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Purpose: To investigate the safety and efficacy of percutaneous or open irreversible electroporation (IRE) in a prospective cohort of patients with locally advanced, unresectable perihilar cholangiocarcinoma (PHC)., Materials and Methods: In a multicenter Phase I/II study, patients with unresectable PHC due to extensive vascular involvement or N2 lymph node metastases or local recurrence after resection for PHC were included and treated by open or percutaneous IRE combined with palliative chemotherapy (current standard of care). The primary outcome was the number of major adverse events occurring within 90 d after IRE (grade ≥3), and the upper limit was predefined at 60%. Secondary outcomes included technical success rate, hospital stay, and overall survival (OS)., Results: Twelve patients (mean age, 63 y ± 12) were treated with IRE. The major adverse event rate was 50% (6 of 12 patients), and no 90-d mortality was observed. All procedures were technically successful, with no intraprocedural adverse events requiring additional interventions. The median OS from diagnosis was 21 mos (95% confidence interval, 15-27 mos), with a 1-y survival rate of 75% after IRE., Conclusions: Percutaneous IRE in selected patients with locally advanced PHC seems feasible, with a major adverse event rate of 50%, which was below the predefined upper safety limit in this prospective study. Future comparative research exploring the efficacy of IRE is warranted., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Standard portal vein resection (PVR) has been proposed to improve oncological outcomes in patients with perihilar cholangiocarcinoma (PHC), however it potentially introduces an increased risk of morbidity. The policy in Amsterdam UMC(AMC) is to resect the portal vein bifurcation selectively when involved, while in Charité-Universitätsmedizin Berlin, standard PVR is performed with right trisectionectomy. The objective of this study was to analyze postoperative outcomes and survival after standard or selective PVR for PHC., Methods: A retrospective study was performed including PHC-patients undergoing right-sided resection in Amsterdam (2000-2018) and Berlin (2005-2015). Primary outcomes were 90-day mortality, severe morbidity (Clavien-Dindo≥3), and overall survival (OS). A propensity score comparison (1:1 ratio) was performed corrected for age/sex/ASA/jaundice/tumor diameter/N-stage/Bismuth-Corlette type-IV., Results: A total of 251 patients who underwent right-sided resection for PHC were evaluated: 87 in the selective (Amsterdam) and 164 in the standard PVR-group (Berlin). Major differences in baseline characteristics were observed, with higher ASA and AJCC-stage in the standard PVR-group (Berlin). Severe morbidity and 90-day mortality were comparable before matching (selective/Amsterdam:68% and 19%, standard/Berlin:61% and 17%,p = 0.284 and p = 0.746, respectively). After propensity score matching, both short term outcomes and OS were comparable (selective/Amsterdam (n = 45) 33 months (95%CI:20-45), standard/Berlin (n = 45) 31 months (95%CI:24-38,p = 0.747))., Conclusion: In this combined cohort, standard PVR was not associated with increased severe morbidity or mortality. After propensity score matching, survival was comparable after selective (Amsterdam) and standard PVR (Berlin)., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: In this retrospective cohort study, the potential of gemcitabine (gem)/cisplatin (cis) chemotherapy as future preoperative therapy for patients with unresectable locally advanced or borderline resectable intrahepatic, perihilar, and mid-cholangiocarcinoma was investigated., Methods: All patients with intrahepatic, perihilar, and mid-cholangiocarcinoma presented at Amsterdam UMC between January 2016 and October 2019 were included. The radiologic response after 3 and/or 6 cycles of gem/cis chemotherapy in patients with unresectable locally advanced or borderline resectable disease was derived from the original radiologic reports and subsequently re-evaluated for surgical exploration by consensus reading of 2 HPB surgeons and 1 radiologist., Results: Overall, 65 of 364 patients had a locally advanced or borderline resectable disease. Twenty-eight patients were treated with palliative chemotherapy, including 25 (89.3%) patients who received more than 3 cycles. Twenty-two patients (88.0%) and 13 patients (46.4%) showed RECIST stable disease or partial response after 3 and 6 cycles of