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In the current setting of organ shortage, brain-dead liver donors with recent liver trauma (RLT) represent a potential pool of donors. Yet, data on feasibility and safety of liver transplantation (LT) using grafts with RLT are lacking.All liver grafts from brain-dead donors with RLT proposed for LT between 2010 and 2018 were identified from the nationwide CRISTAL registry of the Biomedicine Agency. The current study aimed at evaluating 1-y survival as the primary endpoint.Among 11 073 LTs, 142 LTs (1.3%) using grafts with RLT were performed. These 142 LTs, including 23 split LTs, were performed from 131 donors (46.1%) of 284 donors with RLT proposed for LT. Transplanted grafts were procured from donors with lower liver enzymes levels (P 0.001) and less advanced liver trauma according to the American Association for the Surgery of Trauma liver grading system (P 0.001) compared with not transplanted grafts. Before allocation procedures, 20 (7%) of 284 donors underwent damage control intervention. During transplantation, specific liver trauma management was needed in 19 patients (13%), consisting of local hemostatic control (n = 15), partial hepatic resection on back-table (n = 3), or perihepatic packing (n = 1). Ninety-day mortality and severe morbidity rates were 8.5% (n = 12) and 29.5% (n = 42), respectively. One-year overall and graft survival rates were 85% and 81%, and corresponding 5-y rates were 77% and 72%, respectively.Using liver grafts from donors with RLT seems safe with acceptable long-term outcomes. All brain-dead patients with multiorgan trauma, including liver injury, should be considered for organ allocation.

Biallelic somatic mutations of TCF1 coding for hepatocyte nuclear factor 1α (HNF1α) are found in 50% of the hepatocellular adenoma (HCA) cases usually associated with oral contraception. In rare cases, HNF1α germ line mutations could also predispose to familial adenomatosis. In order to identify new genetic factors predisposing to HNF1α-mutated HCA, we searched for mutations in genes involved in the metabolism of estrogen. For 10 genes (CYP1A1, CYP1A2, CYP3A4, CYP3A5, COMT, UGT2B7, NQO1, GSTM1, GSTP1, and GSTT1), we did not find mutations nor differences in the allele distribution among 32 women presenting HNF1α-mutated adenomas compared with 58 controls. In contrast, we identified a CYP1B1 germ line heterozygous mutation in 4 of 32 women presenting HNF1α-mutated adenomas compared with none in 58 controls. We confirmed these results with the identification of four additional CYP1B1 mutations in a second series of 26 cases. No mutations were found in the control group, which was extended to 98 individuals, and only a known rare genetic variant was observed in two controls (P = 0.0003). We did an ethoxyresorufin O-deethylase assay to evaluate the functional consequence of the CYP1B1 mutations. We found reduced enzymatic activity in each CYP1B1 variant. In addition, an E229K CYP1B1 mutation was found in a woman with a germ line HNF1α mutation in a familial adenomatosis context. In this large family, all three patients with adenomatosis bore both HNF1 and CYP1B1 germ line mutations. In conclusion, our data suggested that CYP1B1 germ line–inactivating mutations might increase the incidence of HCA in women with HNF1α mutations. [Cancer Res 2007;67(6):2611–6]

Supplementary Table 1 from Association of CYP1B1 Germ Line Mutations with Hepatocyte Nuclear Factor 1α–Mutated Hepatocellular Adenoma

