baseline to month-12.Fifty-five patients were enrolled in each study arm. Mean Tacrolimus levels remained comparable in both groups from day-10 throughout the study period. A significant difference in delta creatinine was observed between rATG and SOC groups at 9-months (p=0.03) but not at month-12 (p=0.05). eGFR levels remained comparable between cohorts at all time points. Rates of biopsy-proven acute rejection at 1-year were similar between groups (16.3 vs 12.7%, p= 0.58). rATG showed no significant adverse effects. Survival at 12-months was comparable between groups (p= 0.48).Although the use of induction rATG and concurrent CNI deferral in this study did not demonstrate a significant difference in delta creatinine at 1 year, these results indicate a potential role for rATG in preserving early kidney function, especially when considered with CNI deferral beyond 10 days and/or lower target Tacrolimus levels, with acceptable safety and treatment efficacy.

  View details for DOI 10.1097/TP.0000000000003904

  View details for PubMedID 34319926

• The utility of laparoscopic ultrasound during minimally invasive liver procedures in patients with malignant liver tumors who have undergone preoperative magnetic resonance imaging. Surgical endoscopy Kose, E., Kahramangil, B., Purysko, A. S., Aydin, H., Donmez, M., Sasaki, K., Kwon, C. H., Quintini, C., Aucejo, F., Berber, E. 2021

  Abstract

  The aim of this study was to assess the utility of laparoscopic ultrasound (LUS) during minimally invasive liver procedures in patients with malignant liver tumors who underwent preoperative magnetic resonance imaging (MRI).Medical records of patients with malignant liver lesions who underwent laparoscopic liver surgery between October 2005 and January 2018 and who underwent an MRI examination at our institution within a month before surgery were collected from a prospectively maintained database. The size and location of tumors detected on LUS, as well as whether they were seen on preoperative imaging, were recorded. Univariate and multivariate regression analyses were performed to identify factors that were associated with the detection of liver lesions on LUS that were not seen on preoperative MRI.A total of 467 lesions were identified in 147 patients. Tumor types included colorectal cancer metastasis (n = 53), hepatocellular cancer (n = 38), neuroendocrine metastasis (n = 23), and others (n = 33). Procedures included ablation (67%), resection (23%), combined resection and ablation (6%), and diagnostic laparoscopy with biopsy (4%). LUS identified 39 additional lesions (8.4%) that were not seen on preoperative MRI in 14 patients (10%). These were colorectal cancer (n = 20, 51%), neuroendocrine (n = 11, 28%) and other metastases (n = 8, 21%). These additional findings on LUS changed the treatment plan in 13 patients (8.8%). Factors predicting tumor detection on LUS but not on MRI included obesity (p = 0.02), previous exposure to chemotherapy (p < 0.001), and lesion size < 1 cm (p < 0.001).This study demonstrates that, despite advances in MRI, LUS performed during minimally invasive liver procedures may detect additional tumors in 10% of patients with liver malignancies, with the highest yield seen in obese patients with previous exposure to chemotherapy. These results support the routine use of LUS by hepatic surgeons.

  View details for DOI 10.1007/s00464-021-08849-5

  View details for PubMedID 34734301

• Two pumps or one pump? A comparison of human liver normothermic machine perfusion devices for transplantation. Artificial organs Liu, Q., Del Prete, L., Hassan, A., Pezzati, D., Bilancini, M., D'Amico, G., Diago Uso, T., Hashimoto, K., Aucejo, F., Fujiki, M., Sasaki, K., Kwon, C. H., Eghtesad, B., Miller, C., Quintini, C. 2021

  Abstract

  Normothermic machine perfusion provides continuous perfusion to ex situ hepatic grafts through the portal vein and the hepatic artery. Because the portal vein has high flow with low pressure and the hepatic artery has low flow with high pressure, different types of perfusion machines have been employed to match the two vessels' infusion hemodynamics.We compared transplanted human livers perfused through a 2-pump (n=9) versus a 1-pump perfusion system (n=6) where a C-clamp is used as a tubing constrictor to regulate hemodynamics.There was no significant difference between groups in portal vein or hepatic artery flow rate. The 1-pump group had more hemoglobin in the perfusate. However, there was no significant difference in plasma hemoglobin between the 2-pump and 1-pump groups at each time point or in the change in levels, proving no hemolysis occurred due to C-clamp tube constriction. After transplantation, the 2-pump group had two cases of early allograft dysfunction, whereas the 1-pump group had no early allograft dysfunction. There was no graft failure or patient death in either group during follow-up ranging from 20-52 months.Our data show that the 1-pump design provided the same hemodynamic output as the 2-pump design, with no additional hemolytic risk, but with the benefits of lower costs, easier transport and faster and simpler setting.

  View details for DOI 10.1111/aor.14150

  View details for PubMedID 34904245

• Tumor Burden Dictates Prognosis Among Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma: A Tool to Guide Post-Resection Adjuvant Chemotherapy? Annals of surgical oncology Tsilimigras, D. I., Hyer, J. M., Paredes, A. Z., Moris, D., Sahara, K., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Soubrane, O., Koerkamp, B. G., Endo, I., Sasaki, K., Aucejo, F., Zhang, X., Pawlik, T. M. 2020

  Abstract

  INTRODUCTION: While tumor burden (TB) has been associated with outcomes among patients with hepatocellular carcinoma, the role of overall TB in intrahepatic cholangiocarcinoma (ICC) remains poorly defined.METHODS: Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified from a multi-institutional database. The impact of TB on overall (OS) and disease-free survival (DFS) was evaluated in the multi-institutional database and validated externally.RESULTS: Among 1101 patients who underwent curative-intent resection of ICC, 624 (56.7%) had low TB, 346 (31.4%) medium TB, and 131 (11.9%) high TB. OS incrementally worsened with higher TB (5-year OS; low TB: 48.3% vs medium TB: 29.8% vs high TB: 17.3%, p<0.001). Similarly, patients with low TB had better DFS compared with medium and high TB patients (5-year DFS: 38.3% vs 18.7% vs 6.9%, p<0.001). On multivariable analysis, TB was independently associated with OS (medium TB: HR=1.40, 95% CI 1.14-1.71; high TB: HR=1.89, 95% CI 1.46-2.45) and DFS (medium TB, HR=1.61, 95% CI 1.33-1.96; high TB: HR=2.03, 95% CI 1.56-2.64). Survival analysis revealed an excellent prognostic discrimination using the TB among the external validation cohort (3-year OS; low TB: 44.8%, medium TB: 29.3%; high TB: 23.3%, p=0.03; 3-year DFS: low TB: 32.7%, medium TB: 10.7%; high TB: 0%, p<0.001). While neoadjuvant chemotherapy was not associated with survival across the TB groups, receipt of adjuvant chemotherapy was associated with increased survival among patients with high TB (5-year OS: 24.4% vs 13.4%, p=0.02).CONCLUSION: Overall TB dictated prognosis among patients with resectable ICC. TB may be used as a tool to help guide post-resection treatment strategies.

  View details for DOI 10.1245/s10434-020-09393-7

  View details for PubMedID 33259043

• A Novel Machine-Learning Approach to Predict Recurrence After Resection of Colorectal Liver Metastases. Annals of surgical oncology Paredes, A. Z., Hyer, J. M., Tsilimigras, D. I., Moro, A., Bagante, F., Guglielmi, A., Ruzzenente, A., Alexandrescu, S., Makris, E. A., Poultsides, G. A., Sasaki, K., Aucejo, F. N., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: Surgical resection of hepatic metastases remains the only potentially curative treatment option for patients with colorectal liver metastases (CRLM). Widely adopted prognostic tools may oversimplify the impact of model parameters relative to long-term outcomes.METHODS: Patients with CRLM who underwent a hepatectomy between 2001 and 2018 were identified in an international, multi-institutional database. Bootstrap resampling methodology used in tandem with multivariable mixed-effects logistic regression analysis was applied to construct a prediction model that was validated and compared with scores proposed by Fong and Vauthey.RESULTS: Among 1406 patients who underwent hepatic resection of CRLM, 842 (59.9%) had recurrence. The full model (based on age, sex, primary tumor location, T stage, receipt of chemotherapy before hepatectomy, lymph node metastases, number of metastatic lesions in the liver, size of the largest hepatic metastases, carcinoembryonic antigen [CEA] level and KRAS status) had good discriminative ability to predict 1-year (area under the receiver operating curve [AUC], 0.693; 95% confidence interval [CI], 0.684-0.704), 3-year (AUC, 0.669; 95% CI, 0.661-0.677), and 5-year (AUC, 0.669; 95% CI, 0.661-0.679) risk of recurrence. Studies analyzing validation cohorts demonstrated similar model performance, with excellent model accuracy. In contrast, the AUCs for the Fong and Vauthey scores to predict 1-year recurrence were only 0.527 (95% CI, 0.514-0.538) and 0.525 (95% CI, 0.514-0.533), respectively. Similar trends were noted for 3- and 5-year recurrence.CONCLUSION: The proposed clinical score, derived via machine learning, which included clinical characteristics and morphologic data, as well as information on KRAS status, accurately predicted recurrence after CRLM resection with good discrimination and prognostic ability.

  View details for DOI 10.1245/s10434-020-08991-9

  View details for PubMedID 32779049

• Prognostic factors differ according to KRAS mutational status: A classification and regression tree model to define prognostic groups after hepatectomy for colorectal liver metastasis. Surgery Moro, A., Mehta, R., Tsilimigras, D. I., Sahara, K., Paredes, A. Z., Bagante, F., Guglielmi, A., Alexandrescu, S., Poultsides, G. A., Sasaki, K., Aucejo, F. N., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: Although KRAS mutation status is known to affect the prognosis of patients with colorectal liver metastasis, the hierarchical association between other prognostic factors and KRAS status is not fully understood.METHODS: Patients who underwent a hepatectomy for colorectal liver metastasis were identified in a multi-institutional international database. A classification and regression tree model was constructed to investigate the hierarchical association between prognostic factors and overall survival relative to KRAS status.RESULTS: Among 1,123 patients, 29.9% (n= 336) had a KRAS mutation. Among wtKRAS patients, the classification and regression tree model identified presence of metastatic lymph nodes as the most important prognostic factor, whereas among mtKRAS patients, carcinoembryonic antigen level was identified as the most important prognostic factor. Among patients with wtKRAS, the highest 5-year overall survival (68.5%) was noted among patients with node negative primary colorectal cancer, solitary colorectal liver metastases, size <4.3 cm. In contrast, among patients with mtKRAS colorectal liver metastases, the highest 5-year overall survival (57.5%) was observed among patients with carcinoembryonic antigen <6 mg/mL. The classification and regression tree model had higher prognostic accuracy than the Fong score (wtKRAS [Akaike's Information Criterion]: classification and regression tree model 3334 vs Fong score 3341; mtKRAS [Akaike's Information Criterion]: classification and regression tree model 1356 vs Fong score 1396).CONCLUSION: Machine learning methodology outperformed the traditional Fong clinical risk score and identified different factors, based on KRAS mutational status, as predictors of long-term prognosis.

  View details for DOI 10.1016/j.surg.2020.05.019

  View details for PubMedID 32675031

• The Impact of Preoperative CA19-9 and CEA on Outcomes of Patients with Intrahepatic Cholangiocarcinoma. Annals of surgical oncology Moro, A., Mehta, R., Sahara, K., Tsilimigras, D. I., Paredes, A. Z., Farooq, A., Hyer, J. M., Endo, I., Shen, F., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Soubrane, O., Koerkamp, B. G., Sasaki, K., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: The objective of the current study was to assess the impact of serum CA19-9 and CEA and their combination on survival among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC).METHODS: Patients who underwent curative-intent resection of ICC between 1990 and 2016 were identified using a multi-institutional database. Patients were categorized into four groups based on combinations of serum CA19-9 and CEA (low vs. high). Factors associated with 1-year mortality after hepatectomy were examined.RESULTS: Among 588 patients, 5-year OS was considerably better among patients with low CA19-9/low CEA (54.5%) compared with low CA19-9/high CEA (14.6%), high CA19-9/low CEA (10.0%), or high CA19-9/high CEA (0%) (P<0.001). No difference in 1-year OS existed between patients who had either high CA19-9 (high CA19-9/low CEA:70.4%) or high CEA levels (low CA19-9/high CEA:72.5%) (P=0.92). Although patients with the most favorable tumor marker profile (low CA19-9/low CEA) had the best 1-year survival (87.9%), 15.1% (n=39) still died within a year of surgery. Among patients with low CA19-9/low CEA, a high neutrophil-to-lymphocyte ratio (NLR) (odds ratio 1.09; 95% confidence interval 1.03-1.64) and large size tumor (odds ratio 3.34; 95% confidence interval 1.40-8.10) were associated with 1-year mortality (P<0.05).CONCLUSIONS: Patients with either a high CA19-9 and/or high CEA had poor 1-year survival. High NLR and large tumor size were associated with a greater risk of 1-year mortality among patients with favorable tumor marker profile.

  View details for DOI 10.1245/s10434-020-08350-8

  View details for PubMedID 32198569

• Hepatocellular carcinoma tumour burden score to stratify prognosis after resection BRITISH JOURNAL OF SURGERY Tsilimigras, D. I., Moris, D., Hyer, J. M., Bagante, F., Sahara, K., Moro, A., Paredes, A. Z., Mehta, R., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Sasaki, K., Rodarte, A., Aucejo, F. N., Pawlik, T. M. 2020; 107 (7): 854-864

  Abstract

  Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system.Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage.Among 1053 patients, 63 (6·0 per cent) had BCLC-0, 826 (78·4 per cent) BCLC-A and 164 (15·6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0·175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC-B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010).The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.

  View details for DOI 10.1002/bjs.11464

  View details for Web of Science ID 000513278000001

  View details for PubMedID 32057105

• Very Early Recurrence After Liver Resection for Intrahepatic Cholangiocarcinoma: Considering Alternative Treatment Approaches. JAMA surgery Tsilimigras, D. I., Sahara, K. n., Wu, L. n., Moris, D. n., Bagante, F. n., Guglielmi, A. n., Aldrighetti, L. n., Weiss, M. n., Bauer, T. W., Alexandrescu, S. n., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G. n., Pulitano, C. n., Shen, F. n., Soubrane, O. n., Koerkamp, B. G., Moro, A. n., Sasaki, K. n., Aucejo, F. n., Zhang, X. F., Matsuyama, R. n., Endo, I. n., Pawlik, T. M. 2020

  Abstract

  Although surgery offers the best chance of a potential cure for patients with localized, resectable intrahepatic cholangiocarcinoma (ICC), prognosis of patients remains dismal largely because of a high incidence of recurrence.To predict very early recurrence (VER) (ie, recurrence within 6 months after surgery) following resection for ICC in the pre- and postoperative setting.Patients who underwent curative-intent resection for ICC between May 1990 and July 2016 were identified from an international multi-institutional database. The study was conducted at The Ohio State University in collaboration with all other participating institutions. The data were analyzed in December 2019.Two logistic regression models were constructed to predict VER based on pre- and postoperative variables. The final models were used to develop an online calculator to predict VER and the tool was internally and externally validated.Among 880 patients (median age, 59 years [interquartile range, 51-68 years]; 388 women [44.1%]; 428 [50.2%] white; 377 [44.3%] Asian; 27 [3.2%] black]), 196 (22.3%) developed VER. The 5-year overall survival among patients with and without VER was 8.9% vs 49.8%, respectively (P < .001). A preoperative model was able to stratify patients relative to the risk for VER: low risk (6-month recurrence-free survival [RFS], 87.7%), intermediate risk (6-month RFS, 72.3%), and high risk (6-month RFS, 49.5%) (log-rank P < .001). The postoperative model similarly identified discrete cohorts of patients based on probability for VER: low risk (6-month RFS, 90.0%), intermediate risk (6-month RFS, 73.1%), and high risk (6-month RFS, 48.5%) (log-rank, P < .001). The calibration and predictive accuracy of the pre- and postoperative models were good in the training (C index: preoperative, 0.710; postoperative, 0.722) as well as the internal (C index: preoperative, 0.715; postoperative, 0.728; bootstrapping resamples, n = 5000) and external (C index: postoperative, 0.672) validation data sets.An easy-to-use online calculator was developed to help clinicians predict the chance of VER after curative-intent resection for ICC. The tool performed well on internal and external validation. This tool may help clinicians in the preoperative selection of patients for neoadjuvant therapy as well as during the postoperative period to inform surveillance strategies.

  View details for DOI 10.1001/jamasurg.2020.1973

  View details for PubMedID 32639548

• Evaluating the Accuracy of the Endoscopic ABC Classification System in Diagnosing Helicobacter pylori-Infected Gastritis. Digestion Inui, M., Ohwada, S., Inui, Y., Kondo, Y., Moro, A., Sasaki, K. 2020; 101 (3): 298-307

  Abstract

  Evaluating the accuracy of the modified Endoscopic ABC (Endo ABC) classification with an electronic endoscopy with narrow band imaging without magnification in diagnosing Helicobacter pylori (H. pylori)-infected gastritis.A total of 576 patients were enrolled and they underwent modified Endo ABC. They were stratified into 5 groups (A to E) based on the grades of endoscopic findings. H. pylori-infected gastritis status was determined in the following ways: current H. pylori gastritis was defined as active gastritis and/or chronic atrophic gastritis (CAG) seen on endoscopy and positive H. pylori test, naïve H. pylori gastritis was defined as regular arrangement of collecting venules in the angle of the lesser curvature without CAG and negative H. pylori test, and previous H. pylori gastritis was defined as negative H. pylori tests regardless of the presence of CAG.Endo A has 97% accuracy and 100% positive predictive value in diagnosing naïve H. pylori gastritis. Endo E has 97% accuracy and 100% positive predictive value in diagnosing previous H. pylori gastritis. The accuracy of Endo B and Endo C in diagnosing current H. pylori gastritis was 89 and 82% respectively. Endo D has 87% accuracy in diagnosing previous H. pylori gastritis.This study showed that the modified Endo ABC classification enables to accurately determine the H. pylori-infected gastritis status.

  View details for DOI 10.1159/000498966

  View details for PubMedID 30982050

• Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients. Hepatology (Baltimore, Md.) Firl, D. J., Sasaki, K., Agopian, V. G., Gorgen, A., Kimura, S., Dumronggittigule, W., McVey, J. C., Iesari, S., Mennini, G., Vitale, A., Finkenstedt, A., Onali, S., Hoppe-Lotichius, M., Vennarecci, G., Manzia, T. M., Nicolini, D., Avolio, A. W., Agnes, S., Vivarelli, M., Tisone, G., Ettorre, G. M., Otto, G., Tsochatzis, E., Rossi, M., Viveiros, A., Cillo, U., Markmann, J. F., Ikegami, T., Kaido, T., Lai, Q., Sapisochin, G., Lerut, J., Aucejo, F. N. 2020; 71 (2): 569-582

  Abstract

  Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha-fetoprotein, Model for End-Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest-risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest-risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2-14.2] vs. 70.6% [48.3-92.9] and PDC:4.6% [0.1%-9.8%] vs. 47.1% [22.6-71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C-index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index = 0.71) and OS (C-index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.

  View details for DOI 10.1002/hep.30838

  View details for PubMedID 31243778

• Too Much, Too Little, or Just Right? The Importance of Allograft Portal Flow in Deceased Donor Liver Transplantation. Transplantation Matsushima, H., Sasaki, K., Fujiki, M., Uso, T. D., Aucejo, F., Kwon, C. H., Eghtesad, B., Miller, C., Quintini, C., Hashimoto, K. 2020; 104 (4): 770-778

  Abstract

  While portal flow (PF) plays an important role in determining graft outcomes in living donor liver transplantation, its impact in deceased donor liver transplantation (DDLT) is unclear. The aim of this study was to investigate the correlations between graft PF and graft outcomes in DDLT.We retrospectively investigated 1001 patients who underwent DDLT between January 2007 and June 2017 at our institution. The patients were divided into 3 groups according to hazard ratio for 1-year graft loss at each PF value, which was standardized with graft weight. Graft and recipient outcomes were compared between the groups.The low-PF group (PF < 65 mL/min/100 g, n = 210, P = 0.011) and the high-PF group (PF ≥ 155 mL/min/100 g, n = 159, P = 0.018) showed significantly poorer 1-year graft survival compared with the intermediate-PF group (PF ≥ 65 mL/min/100 g and < 155 mL/min/100 g, n = 632). The patients in the low-PF group had severe reperfusion injury and were more frequently complicated with primary nonfunction (P = 0.013) and early allograft dysfunction (P < 0.001) compared with the other groups. In contrast, the patients in the high-PF group had milder reperfusion injury, but had lower intraoperative hepatic artery flow with higher incidence of hepatic artery thrombosis (P = 0.043) and biliary complication (P = 0.041) compared with the other groups.These results suggest that intraoperative PF plays an important role in determining early graft outcomes after DDLT.

  View details for DOI 10.1097/TP.0000000000002968

  View details for PubMedID 31568395

• Ex Situ Liver Machine Perfusion: The Impact of Fresh Frozen Plasma. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Liu, Q., Hassan, A., Pezzati, D., Soliman, B., Lomaglio, L., Grady, P., Del Angel Diaz, L., Simioni, A., Maikhor, S., Etterling, J., D'Amico, G., Iuppa, G., Diago Uso, T., Hashimoto, K., Aucejo, F., Fujiki, M., Eghtesad, B., Sasaki, K., Kwon, C. H., Cywinski, J., Irefin, S., Bennett, A., Baldwin, W., Miller, C., Quintini, C. 2020; 26 (2): 215-226

  Abstract

  The primary aim of this single-center, phase 1 exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of a fresh frozen plasma (FFP)-based perfusate in ex situ liver normothermic machine perfusion (NMP) preservation. Using an institutionally developed perfusion device, 21 livers (13 donations after brain death and 8 donations after circulatory death) were perfused for 3 hours 21 minutes to 7 hours 52 minutes and successfully transplanted. Outcomes were compared in a 1:4 ratio to historical control patients matched according to donor and recipient characteristics and preservation time. Perfused livers presented a very low resistance state with high flow during ex situ perfusion (arterial and portal flows 340 ± 150 and 890 ± 70 mL/minute/kg liver, respectively). This hemodynamic state was maintained even after reperfusion as demonstrated by higher arterial flow observed in the NMP group compared with control patients (220 ± 120 versus 160 ± 80 mL/minute/kg liver, P = 0.03). The early allograft dysfunction (EAD) rate, peak alanine aminotransferase (ALT), and peak aspartate aminotransferase (AST) levels within 7 days after transplantation were lower in the NMP group compared with the control patients (EAD 19% versus 46%, P = 0.02; peak ALT 363 ± 318 versus 1021 ± 999 U/L, P = 0.001; peak AST 1357 ± 1492 versus 2615 ± 2541 U/L, P = 0.001 of the NMP and control groups, respectively). No patient developed ischemic type biliary stricture. One patient died, and all other patients are alive and well at a follow-up of 12-35 months. No device-related adverse events were recorded. In conclusion, with this study, we showed that ex situ NMP of human livers can be performed safely and effectively using a noncommercial device and an FFP-based preservation solution. Future studies should further investigate the impact of an FFP-based perfusion solution on liver hemodynamics during ex situ normothermic machine preservation.

  View details for DOI 10.1002/lt.25668

  View details for PubMedID 31642164

• A comparison of indocyanine green fluorescence and laparoscopic ultrasound for detection of liver tumors. HPB : the official journal of the International Hepato Pancreato Biliary Association Kose, E., Kahramangil, B., Aydin, H., Donmez, M., Takahashi, H., Acevedo-Moreno, L. A., Sasaki, K., Aucejo, F., Berber, E. 2020; 22 (5): 764-769

  Abstract

  Indocyanine green (ICG) fluorescence imaging (ICG-FI) has been suggested for intraoperative identification of liver tumors. We aim to compare the intraoperative diagnostic utility of this imaging modality with laparoscopic ultrasound (LUS).This is an IRB-approved prospective study. ICG was administered intravenously 1-2 days before surgery. The findings on ICG-FI were compared to those on preoperative cross-sectional imaging (POCSI), LUS, diagnostic laparoscopy (DL).A total of 144 lesions (62 superficial [visible on DL] and 82 deep) were detected in the study patients. POCSI identified 74%, LUS identified 92%, and ICG-FI identified 43%. ICG-FI detection rate was higher for superficial (95%) versus deep lesions (4%). 3% (4/144) of all lesions were seen only on ICG-FI. However, all of these lesions were small and superficial lesions that were apparent on DL.Although ICG-FI allowed detection of small superficial lesions that were not identifiable by POCSI or LUS, these lesions were apparent on DL even before ICG-FI. Therefore, its utility as an intraoperative diagnostic modality is limited at the dosage and timing used in the study. We believe that rather than a diagnostic tool, it has more potential for a dynamic use in guiding the resection of superficial lesions and delineating segmental/lobar anatomy.

