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Abstract: Background: Acute rejection is still a common complication of hepatic transplantation. The diagnosis, based on the histological examination of the graft, may be difficult to confirm in the setting of combined hepatitis C virus infection. The presence of C4d in the portal capillaries could facilitate differentiation between acute rejection and relapsed hepatitis C. The deposit of C4d provides evidence of activation of humoral immunity. To attempt to confirm this hypothesis, we searched for the presence of C4d in posttransplant hepatic biopsies. Methods: Thirty-six biopsies from 34 patients were analyzed retrospectively. The samples had been requested for one of the following reasons: suspected rejection, relapsed hepatitis C infection, or systematic check-up 1 year after the transplant. Results: C4d expression was common in biopsies classified as acute rejection (33%) and chronic rejection (100%). C4d was never detected in the event of recurrent hepatitis C infection without rejection. Conclusion: These results, which are comparable to recently published data, give credence to the theory that C4d could be used as a marker for rejection following hepatic transplantation. [Copyright &y& Elsevier]

When liver graft procurements take place in the late afternoon or in the evening, transplantation is often performed at night when alertness and psychomotor abilities may be altered. Our objective was to determine whether liver transplantation performed at night increases severe 90-day postoperative complication rates. In this observational study, we analyzed all consecutive patients who were transplanted between January 1, 2012 and December 31, 2018. Outcomes were compared according to whether all or part of the liver transplantation was performed or not (control group) at late night, i.e., between midnight and 5 a.m. The main outcome was rate of Clavien-Dindo ≥ IIIb complications within 90 days post-transplantation. 790 liver transplantations were analyzed. In a multivariable analysis adjusted for cold ischemic time, late-night procedures required more blood transfusions (P = 0.010) and had higher odds of severe complication occurrence than controls (odds ratio 1.67; 95% CI, [1.10-2.54]). One-year graft and patient survival was similar. We conclude that the organization of liver transplant surgery should be reconsidered to avoid LN surgery as much as can be done. Except to create teams dedicated to night work (which represents a considerable cost), such organization may require safe extension of liver graft preservation times. The alternative could be to extend the use of oxygenated machine perfusion preservation with the unique purpose of safely extending the graft preservation time., (© 2024. Italian Society of Surgery (SIC).)

Background: Laparoscopic right anterior sectionectomy (LRAS) remains a technically demanding procedure as it requires two transection planes where the middle and right hepatic veins run; however, the main difficulty is locating these two planes 1-3 . The aim of this video was to show the technique of an LRAS performed with a transparenchymal glissonean pedicle approach and guided by indocyanine green (ICG) staining., Methods: This was the case of an 80-year-old man with a history of hemochromatosis and normal liver function. He was diagnosed with a 6 cm hepatocellular carcinoma (HCC) located at segment 8, close to the right anterior pedicle., Results: The technique consisted of parenchymal transection along the main portal fissure along the right border of the middle hepatic vein. Opening the liver facilitated access to the right anterior glissonean pedicle and selective transparenchymal clamping. A negative-stain ICG test permitted to demarcate the transection line along the right lateral portal fissure. The parenchymal transection was carried out in a caudal approach, along two perfectly marked planes, preserving the middle and right hepatic veins. The duration of the procedure was 200 min and blood loss was 300 mL. Postoperative course was uneventful and the patient was discharged on the third postoperative day., Conclusion: Guidance during resection, and protection of the right posterior pedicle and right hepatic vein are the key points of the LRAS. The glissonean approach and the ICG imaging technology are of great help in resolving these difficulties., (© 2024. Society of Surgical Oncology.)

Background: Although the incidence of BTC is raising, national healthcare strategies to improve care lack. We aimed to explore patient clinical care pathways and strategies to improve biliary tract cancer (BTC) care., Methods: We analysed the French National Healthcare database of all BTC inpatients between January 1, 2017 and December 31, 2021. Multinomial logistic regression adjusted odds ratios (aOR) were used to identify healthcare organisation factors that influenced access to curative care both overall and in a longitudinal sensibility analysis using optimal matching and hierarchical ascending classification to detect a subgroup of curative-care patients with a high survival over a two-year period., Results: A total of 19,825 new BTC patients and three clinical care pathways (CCP) were identified: 'Palliative care' (PC-CCP), 'Non-curative Care' (NCC-CCP) and 'Curative Care' (CC-CCP) involving 7669 (38.7%), 7721 (38.9%) and 4435 (22.4%) patients respectively. Out of 1200 centers involved in BTC treatment, 84%, 11% and 5% were of low- (<15 patients/year), medium- (15-30 patients/year) and high-volume (>30 patients/year) respectively. Among patient, tumor and hospital factors, BTC management in academic (aOR: 2.32; 95%CI: 1.98-2.71), private (2.51; 2.22-2.83), semi-private (2.25; 1.91-2.65) and in high- (2.09; 1.81-2.42) or medium-volume (1.49; 1.33-1.68) centers increased probability to CC-CCP. These results were maintained in a longitudinal cluster of 2363 (53%) CC-CCP patients presenting a higher two-year survival compared with the rest [96.4% (95.1; 97.6) vs. 38.8% (36.3; 41.4), log-rank p < 0.001]., Conclusions: Among factors subject to healthcare policy improvement, the volume and type of centers managing BTC strongly influenced access to curative care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In the era of innovating minimal invasive surgery, laparoscopic right posterior sectionectomy (RLPS) is considered a technically challenging procedure for its deeply anatomic location. 1,2 Performed by experienced surgeons, it has been shown to be a safe and feasible procedure. 3-6 The purpose of this video was to show the technique of a RLPS., Methods: This is the case of a 70-year-old man who was treated for a mid-rectum adenocarcinoma with two synchronous liver metastases located in the posterior sector of the right liver. Tumor board decision was chemoradiotherapy followed by a simultaneous rectal and hepatic surgery., Results: An extrahepatic Glissonian approach of the right posterior pedicle was performed. After selective clamping of the right posterior pedicle and injection of indocyanine green, the right portal fissure between the two sectors of the right liver appeared. The parenchymal transection performed in a caudal approach, along a perfectly marked plane. One metastasis was in contact with the right hepatic vein. Because R1 vascular surgery has demonstrated similar oncological outcomes to R0 resection, we detached the metastasis from the vein to preserve a good venous drainage of the remaining right liver. 7 The procedure was completed with a laparoscopic anterior resection of the rectum. The duration of the liver resection was 200 min, and blood loss was 300 ml. Postoperative course was uneventful, and the patient was discharged on postoperative Day 10., Conclusions: Laparoscopic right posterior sectionectomy is a safe and feasible procedure. 3-6 However, it is technically challenging and requires advanced experience in liver and laparoscopic surgery. 5,6 ., (© 2024. Society of Surgical Oncology.)