Background The Mayo protocol for liver transplantation in patients with unresectable perihilar cholangiocarcinoma is based on strict selection and neoadjuvant chemoradiotherapy. The role of neoadjuvant chemoradiotherapy in this scenario remains unclear. The aim of this study was to compare outcomes after transplantation for perihilar cholangiocarcinoma using strict selection criteria, either with or without neoadjuvant chemoradiotherapy. Methods This was an international, multicentre, retrospective cohort study of patients who underwent transplantation between 2011 and 2020 for unresectable perihilar cholangiocarcinoma using the Mayo selection criteria and receiving neoadjuvant chemoradiotherapy or not receiving neoadjuvant chemoradiotherapy. Endpoints were post-transplant survival, post-transplant morbidity rate, and time to recurrence. Results Of 49 patients who underwent liver transplantation for perihilar cholangiocarcinoma, 27 received neoadjuvant chemoradiotherapy and 22 did not. Overall 1-, 3-, and 5-year post-transplantation survival rates were 65 per cent, 51 per cent and 41 per cent respectively in the group receiving neoadjuvant chemoradiotherapy and 91 per cent, 68 per cent and 53 per cent respectively in the group not receiving neoadjuvant chemoradiotherapy (1-year hazards ratio (HR) 4.55 (95 per cent c.i. 0.98 to 21.13), P = 0.053; 3-year HR 2.07 (95 per cent c.i. 0.78 to 5.54), P = 0.146; 5-year HR 1.71 (95 per cent c.i. 0.71 to 4.09), P = 0.229). Hepatic vascular complications were more frequent in the group receiving neoadjuvant chemoradiotherapy compared with the group not receiving neoadjuvant chemoradiotherapy (nine of 27 versus two of 22, P = 0.045). In multivariable analysis, tumour recurrence occurred less frequently in the group receiving neoadjuvant chemoradiotherapy (HR 0.30 (95 per cent c.i. 0.09 to 0.97), P = 0.044). Conclusion In selected patients undergoing liver transplantation for perihilar cholangiocarcinoma, neoadjuvant chemoradiotherapy resulted in a lower risk of tumour recurrence, but was associated with a higher rate of early hepatic vascular complications. Adjustments in neoadjuvant chemoradiotherapy reducing the risk of hepatic vascular complications, such as omitting radiotherapy, may further improve the outcome in patients undergoing liver transplantation for perihilar cholangiocarcinoma.

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.

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Immune checkpoint blockade primarily benefits patients with viral HCC. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by the emergence of high entropy myeloid cell states and myeloid-biased NK cell differentiation. We identify a discrete population of tumor-infiltrating myeloid cells, predominant in the steatohepatitis setting, that expresses a variety of myeloid lineage-affiliated genes, including granulocyte, macrophage and dendritic cell features, and can be identified in HCC tumors based on selective dual expression ofTREM1andCD163. Functional characterization reveals that TREM1+CD163+myeloid cells highly express TGFβ and IL-13RA, localize to HCC fibrotic lesions, and potently suppress T cell effector functionsex vivo, a function further potentiated by TREM1 engagement. We refer to this population as TREM1+CD163+regulatory myeloid cells (TREM1+CD163+Mreg). Deconvolution analyses in large cohorts of patients with HCC and other solid tumors reveals that the density of TREM1+CD163+Mregincreases in advanced stages, associates with poor prognosis, and therapeutic resistance to PD-1 blockade. Our data support myeloid subset-targeted immunotherapies to treat HCC and identify TREM1 as a therapeutic target.HIGHLIGHTSAtlas of hepatic innate immune cells (100,000 transcriptomes) from patients with HCCCore signatures to identify, discriminate and localize innate lymphoid and myeloid cellsA population of TREM1+CD163+myeloid cells, referred to as TREM1+CD163+Mreg, expands in steatohepatitis HCCTREM1+CD163+Mregexpress granulocyte- and macrophage/dendritic cell-lineage genesTREM1+CD163+Mregpotently suppress T cell effector functions, which is potentiated by TREM1 engagement by cognate ligandsTREM1+CD163+Mregproduce high levels of TGFβ and populate fibrotic lesionsThe density of TREM1+CD163+Mregincreases in advanced HCC and associate with poor patient survivalThe density of TREM1+CD163+Mregassociates with resistance to immune checkpoint blockade in other solid tumors