chemotherapy, respectively. Three patients experienced grade 3 adverse events. Consensus reading concluded that exploration could have been reconsidered in 7 of 28 patients (25.0%)., Conclusion: Gem/cis may be a safe and feasible preoperative treatment in initially unresectable locally advanced or borderline resectable cholangiocarcinoma. In addition, the findings of this study support to always rediscuss patients with stable or responsive disease in multidisciplinary team meetings to reconsider resection. Besides, prospective studies are needed to investigate this effect further and, based on these preliminary data, seem feasible in this setting., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Liver transplantation (LT) has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma (pCCA) in the Mayo Clinic with a reported 5-year overall survival (OS) of 53% on intention-to-treat analysis. The objective of this study was to estimate eligibility for LT in a cohort of pCCA patients in two tertiary referral centers., Methods: Patients diagnosed with pCCA between 2002 and 2014 were included from two tertiary referral centers in the Netherlands. The selection criteria used by the Mayo Clinic were retrospectively applied to determine the proportion of patients that would have been eligible for LT., Results: A total of 732 consecutive patients with pCCA were identified, of whom 24 (4%) had PSC-associated pCCA. Overall, 154 patients had resectable disease on imaging and 335 patients were ineligible for LT because of lymph node or distant metastases. An age limit of 70 years led to the exclusion of 50 patients who would otherwise be eligible for LT. After applying the Mayo Clinic criteria, only 34 patients (5%) were potentially eligible for LT. Median survival from diagnosis for these 34 patients was 13 months (95% CI 3-23)., Conclusion: Only 5% of all patients presenting with pCCA were potentially eligible for LT under the Mayo criteria. Without transplantation, a median OS of about 1 year was observed.

Background: According to international guidelines, induction therapy may be considered in selected patients with initially unresectable locally advanced cholangiocarcinoma. The criteria for (un)resectability in cholangiocarcinoma varies between studies and no consensus-based agreement is available about these criteria. By performing a systematic literature review, we aimed to investigate the efficacy and safety of systemic induction therapy in initially unresectable locally advanced perihilar (pCCA) and intrahepatic cholangiocarcinoma (iCCA) and summarize resectability criteria used across studies., Methods: A literature search was performed in PubMed, EMBASE, Web of Science and Cochrane library to identify studies on systemic induction therapy in locally advanced pCCA and/or iCCA. The primary outcome was resection rate (RR) after induction therapy and secondary outcomes were overall survival (OS) and objective response rate (ORR)., Results: Ten studies with a total of 1167 patients met the inclusion criteria and were included in this review. Among these patients, 334 (28.6%) were treated with systemic induction therapy. Across the studies, different types of chemotherapy regimens were administered (e.g., gemcitabine (based) chemotherapy and 5-FU (based) chemotherapy). Only six studies provided sufficient data and were used to analyze pooled (radical) resection rates. After induction therapy, 94 patients (39.2%) underwent a resection, of which R0 resections (22.9%). Pooled data on OS showed, better OS for chemotherapy plus resection versus chemotherapy only (pooled HR = 0.31, 95% CI = 0.19-0.50; P value < 0.0001)., Conclusion: Adequately selected patients with locally advanced pCCA or iCCA may benefit from induction therapy followed by surgical resection. Prospective randomized controlled trials are warranted., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers., Method: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed., Results: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival., Conclusion: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Outcomes for the four anatomical subtypes of biliary tract carcinoma (BTC) - intrahepatic, perihilar and distal cholangiocarcinoma (ICC, PHCC, DCC) and gallbladder carcinoma (GBC) - are often combined. However, large cohorts comparing short- and long-term outcomes for the anatomical subtypes of BTC are lacking., Methods: All patients who underwent resection for pathology proven ICC, PHCC, DCC or GBC (2000-2016) from a single Western high-volume center were retrospectively selected. Clinicopathological characteristics, short- and long-term outcomes were compared between the four anatomical subtypes., Results: Overall, 361 patients with resected BTC were included (33 ICC, 135 PHCC, 148 DCC, 45 GBC). Clavien-Dindo grade III or higher complications were 48%, 51%, 36% and 8% (p < 0.001) and 90-day mortality was 9%, 15%, 3%, 4% (p < 0.001), for ICC, PHCC, DCC, GBC. Median overall survival was 37, 42, 29 and 41 months (p = 0.722), for ICC, PHCC, DCC, GBC. Five-year survival ranged between 29% and 37%. Anatomical subtype was not an independent predictor for overall survival., Conclusion: In this large single-center cohort of resected BTC, major morbidity and 90-day mortality varied between the four anatomical subtypes of BTC, mainly due to differences in surgical approach However, a significant difference in overall survival was not detected., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

In perihilar cholangiocarcinoma (PHC), interpretation of the resection specimen is challenging for pathologists and clinicians alike. Thorough and correct reporting is necessary for reliable interpretation of residual disease status. The aim of this study is to assess completeness of PHC pathology reports in a single center and assess what hampers interpretation of pathology reports by clinicians. Pathology reports of patients resected for PHC at a single expert tertiary center drafted between 2000 and 2018 were assessed. Reports were assessed regarding completeness, according to the guideline of the International Collaboration on Cancer Reporting (ICCR). A total of 146 reports were assessed. Prognostic tumor characteristics such as vasoinvasive growth and perineural growth were missing in 30/146 (34%) and 22/146 (15%), respectively. One or more planes were missing in 94/146 (64%) of the reports, with the periductal dissection plane missing in 51/145 (35%). Residual disease could be re-classified from R0 to R1 in 22 patients (15%). Reasons for R1 in these patients were the presence of a positive periductal dissection plane (n = 2), < 1-mm margin at the periductal dissection plane (n = 11), or liver parenchyma (n = 9). Completeness of reports improved significantly when drafted by an expert HPB pathologist. This study demonstrates that pathology reporting of PHC is challenging. Reports are frequently incomplete and often do not incorporate assessment of all resection planes and the dissection plane. The periductal dissection plane is frequently overlooked, but is a major cause of residual disease.

Background: Morbidity and mortality after hepatectomy for perihilar cholangiocarcinoma are known to be high. However, reported postoperative outcomes vary, with notable differences between Western and Asian series. We aimed to determine morbidity and mortality rates after major hepatectomy in patients with perihilar cholangiocarcinoma and assess differences in outcome regarding geographic location and hospital volume., Methods: A systematic review was performed by searching the MEDLINE and EMBASE databases through November 20, 2017. Risk of bias was assessed and meta-analysis and metaregression were performed using a random effects model., Results: A total of 51 studies were included, representing 4,634 patients. Pooled 30-day and 90-day mortality were 5% (95% CI 3%-6%) and 9% (95% CI 6%-12%), respectively. Pooled overall morbidity and severe morbidity were 57% (95% CI 50%-64%) and 40% (95% CI 34%-47%), respectively. Western studies compared with Asian studies had a significantly higher 30-day mortality, 90-day mortality, and overall morbidity: 8% versus 2% (P < .001), 12% versus 3% (P < .001), and 63% versus 54% (P = .048), respectively. This effect on mortality remained significant after correcting for hospital volume. Univariate metaregression analysis showed no influence of hospital volume on mortality or morbidity, but when corrected for geographic location, higher hospital volume was associated with higher severe morbidity (P = .039)., Conclusion: Morbidity and mortality rates after major hepatectomy for perihilar cholangiocarcinoma are high. The Western series showed a higher mortality compared with the Asian series, even when corrected for hospital volume. Standardized reporting of outcomes is necessary. Underlying causes for differences in outcomes between Asian and Western centers, such as differences in treatment strategies, should be further analyzed., (Copyright © 2019 Elsevier Inc. All rights reserved.)