  View details for DOI 10.1016/j.hpb.2019.10.005

  View details for PubMedID 31653594

• Can pretransplant TIPS be harmful in liver transplantation? A propensity score matching analysis. Surgery Matsushima, H., Fujiki, M., Sasaki, K., Cywinski, J. B., D'Amico, G., Uso, T. D., Aucejo, F., David Kwon, C. H., Eghtesad, B., Miller, C., Quintini, C., Hashimoto, K. 2020; 168 (1): 33-39

  Abstract

  Transjugular intrahepatic portosystemic shunt has been established as an effective treatment for complicated portal hypertension. This retrospective study investigated the effect of pretransplant transjugular intrahepatic portosystemic shunt placement on intraoperative graft hemodynamics and surgical outcomes after liver transplantation.Of 1,081 patients who underwent liver transplantation between January 2007 and June 2017 at Cleveland Clinic (OH, USA), 130 patients had transjugular intrahepatic portosystemic shunt placement before liver transplant. We performed a 1:2 propensity score matching to compare intraoperative graft hemodynamics and surgical outcomes between the transjugular intrahepatic portosystemic shunt group (n = 130) and the no-transjugular intrahepatic portosystemic shunt group (n = 260).The transjugular intrahepatic portosystemic shunt did not increase operative time, the volume of blood transfusion, duration of hospital stay, or complication rates. Graft and patient survivals were similar between the groups. Mean intraoperative cardiac output and graft portal flow in the transjugular intrahepatic portosystemic shunt group were greater than in the no-transjugular intrahepatic portosystemic shunt group (P = .03 and P = .003, respectively). In multivariate analysis, male sex, younger age, low platelet count, absence of portal vein thrombosis, and pretransplant transjugular intrahepatic portosystemic shunt placement were independently associated with increased portal flow volume (P < or = 0.03 each). Transjugular intrahepatic portosystemic shunt malposition was observed in 17 patients (13.1%). The 1-year patient survival was 70.6% with transjugular intrahepatic portosystemic shunt malposition and 92.0% without transjugular intrahepatic portosystemic shunt malposition (P = .01).Our findings suggest that pretransplant transjugular intrahepatic portosystemic shunt placement increases graft portal flow but does not compromise surgical outcomes after liver transplantation. Transjugular intrahepatic portosystemic shunt malposition, however, is not uncommon and may increase the complexity of transplantation.

  View details for DOI 10.1016/j.surg.2020.02.017

  View details for PubMedID 32268937

• Does graft hemodynamics affect the risk of hepatocellular carcinoma recurrence after liver transplantation? Clinical transplantation Matsushima, H., Acevedo-Moreno, L. A., Sasaki, K., Fujiki, M., Kwon, C. H., Uso, T. D., D'Amico, G., Aucejo, F., Eghtesad, B., Miller, C., Quintini, C., Hashimoto, K. 2020; 34 (8): e14004

  Abstract

  Although experimental studies have reported that hepatic ischemia-reperfusion injury promotes tumor growth and metastases, the impact of graft hemodynamics on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is unclear. To investigate the association between graft hemodynamics and HCC recurrence after LT, we conducted a retrospective analysis of 279 patients who underwent LT for HCC. Graft hemodynamics including portal vein flow (PVF), hepatic artery flow (HAF), and total hepatic flow (THF) was analyzed as a predictor of HCC recurrence, using competing risk regression analyses. The cutoff values of PVF, HAF, and THF were set at the lower quartile of distribution. A cumulative recurrence curve demonstrated that low THF (<1511 mL/min, P = .005) was significantly associated with increased recurrence, whereas neither low PVF (<1230 mL/min, P = .150) nor low HAF (<164 mL/min, P = .110) was significant. On multivariate analysis, outside Milan criteria (sub-hazard ratio [SHR] = 3.742; P < .001), microvascular invasion (SHR = 3.698; P < .001), and low THF (SHR = 2.359; P = .010) were independently associated with increased HCC recurrence. In conclusion, our findings suggest that graft hemodynamics may play an important role in HCC recurrence after LT.

  View details for DOI 10.1111/ctr.14004

  View details for PubMedID 32515016

• Risk assessment criteria in liver transplantation for hepatocellular carcinoma: proposal to improve transplant oncology. Hepatic oncology McVey, J. C., Sasaki, K., Firl, D. J. 2020; 7 (3): HEP26

  Abstract

  Liver transplantation for hepatocellular carcinoma has proved to be a highly effective cure if the right patient can be selected. Milan criteria has traditionally guided physicians toward appropriate liver allocation but changes in clinical practice, patient populations and recent developments in biomarkers are decreasing Milan criteria's utility. At the same time, the literature has flooded with a diversity of new criteria that demonstrate strong predictive power and are better suited for current clinical practice. In this article, the utility of newly proposed criteria will be reviewed and important issues to improve future criteria will be addressed in hopes of opening a discussion on how key questions surrounding criteria for liver transplantation of hepatocellular carcinoma can be answered.

  View details for DOI 10.2217/hep-2020-0003

  View details for PubMedID 32774836

  View details for PubMedCentralID PMC7399580

• Combination surgery for hepatocellular carcinoma: slashing and burning to improved survival. Annals of translational medicine McVey, J. C., Sasaki, K. 2020; 8 (16): 984

  View details for DOI 10.21037/atm-2020-74

  View details for PubMedID 32953784

  View details for PubMedCentralID PMC7475510

• Nutrition Support in Liver Transplantation and Postoperative Recovery: The Effects of Vitamin D Level and Vitamin D Supplementation in Liver Transplantation. Nutrients Doi, J., Moro, A., Fujiki, M., Eghtesad, B., Quintini, C., Menon, K. V., Hashimoto, K., Sasaki, K. 2020; 12 (12)

  Abstract

  Vitamin D plays an important role in the arena of liver transplantation. In addition to affecting skeletal health significantly, it also clinically exerts immune-modulatory properties. Vitamin D deficiency is one of the nutritional issues in the perioperative period of liver transplantation (LT). Although vitamin D deficiency is known to contribute to higher incidences of acute cellular rejection (ACR) and graft failure in other solid organ transplantation, such as kidneys and lungs, its role in LT is not well understood. The aim of this study was to investigate the clinical implication of vitamin D deficiency in LT. LT outcomes were reviewed in a retrospective cohort of 528 recipients during 2014-2019. In the pre-transplant period, 55% of patients were vitamin-D-deficient. The serum vitamin D level was correlated with the model for end-stage liver disease (MELD-Na) score. Vitamin D deficiency in the post-transplant period was associated with lower survival after LT, and the post-transplant supplementation of vitamin D was associated with a lower risk of ACR. The optimal vitamin D status and vitamin D supplementation in the post-transplant period may prolong survival and reduce ACR incidence.

  View details for DOI 10.3390/nu12123677

  View details for PubMedID 33260597

  View details for PubMedCentralID PMC7759902

• Resection of Colorectal Liver Metastasis: Prognostic Impact of Tumor Burden vs KRAS Mutational Status. Journal of the American College of Surgeons Tsilimigras, D. I., Hyer, J. M., Bagante, F. n., Guglielmi, A. n., Ruzzenente, A. n., Alexandrescu, S. n., Poultsides, G. n., Sasaki, K. n., Aucejo, F. n., Pawlik, T. M. 2020

  Abstract

  Prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status following hepatic resection remains ill-defined.Patients undergoing hepatectomy for CRLM between 2001-2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status [wild type (wtKRAS) versus mutated (mutKRAS)] was assessed.Among 1,361 patients, median number of metastatic lesions was 2 (IQR:1-3) and median size of largest metastatic lesion was 3.0cm (IQR:2.0-5.0cm) resulting in a median TBS of 4.1(IQR:2.8-6.1); KRAS status was wtKRAS (n=420, 30.9%), mutKRAS (n=251, 18.4%), and unknown (n=690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI: 45.2-53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS:49.4% vs. high TBS:36.7%), as was KRAS mutational status (5-year OS, wtKRAS:48.2% vs. mutKRAS:31.1%; unknown-KRAS:44.0%)(both p<0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs. high TBS: 38.4%, p=0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs. high TBS: 26.7%, p=0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes as patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs. 37.4%, respectively; p=0.59). On multivariable analysis, while TBS was associated with OS among patients with wt-KRAS CRLM (HR 1.43, 95%CI 1.02-2.00; p=0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92-1.99; p=0.12).While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM.

  View details for DOI 10.1016/j.jamcollsurg.2020.11.023

  View details for PubMedID 33383214

• KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases Margonis, G. A., Amini, N., Andreatos, N., Sasaki, K., Mcvey, J., Mirza, M. B., Warner, S., Buettner, S., Barbon, C., Wang, J., Pulvirenti, A., Angelou, A., Kamphues, C., Antoniou, E., Pikoulis, E., Pawlik, T. M., Kaczirek, K., Poultsides, G., Wagner, D., Endo, I., Imai, K., Aucejo, F., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. ELSEVIER SCI LTD. 2019: 1527–34

  View details for DOI 10.1016/j.hpb.2019.03.368

  View details for Web of Science ID 000496805100015

• Prognostic Impact of KRAS Mutational Status in Patients with Colorectal Cancer Liver Metastases Differs According to the Location of the Primary Tumor Amini, N., Margonis, G., Kreis, M. E., Poultsides, G. A., Sasaki, K., Wagner, D., Pikoulis, E., Weiss, M. J., Wolfgang, C. L., Safar, B. ELSEVIER SCIENCE INC. 2019: S69–S70

  View details for Web of Science ID 000492740900114

• OUTCOMES OF LIVER TRANSPLANTATION IN PATIENTS WITH PRE-EXISTING CORONARY ARTERY DISEASE Reznicek, E., Montane, B., Sims, A., Beard, J., Sasaki, K., Fares, M., Sharma, V., Cywinski, J., Quintini, C., Aucejo, F. N., Eghtesad, B., Miller, C. M., Menon, K. WILEY. 2019: 689A

  View details for Web of Science ID 000488653502290

• THE EFFECT OF DONOR CARDIOPULMONARY RESUSCITATION DURATION ON LIVER TRANSPLANTATION OUTCOME: A PROPENSITY SCORE MATCHED ANALYSIS OF NATIONAL DATA Hassan, A., Liu, Q., Pezzati, D., Uso, T., Sasaki, K., Hashimoto, K., Aucejo, F., Fujiki, M., Miller, C., Quintini, C. WILEY. 2019: 115

  View details for Web of Science ID 000491488701369

• Discordance in prediction of prognosis among patients with intrahepatic cholangiocarcinoma: A preoperative vs postoperative perspective JOURNAL OF SURGICAL ONCOLOGY Moro, A., Paredes, A. Z., Farooq, A., Sahara, K., Tsilimigras, D., Mehta, R., Endo, I., Guglielmi, A., Aldrighetti, L., Alexandrescu, S., Marques, H. P., Shen, F., Koerkamp, B. G., Sasaki, K., Pawlik, T. M., Weiss, M., Bauer, T. W., Poultsides, G. A., Maithel, S. K., Martel, G., Pulitano, C., Soubrane, O., Int Intrahepatic Cholangiocarcinom 2019

  Abstract

  The objective of the current study was to characterize patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent surgery with discordant preoperative and postoperative prediction scores and determine factors associated with prediction discrepancy.Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified in a multi-institutional international database. Preoperative and postoperative prognostic models were designed and discordant prognostic scores were identified. A multivariable logistic regression analysis was completed to determined factors associated with score discordance.Among 1149 patients, those who had concordant prediction scores were older (median age, 60 vs 56), and more likely to have a smaller median tumor size (6.0 vs 7.5 cm) (all P < .05). On multivariable logistic analysis, patients with higher neutrophil-lymphocyte ratio (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.09-1.19), higher CEA levels (OR, 1.25; 95% CI, 1.04-1.50), larger tumors (OR, 1.10; 95% CI, 1.04-1.15) and suspicious lymph nodes (OR, 2.05; 95% CI, 1.25-3.36) were more likely to have preoperative and postoperative score discordance. Older patients had decreased odds of having score discordance (OR, 0.98; 95% CI, 0.96-0.99). Patients with score discordance had worse overall survival compared with patients with concordant scores (median:15.9 vs 21.7 months, P < .05).Score discordance may reflect an aggressive variant of ICC that would benefit from early integration of multidisciplinary treatment strategies.

  View details for DOI 10.1002/jso.25671

  View details for Web of Science ID 000481226300001

  View details for PubMedID 31410852

• The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status: A Study By the International Genetic Consortium for Colorectal Liver Metastasis. Annals of surgery Margonis, G. A., Amini, N., Buettner, S., Kim, Y., Wang, J., Andreatos, N., Wagner, D., Sasaki, K., Beer, A., Kamphues, C., Morioka, D., Loes, I. M., Imai, K., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P. E., Burkhart, R., Endo, I., Baba, H., Mischinger, H. J., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019

  Abstract

  OBJECTIVE: To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status.BACKGROUND: Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors.METHODS: Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status.RESULTS: 277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38).CONCLUSIONS: This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.

  View details for DOI 10.1097/SLA.0000000000003504

  View details for PubMedID 31389831

• Conditional probability of graft survival in liver transplantation using donor after circulation death Sasaki, K., Mcvey, J., Firl, D., Moro, A., Okubo, K., Fujiki, M., Diago-Uso, T., Aucejo, F., Kwon, C. D., Eghtesad, B., Quintini, C., Miller, C., Hashimoto, K. LIPPINCOTT WILLIAMS & WILKINS. 2019: 28

  View details for Web of Science ID 000494805000046

• The prognostic impacts of donor gender in deceased donor liver transplantation for hepatocellular carcinoma Okubo, K., Sasaki, K., Moro, A., Fujiki, M., Uso, D. T., Eghtesad, B., Kwon, D., Miller, C., Quintini, C., Hashimoto, K., Aucejo, F. LIPPINCOTT WILLIAMS & WILKINS. 2019: 357-358

  View details for Web of Science ID 000494805000686

• Pre-implantation splenectomy and triple vessel outflow technique in left-lobe living donor liver transplantation Fujiki, M., Matsushima, H., Sasaki, K., Quintini, C., Aucejo, F., Diago, T., Eghtesad, B., Miller, C., Hashimoto, K. LIPPINCOTT WILLIAMS & WILKINS. 2019: 411

  View details for Web of Science ID 000494805000790

• Expansion of the use of left lobe grafts in adult liver transplantation in a US center: different strategy between deceased and living donor grafts Fujiki, M., Matsushima, H., Sasaki, K., Quintini, C., Aucejo, F., Diago, T., Eghtesad, B., Miller, C., Hashimoto, K. LIPPINCOTT WILLIAMS & WILKINS. 2019: 193-194

  View details for Web of Science ID 000494805000354

• Predictive model of morbidity and mortality for simultaneous liver transplantation and cardiac surgery: an innovative proposal Uso, D. T., Amico, G., Armanyous, S., Lomaglio, L., Hashimoto, K., Eghtesad, B., Aucejo, F., Fujiki, M., Sasaki, K., Kwon, D., Fares, M., Tong, M., Diago Torrent, J. L., Menon, N., Miller, C., Quintini, C. LIPPINCOTT WILLIAMS & WILKINS. 2019: 379

  View details for Web of Science ID 000494805000725

• Renoportal anastomosis in liver transplantation: results from a propensity score-based outcome analysis D'Amico, G., Armanyous, S., Lomaglio, L., Uso, D. T., Hashimoto, K., Eghtesad, B., Fujiki, M., Aucejo, F., Sasaki, K., Kwon, D., Matsushima, H., Lindenmeyer, C. C., Miller, C., Quintini, C. LIPPINCOTT WILLIAMS & WILKINS. 2019: 101

  View details for Web of Science ID 000494805000168

• Risk stratification of patients undergoing simultaneous liver transplantation and cardiac surgery Uso, D. T., D'Amico, G., Armanyous, S., Lomaglio, L., Eghtesad, B., Fujiki, M., Aucejo, F., Sasaki, K., Menon, N., Fares, M., Tong, M., Hashimoto, K., Miller, C., Quintini, C. LIPPINCOTT WILLIAMS & WILKINS. 2019: 67-68

  View details for Web of Science ID 000494805000112

• A randomized controlled clinical trial of Thymoglobulin (R) and extended delay of calcineurin inhibitor therapy for renal protection after liver transplantation: A multicenter study Eghtesad, B., Shah, S., Zervos, B., Zimmerman, M., Hernandez, C. L., Sasaki, K., Diago, T., Hashimoto, K., Aucejo, F., Fujiki, M., Block-Beach, H., Patterson, A., Miller, C., Quintini, C., Fung, J. LIPPINCOTT WILLIAMS & WILKINS. 2019: 95

  View details for Web of Science ID 000494805000158

• Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients. Annals of surgery Margonis, G. A., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Barbon, C., Beer, A., Kamphues, C., Loes, I. M., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P. E., Cameron, J. L., Mischinger, H. J., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019; 269 (6): 1129–37

  Abstract

  OBJECTIVE: To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis.BACKGROUND: CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery.METHODS: CS analysis was performed in 1099 patients of an international, multi-institutional cohort. Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3 rates was used to estimate the changing prognostic power of selected variables over time. A d < 0.1 indicated very small differences between groups, 0.1 ≤ d < 0.3 indicated small differences, 0.3 ≤ d < 0.5 indicated moderate differences, and d ≥ 0.5 indicated strong differences.RESULTS: According to OS estimates calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1 margin status, resected extrahepatic disease, patient age, primary tumor lymph node metastasis, tumor number, and carcinoembryonic antigen levels independently predicted worse survival. However, when temporal changes in the prognostic impact of these variables were considered using CS3 estimates, BRAF mutation dominated prognosis during the first year (d = 0.48), whereas surgeon-related variables (ie, surgical margin and resected extrahepatic disease) determined prognosis thereafter (d ≥ 0.5). Traditional clinicopathologic factors affected survival constantly, but only to a moderate degree (0.3 ≤ d < 0.5).CONCLUSIONS: The impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3 changed dramatically over time. Specifically, BRAF mutation status dominated prognosis in the first year, whereas positive surgical margins and resected extrahepatic disease determined prognosis thereafter.

  View details for PubMedID 31082912

• Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases A Multi-institutional, International Analysis of 1099 Patients ANNALS OF SURGERY Margonis, G., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Barbon, C., Beer, A., Kamphues, C., Loes, I., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P., Cameron, J. L., Mischinger, H., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019; 269 (6): 1129–37

  View details for DOI 10.1097/SLA.0000000000002664

  View details for Web of Science ID 000480730100028

• TOWARD PURE LAPAROSCOPIC LIVING DONOR HEPATECTOMY; CLEVELAND CLINIC EXPERIENCE Sasaki, K., Alameh, A., Moro, A., Okubo, K., Berber, E., Quintini, C., Kwon, C., Hashimoto, K., Aucejo, F. W B SAUNDERS CO-ELSEVIER INC. 2019: S1359

  View details for Web of Science ID 000467106005312

• KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases. HPB : the official journal of the International Hepato Pancreato Biliary Association Margonis, G. A., Amini, N., Andreatos, N., Sasaki, K., McVey, J., Mirza, M. B., Warner, S., Buettner, S., Barbon, C., Wang, J., Pulvirenti, A., Angelou, A., Kamphues, C., Antoniou, E., Pikoulis, E., Pawlik, T. M., Kaczirek, K., Poultsides, G., Wagner, D., Endo, I., Imai, K., Aucejo, F., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019

  Abstract

  BACKGROUND: A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined.METHODS: Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (>50% vs <50%, respectively). Multivariable logistic regression was used to identify factors associated with major response.RESULTS: 319 patients met inclusion criteria. 229 patients had a KRAS wild-type (wtKRAS) tumor and 90 harbored KRAS mutations (mutKRAS). A major pathologic response was more commonly noted in patients with wtKRAS compared to mutKRAS (48.5% vs 33.3%, P=0.01) and wtKRAS status remained independently associated with a major response (P=0.04). On a codon-specific level, major pathologic response occurred less frequently in those with codon 13 mutations (17.7%) compared to those with codon 12 (35.4%), and other KRAS mutations (33.3%). Importantly, codon 13 mutations were independently associated with minor pathologic response (P=0.023).CONCLUSIONS: Patients with wtKRAS tumors appear to have the highest likelihood of experiencing a major response after preoperative chemotherapy. Future studies in "all-comer" cohorts are needed to confirm these findings and further investigate the response of codon 13 mutations.

  View details for PubMedID 30979646

• Correlations between Preoperative Hepatic Venous Pressure Gradient and Graft Hemodynamics after Reperfusion in living Donor Liver Transplantation. Matsushima, H., Fujiki, M., Sasaki, K., Aucejo, F., Usu, T., Kwon, C., Eghtesad, B., Miller, C., Quintini, C., Hashimoto, K. WILEY. 2019: 882

  View details for Web of Science ID 000474897602717

• The Risks Are Not Always The Same; Peak Timing Of Risk In Liver Transplantation. Sasaki, K., McVey, J., Firl, D., Okubo, K., Fujiki, M., Uso, T., Kwon, D., Eghtesad, B., Quintini, C., Miller, C., Aucejo, F., Hasimoto, K. WILEY. 2019: 712

  View details for Web of Science ID 000474897602302

• A Randomized Controlled Clinical Trial of Thymoglobulin (R) and Extended Delay of Calcineurin Inhibitor Therapy for Renal Protection after Liver Transplantation: A Multicenter Study. Coromina, L., Shah, S., Xervos, B., Zimmerman, M., Sasaki, K., Diago, T., Hashimoto, K., Aucejo, F., Fujiki, M., Block-Beach, H., Patterson, A., Miller, C., Quintini, C., Eghtesad, B. WILEY. 2019: 554-555

  View details for Web of Science ID 000474897601557

• Renoportal Anastomosis in Liver Transplantation: Results from a Propensity Score-Based Outcome Analysis. D'Amico, G., Armanyous, S., Lomaglio, L., Uso, T., Hashimoto, K., Eghtesad, B., Fujiki, M., Aucejo, F., Sasaki, K., Matsushima, H., Lindenmeyer, C., Miller, C., Quintini, C. WILEY. 2019: 413

  View details for Web of Science ID 000474897601226

• Halt-hcc At The Time Of Listing Is Superior To Other Allocation Metrics At Predicting Waitlist Dropout; An Srtr Analysis. Mcvey, J. C., Sasaki, K., Firl, D. J., Miller, C. M., Hashimoto, K., Quintini, C., Aucejo, F. N. WILEY. 2019: 563-564

  View details for Web of Science ID 000474897601575

• Proximal Splenic Artery Embolization Is A Safe And Effective Tool To Treat Two Sides Of The Same Coin After Liver Transplant: Persistent High Hepatic Artery Resistive Index And Refractory Ascites And Hydrothorax Due To Portal Hyperperfusion. Lomaglio, L., Matsushima, H., Simioni, A., D'Amico, G., Uso, T., Hashimoto, K., Eghtesad, B., Fujiki, M., Aucejo, F., Sasaki, K., Kwon, C., Coppa, C., Molano, M., Miller, C., Quintini, C. WILEY. 2019: 873

  View details for Web of Science ID 000474897602691

• Nothing Lasts Forever, So Of The Donor Risk Index For Liver Transplant. Okubo, K., Sasaki, K., Moro, A., Mcbey, J., Fujiki, M., Uso, T., Eghtesad, B., Kwon, D., Miller, C., Quintini, C., Hashimoto, K., Aucejo, F. WILEY. 2019: 462-463

  View details for Web of Science ID 000474897601341

• The Utility Of Intraoperative Vascular Anastomotic Inflow Measurements In Donation After Circulatory Death (DCD) Liver Transplantation. Nair, A., Hernandez, L., Sasaki, K., Kwon, C., Uso, T., Fujiki, M., Aucejo, F., Hashimoto, K., Eghtesad, B., Miller, C., Quintini, C. WILEY. 2019: 991

  View details for Web of Science ID 000474897603219

• The Impact of Portal Flow after Reperfusion on Graft Outcomes after Deceased Donor Liver Transplantation. Matsushima, H., Sasaki, K., Fujiki, M., Uso, T., Eghtesad, B., Aucejo, F., Kwon, C., Miller, C., Quintini, C., Hashimoto, K. WILEY. 2019: 414

  View details for Web of Science ID 000474897601227

• Risk Stratification of Patients Undergoing Simultaneous Liver Transplantation and Cardiac Surgery. Uso, T., D'Amico, G., Armanyous, S., Lomaglio, L., Eghtesad, B., Fujiki, M., Aucejo, F., Sasaki, K., Menon, N. K., Fares, M., Tong, M., Hashimoto, K., Miller, C., Quintini, C. WILEY. 2019: 707

  View details for Web of Science ID 000474897602288

• Proximal Splenic Artery Embolization For Refractory Ascites And Hydrothorax After Liver Transplant: A Single Center Analysis Of Factors Associated With Success. Lomaglio, L., D'Amico, G., Armanyous, S., Uso, T., Hashimoto, K., Eghtesad, B., Fujiki, M., Aucejo, F., Sasaki, K., Kwon, C., Coppa, C., Molano, M., Lindenmeyer, C., Miller, C., Quintini, C. WILEY. 2019: 414-415

  View details for Web of Science ID 000474897601229

• The Prognostic Role of Primary Tumor Site Differs Among Patients with Colon Cancer Liver Metastases According to the KRAS Mutational Status Margonis, G., Amini, N., Buettner, S., Andreatos, N., Wagner, D., Kazunari, S., Wang, J., Sun, G., Pulvirenti, A., Beer, A., Kamphues, C., Morioka, D., Loes, I., Imai, K., He, J., Pawlik, T., Kaczirek, K., Poultsides, G., Lonning, P., Burkhart, R., Endo, I., Baba, H., Mischinger, H., Aucejo, F., Kreis, M., Wolfgang, C., Weiss, M. SPRINGER. 2019: S31

  View details for Web of Science ID 000459144900070

• Proximal Splenic Artery Embolization Refractory Ascites and Hydrothorax after Liver Transplantation: The Cleveland Clinic Experience Lomaglio, L., Armanyous, S., D'Amico, G., Hassan, A., Liu, Q., Uso, T., Hashimoto, K., Eghtesad, B., Aucejo, F., Fujiki, M., Sasaki, K., Molano, M., Coppa, C., Miller, C., Quintini, C. WILEY. 2019: 65

  View details for Web of Science ID 000457809000110

• Biliary Mucinous Cystic Neoplasm: a Classic Presentation of a Rare Neoplasm. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Sharma, S., Sasaki, K., Allende, D., Bennett, A., Aucejo, F. N. 2019; 23 (4): 874-876

  Abstract

  Biliary mucinous cystic neoplasms are rare parenchymal neoplasms with a considerable malignant potential. Due to a lack of diagnostic imaging criteria, histopathologic evaluation remains the definitive method of diagnosis. Resection is the treatment of choice. Here, the authors present a case of biliary mucinous neoplasm in a 39-year-old female with the associated radiographic and histopathologic findings.