OBJECTIVE Our aim was to determine independent risk factors of clinical bleeding of hepatocellular adenoma (HCA) to define a better management strategy. SUMMARY BACKGROUND DATA HCA is a rare benign liver tumor with severe complications: malignant transformation that is rare (5%-8%) and more often, hemorrhage (20%-27%). To date, only size > 5 cm and histological subtype (possibly sonic hedgehog) are associated with bleeding, but these criteria are not clearly established. METHODS We retrospectively collected data from a cohort of 268 patients with HCA managed in our tertiary center, from 1984 to 2020 and focused on clinical bleeding. Hemorrhage was considered severe when it required intensive care and moderate when bleeding symptoms required a hospitalization. We included 261 patients, of whom 130 (49.8%) had multiple HCAs or liver adenomatosis. All surgical specimen and liver biopsy were reviewed by an experienced liver pathologist and reclassified in the light of the current immunohistochemistry. Mean duration of follow-up was 93.3 months (range 1-363). We analyzed type, frequency, consequences of bleeding, and risk factors among clinical data and HCA characteristics. RESULTS Eighty-three HCA (31.8%) were hemorrhagic. There were 4 pregnant women with 1 newborn death. One patient died before treatment. Surgery was performed in 78 (94.0%) patients. Mortality was nil and severe complications occurred in 11.5%. Multivariate analysis identified size (OR 1.02 [1.01-1.02], P < 0.001), shHCA (OR 21.02 [5.05-87.52], P < 0.001), b-catenin mutation on exon 7/8 (OR 6.47 [1.78-23.55], P = 0.0046), chronic alcohol consumption (OR 9.16 [2.47-34.01], P < 0.001) as independent risk factors of clinical bleeding. CONCLUSIONS This series, focused on the hemorrhagic risk of HCA, shows that size, but rather more molecular subtype is determinant in the natural history of HCA.

Background and Aims : Through an exploratory proteomic approach based on typical hepatocellular adenomas (HCAs), we previously identified a diagnostic biomarker for a distinctive subtype of HCA with high risk of bleeding, already validated on a multicenter cohort. We hypothesized that the whole protein expression deregulation profile could deliver much more informative data for tumor characterization. Therefore, we pursued our analysis with the characterization of HCA proteomic profiles, evaluating their correspondence with the established genotype/phenotype classification and assessing whether they could provide added diagnosis and prognosis values. Approach and Results : From a collection of 260 cases, we selected 52 typical cases of all different subgroups on which we built a reference HCA proteomics database. Combining laser microdissection and mass-spectrometry–based proteomic analysis, we compared the relative protein abundances between tumoral (T) and nontumoral (NT) liver tissues from each patient and we defined a specific proteomic profile of each of the HCA subgroups. Next, we built a matching algorithm comparing the proteomic profile extracted from a patient with our reference HCA database. Proteomic profiles allowed HCA classification and made diagnosis possible, even for complex cases with immunohistological or genomic analysis that did not lead to a formal conclusion. Despite a well-established pathomolecular classification, clinical practices have not substantially changed and the HCA management link to the assessment of the malignant transformation risk remains delicate for many surgeons. That is why we also identified and validated a proteomic profile that would directly evaluate malignant transformation risk regardless of HCA subtype. Conclusions : This work proposes a proteomic-based machine learning tool, operational on fixed biopsies, that can improve diagnosis and prognosis and therefore patient management for HCAs.

Purpose: We investigated the long-term safety and efficacy of hepatic transarterial embolization (TAE) in patients with symptomatic polycystic liver disease (PLD). Materials and Methods: A total of 26 patients were included, mean age of 52.3 years (range: 33–78 years), undergoing 32 TAE procedures between January 2012 and December 2019 were included in this retrospective study. Distal embolization of the segmental hepatic artery was performed with 300–500 µm embolic microspheres associated with proximal embolization using microcoils. The primary endpoint was clinical efficacy, defined by an improvement in health-related quality of life using a modified Short Form-36 Health Survey and improvement in symptoms (digestive or respiratory symptoms and chronic abdominal pain), without invasive therapy during the follow-up period. Secondary endpoints were a decrease in total liver volume and treated liver volume and complications. Results: Hepatic embolization was performed successfully in 30 of 32 procedures with no major adverse events. Clinical efficacy was 73% (19/26). The mean reduction in hepatic volume was −12.6% at 3 months and −27.8% at the last follow-up 51 ± 15.2 months after TAE (range: 30–81 months; both ps < 0.01). The mean visual analog scale pain score was 5.4 ± 2.8 before TAE and decreased to 2.7 ± 1.9 after treatment. Three patients had minor adverse events, and one patient had an adverse event of moderate severity. Conclusion: Hepatic embolization using microspheres and microcoils is a safe and effective treatment for PLD that improves symptoms and reduces the volume of hepatic cysts.

Resume Cette image a pour but d’illustrer le diagnostic d’une hernie de Bochdalek chez une patiente de 39 ans prise en charge en urgence. Celui-ci a ete fait au moyen d’un scanner et selon les constatations peroperatoires. Le traitement a consiste en une cœlioscopie premiere, convertie devant l’incarceration grelique irreductible, avec reparation herniaire par raphie simple et drainage thoracique.

