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Anna Sessa,1– 3 Sébastien Mulé,2– 4 Raffaele Brustia,2,3,5 Hélène Regnault,1,3 Athena Galletto Pregliasco,4 Rami Rhaiem,6,7 Vincent Leroy,1– 3 Daniele Sommacale,2,3,5 Alain Luciani,2– 4 Julien Calderaro,2,3,8 Giuliana Amaddeo1– 3 1Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France; 2Université Paris-Est Créteil, Faculté de Médecine, Créteil, France; 3Inserm, U955, Team 18, Créteil, France; 4Medical Imaging Department, AP-HP, Henri Mondor University Hospital, Créteil, France; 5Department of Digestive and Hepato-Pancreato-Biliary Surgery, AP-HP, Henri Mondor University Hospital, Créteil, France; 6Department of Hepato-Biliary Pancreatic and Digestive Oncological Surgery, Robert Debré University Hospital, Reims, France; 7Reims Champagne-Ardenne University, Reims, France; 8Department of Pathology, APHP, Henri Mondor University Hospital, Créteil, FranceCorrespondence: Giuliana Amaddeo; Anna Sessa, Hepatology Department, APHP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, Créteil, 94000, France, Tel +33 149812353, Email giuliana.amaddeo@aphp.fr; asessa1990@gmail.comAbstract: The subject of this narrative review is macrotrabecular-massive hepatocellular carcinoma (MTM‐HCC). Despite their rarity, these tumours are of general interest because of their epidemiological and clinical features and for representing a distinct model of the interaction between the angiogenetic system and neoplastic cells. The MTM‐HCC subtype is associated with various adverse biological and pathological parameters (the Alfa-foetoprotein (AFP) serum level, tumour size, vascular invasion, and satellite nodules) and is a key determinant of patient prognosis, with a strong and independent predictive value for early and overall tumour recurrence. Gene expression profiling has demonstrated that angiogenesis activation is a hallmark feature of MTM-HCC, with overexpression of both angiopoietin 2 (ANGPT2) and vascular endothelial growth factor A (VEGFA).Keywords: hepatocellular carcinoma, macrotrabecular, angiopoietin 2 inhibitors, TP53, immunotherapy

Introduction: Besides the role played by environmental factors and their epigenetic influences, scientific researchers showed that the susceptibility to develop an eating disorder among bipolar people is due to genetic factors. Objectives: To review the genetic factors behind eating disorders, highlight the role of genetics and epigenetics in the comorbidity of bipolar and eating disorders. Methods: To delineate the role of genetics and epigenetics in eating disorders and bipolar disorders as two related mental illness, we comprehensively reviewed the scientific literature using GWAS (genome wide association studies) catalog databases to find genome-wide association studies carried out on patients with bipolar disorder EFO_0005203 and eating disorder comorbid condition (anorexia nervosa, binge eating, bulimia nervosa) EFO_0005203. Results: GWAS of eating disorders were found in 33 studies with 324 associations whereas those of bipolar disorder were found in 114 studies with 1469 associations. GWAS of eating disorders within bipolar disorders revealed 182 and 134 associations, as well as 10 and 8 publications respectively. Only anorexia nervosa and binge eating were studied in association with bipolar disorders. The genetic variants were protein coding genes (CUBN, FAM228B, FXR1, etc.), non-coding RNA genes (SOX2-OT, MMADHC-DT, etc.), and pseudo-genes (RNU1-23P, CACYBPP2, etc.). Conclusions: About 300 genetic variants are associated with eating disorder as a comorbid condition of bipolar disorders. These variants may play a crucial role in the causes and mechanisms of eating disorders and should be more investigated towards more precise clinical and genetic entities. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

B Background: b Microwave ablation(mwa) is gaining wide acceptance. B Results: b Surgery was performed by laparoscopy in 7 patients, by laparotomy in 13 patients and by thoracotomy in one case with CLM in segment VIII. Thirteen patients had associated mwa with minor liver resections, 4 patients had associated colorectal resections and only 4 patients had only mwa.Four patients were treated for local recurrence within a previous wedge resection or RFA. [Extracted from the article]

