Faculty Bibliography

BACKGROUND:Minimally invasive liver surgery (MILS) is superior to open surgery when considering decreased blood loss, fewer complications, shorter hospital stay, and similar or improved oncologic outcomes. However, operative limitations in laparoscopic hepatectomy have curved its applicability and momentum of complex minimally invasive liver surgery. Transitioning to robotic hepatectomy may bridge this complexity gap. METHODS:Retrospective cohort study conducted on comparable hepatectomies (open, laparoscopic, robotic) for benign or malignant diseases at Weill Cornell by three surgeons from 2017 to 2023. Case volume and Iwate difficulty scoring were examined over time by surgical approach. Outcome associations (operative time, estimated blood loss, length of stay, 90-day complications, open conversion, and resection margin) were analyzed using generalized estimating equations to account for the hierarchical data structure of different surgeons and controlled for clinical covariates. RESULTS:Among 353 hepatectomies, 112 were open (OH), 107 were laparoscopic (LH), and 134 were robotic (RH). OH patients were more likely to have malignant pathology (83% vs. LH 69%, RH 57%) and less likely to have cirrhosis (6% vs. LH 6%, RH 14%). OH and RH had similar case complexity (Median Iwate: OH 7 vs. RH 7). After adjustments, LH and RH had 39% and 43% shorter median lengths of stay, respectively, and 89% and 62% lower odds of complications compared to OH. RH had 87% lower odds of conversion to OH compared to LH. The odds of R0 resection were similar between LH, RH, and OH. These results remained consistent in high difficulty cases (Iwate 7-12). Over the study period, RH usage increased from 36 to 68%, while LH decreased from 39 to 9%. By 2023, RH was predominantly used over OH (74% vs.26%). CONCLUSION/CONCLUSIONS:The transition from laparoscopic to all-robotic approach resulted in increased case volume and complexity in MILS, largely improving perioperative outcomes in hepatectomy.

BACKGROUND:In the current "sickest first" allocation policy for limited deceased liver grafts, identifying patients "too sick to transplant" before transplantation is crucial to optimize outcomes. This study aimed to predict futile outcomes following deceased donor liver transplantation (DDLT) in patients with Model for End-Stage Liver Disease-Sodium (MELD-Na) scores ≥30. METHODS:This international multicenter study was conducted as part of the International Society of Liver Surgeons. We collected data from patients with a MELD-Na score ≥30 who underwent DDLT. A total of 994 patients were enrolled between 2010-2021, including 654 from the Republic of Korea, 224 from the US, and 116 from other regions. Futility was defined as death within three months or during the hospital stay following a DDLT. After exclusion, 160 (16.6%) patients were classified into a futile group and 803 (83.4%) into a non-futile group. RESULTS:The MELD-Na scores collected at three time points (listing, matching, and transplantation) were comparable between the groups (P = 0.442, P = 0.180, and P = 0.554, respectively). Regarding concomitant organ failure factors, the futile group showed a higher incidence of organ dysfunction across all measured parameters, including the use of mechanical ventilators, continuous renal replacement therapy (CRRT), pneumonia, bacteremia, and vasopressor use (all P<0.01). Independent risk factors for futile outcome were recipient age (≥65 years), body mass index (<18.5 kg/m2), mechanical ventilator use, CRRT (≥1 week), and prolonged ICU stay before transplantation (≥2 weeks). The futility rate was 53.3% in patients with ≥3 risk factors (P<0.001). We developed a nomogram to predict futility after DDLT based on multivariate regression analysis, which showed a better predictive power than previous models. CONCLUSIONS:The risk factors and new nomogram, which adequately reflect concomitant organ failure before liver transplantation, could effectively predict the risk of futile outcomes after DDLT and contribute to decision-making regarding transplantation eligibility in clinical practice.

BACKGROUND:Since February 2020, exception points have been allocated equivalent to the median model for end-stage liver disease at transplant within 250 nautical miles of the transplant center (MMaT/250). We compared transplant rate and waitlist mortality for hepatocellular carcinoma (HCC) exception, non-HCC exception, and non-exception candidates to determine whether MMaT/250 advantages (or disadvantages) exception candidates. METHODS:Using Scientific Registry of Transplant Recipients data, we identified 23 686 adult, first-time, active, deceased donor liver transplant (DDLT) candidates between February 4, 2020, and February 3, 2022. We compared DDLT rates using Cox regression, and waitlist mortality/dropout using competing risks regression in non-exception versus HCC versus non-HCC candidates. RESULTS:Within 24 mo of study entry, 58.4% of non-exception candidates received DDLT, compared with 57.8% for HCC candidates and 70.5% for non-HCC candidates. After adjustment, HCC candidates had 27% lower DDLT rate (adjusted hazard ratio = 0.680.730.77) compared with non-exception candidates. However, waitlist mortality for HCC was comparable to non-exception candidates (adjusted subhazard ratio [asHR] = 0.931.031.15). Non-HCC candidates with pulmonary complications of cirrhosis or cholangiocarcinoma had substantially higher risk of waitlist mortality compared with non-exception candidates (asHR = 1.271.702.29 for pulmonary complications of cirrhosis, 1.352.043.07 for cholangiocarcinoma). The same was not true of non-HCC candidates with exceptions for other reasons (asHR = 0.540.881.44). CONCLUSIONS:Under MMaT/250, HCC, and non-exception candidates have comparable risks of dying before receiving liver transplant, despite lower transplant rates for HCC. However, non-HCC candidates with pulmonary complications of cirrhosis or cholangiocarcinoma have substantially higher risk of dying before receiving liver transplant; these candidates may merit increased allocation priority.