Introduction: This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org)., Methods: This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC. Recommendations were graded in three categories (A, B and C) according to the level of scientific evidence until August 2023., Results: BTC diagnosis and staging is mainly based on enhanced computed tomography, magnetic resonance imaging and (endoscopic) ultrasound-guided biopsy. Treatment strategy depends on BTC subtype and disease stage. Surgery followed by adjuvant capecitabine is recommended for localised disease. No neoadjuvant treatment is validated to date. Cisplatin-gemcitabine chemotherapy combined to the anti-PD-L1 inhibitor durvalumab is the first-line standard of care for advanced disease. Early systematic tumour molecular profiling is recommended to screen for actionable alterations (IDH1 mutations, FGFR2 rearrangements, HER2 amplification, BRAF V600E mutation, MSI/dMMR status, etc.) and guide subsequent lines of treatment. In the absence of actionable alterations, FOLFOX chemotherapy is the only second-line standard-of-care. No third-line chemotherapy standard is validated to date., Conclusion: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice. Each individual BTC case should be discussed by a multidisciplinary team., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gael Roth declares consulting or advisory role or invitation as a speaker for Servier, AstraZeneca, Bristol-Myers Squibb, MSD, Amgen, Ipsen, Accord Healthcare, Pierre Fabre, Incyte, Netris Pharma and Alpha Tau, as well as travel accommodations, or expenses from Servier, AstraZeneca, Bristol Myers Squibb, MSD, Roche, Amgen, Viatris, Pierre Fabre and Ipsen. Research funding by Genoscience Pharma, Netris Pharma. Matthieu Sarabi declares consultancy/honoraria AstraZeneca, Servier, Roche and accommodations or expenses from Ipsen. Jean-Frédéric Blanc declares honoraria from incyte, servier, AZ, Roche, Tahio oncology, MSD. Anne-Laure Bretagne-Bignon declares consulting for Astra Zeneca, Servier, Ipsen and accommodations or congress registration support for Merck and Ipsen. Romain Coriat declares honoraria for lectures and Advisory board for: BAYER, Servier, Pierre Fabre, AAA, Merck, Amgen. Christelle de la Fouchardière declares holding an advisory role with Amgen, Bayer, BMS, Daichi-Sankyo, Eisai, Imescia, Incyte, Lilly, Merck, MSD, Pierre Fabre Oncologie, Roche, and Servier; receiving grants from Pierre Fabre and Servier outside of the submitted work; receiving fees from Ipsen, Eisai, Pierre Fabre, Servier, being an invited speaker outside of the submitted work. Julien Edeline declares consulting or advisory role for BTG, Bristol Myers Squibb, AstraZeneca, Bayer, Ipsen, AstraZeneca, MSD, Eisai, Boston Scientific, Roche, Basilea, Merck Serono, Servier; research Funding from Bristol Myers Squibb (Inst), BeiGene (Inst); travel, accommodations or expenses from Amgen, Bristol Myers Squibb, Roche. Astrid Lièvre declares honoraria for lectures from Amgen, Astellas, Astra-Zeneca, Bayer, BMS, Incyte, Ipsen, Leo-pharma, Mylan, Novartis, Pierre Fabre, Roche, Servier and Viatris; consulting/advisory relationship from AAA, Astellas, Bayer, BMS, Incyte, Pierre Fabre and Servier; travel, accommodations or congress registration support from Bayer, Boehringer, Ipsen, Mylan, MSD, Pierre Fabre, Roche and Servier; research funding from Bayer (Inst), Lilly (Inst). Sylvain Manfredi declares travel accommodation from MSD, AMGEN. Cindy Neuzillet declares Honoraria and consulting from Amgen, AstraZeneca, Baxter, Bristol-Myers Squibb, Fresenius Kabi, Incyte Biosciences, Merck, MSD, Mundipharma, Novartis, Nutricia, OSE Immunotherapeutics, Pierre Fabre, Roche, Sanofi, Servier, Viatris, as well as research funding AstraZeneca, Bristol-Myers Squibb, Fresenius Kabi, Nutricia, OSE Immunotherapeutics, Roche, Servier, Viatris. Valérie Paradis declares honoraria for lectures from Incyte. Anthony Turpin declares personal fees from Servier, Viatris, Incyte Bioscience, BMS, Merck and grants and personal fees from AstraZeneca and MSD. Olivier Bouché declares consulting or advisory role for Pierre Fabre, Amgen, Bayer, Servier, MSD, Deciphera, Apmonia Therapeutics and Merck outside the submitted work. David Malka declares honoraria for Roche, Amgen, Bayer, Merck Serono, Servier, Sanofi, Pierre Fabre, Viatris, Bristol Myers Squibb, MSD Oncology, LEO Pharma, Incyte, AstraZeneca; consulting or advisory role: Roche, Sanofi, Merck Serono, MSD, Servier, Bayer, Incyte, Amgen, Bristol Myers Squib, Taiho Oncology, AbbVie, AstraZeneca, Pierre Fabre; travel, accommodations or expenses from Roche, Bayer, Sanofi, Merck Serono, Amgen, Servier, Pierre Fabre, Bristol Myers Squibb/Pfizer, MSD, Viatris. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Interim analysis of the DOSISPHERE-01 study demonstrated a strong improvement in response and overall survival (OS) on using 90 Y-loaded glass microspheres with personalized dosimetry compared with standard dosimetry in patients with nonoperable locally advanced hepatocellular carcinoma. This report sought to provide a long-term analysis of OS. Methods: In this phase II study (ClinicalTrials.gov identifier NCT02582034), treatment was randomly assigned (1:1) with the goal to deliver either at least 205 Gy (if possible >250-300 Gy) to the index lesion in the personalized dosimetry approach (PDA) or 120 ± 20 Gy to the treated volume in the standard dosimetry approach (SDA). The 3-mo response of the index lesion was the primary endpoint, with OS being one of the secondary endpoints. This report is a post hoc long-term analysis of OS. Results: Overall, 60 hepatocellular carcinoma patients with at least 1 lesion larger than 7 cm and more than 30% of hepatic reserve were randomized (intent-to-treat population: PDA, n = 31; SDA, n = 29), with 56 actually treated (modified intent-to-treat population: n = 28 in each arm). The median follow-up for long-term analysis was 65.8 mo (range, 2.1-73.1 mo). Median OS was 24.8 mo and 10.7 mo (hazard ratio [HR], 0.51; 95% CI, 0.29-0.9; P = 0.02) for PDA and SDA, respectively, in the modified intent-to-treat population. Median OS was 22.9 mo for patients with a tumor dose of at least 205 Gy, versus 10.3 mo for those with a tumor dose of less than 205 Gy (HR, 0.42; 95% CI, 0.22-0.81; P = 0.0095), and was 22.9 mo for patients with a perfused liver dose of 150 Gy or higher, versus 10.3 mo for those with a perfused liver dose of less than 150 Gy (HR, 0.42; 95% CI, 0.23-0.75; P = 0.0033). Lastly, median OS was not reached in patients who were secondarily resected ( n = 11, 10 in the PDA group and 1 in the SDA group), versus 10.8 mo in those without secondary resection ( n = 45) (HR, 0.17; 95% CI, 0.065-0.43; P = 0.0002). Only resected patients displayed favorable long-term OS rates, meaning an OS of more than 50% at 5 y. Conclusion: After longer follow-up, personalized dosimetry sustained a meaningful improvement in OS, which was dramatically improved for patients who were accurately downstaged toward resection, including most portal vein thrombosis patients., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Backgound and Aims: In advanced, liver-only intrahepatic cholangiocarcinoma (iCCA), selective internal radiation therapy (SIRT) has been suggested as promising in nonrandomized studies. We aimed to compare data from patients with advanced, liver-only iCCA treated in the first line in clinical trials with either chemotherapy alone or the combination with SIRT., Approach and Results: We collected individual patients' data from the ABC-01, ABC-02, ABC-03, BINGO, AMEBICA, and MISPHEC prospective trials. Data from patients with liver-only iCCA treated in chemotherapy-only arms of the first 5 trials were compared with data from patients treated with SIRT and chemotherapy in MISPHEC. Emulated target trial paradigm and Inverse Probability of Treatment Weighting (IPTW methods) using the propensity score were used to minimize biases. We compared 41 patients treated with the combination with 73 patients treated with chemotherapy alone, the main analysis being in 43 patients treated with cisplatin-gemcitabine or gemcitabine-oxaliplatin. After weighting, overall survival was significantly higher in patients treated with SIRT: median 21.7 months (95% CI: 14.1; not reached) versus 15.9 months(95% CI: 9.8; 18.9), HR = 0.59 (95% CI: 0.34; 0.99), p = 0.049. Progression-free survival was significantly improved: median 14.3 months (95% CI: 7.8; not reached) versus 8.4 months (95% CI: 5.9; 12.1), HR = 0.52 (95% CI: 0.31; 0.89), p < 0.001. Results were confirmed in most sensitivity analyses., Conclusions: This analysis derived from prospective clinical trials suggests that SIRT combined with chemotherapy might improve outcomes over chemotherapy alone in patients with advanced, liver-only iCCA. Randomized controlled evidence is needed to confirm these findings., (Copyright © 2023 American Association for the Study of Liver Diseases.)