  View details for DOI 10.1007/s11605-018-3768-z

  View details for PubMedID 29679341

• Renoportal anastomosis in liver transplantation and its impact on patient outcomes: a systematic literature review. Transplant international : official journal of the European Society for Organ Transplantation D'Amico, G., Hassan, A., Diago Uso, T., Hashmimoto, K., Aucejo, F. N., Fujiki, M., Eghtesad, B., Sasaki, K., Lindenmeyer, C. C., Miller, C. M., Quintini, C. 2019; 32 (2): 117-127

  Abstract

  Portal vein thrombosis (PVT) is commonly encountered during liver transplantation (LT). Depending on the grade of thrombosis, varied management strategies are indicated. The aims of this study are to clarify the contemporary role of renoportal anastomosis (RPA) in patients with splanchnic vein thrombosis (SVT) undergoing LT and to systematically analyze all reported cases of RPA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta- Analyses statement guidelines. The study was limited to studies reported in English between January 1997 and May 2017. Only retrospective single center studies were included in the analysis. A total of 66 patients with SVT were reported to have undergone RPA during LT. Transient renal dysfunction was reported in 12 patients (18.1%), variceal hemorrhage in 2 patients (3%), early portal vein (PV) re-thrombosis in 2 patients (3%), chronic renal dysfunction in 2 patients (3%), and late PV re-thrombosis in 1 patient (1.5%). The overall patient and graft survival were each 80%. This analysis illustrates the decades-long evolution of a technique practiced across the field of transplantation. Postoperative complications and graft survival appear to be encouraging, even in the setting of SVT.

  View details for DOI 10.1111/tri.13368

  View details for PubMedID 30362294

• The impact of resection margin on overall survival for patients with colon cancer liver metastasis varied according to the primary cancer location. HPB : the official journal of the International Hepato Pancreato Biliary Association McVey, J. C., Sasaki, K., Margonis, G. A., Nowacki, A. S., Firl, D. J., He, J., Berber, E., Wolfgang, C., Miller, C. C., Weiss, M., Aucejo, F. N. 2019; 21 (6): 702-710

  Abstract

  Investigation into right and left-sided primary colon liver metastasis (CLM) has revealed differences in the tumor biology and prognosis. This indicates that preoperative and operative factors may affect outcomes of right-sided primary CLM differently than left. This retrospective analysis investigated the effects of resection margin stratified by left and right-sided primary CLM on overall survival (OS) for patients undergoing hepatectomy.A total of 732 patients undergoing hepatic resection for CLM at the Cleveland Clinic and Johns Hopkins were identified between 2002 and 2016. Clinically significant variables were analyzed using Cox proportional hazard regression. The cohort was then divided into patients with right and left-sided CLM and analyzed separately using Kaplan Meier analysis and Cox proportional hazard regression.Cox proportional hazard regression showed that left-sided CLM with an R0 margin was a statistically significant predictor of OS even after controlling for other important factors (HR = 0.629, P = 0.024) but right-sided CLM with R0 margin was not (HR = 0.788, P = 0.245). Kaplan-Meier analysis demonstrated that patients with a left-sided CLM and R0 margin had the best prognosis (P = 0.037).Surgical margin is an important prognostic factor for left-sided primary CLM but tumor biology may override surgical technique for right-sided CLM.

  View details for DOI 10.1016/j.hpb.2018.11.001

  View details for PubMedID 30501989

• Toward the universal scoring system in treatment for patients with hepatocellular carcinoma. Journal of hepatology Kusakabe, J., Firl, D. J., Sasaki, K. 2019; 70 (3): 568-570

  View details for DOI 10.1016/j.jhep.2018.10.024

  View details for PubMedID 30554931

• Elevated Risk of Split-Liver grafts in adult liver Transplantation: Statistical Artifact or Nature of the Beast? Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Sasaki, K., Firl, D. J., McVey, J. C., Schold, J. D., Iuppa, G., Diago Uso, T., Fujiki, M., Aucejo, F. N., Quintini, C., Eghetsad, B., Miller, C. M., Hashimoto, K. 2019; 25 (5): 741-751

  Abstract

  A recent study using US national registry data reported, using Cox proportional hazards (PH) models, that split-liver transplantation (SLT) has improved over time and is no more hazardous than whole-liver transplantation (WLT). However, the study methods violated the PH assumption, which is the fundamental assumption of Cox modeling. As a result, the reported hazard ratios (HRs) are biased and unreliable. This study aimed to investigate whether the risk of graft survival (GS) in SLT has really improved over time, ensuring attention to the PH assumption. This study included 80,998 adult deceased donor liver transplantation (LT) (1998-2015) from the Scientific Registry Transplant Recipient. The study period was divided into 3 time periods: era 1 (January 1998 to February 2002), era 2 (March 2002 to December 2008), and era 3 (January 2009 to December 2015). The PH assumption was tested using Schoenfeld's test, and where the HR of SLT violated the assumption, changes in risk for SLT over time from transplant were assessed. SLT was performed in 1098 (1.4%) patients, whereas WLT was used in 79,900 patients. In the Cox PH analysis, the P values of Schoenfeld's global tests were <0.05 in all eras, which is consistent with deviation from proportionality. Assessing HRs of SLT with a time-varying effect, multiple Cox models were conducted for post-LT intervals. The HR curves plotted according to time from transplant were higher in the early period and then decreased at approximately 1 year and continued to decrease in all eras. For 1-year GS, the HRs of SLT were 1.92 in era 1, 1.52 in era 2, and 1.47 in era 3 (all P < 0.05). In conclusion, the risk of SLT has a time-varying effect and is highest in the early post-LT period. The risk of SLT is underestimated if it is evaluated by overall GS. SLT was still hazardous if the PH assumption was considered, although it became safer over time.

  View details for DOI 10.1002/lt.25409

  View details for PubMedID 30615254

• Goodbye for Good: Stepping Away From Recurrence. Gastroenterology Moro, A., Okubo, K., Sasaki, K. 2019; 156 (8): 2353-2354

  View details for DOI 10.1053/j.gastro.2018.12.048

  View details for PubMedID 30880021

• Care After Liver Resection for Hepatocellular Carcinoma. JAMA surgery Okubo, K., Moro, A., Sasaki, K. 2019; 154 (6): 568-569

  View details for DOI 10.1001/jamasurg.2019.0149

  View details for PubMedID 30892576

• Predictive Value of Hepatic Venous Pressure Gradient for Graft Hemodynamics in Living Donor Liver Transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Matsushima, H., Fujiki, M., Sasaki, K., Rotroff, D. M., Sands, M., Bayona Molano, M. D., Aucejo, F., Diago Uso, T., Eghtesad, B., Miller, C., Quintini, C., Hashimoto, K. 2019; 25 (7): 1034-1042

  Abstract

  The hepatic venous pressure gradient (HVPG) measurement is known to correlate with the severity of portal hypertension in patients with liver cirrhosis. This retrospective study investigated the clinical value of preoperative measurement of HVPG in patients who underwent adult-to-adult living donor liver transplantation (LDLT) and its predictive value for hepatic hemodynamics after graft reperfusion. For this study, 75 patients who underwent adult-to-adult LDLT were divided into 2 groups (HVPG <16 mm Hg or HVPG ≥16 mm Hg) to investigate the correlation between preoperative HVPG and characteristics and surgical outcomes of the patients, including portal vein flow (PVF) and hepatic artery flow (HAF) after graft reperfusion. In total, 35 (46.7%) patients had an HVPG ≥16 mm Hg. These patients had significantly higher international normalized ratio values, serum creatinine levels, and Model for End-Stage Liver Disease scores compared with the 40 patients with HVPG <16 mm Hg. They also had higher rates of variceal bleeding, encephalopathy, and intractable ascites as well as lower serum albumin levels and platelet counts compared with those patients with HVPG <16 mm Hg. Portal inflow modulation (PIM) was frequently performed in the patients with HVPG ≥16 mm Hg compared with those with HVPG <16 mm Hg. No significant differences in surgical outcomes after LDLT were found between these 2 groups except for postoperative ascites. Preoperative HVPG showed a positive correlation with PVF and a negative correlation with HAF after graft reperfusion (false discovery rate [FDR] P = 0.08 and FDR P = 0.08, respectively). In linear regression analyses, preoperative HVPG was independently associated with PVF after graft reperfusion. In conclusion, our findings indicate that preoperative HVPG is associated with hepatic hemodynamics after graft implantation in LDLT. HVPG as a routine preoperative evaluation may be helpful for surgical planning of PIM.

  View details for DOI 10.1002/lt.25471

  View details for PubMedID 30980599

• Improved Survival Following Living Donor Liver Transplantation for Pediatric Acute Liver Failure: Analysis of 20 Years of US National Registry Data. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Firl, D. J., Sasaki, K., McVey, J., Hupertz, V., Radhakrishnan, K., Fujiki, M., Eghtesad, B., Miller, C. M., Quintini, C., Hashimoto, K. 2019; 25 (8): 1241-1250

  Abstract

  This study estimated the utility of technical variant grafts (TVGs), such as split/reduced liver transplantation (SRLT) and living donor liver transplantation (LDLT), in pediatric acute liver failure (PALF). PALF is a devastating condition portending a poor prognosis without liver transplantation (LT). Pediatric candidates have fewer suitable deceased donor liver transplantation (DDLT) donor organs, and the efficacy of TVG in this setting remains incompletely investigated. PALF patients from 1995 to 2015 (age <18 years) were identified using the Scientific Registry of Transplant Recipients (n = 2419). Cox proportional hazards model and Kaplan-Meier curves were used to assess outcomes. Although wait-list mortality decreased (19.1% to 9.7%) and successful transplantations increased (53.7% to 62.2%), patients <1 year of age had persistently higher wait-list mortality rates (>20%) compared with other age groups (P < 0.001). TVGs accounted for only 25.7% of LT for PALF. In the adjusted model for wait-list mortality, among other factors, increased age (subhazard ratio [SHR], 0.97 per year; P = 0.020) and access to TVG were associated with decreased risk (SHR, 0.37; P < 0.0001). LDLT recipients had shorter median waiting times compared with DDLT (LDLT versus DDLT versus SRLT, 3 versus 4 versus 5 days, respectively; P = 0.017). In the adjusted model for post-LT survival, LDLT was superior to DDLT using whole grafts (SHR, 0.41; P = 0.004). However, patient survival after SRLT was not statistically different from DDLT (SHR, 0.75; P = 0.165). In conclusion, despite clear advantages to reduce wait-list mortality, TVGs have been underutilized in PALF. Early access to TVG, especially from LDLT, should be sought to further improve outcomes.

  View details for DOI 10.1002/lt.25499

  View details for PubMedID 31119826

• Sufficient hepatic artery flow compensates for poor portal vein flow after liver transplantation in patients with portal vein thrombosis. Clinical transplantation Sasaki, K., McVey, J. C., Firl, D. J., Andreatos, N., Moro, A., Coromina Hernandez, L., Matsushima, H., Teresa, D. U., Fujiki, M., Aucejo, F. N., Quintini, C., Kwon, C. D., Eghtesad, B., Miller, C. M., Hashimoto, K. 2019; 33 (11): e13723

  Abstract

  Portal vein thrombosis (PVT) does not preclude liver transplantation (LT), but poor portal vein (PV) flow after LT remains a predictor of poor outcomes. Given the physiologic tendency of the hepatic artery (HA) to compensate for low PV flow via vasodilation, we investigated whether adequate HA flow would have a favorable prognostic impact among patients with low PV flow following LT.This study included 163 patients with PVT who underwent LT between 2004 and 2015. PV and HA flow were categorized into quartiles, and their association with 1-year graft survival (GS) and biliary complication rates was assessed. For both the HA and the PV, patients at the lowest two quartiles were categorized as having low flow and the remainder as having high flow.The median MELD score was 22 and 1-year GS was 87.3%. As expected, GS paralleled PV flow with patients at the lowest flow quartile faring the worst. In combination of PV and HA flows, high HA flow was associated with improved 1-year GS among patients with low PV flow (P = .03). Similar findings were observed with respect to biliary complication rates.Sufficient HA flow may compensate for poor PV flow. Consequently, meticulous HA reconstruction may be central to achieving optimal outcomes in PVT cases.

  View details for DOI 10.1111/ctr.13723

  View details for PubMedID 31583762

• Prognostication of inflammatory cells in liver transplantation: Is the waitlist neutrophil-to-lymphocyte ratio really predictive of tumor biology? Clinical transplantation McVey, J. C., Sasaki, K., Firl, D. J., Fujiki, M., Diago-Uso, T., Quintini, C., Eghtesad, B., Miller, C. C., Hashimoto, K., Aucejo, F. N. 2019; 33 (12): e13743

  Abstract

  The objective of this retrospective study was to characterize the neutrophil to lymphocyte ratio (NLR) on the waitlist and determine its prognostic utility in liver transplantation (LT) for hepatocellular carcinoma (HCC) with special focus on longitudinal data. Biomarkers such as pre-operative NLR have been suggested to predict poor oncological outcomes for patients with HCC seeking LT. NLR's utility is thought to be related to tumor biology. However, recent studies have demonstrated that a high NLR conveys worse outcomes in non-HCC cirrhotics. This study investigated the relationship between NLR, liver function, tumor factors and patient prognosis.Patients with HCC undergoing LT were identified between 2002 and 2014 (n = 422). Variables of interest were collected longitudinally from time of listing until LT. The prognostic utility of NLR was assessed using Kaplan-Meier and Cox Proportional Hazard regression. Associations between NLR and MELD-Na, AFP, and tumor morphology were also assessed.NLR demonstrated a positive correlation with MELD-Na at LT (R2 = 0.125, P < 0.001) and had parallel trends over time. The lowest NLR quartile had a median MELD-Na of 9 while the highest had a median MELD-Na of 19. There were minimal differences in AFP, tumor morphology, and rates of vascular invasion between quartiles. NLR was a statistically significant predictor of OS (HR = 1.64, P = 0.017) and recurrence (HR = 1.59, P = 0.016) even after controlling for important tumor factors. However, NLR lost its statistical significance when MELD-Na was added to the Cox regression model (OS: HR = 1.46, P = 0.098) (recurrence: HR = 1.40, P = 0.115).NLR is a highly volatile marker on the waitlist that demonstrates a significant correlation and collinearity with MELD-Na temporally and at the time of LT. These characteristics of NLR bring into question its utility as a predictive marker in HCC patients.

  View details for DOI 10.1111/ctr.13743

  View details for PubMedID 31655000

• Renoportal Anastomosis for Complete Portal Vein Thrombosis: The Cleveland Clinic Experience Lomaglio, L., Armanyous, S., D'Amico, G., Hassan, A., Liu, Q., Nair, A., Uso, T., Hashimoto, K., Eghtesad, B., Aucejo, F., Fujiki, M., Sasaki, K., Miller, C., Quintini, C. WILEY. 2019: 66

  View details for Web of Science ID 000457809000111

• The prognosis of colorectal cancer liver metastases associated with inflammatory bowel disease: An exploratory analysis JOURNAL OF SURGICAL ONCOLOGY Margonis, G., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Galjart, B., Kamphues, C., Pawlik, T. M., Poultsides, G., Kaczirek, K., Lonning, P., Verhoef, C., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018; 118 (7): 1074-1080

  View details for DOI 10.1002/jso.25251

  View details for Web of Science ID 000449560900002

• Combined Hepatic Resection and Radio-frequency Ablation for Patients with Colorectal Cancer Liver Metastasis: A Viable Option for Patients with a Large Number of Tumors ANTICANCER RESEARCH Masuda, T., Margonis, G., Andreatos, N., Wang, J., Warner, S., Mirza, M., Angelou, A., Damaskos, C., Garmpis, N., Sasaki, K., He, J., Imai, K., Yamashita, Y., Wolfgang, C. L., Baba, H., Weiss, M. J. 2018; 38 (11): 6353-6360

  Abstract

  Radiofrequency ablation (RFA) is thought to result in inferior prognosis than hepatic resection among patients with colorectal liver metastasis (CRLM). However, resection plus RFA may be an option for patients with a large number of tumors (≥4 liver lesions) and borderline resectability.A total of 717 patients with CRLM who underwent hepatic resection +/- RFA at two tertiary institutions between 09/01/2000-12/01/2015 were eligible for inclusion in this study.Among patients with <4 lesions (n=568), OS in the resection + RFA group (n=48) was significantly worse than in the resection alone group (n=520) (5-year OS: 34.4 % versus 58.9%, p=0.007). Conversely, in patients with ≥4 lesions, OS in the resection + RFA (n=68) and resection alone(n=81) groups were not significantly different (5-year OS: 31.9% versus 34.1%, p=0.48). In patients with <4 lesions, carcinoembryonic antigen (CEA) ≥30 ng/ml, extrahepatic metastasis, preoperative chemotherapy and resection + RFA were independently associated with poor prognosis. Interestingly, in patients with ≥4 lesions, positive primary lymph nodes, KRAS mutation, CEA ≥30 ng/ml and extrahepatic metastasis were independent predictors of poor prognosis; however, the combination of hepatic resection with RFA was not associated with worse survival (p=0.93).Although surgeons should always strive for R0 resection when feasible, combined resection and RFA may be a viable alternative for CRLM patients with a large number of tumors.

  View details for DOI 10.21873/anticanres.12993

  View details for Web of Science ID 000449973000029

  View details for PubMedID 30396957

• Serum tumor markers enhance the predictive power of the AJCC and LCSGJ staging systems in resectable intrahepatic cholangiocarcinoma HPB Sasaki, K., Margonis, G. A., Andreatos, N., Chen, Q., Barbon, C., Bagante, F., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Endo, I., Aucejo, F. N., Pawlik, T. M. 2018; 20 (10): 956–65

  Abstract

  While several prognostic models have been developed to predict long-term outcomes in resectable intrahepatic cholangiocarcinoma (ICC), their prognostic discrimination remains limited. The addition of tumor markers might improve the prognostic power of the classification schemas proposed by the AJCC 8th edition and the Liver Cancer Study Group of Japan (LCSGJ).The prognostic discrimination of the AJCC and the LCSGJ were compared before and after the addition of CA 19-9 and CEA, using Harrell's C-index, net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) in an international, multi-institutional cohort.Eight hundred and five surgically treated patients with ICC that met the inclusion criteria were identified. On multivariable analysis, CEA5 ng/mL, 100IU/mL CA 19-9< 500IU/mL and CA 19-9500 IU/mL were associated with worse overall survival. The C-index of the AJCC and the LCSGJ improved from 0.540 to 0.626 and 0.553 to 0.626, respectively following incorporation of CA 19-9 and CEA. The NRI and IDI metrics confirmed the superiority of the modified AJCC and LCSGJ, compared to the original versions.The inclusion of preoperative CA 19-9 and CEA in the AJCC and LCSGJ staging schemas may improve prognostic discrimination among surgically treated patients with ICC.

  View details for PubMedID 29887261

• The prognosis of colorectal cancer liver metastases associated with inflammatory bowel disease: An exploratory analysis. Journal of surgical oncology Margonis, G. A., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Galjart, B., Kamphues, C., Pawlik, T. M., Poultsides, G., Kaczirek, K., Lonning, P. E., Verhoef, C., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018

  Abstract

  BACKGROUND AND OBJECTIVES: In contrast with sporadic colorectal cancer liver metastases (CRLM), inflammatory bowel disease (IBD)-related CRLM have not been studied to date.METHODS: Patients who underwent resection for IBD-related and sporadic CRLM from 2000 to 2015 were identified from an international registry and matched for pertinent prognostic variables. Overall survival (OS) and recurrence-free survival (RFS) were subsequently assessed.RESULTS: Twenty-eight patients had IBD-related CRLM. Synchronous extrahepatic disease was more common in IBD-related CRLM patients than patients with sporadic CRLM (28.6% vs 8.3%; P<0.001), most commonly located in the lungs. In multivariable analysis, IBD did not have a significant influence on OS ( P=0.835), and had a hazard ratio (HR) close to 1 (HR, 0.95; 95% confidence interval [CI], 0.57-1.57). IBD was also not associated with inferior RFS (HR, 1.07; 95%CI, 0.68-1.68; P=0.780). Among patients with IBD-related CRLM, 9(50%) had isolated intrahepatic recurrence and 8(44.4%) isolated extrahepatic recurrence, while only 1(5.6%) developed combined recurrence. Of those who experienced recurrence after resection of IBD-related CRLM, 10 had their recurrence treated with curative intent.CONCLUSIONS: Patients with IBD-related CRLM had similar survival compared with patients with sporadic CRLM, even though they more often present with extrahepatic disease. In addition, patients with IBD-related CRLM may experience patterns of recurrence different from patients with sporadic CRLM.

  View details for PubMedID 30261094

• Long-Term Follow-Up of Patients with Primary Sclerosing Cholangitis Undergoing Liver Transplantation with Duct-to-Duct Biliary Eghtesad, B., Hernandez, L., Diago, T., Hashimoto, K., Fujiki, M., Quintini, C., Aucejo, F., Sasaki, K., Menon, N., Hassan, A., Miller, C., Fung, J. LIPPINCOTT WILLIAMS & WILKINS. 2018: S876

  View details for DOI 10.1097/01.tp.0000543960.13870.fb

  View details for Web of Science ID 000444541201681

• Colorectal Liver Metastases: Does the Future of Precision Medicine Lie in Genetic Testing? JOURNAL OF GASTROINTESTINAL SURGERY Barbon, C., Margonis, G., Andreatos, N., Rezaee, N., Sasaki, K., Buettner, S., Damaskos, C., Pawlik, T. M., He, J., Wolfgang, C. L., Weiss, M. J. 2018; 22 (7): 1286-1296

  Abstract

  Colorectal liver metastases (CRLM) present an important clinical challenge in both surgical and medical oncology. Despite improvements in management, survival among patients undergoing resection of CRLM is still very variable and there is a paucity of clinical trial data and reliable biomarkers that could guide prognostic forecasts, treatment selection, and follow-up. Fortunately, recent advances in molecular biology and tumor sequencing have identified a number of critical genetic loci and proliferation markers that may hold the key to understanding the biologic behavior of CRLM; specifically, mutations of KRAS, BRAF, TP53, PIK3CA, APC, expression of Ki-67, and the presence of microsatellite instability appear to have a decisive impact on prognosis and response to treatment in patients with CRLM. While the applicability of genetic biomarkers in everyday clinical practice remains conditional on the development of inexpensive bedside sequencing, targeted therapies, and the conduct of appropriate clinical trials, the promise of personalized treatment may be closer to realization than ever before.