Resume But de l’etude Le but de l’etude etait d’evaluer le role pronostique de 4 solutions de conservation en transplantation hepatique (TH). Patients et methodes Il s’agit d’une etude retrospective a partir de toutes les TH de tous les centres francais (n = 22) enregistrees dans la base de donnees prospective de l’Agence de la Biomedecine (Cristal) entre 2008 et 2013. Les solutions de preservation utilisees etaient : Celsior, IGL-1, SCOT 15 ou UW. Les criteres d’exclusion etaient : solution inconnue ou inhomogene ou solution HTK (3 % seulement des TH). Le critere principal de jugement etait la survie des patients. Les criteres secondaires etaient la survie des greffons et la duree de reanimation. Resultats Parmi 6347 TH realisees, 4928 ont ete incluses pour lesquelles la solution de preservation utilisee etaient Celsior (30 %), IGL-1 (44 %), SCOT 15 (10 %) et UW (16 %). La survie des patients etait de 86 %, 80 % et 74 % a 1, 3 et 5 ans, respectivement, sans difference entre les 4 solutions (p = 0,78). La survie des greffons etait respectivement de 82 %, 75 % et 69 % a 1, 3 et 5 ans, sans difference entre les 4 solutions (p = 0,80). Le sejour en reanimation etait different selon la solution utilisee en analyse univariee (p Conclusion Le type de solution de conservation utilisee (Celsior, IGL-1, SCOT 15 ou UW) n’a pas d’influence sur la survie des patients ou des greffons apres TH.

International audience; Background: Few series of cavoportal (CPA) or renoportal (RPA) anastomosis have been published and their survival rates have never been compared. The objective of this study was to evaluate perioperative and long-term outcomes of CPA and RPA in a nationwide multicentric series and to compare hemitranspositions (HT) to paired ortho-topic liver transplantations (OLT). Material/Methods: HT performed in France up to April 2019 were analyzed. Endpoints were the incidence of severe (Clavien-Dindo>IIIa) 90-day perioperative complications and long-term patient and graft survival. Results: Sixty-four HT (13 CPA, 51 RPA) were performed in 59 patients. The rates of perioperative CD>IIIa complica-tions were 64% and 49% in patients with CPA and RPA, respectively (P=0.59), and the rates of portal throm-bosis and ascites were 38.5% and 9.8% (p=0.023) and 53.8% and 21.6% (p=0.049) in patients with CPA and RPA, respectively. The patient and graft perioperative survival rates were 54.4% and 83.3% (HR=3.2; CI 95 [1.1-9.9]; p=0.039) and 54.4% and 77.1% (HR=2.2; CI 95 [0.77-6.4]; P=0.14) in the CPA and RPA groups, respec-tively. Five-year patient survival was 36.4% and 61.8% in the CPA and RPA groups, respectively (HR=2.5; CI 95 [1-6.1]; P=0.039). Compared with OLT grafts, long-term HT graft survival rates were not different (HR=1.7; CI 95 [0.96-3.1]; P=0.066), while patient survival rates were lower in the HT group (HR=4.6; CI 95 [2-11]; P

Acute intermittent porphyria (AIP), caused by heterozygous germline mutations of the heme synthesis pathway enzyme HMBS (hydroxymethylbilane synthase), confers a high risk of hepatocellular carcinoma (HCC) development. Yet, the role of HMBS in liver tumorigenesis remains unclear.Herein, we explore HMBS alterations in a large series of 758 HCC cases, including 4 patients with AIP. We quantify the impact of HMBS mutations on heme biosynthesis pathway intermediates and we investigate the molecular and clinical features of HMBS-mutated tumors.We identify recurrent bi-allelic HMBS inactivation, both in patients with AIP acquiring a second somatic HMBS mutation and in sporadic HCC with 2 somatic hits. HMBS alterations are enriched in truncating mutations, in particular in splice regions, leading to abnormal transcript structures. Bi-allelic HMBS inactivation results in a massive accumulation of its toxic substrate porphobilinogen and synergizes with CTNNB1-activating mutations, leading to the development of well-differentiated tumors with a transcriptomic signature of Wnt/β-catenin pathway activation and a DNA methylation signature related to ageing. HMBS-inactivated HCC mostly affects females, in the absence of fibrosis and classical HCC risk factors.These data identify HMBS as a tumor suppressor gene whose bi-allelic inactivation defines a homogenous clinical and molecular HCC subtype.Heme (the precursor to hemoglobin, which plays a key role in oxygen transport around the body) synthesis occurs in the liver and involves several enzymes including hydroxymethylbilane synthase (HMBS). HMBS mutations cause acute intermittent porphyria, a disease caused by the accumulation of toxic porphyrin precursors. Herein, we show that HMBS inactivation is also involved in the development of liver cancers with distinct clinical and molecular characteristics.

