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Stéphanie Gonvers,1,2 Sebastiao N Martins-Filho,3 André Hirayama,4 Julien Calderaro,5 Rebecca Phillips,3 Emilie Uldry,1,2 Nicolas Demartines,1,2 Emmanuel Melloul,1,2 Young Nyun Park,6 Valérie Paradis,7 Swan N Thung,8 Venancio Alves,4 Christine Sempoux,2,9 Ismail Labgaa1,2 1Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland; 2Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland; 3Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada; 4Department of Pathology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; 5Department of Pathology, APHP, Henri Mondor University Hospital, Creteil, Val-de-Marne, France; 6Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 7Department of Pathology, APHP, Beaujon University Hospital, Clichy, France; 8Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 9Department of Pathology, Lausanne University Hospital (CHUV), Lausanne, SwitzerlandCorrespondence: Ismail Labgaa, Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, CH-1011, Lausanne, Switzerland, Tel +41 0 79 556 68 47, Email ismail.labgaa@chuv.chAbstract: The macroscopic appearance of a tumor such as hepatocellular carcinoma (HCC) may be defined as its phenotype which is de facto dictated by its genotype. Therefore, macroscopic characteristics of HCC are unlikely random but rather reflect genomic traits of cancer, presumably acting as a valuable source of information that can be retrieved and exploited to infer prognosis. This review aims to provide a comprehensive overview of the available data on the prognostic value of macroscopic characterization in HCC. A total of 57 studies meeting eligible criteria were identified, including patients undergoing liver resection (LR; 47 studies, 83%) or liver transplant (LT; 9 studies, 16%). The following macroscopic variables were investigated: tumor size (n = 42 studies), number of nodules (n = 28), vascular invasion (n = 24), bile duct invasion (n = 6), growth pattern (n = 15), resection margin (n = 11), tumor location (n = 6), capsule (n = 2) and satellite (n = 1). Although the selected studies provided insightful data with notable prognostic performances, a lack of standardization and substantial gaps were noted in the report and the analysis of gross findings. This topic remains incompletely covered. While the available studies underscored the value of macroscopic variables in HCC prognostication, important lacks were also observed. Macroscopic characterization of HCC is likely an underexploited source of prognostic factors that must be actively explored by future multidisciplinary research. Keywords: liver cancer, HCC, prognostication, gross, survival, recurrence

Background: The clinical and economic impacts of enhanced recovery after surgery (ERAS) programmes have been demonstrated extensively. Whether ERAS protocols also have a biological effect remains unclear. This study aimed to investigate the biological impact of an ERAS programme in patients undergoing liver surgery. Methods: A retrospective analysis of patients undergoing liver surgery (2010-2018) was undertaken. Patients operated before and after ERAS implementation in 2013 were compared. Surrogate markers of surgical stress were monitored: white blood cell count (WBC), C-reactive protein (CRP) level, albumin concentration, and haematocrit. Their perioperative fluctuations were defined as Δvalues, calculated on postoperative day (POD) 0 for Δalbumin and Δhaematocrit and POD 2 for ΔWBC and ΔCRP. Results: A total of 541 patients were included, with 223 and 318 patients in non-ERAS and ERAS groups respectively. Groups were comparable, except for higher rates of laparoscopy (24.8 versus 11.2 per cent; P < 0.001) and major resection (47.5 versus 38.1 per cent; P = 0.035) in the ERAS group. Patients in the ERAS group showed attenuated ΔWBC (2.00 versus 2.75 g/l; P = 0.013), ΔCRP (60 versus 101 mg/l; P <0.001) and Δalbumin (12 versus 16 g/l; P < 0.001) compared with those in the no-ERAS group. Subgroup analysis of open resection showed similar results. Multivariable analysis identified ERAS as the only independent factor associated with high ΔWBC (odds ratio (OR) 0.65, 95 per cent c.i. 0.43 to 0.98; P = 0.038), ΔCRP (OR 0.41, 0.23 to 0.73; P = 0.003) and Δalbumin (OR 0.40, 95 per cent c.i. 0.22 to 0.72; P = 0.002). Conclusion: Compared with conventional management, implementation of ERAS was associated with an attenuated stress response in patients undergoing liver surgery. [ABSTRACT FROM AUTHOR]