  View details for DOI 10.1007/s11605-018-3766-1

  View details for Web of Science ID 000437762000018

  View details for PubMedID 29644557

• Association of BRAF Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer JAMA SURGERY Margonis, G., Buettner, S., Andreatos, N., Kim, Y., Wagner, D., Sasaki, K., Beer, A., Schwarz, C., Loes, I., Smolle, M., Kamphues, C., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P., Cameron, J. L., Burkhart, R. A., Gerger, A., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018; 153 (7): e180996

  Abstract

  BRAF mutations are reportedly associated with aggressive tumor biology. However, in contrast with primary colorectal cancer, the association of V600E and non-V600E BRAF mutations with survival and recurrence after resection of colorectal liver metastases (CRLM) has not been well studied.To investigate the prognostic association of BRAF mutations with survival and recurrence independently and compared with other prognostic determinants, such as KRAS mutations.In this cohort study, all patients who underwent resection for CRLM with curative intent from January 1, 2000, through December 31, 2016, at the institutions participating in the International Genetic Consortium for Colorectal Liver Metastasis and had data on BRAF and KRAS mutational status were retrospectively identified. Multivariate Cox proportional hazards regression models were used to assess long-term outcomes.Hepatectomy in patients with CRLM.The association of V600E and non-V600E BRAF mutations with disease-free survival (DFS) and overall survival (OS).Of 853 patients who met inclusion criteria (510 men [59.8%] and 343 women [40.2%]; mean [SD] age, 60.2 [12.4] years), 849 were included in the study analyses. Forty-three (5.1%) had a mutated (mut) BRAF/wild-type (wt) KRAS (V600E and non-V600E) genotype; 480 (56.5%), a wtBRAF/wtKRAS genotype; and 326 (38.4%), a wtBRAF/mutKRAS genotype. Compared with the wtBRAF/wtKRAS genotype group, patients with a mutBRAF/wtKRAS genotype more frequently were female (27 [62.8%] vs 169 [35.2%]) and 65 years or older (22 [51.2%] vs 176 [36.9%]), had right-sided primary tumors (27 [62.8%] vs 83 [17.4%]), and presented with a metachronous liver metastasis (28 [64.3%] vs 229 [46.8%]). On multivariable analysis, V600E but not non-V600E BRAF mutation was associated with worse OS (hazard ratio [HR], 2.76; 95% CI, 1.74-4.37; P < .001) and DFS (HR, 2.04; 95% CI, 1.30-3.20; P = .002). The V600E BRAF mutation had a stronger association with OS and DFS than the KRAS mutations (β for OS, 10.15 vs 2.94; β for DFS, 7.14 vs 2.27).The presence of the V600E BRAF mutation was associated with worse prognosis and increased risk of recurrence. The V600E mutation was not only a stronger prognostic factor than KRAS but also was the strongest prognostic determinant in the overall cohort.

  View details for PubMedID 29799910

• Sufficient Hepatic Artery Flow Redeems Poor Portal Vein Flow after Liver Transplantation in Patients with Porta Vein Thrombosis. Hernandez, L., Sasaki, K., Firl, D., McVey, J., Fujiki, M., Aucejo, F., Eghtesad, B., Quintini, C., Miller, C., Hashimoto, K. WILEY. 2018: 556

  View details for Web of Science ID 000431965402235

• Impact of Surgical Margin Width on Recurrence and Overall Survival Following R0 Hepatic Resection of Colorectal Metastases A Systematic Review and Meta-analysis ANNALS OF SURGERY Margonis, G. A., Sergentanis, T. N., Ntanasis-Stathopoulos, I., Andreatos, N., Tzanninis, I., Sasaki, K., Psaltopoulou, T., Wang, J., Buettner, S., Papalois, A. E., He, J., Wolfgang, C. L., Pawlik, T. M., Weiss, M. J. 2018; 267 (6): 1047-1055

  Abstract

  To examine the impact of surgical margin width on survival following R0 hepatic resection for colorectal metastases (CRLM).Although negative resection margin is considered of paramount importance for the prognosis of patients with colorectal liver metastases, optimal resection margin width remains controversial.Eligible studies examining the association between margin status after R0 hepatic resection for CRLM and survival, including overall survival (OS) and disease-free survival (DFS) were sought using the Medline, Cochrane, and EMBASE databases. Random-effects models were used for the calculation of pooled relative risks (RRs) with their 95% confidence intervals (95% CIs).Thirty-four studies were deemed eligible for inclusion representing a cohort of 11,147 hepatic resections. Wider resection margin (>1 vs <1 cm) was significantly associated with improved OS at 3 years (pooled RR = 0.86, 95% CI: 0.79-0.95), 5 years (pooled RR = 0.91, 95% CI: 0.85-0.97), and 10 years (pooled RR = 0.94, 95% CI: 0.88-1.00). Similarly, DFS was positively associated with >1 cm resection margin at 3, 5, and 10 years. Interestingly, >1 mm (vs <1 mm) resection margin was significantly associated with improved OS at all-time points. Meta-regression analyses did not reveal any significant modifying role of the study features under investigation, such as the administration of neoadjuvant/adjuvant therapy.Importantly, our findings suggest that while a >1 mm margin is associated with better prognosis than a submillimeter margin, achieving a margin >1 cm may result in even better oncologic outcomes and should be considered if possible.

  View details for DOI 10.1097/SLA.0000000000002552

  View details for Web of Science ID 000434301200017

  View details for PubMedID 29189379

• Clinical Impacts of Deceased Donor Oxygenation Status in Liver Transplant. Okamoto, T., Sasaki, K., Niikawa, H., Fujiki, M., Quintini, C., Hashimoto, K., Miller, C., Abu-Elmagd, K., McCurry, K., Fung, J. WILEY. 2018: 896-897

  View details for Web of Science ID 000431965404162

• Impact of Sever Hypoxemia after Liver Tansplantation in Hepatopulmonary Syndrome. Pitchaimuthu, M., Fujiki, M., Sasaki, K., Hashimoto, K., Eghtesad, B., Miller, C., Quintini, C. WILEY. 2018: 851

  View details for Web of Science ID 000431965404023

• The Neutrophil to Lymphocyte Ratio is Confounded by MELD in Hepatocellular Carcinoma Patients Undergoing Liver Transplantation. McVey, J., Sasaki, K., Dan, F., Cristiano, Q., Koji, H., Charles, M., Federico, A. WILEY. 2018: 567

  View details for Web of Science ID 000431965402270

• Split/Reduced Liver Grafts in Adult Liver Transplantation, No Longer a Risk for Graft Loss. Sasaki, K., Firl, D., McVey, J., Iuppa, G., Fujiki, M., Uso, T., Aucejo, F., Eghtesad, B., Quintini, C., Miller, C., Hashimoto, K. WILEY. 2018: 457

  View details for Web of Science ID 000431965401550

• Long-term follow-up of patients with primary sclerosing cholangitis undergoing liver transplantation with duct-to-duct biliary Eghtesad, B., Hernandez, C. L., Diago, T., Hashimoto, K., Fujiki, M., Quintini, C., Aucejo, F., Iuppa, G., Sasaki, K., Hassan, A., Menon, N., Miller, C., Fung, J. LIPPINCOTT WILLIAMS & WILKINS. 2018: 151

  View details for Web of Science ID 000436897700295

• Double KRAS and BRAF Mutations in Surgically Treated Colorectal Cancer Liver Metastases: An International, Multi-institutional Case Series ANTICANCER RESEARCH Deshwar, A., Margonis, G., Andreatos, N., Barbon, C., Wang, J., Buettner, S., Wagner, D., Sasaki, K., Beer, A., Loes, I., Pikoulis, E., Damaskos, C., Garmpis, N., Kamphues, K., He, J., Kaczirek, K., Poultsides, G., Lonning, P., Mischinger, H., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weis, M. J. 2018; 38 (5): 2891–95

  Abstract

  While previously believed to be mutually exclusive, concomitant mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS)- and V-raf murine sarcoma b-viral oncogene homolog B1 (BRAF)-mutated colorectal carcinoma (CRC), has been described in rare instances and been associated with advanced-stage disease. The present case series is the first to report on the implications of concurrent KRAS/BRAF mutations among surgically treated patients, and the largest set of patients with surgically treated colorectal liver metastasis (CRLM) and data on KRAS/BRAF mutational status thus far described.We present cases from an international, multi-institutional cohort of patients that underwent hepatic resection for CRLM between 2000-2015 at seven tertiary centers. The incidence of KRAS/BRAF mutation in patients with CRLM was 0.5% (4/820). Of these cases, patient 1 (T2N1 primary, G13D/V600E), patient 2 (T3N1 primary, G12V/V600E) and patient 3 (T4N2 primary, G13D/D594N) succumbed to their disease within 485, 236 and 79 days respectively, post-hepatic resection. Patient 4 (T4 primary, G12S/G469S) was alive 416 days after hepatic resection.The present case series suggests that the incidence of concomitant KRAS/BRAF mutations in surgical cohorts may be higher than previously hypothesized, and associated with more variable survival outcomes than expected.

  View details for PubMedID 29715113

• Preoperative Risk Score and Prediction of Long-Term Outcomes after Hepatectomy for Intrahepatic Cholangiocarcinoma Sasaki, K., Margonis, G. A., Andreatos, N., Bagante, F., Weiss, M., Barbon, C., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Aucejo, F. N., Pawlik, T. M. ELSEVIER SCIENCE INC. 2018: 393–405

  Abstract

  Accurate prediction of prognosis for patients with intrahepatic cholangiocarcinoma (ICC) remains a challenge. We sought to define a preoperative risk tool to predict long-term survival after resection of ICC.Patients who underwent hepatectomy for ICC at 1 of 16 major hepatobiliary centers between 1990 and 2015 were identified. Clinicopathologic data were analyzed and a prognostic model was developed based on the regression β-coefficients on data in training set. The model was subsequently assessed using a validation set.Among 538 patients, most patients had a solitary tumor (median tumor number 1; interquartile range 1 to 2) and median tumor size was 5.7 cm (interquartile range 4.0 to 8.0 cm). Median and 5-year overall survival was 39.0 months and 39.0%, respectively. On multivariable analyses, preoperative factors associated with long-term survival included tumor size (hazard ratio [HR] 1.12; 95% CI 1.06 to 1.18), natural logarithm carbohydrate antigen 19-9 level (HR 1.33; 95% CI 1.22 to 1.45), albumin level (HR 0.76; 95% CI 0.55 to 0.99), and neutrophil to lymphocyte ratio (HR 1.05; 95% CI 1.02 to 1.09). A weighted composite prognostic score was constructed based on these factors: [9 + (1.12 × tumor size) + (2.81 × natural logarithm carbohydrate antigen 19-9) + (0.50 × neutrophil to lymphocyte ratio) + (-2.79 × albumin)]. The model demonstrated good performance in the testing (area under the curve 0.696) and validation (0.691) datasets. The model performed better than both the T categories (area under the curve 0.532) and the cumulative stage classifications in the American Joint Committee on Cancer staging manual, 8th edition (area under the curve 0.559). When assessing risk of death within 1 year of operation, a risk score ≥25 had a positive predictive value of 59.8% compared with a positive predictive value of 35.3% for American Joint Committee on Cancer staging manual, 8th edition T4 disease and 31.8% for stage IIIB disease.Postsurgical long-term outcomes could be predicted using a composite weighted scoring system based on preoperative clinical parameters. The preoperative risk model can be used to inform patient to provider conversations and expectations before operation.

  View details for PubMedID 29274841

• Postoperative low hepatitis C virus load predicts long-term outcomes after hepatectomy for hepatocellular carcinoma Sasaki, K., Shindoh, J., Nishioka, Y., Sugawara, T., Margonis, G. A., Andreatos, N., Pawlik, T. M., Hashimoto, M. WILEY. 2018: 902-911

  Abstract

  Preoperative hepatitis C virus (HCV) viral load is known to predict long-term outcomes after hepatectomy for HCV-related hepatocellular carcinoma (HCC). This study sought to examine the hypothesis that postoperative and preoperative HCV viral-load have similar prognostic implications, as well as determine a target viral-load that will improve long-term postoperative outcomes.One hundred and eighty-one patients who underwent curative hepatectomy for HCV-related HCC were divided into five groups according to time-weighted average viral load. The cumulative-recurrence curves of the five groups were compared to identify prognostic trends. The optimal cut-off viral load value related to recurrence was also investigated.The five cumulative-recurrence curves were separated into two clusters according to viral load. Patients with a negative viral load had comparable recurrence curves to patients with the lowest viral-load (P = 0.907); both of these patient groups had more favorable outcomes than patients with a viral load categorized in the other groups (all P < 0.050). The optimal cut-off based on maximum HR method (> or ≤4.0 log10  IU/mL) was a strong prognostic indicator of recurrence in multivariate analysis (HR 3.09; 95%CI 1.96-5.04; P < 0.001).Postoperative HCV viral load correlated with long-term surgical outcomes. A low viral load (≤4.0 log10  IU/mL) independently predicted better long-term outcomes.

  View details for DOI 10.1002/jso.25015

  View details for Web of Science ID 000434145500012

  View details for PubMedID 29473962

• Microsatellite instability in resectable colorectal liver metastasis: An international multi-institutional analysis. Margonis, G., Buettner, S., Wagner, D., McVey, J., Andreatos, N., Beer, A., Sasaki, K., He, J., Kaczirek, K., Poultsides, G. A., Cameron, J. L., Mischinger, H., Aucejo, F., Wolfgang, C., Weiss, M. J. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.4_suppl.220

  View details for Web of Science ID 000436174100211

• Impact of Severe Hypoxemia After Liver Transplantation in Hepatopulmonary Syndrome Pitchaimuthu, M., Fujiki, M., Sasaki, K., Hashimoto, K., Eghtesad, B., Miller, C., Quintini, C. WILEY. 2018: 77

  View details for Web of Science ID 000419034500150

• The Tumor Burden Score: A New "Metro-ticket" Prognostic Tool For Colorectal Liver Metastases Based on Tumor Size and Number of Tumors ANNALS OF SURGERY Sasaki, K., Morioka, D., Conci, S., Margonis, G. A., Sawada, Y., Ruzzenente, A., Kumamoto, T., Iacono, C., Andreatos, N., Guglielmi, A., Endo, I., Pawlik, T. M. 2018; 267 (1): 132-141

  Abstract

  To apply the principles of the Metro-ticket paradigm to develop a prognostic model for patients undergoing hepatic resection of colorectal liver metastasis (CRLM).Whereas the hepatocellular "Metro-ticket" prognostic tool utilizes a continuum of tumor size and number, a similar concept of a CRLM Metro-ticket paradigm has not been investigated.Tumor Burden Score (TBS) was defined using distance from the origin on a Cartesian plane incorporating maximum tumor size (x-axis) and number of lesions (y-axis). The discriminatory power [area under the curve (AUC)] and goodness-of-fit (Akaike information criteria) of the TBS model versus standard tumor morphology categorization were assessed. The TBS model was validated using 2 external cohorts from Asia and Europe.TBS (AUC 0.669) out-performed both maximum tumor size (AUC 0.619) and number of tumors (AUC 0.595) in predicting overall survival (OS) (P < 0.05). As TBS increased, survival incrementally worsened (5-year OS: zone 1, zone 2, and zone 3-68.9%, 49.4%, and 25.5%; P < 0.05). The stratification of survival based on traditional tumor size and number cut-off criteria was poor. Specifically, 5-year survival for patients in category 1, category 2, and category 3 was 58.3%, 45.5%, and 50.6%, respectively (P > 0.05). The corrected Akaike score information criteria value of the TBS model (2865) was lower than the traditional tumor morphologic categorization model (2905). Survival analysis revealed excellent prognostic discrimination for the TBS model among patients in both external cohorts (P< 0.05).An externally validated "Metro-ticket" TBS model had excellent prognostic discriminatory power. TBS may be an accurate tool to account for the impact of tumor morphology on long-term survival among patients undergoing resection of CRLM.

  View details for DOI 10.1097/SLA.0000000000002064

  View details for Web of Science ID 000418863400028

  View details for PubMedID 27763897

• Effect of Increased Intra-abdominal Pressure on Liver Histology and Hemodynamics: An Experimental Study IN VIVO Antoniou, E. A., Kairi, E., Margonis, G. A., Andreatos, N., Sasaki, K., Damaskos, C., Garmpis, N., Samaha, M., Argyra, E., Polymeneas, G., Weiss, M. J., Pawlik, T. M., Voros, D., Kouraklis, G. 2018; 32 (1): 85-91

  Abstract

  While reduction of portal venous (PV) blood flow has been described in animal models of intra-abdominal hypertension, reports on compensatory changes in hepatic arterial (HA) flow, known as the hepatic arterial buffer response are controversial.Pneumoperitoneum with helium was induced in 13 piglets. Hemodynamic measurements and pathological assessment were conducted at baseline and during the three subsequent phases: Phase A: 45 minutes with a stable intra-abdominal pressure of 25 mmHg; phase B: 45 minutes with a stable intra-abdominal pressure of 40 mmHg; and phase C during which the abdomen was re-explored and reperfusion of the liver was allowed to take place.Phase B pressure was significantly greater than phase A pressure in both the PV and the inferior vena cava, demonstrating a positive association between escalating intra-abdominal hypertension and the pressure in these two vessels (all p<0.001). In contrast, HA pressure was comparable between baseline and phase A, while it tended to decrease in phase B. Regarding histology, the most notable abnormality was the presence of inflammatory infiltrates and hepatocyte necrosis.Helium-insufflation increased PV pressure with a partial compensatory decrease of HA pressure. Nonetheless, findings consistent with hepatic ischemia were observed on pathology.

  View details for DOI 10.21873/invivo.11208

  View details for Web of Science ID 000419189400012

  View details for PubMedID 29275303

  View details for PubMedCentralID PMC5892635

• Combining the Old With the New: The Next Journey of the Clinical Risk Score. Annals of surgery Takahashi, H., Sasaki, K., Naples, R., Aucejo, F. N., Miller, C. M. 2018; 268 (6): e44-e45

  View details for DOI 10.1097/SLA.0000000000002535

  View details for PubMedID 29194087

• Reframing the approach to patients with hepatocellular carcinoma: Longitudinal assessment with hazard associated with liver transplantation for HCC (HALTHCC) improves ablate and wait strategy. Hepatology (Baltimore, Md.) Firl, D. J., Kimura, S., McVey, J., Hashimoto, K., Yeh, H., Miller, C. M., Markmann, J. F., Sasaki, K., Aucejo, F. N. 2018; 68 (4): 1448-1458

  Abstract

  Patients with hepatocellular carcinoma (HCC) are screened at presentation for appropriateness of liver transplantation (LT) using morphometric criteria, which poorly specifies risk. Morphology is the crux of measuring tumor response to locoregional therapy (LRT) using modified Response Evaluation Criteria in Solid Tumors (mRECIST). This study investigated the utility of following a continuous risk score (hazard associated with liver transplantation in hepatocellular carcinoma; HALTHCC) to longitudinally assess risk. This multicenter, retrospective study from 2002 to 2014 enrolled 419 patients listed for LT for HCC. One cohort had LRT while waiting (n = 351), compared to the control group (n = 68) without LRT. Imaging studies (n = 2,085) were collated to laboratory data to calculate HALTHCC, MORAL, Metroticket 2.0, and alpha fetoprotein (AFP) score longitudinally. Cox proportional hazards evaluated associations of HALTHCC and peri-LRT changes with intention-to-treat (ITT) survival (considering dropout or post-LT mortality), and utility was assessed with Harrell's C-index. HALTHCC better predicted ITT outcome (LT = 309; dropout = 110) when assessed closer to delisting (P < 0.0001), maximally just before delisting (C-index, 0.742 [0.643-0.790]). Delta-HALTHCC post-LRT was more sensitive to changes in risk than mRECIST. HALTHCC score and peri-LRT percentage change were independently associated with ITT mortality (hazard ratio = 1.105 [1.045-1.169] per point and 1.014 [1.004-1.024] per percent, respectively).HALTHCC is superior in assessing tumor risk in candidates awaiting LT, and its utility increases over time. Peri-LRT relative change in HALTHCC outperforms mRECIST in stratifying risk of dropout, mortality, and recurrence post-LT. With improving estimates of post-LT outcomes, it is reasonable to consider allocation using HALTHCC and not just waiting time. Furthermore, this study supports a shift in perspective, from listing to allocation, to better utilize precious donor organs. (Hepatology 2018).

  View details for DOI 10.1002/hep.29907

  View details for PubMedID 29604231

• Predicting Outcomes of Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma. Gastroenterology Firl, D. J., Sasaki, K., Aucejo, F. N. 2018; 154 (6): 1856-1857

  View details for DOI 10.1053/j.gastro.2017.11.296

  View details for PubMedID 29621517

• Preoperative bevacizumab and volumetric recovery after resection of colorectal liver metastases JOURNAL OF SURGICAL ONCOLOGY Margonis, G., Buettner, S., Andreatos, N., Sasaki, K., Pour, M., Deshwar, A., Wang, J., Ghasebeh, M., Damaskos, C., Rezaee, N., Pawlik, T. M., Wolfgang, C. L., Kamel, I. R., Weiss, M. J. 2017; 116 (8): 1150-1158

  Abstract

  While preoperative treatment is frequently administered to CRLM patients, the impact of chemotherapy, with or without bevacizumab, on liver regeneration remains controversial.The early and late regeneration indexes were defined as the relative increase in liver volume (RLV) within 2 and 9 months from surgery. Regeneration rates of the preoperative treatment groups were compared.Preoperative chemotherapy details and volumetric data were available for 185 patients; 78 (42.2%) received preoperative chemotherapy with bevacizumab (Bev+), 46 (24.8%) received chemotherapy only (Bev-), and 61 (33%) received no chemotherapy. Patients in the Bev+ and Bev- groups received similar chemotherapy cycles (4 [3-6] vs 4 [4-6]; P = 0.499). Despite the comparable clinicopathological characteristics and Resected Volume/Total Liver Volume (TLV) at surgery (P = 0.944) of both groups, Bev+ group had higher early and late regeneration (17.2% vs 4.3%; P = 0.035 and 14.0% vs 9.4%; P = 0.091, respectively). Of note, early and late regeneration rates (3.7% and 10.9% vs 6.6% and 5.5%, respectively) were comparable between the no chemotherapy and Bev- groups (all P > 0.05). In multivariable analysis -adjusted for gender, age, portal vein embolization, preoperative chemotherapy, resected liver volume, tumor number, postoperative chemotherapy, fibrosis, steatosis- bevacizumab independently predicted early liver regeneration (P = 0.019).Our findings suggest that preoperative bevacizumab administered along with chemotherapy was associated with enhanced volumetric restoration. Interestingly, this effect was more pronounced among patients who received oxaliplatin-based regimens and bevacizumab compared to those treated with irinotecan-based regimens and bevacizumab.

  View details for DOI 10.1002/jso.24769

  View details for Web of Science ID 000419651200024

  View details for PubMedID 28743167

• Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Liver Metastases Margonis, G., Amini, N., Wang, J., Andreatos, N., Rezaee, N., Buettner, S., Deshwar, A., Sasaki, K., Wolfgang, C. L., Weiss, M. J. ELSEVIER SCIENCE INC. 2017: E128-E129

  View details for DOI 10.1016/j.jamcollsurg.2017.07.872

  View details for Web of Science ID 000413319300312

• Anatomical Resections Improve Disease-free Survival in Patients With KRAS-mutated Colorectal Liver Metastases ANNALS OF SURGERY Margonis, G. A., Buettner, S., Andreatos, N., Sasaki, K., Ijzermans, J. M., van Vugt, J. A., Pawlik, T. M., Choti, M. A., Cameron, J. L., He, J., Wolfgang, C. L., Weiss, M. J. 2017; 266 (4): 641-649

  Abstract

  To investigate the potential clinical advantage of anatomical resection versus nonanatomical resection for colorectal liver metastases, according to KRAS mutational status.KRAS-mutated colorectal liver metastases (CRLM) are known to be more aggressive than KRAS wild-type tumors. Although nonanatomical liver resections have been demonstrated as a viable approach for CRLM patients with similar oncologic outcomes to anatomical resections, this may not be the case for the subset of KRAS-mutated CRLM.389 patients who underwent hepatic resection of CRLM with known KRAS mutational status were identified. Survival estimates were calculated using the Kaplan-Meier method, and multivariable analysis was conducted using the Cox proportional hazards regression model.In this study, 165 patients (42.4%) underwent nonanatomical resections and 140 (36.0%) presented with KRAS-mutated CRLM. Median disease-free survival (DFS) in the entire cohort was 21.3 months, whereas 1-, 3-, and 5-year DFS was 67.3%, 34.9%, and 31.5% respectively. Although there was no difference in DFS between anatomical and nonanatomical resections in patients with KRAS wild-type tumors (P = 0.142), a significant difference in favor of anatomical resection was observed in patients with a KRAS mutation (10.5 vs. 33.8 months; P < 0.001). Five-year DFS was only 14.4% in the nonanatomically resected group, versus 46.4% in the anatomically resected group. This observation persisted in multivariable analysis (hazard ratio: 0.45; 95% confidence interval: 0.27-0.74; P = 0.002), when corrected for number of tumors, bilobar disease, and intraoperative ablations.Nonanatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Because of the aggressive nature of KRAS-mutated CRLM, more extensive anatomical hepatectomies may be warranted.