Pancreatic ductal adenocarcinoma (PDAC) patients eligible for curative surgery undergo unpredictable disease relapse. Even patients with a good pathological response after neoadjuvant treatment (NAT) remain susceptible to recurrent PDAC. Molecular analysis of R0 margins may identify patients with a worse prognosis. The molecular status of mutant KRAS (exon 2, codon 12/13) was analysed retrospectively by digital droplet PCR in tumour areas, venous and resection margins of resected tumours, either undergoing up-front surgery (UFS) or after NAT with a good pathological response. Expectedly, tumour tissues or remnants from patients who underwent NAT presented lower KRAS mutant allele frequencies (MAF) than patients eligible for UFS. Similarly, ypT1 tumour MAFs were greater than the ypT0 tumour remnant MAFs in the NAT group. Mutant KRAS status in margins did not distinguish NAT subgroups. It was not predictive of shorter recurrence-free or overall survival within or between groups. KRAS-double negativity in both venous and resection margins did not identify patients with a better prognosis, regardless of the groups. The cohorts ‘sizes were small due to limited numbers of patients meeting the inclusion criteria, but KRAS-positivity or MAFs in resection and venous margins did not carry prognostic value. Comparison of margins from good versus bad responders receiving NAT may provide better clinical value.

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

Background: Pancreatic ductal adenocarcinoma (PDAC) patients eligible for curative surgery undergo unpredictable disease relapse. Post-surgery tools’ prognostic value is insufficient. Even patients with good pathological response after neo-adjuvant treatment (NAT) remain susceptible to recurrent PDAC. Molecular analysis of R0 margins may identify patients with worse prognosis. Methods: Retrospective analysis of patients, either eligible for up-font surgery (UFS, n=17) or resected patients who underwent NAT with good pathological responses (n=18), collected progression-free and overall survivals 33 months ±17 months post-surgery and examined the molecular status of mutant KRAS by droplet digital PCR.Results: Expectedly, KRAS mutant allele frequencies (MAF) were higher in UFS than in NAT tumor tissues or remnants, and in the ypT1 than the ypT0 tumors in the NAT group. Mutant KRAS positivity or MAFs in margins did not identify patients with detectable pathological disease in the NAT group, nor was it predictive of shorter recurrence-free or overall survival within or between groups. KRAS-double positivity in both venous and tumor resection margins did not identify patients with worse prognosis, regardless of the groups.Conclusion: The cohorts ‘sizes were small due to limited numbers of patients meeting the inclusion criteria, but KRAS-positivity or MAFs in resection and venous margins did not carry prognostic value. Comparison of margins from good versus bad responders receiving NAT may carry a better clinical value.Trial registration: The up-front surgery, PANC-CTC, cohort was granted French Ministry of Research “Comité de Protection des Personnes, CPP” approval under the number 2016-A00431-50. Its clinical trial number is #NCT03032913. The Neoadjuvant Therapy (NAT) good responder cohort was retrospectively registered. Patients ‘consents were collected and the study was declared and approved by Bordeaux University Hospital ethic comity.

Neoadjuvant treatment (NAT) is debated for borderline resectable pancreatic cancer (BRPC). This retrospective study assessed the impact of NAT on R0 rate and survival for BRPC patients in comparison with upfront surgery (US).Between 2010 and 2017 patient records for all consecutive patients treated for BRPC according to NCCN 2017 were reviewed. The endpoints analysed were R0 rate, recurrence-free-survival (RFS) and overall survival (OS).Seventy-nine patients were included: 63 (79.7%) patients received NAT and 16 (20.3%) were upfront operated. NAT consisted in FOLFIRINOX (median cycles: 5, range 4-8) followed by chemoradiation (NAT permitted a high R0 rate with a 0- or 1-mm clearance margin and was associated with better RFS and OS for patients with BRPC.

To date, genomic analyses of hepatocellular carcinoma (HCC) have been limited to early stages obtained from liver resection. We aim to describe the genomic profiling of HCC from early to advanced stages. We analyzed 801 HCC from 720 patients (410 resections, 137 transplantations, 122 percutaneous ablations, and 52 noncurative) for 190 gene expressions and for 31 gene mutations. Forty-one advanced HCC and 156 whole exome of Barcelona Clinic Liver Cancer (BCLC) 0/A were analyzed by whole-exome sequencing. Genomic profiling was correlated with tumor stages, clinical features, and survival. Our cohort included patients classified in BCLC stage 0 (9.4%), A (59.5%), B (16.2%), and C (14.9%). Among the overall 801 HCC, the most frequently mutated genes were telomerase reverse transcriptase (TERT) (58.1%), catenin beta 1 (CTNNB1) (30.7%), tumor protein 53 (TP53; 18.7%), AT-rich interaction domain 1A (ARID1A) (13%), albumin (11.4%), apolipoprotein B (APOB) (9.4%), and AXIN1 (9.2%). Advanced-stage HCC (BCLC B/C) showed higher frequencies of splicing factor 3b subunit 1 (SF3B1) (P = 0.0003), TP53 (P = 0.0006), and RB Transcriptional Corepressor 1 mutations (P = 0.03). G1-G6 transcriptomic classification and the molecular prognostic 5-gene score showed different distributions according to the stage of the disease and the type of treatment with an enrichment of G3 (P < 0.0001), poor prognostic score (P < 0.0001), and increased proliferation and dedifferentiation at the transcriptomic level in advanced HCC. The 5-gene score predicted survival in patients treated by resection (P < 0.0001) and ablation (P = 0.01) and in advanced HCC (P = 0.04). Twenty-two percent of advanced HCC harbored potentially druggable genetic alterations, and MET amplification was associated with complete tumor response in patients with advanced HCC treated by a specific MET inhibitor. Conclusion: Genomic analysis across the different stages of HCC revealed the mechanisms of tumor progression and helped to identify biomarkers of response to targeted therapies.

Summary Background and aims Stopping oral contraceptives following nodule detection usually prevents further hepatocellular growth (HCA); rare cases of growth have been reported after surgery. The aim of the study was to review our resected HCA cases and their outcomes and more specifically, growth. Methods We retrieved all HCA cases that required a second intervention and HCA growth cases of none resected HCA after resection of one or several HCAs. Results Out of the 210 resected classified HCA cases, a second resection was performed in 5 cases, 4 of which were in women with HNF1alpha-inactivated adenomatosis (H-adenomatosis) and had a favorable outcome. The fifth case was the occurrence of an inflammatory HCA, 3 years after resection of a previous one. Of the 65 resected HNF1-inactivated HCAs (H-HCAs), the nodules that remained continued to increase very slowly in 3 adenomatosis cases. After surgery, the liver became dysmorphic years later in one case, and the nodules grew but not significantly in another case. After the diagnosis of adenomatosis, progressive growth leads to surgery 12 years later in the last case. Conclusion These results confirm that, in rare H-adenomatosis, size of nodules may increase very slowly, probably in part through coalescence of micro H-HCAs and leading occasionally to a second resection.

Resume Le plan cancer a pose le cadre de bonnes pratiques du parcours de soins pour le malade cancereux. Les decisions doivent etre prises en reunion de concertation pluridisciplinaire (RCP) et un plan personnalise de soins (PPS) doit etre etabli pour chaque patient. Le carcinome hepatocellulaire (CHC) est un cancer frequent avec des traitements complexes justifiant de lui reserver une reunion dediee. Les centres de coordination en cancerologie (3C) assurent l’organisation et le bon fonctionnement des RCP. Cette evaluation multidisciplinaire, standardisee et systematique des patients porteurs de CHC permet une prise en charge personnalisee des patients et les orientent vers une prise en charge soit curative (transplantation, resection chirurgicale, ablathermie), soit palliative (chimioembolisation, radiotherapie, traitement systemique, soins de support). Les RCP permettent de reunir tous les acteurs prenant en charge le CHC, de produire un document opposable justifiant les decisions et constituent souvent une etape indispensable pour l’inclusion des patients dans un essai clinique. Elle doit se derouler selon un schema systematique dans une demarche allant du diagnostic jusqu’a la mise en traitement et se poursuivant tout au long de la prise en charge therapeutique. Les nombreux progres des traitements des CHC ont rendu leur prise en charge complexe avec eventuellement le recours a la transplantation hepatique (TH) dont l’acces est reglemente par l’agence de biomedecine (ABM) qui impose de fournir les comptes rendus de RCP. La RCP, qui doit repondre a des criteres qualites precis, est le gage d’une prise en charge efficace s’appuyant sur les recommandations mais adaptee a chaque patient.

Hepatocellular adenomas (HCA) are rare benign hepatocellular tumors occurring mainly in women taking oral contraceptives with 2 major complications: severe bleeding and malignant transformation that can be avoided if nodules exceeding 5 cm are resected. This simple attitude has been challenged in the recent years with HCA in men, in young adolescent, in aged persons, and complications in hepatocellular adenomas below 5 cm. The discovery of specific mutations leading to specific phenotypes has modified the clinical spectrum of the disease. The phenotypic immune classification of HCA based on the molecular classification is being widely used in liver referral centers. The aim of this snapshot is to briefly present for each subtype the clinical, pathological, immuno-pathological criteria as well as the risk of complications and guidelines for treatment and management.

Intrahepatic cholangiocarcinoma is a rare disease with a poor prognosis. In patients where surgical resection is possible, outcome is influenced by perioperative morbidity and lymph node status. Laparoscopic liver resection is associated with improved clinical and oncological outcomes in primary and metastatic liver cancer compared with open liver resection, but evidence on intrahepatic cholangiocarcinoma is still insufficient. The primary aim of this study was to compare overall survival for a large series of patients treated for intrahepatic cholangiocarcinoma by open or laparoscopic approach. Secondary objectives were to compare disease-free survival, predictors of death, and recurrence.Patients treated with laparoscopic or open liver resection for intrahepatic cholangiocarcinoma from 2000 to 2018 from 3 large international databases were analyzed retrospectively. Each patient in the laparoscopic resection group (case) was matched with 1 open resection control (1:1 ratio), through a propensity score calculated on clinically relevant preoperative covariates. Overall and disease-free survival were compared between the matched groups. Predictors of mortality and recurrence were analyzed with Cox regression, and the Textbook Outcomes were described.During the study period, 855 patients met the inclusion criteria (open liver resection = 709, 82.9%; laparoscopic liver resection = 146, 17.1%). Two groups of 89 patients each were analyzed after propensity score matching, with no significant difference regarding pre- and postoperative variables. Overall survival at 1, 3, and 5 years was 92%, 75%, and 63% in the laparoscopic liver resection group versus 92%, 58%, and 49% in the open liver resection group (P = .0043). Adjusted Cox regression revealed severe postoperative complications (hazard ratio: 10.5, 95% confidence interval [1.01-109] P = .049) and steatosis (hazard ratio: 13.8, 95% confidence interval [1.23-154] P = .033) as predictors of death, and transfusion (hazard ratio: 19.2, 95% confidence interval [4.04-91.4] P.001) and severe postoperative complications (hazard ratio: 4.07, 95% confidence interval [1.15-14.4] P = .030) as predictors of recurrence.The survival advantage of laparoscopic liver resection over open liver resection for intrahepatic cholangiocarcinoma is equivocal, given historical bias and missing data.

The purpose of this image is to illustrate a Bochdalek hernia diagnosis in a 39-year-old female patient treated on an emergency basis by means of CT-scan and following perioperative observation. Treatment consisted in initial laparoscopy that due to irreducible bowel incarceration was converted into hernia repair surgery through simple suture and thoracic drainage.

Background Sacrificing a replaced right hepatic artery (rRHA) from the superior mesenteric artery is occasionally necessary to obtain an R0 resection after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA). Preoperative embolization (PEA) of the rRHA has been proposed to avoid the onset of postoperative biliary and ischemic liver complications. Methods Eighteen patients with cephalic PA with an rRHA underwent PEA of the rRHA from 2013 to 2019. The monitoring after embolization and PD was systematic and included a clinical-biological evaluation and a computed tomography scan. This study aimed to determine the feasibility of PEA of the rRHA, postoperative morbidity at 90 days, and quality of oncologic resection after PD. Results Feasibility of PEA was 100% without complications. A PD was performed in 16/18 patients. Mortality was 2/16 with one death after septic shock with hepatic ischemia without an arterial obstruction. Overall morbidity was 44% including one hepatic abscess after hepatic ischemia (6%). Two resections were R1 ( Conclusion PEA of the rRHA before PD was safe and reproducible. PEA of the rRHA followed by en bloc PD resection seems to limit the risk of bilio-hepatic ischemia and could facilitate oncologic resection.

OBJECTIVE The aim of this retrospective study was to compare portal vein embolization (PVE) and radiologica simultaneous portohepatic vein embolization (RASPE) for future liver remnant (FLR) growth in terms of feasibility, safety, and efficacy. SUMMARY OF BACKGROUND DATA After portal vein embolization (PVE), 15% of patients remain ineligible for hepatic resection due to insufficient hypertrophy of the FLR. RASPE has been proposed to induce FLR growth. MATERIALS AND METHODS Between 2016 and 2018, 73 patients were included in the study. RASPE was proposed for patients with a ratio of FLR to total liver volume (FLR/TLV) of

Approximately 80% of patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). The effect of IBD on the outcomes of liver transplantation (LT) for PSC is unclear. We retrospectively collected data from adults who underwent LT for PSC from 1989 to 2017 in four French LT centers. We compared the rates of patient and graft survivals and of complications after LT. Among 87 patients, 52 (60%) had pre-existing IBD. Excluding those who died within the first 3 months, the 10-year patient survival and graft survival rates were 92.6% (95% confidence interval [CI] 84.3-100) and 77.1% (95% CI 53.8-85.3) in the PSC with IBD (PSC-IBD) group and 97.1% (95% CI 91.4-100) (p = 0.44) and 83.2% (95% CI 69.6-96.9) (p = 0.43) in the isolated PSC group, respectively. Exposure to azathioprine after LT was significantly associated with mortality (odds ratio [OR] 15.55 [95% CI 1.31-184.0], p = 0.03), whereas exposure to mycophenolate mofetil was associated with improved survival (OR 0.17 [95% CI 0.04-0.82], p = 0.03), which may be an era effect. Exposure to cyclosporine was associated with graft loss, albeit at borderline significance: OR 3.60 [95% CI 0.96-13.42] (p = 0.06). The rate of recurrent PSC was 21% in the PSC-IBD group and 11% in the isolated PSC group (p = 0.24). The incidence of severe infection was 125 per 1000 person-years in both groups. Exposure to mycophenolate mofetil was associated with a lower risk of infection (OR 0.26 [95% CI 0.08-0.85] p = 0.03). The presence of IBD was associated with cytomegalovirus infection (OR 3.24 [95% CI 1.05-9.98], p = 0.04). The crude incidence of skin cancer was higher in the PSC-IBD group (p = 0.06). One case of colorectal cancer occurred in a patient with IBD. CONCLUSION: IBD prior to LT for PSC may not affect patient or transplant survival but may increase the risk of cytomegalovirus infection.

International audience; Objective - The goal of this study was to evaluate the prognostic role of four preservation solutions in liver transplantation (LT). Patients and methods - This is a retrospective study originating from 22 French centers performing LT, registered in the prospective databank of the Cristal Biomedicine Agency between 2008 and 2013. The preservation solutions used were Celsior (CS), Institut Georges Lopez (IGL)-1, Solution de Conservation des Organes et des Tissus (SCOT) 15 and University of Wisconsin (UW) solutions. Exclusion criteria were preservation with unknown or inhomogeneous solutions, or Histidine-tryptophan-ketoglutarate (HTK) solution (representing only 3% of LT). Patient survival was the main endpoint. Secondary endpoints were graft survival and duration of stay in intensive care. Results - Of 6347 LT performed, 4928 were included in this study, for which the distribution of preservation solution was CS (30%), IGL-1 (44%), SCOT 15 (10%) and UW (16%). Patient survival was 86%, 80% and 74% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.78). Graft survival was 82%, 75% and 69% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.80). Duration of intensive care was different according to the solution used in univariate analysis (P