Introduction: Partial hepatectomy (PH) remains associated with complication rates around 30-50%. Delayed return of gastrointestinal function (DRGF) has been reported in 10-20%. This study aimed to assess DRGF predictors after PH., Methods: This study included all consecutive adult patients undergoing PH between January 01, 2010, and December 12, 2019. DRGF was defined as the need for postoperative nasogastric tube (NGT) insertion. Patients leaving the operation room with a NGT were excluded. Independent DRGF predictors were identified with multivariable logistic binary regression., Results: A total of 501 patients were included. DRGF occurred in 82 patients (16%). Among DRGF patients, 17% (n = 14) needed a second NGT placement. DRGF incidences were similar before and after Enhanced Recovery after Surgery implementation in 2013 (16/78 = 20% vs. 66/423 = 16%, p = 0.305). A hundred-and-twelve patients (22%) underwent a minimally invasive approach and DRGF incidence was significantly lower in this group (5/112 = 4.5% vs. 77/389 = 19.8%, p < 0.001). DRGF was more frequent after major PH (55/238 = 23% vs. 27/263 = 10%, p < 0.001). DRGF occurred more often in patients with preoperative embolization (26/88 = 30% vs. 55/407 = 14%, p < 0.001), biliary anastomosis (20/48 = 42% vs. 61/450 = 14%, p < 0.001), and extrahepatic resection (37/108 = 34% vs. 45/393 = 11%, p < 0.001). Patients with DRGF had longer median operation duration (374 vs. 263 min, p < 0.001), more biliary leaks/bilomas (27/82 = 33% vs. 33/419 = 7.9%, p < 0.001), and higher median blood loss (1,088 vs. 701 mL, p < 0.001). DRGF patients developed more pneumonia (14/22 = 64% vs. 8/22 = 36%, p < 0.001) and had longer median length of stay (19 vs. 8 days, p < 0.001). On multivariable analysis, operation duration (OR 1.005, 95% CI: 1.002-1.008, p < 0.001), major hepatectomy (OR 3.606, 95% CI: 1.931-6.732), and postoperative biloma/biliary leak (OR 6.419, 95% CI: 3.019-13.648, p < 0.001) were independently associated with DRGF occurrence., Conclusion: Postoperative DRGF occurred in 16% of the patients and was associated with a longer length of stay. Surgery duration, major PH and postoperative biloma/biliary leak were found as independent predictors of DRGF., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: Pancreatic ductal adenocarcinoma (PDAC) has been shown to have a lower incidence in patients with blood group O. It is currently uncertain if patients with group O have a better prognosis after pancreatectomy. This study assessed the overall survival (OS) and disease-free survival (DFS) of PDAC patients who underwent upfront pancreatoduodenectomy based on ABO blood groups., Methods: A cross-sectional study was performed including patients from two university centers. All consecutive head PDAC patients who underwent upfront pancreatoduodenectomy from 2000 to 2016 were included. OS and DFS were compared between blood groups A, B, AB, and O using Kaplan-Meier curves and log-rank tests., Results: A total of 438 patients were included (215 women, median age 67). Pre- and intraoperative details were comparable between all subgroups. Median OS did not differ between the four blood groups (A: 23 months, 95% CI 18-28; B: 32, 95% CI 20-44; AB: 37, 95% CI 18-56 and O: 26, 95% CI 20-32, p = 0.192). Median DFS were also similar (A: 19 months, 95% CI 15-23; B: 26, 95% CI 19-33; AB: 35, 95% CI 15-55 and O: 22, 95% CI 15-29, p = 0.441). There was no OS difference between O and non-O groups (median: 26 months, 95% CI 20-33 vs. 25 months, 95% CI 20-30, p = 0.773). On multivariable analysis blood groups were not prognostic of OS. Only lymph node involvement, tumor differentiation, and adjuvant chemotherapy were independent prognostic factors., Conclusion: OS and DFS were similar between all four blood groups after pancreatoduodenectomy. Independent predictors of OS were associated with tumor characteristics and adjuvant treatment., (© 2024. The Author(s).)

Kidney transplantation (KT) is associated with a substantial risk of postoperative complications (POC) for which performant predictors are lacking. Data showed that a perioperative gain of weight (ΔWeight) was associated with higher risk of POC, but it remains unexplored in KT. This retrospective study aimed to investigate the association between ΔWeight and POC after KT. ΔWeight was calculated on postoperative day (POD) 2. POC were graded according to the Dindo-Clavien classification. Primary endpoint was overall POC. A total of 242 patients were included and 174 (71.9%) complications were reported. Patients showed a rapid gain of weight after KT. Mean ΔWeight was 7.83 kg (± 3.20) compared to 5.3 kg (± 3.56) in patients with and without complication, respectively (p = 0.0005). ΔWeight showed an accuracy of 0.74 for overall POC. A cut-off of 8.5 kg was determined. ΔWeight ≥ 8.5 kg was identified as an independent predictor of overall POC on multivariable analysis (OR 2.04; 95% CI 1.08-3.84; p = 0.025). ΔWeight ≥ 8.5 kg appeared as an independent predictor of POC after KT. These results stress the need to monitor weight in KT and to further investigate this surrogate with future studies assessing its clinical relevance., (© 2024. The Author(s).)

Purpose: Statin treatment has been shown in certain population studies and meta-analyses to improve survival of patients with pancreatic ductal adenocarcinoma (PDAC). This study assessed if patients with statin treatment had better overall survival (OS) and disease-free survival (DFS) after upfront pancreatoduodenectomy for PDAC., Methods: Consecutive PDAC patients were retrospectively collected from three centers in Europe and USA (study period: 2000-2017). Adult patients who underwent upfront pancreatoduodenectomy and survived the first 90 postoperative days were included. Patients with metastasis at diagnosis or with macroscopic incomplete resection were excluded. Patients were considered under statin if started at least one month before pancreatoduodenectomy. Survival rates were calculated using Kaplan-Meier method and compared with log-rank test., Results: A total of 496 patients were included. Median age was 67 years (IQR 59-75), 48% (n = 236) were women, and 141 patients (28%) received statin treatment already preoperatively. Patients with and without statin treatment were comparable in terms of demographics and pre-/intraoperative characteristics, except for age and pre-existing diabetes. Median OS and DFS were similar in patients with and without statin treatment (OS: 29, 95% CI 22-36 vs. 27 months, 95% CI 22-32, p = 0.370, DFS: 18, 95% CI 14-22 vs. 16 months, 95% CI 14-18, p = 0.430). On multivariable Cox regression, lymph node involvement (HR 1.9, 95% CI 1.6-2.2, p < 0.001), tumor differentiation (HR 1.3, 95% CI 1.1-1.6, p = 0.003), and postoperative chemotherapy (HR 0.5, 95% CI 0.4-0.7, p < 0.001) were predictors of OS, whereas statin treatment was not a prognostic factor (HR 0.9, 95% CI 0.7-1.2, p = 0.376)., Conclusion: In this international cohort of PDAC patients, statin treatment did not influence survival after upfront pancreatoduodenectomy. Nodal involvement, tumor differentiation, and postoperative chemotherapy were independent predictors of OS., (© 2023. The Author(s).)

Purpose: This prospective study aimed to analyze the functional, biological, and radiological aspects of the pancreatic anastomosis 1 year after pancreatoduodenectomy (PD)., Methods: From 2016 to 2019, patients with PD indication were screened. Questionnaires about pancreas insufficiency, fecal elastase tests, and magnetic resonance imaging (MRI) were performed before and 1 year after PD., Results: Twenty patients were prospectively included. The only difference between pre- and postoperative questionnaires was constipation (less frequent 1 year after PD). Median pre- and postoperative fecal elastase levels were 96 μg/g (IQR 15-196, normal value > 200) and 15 μg/g (IQR 15-26, p = 0.042). There were no significant differences in terms of main pancreatic duct (MPD) size (4, IQR 3-5 vs. 4 mm, IQR 3-5, p = 0.892), border regularity, stenosis, visibility, image improvement, and secondary pancreatic duct dilation before and after secretin injection. All patients but one (2 refused and 2 were lost to follow-up, 15/16, 94%) had a patent pancreaticojejunal anastomosis on 1-year MRI., Conclusion: Although median 1-year fecal elastase was significantly lower than preoperatively, suggesting that exocrine secretion was altered, the anatomical outcome as assessed by MRI was excellent showing high patency rate (15/16, 94%) at 1 year. This emphasizes the difference between anatomy and function., (© 2023. The Author(s).)

Alveolar echinococcosis is an endemic parasitosis in Switzerland. This pathology mainly infects the liver and develops similarly as a malignant tumor with its ability to spread into the hepatic parenchyma and its capacity of developing distant lesions via hematogenous dissemination. Treatment is based on complete surgical resection coupled with albendazole treatment. Recently, ex vivo liver resections with auto-transplantation have been shown to be feasible in case of end-stage alveolar echinococcosis. Moreover, new biomarkers such as programmed death-ligand 1 (PD-L1), a protein with immunomodulation property, have shown their potential impact on the treatment and follow-up of patients with alveolar echinococcosis., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: The carcinogenic effect of arsenic (As) has been documented in lung, bladder and skin cancers but remains unclear for digestive cancers, although metabolic pathways of As and recent data suggest that it may be an important determinant in these malignancies as well., Objective: This study aimed to systematically review the available literature investigating the potential association between As and digestive cancers., Methods: An extensive search was conducted in Medline Ovid SP, Cochrane, PubMed, Embase.com, Cochrane Library Wiley, Web of Science and Google Scholar. Studies providing original data in humans, with As measurement and analysis of association with digestive cancers including esogastric cancers (esophagus and stomach), hepato-pancreatico-biliary (HPB) cancers (including biliary tract, liver and pancreas) and colorectal cancers were eligible., Results: A total of 35 studies were identified, 17 ecological, 13 case-control and 5 cohort studies. Associations between As and digestive cancers were reported for both risks of incidence and cancer-related mortality. Overall, 43% (3/7) and 48% (10/21) studies highlighted an association between As and the incidence or the mortality of digestive cancers, respectively., Conclusions: A substantial proportion of studies exploring the potential link between As and digestive cancers suggested an association, particularly in HPB malignancies. These findings emphasize the need to further investigate this topic with dedicated and high-quality studies, as it may have an important impact, including for prevention strategies., (© 2023. The Author(s).)