  View details for DOI 10.1097/SLA.0000000000002367

  View details for Web of Science ID 000411329400011

  View details for PubMedID 28657938

• Prognostic Relevance of KRAS Mutational Status in Patients with Resectable Colorectal Liver Metastases and Concurrent Extrahepatic Disease Margonis, G., Amini, N., Andreatos, N., Deshwar, A., Rezaee, N., Buettner, S., Wang, J., Sasaki, K., Wolfgang, C. L., Weiss, M. J. ELSEVIER SCIENCE INC. 2017: E126-E127

  View details for DOI 10.1016/j.jamcollsurg.2017.07.866

  View details for Web of Science ID 000413319300306

• The prognostic utility of the "Tumor Burden Score" based on preoperative radiographic features of colorectal liver metastases JOURNAL OF SURGICAL ONCOLOGY Sasaki, K., Margonis, G. A., Andreatos, N., Zhang, X., Buettner, S., Wang, J., Deshwar, A., He, J., Wolfgang, C. L., Weiss, M., Pawlik, T. M. 2017; 116 (4): 515-523

  Abstract

  Recently, a tumor-burden "metro ticket" score (TBS) based on final pathology was proposed to predict outcome following resection of colorectal liver metastasis (CRLM). We sought to validate the TBS prognostic tool using preoperative radiologic cross-sectional imaging.Imaging TBS was defined on a Cartesian plane that incorporated both maximum tumor size (x-axis) and lesion number (y-axis) assessed by pre-operative imaging. The discriminatory power (area under the curve [AUC]) and goodness-of-fit (Harrel's C statistic and Somer's D statistics) of the imaging TBS model was assessed.Imaging and pathologic TBS correlated strongly (r = 0.76, P < 0.01). Among patients treated with neoadjuvant therapy, the correlation was strongest among patients with progressive disease/stable disease (PD/SD) (r = 0.81). Discriminatory power of the imaging-based versus pathology-based TBS models were comparable (AUC 0.64 vs. 0.67, respectively P > 0.05). An incremental worsening of long-term survival was noted as the imaging TBS increased (5-year OS: Zone1, Zone2, and Zone3-61.3%, 46.7%, and 38.5%, respectively; P = 0.03). The imaging-based TBS model outperformed the "classic" pathology-based Fong score (Harrel's C-index: imaging TBS-0.56 vs. Fong score-0.53; Somers'D-index: imaging TBS-012 vs. Fong score-0.06).Imaging-based TBS was superior to traditional tumor size and number and was comparable to pathology-based TBS. Imaging-based TBS may have the potential to facilitate improved preoperative risk stratification of patients with CRLM.

  View details for DOI 10.1002/jso.24678

  View details for Web of Science ID 000408642900012

  View details for PubMedID 28543544

• Efficacy and safety of self-expandable metallic stent placement for malignant colorectal obstruction Sasaki, K. WILEY. 2017: 244

  View details for Web of Science ID 000423279700575

• The Prognostic Impact of Determining Resection Margin Status for Multiple Colorectal Metastases According to the Margin of the Largest Lesion ANNALS OF SURGICAL ONCOLOGY Sasaki, K., Margonis, G. A., Maitani, K., Andreatos, N., Wang, J., Pikoulis, E., He, J., Wolfgang, C. L., Weiss, M., Pawlik, T. M. 2017; 24 (9): 2438-2446

  Abstract

  Although the prognostic role of surgical margin status after resection of colorectal liver metastasis (CRLM) has been previously examined, controversy still surrounds the importance of surgical margin status in patients with multiple tumors.Patients who underwent curative-intent surgery for CRLM from 2000 to 2015 and who presented with multiple tumors were identified. Patients with R1 resection status determined by the closest resection margin of the non-largest tumor were classified as R1-Type 1; patients with R1 status determined by the resection margin of the largest tumor were defined as R1-Type 2. Data regarding surgical margin status, size of tumors, and overall survival (OS) were collected and assessed.A total of 251 patients met inclusion criteria; 156 patients (62.2%) had a negative margin (R0), 50 had an R1-type 1 (19.9%), and 45 had an R1-type 2 (17.9%) margin. Median and 5-year OS in the entire cohort was 56.4 months and 48.0%, respectively. When all R1 (Type 1 + Type 2) patients were compared with R0 patients, an R1 was not associated with worse prognosis (P = 0.05). In contrast, when R1-type 2 patients were compared with R0 patients, an R1 was strongly associated with worse OS (P = 0.009). On multivariate analysis, although the prognostic impact of all R1 was not associated with OS (hazard ratio [HR] 1.56; P = 0.08), R1-Type 2 margin status independently predicted a poor outcome (HR 1.93; P = 0.03).The impact of margin status varied according to the size of the tumor assessed. While R1 margin status defined according to the non-largest tumor was not associated with OS, R1 margin status relative to the largest index lesion was associated with prognosis.

  View details for DOI 10.1245/s10434-017-5904-5

  View details for Web of Science ID 000407040500005

  View details for PubMedID 28695393

• Increased kinetic growth rate during late phase liver regeneration impacts the risk of tumor recurrence after colorectal liver metastases resection HPB Margonis, G. A., Sasaki, K., Andreatos, N., Pour, M., Shao, N., Ghasebeh, M., Buettner, S., Antoniou, E., Wolfgang, C. L., Weiss, M., Kamel, I. R., Pawlik, T. M. 2017; 19 (9): 808-817

  Abstract

  Although experimental data strongly support the pro-tumorigenic role of postoperative liver regeneration, this hypothesis has not been clinically investigated. We aimed to examine the impact of liver regeneration determined by volumetric imaging on recurrence following resection of colorectal liver metastasis (CRLM).Resected liver volume was subtracted from total liver volume (TLV) to define postoperative remnant liver volume (RLVp). Early and late kinetic growth rates (KGR) were defined as the postoperative increases in liver volume within 2-3 and 8-10 months from surgery, respectively, divided by the corresponding time interval.Median early and late KGR was 2.6%/month (IQR: -0.9 to 12.3) and 1.0%/month (IQR: -0.64 to 2.91), respectively. Late KGR predicted intrahepatic recurrence after 1 year from surgery (AUC 0.677, P = 0.011). Specifically, patients with a late KGR ≥1% had a higher cumulative risk of recurrence compared with patients with a KGR <1% (P = 0.038). In multivariate analysis, KGR ≥1% independently predicted recurrence (P = 0.027).A KGR ≥1% during the late regeneration phase was associated with increased risk of intrahepatic recurrence. These data may inform the timing of adjuvant therapy administration and focus surveillance strategies for high-risk patients.

  View details for DOI 10.1016/j.hpb.2017.05.002

  View details for Web of Science ID 000410788400009

  View details for PubMedID 28602644

• Prognostic impact of margin status in liver resections for colorectal metastases after bevacizumab BRITISH JOURNAL OF SURGERY Sasaki, K., Margonis, G. A., Andreatos, N., Wilson, A., Weiss, M., Wolfgang, C., Sergentanis, T. N., Polychronidis, G., He, J., Pawlik, T. M. 2017; 104 (7): 926-935

  Abstract

  Margin status with resection of colorectal liver metastasis (CRLM) was an important prognostic factor in the years before the introduction of biological chemotherapy. This study examined outcomes following CRLM resection in patients who received neoadjuvant chemotherapy with or without the monoclonal antiangiogenic antibody bevacizumab.Patients who underwent surgery for CRLM at the Johns Hopkins Hospital between 2000 and 2015 were identified from an institutional database. Data regarding surgical margin status, preoperative bevacizumab administration and overall survival (OS) were assessed using multivariable analyses.Of 630 patients who underwent CRLM resection, 417 (66·2 per cent) received neoadjuvant chemotherapy with (214, 34·0 per cent) or without (203, 32·2 per cent) bevacizumab. The remaining 213 (33·8 per cent) did not receive neoadjuvant chemotherapy. Univariable analysis found that positive margins were associated with worse 5-year OS than R0 resection (36·2 versus 54·9 per cent; P = 0·005). After dichotomizing by the receipt of preoperative bevacizumab versus chemotherapy alone, the prognostic value of pathological margin persisted among patients who did not receive preoperative bevacizumab (5-year OS 53·0 versus 37 per cent after R0 versus R1 resection; P = 0·010). OS was not significantly associated with margin status in bevacizumab-treated patients (5-year OS 46·8 versus 33 per cent after R0 versus R1 resection; P = 0·081), in whom 5-year survival was slightly worse (presumably reflecting more advanced disease) than among patients treated with cytotoxic agents alone. Pathological margin status was not significantly associated with 5-year OS in patients with a complete or near-complete response to chemotherapy and bevacizumab (43 versus 30 per cent after R0 versus R1 resection; P = 0·917), but this may be due to a type II error.The impact of margin status varied according to the receipt of bevacizumab. Bevacizumab may have a role to play in improving outcomes among patients with more advanced disease.

  View details for DOI 10.1002/bjs.10510

  View details for Web of Science ID 000402756600017

  View details for PubMedID 28266705

• Prognostic impact of complications after resection of early stage hepatocellular carcinoma JOURNAL OF SURGICAL ONCOLOGY Margonis, G., Sasaki, K., Andreatos, N., Nishioka, Y., Sugawara, T., Amini, N., Buettner, S., Hashimoto, M., Shindoh, J., Pawlik, T. M. 2017; 115 (7): 791-804

  Abstract

  Resection is the most effective treatment for HCC. However, postoperative morbidity is common and its impact on long-term oncological outcome remains unclear.Long-term outcomes of 774 patients who underwent curative resection for early stage HCC at Johns Hopkins Hospital and Toranomon Hospital were investigated after stratifying by the development of postoperative overall and infectious complications.A minor or major postoperative complication developed in 281 and 65 patients, respectively, while postoperative mortality was 1.3% (n = 10). The 5-year cumulative recurrence and overall survival(OS) rates were 57.2% and 76.4%, respectively. Overall postoperative complications independently predicted worse OS in multivariable analysis (HR = 1.42, P = 0.021). Complication severity did not correlate with OS (P > 0.05). While infectious complications were not independent predictors of OS, the combination of blood transfusion and infectious complications led to significantly worse OS (66.3% vs. 44.9%, P = 0.008). Postoperative complications also correlated with increased recurrence risk, but only in patients with non-cirrhotic parenchyma (55.0% vs. 47.7%, P = 0.035) or non-viral hepatitis (55.6% vs. 44.4%, P = 0.002).Post-operative morbidity independently predicted poor OS following hepatectomy for early stage HCC. A similar effect on recurrence was noted only in patients with favorable etiopathologic factors. Finally, the combination of peri-operative transfusion and subsequent infectious complications was associated with a synergistic negative effect on prognosis.

  View details for DOI 10.1002/jso.24576

  View details for Web of Science ID 000403348600005

  View details for PubMedID 28205284

• Frailty as a Risk Predictor of Morbidity and Mortality Following Liver Surgery JOURNAL OF GASTROINTESTINAL SURGERY Gani, F., Cerullo, M., Amini, N., Buettner, S., Margonis, G. A., Sasaki, K., Kim, Y., Pawlik, T. M. 2017; 21 (5): 822-830

  Abstract

  Given the increasing number of elderly and comorbid patients undergoing surgery, there is increased interest in preoperatively identifying patients at high risk of morbidity and mortality following liver resection. We sought to develop and validate the use of a frailty index (FI) to predict poor postoperative outcomes following liver surgery.Patients undergoing a liver resection were identified using the National Surgical Quality Improvement Program Hepatectomy-targeted database for 2014 and randomized into a training or validation cohort. Multivariable logistic regression analysis was performed to develop a revised frailty index (rFI) to predict adverse postoperative clinical outcomes. Leave one out cross-validation was performed to validate the proposed rFI.A total of 2714 patients were identified who met the inclusion criteria. Postoperatively, 826 patients (30.4%) developed a postoperative complication, while 39 patients died within 30 days of surgery. Five preoperative variables (ASA class, BMI, serum albumin, hematocrit, underlying pathology, and type of liver resection) were used to develop the rFI. The rFI demonstrated good discrimination (AUROC = 0.68) and outperformed the previously proposed modified frailty index (mFI; AUROC = 0.53, p < 0.001) when evaluated among patients included in the training cohort. On validation, the rFI demonstrated good model discrimination (AUROC = 0.68) and was accurately able to risk-stratify patients within the validation cohort at risk for developing a postoperative complication, prolonged length-of-stay, and postoperative mortality (all p < 0.05).Frailty, as measured by the rFI, was predictive of increased risk of morbidity and mortality following liver surgery and can be used to guide patient decision-making.

  View details for DOI 10.1007/s11605-017-3373-6

  View details for Web of Science ID 000399832800009

  View details for PubMedID 28265844

• Effect of Background Liver Cirrhosis on Outcomes of Hepatectomy for Hepatocellular Carcinoma JAMA SURGERY Sasaki, K., Shindoh, J., Margonis, G. A., Nishioka, Y., Andreatos, N., Sekine, A., Hashimoto, M., Pawlik, T. M. 2017; 152 (3): e165059

  Abstract

  Background hepatocarcinogenesis is considered a major cause of postoperative recurrence of de novo hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). The degree of underlying liver injury has reportedly correlated with surgical outcomes of HCC. However, the pattern and annual rate of recurrence of postoperative de novo HCC are still unclear.To clarify the pattern and rate of recurrence of de novo HCC in patients with LC.Data from 799 patients who underwent curative hepatectomy for HCC at Toranomon Hospital and The Johns Hopkins Hospital between January 1, 1995, and December 31, 2014, were retrospectively collected and analyzed. Of the patients who underwent curative hepatectomy for HCC, 424 met inclusion criteria: 73 with normal liver (NL) and 351 with LC. Sixty-four patients who had histologically proven NL parenchyma were matched with an equal number of patients who had established LC, and postoperative outcomes were compared.Hepatectomy in patients with HCC.Patterns of recurrence of HCC and chronological changes in recurrence rates.Among 128 matched patients in the study (mean [SD] age, 64.0 [12.7] years; 93 men and 35 women) 1-, 3-, and 5-year cumulative recurrence was 17.2%, 23.0%, and 37.5%, respectively, in the NL group vs 25.0%, 55.5%, and 72.1%, respectively, in the LC group (P = .001). The 3- and 5-year disease-specific survival was 85.7% and 75.4%, respectively, in the NL group vs 74.9% and 59.1%, respectively, in the LC group (P = .04). The median annual incidence of postoperative recurrence of HCC within 5 years after surgery was lower in the NL group (5.9%) compared with the LC group (12.7%) (P = .003). Assessment of recurrence patterns revealed that multiple recurrences near the resection margin or at extrahepatic sites were more frequent in the NL group (9 [50.0%] vs 6 [15.4%]; P = .01), whereas solitary recurrence at a distant site was more common in the LC group (21 [53.8%] vs 1 [5.6%]; P < .001).Comparison of the patterns and annual incidence of recurrence of HCC demonstrated that the poorer prognosis in the LC group was likely owing to a higher hepatocarcinogenic potential among patients with cirrhosis. Annual recurrence rates in the 2 groups indicate that de novo recurrence may continuously occur from the early postoperative period until the late period after resection of HCC.

  View details for DOI 10.1001/jamasurg.2016.5059

  View details for Web of Science ID 000398101400004

  View details for PubMedID 28052155

• Impact of Viral Etiology on Postoperative De Novo Recurrence After Hepatectomy for Hepatocellular Carcinoma in Cirrhotic Patients JOURNAL OF GASTROINTESTINAL SURGERY Sasaki, K., Shindoh, J., Nishioka, Y., Margonis, G. A., Sugawara, T., Andreatos, N., Hashimoto, M., Pawlik, T. M. 2017; 21 (3): 487-495

  Abstract

  Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) are associated with viral hepatitis, especially hepatitis B virus (HBV) and hepatitis C virus (HCV). Whether differences exist in postoperative de novo carcinogenesis from established cirrhosis according to viral etiology remains unclear.Data from 313 LC patients with viral hepatitis (HBV-LC, n = 108 and HCV-LC, n = 205) who underwent curative-intent hepatectomy for HCC were retrospectively collected. Clinicopathological characteristics, cumulative recurrence, chronological change of recurrence rate, and predictors of recurrence were analyzed.Baseline patient characteristics were different among patients with HBV versus HCV as HCC-LC patients had a lower albumin, higher alanine transaminase, and higher incidence of tumor multicentricity (all P < 0.050). The 1-, 3-, and 5-year cumulative recurrence was 16.7, 38.6, and 53.7% in HBV-LC versus 20.8, 52.2, and 71.6% in HCV-LC (P = 0.002) patients, respectively. The postoperative annual recurrence rates of HCV-LC were consistently higher than that of HBV-LC patients. After matching on clinicopathologic characteristics, while recurrence was comparable in the early time period, HCV-LC patients had a 2-5% higher incidence of recurrence compared with HBV-LC patients after 20 months post-resection. On multivariable analysis, HCV infection was an independent predictor of recurrence (HR 1.55; 95% CI 1.13-2.13).HCV-related LC was associated with a higher postoperative de novo carcinogenesis than HBV-related LC. Establishment of different treatment algorithms as well as follow-up surveillance protocols stratified by viral etiology may be warranted.

  View details for DOI 10.1007/s11605-016-3344-3

  View details for Web of Science ID 000395392100008

  View details for PubMedID 28050767

• The Impact of Primary Colorectal Cancer Location on the Overall Survival in Patients with Colorectal Cancer Liver Metastasis Hammad, A., Sasaki, K., Miller, C., Quintini, C., Berber, E., Aucejo, F. SPRINGER. 2017: S84-S85

  View details for Web of Science ID 000435672100219

• Albumin-Bilirubin Score: Predicting Short-Term Outcomes Including Bile Leak and Post-hepatectomy Liver Failure Following Hepatic Resection JOURNAL OF GASTROINTESTINAL SURGERY Andreatos, N., Amini, N., Gani, F., Margonis, G. A., Sasaki, K., Thompson, V. M., Bentrem, D. J., Hall, B. L., Pitt, H. A., Wilson, A., Pawlik, T. M. 2017; 21 (2): 238-248

  Abstract

  Post-operative bile leak (BL) and post hepatectomy liver failure (PHLF) are the major potential sources of morbidity among patients undergoing liver resection. We sought to define the incidence of BL and PHLF among a large cohort of patients, as well as examine the prognostic impact of model for end-stage liver disease (MELD) and albumin-bilirubin (ALBI) scores to predict these short-term outcomes.Patients who underwent a hepatectomy between January 1, 2014 and December 31, 2014 were identified using the National Surgical Quality Improvement Program (NSQIP) liver-targeted database. Risk factors for BL and PHLF were identified using multivariable logistic regression.Among the 3064 patients identified, median age was 60 years (IQR 50-68). Most patients underwent surgery (78.9 %) for malignant lesions. Post-operatively, 250 (8.5 %) patients experienced a BL while PHLF occurred in 149 cases (4.9 %). Both MELD (MELD <10 4.9 %; MELD ≥10, 10 %; P = 0.001) and ALBI (grade 1, 4.0 %; grade 2, 7.2 %; grade 3, 10.0 %; P = 0.001) were associated with PHLF occurrence, while only ALBI predicted PHLF severity (P = 0.008). Moreover, ALBI was associated with BL (grade 1, 7.1 %; grade 2, 11.5 %; grade 3, 14.0 %; P < 0.001), whereas MELD was not (MELD <10, 8.4 %; MELD ≥10, 11.2 %; P = 0.13). On multivariable analysis, ALBI grade 2/3 was associated with PHLF (OR 1.57, 95 % CI 1.08-2.27; P = 0.02), PHLF severity (OR 3.06, 95 % CI 1.50-6.23; P = 0.003), and the development of a BL (OR 1.35, 95 % CI 1.02-1.80; P = 0.04).The ALBI score was associated with short-term post-operative outcomes following hepatic resection and represents a useful pre-operative risk-assessment tool to identify patients at risk for adverse post-operative outcomes.

  View details for DOI 10.1007/s11605-016-3246-4

  View details for Web of Science ID 000393825300005

  View details for PubMedID 27619809

• Perioperative Hyperglycemia and Postoperative Outcomes in Patients Undergoing Resection of Colorectal Liver Metastases Margonis, G., Amini, N., Sasaki, K., Kim, Y., Merath, K., Buettner, S., Pikoulis, E., Andreatos, N., Wagner, D., Antoniou, E., Pawlik, T. M. SPRINGER. 2017: 228-237

  Abstract

  There is limited evidence characterizing the impact of glycemic alterations on short-term outcomes among patients undergoing resection of colorectal liver metastases (CRLM).Hyperglycemia was defined as a glucose value >125 mg/dl according to WHO definition. The impact of early postoperative hyperglycemia on short-term postoperative outcomes was assessed.The mean postoperative glucose value was 128 mg/dl; 30 (9.8 %) patients had normal fasting glucose (<100 mg/dl), 106 patients had glucose intolerance (100-125 mg/dl), and 170 (55.5 %) patients had hyperglycemia (>125 mg/dl). A postoperative complication occurred in 101 patients (morbidity, 33.1 %); among patients who experienced a complication, an infectious complication was most common (38.6 %). After controlling for clinical factors, patients with hyperglycemia had an increased risk of overall complications [odds ratio (OR) 4.11; 95 % confidence interval (CI) 1.96-8.62, P < 0.001]. This was the case for both patients with and without diabetes (P < 0.05). Patients with hyperglycemia on the day of surgery were also at an increased risk of infections [OR 9.17; 95 % CI 2.26-37.13, P = 0.002] and had a longer hospital stay (normal glucose, 4 days vs. glucose 100-125 mg/dl, 4 days vs. glucose >125 mg/dl, 5 days, P < 0.001).Early postoperative hyperglycemia was associated with adverse outcomes in patients with and without diabetes who underwent resection of CRLM. Perioperative glucose evaluation may be an important quality target.

  View details for DOI 10.1007/s11605-016-3278-9

  View details for Web of Science ID 000393825300004

  View details for PubMedID 27678503

• Development and validation of the HALT-HCC score to predict mortality in liver transplant recipients with hepatocellular carcinoma: a retrospective cohort analysis. The lancet. Gastroenterology & hepatology Sasaki, K., Firl, D. J., Hashimoto, K., Fujiki, M., Diago-Uso, T., Quintini, C., Eghtesad, B., Fung, J. J., Aucejo, F. N., Miller, C. M. 2017; 2 (8): 595-603

  Abstract

  Tumour morphological criteria for determining the appropriateness of liver transplantation in patients with hepatocellular carcinoma poorly estimate post-transplantation mortality. The aim of this study was to develop and assess the utility of a continuous risk score in predicting overall survival following liver transplantation for hepatocellular carcinoma.We did a retrospective cohort analysis to develop a continuous multivariable risk score for assessment of overall survival following liver transplantation for hepatocellular carcinoma. We used data from 420 patients with hepatocellular carcinoma who underwent liver transplantation between Jan 1, 2002, and Oct 31, 2014, at the Cleveland Clinic Foundation (CCF), Cleveland, OH, USA. The model we developed (Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma; HALT-HCC) assessed the association of the following previously reported variables of interest with overall survival by use of multivariate Cox regression: MELD-sodium (MELD-Na), tumour burden score (TBS), alpha-fetoprotein (AFP), year of transplantation, underlying cause of cirrhosis, neutrophil-lymphocyte ratio, history of locoregional therapy, and Milan criteria status. Once the risk equation was generated, validation and calibration of risk assessment was done with nationwide data for the same time period from the Scientific Registry of Transplant Recipients (SRTR; n=13 717).The risk equation was generated as (1·27 × TBS) + (1·85 × lnAFP) + (0·26 × MELD-Na) and the HALT-HCC score ranged from 2·40 to 46·42 in the CCF cohort. In the validation cohort, prognosis worsened with increasing HALT-HCC score (5-year overall survival of 78·7% [95% CI 76·9-80·4] for quartile 1, 74·5% [72·6-76·2] for quartile 2, 71·8% [70·1-73·5] for quartile 3, and 61·5% [59·6-63·3] for quartile 4; p<0·0001). Multivariate Cox modelling showed that HALT-HCC was significantly associated with overall survival (hazard ratio [HR] 1·06 per point, 95% CI 1·05-1·07), even after adjustment for risk factors not related to hepatocellular carcinoma. Assessment of discrimination revealed a C-index of 0·613 (95% CI 0·602-0·623). Calibration coefficients for linear regressions of observed versus predicted mortality were 1·001 (95% CI 0·998-1·007) at 1 year and 0·982 (0·980-0·987) at 2 years after transplantation. Patients within and outside the Milan criteria showed similar risk of death when stratified by HALT-HCC score. Among the 12 754 patients who met the Milan criteria, 2714 were shown to have poor prognosis after transplantation after stratification by HALT-HCC score with a cutoff of 17; conversely, among the 963 patients who did not meet the Milan criteria, 287 had demonstrably good prognosis.The HALT-HCC score might enable clinicians to accurately assess post-transplantation survival in patients with hepatocellular carcinoma by use of individualised, preoperatively assessed characteristics. However, further studies are needed before adoption.None.

  View details for DOI 10.1016/S2468-1253(17)30106-1

  View details for PubMedID 28546007

• KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases ANNALS OF SURGICAL ONCOLOGY Margonis, G. A., Sasaki, K., Andreatos, N., Kim, Y., Merath, K., Wagner, D., Wilson, A., Buettner, S., Amini, N., Antoniou, E., Pawlik, T. M. 2017; 24 (1): 264-271

  Abstract

  The optimal tumor-free margin width remains controversial and may be inappropriate to investigate without considering differences in the underlying tumor biology.R1 resection was defined as margin clearance less than 1 mm. R0 resection was further divided into 3 groups: 1-4, 5-9, and ≥10 mm. The impact of margin width on overall survival (OS) relative to KRAS status [wild type (wtKRAS) vs. mutated (mutKRAS)] was assessed.A total of 411 patients met inclusion criteria. Median patient age was 58 years (interquartile range, 49.7-66.7); most patients were male (n = 250; 60.8 %). With a median follow-up of 28.3 months, median and 5-year OS were 69.8 months and 55.1 %. Among patients with wtKRAS tumors, although margin clearance of 1-4 mm or more was associated with improved OS compared to R1 (all P < 0.05), no difference in OS was observed when comparing margin clearance of 1-4 mm to the 5-9 mm and the ≥10 mm groups (all P > 0.05). In contrast, among patients with mutKRAS tumors, all three groups of margin clearance (1-4, 5-9, and ≥10 mm) fared no better in terms of 5-year survival compared to R1 resection (all P > 0.05).While a 1-4 mm margin clearance in patients with wtKRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status-including a 1 cm margin-did not improve survival among patients with mutKRAS tumors.