The exploitation of food industry wastes and their conversion into value-added products present a promising and continuously growing field, given the diversity of elaborated wastes. The current work aimed to utilize sweet cheese whey as a growth medium for acid protease production by a local fungus strain. The biochemical and physicochemical properties of the cheese whey, such as pH, conductivity, chemical oxygen demand, biological oxygen demand (BOD 5 ), total nitrogen and protein contents, and mineral salts, were assessed using various analytical methods. The effect of certain parameters on acid protease production by Mucor circinelloides MG603064.1 through the SmF process was investigated using the conventional design method "One factor at a time". Subsequent to characterization, the crude extract was used in a trial to create fromage frais , compared to the commercial rennin CHY-MAX ® Powder Extra. Cheese whey characterization revealed its richness in total nitrogen (1.044 ± 0.044 g/l), protein content (6.52 ± 0.04 g/l), and principal mineral salts: calcium (1.637 ± 0.037 g/l), phosphorus (1.173 ± 0.023 g/l), and chloride (1.66 ± 0.09 g/l). The optimal values of the SmF process for acid protease production, such as the inoculum size, beef extract, and KH 2 PO 4 supplements, the initial pH of cheese whey, and incubation temperature were, respectively, 11% (v/v), 0.4% (w/v), 0.5% (w/v), 5.5, and 30°C. Under these conditions, the lowest milk-clotting time of 290 s was achieved, representing an 18.41-fold increase compared to the initial step using the unoptimized medium. The enzyme showed maximum milk-clotting activity at pH 5, a temperature of 60°C, and in the presence of 0.025 M of CaCl 2 . The enzyme activity also significantly improved with sonication (35 kHz) for 10 min. The crude extract of M. circinelloides ensured the production of fresh cheese samples with characteristics roughly similar to those obtained by the control (CHY-MAX ® rennin). The acid protease of M. circinelloides could successfully substitute the conventional rennin in the manufacture of fresh cheese., Competing Interests: The authors declare no conflict of interest., (© 2023 Institute of Bioorganic Chemistry, Polish Academy of Sciences.)