With the increasing incidence of hepatocellular carcinoma (HCC) in both the United States and globally, the role of liver transplantation in management continues to be an area of active conversation as it is often considered the gold standard in the treatment of HCC. The use of living donor liver transplantation (LDLT) and the indications in the setting of malignancy, both generally and in HCC specifically, are frequently debated. In terms of both overall survival and recurrence-free survival, LDLT is at least equivalent to DDLT, especially when performed for disease within Milan criteria. Emerging and compelling evidence suggests that LDLT is superior to DDLT in treating HCC as there is a significant decrease in waitlist mortality. As the oncologic indications for liver transplantation continue to expand and the gap between organ demand and organ availability continues to worsen, high volumes centers should consider using LDLT to shrink the ever-expanding waitlist.

INTRODUCTION/BACKGROUND:Minimally invasive liver resection (MILR) is performed for other gastrointestinal applications. At our centre, all liver resections are systematically performed using a minimally invasive approach. This study aimed to describe our experience in minimising open surgery and emphasised the importance of minimally invasive surgery. PATIENTS AND METHODS/METHODS:We retrospectively reviewed 260 patients who underwent liver surgery and compared the surgical outcomes between the open and MILR groups. RESULTS:A total of 154 patients (68%) underwent MILR. The proportion of patients who underwent prior abdominal surgery and resection was higher in the open surgery group. However, the proportion of patients with liver cirrhosis was similar between the two groups. The MILR group was superior in terms of operative time, blood loss, Pringle manoeuvre rate and mean hospital stay. In addition, major complication and bile leak rates were lower in the MILR group. No significant differences in the tumour size, number of lesions or underlying liver pathology were observed between the two groups. CONCLUSION/CONCLUSIONS:Acceptable outcomes can be achieved even when the minimally invasive approach is considered the primary option for all patients who require liver resection. Minimally invasive tools are necessary for the modern practice of liver surgery; therefore, laparoscopic or robotic surgery should be included in the armamentarium of liver surgeons.

BACKGROUND:Recurrence of intrahepatic cholangiocarcinoma (ICC) after liver resection (LR) remains high, and optimal therapy for recurrent ICC is challenging. Herein, we assess the outcomes of patients undergoing repeat resection for recurrent ICC in a large, international multicenter cohort. PATIENTS AND METHODS/METHODS:Outcomes of adults from six large hepatobiliary centers in North America, Europe, and Asia with recurrent ICC following primary LR between 2001 and 2015 were analyzed. Cox models determined predictors of post-recurrence survival. RESULTS:Of patients undergoing LR for ICC, 499 developed recurrence. The median time to recurrence was 10 months, and 47% were intrahepatic. Overall 3-year post-recurrence survival rate was 28.6%. In total, 121 patients (25%) underwent repeat resection, including 74 (61%) repeat LRs. Surgically treated patients were more likely to have solitary intrahepatic recurrences and significantly prolonged survival compared with those receiving locoregional or systemic therapy alone with a 3-year post-recurrence survival rate of 47%. Independent predictors of post-recurrence death included time to recurrence < 1 year [HR 1.66 (1.32-2.10), p < 0.001], site of recurrence [HR 1.74 (1.28-2.38), p < 0.001], macrovascular invasion [HR 1.43 (1.05-1.95), p = 0.024], and size of recurrence > 3 cm [HR 1.68 (1.24-2.29), p = 0.001]. Repeat resection was independently associated with decreased post-recurrence death [HR 0.58 0.43-0.78), p < 0.001]. CONCLUSIONS:Repeat resection for recurrent ICC in select patients can result in extended survival. Thus, challenging the paradigm of offering these patients locoregional or chemo/palliative therapy alone as the mainstay of treatment.

OBJECTIVE:To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND:LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS:Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS:Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival 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-year 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.