B Background: b Major hepatectomy (MH) can lead to an increasing portal pressure(PP) and to lesions of the hepatic parenchyma. The aim of this study was to assess the effect of a high PP in the course of MH and to evaluate the impact of somatostatin in PP modulation and in liver function preservation Patients were divided into two groups according to PHPP: Group A(PHPP>20 mmHg)and group B(PHPP<20 mmHg)with respectively 13 and 17 patients. [Extracted from the article]

Bleeding after pancreatico-duodenectomy (PD) is a serious complication with high rates of morbidity and mortality. Interventional radiology techniques' using embolization and/or stenting is the optimal management. In case of hemodynamic instability, surgical treatment is mandatory, but its mortality rate is considerable. Herein, we report the management of massive bleeding in a 52-year-old-male patient, 3 weeks after PD. The patient suffered severe hemorrhage with two cardiac arrests and surgical treatment was performed immediately after resuscitation. A defect in the distal part of the hepatic artery was repaired using a peritoneal patch. A postoperative CT scan confirmed bleeding control and the presence of a pseudoaneurysm within the patch area. The second step of the treatment was to perform selective embolization. The course was uneventful, and the patient was discharged 6 weeks later. [ABSTRACT FROM AUTHOR]

B Background: b Laparoscopic liver resection (LLR) is increasingly performed worldwide. B Methods: b Between September 2012 and November 2016, among 282 patients who underwent liver resections, 103 (36.5%) were LLR. Biliary cysts and laparoscopic thermal ablation (TA) without liver resection were excluded. [Extracted from the article]