This research paper focused on the monitoring of marine sites using mussels, which are highly valuable organisms in assessing environmental health. However, a significant challenge arises when determining the appropriate size of mussels for monitoring purposes. The objective of this study was to examine the levels of Cd, Pb, As, and Co in three different size classes of two mussel species, Mytilus galloprovincialis and Perna perna, collected from three sites along the Algerian coast, each exhibiting varying degrees of pollution.At each of the study sites, a total of thirty individuals from small, medium, and large size classes of mussels were collected during four different time periods. The mussels were then dissected, and the concentrations of Cd, Pb, As, and Co were measured in the entire flesh of the mussels using ICP-MS.Across the various study sites, the concentrations of cadmium, lead, arsenic, and cobalt ranged from 0.06 to 1.32 mg/kg, 0.09 to 12.56 mg/kg, 4.23 to 18.31 mg/kg, and 0.11 to 1.85 mg/kg, respectively. Interestingly, the distribution of these metals in the three different size classes of mussels followed a consistent pattern at all the study sites. Large mussels exhibited higher concentrations, while small and medium-sized mussels displayed lower levels. These findings highlight substantial spatial and temporal variations in metal concentrations within the studied sites., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft preservation in the donation after brainstem death (DBD) context. Uterus transplantation is a new surgical approach to treating absolute uterine infertility; it can be performed after living donation or after DBD. In the DBD context, the uterus is typically the last organ removed after other vital organs, with the exception of the Baylor team, which removes the uterus first. This key aspect imposes an unavoidable mild temperature ischemia for >1 hour on the uterus during the removal of the vital abdominal and chest organs. In renal transplantation, the perfusion machine reduces the risk of delayed graft function; thus, we hypothesized that machine perfusion could result in a reduction of uterus graft dysfunction. The uterus graft dysfunction could be expressed by a low embryo implantation rate, pregnancy loss, or vascular pregnancy diseases such as preeclampsia or fetal growth restriction." To date, static cold storage of the uterus is the only standard method for preservation before transplantation. HMP is an emerging method that could potentially improve the preservation of the uterus to enhance graft preservation in the DBD context., Design: This video article shows all the technical details of using the HMP for uterine transplantation., Setting: University., Animals: Porcine model., Intervention: Porcine uterus was retrieved from a DBD domestic animal model and flushed with KPS MP (Bridge To Life Ltd in UK) at 4 °C. After vascular preparation on the back table, the uterus was perfused using KPS MP through a cannula in the aorta using the VitaSmart device (Bridge To Life Ltd in UK) for 18 hours. Then, the uterus was transplanted to the porcine recipient., Main Outcome Measures: The macroscopic appearance of the uterus at the end of HMP and the assessment of the uterus vascularization after transplantation in the recipient compared with the native uterus., Results: This video shows the cannulation of the iliac vessels, cooling and removal of the uterus on a porcine model, uterus preservation using HMP during 18 hours, and then UT in a new recipient pig with the reperfusion of the transplanted uterus next to the native, intact uterus of the recipient. The macroscopic appearance of the uterus at the end of HMP appeared viable and was perfectly flushed. The assessment of the uterus vascularization after transplantation in the recipient was similar to that of the native uterus. To our knowledge, we describe here for the first time the UT procedure in DBD context on an animal model and the use of HMP for uterus preservation in UT programs; this could increase the number of uterine grafts available for a greater number of female recipients., Conclusion: Hypothermic machine perfusion could allow the duration of cold ischemia to be prolonged without altering the uterine graft. Nevertheless, this assertion has to be validated in a human context., Competing Interests: Declaration of interests L.D. has received nonfinancial support (loan of infusion machine) from VitaSmart for the submitted work and funding from Biomedicine Agency call for tenders Graft. C.S. has nothing to disclose. K.B. reports nonfinancial support (loan of infusion machine) from VitaSmart for the submitted work. D.V.L. has nothing to disclose. S.J. has nothing to disclose. N.R.L. has nothing to disclose. E.F. has nothing to disclose. V.L. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate the efficacy of yttrium-90 transarterial radioembolization (TARE) to convert to resection initially unresectable, single, large (≥5 cm) hepatocellular carcinoma (HCC)., Background: TARE can downsize cholangiocarcinoma to resection but its role in HCC resectability remains debatable., Methods: All consecutive patients with a single large HCC treated between 2015 and 2020 in a single tertiary center were reviewed. When indicated, patients were either readily resected (upfront surgery) or underwent TARE. TARE patients were converted to resection (TARE surgery) or not (TARE-only). To further assess the effect of TARE on the long-term and short-term outcomes, a propensity score matching analysis was performed., Results: Among 216 patients, 144 (66.7%) underwent upfront surgery. Among 72 TARE patients, 20 (27.7%) were converted to resection. TARE-surgery patients received a higher mean yttrium-90 dose that the 52 remaining TARE-only patients (211.89±107.98 vs 128.7±36.52 Gy, P <0.001). Postoperative outcomes between upfront-surgery and TARE-surgery patients were similar. In the unmatched population, overall survival at 1, 3, and 5 years was similar between upfront-surgery and TARE-surgery patients (83.0%, 60.0%, 47% vs 94.0%, 86.0%, 55.0%, P =0.43) and compared favorably with TARE-only patients (61.0%, 16.0% and 9.0%, P <0.0001). After propensity score matching, TARE-surgery patients had significantly better overall survival than upfront-surgery patients ( P =0.021), while disease-free survival was similar ( P =0.29)., Conclusion: TARE may be a useful downstaging treatment for unresectable localized single large HCC providing comparable short-term and long-term outcomes with readily resectable tumors., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities., Background: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures., Methods: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient., Results: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months., Conclusion: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor after hepatocellular carcinoma (HCC). Management depends on their resectability at the time of diagnosis. Two types can be distinguished by imaging: resectable ICCs amenable to surgery and locally advanced and/or metastatic ICCs, that are treated by chemotherapy, radiotherapy or loco-regional treatment (radioembolization, chemoembolization, intra-arterial chemotherapy and thermoablation). Over the last decade, the management strategy for these tumors has been modified by the appearance of loco-regional treatments as well as the introduction of immunotherapy that have shown their efficacy in the control of ICC. The aim of this review is to describe the current status of treatments for ICCs, as well as the different therapeutic strategies being assessed., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The aim of our study is to evaluate anti-inflammatory effect of Chamaemelum nobile. Aqueous extracts were administrated to Wistar rats in bronchial-inflammation experimentally induced by an allergen and ovalbumin, administered intraperitoneally / intranasally (20mg/kg/day). Experimentation showed disturbances in bronchoalveolar fluid with increased leukocyte and lymphocyte levels as well as IL-4 concentration in the lungs and erythrocytes associated with high lipid peroxidation. There were disturbances in enzymatic and non-enzymatic antioxidant defense system. Lungs histopathological showed an inflammatory lymphoplasmacytic infiltrate, moderate edema of alveoli, vascular congestion and suffusion hemorrhage. Administration of aqueous extract to OVA-sensitized rats caused a significant and very highly significant improvement of MDA levels in lungs, erythrocytes, GSH, GPx, GST, catalase and SOD. We notice a decrease in IL-4 in LBA and lungs alongside reduced inflammatory cell infiltration, mild bronchiolar dilation, mild alveolar edema and normal cell morphology allowing us to conclude on the effectiveness of anti-inflammatory activity of Roman chamomile.

Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management., Methods: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements., Results: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term "early metachronous metastases" applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with "late metachronous metastases" applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed., Conclusions: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management., Methods: This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements., Results: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed., Conclusion: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd and published by Elsevier Ltd on behalf of the International Hepato-Pancreato-Biliary Association Inc.)

Background: Acute liver failure (ALF) is a rare but life-threatening condition mostly requiring intensive care unit (ICU) admission. ALF induces immune disorders and may promote infection acquisition. However, the clinical spectrum and impact on patients' prognosis remain poorly explored., Methods: We conducted a retrospective single-centre study on patients admitted for ALF to the ICU of a referral University Hospital from 2000 to 2021. Baseline characteristics and outcomes according to the presence of infection until day 28 were analysed. Risk factors for infection were determined using logistic regression. The impact of infection on 28-day survival was assessed using the proportional hazard Cox model., Results: Of the 194 patients enrolled, 79 (40.7%) underwent infection: community-acquired, hospital-acquired before ICU and ICU-acquired before/without and after transplant in 26, 23, 23 and 14 patients, respectively. Most infections were pneumonia (41.4%) and bloodstream infection (38.8%). Of a total of 130 microorganisms identified, 55 were Gram-negative bacilli (42.3%), 48 Gram-positive cocci (36.9%) and 21 were fungi (16.2%). Obesity (OR 3.77 [95% CI 1.18-14.40]; p  = .03) and initial mechanical ventilation (OR 2.26 [95% CI 1.25-4.12]; p  = .007) were independent factors associated with overall infection. SAPSII > 37 (OR 3.67 [95% CI 1.82-7.76], p  < .001) and paracetamol aetiology (OR 2.10 [95% CI 1.06-4.22], p  = .03) were independently associated with infection at admission to ICU. On the opposite, paracetamol aetiology was associated with lower risk of ICU-acquired infection (OR 0.37 [95% CI 0.16-0.81], p  = .02). Patients with any type of infection had lower day 28 survival rates (57% versus 73%; HR 1.65 [1.01-2.68], p  = .04). The presence of infection at ICU admission ( p  = .04), but not ICU-acquired infection, was associated with decreased survival., Conclusions: The prevalence of infection is high in ALF patients which is associated with a higher risk of death. Further studies assessing the use of early antimicrobial therapy are needed.

The Multiple Linear Regression (MLR) technique was used to determine the relationship between the integrated biomarker response index (IBR) with the most important confounding factors (Temperature, pH, Salinity and Dissolved oxygen), in order to define: (1) the baseline assessment criteria (BAC), (2) the environmental assessment criteria (EAC) and (3) the BouIsmail Bay (BIB) -Taxonomy by using Mytilus galloprovincialis sampled from two references sites in BIB (W. Tipaza, Algeria) during one season. Therefore, our results show that, the temperature appeared as a major factor for the explanation of the model. The coefficients of determination and F values for IBR validated the efficiency of model. In addition, the use MLR, BAC and EAC values in BIB-Taxonomy can deference between unpolluted and polluted areas in BouIsmail Bay in particular and Algerian Bays in general. This approach is therefore a valuable tool that could be used for monitoring the coastal sites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Therapeutic targeting of the transforming growth factor beta (TGFβ) pathway in cancer represents a clinical challenge since TGFβ exhibits either tumor suppressive or tumor promoting properties, depending on the tumor stage. Thus, treatment with galunisertib, a small molecule inhibitor of TGFβ receptor type 1, demonstrated clinical benefits only in subsets of patients. Due to the functional duality of TGFβ in cancer, one can hypothesize that inhibiting this pathway could result in beneficial or adverse effects depending on tumor subtypes. Here, we report distinct gene expression signatures in response to galunisertib in PLC/PRF/5 and SNU-449, two cell lines that recapitulate human hepatocellular carcinoma (HCC) with good and poor prognosis, respectively. More importantly, integrative transcriptomics using independent cohorts of patients with HCC demonstrates that galunisertib-induced transcriptional reprogramming in SNU-449 is associated with human HCC with a better clinical outcome (i.e., increased overall survival), while galunisertib-induced transcriptional reprogramming in PLC/PRF/5 is associated with human HCC with a worse clinical outcome (i.e., reduced overall survival), demonstrating that galunisertib could indeed be beneficial or detrimental depending on HCC subtypes. Collectively, our study highlights the importance of patient selection to demonstrate a clinical benefit of TGFβ pathway inhibition and identifies Serpin Family F Member 2 (SERPINF2) as a putative companion biomarker for galunisertib in HCC., (© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Marine pollutants such as heavy metals (HMs) are considered among the most copious oxidative stress (OS) inducers in marine organisms which leads to reactive oxygen species (ROS) formation. Complementary to our previous bioassays studies, the present research focuses on Catalase (CAT), Glutathione S-transferase (GST) and Malondialdehyde (MDA) as oxidative stress biomarkers and the integrated biomarker response (IBR) indexes (IBR 1 and IBR 2 ) as an ecotoxicological assessment tool in Mytilus galloprovincialis using central composite face centered (CCF) design. The oxidative stress biomarkers were measured in adult mussels (45-55 mm) on 3 days-exposed under different sub-lethal concentrations of cadmium (Cd), zinc (Zn), and copper (Cu). Using multiple regressions, ANOVA analysis revealed that experimental data fitted to second-order (quadratic) polynomial equations. The results showed that types, concentrations and metals combinations has a direct effect in CAT and GST activities, MDA level and IBR indexes. Additionally, metal-metal interactions were found synergistic (supra-additive), antagonistic (infra-additive) or zero interaction in the toxicological effect. As necessary, the optimization of the experimental results was done in order to determine the optimal conditions for the oxidative stress responses and IBR indexes. It was demonstrated that the CCF design combined with the multi-biomarker approach and IBR index can be used as an appropriate tool in ecotoxicological modulation and prediction of oxidative stress and antioxidant status by heavy metals in the mussels Mytilus galloprovincialis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: A transjugular intrahepatic portosystemic shunt (TIPS) before the liver transplantation (LT) has been considered a contraindication in cases of hepatocellular carcinoma (HCC) because of the risk of tumour growth. We aimed to assess the impact of TIPS on incidental HCC and oncological outcomes in transplanted patients with pre-existing HCC., Methods: All consecutive transplanted patients for cirrhosis who had a previous TIPS with or without HCC were included. Between 2007 and 2014, 1912 patients were transplanted. We included 122 (6.3%) patients having TIPS before LT. A 1:3 matched cohort of 366 patients (18.9%) having LT without previous TIPS was selected using a propensity score. Incidental HCC rate and risk factor of HCC recurrence were evaluated using multivariate analysis with a competing risk model., Results: Before LT, in the TIPS group, 27 (22.1%) had an HCC vs. 81 (22.1%) in the control group (p = 1). The incidental HCC rate was similar: 10.5% (10/95) in the TIPS group vs. 6.3% (18/285) in the control group (p = 0.17). Recurrence occurred in 1/27 (3.7%) patient in the TIPS group and in 7/81 (8.6%) patients in the control group, without significant difference (p = 0.51). After multivariate regression, patient's gender (p < 0.01) was significantly associated with HCC recurrence while a tumour within Milan criteria (p = 0.01, sHR: 0.17 [0.04; 0.7]) and an incidental HCC (p<0.01) were found to be protector factors against HCC recurrence., Conclusion: TIPS did not worsen the prognosis of transplanted patients for HCC. TIPS should no longer be contraindicated for oncological reasons in patients with HCC waiting for an LT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: With a mortality rate of up to 30%, post-pancreatectomy hemorrhage (PPH) remains a serious complication after pancreatoduodenectomy (PD) for cancer. Little is known about the long-term survival of patients after PPH. This retrospective study aimed to evaluate the impact of PPH on long-term survival after PD., Methods: The study included 830 patients (PPH, n = 101; non-PPH, n = 729) from two centers, who underwent PD for oncological indications. PPH was defined as any bleeding event occurring within 90 days after surgery. A flexible parametric survival model was used to determine the evolution of the risk of death over time., Results: At postoperative day 90, PPH significantly increased the mortality rate (PPH vs. non-PPH: 19.8% vs. 3.7%, p < 0.0001) and severe postoperative complication rate (85.1% vs. 14.1%, p < 0.0001), and decreased median survival (18.6 months vs. 30.1 months, p = 0.0001). PPH was associated with an increased mortality risk until the sixth postoperative month. After this 6-month period, PPH had no more influence on mortality., Conclusions: PPH had a negative impact on the short-term overall survival beyond postoperative day 90 and up to six months after PD. However, compared to non-PPH patients, this adverse event had no impact on mortality after a 6-month period.

Background: Bacteriobilia may increase the rate of deep infectious complications (DIC) after pancreaticoduodenectomy. To better adjust prophylactic and empirical antibacterial treatment, we aimed to characterize bacteriobilia in patients with preoperative endoprosthesis, and its association with postoperative DIC., Methods: All patients who underwent pancreaticoduodenectomy in our center between 2010 and 2019 were included. The association between microbiological findings from bile samples, and postoperative DIC was analyzed, and we compared microbiology data between 2010-2014 and 2015-2019 periods., Results: We enrolled 578 patients (median age 67 years [59-72], 58.7% males), of whom 220 (38.1%) had preoperative biliary endoprosthesis, with 197 (89.5%) positive preoperative bile samples pathogens were Enterobacterales, enterococci, and Candida albicans. The incidence of DIC was similar in patients with or without endoprosthesis (20.4% vs 17.8%, P = .352). Bacterial isolates collected during 2015-2019 were more resistant to cefotaxime than those recovered from 2010-2014 (45.5% vs 25.5%, P = .009). The only independent risk factor for DIC in patients with endoprosthesis was cefotaxime resistance in bile (hazard ratio 3.027 [1.115-8.216], P = .03)., Conclusions: The incidence of DIC is high after pancreaticoduodenectomy, with or without endoprosthesis, despite routine postoperative treatment. Cefotaxime resistance, the only independent predictor of DIC in patients with endoprosthesis, has increased over time. Hence, cefotaxime may no longer be an appropriate empirical treatment., (© 2022 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background & Aims: Liver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it., Method: This retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies., Results: We analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT <65 years (odds ratio [OR] 4.214; p = 0.044), high-density lipoprotein-cholesterol <1.15 mmol/L after LT (OR 3.463; p = 0.013) and grade ≥2 steatosis on the graft at 1 year after LT (OR 10.196; p = 0.001). The cumulative incidence of advanced fibrosis (F3-F4) was 20.0% at 5 years after LT and significant risk factors from multivariate analysis were metabolic syndrome before LT (OR 8.550; p = 0.038), long-term use of cyclosporine (OR 11.388; p = 0.031) and grade ≥2 steatosis at 1 year after LT (OR 10.720; p = 0.049). No re-LT was performed for NAFLD cirrhosis recurrence., Conclusion: Our results strongly suggest that recurrence of initial disease after LT for NAFLD is inevitable and progressive in a large proportion of patients; the means to prevent it remain to be further evaluated., Impact and Implications: Non-alcoholic fatty liver disease (NAFLD) is a growing indication for liver transplantation, but the analysis of disease recurrence, based on graft liver biopsies, has been poorly studied. Cumulative incidences of steatosis, steatohepatitis and NAFLD-related significant fibrosis recurrence at 5 years were 85.0%, 60.3% and 48.0%, respectively. Grade ≥2 steatosis on graft biopsy at 1 year (present in 25% of patients) is highly predictive of recurrence of steatohepatitis and advanced fibrosis: bariatric surgery should be discussed in these patients specifically., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

The impact of body composition (BC) on the prognosis of resected intrahepatic cholangiocarcinoma (ICC) has been poorly studied. Aims: i) to evaluate the prevalence of low muscle mass (MM) in patients; ii) to assess the impact of BC on patient overall survival (OS) and disease-free survival (DFS), and iii) on the incidence of postoperative complications. All consecutive patients who underwent liver resection for ICC between 2004 and 2016 and who had preoperative CT scans were included. Ninety-three patients were included. Sixty percent (55/91) had low total MM. On multivariable analysis, high visceral fat (HR 2.48, CI95% [1.63; 3.77], p  < 0.0001), nodules >1 (HR 3.15 [1.67; 5.93], p  = 0.0004), involvement adjacent organ (HR 6.67 [1.88; 23.69], p  = 0.003), and postoperative sepsis (HR 3.04 [1.54; 5.99], p  = 0.0013) were independently associated with OS. High visceral fat (HR 2.10 [1.31; 3.38], p  = 0.002], nodules >1 (HR 3.01, [1.49; 6.10], p  = 0.002), postoperative sepsis (HR 5.16 [2.24; 11.89], p  = 0.0001), ASA score ( p  = 0.02) and perineural invasion (HR 3.30 [1.62; 6.76], p  = 0.001) were independently associated with lower DFS. Conclusion: 60% of ICC patients had low MM before surgery. High visceral fat, but not muscle mass, was an independent prognostic factor for poor OS and DFS in European patients with resected ICC.

Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds., Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds., Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria ( p <0.0001). At last tumor reassessment before LT, c-statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs . 0.68; p  = 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models ( "within-ALL") at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6)., Conclusions: In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach., Impact and Implications: Composite models were recently proposed for the selection of liver transplant (LT) candidates among individuals with hepatocellular carcinoma (HCC). We found that both the AFP score and Metroticket 2.0 predicted post-LT HCC recurrence and survival better than Milan criteria; the Metroticket 2.0 did not result in better reclassification for transplant selection compared to the AFP score, with predictive gaps and overlaps between the two models; patients who met low-risk thresholds for both models had the lowest 5-year recurrence rate. We propose prospectively testing the combination of both models, to further optimize the LT selection process for candidates with HCC., Competing Interests: The authors of this manuscript have no conflicts of interest to disclose as described by JHEP Reports. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Authors.)

Because of a narrow therapeutic index and a wide inter- and intra-patient variability, therapeutic drug monitoring of the immunosuppressant drug tacrolimus (TAC) based on whole-blood concentrations (C blood ) is mandatory in solid organ transplant recipients. Using peripheral blood mononuclear cells concentrations (C PBMC ) could improve patient outcomes. The poor correlation between C blood and C PBMC makes hypothesize that drug transporters are implicated in the intracellular accumulation of TAC. The aim of this work was therefore to clinically study: i) the role of genetic variants and ii) the effect of mRNA and protein expression of 4 drug transporters on the TAC C PBMC/blood ratio. In addition, functional in vitro experiments were performed to mechanistically validate the clinical observations. Genetic variants of ABCB1/P-gp and SLC28A3/CNT3 did not influence TAC C PBMC in liver transplant recipients (LTR). ABCC2/MRP2 at the mRNA level; ABCB1/P-gp, SLC28A3/CNT3 and SLC29A1/ENT1 at the protein level; correlated with the C PBMC/blood in kidney and LTR. In vitro results suing transporter-expressing cells confirmed that TAC is substrate of P-gp but not MRP2, whereas experiments remained inconclusive for CNT3 and ENT1. In conclusion, the genetic-transcription-protein-functional approach presented in this work provides new insights in the understanding of TAC transport at the T lymphocyte plasma membrane., Competing Interests: Declaration of competing interest Gwendal Coste's Ph.D. has been partly funded by Astellas Pharma. Florian Lemaitre has been invited to participation in congresses by Chiesi and Sandoz., (Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes., Background: DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF., Methods: The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out., Results: A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P =0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P =0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar., Conclusion: The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Uterine transplantation is on the rise worldwide. In contrast to its arterial anatomy, venous drainage of the uterus is poorly defined in the literature. Our aim was to provide a standardized description of uterine veins through a multimodal approach to establish anatomical landmarks for the uterine transplantation surgeon. Data were obtained from: (1) an anatomical study of eight fresh female cadavers (16 hemipelves) studied separately by an extra fascial dissection from the iliac bifurcation to the uterine pedicle, with analysis of the urinary tract and nerve structures and (2) a virtual anatomical study from the Anatomage® Table comprising a high-fidelity virtual reconstruction of two deceased female subjects by imaging and anatomical methods. An inconstant duality of uterine veins was identified: a deep uterine vein of larger caliber and a superficial uterine vein observed in 25% of cases. A close relationship of the ureter passing posterior to the superficial uterine vein and anterior to the deep uterine vein was evident in the parametrium. The inferior hypogastric plexus was identified in all cases immediately behind the deep uterine vein. The data obtained from the fresh female cadavers were validated by the Anatomage® Table. We describe the close relationship of the uterine veins with the ureter and the inferior hypogastric plexus. This knowledge represents a surgical landmark to support the success of uterine transplantation by respecting both the graft and the safety of the living donor by limiting the risk of injuries during uterus procurement., (© 2022 American Association for Clinical Anatomists and the British Association for Clinical Anatomists.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To define benchmark cutoffs for redo liver transplantation (redo-LT)., Background: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT., Methods: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers., Results: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks., Conclusion: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Liver transplantation (LT) is the treatment of end-stage non-alcoholic liver disease (NAFLD), that is decompensated cirrhosis and/or complicated by hepatocellular carcinoma (HCC). Few data on long-term outcome are available. The aim of this study was to evaluate overall patient and graft survivals and associated predictive factors., Method: This retrospective multicentre study included adult transplant patients for NAFLD cirrhosis between 2000 and 2019 in participating French-speaking centres., Results: A total of 361 patients (69.8% of male) were included in 20 centres. The median age at LT was 62.3 years [57.4-65.9] and the median MELD score was 13.9 [9.1-21.3]; 51.8% of patients had HCC on liver explant. Between 2004 and 2018, the number of LT for NAFLD cirrhosis increased by 720%. A quarter of the patients had cardiovascular history before LT. Median follow-up after LT was 39.1 months [15.8-72.3]. Patient survival at 1, 5 and 10 years after LT was 89.3%, 79.8% and 68.1% respectively. The main causes of death were sepsis (37.5%), malignancies (29.2%) and cardiovascular events (22.2%). In multivariate analysis, three risk factors for overall mortality after LT were recipient pre-LT BMI < 32 kg/m 2 at LT time (OR: 2.272; p = .012), pre-LT angioplasty during CV check-up (OR: 2.916; p = .016), a combined donor and recipient age over 135 years (OR: 2.020; 95%CI: p = .035)., Conclusion: Survival after LT for NAFLD cirrhosis is good at 5 years. Donor and recipient age, and cardiovascular history, are major prognostic factors to consider., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background : to date, long-term outcomes of R1 vascular (R1vasc) and R1 parenchymal (R1par) resections in the setting of intrahepatic cholangiocarcinoma (iCCA) have been examined in only one study which did not find significant difference. Patients and Methods : we analyzed consecutive patients who underwent iCCA resection between 2000 and 2019 in two tertiary French medical centers. We report overall survival (OS) and disease-free-survival (DFS). Univariate and multivariate analyses were performed to determine associated factors. Results : 195 patients were analyzed. The number of R0, R1par and R1vasc patients was 128 (65.7%), 57 (29.2%) and 10 (5.1%), respectively. The 1- and 2-year OS rates in the R0, R1par and R1vasc groups were 83%, 87%, 57% and 69%, 75%, 45%, respectively ( p = 0.30). The 1- and 2-year DFS rates in the R0, R1par and R1vasc groups were 58%, 50%, 30% and 43%, 28%, 10%, respectively ( p = 0.019). Resection classification (HR 1.56; p = 0.003) was one of the independent predictors of DFS in multivariate analysis. Conclusions : the survival outcomes after R1par resection are intermediate to those after R0 or R1vasc resection. R1vasc resection should be avoided in patients with iCCA as it does not provide satisfactory oncological outcomes.

Background: Selection of liver grafts suitable for transplantation (LT) mainly depends on a surgeon's subjective assessment. This study aimed to investigate the role of radiomic analysis of donor-liver CTs after brain death (DBD) to predict the occurrence of early posttransplant allograft dysfunction (EAD)., Methods: We retrospectively extracted and analyzed the left lobe radiomic features from CT scans of DBD livers in training and validation cohorts. Multivariate analysis was performed to identify predictors of EAD., Results: From 126 LTs included in the study in the training cohort, 27 (21.4%) had an EAD. For each patient, 279 radiomic features were extracted of which 5 were associated with EAD (AUC = 0.81) (95% CI 0.72-0.89). Among donor and recipient clinical characteristics, cardiac arrest, steatosis on donor's CT, cold ischemic time and age of recipient were also identified as independent risk factors for EAD. Combined radiomic signature and clinical risk factors showed a strong predictive performance for EAD with a C-index of 0.90 (95% CI 0.84-0.96). A validation cohort of 23 patients confirmed these results., Conclusion: Radiomic signatures extracted from donor CT scan, independently or combined with clinical risk factors is an objective and accurate biomarker for prediction of EAD after LT., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Transarterial radioembolization (TARE) with yttrium-90 ( 90 Y) glass microspheres is an efficacious option for converting appropriately selected patients with borderline-resectable hepatocellular carcinoma (HCC) to surgical candidacy., Methods: In 2018 and 2019, a diverse multidisciplinary group of surgical and interventional experts with experience using 90 Y for downstaging and bridging to liver transplant convened to review peer-reviewed literature and personal experience in the use of 90 Y to convert borderline resectable liver cancer patients to surgical candidacy. The working group included surgical oncologists specializing in liver cancer, liver transplant surgeons with experience in complex hepatobiliary surgery, and interventional radiologists with experience using 90 Y., Results: This document presents expert recommendations based upon the group's experience and consensus., Conclusions: By combining related evidence from the literature with expert experiences with TARE in surgical candidates, these recommendations aim to demonstrate the safety, efficacy, and feasibility of TARE in converting borderline-resectable patients to surgical options. The document also addresses the concerns about potential complications associated with TARE during the surgical intervention., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed., Methods: All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching., Results: Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002)., Conclusions: ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

How the side of an extended liver resection impacts the postoperative prognosis of advanced perihilar cholangiocarcinoma (PHC) is still controversial. We compared the outcomes of right (RTS) and left trisectionectomies (LTS) in Bismuth-Corlette (BC) type IV PHC resection. All patients undergoing RTS or LTS for BC type IV PHC in a single tertiary center between January 2012 and December 2019 were compared retrospectively. The endpoints were perioperative outcomes, long-term overall (OS), and disease-free survival (DFS). Among 67 hepatic resections for BC type IV PHC, 25 (37.3%) were LTS and 42 (63.7%) were RTS. Portal vein and artery resection rates were 40% and 52.4% (p = 0.29), and 24% and 0% (p < 0.001) in the LTS and RTS groups, respectively. The severe complication (Clavien−Dindo > IIIa) rate was comparable (36% vs. 21.5%, p = 0.357) while the postoperative liver failure (POLF) rate was lower in the LTS group (16% vs. 38%, p = 0.048). The R0 resection rate was similar between groups (81% vs. 92%; p = 0.154). The five-year OS rate was higher in the LTS group (66% vs. 30%, p = 0.009) while DFS was comparable (43% vs. 18%, p = 0.11). Based on multivariable analysis, the side of the trisectionectomy was an independent predictor of OS. Compared with RTS, LTS is associated with lower POLF and higher overall survival despite more frequent arterial reconstructions in type IV PHC. Although technically more demanding, LTS may be preferred in the treatment of advanced PHC.

Background: The futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era., Methods: 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., Results: A total of 10,172 cases were analysed. Recipient age >65 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., Conclusion: 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., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. All rights reserved.)