IMPORTANCE/UNASSIGNED:Long-term oncologic outcomes of robotic surgery remain a hotly debated topic in surgical oncology, but sparse data have been published thus far. OBJECTIVE/UNASSIGNED:To analyze short- and long-term outcomes of robotic liver resection (RLR) for hepatocellular carcinoma (HCC) from Western high-volume centers to assess the safety, reproducibility, and oncologic efficacy of this technique. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study evaluated the outcomes of patients receiving RLR vs open liver resection (OLR) for HCC between 2010 and 2020 in 5 high-volume centers. After 1:1 propensity score matching, a group of patients who underwent RLR was compared with a validation cohort of OLR patients from a high-volume center that did not perform RLR. MAIN OUTCOMES AND MEASURES/UNASSIGNED:A retrospective analysis was performed of prospectively maintained databases at 2 European and 2 US institutions of patients who underwent RLR for HCC between January 1, 2010, and September 30, 2020. The main outcomes were safety and feasibility of RLR for HCC and its oncologic outcomes compared with a European OLR validation cohort. A 2-sided P < .05 was considered significant. RESULTS/UNASSIGNED:The study included 398 patients (RLR group: 125 men, 33 women, median [IQR] age, 66 [58-71] years; OLR group: 315 men, 83 women; median [IQR] age, 70 [64-74] years), and 106 RLR patients were compared with 106 OLR patients after propensity score matching. The RLR patients had a significantly longer operative time (median [IQR], 295 [190-370] minutes vs 200 [165-255] minutes, including docking; P < .001) but a significantly shorter hospital length of stay (median [IQR], 4 [3-6] days vs 10 [7-13] days; P < .001) and a lower number of admissions to the intensive care unit (7 [6.6%] vs 21 [19.8%]; P = .002). Incidence of posthepatectomy liver failure was significantly lower in the RLR group (8 [7.5%] vs 30 [28.3%]; P = .001), with no cases of grade C failure. The 90-day overall survival rate was comparable between the 2 groups (RLR, 99.1% [95% CI, 93.5%-99.9%]; OLR, 97.1% [95% CI, 91.3%-99.1%]), as was the cumulative incidence of death related to tumor recurrence (RLR, 8.8% [95% CI, 3.1%-18.3%]; OLR, 10.2% [95% CI, 4.9%-17.7%]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study represents the largest Western experience to date of full RLR for HCC. Compared with OLR, RLR performed in tertiary centers represents a safe treatment strategy for patients with HCC and those with compromised liver function while achieving oncologic efficacy.

Despite a documented survival benefit, older liver donor (OLD, age ≥70) graft offers are frequently declined, with utilization worsening over the last decade. To understand how offer acceptance varies by center, we studied 1113 eventually transplanted OLD grafts from 2009 to 2017 using Scientific Registry of Transplant Recipients (SRTR) data and random-intercept multilevel logistic regression. To understand how center-level acceptance of OLD graft offers might be associated with waitlist and posttransplant outcomes, we studied all adult, actively listed, liver-only candidates and recipients during the study period using Poisson regression (transplant rate), competing risks regression (waitlist mortality), and Cox regression (posttransplant mortality). Among 117 centers, OLD offer acceptance ranged from 0 (23 centers) to 95 acceptances, with a median odds ratio of 2.88. Thus, a candidate may be three times as likely to receive an OLD graft simply by listing at a different center. Centers in the highest quartile (Q4) of OLD acceptance (accepted 39% of OLD offers) accepted more nationally shared organs (Q4 versus Q1: 14.1% versus 0.0%, P < 0.001) and had higher annual liver transplant volume (Q4 versus Q1: 80 versus 21, P < 0.001). After adjustment, nationally shared OLD offers (adjusted odds ratio [aOR]: 0.16, 95% confidence interval [CI]: 0.13-0.20) and offers to centers with higher median Model for End-Stage Liver Disease (MELD) at transplant (aOR: 0.74, 95% CI: 0.62-0.87) were less likely to be accepted. OLD offers to centers with higher annual transplant volume were more likely to be accepted (aOR: 1.21, 95% CI: 1.14-1.30). Additionally, candidates listed at centers within the highest quartile of OLD graft offer acceptance had higher deceased donor liver transplantation (DDLT) rates (adjusted incidence rate ratio: 1.45, 95% CI: 1.41-1.50), lower waitlist mortality (adjusted subhazard ratio: 0.76, 95% CI: 0.72-0.76), and similar posttransplant survival (adjusted hazard ratio: 0.93, 95% CI: 0.86-1.01) when compared with those listed at centers in the lowest quartile of OLD graft offer acceptance. The wide variation in OLD offer acceptance supports the need for optimizing the organ offer process and efficiently directing OLD offers to centers more likely to use them.

Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease.