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The futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era.The aim was to assess the effect of older age on outcome after liver transplantation. We used the ELTR to study the relationship between recipient age and post-transplant outcome. Young and elderly recipients were compared using a PSM method.A total of 10,172 cases were analysed. Recipient age65 years was identified as an independent risk factor associated with reduced patient survival (HR:1.42 95%CI:1.23-1.65,p 0.001). After PSM, 2124 patients were matched, and the same association was found between elderly recipients and patient survival and graft survival (p 0.001). As hepatocellular carcinoma and alcoholic cirrhosis were independent prognostic factors for patient and graft survival a propensity score-matching was performed for each. Patient and graft survival were significantly worse (p 0.05) in the alcoholic cirrhosis elderly group. However, patient and graft survival in the hepatocellular carcinoma cohort were similar (p 0.05) between groups.Liver transplantation is an acceptable and safe curative option for elderly transplant candidates, with worse long-term outcomes compare to young candidates. The underlying liver disease for liver transplantation has a significant impact on the selection of elderly patients.

The results of this study were presented during the 13th Congress of the E-AHPBA on June 3th 2019, in Amsterdam.; International audience; BACKGROUND: Major bile duct injuries (BDI) following cholecystectomy require complex reconstructive surgery. The aim was to collect the liver transplantations (LT) performed in France for major BDI following cholecystectomy, to analyze the risk factors and to report the results. METHODS: National multicenter observational retrospective study. All the patients who underwent a LT in France between 1994 and 2017, for BDI following cholecystectomy, were included. RESULTS: 30 patients were included. 25 BDI occurred in non hepato-biliary expert centers, 20 were initially treated in these centers. Median time between injury and LT was 3 years in case of an associated vascular injury (11 injuries), versus 11.7 years without vascular injury (p = 0.006). Post-transplant morbidity rate was 86.7%, mortality 23.5% at 5 years. CONCLUSION: Iatrogenic BDI remains a real concern with severe cases, associated with vascular damages or leading to cirrhosis, with no solution but LT. It is associated with high morbidity and not optimal results. This enlights the necessity of early referral of all major BDI in expert centers to prevent dramatic outcome. Decision to perform transplantation should be taken before dismal infectious situations or biliary cirrhosis and access to graft should be facilitated by Organ Sharing Organizations.

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

Background. The influence of sex on primary sclerosing cholangitis (PSC), pre- and postliver transplantation (LT) is unclear. Aims are to assess whether there have been changes in incidence, profile, and outcome in LT-PSC patients in Europe with specific emphasis on sex. Methods. Analysis of the European Liver Transplant Registry database (PSC patients registered before 2018), including baseline demographics, donor, biochemical, and clinical data at LT, immunosuppression, and outcome. Results. European Liver Transplant Registry analysis (n = 6463, 32% female individuals) demonstrated an increasing number by cohort (1980-1989, n = 159; 1990-1999, n = 1282; 2000-2009, n = 2316; 2010-2017, n = 2549) representing on average 4% of all transplant indications. This increase was more pronounced in women (from 1.8% in the first cohort to 4.3% in the last cohort). Graft survival rate at 1, 5, 10, 15, 20, and 30 y was 83.6%, 70.8%, 57.7%, 44.9%, 30.8%, and 11.6%, respectively. Variables independently associated with worse survival were male sex, donor and recipient age, cholangiocarcinoma at LT, nondonation after brain death donor, and reduced size of the graft. These findings were confirmed using a more recent LT population closer to the current standard of care (LT after the y 2000). Conclusions. An increasing number of PSC patients, particularly women, are being transplanted in European countries with better graft outcomes in female recipients. Other variables impacting outcome include donor and recipient age, cholangiocarcinoma, nondonation after brain death donor, and reduced graft size.

BACKGROUND: Obesity is associated with increased oncological risk and outcomes but the evidence surrounding the effect of body mass index (BMI) on increased risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is still questionable. The purpose of this retrospective study of a large cohort of adult patients transplanted for HCC was to investigate the effect of BMI on the incidence of HCC recurrence and outcome. METHODS: Data from 427 adult recipients transplanted for HCC between 2000 and 2017 were collected. Patients were classified at time of LT according to the World Health Organization BMI classification into 3 groups; group 1: BMI

Background The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with transarterial radioembolisation (TARE) or sorafenib. Methods This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models. Results A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) versus 2.6 months (95% CI 2.0–3.0) in the TARE and sorafenib groups, respectively. Conclusions HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.

Summary High‐risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end‐stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low‐risk (0–3), medium‐risk (4–5), and high‐risk (6–10) groups were identified with significantly different 5‐year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P, The retransplantation risk score.

BACKGROUND Surgical resection and radiofrequency ablation (RFA) represent two possible strategy in treatment of hepatocellular carcinoma (HCC) in Milan criteria. AIM To evaluate short- A nd long-term outcome in elderly patients (70 years) with HCC in Milan criteria, which underwent liver resection (LR) or RFA. METHODS The study included 594 patients with HCC in Milan criteria (429 in LR group and 165 in RFA group) managed in 10 European centers. Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching (PSM) and Cox regression. RESULTS After PSM, we compared 136 patients in the LR group with 136 patients in the RFA group. Overall survival at 1, 3, and 5 years was 91%, 80%, and 76% in the LR group and 97%, 67%, and 41% in the RFA group respectively (P = 0.001). Diseasefree survival at 1, 3, and 5 years was 84%, 60% and 44% for the LR group, and 63%, 36%, and 25% for the RFA group (P = 0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group (1% vs 11%, P = 0.001) in association with a shorter length of stay (2 d vs 7 d, P = 0.001).In multivariate analysis, Model for End-stage Liver Disease (MELD) score (10) [odds ratio (OR) = 1.89], increased value of international normalized ratio (1.3) (OR = 1.60), treatment with radiofrequency (OR = 1.46) ,and multiple nodules (OR = 1.19) were independent predictors of a poor overall survival while a high MELD score (10) (OR = 1.51) and radiofrequency (OR = 1.37) were independent factors associated with a higher recurrence rate. CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications, surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients (70 years) with HCC in Milan criteria. © 2021 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved.

Two‐stage hepatectomy (TSH) is one of the specific surgical techniques that can expand the pool of resectable patients with initially unresectable colorectal liver metastases (CRLM). The indication of TSH for CRLM is only bilateral, multinodular disease, which cannot be resected by a single hepatectomy. TSH is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long‐term outcomes. However, not all eligible patients can benefit from the TSH strategy. One of the most important issues is dropout from the strategy (failure to complete both of the two sequential procedures), because the survival of such patients is drastically worse compared with patients who can complete both stages. Another important issue is the early recurrence rate and subsequent poor survival even after completion of TSH. Thus, the selection of appropriate patients who can really benefit from the TSH strategy is crucial. This review discusses the optimal patient selection for TSH, which should be helpful for the development of treatment strategies for patients with extensive CRLM., Although two‐stage hepatectomy (TSH) for extensive colorectal liver metastases (CRLM) is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long‐term outcomes, not all eligible patients can benefit from this strategy. In this review, we discuss the optimal patient selection for TSH, which should be helpful for the development of treatment strategies for patients with extensive CRLM.