  View details for DOI 10.1245/s10434-016-5609-1

  View details for Web of Science ID 000391510400039

  View details for PubMedID 27696170

• Pre-hepatectomy carcinoembryonic antigen (CEA) levels among patients undergoing resection of colorectal liver metastases: do CEA levels still have prognostic implications? HPB Sasaki, K., Margonis, G. A., Andreatos, N., Wilson, A., Gani, F., Amini, N., Pawlik, T. M. 2016; 18 (12): 1000-1009

  Abstract

  The impact of prehepatectomy carcinoembryonic antigen (CEA) levels in the era of modern chemotherapy and expanded surgical indications for colorectal liver metastasis (CRLM) remains not well defined.484 patients were identified and divided into two groups by surgical time period (group 1: 2000-2007 vs. group 2: 2008-2015). The prognostic significance of pre-hepatectomy CEA was determined by assessing the HRs associated with various cut-off levels ranging from 5 to 200 ng/mL.Median CRLM number was comparable in both groups (group 1: 2 vs. group 2: 2, P = 0.504). Bilobar disease was more frequent in group 2 (30.1% vs. 42.5%, P = 0.006). The administration of modern chemotherapy and/or biologic agents increased over time (49.5% vs. 67.9%, P < 0.001). Preoperative CEA independently predicted OS in group 1, even with a cut-off as low as >5 ng/mL. However, in group 2 it predicted recurrence and survival only after exceeding 70 and 50 ng/mL, respectively. Of note, in group 2, CEA was strongly associated with survival when CEA levels exceeded 70 ng/mL (HR 4.84).While pre-hepatectomy CEA level may still have prognostic utility in CRLM resection, the optimal cut-off value has increased in the era of modern chemotherapy.

  View details for DOI 10.1016/j.hpb.2016.09.004

  View details for Web of Science ID 000390044100005

  View details for PubMedID 27769662

  View details for PubMedCentralID PMC5144549

• The prognostic implications of primary colorectal tumor location on recurrence and overall survival in patients undergoing resection for colorectal liver metastasis JOURNAL OF SURGICAL ONCOLOGY Sasaki, K., Andreatos, N., Margonis, G. A., He, J., Weiss, M., Johnston, F., Wolfgang, C., Antoniou, E., Pikoulis, E., Pawlik, T. M. 2016; 114 (7): 803-809

  Abstract

  The prognostic impact of primary colorectal cancer (CRC) location following resection of colorectal liver metastasis (CRLM) remains largely unknown. We sought to characterize the prognostic implications of primary tumor location among patients who underwent curative-intent hepatectomy for CRLM.Tumors of the cecum, ascending, and transverse colon were defined as right-sided; tumors of the sigmoid flexure, descending, and sigmoid colon were defined as left-sided. Clinicopathologic and long-term survival data were collected and assessed using univariable and multivariable analyses.About 475 patients who underwent CRLM resection at a single institution were included; most patients had left-sided tumors (n = 284). Median and 5-year RFS was 20.2 months and 28.0%, respectively. Patients who had a left-sided primary tumor had a shorter RFS compared with patients who had a right-sided tumor (P = 0.01). Although site of and time to recurrence did not differ between the two groups (P > 0.05), patients with right-sided primary tumors were more likely to recur with advanced disease (i.e., ≥4 recurrent lesions) (P < 0.01). In turn, patients with right-sided tumors had both worse OS (P = 0.03) and worse survival after recurrence (P = 0.01).While patients with right-sided tumors experienced longer RFS, when these patients did recur following CRLM resection, disease extent was more advanced. In turn, OS following recurrence was shorter among patients with right-sided CRC. J. Surg. Oncol. 2016;114:803-809. © 2016 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24425

  View details for Web of Science ID 000387028900005

  View details for PubMedID 27792291

• Is resection of pancreatic adenocarcinoma with synchronous hepatic metastasis justified? A review of current literature ANZ JOURNAL OF SURGERY Antoniou, E., Margonis, G. A., Sasaki, K., Andreatos, N., Polychronidis, G., Pawlik, T. M., Pikoulis, E. 2016; 86 (12): 973-977

  Abstract

  Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal neoplastic process, largely due to the presence of disseminated disease at presentation. As such, evidence-based management of metastatic disease is integral to patient care in such circumstances. This review aimed to summarize the current state of knowledge regarding the potential effectiveness of liver metastasectomy in the setting of PDAC.A structured review of the literature was performed from April to May 2016, using the PubMed database. Relevant original research articles and systematic reviews/meta-analyses published between 1990 and 2015 were considered eligible. The primary endpoint was overall survival in patients undergoing resection for PDAC and liver metastasectomy. Studies reporting on fewer than 10 patients were excluded.Ultimately, eight studies met our inclusion criteria. Their results suggest that hepatic metastasectomy for PDAC is a safe procedure, with a potential survival benefit for carefully selected patients, particularly those with metachronous metastases. Nonetheless, small sample sizes and inconsistent use of appropriate controls preclude generalization of these findings.Multi-institutional prospective studies are required to fully delineate the potential therapeutic utility and operative indications of liver metastasectomy in the setting of modern interdisciplinary management of PDAC.

  View details for DOI 10.1111/ans.13738

  View details for Web of Science ID 000389333500006

  View details for PubMedID 27580713

• Combined resection and RFA in colorectal liver metastases: stratification of long-term outcomes JOURNAL OF SURGICAL RESEARCH Sasaki, K., Margonis, G. A., Andreatos, N., Kim, Y., Wilson, A., Gani, F., Amini, N., Pawlik, T. M. 2016; 206 (1): 182-189

  Abstract

  Combined hepatic resection and radiofrequency ablation (resection-RFA) is a widely accepted multidisciplinary treatment for unresectable colorectal cancer liver metastases. Worse prognosis after resection-RFA is correlated to tumor morphology, although unfavorable morphology is inherent to this patient cohort. This study aimed to select patients who may or may not benefit from resection-RFA with the aid of tumor biology.Data from 485 patients who underwent curative hepatectomy with or without concurrent RFA were retrospectively collected and analyzed. Clinicopathologic characteristics, predictors of overall survival (OS), and OS of patients stratified by tumor biology in resection-RFA were analyzed.Combined resection-RFA was performed in 86 patients (17.7%) and a standalone resection in 399 patients. Baseline patients' characteristics of the resection-RFA group were significantly different in terms of median number of tumors (5 versus 2) and bilobar distribution (84.9% versus 29.1%) from those of the resection-only group. Multivariate analysis identified four independent predictors of decreased OS in the resection-RFA group. Three were related to tumor biology: primary tumor nodal metastases (hazard ratio [HR], 2.32; 95% confidence interval (95% CI), 1.16-4.64], Kirsten rat sarcoma viral oncogene homolog mutation (HR, 2.64; 95% CI, 1.36-5.14), and preoperative high carcinoembryonic antigen (HR, 2.33; 95% CI, 1.13-4.81), and one related to tumor morphology-ablated lesions ≥3 (HR, 2.05; 95% CI, 1.41-3.80; P = 0.023). To examine the prognostic influence of tumor biology, the resection-RFA group was stratified into two groups by number of predictors related to tumor biology (low risk: 0-1 risk factors; n = 56 and high risk: 2-3 risk factors; n = 30). Median OS of the low risk, high risk, and resection-alone groups were 61.8, 20.7, and 75.3 mo, respectively. The 5-y OS rate was similar between the low risk and resection-alone group (52.7% versus 58.7%, respectively; P = 0.323).Patients with low-risk tumors undergoing a combined resection-RFA approach had roughly comparable OS to those who only underwent resection, irrespective of advanced tumor morphology. Combined resection-RFA procedures might be of value to these patients.

  View details for DOI 10.1016/j.jss.2016.06.098

  View details for Web of Science ID 000387982900028

  View details for PubMedID 27916360

• Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases JOURNAL OF GASTROINTESTINAL SURGERY Margonis, G., Sasaki, K., Kim, Y., Samaha, M., Buettner, S., Amini, N., Antoniou, E., Pawlik, T. M. 2016; 20 (11): 1821-1829

  Abstract

  The interplay of tumor biology and surgical margin status after resection for colorectal liver metastasis (CRLM) remains controversial. Consequently, we sought to determine the impact of surgical margin status on overall survival (OS) stratified by KRAS mutational status.Four hundred eighty-five patients with known KRAS mutational status were identified. Clinicopathologic and long-term survival data were collected and assessed.On pathology, most patients (n = 380; 78.3 %) had an R0 margin, while 105 (21.7 %) had an R1. Roughly two thirds of tumors were KRAS wild type (wtKRAS) (n = 307, 63.3 %), while 36.7 % (n = 178) had KRAS mutations (mutKRAS). Median and 5-year OS of the entire cohort was 65.8 months and 53.8 %, respectively. An R1 resection was associated with worse 5-year OS compared with R0 (42.4 % vs. 57.1 %; hazard ratio (HR) 1.82, 95 % CI 1.28-2.57; P = 0.001). After controlling for KRAS status, the survival benefit associated with an R0 resection persisted only among patients with wtKRAS tumors (HR 2.16, 95 % CI 1.42-3.30; P < 0.001). In contrast, surgical margin had no impact on OS among patients with mutKRAS tumors (5-year OS R0, 40.7 % vs. R1, 46.7 %; HR 1.34, 95 % CI 0.73-2.48; P = 0.348).The impact of margin status differed by KRAS mutation status. An R0 margin only provided a survival benefit to patients with wtKRAS tumors. Tumor biology and not surgical technique determined prognosis.

  View details for DOI 10.1007/s11605-016-3198-8

  View details for Web of Science ID 000387032200006

  View details for PubMedID 27384430

• Sarcopenia predicts costs among patients undergoing major abdominal operations SURGERY Gani, F., Buettner, S., Margonis, G. A., Sasaki, K., Wagner, D., Kim, Y., Hundt, J., Kamel, I. R., Pawlik, T. M. 2016; 160 (5): 1162-1171

  Abstract

  Although sarcopenia has been identified as a predictor of poor, postoperative, clinical outcomes, the financial impact of sarcopenia remains undetermined. We sought to evaluate the relationship between sarcopenia and hospital finances among a cohort of patients undergoing a hepato-pancreatico-biliary or colorectal resection.Clinical, financial, and morphometric data were collected for 1,169 patients undergoing operative resection between January 2011 and December 2013 at the Johns Hopkins Hospital. Multivariable regression analysis was performed to assess the relationship between sarcopenia and total hospital costs.Using sex-specific cutoffs for total psoas volume, 293 patients were categorized as sarcopenic. The presence of sarcopenia was associated with a $14,322 increase in the total hospital cost (median covariate-adjusted cost, sarcopenia versus no sarcopenia: $38,804 vs $24,482, P < .001). Patients who presented with sarcopenia demonstrated a higher total hospital cost within the subgroup of patients who developed a postoperative complication (sarcopenia versus no sarcopenia: $65,856 vs $59,609) and among those patients who did not develop a postoperative complication (sarcopenia versus no sarcopenia: $26,282 vs $23,763, both P < .001). Similarly, total hospital costs were higher among patients presenting with sarcopenia regardless of the length of stay for index admission (observed:expected, length of stay < 1: sarcopenia versus no sarcopenia: $25,038 vs $22,827; observed:expected, length of stay > 1: sarcopenia versus no sarcopenia: $43,283 vs $38,679, both P < .001).As measured by sarcopenia, patient frailty is inversely related to total hospital costs. Sarcopenia represents a novel tool for forecasting patient outcomes and operative costs and can be used to inform quality improvement and cost containment strategies.

  View details for DOI 10.1016/j.surg.2016.05.002

  View details for Web of Science ID 000387633300007

  View details for PubMedID 27302103

• Radiofrequency Ablation Combined with Hepatic Resection for Colorectal Liver Metastasis: Biology Dictates Long-Term Outcomes Sasaki, K. S., Margonis, G., Kim, Y., Wilson, A., Gani, F., Amini, N., Pawlik, T. M. ELSEVIER SCIENCE INC. 2016: E144

  View details for DOI 10.1016/j.jamcollsurg.2016.08.370

  View details for Web of Science ID 000395825100318

• Prognostic Implication of KRAS Status after Hepatectomy for Colorectal Liver Metastases Varies According to Primary Colorectal Tumor Location ANNALS OF SURGICAL ONCOLOGY Sasaki, K., Margonis, G. A., Wilson, A., Kim, Y., Buettner, S., Andreatos, N., Gani, F., Amini, N., Spolverato, G., Pawlik, T. M. 2016; 23 (11): 3736-3743

  Abstract

  Right-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. We sought to investigate the variable prognostic implication of KRAS mutation after hepatectomy for colorectal liver metastases (CRLM) according to the site of primary CRC.A total of 426 patients who underwent a curative-intent hepatic resection and whose KRAS status was available were identified. Clinicopathologic characteristics and long-term outcomes were stratified by KRAS status (wild type vs. mutant type) and primary tumor location (right-sided vs. left-sided). Cecum, right and transverse colon were defined as right-sided, whereas left colon and rectum were defined as left-sided.Among patients with a right-sided CRC, 5-year recurrence-free survival (RFS) and overall survival (OS) were not correlated with KRAS status (wild type: 30.8 and 47.2 % vs. mutant type: 38.5 and 49.1 %, respectively) (both P > 0.05). Specifically, mutant-type KRAS was not associated with either RFS or OS on multivariable analysis (hazard ratio [HR] 1.51, 95 % confidence interval [CI] 0.73-3.14, P = 0.23 and HR 1.03, 95 % CI 0.51-2.08, P = 0.95, respectively). In contrast, among patients who underwent resection of CRLM from a left-sided primary CRC, 5-year RFS and OS were worse among patients with mutant-type KRAS (wild type: 23.7 and 57.2 % vs. mutant type: 19.6 and 38.2 %, respectively) (both P < 0.05). On multivariable analysis, mutant-type KRAS remained independently associated with worse RFS and OS among patients with a left-sided primary CRC (HR 1.57, 95 % CI 1.01-2.44, P = 0.04 and HR 1.81, 95 % CI 1.11-2.96, P = 0.02, respectively).KRAS status has a variable prognostic impact after hepatic resection for CRLM depending on the site of the primary CRC. Future studies examining the impact of KRAS status on prognosis after hepatectomy should take into account the primary CRC tumor site.

  View details for DOI 10.1245/s10434-016-5361-6

  View details for Web of Science ID 000382930000045

  View details for PubMedID 27352204

• Prognostic Role of BRAF Mutations in Colorectal Cancer Liver Metastases ANTICANCER RESEARCH Pikoulis, E., Margonis, G. A., Andreatos, N., Sasaki, K., Angelou, A., Polychronidis, G., Pikouli, A., Riza, E., Pawlik, T. M., Antoniou, E. 2016; 36 (9): 4805-4811

  Abstract

  The impact of tumor biology on prognosis in patients with colorectal liver metastasis (CRLM) has been the topic of intense research. Specifically, the presence of BRAF mutations has been recently associated with adverse long-term outcomes. We examined the existing literature on the prognostic implications of BRAF mutations in patients with CRLM.A structured review of the literature was performed between 5/1/2016 and 6/1/2016 using the PubMed database. Original research articles published between 1/1/2010 and 4/01/2016 were considered eligible. The primary end-points were overall survival (OS)/disease-specific survival (DSS) and recurrence-free survival (RFS) among patients with BRAF mutated CRLM who underwent resection.Eight studies were included. All studies reported on OS/DSS, while 6 reported on RFS. BRAF mutant status was a strong independent predictor of both worse OS/DSS and RFS in 7 and 4 studies, respectively.BRAF-mutant lesions are consistently associated with poor prognosis. Consequently, the indications of CRLM resection in this patient group should be reconsidered.

  View details for DOI 10.21873/anticanres.11040

  View details for Web of Science ID 000384001800060

  View details for PubMedID 27630332

• Codon 13 KRAS mutation predicts patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases CANCER Margonis, G. A., Kim, Y., Sasaki, K., Samaha, M., Amini, N., Pawlik, T. M. 2016; 122 (17): 2698-2707

  Abstract

  Investigations regarding the impact of tumor biology after surgical management of colorectal liver metastasis have focused largely on overall survival. We investigated the impact of codon-specific KRAS mutations on the rates and patterns of recurrence in patients after surgery for colorectal liver metastasis (CRLM).All patients who underwent curative-intent surgery for CRLM between 2002 and 2015 at Johns Hopkins who had available data on KRAS mutation status were identified. Clinico-pathologic data, recurrence patterns, and recurrence-free survival (RFS) were assessed using univariable and multivariable analyses.A total of 512 patients underwent resection only (83.2%) or resection plus radiofrequency ablation (16.8%). Although 5-year overall survival was 64.6%, 284 (55.5%) patients recurred with a median RFS time of 18.1 months. The liver was the initial recurrence site for 181 patients, whereas extrahepatic recurrence was observed in 162 patients. Among patients with an extrahepatic recurrence, 102 (63%) had a lung recurrence. Although overall KRAS mutation was not associated with overall RFS (P = 0.186), it was independently associated with a worse extrahepatic (P = 0.004) and lung RFS (P = 0.007). Among patients with known KRAS codon-specific mutations, patients with codon 13 KRAS mutation had a worse 5-year extrahepatic RFS (P = 0.01), whereas codon 12 mutations were not associated with extrahepatic (P = 0.11) or lung-specific recurrence rate (P = 0.24). On multivariable analysis, only codon 13 mutation independently predicted worse overall extrahepatic RFS (P = 0.004) and lung-specific RFS (P = 0.023).Among patients undergoing resection of CRLM, overall KRAS mutation was not associated with RFS. KRAS codon 13 mutations, but not codon 12 mutations, were associated with a higher risk for overall extrahepatic recurrence and lung-specific recurrence. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2698-2707. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30085

  View details for Web of Science ID 000383617200013

  View details for PubMedID 27244540

• Activating KRAS mutation is prognostic only among patients who receive preoperative chemotherapy before resection of colorectal liver metastases JOURNAL OF SURGICAL ONCOLOGY Margonis, G., Kim, Y., Sasaki, K., Samaha, M., Buettner, S., Amini, N., Pawlik, T. M. 2016; 114 (3): 361-367

  Abstract

  While the prognostic role of KRAS status after resection of CRLM has been previously explored, the importance of KRAS status relative to the receipt of preoperative chemotherapy remains largely unknown.A total of 430 patients who underwent curative-intent surgery for CRLM between 2000 and 2015 and who had available KRAS genotype data were identified. Data regarding KRAS mutation status, receipt of preoperative chemotherapy, and overall survival (OS) were assessed using univariable and multivariable analyses.Median patient age was 58 years (IQR, 50.4-66.4 years). A total of 258 patients (60.0%) received preoperative chemotherapy, while 172 (40.0%) had upfront surgery. Median and 5-year OS in the entire cohort was 65.1 months and 53.2%, respectively. KRAS mutation was associated with a worse 5-year OS compared with wild-type tumors (HR 1.41; P = 0.042). After stratifying by the receipt of preoperative chemotherapy, the prognostic value of KRAS mutation only persisted among patients who had received preoperative chemotherapy (HR 1.67; P = 0.012). In contrast, KRAS mutation status had no impact on OS among patients who had not received preoperative chemotherapy (P = 0.597).KRAS mutation status was an independent predictor of OS among patients undergoing liver resection of CRLM. However, after stratifying by receipt of preoperative chemotherapy, KRAS was informative relative to prognosis only among patients who received preoperative chemotherapy. J. Surg. Oncol. 2016;114:361-367. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24319

  View details for Web of Science ID 000383779200018

  View details for PubMedID 27264476

• From bench to bedside: Clinical implications of KRAS status in patients with colorectal liver metastasis SURGICAL ONCOLOGY-OXFORD Andreatos, N., Ronnekleiv-Kelly, S., Margonis, G. A., Sasaki, K., Gani, F., Amini, N., Wilson, A., Pawlik, T. M. 2016; 25 (3): 332-338

  Abstract

  While the role of KRAS in the molecular genetics of colorectal cancer has been studied extensively, its prognostic impact in colorectal liver metastases (CRLM) has only recently been examined. This review aimed to summarize currently reported findings on the clinical implications of KRAS mutant (mut-KRAS) status for patients with CRLM.The Pubmed database was searched for relevant articles published from 01/01/2010 to 02/01/2016. Overall survival (OS) and recurrence free survival (RFS) as well as patterns of recurrence were the primary endpoints, but consideration was given to secondary outcomes when the respective findings were of clinical interest.Out of the 266 studies screened, 15 were included in our review. Fourteen studies were retrospective cohorts while one was a systematic review/meta-analysis. Among the 14 retrospective studies, 12 reported OS with 9 detecting a negative association with mut-KRAS status. Similarly, 11 out of 14 retrospective cohorts reported RFS with 6 detecting a negative association with mut-KRAS status. Five studies examined patterns of recurrence, with 4 detecting increased extrahepatic recurrence in the mut-KRAS group. One study examined the different effects of codon-specific KRAS mutations on prognosis.mut-KRAS status predisposes to worse RFS and OS in patients with CRLM, possibly as a result of aggressive tumor biology. Early unresectable extrahepatic recurrence is more frequent in this patient group and may underlie the unfavorable prognosis. Future research should focus on characterizing the distinct effects of codon-specific KRAS mutations as well their interplay with other less common genetic mutations.

  View details for DOI 10.1016/j.suronc.2016.07.002

  View details for Web of Science ID 000382233800030

  View details for PubMedID 27566041

• Rates and patterns of recurrence after curative intent resection for gallbladder cancer: a multi-institution analysis from the US Extra-hepatic Biliary Malignancy Consortium. HPB Margonis, G. A., Gani, F., Buettner, S., Amini, N., Sasaki, K., Andreatos, N., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016

  Abstract

  Gallbladder cancer is a relatively rare malignancy. The current study aimed to define the incidence and patterns of recurrence following gallbladder cancer resection.Using a multi-institutional cohort we identified 217 patient undergoing curative intent surgery for gallbladder cancer. Patterns of recurrence were classified as locoregional and distant recurrence.At last follow-up, 76 patients (35.0%) had experienced a recurrence (locoregional only, n = 12, 15.8%; distant only, n = 50, 65.8%; locoregional and distant, n = 14, 18.4%). Median time to recurrence was 9.5 months (IQR 4.7-17.6) and was not associated with recurrence site (all p > 0.05). On multivariable analysis, T3 disease (HR = 8.44, p = 0.014), lymphovascular invasion (HR = 4.24, p < 0.001) and residual disease (HR = 2.04, p = 0.042) were associated with an increased risk of recurrence. Patients who recurred demonstrated a worse 1-, 3- and 5-year OS (1-year OS: 91.3% vs. 68.6%, p = 0.001, 3-year OS: 79.3% vs. 28.7%, p < 0.001, and 5-year OS: 75.9% vs. 16.0%, p < 0.001). After adjusting for other risk factors, recurrence was independently associated with a decreased OS (HR = 3.71, p = 0.006). Of note, receipt of adjuvant therapy was associated with improved OS (HR = 0.56, p = 0.027) among those patients who developed a tumor recurrence.Over one-third of patients experienced a recurrence after gallbladder cancer surgery. While chemotherapy did not decrease the rate of recurrence, patients who experienced recurrence after administration of adjuvant treatment faired better than patients who did not receive adjuvant therapy.

  View details for DOI 10.1016/j.hpb.2016.05.016

  View details for PubMedID 27527802

  View details for PubMedCentralID PMC5094487

• The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis. HPB Margonis, G. A., Buettner, S., Sasaki, K., Kim, Y., Ratti, F., Russolillo, N., Ferrero, A., Berger, N., Gamblin, T. C., Poultsides, G., Tran, T., Postlewait, L. M., Maithel, S., Michaels, A. D., Bauer, T. W., Marques, H., Barroso, E., Aldrighetti, L., Pawlik, T. M. 2016; 18 (8): 700-705

  Abstract

  Data on surgical management of breast liver metastasis are limited. We sought to determine the safety and long-term outcome of patients undergoing hepatic resection of breast cancer liver metastases (BCLM).Using a multi-institutional, international database, 131 patients who underwent surgery for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome data were collected and analyzed.Median tumor size of the primary breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor nodal metastasis. The median time from diagnosis of breast cancer to metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis. An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was 53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03, 95% CI 1.01-1.06; p = 0.002) remained associated with worse OS.In selected patients, resection of breast cancer liver metastases can be done safely and a subset of patients may derive a relatively long survival, especially from a margin negative resection.

