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Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors

Dageforde, Leigh Anne; Vachharajani, Neeta; Tabrizian, Parissa; Agopian, Vatche; Halazun, Karim; Maynard, Erin; Croome, Kristopher; Nagorney, David; Hong, Johnny C; Lee, David; Ferrone, Cristina; Baker, Erin; Jarnagin, William; Hemming, Alan; Schnickel, Gabriel; Kimura, Shoko; Busuttil, Ronald; Lindemann, Jessica; Florman, Sander; Holzner, Matthew L; Srouji, Rami; Najjar, Marc; Yohanathan, Lavanya; Cheng, Jane; Amin, Hiral; Rickert, Charles A; Yang, Ju Dong; Kim, Joohyun; Pasko, Jennifer; Chapman, William C; Majella Doyle, Maria B
BACKGROUND:Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA. STUDY DESIGN:Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis. RESULTS:Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001). CONCLUSIONS:Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.
PMID: 33316425
ISSN: 1879-1190
CID: 5143552

RAPID-ly Increasing the Availability of Livers? [Comment]

Halazun, Karim J
PMID: 33142036
ISSN: 1527-6473
CID: 5143532

SARS-CoV-2 infection increases tacrolimus concentrations in solid-organ transplant recipients [Letter]

Salerno, David M; Kovac, Danielle; Corbo, Heather; Jennings, Douglas L; Lee, Jennifer; Choe, Jason; Scheffert, Jenna; Hedvat, Jessica; Chen, Justin; Tsapepas, Demetra; Rosenblatt, Russell; Samstein, Benjamin; Halazun, Karim; Verna, Elizabeth; Pereira, Marcus; Brennan, Corey; Husain, Syed A; Mohan, Sumit; Brown, Robert S
PMCID:7883259
PMID: 33336440
ISSN: 1399-0012
CID: 5143562

Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria

Kardashian, Ani; Florman, Sander S; Haydel, Brandy; Ruiz, Richard M; Klintmalm, Goran B; Lee, David D; Taner, C Burcin; Aucejo, Federico; Tevar, Amit D; Humar, Abhinav; Verna, Elizabeth C; Halazun, Karim J; Chapman, William C; Vachharajani, Neeta; Hoteit, Maarouf; Levine, Matthew H; Nguyen, Mindie H; Melcher, Marc L; Langnas, Alan N; Carney, Carol A; Mobley, Constance; Ghobrial, Mark; Amundsen, Beth; Markmann, James F; Sudan, Debra L; Jones, Christopher M; Berumen, Jennifer; Hemming, Alan W; Hong, Johnny C; Kim, Joohyun; Zimmerman, Michael A; Nydam, Trevor L; Rana, Abbas; Kueht, Michael L; Fishbein, Thomas M; Markovic, Daniela; Busuttil, Ronald W; Agopian, Vatche G
BACKGROUND AND AIMS:The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013). APPROACH AND RESULTS:Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001). CONCLUSIONS:In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.
PMID: 32124453
ISSN: 1527-3350
CID: 5143442

Living Donor Liver Transplant: Send in the Robots [Comment]

Halazun, Karim J; Samstein, Benjamin
PMID: 32890445
ISSN: 1527-6473
CID: 5143522

Ex Vivo Resection and Autotransplantation for Conventionally Unresectable Tumors - An 11-year Single Center Experience

Kato, Tomoaki; Hwang, Regina; Liou, Peter; Weiner, Joshua; Griesemer, Adam; Samstein, Benjamin; Halazun, Karim; Mathur, Abhishek; Schwartz, Gary; Cherqui, Daniel; Emond, Jean
BACKGROUND AND AIMS:Ex vivo surgery may provide a chance at R0 resection for conventionally unresectable tumors. However, long-term outcomes have not been well documented. In this study, we analyze our 11-year outcomes to define its role. STUDY DESIGN:We retrospectively analyzed 46 consecutive patients who underwent ex vivo surgery at our institution 2008-2019. RESULTS:The types of tumors were: carcinoma (n = 20), sarcoma (n = 20) and benign to low grade tumor (n = 6). The type of ex vivo surgery was chosen based on tumor location and vascular involvement. The most commonly performed procedure was ex vivo hepatectomy (n = 18), followed by ex vivo resection and intestinal autotransplantation (n = 12), ex vivo Whipple procedure and liver autotransplantation (n = 8) and multivisceral ex vivo procedure (n = 7). Twenty-three patients (50%) are currently alive with median follow-up of 4.0-years (11 months-11.8 years). The overall survival was 70%/59%/52%, at 1-/3-/5-years, respectively. Patient survival for benign to low grade tumors, sarcoma, and carcinoma was 100%/100%/100%, 65%/60%/50%, and 65%/45%/40%, at 1-/3-/5-years, respectively. Ninety-one percent patients had R0 resection, and 57% had no recurrence to date with median follow-up of 3.1-years. Two patients (4.3%) died within 30 days due to sepsis and gastroduodenal artety (GDA) stump blowout. Two additional patients died between 30 and 90 days due to sepsis. Perioperative mortality in the last 23 consecutive cases was limited to 1 patient who died of sepsis between 30 and 90 days. CONCLUSIONS:For a selected group of patients with conventionally unresectable tumors, ex vivo surgery can offer effective surgical removal with a reasonably low perioperative mortality at experienced centers.
PMID: 32833756
ISSN: 1528-1140
CID: 5143512

Liver transplantation and hepatobiliary surgery in 2020 [Editorial]

Ekser, Burcin; Halazun, Karim J; Petrowsky, Henrik; Balci, Deniz
PMCID:7369005
PMID: 32698032
ISSN: 1743-9159
CID: 5143502

Robotic liver resection: Hurdles and beyond [Editorial]

Di Benedetto, Fabrizio; Petrowsky, Henrik; Magistri, Paolo; Halazun, Karim J
Laparoscopy is currently considered the standard of care for certain procedures such as left-lateral sectionectomies and wedge resections of anterior segments. The role of robotic liver surgery is still under debate, especially with regards to oncological outcomes. The purpose of this review is to describe how the field of robotic liver surgery has expanded, and to identify current limitations and future perspectives of the technology. Available evidences suggest that oncologic results after robotic liver resection are comparable to open and laparoscopic approaches for hepatocellular carcinoma and colorectal liver metastases, with identifiable advantages for cirrhotic patients and patients undergoing repeat resections. Excellent outcomes and optimal patient safety can be only achieved with specific hepato-biliary and general minimally invasive training to overcome the learning curve.
PMID: 32504813
ISSN: 1743-9159
CID: 5143492

An international multicenter study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise

Chew, Claire Alexandra; Iyer, Shridhar Ganpathi; Kow, Alfred Wei Chieh; Madhavan, Krishnakumar; Wong, Andrea Sze Teng; Halazun, Karim J; Battula, Narendra; Scalera, Irene; Angelico, Roberta; Farid, Shahid; Buchholz, Bettina M; Rotellar, Fernando; Chan, Albert Chi-Yan; Kim, Jong Man; Wang, Chih-Chi; Pitchaimuthu, Maheswaran; Reddy, Mettu Srinivas; Soin, Arvinder Singh; Derosas, Carlos; Imventarza, Oscar; Isaac, John; Muiesan, Paolo; Mirza, Darius F; Bonney, Glenn Kunnath
BACKGROUND & AIMS:The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS:We performed an international multicenter study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the quadripartite equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS:Seventeen large- and medium-sized liver transplant centers from 12 countries across 4 continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a "sickest-first" approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - recipient outcome, donor/graft safety, waiting list mortality and healthcare resources - for 7 countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS:This four-dimensional model of quadripartite equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems. LAY SUMMARY:There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources during the COVID-19 pandemic. We describe a four-dimensional model of quadripartite equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems.
PMCID:7245234
PMID: 32454041
ISSN: 1600-0641
CID: 5143482

Expanding the donor pool for liver transplantation with marginal donors [Editorial]

Goldaracena, Nicolas; Cullen, J Michael; Kim, Dong-Sik; Ekser, Burcin; Halazun, Karim J
The current supply of acceptable donor livers is not sufficient to meet the demands of listed patients awaiting transplantation resulting in thousands of deaths each year. Increased utilization of marginal livers may help alleviate this supply/demand mismatch by expanding the donor liver pool. The current status of liver transplantation using marginal donor grafts and efforts to optimize usage are discussed with attention to elderly donors, steatotic livers, donors after circulatory death, and split liver grafts.
PMID: 32422385
ISSN: 1743-9159
CID: 5143472