Hepatocellular carcinoma recurrence after liver transplantation is a well-known complication but the development of de novo hepatocellular carcinoma in non-cirrhotic allograft with no previous history of hepatic malignancy either in the donor or the recipient is extremely rare. A 33-year-old man underwent deceased donor liver transplantation due to HBV-HDV cirrhosis in 1991. The donor was healthy, with negative viral serology. Pretransplant assessment and explant liver pathology revealed no tumor. He developed an 8 cm mediastinal thymus cancer in 2014, a chronic myeloid leukemia in 2015 and a 16 mm renal cell carcinoma in 2017. After 27 years, in 2018, his routine follow-up sonography showed incidentally a 37 mm hepatic nodule in segment VII which revealed after percutaneous liver guided biopsy a hepatocellular carcinoma. As no extra hepatic metastasis was noted, segmentectomy was done. The pathological report confirmed a moderately differentiated hepatocellular carcinoma nodule of 50 mm diameter with absence of microvascular invasion and the non-tumoral liver showed histological features of NASH (SAF score: S1A2F3, NAS score: A3F3 and LAFSc:5) with absence of HBsAg and HBcAg. This case emphasizes the importance of long-term close surveillance by imaging of the graft even in the absence of viral recurrence and graft cirrhosis.

Recurrent attacks of acute intermittent porphyria (AIP) result in poor quality of life and significant risks of morbidity and mortality. Liver transplantation (LT) offers a cure, but published data on outcomes after LT are limited. We assessed the pretransplant characteristics, complications, and outcomes for patients with AIP who received a transplant. Data were collected retrospectively from the European Liver Transplant Registry and from questionnaires sent to identified transplant and porphyria centers. We studied 38 patients who received transplants in 12 countries from 2002 to 2019. Median age at LT was 37 years (range, 18-58), and 34 (89%) of the patients were women. A total of 9 patients died during follow-up, and 2 patients were retransplanted. The 1-year and 5-year overall survival rates were 92% and 82%, which are comparable with other metabolic diseases transplanted during the same period. Advanced pretransplant neurological impairment was associated with increased mortality. The 5-year survival rate was 94% among 19 patients with moderate or no neuropathy at LT and 83% among 10 patients with severe neuropathy (P = 0.04). Pretransplant renal impairment was common. A total of 19 (51%) patients had a GFR < 60 mL/minute. Although few patients improved their renal function after LT, neurological impairments improved, and no worsening of neurological symptoms was recorded. No patient had AIP attacks after LT, except for a patient who received an auxiliary graft. LT is a curative treatment option for patients with recurrent attacks of AIP. Severe neuropathy and impaired renal function are common and increase the risk for poor outcomes. If other treatment options fail, an evaluation for LT should be performed early. ispartof: LIVER TRANSPLANTATION vol:27 issue:4 pages:491-501 ispartof: location:United States status: published

Improved chemotherapy response rates have lead to "disappearing" colorectal liver metastases (dCRLM). We aim to assess management patterns of dCRLM from an international body of hepatobiliary surgeons.A survey was designed, tested for item relevance, readability and content validity, and distributed to the AHPBA, IHPBA and ANZHPBA.The majority of 226 respondents were15 years from training (69%), practiced in academia (82%) and devoted50% of their practice to hepatobiliary (75%). Surgeons utilize CT(45%) or MRI(47%) for preoperative planning with a preferred imaging interval of6 weeks. Nearly all have experienced dCRLM (99%) and 63% of surgeons have waited a few months to assess for durability of response prior to definitive surgical/ablative therapy. Only 24% place fiducial markers for lesions1-cm prior to neoadjuvant chemotherapy. Intra-operatively, 97% of surgeons perform ultrasound, and 71% ablation. When a tumor has "disappeared," 49% elect for observation and 31% resect if the dCRLM is superficial. Of those electing observation, 87% believe there is effective treatment with progression on surveillance imaging.Nearly all surgeons have experienced dCRLM with half choosing observation over intervention due to the belief that these lesions may be re-addressed in the future.

Background & Aims Despite improvements in medical and surgical techniques, post-hepatectomy liver failure (PHLF) remains the leading cause of postoperative death. High postoperative portal vein pressure (PPV) and portocaval gradient (PCG), which cannot be predicted by current tools, are the most important determinants of PHLF. Therefore, we aimed to evaluate a digital twin to predict the risk of postoperative portal hypertension (PHT). Methods We prospectively included 47 patients undergoing major hepatectomy. A mathematical (0D) model of the entire blood circulation was assessed and automatically calibrated from patient characteristics. Hepatic flows were obtained from preoperative flow MRI (n = 9), intraoperative flowmetry (n = 16), or estimated from cardiac output (n = 47). Resection was then simulated in these 3 groups and the computed PPV and PCG were compared to intraoperative data. Results Simulated post-hepatectomy pressures did not differ between the 3 groups, comparing well with collected data (no significant differences). In the entire cohort, the correlation between measured and simulated PPV values was good (r = 0.66, no adjustment to intraoperative events) or excellent (r = 0.75) after adjustment, as well as for PCG (respectively r = 0.59 and r = 0.80). The difference between simulated and measured post-hepatectomy PCG was ≤3 mmHg in 96% of cases. Four patients suffered from lethal PHLF for whom the model satisfactorily predicted their postoperative pressures. Conclusions We demonstrated that a 0D model could correctly anticipate postoperative PHT, even using estimated hepatic flow rates as input data. If this major conceptual step is confirmed, this algorithm could change our practice toward more tailor-made procedures, while ensuring satisfactory outcomes. Lay summary Post-hepatectomy portal hypertension is a major cause of liver failure and death, but no tool is available to accurately anticipate this potentially lethal complication for a given patient. Herein, we propose using a mathematical model to predict the portocaval gradient at the end of liver resection. We tested this model on a cohort of 47 patients undergoing major hepatectomy and demonstrated that it could modify current surgical decision-making algorithms.

Postoperative early recurrence after hepatic resection for hepatocellular carcinoma (HCC) poses a challenge to surgeons, and the effect of a surgical margin is still controversial. This study aimed to identify an ideal margin to prevent early recurrence. A total of 226 consecutive patients who underwent primary curative hepatic resection for solitary and primary HCC were enrolled. The definition of early recurrence was determined using the minimum P value approach. Logistic regression analysis was used to identify the risk factors of early recurrence. The receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off of the surgical margin and early recurrence. Recurrence within 8 months induced the poorest overall survival (P = 2×10−15). ROC analysis showed that the optimal cut-off value of the surgical margin was 7 mm. The risk factors of early recurrence (≤ 8-month recurrence) were preoperative alpha-fetoprotein levels ≥ 100 ng/ml (Odds ratio [OR] 4.92 [2.28–10.77], P 7-mm margin is important to prevent early recurrence. Patients with HCC and alpha-fetoprotein levels > 100 ng/ml, non-capsule formation, or microvascular invasion may have a survival benefit from a ≥ 7-mm margin.

Background Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. Methods Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. Results The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. Conclusions These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.

The triplet combination of irinotecan, oxaliplatin and fluorouracil is an active frontline regimen in metastatic colorectal cancer, but scarce data exist on its use as salvage treatment. We aimed at assessing its safety and efficacy profiles with its circadian-based administration (chronoIFLO5) as either first- or second-line treatment, within the time-finding EORTC 05011 trial. Five-day chronoIFLO5 was administered every 3 weeks in patients with PS 0, 1 or 2. It consisted of chronomodulated irinotecan (180 mg/sqm), oxaliplatin (80 mg/sqm) and fluorouracil-leucovorin (2800 and 1200 mg/sqm, respectively). For our study, toxicity and antitumour activity were evaluated separately in first- and second-line settings. Primary endpoints included Grade 3-4 toxicity rates, best objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). One-hundred forty-nine and 44 patients were treated in first-line and second-line settings, respectively, with a total of 1138 cycles with median relative dose intensities of about 90%. Demographics were comparable in the two groups. Thirty-six (24.7%) and 10 (22.2%) patients experienced at least one episode of severe toxicity in first line and second line, respectively. Frontline chronoIFLO5 yielded an ORR of 62.3% [95% CI: 54.2-70.4] and resulted in median PFS and OS of 8.7 months [7.5-9.9] and 19.9 months [15.4-24.5]. Corresponding figures in second line were 37.5% [22.5-52.5], 6.7 months [4.8-8.9] and 16.3 months [11.8-20.8]. International and prospective evaluation revealed the favourable safety and efficacy profiles of chronoIFLO5, both as frontline and as salvage treatment against metastatic colorectal cancer. In particular, encouraging activity in second line was observed, with limited haematological toxicity.

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Background: Post hepatectomy liver failure (PHLF) after ALPPS has been related to the discrepancy between liver volume and function. Pre-operative hepatobiliary scintigraphy (HBS) can predict postoperative liver function and guide when it is safe to proceed with major hepatectomy. Aim of this study was to evaluate the role of HBS in predicting PHLF after ALPPS, defining a safe cut-off. Methods: A multicenter retrospective study was approved by the ALPPS Registry. All patients selected for ALPPS between 2012 and 2018, were evaluated. Every patient underwent HBS during ALPPS evaluation. PHLF was reported according to ISGLS definition, considering grade B or C as clinically significant. Results: 98 patients were included. Thirteen patients experienced PHLF grade B or C (14%) following ALPPS-2. The HBS and the daily gain in volume (KGRFLR) of the future liver remnant (FLR) were significantly lower in PHLF B and C (p = .004 and .041 respectively). ROC curves indicated safe cut-offs of 4.1%/day (AUC = 0.68) for KGRFLR, and of 2.7 %/min/m(2) (AUC = 0.75) for HBSFLR. Multivariate analysis confirmed these cut-offs as variables predicting PHLF after ALPPS-2. Conclusion: Patients presenting a KGRFLR

Background and aims LR and LT are the standard curative options for early HCC. LT provides best long-term survival but is limited by organ shortage. LR, readily available, is hampered by high recurrence rates. Salvage liver transplantation is an efficient treatment of recurrences within criteria. The aim of the study was to identify preoperative predictors of non transplantable recurrence (NTR) to improve patient selection for upfront LR or LT at initial diagnosis. Study design Consecutive LR for transplantable HCC between 2000 and 2015 were studied. A prediction model for NTR based on preoperative variables was developed using sub-distribution hazard ratio after multiple imputation and internal validation by bootstrapping. Model performance was evaluated by the concordance index after correction for optimism. Results A total of 148 patients were included. Five-year overall survival and recurrence free survival were 73.6% and 29.3%, respectively (median follow-up 45.8 months). Recurrence rate was 54.8%. NTR rate was 38.2%. Preoperative model for NTR identified >1 nodule [sub-distribution hazard ratio 2.35 95% confidence interval (CI) 1.35-4.09], AFP >100 ng/mL (2.14 95% CI 1.17-3.93), and F4 fibrosis (1.93 95% CI 1.03-3.62). The apparent concordance index of the model was 0.664 after correction for optimism. In the presence of 0, 1, and ≥2 factors, NTR rates were 2.6%, 22.7%, and 40.9%, respectively. The number of prognostic factors was significantly associated with the pattern of recurrence (P = 0.001) and 5-year recurrence free survival (P Conclusions Cirrhosis, >1 nodule, and AFP >100 ng/mL were identified as preoperative predictors of NTR. In the presence of 2 factors or more upfront transplantation should be probably preferred to resection in regard of organ availability. Other patients are good candidates for LR and salvage liver transplantation should be encouraged in eligible patients with recurrence.

Background: the extent of the COVID-19 pandemic and the resulting response has varied globally. The European and African Hepato-Pancreato-Biliary Association (E-AHPBA), the premier representative body for practicing HPB surgeons in Europe and Africa, conducted this survey to assess the impact of COVID-19 on HPB surgery. Methods: an online survey was disseminated to all E-AHPBA members to assess the effects of the pandemic on unit capacity, management of HPB cancers, use of COVID-19 screening and other aspects of service delivery. Results: overall, 145 (25%) members responded. Most units, particularly in COVID-high countries (>100,000 cases) reported insufficient critical care capacity and reduced HPB operating sessions compared to COVID-low countries. Delayed access to cancer surgery necessitated alternatives including increased neoadjuvant chemotherapy for pancreatic cancer and colorectal liver metastases, and locoregional treatments for hepatocellular carcinoma. Other aspects of service delivery including COVID-19 screening and personal protective equipment varied between units and countries. Conclusion: this study demonstrates that the COVID-19 pandemic has had a profound adverse impact on the delivery of HPB cancer care across the continents of Europe and Africa. The findings illustrate the need for safe resumption of cancer surgery in a “new” normal world with screening of patients and staff for COVID-19., NA

Introduction: The incidence of primary non-function (PNF) after liver transplantation (LT) remains a major concern with the increasing use of marginal grafts. Indocyanine green (ICG) fluorescence is an imaging technique used in hepatobiliary surgery and LT. Because few early predictors are available, we aimed to quantify in real time the fluorescence of grafts during LT to predict their 3 months survival. Patients and methods: After graft revascularization, ICG was intravenously injected, then the fluorescence of the graft was captured with a near infrared camera and postoperatively quantified. A multi-parametric modelling of the parenchymal fluorescence intensity curve was proposed, and a predictive model of graft survival was tested. Results: Between July 2017 and May 2019, 76 LT were included, among which 6 recipients were re-transplanted (re-LT+ ). No side effects of ICG injection were observed. The parameter a150 (temporal course of fluorescence intensity) was significantly higher in the group re-LT+ group (0.022s-1 [0.016-0.035] versus 0.012s-1 [0.009-0.015], p=0.01). This parameter was the only independent predictive factor of graft survival at 3 months (OR=2.4 CI95% [1.05-5.5] p=0.03). The best cut-off for the parameter a150 (0.0155s-1 ) predicted the graft survival at 3 months with a sensitivity of 83% and a specificity of 79% (AUC=0.82 [0.67-0.98], p=0.01). Conclusion: Quantitative assessment of intraoperative ICG fluorescence on the graft was feasible to predict graft survival at 3 months with a good sensitivity and specificity. Further prospective studies should validate these results over larger cohorts and evaluate the clinical impact of this tool.

The least toxic time (LTT) of irinotecan varied by up to 8 hours according to sex and genetic background in mice. The translational relevance was investigated within a randomized trial dataset, where no LTT stood out significantly in the whole population. 130 male and 63 female eligible patients with metastatic colorectal cancer were randomized to receive chronomodulated Irinotecan with peak delivery rate at 1 of 6 clock hours staggered by 4 hours on day 1, then fixed‐time chronomodulated Fluorouracil‐Leucovorin‐Oxaliplatin for 4 days, q3 weeks. The sex‐specific circadian characteristics of grade (G) 3‐4 toxicities were mapped with cosinor and time*sex interactions confirmed with Fisher's exact test. Baseline characteristics of male or female patients were similar in the six treatment groups. Main grade 3‐4 toxicities over six courses were diarrhea (males vs females, 39.2%; vs 46.0%), neutropenia (15.6% vs 15.0%), fatigue (11.5% vs 15.9%), and anorexia (10.0% vs 7.8%). They were reduced following irinotecan peak delivery in the morning for males, but in the afternoon for females, with statistically significant rhythms (P, In this randomized international trial, the hematologic and clinical toxicities of irinotecan were least following dosing in the morning for men and in the afternoon for women with colorectal cancer. Sex‐specific least toxic times of anticancer drugs need further identification in prospective clinical trials.

An aging population has prompted us to evaluate the indications of liver transplantation (LT) in elderly patients more frequently. In this review, we summarize the short- and long-term results after LT in elderly patients and also discuss the criteria used to select patients and how recipient age can challenge current allocation systems. Briefly, the feasibility and early outcomes of LT in elderly patients compare favorably with those of younger patients. Although long-term survival is less than satisfactory, large-scale studies show that the transplant survival benefit is similar for elderly and younger patients. Therefore, age alone does not contraindicate LT; however, screening for cardiopulmonary comorbidities, and asymptomatic malignancies, evaluating nutritional status, and frailty, is crucial to ensure optimal results and avoid futile transplantation.

The clinical significance of discordant radiological and pathological response to preoperative chemotherapy of colorectal liver metastases (CLM) is unknown. From 2011 to 2016, all eligible patients undergoing resection for CLM after preoperative chemotherapy were included at two centres. Patients were categorized according to radiologic response using RECIST as Rad-responders (complete/partial response) or Rad-non responders (stable disease) and according to Blazer et al. pathologic response grade as Path-responders (complete/major response) or Path-non responders (minor response). Survival outcome was analysed according to radiologic and pathologic response. Among 413 patients undergoing resection of CLM, 119 fulfilled the inclusion criteria. Among these, 52 (44%) had discordant radiologic and pathologic response including 27 Rad-non responders/path responders and 25 Rad-responders/Path-non responders. Rad-non responders/path responders and Rad-responders/Path-non responders had similar characteristics except for the proportion receiving more than 6 cycles of preoperative chemotherapy (7/27 vs 16/25; P = 0.017). Median disease-free survival was not different in patients with or without discordant radiologic and pathologic responses (P = 0.195) but the type of discordance had an impact on oncologic outcome as median disease-free survival was 13.9 months (95% CI 5.7–22.2 months) in Rad-non responders/Path responders and 8.6 (6.2 – 10.9 months) in Rad-responders/Path-non responders (P = 0.034). Univariate and multivariate analysis showed that major pathologic response was associated with improved disease-free survival (OR 0.583, 95% CI 0.36–0.95, P = 0.031). A discordant radiologic and pathologic response is common after preoperative chemotherapy for CLM. In these patients, pathologic response drives oncologic outcome.

There are scarce data on the impact of COVID-19 pandemic on liver transplantation (LT) in Europe. The aim of this study was to obtain a preliminary data on incidence, management, and outcome of COVID-19 in liver transplant recipients and candidates in Europe. An Internet-based survey was sent to the centers affiliated with European Liver Transplant Registry (ELTR). One hundred nine out of 149 (73%) of ELTR centers located in 28 European countries (93%) responded. Ninety-four (86%) of the centers tested all donors, and 75 (69%) centers tested all LT recipients for SARS-CoV-2. Seventy-three (67%) centers selected recipients for LT in the COVID-19 pandemic, whereas 33% did not. Eighty-eight centers reported COVID-19 infection in 57 LT candidates and in 272 LT recipients. Overall crude incidence of COVID-19 among LT candidates and recipients was estimated 1.05% (range 0.5–20%) and 0.34% (range 0.1–4.8%), respectively, and it was significantly higher among candidates (P'0.001). Crude rate of death was 18% (10/57) among candidates and 15% (36/244) among recipients. This first large-scale European snapshot study clearly shows that both LT candidates and recipients are at a high risk for COVID-19. These results plead for an early and pro-active screening of COVID-19 symptoms in these populations.

Background Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) represented potential treatments for patients with a single hepatocellular carcinoma (HCC) smaller than 3 cm. As the aging population soared, our study aimed to examine the advantage/drawback balance for these treatments, which should be reassessed in elderly patients. Methods A multicentric retrospective study compared 184 elderly patients (aged >70 years) (86 patients underwent LLR and 98 had RFA) with single ≤3 cm HCC, observed from January 2009 to January 2019. Results After propensity score matching (PSM), the estimated 1- and 3-year overall survival rates were 96.5 and 87.9% for the LLR group, and 94.6 and 68.1% for the RFA group (p = 0.001) respectively. The estimated 1- and 3-year disease-free survival rates were 92.5 and 67.4% for the LLR group, and 68.5 and 36.9% for the RFA group (p = 0.001). Patients with HCC of anterolateral segments were more often treated with laparoscopic resection (47 vs. 36, p = 0.04). The median operative time in the resection group was 205 min and 25 min in the RFA group (p = 0.01). Length of hospital stay was 5 days in the resection group and 3 days in the RFA group (p = 0.03). Conclusion Despite a longer length of hospital stay and operative time, LLR guarantees a comparable postoperative course and a better overall and disease-free survival in elderly patients with single HCC (≤3 cm), located in anterolateral segments.

Assessing the risk of significant macrosteatosis in donors is crucial before considering hepatic graft procurement. We aimed to build a model to predict significant macrosteatosis based on noninvasive methods. From January 2012 to December 2018, liver attenuation indices and liver-to-spleen (L/S) ratio were measured in 639 brain-dead donors by local radiologists. Quantity and quality of steatosis were evaluated by an expert pathologist, blinded for attenuation indices measurement. Macrosteatosis ≥ 30% was found in 33 donors (5.2%). Body weight, body mass index (BMI), abdominal perimeters, history of alcohol abuse, L/S ratio, and liver parenchyma attenuation were associated with macrosteatosis ≥ 30%. The L/S ratio, BMI, and a history of alcohol abuse remained independent predictors in multivariate analysis and were used to build a predictive model (C-index: 0.77). The optimal cutoff to predict macrosteatosis ≥ 60% was 0.85. Our model, including L/S ratio, BMI, and history of alcohol, might be helpful to refine indication for liver biopsy before donation after brain death. External validation is required.

Background Lymphadenectomy ensures accurate staging for patients with intrahepatic cholangiocarcinoma, especially for those without preoperatively suspected positive lymph nodes (clinically node-negative); however, its prognostic value has been poorly documented. The aim of this study was to evaluate the prognostic value of lymphadenectomy on long-term outcomes in patients undergoing surgery for clinically node-negative intrahepatic cholangiocarcinoma. Methods Data from all patients who underwent liver resection with or without lymphadenectomy for preoperatively diagnosed intrahepatic cholangiocarcinoma between 2000 and 2016 at 3 tertiary hepatobiliary centers were analyzed retrospectively. Propensity score matching in a 1:1 ratio was conducted based on clinically relevant covariates between patients with clinically node-negative intrahepatic cholangiocarcinoma who underwent liver resection with (LND group) and without (NLND group) lymphadenectomy. Overall survival and disease-free survival were compared in the matched cohort. Results Among 350 patients who underwent surgery during the study period, 192 (55%) with clinically node-negative intrahepatic cholangiocarcinoma met the inclusion criteria. After propensity score matching, 2 well-balanced groups of 56 patients each were analyzed. There was no significant difference regarding postoperative variables among these 112 matched patients. Patients who underwent a liver resection with lymphadenectomy achieved better 3- and 5-year overall survival (78% and 65% vs 52% and 46%, P = .017) and disease-free survival (46% and 34% vs 31% and 31%; P = .042) compared with patients who underwent liver resection without lymphadenectomy. Conclusion Lymphadenectomy can be associated with better long-term outcomes in patients with node-negative intrahepatic cholangiocarcinoma. Our data may support routine lymphadenectomy for node-negative intrahepatic cholangiocarcinoma with the objective of achieving better long-term outcomes.

Ischemic cholangiopathy (IC) has a known poor prognosis. However, the risks and outcomes of this complication after transcatheter arterial chemoembolization (TACE) in hepatectomized patients are poorly documented. This study aimed to evaluate the incidence of and to identify the predictive factors for IC following TACE for recurrent hepatocellular carcinoma (HCC) after hepatectomy. From a cohort with a total of 486 patients who underwent resection for HCC, we included all consecutive patients who were treated with TACE for recurrent HCC after hepatectomy between 2000 and 2017. IC was defined by the coexistence of biological cholestasis and morphological lesions. A total of 156 patients underwent TACE for the treatment of HCC recurrence after hepatectomy. Of them, eight (5.1%) developed IC. Their prognosis was poor compared with patients without IC (3-year survival 23.4% vs 76.2%; P = 0.008). Two factors, namely, time between hepatectomy and TACE (4.8 months vs. 16.0 months, P = 0.001) and TACE for a remnant liver mobilized during hepatectomy (P = 0.001), were associated with IC. Receiver operating characteristic (ROC) curve analysis showed that 7 months was the more discriminant cutoff for the time period. IC occurred in 33.3% of the patients with the two factors, in 5.0% of those with one factor, and 0% in the absence of any factors. TACE for treating HCC recurrence carries a high risk of IC when performed early after hepatectomy in a previously mobilized liver. Our results might aid in identifying candidates for TACE for recurrent HCC, considering the major effect on patient outcomes.

Background & Aims Selection criteria for hepatectomy in patients with cirrhosis are controversial. In this study we aimed to build prognostic models of symptomatic post-hepatectomy liver failure (PHLF) in patients with cirrhosis. Methods This was a cohort study of patients with histologically proven cirrhosis undergoing hepatectomy in 6 French tertiary care hepato-biliary-pancreatic centres. The primary endpoint was symptomatic (grade B or C) PHLF, according to the International Study Group of Liver Surgery's definition. Twenty-six preoperative and 5 intraoperative variables were considered. An ordered ordinal logistic regression model with proportional odds ratio was used with 3 classes: O/A (No PHLF or grade A PHLF), B (grade B PHLF) and C (grade C PHLF). Results Of the 343 patients included, the main indication was hepatocellular carcinoma (88%). Laparoscopic liver resection was performed in 112 patients. Three-month mortality was 5.25%. The observed grades of PHLF were: 0/A: 61%, B: 28%, C: 11%. Based on the results of univariate analyses, 3 preoperative variables (platelet count, liver remnant volume ratio and intent-to-treat laparoscopy) were retained in a preoperative model and 2 intraoperative variables (per protocol laparoscopy and intraoperative blood loss) were added to the latter in a postoperative model. The preoperative model estimated the probabilities of PHLF grades with acceptable discrimination (area under the receiver-operating characteristic curve [AUC] 0.73, B/C vs. 0/A; AUC 0.75, C vs. 0/A/B) and the performance of the postoperative model was even better (AUC 0.77, B/C vs. 0/A; AUC 0.81, C vs. 0/A/B; p Conclusions By accurately predicting the risk of symptomatic PHLF in patients with cirrhosis, the preoperative model should be useful at the selection stage. Prediction can be adjusted at the end of surgery by also considering blood loss and conversion to laparotomy in a postoperative model, which might influence postoperative management. Lay summary In patients with liver cirrhosis, the risk of a hepatectomy is difficult to appreciate. We propose a statistical tool to estimate this risk, preoperatively and immediately after surgery, using readily available parameters and on online calculator. This model could help to improve the selection of patients with the best risk-benefit profiles for hepatectomy.

Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p 4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or-2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more pre-cise prognostic assessment of patients with ACLF. Lay summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All reserved.

Knowledge of living donor liver transplantation (LDLT) for autoimmune liver diseases (AILDs) is scarce. This study analyzed survival in LDLT recipients registered in the European Liver Transplant Registry with autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC) and the non-autoimmune disorder alcohol-related cirrhosis. In total, 29 902 individuals enrolled between 1998 and 2017 were analyzed, including 1003 with LDLT. Survival from >90 days after LDLT for AILDs in adults was 85.5%, 74.2%, and 58.0% after 5, 10, and 15 years. Adjusted for recipient age, sex, and liver transplantation era, adult PSC patients receiving LDLT showed increased mortality compared to donation after brain death (DBD) (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.36-2.80, p < .001). Pediatric PSC patients showed also increased mortality >90 days after LDLT compared to DBD (HR = 3.00, 95% CI 1.04-8.70, p = .043). Multivariate analysis identified several risk factors for death in adult PSC patients receiving LDLT including a male donor (HR = 2.49, p = .025). Adult PSC patients with LDLT versus DBD conferred increased mortality from disease recurrence (subdistribution hazard ratio [subHR] = 5.36, p = .001) and biliary complications (subHR = 4.40, p = .006) in multivariate analysis. While long-term outcome following LDLT for AILD is generally favorable, PSC patients with LDLT compared to DBD might be at increased risk of death., Astellas Pharma; Novartis; Institut Georges Lopez; Sandoz, The Organ Sharing Organizations: the French ABM (Sami Djabbour), the Dutch NTS (Maaike de Wolf), the Eurotransplant Foundation (Marieke Van Meel), the Spanish RETH (Gloria de la Rosa), the UK-Ireland NHSBT (Michael Daynes), and the Scanditransplant (Ilse Duus Weinreich) are acknowledged for the data cross-check and sharing with the ELTR. The European Liver Transplant Registry is supported by a grant from Astellas Pharma, Novartis, Institut Georges Lopez, and Sandoz and receives logistical support from the Paul Brousse Hospital (AP-HP).

Transplant oncology is a field of growing interest, with increasing number of patients transplanted for cancer [1]. Among such indications, colorectal liver metastasis is under intense scrutiny considering the high number of potential new recipients. The important article by the Oslo group published in the current issue of Transplant International brings more light on their post-transplant fate [2]. Comment on: Dueland S, Smedman TM, Røsok B, Grut H, Syversveen T, Jørgensen LH, Line PD. Treatment of relapse and survival outcomes after liver transplantation in patients with colorectal liver metastases. Transpl Int. 2021 Nov;34(11):2205-2213. doi: 10.1111/tri.13995. PMID: 34792825.

Background The aim was to develop a model to predict clinically significant portal hypertension, hepatic venous pressure gradient (HVPG) ≥10mmHg using pre-operative noninvasive makers. Methods Patients who have been programmed for liver resection/transplantation were enrolled prospectively. Preoperative liver stiffness measurement (LSM), liver function test (LFT), and intraoperative HVPG were assessed. A probability score model to predict HVPG≥10mmHg called HVPG10 score was developed and validated. Results A total of 161 patients [66% men, median age of 63 years] were recruited for the study. Median LSM, and HVPG were 9.5kPa, and 5mmHg respectively. HVPG10 score was developed using independent predictors of HVPG≥10mmHg in the training set were LSM, total bilirubin, alkaline phosphatase, and international normalized ratio. Area under receiver operating curve of HVPG10 score in the training and validation sets were 0.91 and 0.93 respectively with a cutoff of 15. In the overall cohort, HVPG10 score≥15 had 83% accuracy, 90% sensitivity, 81% specificity and 96% negative predictive value in predicting HVPG≥10mmHg. Conclusion HVPG10 score is an easy-to-use noninvasive continuous scale tool to rule out clinically significant portal hypertension in >95% patients with chronic liver disease.

International audience; OBJECTIVE: To compare two techniques of remnant liver hypertrophy in candidates for extended hepatectomy: radiological simultaneous portal vein (PVE) and hepatic vein embolization (HVE); namely liver venous deprivation (LVD), and ALPPS. SUMMARY BACKGROUND DATA: Recent advances in chemotherapy and surgical techniques have widened indications for extended hepatectomy, before which remnant liver augmentation is mandatory. ALPPS and LVD typically show higher hypertrophy rates than PVE, but their respective places in patient management remain unclear. METHODS: All consecutive ALPPS and LVD procedures performed in eight French centers between 2011 and 2020 were included. The main endpoint was the successful resection rate (resection rate without 90-day mortality) analyzed according to an intention-to-treat principle. Secondary endpoints were hypertrophy rates, intra- and post-operative outcomes. RESULTS: Among 209 patients, 124 had LVD 37 [13,1015] days before surgery, while 85 underwent ALPPS with an inter-stages period of 10 [6, 69] days. ALPPS was mostly-performed for colorectal liver metastases (CRLM), LVD for CRLM and perihilar cholangiocarcinoma. Hypertrophy was faster for ALPPS. Successful resection rates were 72.6% for LVD ± rescue ALPPS (n=6) versus 90.6% for ALPPS (p

The impact of aspartate transaminases (AST) and gamma-glutamyl transferase (GGT) in serum of deceased donors on outcomes after liver transplantation (LT) is unclear. This study aimed to explore the relationship between donor highest AST value or first donor GGT value and graft survival. All consecutive patients who underwent a primary LT in a single center with available donor AST (N = 1253) and GGT value (N = 1152) were included. There was no significant association between donor AST and 90-day graft survival. We found a moderate association between GGT and 90-day graft survival. We found a significant interaction with a donor history of alcohol abuse (HAA). The risk of graft loss was associated with AST and GGT in donors with an HAA but remains unchanged in donors without HAA. There was no difference in graft survival according to donor AST or GGT with a cutoff ≥95th percentile (475 UI/l for AST and 170 UI/l for GGT). However, graft survival was significantly decreased when donors combined GGT ≥ 170 UI/l and HAA (61% at one year). Hepatic grafts from donors with high AST or high GGT but without alcohol history and no additional risk factors can be transplanted in low-risk recipient.

International audience; Purpose: The SARAH (Sorafenib Versus Radioembolization in Advanced Hepatocellular Carcinoma) trial (ClinicalTrials.gov Identifier NCT01482442) did not show a significant survival benefit for patients treated with transarterial radioembolization (TARE) compared with continuous oral sorafenib. The improved toxicity profile of patients treated with TARE in the trial, however, could result in a quality of life benefit in economic evaluations. Our objective was to perform a cost-utility analysis of TARE versus sorafenib for locally advanced and inoperable hepatocellular carcinoma.Methods: This study used patient-level data of the SARAH trial regarding resource use, progression-free and overall survival, and quality of life for the within-trial period for the patients who received at least 1 dose of sorafenib or 1 treatment with TARE according to their randomization arm. Data were extrapolated by using a partitioned survival model that incorporated costs and health outcomes, measured in life-years and quality-adjusted life-years (QALYs).Findings: The use of TARE resulted in an average loss of 0.036 life-year and a gain of 0.006 QALY compared with sorafenib. The aerage cost for the TARE arm was €17,179 (95% CI, 9,926-24,280) higher than the sorafenib arm, for an incremental cost-effectiveness ratio of €3,153,086/QALY. The probabilistic sensitivity analysis revealed a 50% risk that the TARE strategy was dominated. TARE was consistently dominated by sorafenib or had an incremental cost-effectiveness ratio more than €450,000/QALY in all sensitivity analyses.Implications: This economic evaluation of SARAH found that using radioembolization with yttrium-90 microspheres for the treatment of hepatocellular carcinoma was not a cost-effective option at the usually accepted willingness-to-pay thresholds.

International audience; BACKGROUND: HCC are known to have satellite nodules and microvascular invasions requiring sufficient margins. An alpha-fetoprotein (AFP) level >100 ng/mL is associated with worse pathological features in HCC. In practice, large resection margins, particularly >1~cm, are infrequently retrieved on the specimens. METHODS: 397 patients from 5 centres were included from 2012 to 2017. The primary endpoint was time-to-recurrence in relation to AFP level (> or or

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.

International audience; In France, the listing for liver transplantation (LT) for hepatocellular carcinoma (HCC) requires an AFP score 3 nodules (current classification), and aimed to propose a new criteria to exclude patients on list at high risk of recurrence. The 3-year OS of patients with 3 HCC at listing was of 90.3% vs. 67.3%, respectively (P = 0.04). At last imaging, eight listed patients presented >= 5 HCC nodules and had a significantly lower OS than = 5 nodules persist or appear after listing. A modification of the AFP score is mandatory to consider exclusion of high-risk patients already listed for LT program.

Simple Summary Recurrence of disease or worsening of liver function after hepatic resection (HR) for hepatocellular carcinoma (HCC) may require secondary liver transplantation (SLT). However, a history of HR is supposed to increase the surgical complexity of LT. This is one of the largest series of SLT and it demonstrates that among all the features analyzed regarding the prior HR, only time interval between HR and SLT was an independent predictor of severe complications after SLT. In particular, an increasing probability of severe complications was observed in those patients who were transplanted close (

Although surgical resection is the only treatment of choice that can offer prolonged survival and a chance of cure in patients with colorectal liver metastases (CRLM), nearly 80% of patients are deemed to be unresectable at the time of diagnosis. Considerable efforts have been made to overcome this initial unresectability, including expanding the indication of surgery, the advent of conversion chemotherapy, and development and modification of specific surgical techniques, regulated under multidisciplinary approaches. In terms of specific surgical techniques, portal vein ligation/embolization can increase the volume of future liver remnant and thereby reduce the risk of hepatic insufficiency and death after major hepatectomy. For multiple bilobar CRLM that were traditionally considered unresectable even with preoperative chemotherapy and portal vein embolization, two‐stage hepatectomy was introduced and has been adopted worldwide with acceptable short‐ and long‐term outcomes. Recently, ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) was reported as a novel variant of two‐stage hepatectomy. Although issues regarding safety remain unresolved, rapid future liver remnant hypertrophy and subsequent shorter intervals between the two stages lead to a higher feasibility rate, reaching 98%. In addition, adding radiofrequency ablation and vascular resection and reconstruction techniques can allow expansion of the pool of patients with CRLM who are candidates for liver resection and thus a cure. In this review, we discuss specific techniques that may expand the criteria for resectability in patients with initially unresectable CRLM.

Although many prognostic factors of primary graft dysfunction after liver transplantation (LT) are available, it remains difficult to predict failure in a given recipient.We aimed to determine whether the intraoperative assay of arterial lactate concentration at the end of LT (LCEOT) might constitute a reliable biological test to predict early outcomes [primary nonfunction (PNF), early graft dysfunction (EAD)].We reviewed data from a prospective database in a single center concerning patients transplanted between January 2015 and December 2016 (n = 296).There was no statistical imbalance between the training (year 2015) and validation groups (year 2016) for epidemiological and perioperative feature. Ten patients (3.4%) presented with PNF, and EAD occurred in 62 patients (20.9%); 9 patients died before postoperative day (POD) 90. LCEOT ≥5 mmol/L was the best cut-off point to predict PNF (Se=83.3%, SP=74.3%, positive likelihood ratio (LR+)=3.65, negative likelihood ratio (LR-)=0.25, diagnostic odds ratio (DOR)=14.44) and was predictive of PNF (P = 0.02), EAD (P = 0.05), and death ≤ POD90 (P = 0.06). Added to the validated BAR-score, LCEOT improved its predictive value regarding POD 90 survival with a better AUC (0.87) than BAR score (0.74). The predictive value of LCEOT was confirmed in the validation cohort.As a reflection of both hypoperfusion and tissue damage, the assay of arterial LCEOT ≥5 mmol/L appears to be a strong predictor of early graft outcomes and may be used as an endpoint in studies assessing the impact of perioperative management. Its accessibility and low cost could impose it as a reliable parameter to anticipate postoperative management and help clinicians for decision-making in the first PODs.

BACKGROUND: Surgical factors and direct cytotoxicity of bile salts on cholangiocytes may play a role in the development of ischemic cholangiopathy (IC) after liver transplantation (LTx). There is no validated consensus on how to protect the bile ducts during procurement, static preservation, and LTx. Meanwhile, IC remains the most troublesome complication after LTx. AIM: To characterize bile duct management techniques during the LTx process among European transplant centers in cases of donation after brain death (DBD) and circulatory death (DCD). METHOD: An European Liver and Intestine Transplant Association-European Liver Transplant Registry web survey designed to conceal respondents' personal information was sent to surgeons procuring and/or transplanting livers in Europe. RESULTS: Sixty-five percent of responses came from large transplant centers (>50 procurements/y). In 8% of DBDs and 14% of DCDs the bile duct is not rinsed. In 46% of DBDs and 52% of DCDs surgeons prefer to remove the gallbladder after graft reperfusion. Protocols concerning preservation solutions (nature, pressure, volume) are extremely heterogeneous. In 54% of DBDs and 61% of DCDs an arterial back table pressure perfusion is performed. Steroids (20%-10%), heparin (72%-60%), prostacyclin (3%-7%), and fibrinolytics (4%-11%) are used as donor-protective interventions in DBD and DCD cases, respectively. In 2% of DBD and 6% of DCD cases a hepatic artery reperfusion is performed first. In 4% of DBD and 6% of DCD cases, fibrinolytics are administered through the hepatic artery during the bench and/or implantation. CONCLUSION: This European web survey shows for the first time the heterogeneity in the management of bile ducts during procurement, preservation, and transplantation in Europe. In the context of sharing more marginal liver grafts, an expert meeting must be organized to formulate guidelines to be applied to protect liver grafts against IC. ispartof: TRANSPLANTATION PROCEEDINGS vol:51 issue:6 pages:1926-1933 ispartof: location:United States status: published

There are few reports on microvascular invasion (MVI) located intra- or extratumorally and prognosis of hepatocellular carcinoma (HCC). The aim of this study was to evaluate patient outcome according to the location of MVI, and to build a nomogram predicting extratumoral MVI. We included 681 consecutive patients who underwent hepatic resection (HR) or liver transplantation (LT) for HCC from January 1994 to June 2012, and evaluated patient outcome according to the degree of vascular invasion (VI). A nomogram for predicting extratumoral MVI was created using 637 patients, excluding 44 patients with macrovascular invasion, and was validated using an internal (n = 273) and external patient cohort (n = 256). The 681 patients were classified into four groups based on pathological examination (148 no VI, 33 intratumoral MVI, 84 extratumoral MVI, and 29 macrovascular invasion in patients who underwent HR; 238 no VI, 50 intratumoral MVI, 84 extratumoral MVI, and 15 macrovascular invasion in patients who underwent LT). Multivariate analysis revealed that extratumoral MVI was an independent risk factor for overall survival in patients who underwent HR (hazard ratio 2.62, p

It is not known whether perioperative chemotherapy, compared with adjuvant chemotherapy alone, improves disease-free survival (DFS) in patients with upfront resectable colorectal liver metastases (CLM). The aim of this study was to estimate the impact of neoadjuvant 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) on DFS in patients with upfront resectable CLM.Consecutive patients who presented with up to five resectable CLM at two Japanese and two French centres in 2008-2015 were included in the study. Both French institutions favoured perioperative FOLFOX, whereas the two Japanese groups systematically preferred upfront surgery plus adjuvant chemotherapy. Inverse probability of treatment weighting (IPTW) and Cox regression multivariable models were used to adjust for confounding. The primary outcome was DFS.Some 300 patients were included: 151 received perioperative chemotherapy and 149 had upfront surgery plus adjuvant chemotherapy. The weighted 3-year DFS rate was 33·5 per cent after perioperative chemotherapy compared with 27·1 per cent after upfront surgery plus adjuvant chemotherapy (hazard ratio (HR) 0·85, 95 per cent c.i. 0·62 to 1·16;Compared with adjuvant chemotherapy, perioperative FOLFOX does not improve DFS in patients with resectable CLM, provided adjuvant chemotherapy is given successfully.Se desconoce si la quimioterapia perioperatoria en comparación con la quimioterapia adyuvante sola mejora la supervivencia libre de enfermedad (Se incluyeron pacientes consecutivos que presentaban hasta cinco CLM resecables en dos centros japoneses y dos centros franceses entre 2008 a 2015. Ambas instituciones francesas favorecían FOLFOX perioperatorio, mientras que los dos grupos japoneses utilizaban sistemáticamente la cirugía de entrada y quimioterapia adyuvante. Se utilizaron la probabilidad inversa del tratamiento ponderado (Se incluyeron 300 pacientes (grupo de quimioterapia perioperatoriaEn comparación con la quimioterapia adyuvante, el FOLFOX perioperatorio no mejora la DFS en CLM resecables siempre y cuando la quimioterapia adyuvante se administre de forma efectiva.

Objective: To evaluate the impact of repeat surgery for recurrence on the long-term survival after 2-stage hepatectomy (TSH) for extensive colorectal liver metastases (CRLM). Background: Although TSH is now deemed effective for selected patients with extensive bilobar CRLM, disease recurrence after TSH is very frequent because of the extensive tumor load. Methods: Among a total cohort of 1235 patients who underwent hepatectomy for CRLM between 1992 and 2012, 139 with extensive bilobar CRLM were scheduled for TSH. Of these, 93 patients had completion of TSH and were enrolled in this study. Results: The 5-year overall survival (OS) rate after TSH was 41.3%. Twenty-two patients (23.7%) had a concomitant extrahepatic disease (EHD), and curative resection of concomitant EHD was achieved in 13 patients. Among the 81 patients who achieved complete tumor removal for primary, CRLM, and concomitant EHD, 62 (76.5%) had recurrence. Repeat surgery was performed in 38 patients; 35 for recurrence after curative surgery and 3 for liver recurrence with unresected concomitant EHD or primary tumor. Of these 38 patients, 31 were salvaged. The patients who underwent repeat surgery had a significantly longer OS than those who did not (45.8% vs 26.3%; P = 0.0041). A multivariate analysis revealed that repeat surgery was an independent prognostic factor of the OS after TSH (hazard ratio 0.31, P = 0.0012). Conclusions: Repeat surgery for recurrence after TSH may be crucial for the long-term survival in patients with extensive bilobar CRLM. Intensive oncosurgical surveillance is essential to avoid missing the chance for repeat surgery after TSH.

BACKGROUND: The importance of primary biliary cholangitis as an indication for liver transplantation has probably been influenced by the introduction of therapies, and changes in selection criteria and disease epidemiology.AIMS: To assess the time trends in liver transplantation for primary biliary cholangitis and to evaluate the characteristics of the patient population during the past three decades.METHODS: Patients undergoing liver transplantation from 1986 to 2015 in centres reporting to the European Liver Transplantation Registry were included. We excluded combined organ transplantations and patients RESULTS: We included 112 874 patients, of whom 6029 (5.3%) had primary biliary cholangitis. After an initial increase in the first decade, the annual number of liver transplantation for primary biliary cholangitis remained stable at around 200. The proportion of liver transplantations for primary biliary cholangitis decreased from 20% in 1986 to 4% in 2015 (P < 0.001). Primary biliary cholangitis was the only indication showing a consistent proportional decrease throughout all decades. From the first to the third decade, the age at liver transplantation increased from 54 (IQR 47-59) to 56 years (IQR 48-62) and the proportion of males increased from 11% to 15% (both P < 0.001).CONCLUSIONS: We have found a proportional decrease in primary biliary cholangitis as indication for liver transplantation. However, despite treatment with ursodeoxycholic acid and improved disease awareness, the absolute annual number of liver transplantations has stabilised.