Background: Gastrointestinal (GI) bleeding is a leading cause of intensive care unit (ICU) admission in pancreatic cancer patients., Aims: To analyze causes, ICU mortality and hemostatic treatment success rates of GI bleeding in pancreatic cancer patients requiring ICU admission., Methods: Retrospective multicenter cohort study between 2009 and 2021. Patients with a recent pancreatic resection surgery were excluded., Results: Ninety-five patients were included (62 % males, 67 years-old). Fifty-one percent presented hemorrhagic shock, 41 % required mechanical ventilation. Main GI bleeding causes were gastroduodenal tumor invasion (32 %), gastroesophageal varices (21 %) and arterial aneurysm (12 %). Arterial aneurysms were more frequent in patients with previous pancreatic resection (36 % vs 2 %, p < 0.001). Hemostatic procedures included gastroduodenal endoscopy in 81 % patients and arterial embolization in 28 % patients. ICU mortality was 19 %. Multivariate analysis identified four variables associated with mortality: performance status >2 (OR 9.34, p = 0.026), mechanical ventilation (OR 14.14, p = 0.003), treatment success (OR 0.09, p = 0.010), hemorrhagic shock (OR 11.24, p = 0.010). Treatment success was 46 % and was associated with aneurysmal bleeding (OR 29.89, p = 0.005), ongoing chemotherapy (OR 0.22, p = 0.016), and prothrombin time ratio (OR 1.05, p = 0.001)., Conclusion: In pancreatic cancer patients with severe GI bleeding, early identification of aneurysmal bleeding (particularly in case of previous resection surgery) and coagulopathy management may increase the treatment success and reduce mortality., Competing Interests: Conflict of interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Knowledge about environmental pancreatic adenocarcinoma (PA) risk factors, including pesticide exposure, remains limited. Organochlorine (OC) accumulates in adipose tissue and can help reflect long-term exposure., Patients and Methods: Age and body mass index (BMI) of patients with PA were matched with those undergoing a surgery for a benign disease on age and BMI (1:1). Targeted analyses screened 345 pesticides and metabolites, including 29 OC, in adipose tissue and urine samples. The primary aim was to investigate the association between organochlorine concentrations in visceral fat or urine, and PA. Adjusted conditional logistic regressions were carried out accounting for multiple testing., Results: Trans-nonachlor (odds ratio [OR] = 1.325, 95% confidence interval [CI] [1.108-1.586]), cis-nonachlor (OR = 15.433, 95% CI [2.733-87.136]), Mirex (OR = 2.853, 95% CI [1.213-6.713]) and 4,4 DDE (OR = 1.019, 95% CI [1.005-1.034]) in fat and a greater number of positive samples (OR = 1.758 95% CI [1.11-2.997]) were significantly associated with higher odds of PA. In contrast, as awaited, urine samples did not yield any statistically significant associations for all tested pesticides., Conclusion: Some OCs were associated with higher odds of PA. The underlying mechanisms of pancreatic aggression need to be investigated to refine these findings., Trial Registration: Clinicaltrials.gov NCT04429490., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios., Competing Interests: Conflicts of interest None., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: KRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status., Methods: All patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival., Results: The analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01-2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06-1.91)., Conclusions: KRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) have a dismal prognosis and any effective neoadjuvant treatment has been validated to date. We aimed to investigate the role of neoadjuvant transarterial chemoembolization (TACE) in upfront resectable HCC larger than 5 cm., Methods: This is a multicentric retrospective study comparing outcomes of large HCC undergoing TACE followed by surgery or liver resection alone before and after propensity-score matching (PSM)., Results: A total of 384 patients were included of whom 60 (15.6%) received TACE. This group did not differ from upfront resected cases neither in terms of disease-free survival (p = 0.246) nor in overall survival (p = 0.276). After PSM, TACE still did not influence long-term outcomes (p = 0.935 and p = 0.172, for DFS and OS respectively). In subgroup analysis, TACE improved OS only in HCC ≥10 cm (p = 0.045), with a borderline significance after portal vein embolization/ligation (p = 0.087) and in single HCC (p = 0.052)., Conclusions: TACE should not be systematically performed in all resectable large HCC. Selected cases could however potentially benefit from this procedure, as patients with huge and single tumors or those necessitating of a PVE., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Combined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma., Methods: Patients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching., Results: During the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan-Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P = .0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P = .19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype., Conclusion: Despite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The SARS-CoV-2 (COVID-19) pandemic required a rapid surge of healthcare capacity to face a growing number of critically ill patients. For this reason, a support reserve of physicians, including surgeons, were required to be reassigned to offer support., Objective: To realize a survey on the educational programs deployed (face-to-face or e-learning focusing on infective area, basic gestures, COVID clinical management and intensive care medicine), and their impact on behavior change (Kirkpatrick 3) of the target population of surgeons, measured on a five modalities Likert scale., Design: Cross-sectional online e-survey (NCT04732858) within surgeons from the Assistance Publique - Hôpitaux de Paris network, metropolitan area of Paris, France., Results: Cross-sectional e-Survey: among 382 surgeons invited, 37 (9.7%) participated. The effectiveness of the educational interventions on behavior changes was rated within the highest region of the Likert scale by 15% ( n  = 3) and 22% ( n  = 6) for 'e-learning' and 'face-to-face' delivery modes, respectively., Conclusions: Despite the low response rate, this survey suggests an overall low impact on behaviour change among responders affiliated to a surgical discipline.

Background: Totally IntraVenous Acess Devices (TIVAD) are used to have long-term bloodstream access. The catheter connected to the subcutaneous chamber may be valved (TIVAD-V) or open-ended (TIVAD-O). Infectious and occlusion complications require the removal of the TIVAD. We compared the two types of catheters (TIVAD-V and TIVAD-O) in terms of time-to-removal and complication rates., Methods: A retrospective study of 636 patients treated for any malignancy using a TIVAD were included. TIVAD complication was defined as the occurrence of infection or occlusion requiring TIVAD removal. Risk factors of complications and time-to-removal of TIVAD were assessed by a Cox proportional hazard analysis., Results: A total of 55 TIVADs (8.7%) were removed including 47 for infection and eight for occlusion in 54 months. There was no significant difference in the frequency of complications between TIVAD-V and TIVAD-O. There was no significant difference in time-to-removal between TIVAD-V and TIVAD-O (17.0 months, IQR [10.5-25.0] and 18.4 months, IQR [11.5-22.9], p  = 0.345, respectively)., Conclusion: There was no difference between TIVAD with valved and open catheter in terms of complications and time-to-removal in patients treated by chemotherapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA., (© 2023. The Author(s).)

Background: Surgical resection (SR) is a potentially curative treatment of hepatocellular carcinoma (HCC) hampered by high rates of recurrence. New drugs are tested in the adjuvant setting, but standardised risk stratification tools of HCC recurrence are lacking., Objectives: To develop and validate a simple scoring system to predict 2-year recurrence after SR for HCC., Methods: 2359 treatment-naïve patients who underwent SR for HCC in 17 centres in Europe and Asia between 2004 and 2017 were divided into a development (DS; n = 1558) and validation set (VS; n = 801) by random sampling of participating centres. The Early Recurrence Score (ERS) was generated using variables associated with 2-year recurrence in the DS and validated in the VS., Results: Variables associated with 2-year recurrence in the DS were (with associated points) alpha-fetoprotein (<10 ng/mL:0; 10-100: 2; >100: 3), size of largest nodule (≥40 mm: 1), multifocality (yes: 2), satellite nodules (yes: 2), vascular invasion (yes: 1) and surgical margin (positive R1: 2). The sum of points provided a score ranging from 0 to 11, allowing stratification into four levels of 2-year recurrence risk (Wolbers' C-indices 66.8% DS and 68.4% VS), with excellent calibration according to risk categories. Wolber's and Harrell's C-indices apparent values were systematically higher for ERS when compared to Early Recurrence After Surgery for Liver tumour post-operative model to predict time to early recurrence or recurrence-free survival., Conclusions: ERS is a user-friendly staging system identifying four levels of early recurrence risk after SR and a robust tool to design personalised surveillance strategies and adjuvant therapy trials., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Eastern data highlight the oncological benefits of the anterior approach (AA) during right hepatectomy (RH) for hepatocellular carcinoma (HCC). However, to our knowledge, previous western data on this topic are scarce. In this study, the oncological outcomes of AA and classical approach (CA) during RH for HCC were compared., Methods: A retrospective inverse propensity score-weighted fashion (IPTW) case-control study was performed in two French hepatobiliary surgery departments. Overall survival (OS), disease-free survival (DFS), and early recurrence rate (within 2 years after surgery) were analyzed., Results: Survival analysis was performed for 114 patients (CA group,60 patients; AA group, 54 patients). Before IPTW adjustment, the 3-year DFS rates were 29.4% (AA group) and 44% (CA group), respectively. No significant differences were found in DFS (HR = 1.1, 95%CI:0.62-1.9, p = 0.77) and OS (HR = 1.2, 95%CI:0.54-2.6, p = 0.66). After IPTW, DFS and OS analyses showed no differences between the two groups (p = 0.77 and p = 0.46, respectively). Early recurrence rates were similar before and after IPTW. Satellite nodules were the only significant independent risk factor for recurrence., Conclusion: AA and CA did not result in significant differences in DFS, OS, or early recurrence after right hepatectomy for HCC before and after IPTW., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Anastomotic leak (AL) is a serious complication in digestive surgery. Early diagnosis might allow clinicians to anticipate appropriate management. The aim of this study was to assess the predictive value of amylase concentration in drain fluid for the early diagnosis of digestive tract AL., Materials and Methods: Hundred and fourteen consecutive patients "at risk" of AL, in whom a flexible drainage was placed by surgeon's choice after digestive anastomosis were included. Patients with eso-gastric, bilio-digestive, and pancreatic anastomoses were excluded. Drain amylase measurement (DAM) was routinely performed on postoperative day (POD) 1, 3, 5-7. DAM values were compared between patients with postoperative AL versus patients without AL. A receiver-operating curve (ROC) with calculation of the areas under the ROC curves area under curves was performed and a cutoff value of DAM was calculated., Results: AL occurred in 25 patients (AL group) and 89 patients did not present AL (C group). The mean DAM was significantly higher in AL group versus C Group on POD 1, 3, and 5. A cutoff value of 307 IU/L predicted the occurrence of AL with a sensitivity and specificity of 91% and 100%, respectively. Positive and negative predictive values were 100% and 97.5%, respectively. Patients with AL had an elevated DAM prior to the appearance of any clinical signs of AL., Conclusion: High level DAM could accurately predict AL for proximal and distal digestive tract anastomoses. This simple, noninvasive, and low-cost method can accurately predict early AL and help physicians to perform appropriate imaging and treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Research in Medical Sciences.)