Heimbach, Julie K.

Objectives: Patients with unresectable hilar cholangiocarcinoma (hCCA) may be eligible for curative treatment through liver transplantation (LT). Neoadjuvant protocols often include radiotherapy (RT), however, there is no standard RT approach. The purpose of this study is to characterize practice patterns of RT use before transplantation for hCCA. Methods: A survey was administered to radiation oncologists practicing at LT centers identified through the U.S. Organ Procurement and Transplant Network and the International Cholangiocarcinoma Research Network. The survey consisted of 13 questions regarding RT details as well as approaches to systemic therapy. For cross-regimen comparison, the cumulative RT tumor dose was standardized using the EQD2 method. Results: Twenty-three centers utilizing neoadjuvant therapy for hCCA were identified. Most respondents (96%) use both chemotherapy and RT as part of their protocol. Elective nodal volumes commonly included the portal vein lymph nodes (91%) and celiac artery lymph nodes (70%). After an initial 45 Gy plan, a wide range of sequential boost regimens was used. The median cumulative dose including boosts to the gross disease was 58 Gy (EQD2) with a wide range of 40 to 110 Gy. Five (22%) include brachytherapy as part of their treatment plan. The majority (96%) used concurrent chemotherapy with fluoropyrimidines. Conclusions: These results suggest significant variability of neoadjuvant RT use for hCCA before LT. A wide range of doses and fractionation schemes are utilized with cumulative doses ranging from 40 to 110 Gy (EQD2). A further study evaluating the efficacy and toxicity of these various approaches is warranted to better inform best practices.

AbstractIntroductionIn October 2021, the American Society of Transplantation (AST) hosted a virtual consensus conference aimed at identifying and addressing barriers to the broader, safe expansion of living donor liver transplantation (LDLT) throughout the United States (US).MethodsA multidisciplinary group of LDLT experts convened to address issues related to financial implications on the donor, transplant center crisis management, regulatory and oversight policies, and ethical considerations by assessing the relative significance of issues in preventing LDLT growth, with proposed strategies to overcome barriers.ResultsLiving liver donors endure multiple obstacles including financial instability, loss of job security, and potential morbidity. These concerns, along with other center, state, and federal specific policies can be perceived as significant barriers to expanding LDLT. Donor safety is of paramount importance to the transplant community; however, regulatory and oversight policies aimed at ensuring donor safety can be viewed as ambiguous and complicated leading to time‐consuming evaluations that may deter donor motivation and program expansion.ConclusionTransplant programs need to establish appropriate crisis management plans to mitigate potential negative donor outcomes and ensure program viability and stability. Finally, ethical aspects, including informed consent for high‐risk recipients and use of non‐directed donors, can be perceived as additional barriers to expanding LDLT.

Background. Model for end-stage liver disease (MELD) exception criteria for portopulmonary hypertension (POPH) were created to prioritize patients for liver transplant before POPH progression. Little is known about trends in POPH exception frequency, disease severity, pulmonary hypertension treatment patterns, or outcomes since the POPH MELD exception began. Methods. Using data from the Organ Procurement and Transplantation Network database, we describe the frequency of POPH MELD exceptions between 2006 and 2019, compare baseline patient characteristics, and characterize trends in liver disease and POPH severity‚ as well as POPH treatment and outcomes‚ over time. To facilitate comparison, we divided this 14-y period into 3 “eras” (2006–2010, 2011–2015, and 2016–2019). Results. Between 2006 and 2019, 504 unique POPH MELD exceptions were granted. Both liver disease severity and patient age have increased over time (P = 0.04 and P = 0.006, respectively). Posttreatment hemodynamic values (mean pulmonary arterial pressure and pulmonary vascular resistance) have significantly improved (P < 0.001 and P = 0.008, respectively). Treatment with endothelin receptor antagonists has become more prevalent, whereas use of parenteral therapy and monotherapy regimens has decreased (P < 0.001). Neither waitlist nor liver transplant mortality outcomes have significantly changed over the eras analyzed. Conclusions. In conclusion, 504 patients have received POPH MELD exceptions between 2006 and 2019. Since 2010, nearly all patients granted POPH MELD exceptions have met hemodynamic criteria for POPH. Over time, there has been a trend toward older age and higher MELD scores with significant changes in pulmonary arterial hypertension treatment patterns and an improvement in posttreatment hemodynamics without major change in outcomes.

BackgroundCurative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown.MethodsThe authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004–2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively.ResultsThe proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015–1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33–0.97) and Black patients (aOR, 0.47; 95% CI, 0.28–0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37–1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01–1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24–4.88) experienced worse OS.ConclusionsMore than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA.

Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014–2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P<0.001). Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.

AbstractBackgroundThere are currently no guidelines pertaining to ERAS pathways in living donor hepatectomy.ObjectivesThe aim of this study was to identify whether surgical technique influences immediate and short‐term outcomes after living liver donation surgery.Data sourcesOvid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.MethodsSystematic review and meta‐analysis following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel (CRD42021260707). Endpoints were mortality, overall complications, serious complications, bile eaks, pulmonary complications, estimated blood loss and length of stay.ResultsOf the 2410 screened articles, 21 articles were included for final analysis; three observational, 13 retrospective cohort, four prospective cohort studies, and one randomized trial. Overall complications were higher with right versus left hepatectomy (26.8% vs. 20.8%; OR 1.4, P = .010). Donors after left hepatectomy had shorter length of stay (MD 1.4 days) compared to right hepatectomy. There was no difference in outcomes after right donor hepatectomy with versus without middle hepatic vein. We had limited data on the influence of incision type and minimally invasive approaches on living donor outcomes, and no data on the effect of operative time on donor outcomes.ConclusionsLeft donor hepatectomy should be preferred over right hepatectomy, as it is related to improved donor short‐term outcomes (QOE; Moderate | Grade of Recommendation; Strong). Right donor hepatectomy with or without MHV has equivalent outcomes (QOE; Moderate | Grade of Recommendation; Strong); no preference is recommended, decision should be based on program's experience and expertise. No difference in outcomes was observed related to incision type, minimally invasive vs. open (QOE; Low | Grade of Recommendation; Weak); no preference can be recommended.

AbstractBackgroundMalnutrition is a known risk factor for postoperative morbidity and mortality in patients awaiting liver transplantation (LT). Malnutrition is a potentially reversible risk factor, though there are no clear guidelines on the best mechanism for an improvement. It also remains unclear if preoperative nutritional interventions have benefits to post‐transplant outcomes for transplant recipients.ObjectivesPrimary objective: To identify if preoperative optimization of nutritional status is associated with improved short‐term outcomes after LT. Secondary Objectives: To determine if preoperative improvement of malnutrition improves short‐term outcomes after LT, as well as if weight loss in obese patients affects short‐term outcomes after LT.Data sourcesOvid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.MethodsSystematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. POSPERO Protocol ID: CRD42021237450Results3851 records were identified in searching the databases, 3843 records were excluded by not fulfilling eligibility criteria. Seven full‐text articles were included for the final analysis of which three were randomized controlled trials, one was prospective observational studies, and three were retrospective observational studies. No appreciable difference in mortality, post‐transplant complication rate was noted across the studies. Length of stay (LOS) was noted to be shorter in two observational studies of Vitamin D deficiency in liver transplant patients.ConclusionsWe have made a weak recommendation supporting pre‐transplant nutritional supplementation due to possible benefit in reducing LOS as well as the lack of harm (Quality of Evidence low | Grade of Recommendation; Weak). No effective conclusions were reached for the secondary objectives due to the conflicting evidence.