  View details for DOI 10.1016/j.hpb.2016.05.014

  View details for PubMedID 27485066

  View details for PubMedCentralID PMC4972375

• Blood loss and outcomes after resection of colorectal liver metastases JOURNAL OF SURGICAL RESEARCH Margonis, G. A., Kim, Y., Samaha, M., Buettner, S., Sasaki, K., Gani, F., Amini, N., Pawlik, T. M. 2016; 202 (2): 473-480

  Abstract

  The influence of intraoperative blood loss (IBL) on long-term outcomes of patients undergoing liver resection for colorectal cancer liver metastases (CRLM) remains not well defined.A total of 433 patients who underwent curative-intent hepatic resection for CRLM between 2000 and 2013 at Johns Hopkins were identified. Demographics, IBL data, and long-term outcomes were collected and analyzed. Clinicopathologic predictors of IBL and the association of IBL and outcomes were assessed.The median patient age was 54 y (interquartile range, 44-64), most patients were male (58.9%; n = 255). At surgery, the median IBL was 400 mL (range, 10-5100 mL). Two-hundred eighty-seven patients (66.3%) had an IBL of >250 mL. Factors associated with increased IBL (>250 mL) on multivariate analysis were male sex (odds ratio [OR], 2.62; 95% confidence interval [CI], 1.68-4.09; P < 0.001), tumor size >3 cm (OR, 1.88; 95% CI, 1.18-2.99; P = 0.008), and major hepatic resection (OR, 3.08; 95% CI, 1.92-4.92; P < 0.001). At a median follow-up time of 30.6 mo, the median survival times were 70.5, 56.4, and 36.9 mo for IBL <250, 250-1000, and >1000 mL, respectively (P = 0.004). IBL >250 mL remained an independent prognostic factor of overall survival in multivariate analysis (hazard ratio, 1.41; 95% CI, 1.01-1.97; P = 0.04) after adjusting for other factors including the receipt of blood transfusion.The magnitude of IBL during CRLM resection was related to biologic characteristics of the tumor and the extent of surgery. Increased IBL during CRLM resection was an independent prognostic factor for worse patient survival. Furthermore, a dose-response relationship between increasing IBL and worsening survival was evident.

  View details for DOI 10.1016/j.jss.2016.01.020

  View details for Web of Science ID 000376334700031

  View details for PubMedID 27038662

• Impact of Early Postoperative Hyperglycemia on Short-Term Outcomes After Resection of Colorectal Liver Metastases Margonis, G. A., Amini, N., Sasaki, K., Wilson, A., Samaha, M., Kim, Y., Pawlik, T. M. W B SAUNDERS CO-ELSEVIER INC. 2016: S1237-S1238

  View details for DOI 10.1016/S0016-5085(16)34184-1

  View details for Web of Science ID 000391783700685

• Inclusion of Sarcopenia Outperforms the Modified Frailty Index in Predicting 1-Year Mortality among 1,326 Patients Undergoing Gastrointestinal Surgery for a Malignant Indication Buettner, S., Wagner, D., Kim, Y., Margonis, G. A., Makary, M. A., Wilson, A., Sasaki, K., Amini, N., Gani, F., Pawlik, T. M. ELSEVIER SCIENCE INC. 2016: 397-407

  Abstract

  Although it is a useful metric for preoperative risk stratification, frailty can be difficult to identify in patients before surgery. We sought to develop a preoperative frailty-risk model combining sarcopenia with clinical parameters to predict 1-year mortality using a cohort of patients undergoing gastrointestinal cancer surgery.We identified 1,326 patients undergoing hepatobiliary, pancreatic, or colorectal surgery between 2011 and 2014. Sarcopenia defined by psoas density was measured using preoperative cross-sectional imaging. Multivariable Cox regression analysis was performed to identify preoperative risk factors associated with 1-year mortality and used to develop a preoperative risk-stratification score.Among all patients identified, 640 (48.3%) patients underwent pancreatic surgery, 347 (26.2%) underwent a hepatobiliary procedure, and 339 (25.5%) a colorectal procedure. Using sex-specific cut-offs, 398 (30.0%) patients were categorized as sarcopenic. Sarcopenic patients were more likely to develop postoperative complications vs non-sarcopenic patients (odds ratio [OR] 1.80, 95% CI 1.42 to 2.29; p < 0.001). Overall 1-year mortality was 9.4%. On multivariable analysis, independent risk factors for 1-year mortality included increasing age (65 to 75 years: [hazard ratio (HR) 1.81, 95% CI 1.05 to 3.14] greater than 75 years [HR 2.79, 95% CI 1.55 to 5.02]), preoperative anemia hemoglobin < 12.5 g/dL (HR 1.68, 95% CI 1.17 to 2.40), and preoperative sarcopenia (HR 1.98, 95% CI 1.36 to 2.88; all p < 0.05). Using these variables, a 28-point weighed composite score was able to stratify patients by their risk for mortality 1 year after surgery (C-statistic = 0.70). The proposed score outperformed other indices of frailty including the modified Frailty Index (C-statistic = 0.55) and the Eastern Cooperative Oncology Group (ECOG) performance score (C-statistic = 0.57) (both p < 0.05).Sarcopenia was combined with clinical factors to generate a composite risk-score that can be used to identify frail patients at greatest risk for 1-year mortality after gastrointestinal cancer surgery.

  View details for DOI 10.1016/j.jamcollsurg.2015.12.020

  View details for Web of Science ID 000374848000012

  View details for PubMedID 26803743

• Frailty As a Predictor of Morbidity and Mortality Following Liver Surgery Gani, F., Cerullo, M., Amini, N., Buettner, S., Margonis, G. A., Sasaki, K., Kim, Y., Pawlik, T. M. W B SAUNDERS CO-ELSEVIER INC. 2016: S1216

  View details for DOI 10.1016/S0016-5085(16)34115-4

  View details for Web of Science ID 000391783700616

• Long-term prognosis after resection of cryptogenic hepatocellular carcinoma BMC SURGERY Ohkura, Y., Sasaki, K., Matsuda, M., Hashimoto, M., Watanabe, G. 2015; 15: 115

  Abstract

  We investigated the patterns and predictors of recurrence and survival in cryptogenic non-B, non-C, non-alcoholic hepatocellular carcinoma (CR-HCC). We compared the findings with those hepatitis virus B (B) and hepatitis virus C (C)-HCC. CR-HCC does not include HCC developed on NASH.From 1990 to 2011, of 676 patients who underwent primary curative liver resection as initial therapy for HCC at our institution, 167 had B-HCC, 401 had C-HCC, and 62 had CR-HCC. Differences between three groups were analyzed using the Chi-squared test. Cumulative overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method, prognostic factors involved in OS/DFS were evaluated by univariate analysis using the log-rank test, and stepwise Cox regression analysis.Liver function was better in CR-HCC than in B/C-HCC, and mean tumor size was larger in CR-HCC than in B/C-HCC. In CR-HCC, OS was equivalent to that of B/C-HCC, and DFS was equivalent to that of B-HCC. Both tumor-related factors and background liver function appeared to be prognostic factors for three groups.Our findings indicate that the probability of survival of advanced CR-HCC was not longer than that of B/C-HCC. Given our findings, a postoperative follow-up protocol for CR-HCC should be established alongside that for B/C-HCC.

  View details for DOI 10.1186/s12893-015-0099-9

  View details for Web of Science ID 000363115700001

  View details for PubMedID 26475278

  View details for PubMedCentralID PMC4609070

• Liver resection for hepatocellular carcinoma using a microwave tissue coagulator: Experience of 1118 cases WORLD JOURNAL OF GASTROENTEROLOGY Sasaki, K., Matsuda, M., Hashimoto, M., Watanabe, G. 2015; 21 (36): 10400-10408

  Abstract

  To present our extensive experience of hepatectomy for hepatocellular carcinoma using a microwave tissue coagulator to demonstrate the effectiveness of this device.A total of 1118 cases (1990-2013) were reviewed, with an emphasis on intraoperative blood loss, postoperative bile leakage and fluid/abscess formation, and adaptability to anatomical resection and hepatectomy with hilar dissection.The median intraoperative blood loss was 250 mL; postoperative bile leakage and fluid/abscess formation were seen in 3.0% and 3.3% of cases, respectively. Anatomical resection was performed in 275 cases, including 103 cases of hilar dissection that required application of microwave coagulation near the hepatic hilum. There was no clinically relevant biliary tract stricture or any vascular problems due to heat injury. Regarding the influence of cirrhosis on intraoperative blood loss, no significant difference was seen between cirrhotic and non-cirrhotic patients (P = 0.38), although cirrhotic patients tended to have smaller tumors and underwent less invasive operations.This study demonstrated outcomes of an extensive experience of hepatectomy using heat coagulative necrosis by microwave tissue coagulator.

  View details for DOI 10.3748/wjg.v21.i36.10400

  View details for Web of Science ID 000362118400014

  View details for PubMedID 26420966

  View details for PubMedCentralID PMC4579886

• Pancreaticogastrostomy in pure laparoscopic pancreaticoduodenectomy-A novel pancreatic-gastric anastomosis technique - BMC SURGERY Matsuda, M., Haruta, S., Shinohara, H., Sasaki, K., Watanabe, G. 2015; 15: 80

  Abstract

  Although many surgical procedures are now routinely performed laparoscopically, pure laparoscopic pancreaticoduodenectomy (LPD) is not commonly performed because of the technical difficulty of pancreatic resection and the associated reconstruction procedures. Several pancreatic-enteric anastomosis techniques for LPD have been reported, but most are adaptations of open procedures. To accomplish pure LPD, we consider it necessary to establish new pancreatic-enteric anastomosis techniques that are specifically developed for LPD and are safe and feasible to perform.One patient developed a postoperative pancreatic fistula (International Study Group of Pancreatic Fistula criteria, grade B) and subsequent postoperative delayed gastric emptying (International Study Group of Pancreatic Surgery criteria, grade C). No other major complications occurred. We developed a novel pancreatic-gastric anastomosis technique that enabled us to safely perform pure LPD. The main pancreatic duct was stented with a 4-Fr polyvinyl catheter during pancreatic resection. A small hole was created in the posterior wall of the stomach and was bluntly dilated. A 5-cm incision was made in the anterior stomach, and the pancreatic drainage tube was passed into the stomach through the hole in the posterior wall. The remnant pancreas was pulled into the stomach, and was easily positioned and secured in place with only four to six sutures between the pancreatic capsule and the gastric mucosa. We used this technique to perform pure LPD in five patients between December 2012 and July 2013.Our new technique is technically easy and provides secure fixation between the gastric wall and the pancreas. This technique does not require main pancreatic duct dilatation, and the risk of intra-abdominal abscess formation due to postoperative pancreatic fistula may be minimized. Although this technique requires further investigation as it may increase the risk of delayed gastric emptying, it may be a useful method of performing pancreaticogastrostomy in pure LPD.ISRCTN16761283 . Registered 16 January 2015.

  View details for DOI 10.1186/s12893-015-0061-x

  View details for Web of Science ID 000357309200001

  View details for PubMedID 26133767

  View details for PubMedCentralID PMC4487839

• Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth BMC MEDICAL IMAGING Ohkura, Y., Sasaki, K., Matsuda, M., Hashimoto, M., Fujii, T., Watanabe, G. 2015; 15: 14

  Abstract

  Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth is extremely rare. Diagnosis of pancreatic cancer on preoperative imaging is difficult when the pancreatic parenchyma is compressed by a pseudocyst and becomes unclear. Despite advances in imaging techniques, accurate preoperative diagnosis of cystic lesions of the pancreas remains difficult. In this case, it was challenging to diagnose pancreatic cancer preoperatively as we could not accurately assess the pancreatic parenchyma, which had been compressed by a moderate-sized cystic lesion with extrapancreatic growth.A 63-year-old woman underwent investigations for epigastric abdominal pain. She had no history of pancreatitis. Although we suspected pancreatic ductal carcinoma with a pancreatic cyst, there was no mass lesion or low-density area suggestive of pancreatic cancer. We did not immediately suspect pancreatic cancer, as development of a moderate-sized cyst with extrapancreatic growth is extremely rare and known tumor markers were not elevated. Therefore, we initially suspected that a massive benign cyst (mucinous cyst neoplasm, serous cyst neoplasm, or intraductal papillary mucinous neoplasm) resulted in stenosis of the main pancreatic duct. We were unable to reach a definitive diagnosis prior to the operation. We had planned a pancreaticoduodenectomy to reach a definitive diagnosis. However, we could not remove the tumor because of significant invasion of the surrounding tissue (portal vein, superior mesenteric vein, etc.). The fluid content of the cyst was serous, and aspiration cytology from the pancreatic cyst was Class III (no malignancy), but the surrounding white connective tissue samples were positive for pancreatic adenocarcinoma on pathological examination during surgery. We repeated imaging (CT, MRI, endoscopic ultrasound, etc.) postoperatively, but there were neither mass lesions nor a low-density area suggestive of pancreatic cancer. In retrospect, we think that the slight pancreatic duct dilation was the only finding suggestive of pancreatic cancer.It is difficult to diagnose pancreatic cancer with pseudocyst preoperatively. If a pancreatic cyst is found in patients who had normal tumor marker levels or no history of pancreatitis, we should always consider the possibility of pancreatic cancer. In such cases, slight pancreatic duct dilation may be a diagnostic clue.

  View details for DOI 10.1186/s12880-015-0055-2

  View details for Web of Science ID 000354351200001

  View details for PubMedID 25948237

  View details for PubMedCentralID PMC4430898

• The Influence of Histological Differentiation Grade on the Outcome of Liver Resection for Hepatocellular Carcinomas 2 cm or Smaller in Size WORLD JOURNAL OF SURGERY Sasaki, K., Matsuda, M., Ohkura, Y., Kawamura, Y., Inoue, M., Hashimoto, M., Ikeda, K., Kumada, H., Watanabe, G. 2015; 39 (5): 1134-1141

  Abstract

  Small hepatocellular carcinomas (HCC) with poorly differentiated components (PDC) are reportedly at risk of dissemination and needle tract seeding after percutaneous radiofrequency ablation, although it is the preferred treatment for HCC ≤ 2 cm because of the low rate of vascular invasion. On the other hand, the clinical outcomes after hepatectomy for these tumors are still unclear because of their rarity.A total of 233 cases of solitary HCC ≤ 2 cm were retrospectively reviewed and divided into two groups according to the presence of PDC: 199 without PDC (NP-HCCs) and 34 with PDC (P-HCCs). The clinicopathological characteristics and prognosis were compared.A comparison of clinicopathological characteristics showed that the elevation of the tumor markers alpha-fetoprotein (AFP) (>20 ng/mL) and des-gamma-carboxyprothrombin (DCP) (>40 AU/L) was significantly frequent in P-HCCs. The 3- and 5-year recurrence-free survival rates for P-HCCS were 39 and 29 %, respectively, which were significantly worse than those for NP-HCCs (64 and 50 %, respectively) (p < 0.01). Initial recurrence of P-HCCs was significantly more frequent, as well as extrahepatic recurrence and advanced recurrence in the early period after the operation. Recurrences with tumor dissemination were observed in 15 % of P-HCCs and 4 % of NP-HCCs (p = 0.03).PDC is present in 15 % of HCC < 2 cm and should be suspected when the both tumor markers are elevated. Moreover, significantly worse post-hepatectomy outcomes such as early advanced recurrence or recurrence with dissemination should be taken into account if PDC is present even in HCCs ≤ 2 cm.

  View details for DOI 10.1007/s00268-014-2806-6

  View details for Web of Science ID 000352083200011

  View details for PubMedID 25287916

• Implication of an extremely high preoperative alpha-fetoprotein value (> 4,000 ng/mL) for the long-term outcomes of hepatectomy for resectable hepatocellular carcinoma SURGERY Sasaki, K., Matsuda, M., Ohkura, Y., Kawamura, Y., Inoue, M., Hashimoto, M., Ikeda, K., Kumada, H., Watanabe, G. 2015; 157 (2): 223-230

  Abstract

  The implication of extremely high preoperative alpha-fetoprotein (AFP) values for the long-term outcomes of hepatectomy for resectable hepatocellular carcinoma (HCC) remains uncertain.A total of 762 hepatectomized HCC patients were divided into 3 groups according to preoperative AFP serum concentrations: 578 patients with AFP <100 ng/mL (low [LAP]), 147 patients with AFP 100-4,000 ng/mL (high [HAP]), and 37 patients with AFP ≥4,000 ng/mL (extremely high [EAP]). The clinicopathologic features and prognosis of the EAP group were compared with those of the other 2 groups to investigate their characteristics and whether the choice of hepatectomy was valid.The EAP group had a greater proportion of younger patients and those with hepatitis B compared with the other 2 groups. Large tumor size, poor histologic differentiation, and microscopic vascular invasion were also more common in the EAP group. The recurrence-free and overall survival rates of the EAP group were worse than those of the LAP group (both P < .01) but were not greatly different from those of the HAP group (P = .65 and P = .80, respectively). When the analysis was limited to solitary HCC cases, both recurrence-free and overall survival rates of EAP were not significantly different from those of LAP (P = .79 and P = .99, respectively).An extremely high AFP level does not provide additional postoperative prognostic implications beyond those provided by a high AFP level. Hepatectomy should be performed without reservation for cases of HCC associated with an extremely high AFP value.

  View details for DOI 10.1016/j.surg.2014.09.010

  View details for Web of Science ID 000348971800007

  View details for PubMedID 25616938

• A Case of Trichilemmal Carcinoma With Distant Metastases in a Kidney Transplantation Patient TRANSPLANTATION PROCEEDINGS Hiramatsu, K., Sasaki, K., Matsuda, M., Hashimoto, M., Eguchi, T., Tomikawa, S., Fujii, T., Watanabe, G. 2015; 47 (1): 155-157

  Abstract

  Transplant recipients receiving immunosuppressants are at a high risk of cancer, especially skin cancer. Trichilemmal carcinoma is comparatively rare compared with other skin cancers. We report here a first case of trichilemmal carcinoma arising in a kidney transplant recipient. A 63-year-old man who had undergone a living donor renal transplantation at the age of 50 years presented with a 15 × 10 mm lesion on his forehead. The pathological diagnosis after resection was trichilemmal carcinoma. Distant metastases involving the lymph nodes, lung, and liver occurred, and the patient died. Given that trichilemmal carcinoma generally has an indolent clinical course and a low metastatic potential, the present case of trichilemmal carcinoma with an aggressive course resulting in distant metastases is rare.

  View details for DOI 10.1016/j.transproceed.2014.10.015

  View details for Web of Science ID 000349499800042

  View details for PubMedID 25645796

• The incidence of multicentric recurrence after liver resection for hepatocellular carcinoma: a matched case-controlled study of hepatocellular carcinoma arising from normal liver and diseased liver Sasaki, K., Matsuda, M., Hashimoto, M., Watanabe, G. ELSEVIER SCIENCE INC. 2014: E46

  View details for DOI 10.1016/j.jamcollsurg.2014.07.506

  View details for Web of Science ID 000361111400101

• Right hepatectomy for giant cavernous hemangioma with diffuse hemangiomatosis around Glisson's capsule WORLD JOURNAL OF GASTROENTEROLOGY Ohkura, Y., Hashimoto, M., Lee, S., Sasaki, K., Matsuda, M., Watanabe, G. 2014; 20 (25): 8312-8316

  Abstract

  Diffuse liver hemangiomatosis with giant cavernous hemangioma in adult is extremely rare. A 35 year-old woman presented to hospital with main complaint of epigastric pain and abdominal fullness. An enhanced computed tomography scan revealed a massive liver tumor in right lobe about 150 mm in size. There was contrast enhancement at the periphery of the mass consistent with a cavernous hemangioma. She underwent right hepatectomy. Histologically, it was diagnosed as a cavernous hemangioma. And also, hemangiomatous lesions were scattered around the Glisson's capsule on the back ground liver. These hemangiomatous lesions were not recognized preoperatively. Even if we couldn't diagnose hemangiomatosis around the main giant hemangioma preoperatively, we need to take enough surgical margins because the giant hemangioma has the potential to have small hemangiomatous lesions around the tumor. We reported right hepatectomy for giant cavernous hemangioma with diffuse hepatic hemangiomatosis without an extrahepatic lesion in an adult.

  View details for DOI 10.3748/wjg.v20.i25.8312

  View details for Web of Science ID 000338520900043

  View details for PubMedID 25009410

  View details for PubMedCentralID PMC4081710

• In Hepatocellular Carcinomas, any Proportion of Poorly Differentiated Components is Associated with Poor Prognosis After Hepatectomy WORLD JOURNAL OF SURGERY Sasaki, K., Matsuda, M., Ohkura, Y., Kawamura, Y., Inoue, M., Hashimoto, M., Ikeda, K., Kumada, H., Watanabe, G. 2014; 38 (5): 1147-1153

  Abstract

  Hepatocellular carcinoma (HCC) often consists of various differentiation components in a single tumor. However, the categorization of histologic grade in hepatectomy for those tumors has not been standardized. Some studies have determined the differentiation grade of the tumor according to its worst component, whereas others have determined it according to its predominant component. The present study aimed to resolve the controversy about whether the worst component or the dominant component determines the nature of the tumor, especially focusing on the presence of a poorly differentiated component (PDC).In total, 427 hepatectomized patients with solitary HCC were divided into three groups, tumors without a PDC (NP), tumors with a PDC but dominantly consisting of non-PDC as poorly contained (PC), and tumors predominantly consisted of a PDC as poorly dominant (PD). PC was compared with PD and NP.Statistical analysis revealed that large tumors and high alpha-fetoprotein level were significantly more frequent in PC than in NP (P < 0.01 and P = 0.04, respectively), although no remarkable difference was observed between PC and PD. Both recurrence-free and overall survival rates were significantly worse in the PC and PD groups than in the NP group (PC vs. NP: P = 0.01 and P < 0.01, PD vs. NP: P < 0.01 and P < 0.01, respectively), but there was no significant difference in these parameters between PC and PD.All HCC, including PDC, should be categorized as poorly differentiated HCC regardless of the predominant differentiation component.

  View details for DOI 10.1007/s00268-013-2374-1

  View details for Web of Science ID 000334437900021

  View details for PubMedID 24305929

• Long-term survival after two surgical resections of peritoneal metastases from hepatocellular carcinoma with an interval of 4 years CLINICAL CASE REPORTS Kitajima, T., Hashimoto, M., Sasaki, K., Matsuda, M., Kuroda, Y., Fujii, T., Watanabe, G. 2014; 2 (2): 37-41

  Abstract

  We propose that surgical resections of peritoneal metastases arising from hepatocellular carcinoma are an option for selected patients with controlled HCC in the liver, and without metastases in other organs, when the complete removal of such metastases can be achieved, especially in the case of patients with normal liver function.

  View details for DOI 10.1002/ccr3.50

  View details for Web of Science ID 000217130000004

  View details for PubMedID 25356240

  View details for PubMedCentralID PMC4184626

• Clinical significance of hepatectomy for primary biliary cirrhosis patients with hepatocellular carcinoma: Report of a single center case series and review of the published work HEPATOLOGY RESEARCH Sasaki, K., Matsuda, M., Ohkura, Y., Kawamura, Y., Inoue, M., Suzuki, Y., Hashimoto, M., Ikeda, K., Kumada, H., Watanabe, G. 2014; 44 (4): 474-480

  Abstract

  Hepatectomy for hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) has seldom been reported, and the clinical significance of this procedure remains unclear, although HCC has often been observed in end-stage PBC patients.To understand the characteristics of hepatectomy on HCC in PBC patients, we examined seven cases at our institute, as well as 22 reported hepatectomy cases in the English-language and Japanese published work. Furthermore, to assess the treatment efficacy of hepatectomy for HCC in PBC patients, we compared these patients with viral hepatitis patients who underwent hepatectomies at our institute during the same period.In the review of 29 cases, more than 70% of the patients were aged over 65 years, and the mean Mayo risk score was low at 5.17. The resected tumors were mainly solitary (79%), and the median maximum tumor size was 37 mm. Approximately two-thirds of the patients met the Milan criteria. In the comparison between the PBC and viral hepatitis cases, there were no differences in the postoperative prognoses, although the tumor size was greater in the PBC cases.Hepatectomy for HCC in selected PBC cases is a feasible and potentially curative treatment option, similar to hepatectomy for HCC in viral hepatitis patients. This procedure is particularly useful for patients with preserved liver function who are not ideal candidates for liver transplantation.

  View details for DOI 10.1111/hepr.12134

  View details for Web of Science ID 000333632700014

  View details for PubMedID 23607898

• Factors associated with early cancer-related death after curative hepatectomy for solitary small hepatocellular carcinoma without macroscopic vascular invasion JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES Sasaki, K., Matsuda, M., Ohkura, Y., Kawamura, Y., Inoue, M., Hashimoto, M., Ikeda, K., Kumada, H., Watanabe, G. 2014; 21 (2): 142-147

  Abstract

  Unexpected early cancer-related death (ECRD) within 2 years due to recurrence after curative hepatectomy for solitary small (<5 cm) hepatocellular carcinoma without macroscopic vascular invasion (SSHCC) is occasionally observed.A total of 415 patients were enrolled (19 patients with ECRD and 396 patients with non-ECRD) to elucidate the risk factors of ECRD after curative hepatectomy for SSHCC. They were initially compared by limiting variables to preoperative factors to reveal predictors that could enable the modification of primary treatment. Subsequently, the same analysis was performed with all variables, including perioperative and histological factors.In the preoperative factors, tumor size > 3 cm and elevation of tumor marker level were independent predictors of ECRD. In the analysis with all variables, excessive intraoperative blood loss, poor differentiation, and microscopic vascular invasion were predictors of ECRD. In the recurrence patterns, 79% of ECRD presented as advanced (four or more lesions) or extra-hepatic recurrence, whereas these accounted for 18% in the non-ECRD.Excessive blood loss during the operation and histopathological findings of microscopic vascular invasion and poor differentiation are predictive factors of cancer-related death within 2 years of a hepatectomy for SSHCC.

  View details for DOI 10.1002/jhbp.13

  View details for Web of Science ID 000329971000012

  View details for PubMedID 23798352

• Hepatectomy for liver abscess caused by stones spilled during laparoscopic cholecystectomy ASIAN JOURNAL OF ENDOSCOPIC SURGERY Hashimoto, M., Sasaki, K., Matsuda, M., Watanabe, G. 2014; 7 (1): 60-62

  Abstract

  An abdominal abscess caused by spilled stones is a serious complication of laparoscopic cholecystectomy that requires drainage or reoperation to remove the scattered stones. Herein, we report the case of a 50-year-old woman, who was on dialysis for renal failure. She underwent major hepatectomy for a liver abscess caused by stones spilled during laparoscopic cholecystectomy.

  View details for DOI 10.1111/ases.12061

  View details for Web of Science ID 000219783800012

  View details for PubMedID 24450346

• Minimum resection margin should be based on tumor size in hepatectomy for hepatocellular carcinoma in hepatoviral infection patients HEPATOLOGY RESEARCH Sasaki, K., Matsuda, M., Ohkura, Y., Kawamura, Y., Hashimoto, M., Ikeda, K., Kumada, H., Watanabe, G. 2013; 43 (12): 1295-1303

  Abstract

  In patients with hepatoviral infection, although a wide resection margin can eradicate the microsatellite lesions around hepatocellular carcinoma (HCC), a large-volume hepatectomy may diminish remaining liver function and become an obstacle for treating recurrent HCC. The optimal width of the resection margin for these patients is still controversial. This study was conducted to investigate the optimal resection margin in hepatectomy for hepatoviral infection patients.We retrospectively investigated the influences of the resection margin status on recurrence patterns and long-term prognosis in a group of 311 HCC patients with hepatoviral infection who had a solitary HCC without perioperative anti-HCC treatment.The resection margin status did not statistically influence the postoperative recurrence-free and overall survival rates (3-year recurrence-free survival of 61.0% vs 55.1%, P = 0.33; 5-year overall survival of 74.9% vs 81.5%, P = 0.77 in without a margin vs with a margin, respectively), although resection without a margin increased the local recurrence with marginal significance (P = 0.055). Regarding the width of the resection margin, in 30-mm or smaller HCC, resection margin did not significantly improve the prognosis among hepatoviral infection patients. However, for tumors larger than 30 mm, a resection margin wider than 3 mm showed significant impacts on the prevention of recurrence in spite of the influence of multicentric carcinogenesis.The resection margin used for eradication of microsatellite lesions showed differences that were dependent on tumor size in hepatoviral infection patients. Resection margin should be based on not only background liver function but also tumor characteristics.

  View details for DOI 10.1111/hepr.12079

  View details for Web of Science ID 000328864000005

  View details for PubMedID 23442021

• Anatomical versus Nonanatomical Resection in Patients with Hepatocellular Carcinoma Located in the Left Lateral Segment AMERICAN SURGEON Sasaki, K., Matsuda, M., Ohkura, Y., Hashimoto, M., Watanabe, G. 2013; 79 (11): 1163-1170

  Abstract

  To date, no reported studies comparing anatomical resection (AR) and nonanatomical resection (NAR) for hepatocellular carcinoma (HCC) have restricted cases by tumor location. Thus, right hepatectomy and left lateral sectionectomy are both analyzed together as AR, whereas limited resection of both peripherally and centrally located liver tumors is categorized as NAR. This categorization may result in inaccurate conclusions in the analyses comparing AR and NAR. We conducted a retrospective comparison between AR (n = 30) and NAR (n = 57) for solitary and small (5 cm or less) HCC limited to the left lateral segment (LLS) to clarify whether AR is superior to NAR for HCC in LLS. The 1-, 3-, and 5-year recurrence-free survival rates were 83.3, 71.3, and 52.9 per cent for the AR group and 82.5, 51.0, and 40.7 per cent for the NAR group, respectively (P = 0.10). The 3-, 5-, and 7-year overall survival rates were 96.0, 82.8, and 77.9 per cent for the AR group and 84.1, 77.0, and 54.2 per cent for the NAR group, respectively (P = 0.07). The postoperative complication, recurrence patterns, and secondary treatment types after recurrence were not significantly different between the two groups. The multivariate analysis including the confounders related to background liver function indicated AR to be a significant protective factor against recurrence, although AR did not influence overall survival. AR was superior to NAR in preventing recurrence without increasing postoperative risks among patients with small solitary HCC limited to the LLS, although AR could not improve overall survival.

  View details for Web of Science ID 000326316600009

  View details for PubMedID 24165251

• Retroperitoneal cavernous hemangioma resected by a pylorus preserving pancreaticoduodenectomy WORLD JOURNAL OF GASTROENTEROLOGY Hanaoka, M., Hashimoto, M., Sasaki, K., Matsuda, M., Fujii, T., Ohashi, K., Watanabe, G. 2013; 19 (28): 4624-4629

  Abstract

  A retroperitoneal hemangioma is a rare disease. We report on the diagnosis and treatment of a retroperitoneal hemangioma which had uncommonly invaded into both the pancreas and duodenum, thus requiring a pylorus preserving pancreaticoduodenectomy (PpPD). A 36-year-old man presented to our hospital with abdominal pain. An enhanced computed tomography scan without contrast enhancement revealed a 12 cm × 9 cm mass between the pancreas head and right kidney. Given the high rate of malignancy associated with retroperitoneal tumors, surgical resection was performed. Intraoperatively, the tumor was inseparable from both the duodenum and pancreas and PpPD was performed due to the invasive behavior. Although malignancy was suspected, pathological diagnosis identified the tumor as a retroperitoneal cavernous hemangioma for which surgical resection was the proper diagnostic and therapeutic procedure. Reteoperitoneal cavernous hemangioma is unique in that it is typically separated from the surrounding organs. However, clinicians need to be aware of the possibility of a case, such as this, which has invaded into the surrounding organs despite its benign etiology. From this case, we recommend that combined resection of inseparable organs should be performed if the mass has invaded into other tissues due to the hazardous nature of local recurrence. In summary, this report is the first to describe a case of retroperitoneal hemangioma that had uniquely invaded into surrounding organs and was treated with PpPD.

  View details for DOI 10.3748/wjg.v19.i28.4624

  View details for Web of Science ID 000322328400023

  View details for PubMedID 23901241

  View details for PubMedCentralID PMC3725390

• Total pancreatectomy for recurrent intraductal papillary mucinous carcinoma in remnant pancreas of pancreaticoduodenectomy for intraductal papillary mucinous adenocarcinoma. BMJ case reports Ohkura, Y., Sasaki, K., Matsuda, M., Hashimoto, M. 2013; 2013

  Abstract

  A 62-year-old man underwent pancreaticoduodenectomy (PD) for intraductal papillary mucinous carcinoma (IPMC) in 2006. No signs of adenocarcinoma at the resection margin were found by intraoperative pathological examination of frozen sections. The postoperative pathological diagnosis was invasive carcinoma derived from IPMC and moderately differentiated tubular adenocarcinoma. A blood analysis in 2011 showed serum (CA19-9) to be increased since the initial resection. Imaging test showed a recurrent tumour at the site of the pancreaticogastrostomy (PG) in the remnant pancreas. We conducted total remnant pancreatectomy for recurrent IPMC and partial gastrectomy. Because both lesions had a histopathological resemblance, the pathological diagnosis was recurrent invasive IPMC. Based on this experience, it is important to facilitate early detection by annual check-up. And also, we recommend PG as a reconstructive intervention in patients at high risk of IPMC recurrence in the remnant pancreas following PD as it is grossly visible on upper gastrointestinal endoscopy.

  View details for DOI 10.1136/bcr-2013-009856

  View details for PubMedID 23709152

• Resection of peritoneal metastases in patients with hepatocellular carcinoma SURGERY Hashimoto, M., Sasaki, K., Moriyama, J., Matsuda, M., Watanabe, G. 2013; 153 (5): 727-731

  Abstract

  Peritoneal metastases from hepatocellular carcinoma are common; they are found in as many as 18% of autopsy cases. Effective treatment for peritoneal metastases, however, has not yet been established.We resected peritoneal metastases 12 times in 9 patients with hepatocellular carcinoma. We assessed the clinical course and outcome of these patients to determine the effectiveness of resecting peritoneal metastases and the factors related to survival.The 1-, 3-, and 5-year survival rates were 58%, 52%, and 42%, respectively. Four patients survived for longer than 2 years without recurrence or with controlled recurrence confined to the liver. Three patients receiving palliative resection had a poor prognosis, with survivals of only 4, 9, and 12 months.Operative resection should be an option for selected patients with peritoneal metastases from hepatocellular carcinoma. Resection of peritoneal metastases should be considered in patients whose primary liver neoplasm is under control and who have no metastases in other organs.

  View details for DOI 10.1016/j.surg.2012.03.031

  View details for Web of Science ID 000318139600018

  View details for PubMedID 22705249

• Complete acute gallbladder torsion diagnosed with abdominal ultrasonography and colour Doppler imaging. BMJ case reports Ohkura, Y., Hashimoto, M., Sasaki, K., Watanabe, G. 2013; 2013

  Abstract

  An 82-year-old woman was admitted to our hospital with a provisional diagnosis of acute cholecystitis. Abdominal ultrasonography and colour Doppler imaging played the most important role in confirming a diagnosis of gallbladder torsion preoperatively, and we decided to treat it laparoscopically. Operative findings showed that gallbladder was rotated 360° counterclockwise around the cystic duct and artery. This was a complete torsion of a gross type I wandering gallbladder. The patient had an uneventful postoperative course and was discharged. Laparoscopic cholecystectomy has recently been recommended for treating gallbladder torsion. Because the gallbladder is typically minimally adherent to the liver bed, cholecystectomy can be performed easily with minimal invasion. Gallbladder torsion is a relatively rare cause of an acute abdomen and is difficult to diagnose preoperatively, but we could diagnose complete, acute gallbladder torsion preoperatively with ultrasonography and colour Doppler imaging in this case, allowing for safe and completely curative laparoscopic cholecystectomy.

  View details for DOI 10.1136/bcr-2012-008460

  View details for PubMedID 23505084

• Single-incision Laparoscopic Cholecystectomy: Comparison Analysis of Feasibility and Safety SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES Sasaki, K., Watanabe, G., Matsuda, M., Hashimoto, M. 2012; 22 (2): 108-113

  Abstract

  To maintain operative safety, patient selection criteria for single-incision laparoscopic cholecystectomy (SILC) are more stringent than that for traditional laparoscopic cholecystectomy (TLC). No other method could demonstrate the same feasibility and safety as TLC because the patient selection criteria were too restrictive for SILC to compare with TLC. In this study, we conducted a comparative study between our original SILC and TLC for demonstrating similar feasibility and safety among patients who had the same selection criteria as that for TLC. A statistical comparison between 114 patients of SILC and 201 patients of TLC was conducted during the same time period. The preoperative patient characteristics for SILC and TLC showed no statistical difference. In the operative result analysis, a significant disadvantage of SILC was the prolongation of operative time by only 15 minutes. The original SILC was as feasible and safe as TLC and virtually scarless cholecystectomy could be performed without any selection criteria. This was performed using only 2 trocars from an umbilical incision and 2 incisionless extracorporeal retraction devices.

  View details for DOI 10.1097/SLE.0b013e3182456e3b

  View details for Web of Science ID 000302771700023

  View details for PubMedID 22487621

• Original single-incision laparoscopic cholecystectomy for acute inflammation of the gallbladder WORLD JOURNAL OF GASTROENTEROLOGY Sasaki, K., Watanabe, G., Matsuda, M., Hashimoto, M. 2012; 18 (9): 944-951

  Abstract

  To investigate the safety and feasibility of our original single-incision laparoscopic cholecystectomy (SILC) for acute inflamed gallbladder (AIG).One hundred and ten consecutive patients underwent original SILC for gallbladder disease without any selection criteria and 15 and 11 of these were diagnosed with acute cholecystitis and acute gallstone cholangitis, respectively. A retrospective review was performed not only between SILC for AIG and non-AIG, but also between SILC for AIG and traditional laparoscopic cholecystectomy (TLC) for AIG in the same period.Comparison between SILC for AIG and non-AIG revealed that the operative time was longer in SILC for AIG (97.5 min vs 85.0 min, P = 0.03). The open conversion rate (2/26 vs 2/84, P = 0.24) and complication rate (1/26 vs 3/84, P = 1.00) showed no differences, but a need for additional trocars was more frequent in SILC for AIG (5/24 vs 3/82, P = 0.01). Comparison between SILC for AIG and TLC for AIG revealed no differences based on statistical analysis.Our original SILC technique was adequately safe and feasible for the treatment of acute cholecystitis and acute gallstone cholangitis.

  View details for DOI 10.3748/wjg.v18.i9.944

  View details for Web of Science ID 000301397000011

  View details for PubMedID 22408354

  View details for PubMedCentralID PMC3297054

• Elevation of Pancreatic Enzymes in Gallbladder Bile Associated with Heterotopic Pancreas. A Case Report and Review of the Literature JOURNAL OF THE PANCREAS Sato, A., Hashimoto, M., Sasaki, K., Matsuda, M., Watanabe, G. 2012; 13 (2): 235-238

  Abstract

  This is the first report associating heterotopic pancreas in the gallbladder and elevated pancreatic enzymes in bile.A 60-year-old woman underwent abdominal ultrasonography at a medical check-up, revealing a nodular protrusion at the neck of the gallbladder. It seemed likely to be a lymph node, but we could not exclude the possibility of gallbladder cancer. In order to make a correct diagnosis, laparoscopic cholecystectomy was successfully performed. Pathological examination revealed heterotopic pancreatic tissue in the gallbladder wall. In addition, we detected elevated levels of amylase and lipase in gallbladder bile.Preoperative diagnosis of heterotopic pancreas in the gallbladder is difficult. However, an increase of pancreatic enzymes in gallbladder bile may potentially play an important role in the occurrence of acalculous cholecystitis and biliary cancer. We need more accumulation of cases to know the true significance of this anomaly.

  View details for Web of Science ID 000213847900030

  View details for PubMedID 22406610

• Living-donor liver transplantation using hyper-reduced graft for a neonatal fulminant hepatic failure PEDIATRICS INTERNATIONAL Sasaki, K., Kasahara, M., Fukuda, A., Kimura, T., Shigeta, T., Tanaka, H., Nakagawa, S., Ito, S., Nakagawa, A. 2011; 53 (2): 247-248

  View details for DOI 10.1111/j.1442-200X.2010.03218.x

  View details for Web of Science ID 000289683100023

  View details for PubMedID 21501310

• Early cystic duct carcinoma of new classification INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS Sasaki, K., Matsuda, M., Hashimoto, M., Harano, T., Fujii, T., Watanabe, G. 2011; 2 (8): 246-249

  Abstract

  Classically defined cystic duct carcinoma is extremely rare owing to its strict diagnostic criteria, which are not suitable in actual clinical settings. Recently, several new classifications of cystic duct carcinoma were reported, which defined it as a tumor with its center located in the cystic duct. On the other hand, the incidence of cystic duct carcinoma, based on the new classifications, is not rare, but all reported cases are advanced.A 77-year-old man with dilatation of the common bile duct, a stricture at the level of the cystic duct junction, and a filling defect of contrast medium into cystic duct in endoscopic retrograde cholangiopancreatography was diagnosed with cystic duct carcinoma. Radical cholecystectomy with bile duct resection was performed. In the resected specimen, we found that a 2 cm tumor whose center was located in the cystic duct and vertically limited to the mucosal layer. Horizontally, the tumor was superficially spread in the gallbladder, which were also limited to the mucosal layer.Here we report a first case of early cystic duct carcinoma diagnosed according to a new classification that had spread superficially into the gallbladder. When treating an early cystic duct carcinoma, it is important to note that even localized carcinoma can potentially invade into adjacent organs or metastasize to regional lymph nodes due to the location of cystic duct.It is suggested that perform radical resection such as cholecystectomy with gallbladder fossa resection, extrahepatic bile duct resection and regional lymphadenectomy is the treatment of choice.

  View details for DOI 10.1016/j.ijscr.2011.08.002

  View details for Web of Science ID 000219456400005

  View details for PubMedID 22096742

  View details for PubMedCentralID PMC3215238

• Living donor liver transplantation for hepatoblastoma with Beckwith-Wiedemann syndrome PEDIATRIC TRANSPLANTATION Sasaki, K., Kasahara, M., Fukuda, A., Shigeta, T., Tanaka, H., Nakagawa, S., Mitsui, K., Harada, R., Nakagawa, A. 2010; 14 (7): E89-E92

  Abstract

  BWS is one of the most well-known somatic overgrowth syndromes, which is characterized by macroglossia, organomegaly, abdominal wall defects, and predisposition to embryonal tumors, such as Wilms' tumor, hepatoblastoma, and adrenocortical carcinoma. We report a case of BWS in a girl with unresectable hepatoblastoma, who received a planned LVDT following neo-adjuvant chemotherapy. This is the first case report of liver transplantation for patients with BWS. Tumor surveillance after transplantation would be necessary to detect possible recurrence of the original disease and development of other malignancies.

  View details for DOI 10.1111/j.1399-3046.2009.01198.x

  View details for Web of Science ID 000283067800003

  View details for PubMedID 19496980

• Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor PEDIATRIC TRANSPLANTATION Shigeta, T., Kasahara, M., Kimura, T., Fukuda, A., Sasaki, K., Arai, K., Nakagawa, A., Nakagawa, S., Kobayashi, K., Soneda, S., Kitagawa, H. 2010; 14 (7): E86-E88

  Abstract

  NICCD is an autosomal recessive genetic disorder, characterized by cholestasis, coagulopathy, hypoglycemia, fatty liver and multiple amino acidemia. NICCD develops in the neonatal/infantile period and has been reported as a "naturally curable" disease within one yr of life. Recently, we experienced an infantile NICCD who developed progressive liver failure, and required subsequent LT using a heterozygote living donor at eight months of age. Diagnosis of NICCD was established before transplantation, and donor evaluation included mutation in the SLC25A13 gene for exclusion of individuals with citrin deficiency citrullinemia. LDLT, from blood type identical mother using a left lateral segment graft, was performed without serious complication. Plasma amino acid concentration was normalized rapidly, and the patient was discharged 30 days after transplant. During one yr follow up, the recipient has been doing well without additional medication for NICCD. NICCD should be considered in the differential diagnosis as a cause of neonatal/infantile cholestatic disease. LT using a heterozygote living donor is an effective alternative in countries where a deceased donor is not available.

  View details for DOI 10.1111/j.1399-3046.2009.01172.x

  View details for Web of Science ID 000283067800002

  View details for PubMedID 19413723

• Original method of transumbilical single-incision laparoscopic deroofing for liver cyst JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES Sasaki, K., Watanabe, G., Matsuda, M., Hashimoto, M., Harano, T. 2010; 17 (5): 733-734

  View details for DOI 10.1007/s00534-010-0279-z

  View details for Web of Science ID 000280845100031

  View details for PubMedID 20703853

• [A case report of advanced gallbladder cancer with multiple liver metastases effectively treated by concentrated therapy with S-1]. Gan to kagaku ryoho. Cancer & chemotherapy Tomizawa, K., Sasaki, K., Matsuda, M., Hashimoto, M., Udagawa, H., Sawada, T., Watanabe, G. 2010; 37 (9): 1779-82

  Abstract

  A 65 -year-old male was admitted to our hospital because of epigastregia. Computed tomography (CT) and abdominal ultrasonography (AUS) revealed advanced gallbladder cancer and two S5 liver metastases. Selective gallbladder angiogram revealed his cystic vein was draining into the portal vein (P5), so cholecystectomy and S4a+S5-subsegmentectomy were performed. Pathological study of the resected specimens showed three liver metastases. After surgical resection lumbar metastasis was suspected, so radiotherapy and UFT at 300mg/day were started. Next, we started oral administration of S-1 alone (100mg/body) for 4 weeks followed by a 2-week rest period as one course. 100mg/day was changed to 80mg/body after 3 courses because of grade 2 neutropenia. A total of 31 courses of S-1 80mg/day were administered postoperatively for five years. The patient is alive and free of disease five years and ten months after the operation.

  View details for PubMedID 20841946

• [Feasibility study of adjuvant chemotherapy with S-1 for pancreatic adenocarcinoma]. Gan to kagaku ryoho. Cancer & chemotherapy Matsuda, M., Watanabe, G., Hashimoto, M., Sasaki, K. 2010; 37 (4): 655-8

  Abstract

  BACKGROUND: The aim of this study was to assess the feasibility of using S-1 as adjuvant chemotherapy after the resection of pancreatic cancer.METHODS: S-1 was initially administered or ally at a dose of 50 mg twice daily for 14 days, followed by a rest period of seven days to complete one course. Administration was repeated with dose escalation in each cycle until the recommended dose (RD; 80 mg/m2, maximum 120 mg/day), unless grade 3 adverse events were observed. Administration was planned to continue at least 6 months (eight courses).RESULTS: Eighteen patients who had undergone resection of pancreatic adenocarcinoma were enrolled in this study. The RD could be administered to 12 patients(67%), and 80% of the RD was given to five patients(28%). Although grade 3 anemia occurred in one patient, grade 4 hematologic adverse events were not observed. Grade 3 cutaneous toxicity (hand-foot syndrome)was observed in two patients. The cumulative relative total administered dose rate of S-1 was 0. 86. The 3-year relapse-free survival rate was 31. 4%, and the median overall survival time was 25. 3 months.CONCLUSIONS: Long-term postoperative administration of S-1 at the RD is safe and appears to be a promising method of adjuvant chemotherapy.

  View details for PubMedID 20414021

• SURGICAL OUTCOME OF LIVING DONOR LIVER TRANSPLANTATION TO NEONATAL/INFANTILE FULMINANT HEPATIC FAILURE Kimura, T., Kasahara, M., Fukuda, A., Shigeta, T., Sasaki, K., Nakagawa, S., Ito, S., Nakagawa, A., Matsui, A. JOHN WILEY & SONS INC. 2009: S104

  View details for Web of Science ID 000267792300109

• Living Donor Liver Transplantation With Vena Cava Reconstruction Using a Cryopreserved Allograft for a Pediatric Patient With Budd-Chiari Syndrome TRANSPLANTATION Sasaki, K., Kasahara, M., Fukuda, A., Shigeta, T., Tanaka, H., Nakagawa, S., Nakagawa, A., Nakayasiro, M. 2009; 87 (2): 304-305

  View details for DOI 10.1097/TP.0b013e3181938b10

  View details for Web of Science ID 000262773600024

  View details for PubMedID 19155990

• Thoracoscopic removal of middle mediastinal schwannoma originating from recurrent nerve THORACIC AND CARDIOVASCULAR SURGEON Sasaki, K., Kohno, T., Mun, M., Yoshiya, T. 2008; 56 (6): 375-377

  Abstract

  Schwannomas of the left recurrent nerve are rare and there is no agreement on how to manage them without causing recurrent nerve dysfunction. We present a 63-year-old male with unspecific clinical symptoms in whom a middle mediastinal mass with a diameter of 5 cm was found incidentally. At thoracoscopic surgery,we found that the encapsulated tumor originated from left recurrent nerve and we performed tumor enucleation without sacrificing the recurrent nerve. The patient did experience postoperative hoarseness and vocal cord paralysis even though we preserved the recurrent nerve. To our knowledge, thoracoscopic removal of a left recurrent nerve schwannoma has not been reported in the literature before.

  View details for DOI 10.1055/s-2008-1038471

  View details for Web of Science ID 000258444800015

  View details for PubMedID 18704866

• Analysis of serum angiogenic factors in a young multiple myeloma patient with high-output cardiac failure INTERNATIONAL JOURNAL OF HEMATOLOGY Sasaki, K., Yamashita, K., Miyoshi, T., Furukawa, Y., Kimura, T., Kita, T., Ichinohe, T., Ishikawa, T., Sasada, M., Uchiyama, T. 2007; 86 (1): 72-76

  Abstract

  Angiogenesis is believed to be involved in the pathogenesis and progression of multiple myeloma (MM). In some young patients, the MM has been reported to be complicated with high-output cardiac failure (HOCF), in which an increase in the vascular bed may be involved in the pathogenesis; however, no throughput studies have been conducted to determine what angiogenic factors are associated with HOCF in MM patients. We experienced a 34-year-old MM patient with HOCF and used the cytokine array system to investigate the expression of angiogenic cytokines and related factors in his serum before and after treatment and to compare the results with those of a healthy volunteer. We treated the patient with chemotherapy in combination with autologous peripheral blood stem cell transplantation. Following the treatment, he showed a good partial response without any signs of cardiac failure. The patient had experienced dramatic increases in the expression levels of angiopoietin 2, insulin-like growth factor-binding protein 6, and glial cell line-derived neurotrophic factor. After treatment, the levels of these factors decreased remarkably in association with an improvement in the patient's clinical condition. We review previous case reports in our discussion of the significance of these findings in the pathogenesis of MM with HOCF.

  View details for DOI 10.1532/IJH97.06226

  View details for Web of Science ID 000249508100014

  View details for PubMedID 17675271