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Limiting the post-weaning intake of the young rabbit is known to improve its resistance to digestive disorders, whereas a degradation of its housing hygiene is assumed to have a negative impact on its health. This study aims at providing insights into the mechanism of digestive health preservation regarding both host (growth and immune response) and its symbiotic digestive microbiota. A 2×2 factorial design from weaning (day 28) to day 64 was set up: ad libitum intake or restricted intake at 70% of ad libitum, and high v. low hygiene of housing (n=105 per group). At day 36 and day 45, 15 animals/group were subcutaneously immunized with ovalbumin (OVA) to assess their specific immune response. Blood was sampled at 36, 45, 57 and 64 days of age to determine total and anti-OVA immunoglobulin type G (IgG) and haptoglobin levels. The cecal bacterial community was explored (18 per group) by 454 pyrosequencing of genes coding for the 16S ribosomal RNA, whereas cecal pH, NH3 and volatile fatty acid (VFA) concentrations were measured to characterize fermentative activity. A 30% reduction in feed intake reduced the growth by only 17% (P

Background: Trifluridine/tipiracil (FTD/TPI) is approved in third-line treatment of patients with advanced/metastatic gastric and gastroesophageal junction adenocarcinomas (aGA/GEJA). The association of oxaliplatin with FTD/TPI is promising and the combination of FTD/TPI + oxaliplatin + nivolumab has shown a predictable and manageable safety profile., Aims: The aim is to evaluate the efficacy and safety of FTD/TPI plus oxaliplatin with or without nivolumab in patients, with HER2 negative aGA/GEJA, unfit for triplet chemotherapy (TFOX/mFLOT regimen), in the first-line metastatic setting in comparison with the standard of care FOLFOX with or without nivolumab., Methods: This study is a prospective randomised, open label, comparative, multicentre, phase II trial designed to include 118 patients. The primary objective is to evaluate the superiority of FTD/TPI plus oxaliplatin with or without nivolumab over FOLFOX regimen with or without nivolumab in terms of PFS in a population of patients non candidate for triplet chemotherapy. Nivolumab will be used for patients whose tumour express PD-L1 with a CPS score ≥5., Discussion: PRODIGE73-UCGI40-LOGICAN study will provide efficacy and safety data on the association of FTD/TPI plus oxaliplatin with or without nivolumab versus FOLFOX regimen with or without nivolumab in first-line palliative setting, in patients with aGA/GEJA (NCT05476796)., Competing Interests: Conflict of interest D.B. reports personal fees as a speaker and/or in an advisory role from Accord Healthcare, Amgen, Sanofi, Servier, and Pierre Fabre, outside the submitted work. O.B. reports personal fees as a speaker and/or in an advisory role from Merck, Bayer, Apmonia Therapeutics, Deciphera, Takeda, MSD, Amgen, Servier, and Pierre Fabre, outside the submitted work. C.C. reports personal fees as speaker and/or in an advisory role from Amgen, Astra-Zeneca, Pierre Fabre, Daiichy Sankyo, BMS, MSD, Merck Serono, Servier, outside the submitted work. O.D. reports personal fees as speaker and/or in an advisory role from Astra-Zeneca, BMS, MSD, Merck Serono, Sanofi, Servier outside the submitted work. DT: Honoraria: Amgen, Roche, Sanofi, Bristol Myers Squibb, Merck Serono, MSD, Bristol Myers Squibb, Servier, Ipsen, Pierre Fabre, AstraZeneca, Takeda, BeiGene, Astra Zeneca. Consulting or Advisory Role: Sanofi, MSD, Pierre Fabre, AstraZeneca, Novartis, Takeda. Research Funding: AstraZeneca (Inst), Servier (Inst), Roche (Inst), MSD (Inst), BTG (Inst). Travel, Accommodations, Expenses: Roche, Amgen, Bristol Myers Squibb, MSD, Pierre Fabre. CDLF: Honoraria: Amgen, AstraZeneca,Bayer, BeiGene, Bristol Myers Squibb, Ipsen, Merck, MSD, Pierre Fabre, Servier, Roche, Sanofi, Takeda. Consulting or Advisory Role: MSD, Pierre Fabre, AstraZeneca, Takeda. Research Funding: Servier (Inst), Roche (Inst), MSD (Inst). Travel, Accommodations, Expenses: Roche, Amgen, MSD, Pierre Fabre, Servier., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Early detection of postoperative infectious complications (IC) is crucial after Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). The aim of this study was to evaluate the predictive role of early postoperative inflammatory biomarkers level for the detection of postoperative IC., Methods: a retrospective study was performed including 199 patients treated with complete CRS/HIPEC for PC from various primary origins from September 2012 to January 2021. Patients were monitored by a routine measurement of inflammatory biomarkers (CRP, leukocytes, neutrophils, lymphocytes, neutrophile-to-lymphocyte ratio and platelets-to-lymphocyte ratio). Inflammatory biomarkers were compared between patients with vs without IC., Results: IC occurred for 68 patients (34.2%). CRP values were significantly higher in patients with IC on POD 3, 5 and 7 (CRP = 166 mg/L [128-244], 155 mg/L [102-222] and 207 mg/L [135-259], respectively). The CRP on POD7, with a cut-off value of 100 mg/L, was an excellent predictor of postoperative IC (AUC = 90.1%). The CRP on POD 5, with a cut-off value of 90 mg/L, was a good predictor of postoperative IC (AUC = 83.2%). NLR values were significantly higher in patients with IC on POD 3, 5 and 7. NLR on POD 5 and 7 higher than 9.7 and 6.3, respectively, were fair predictors (AUC = 70.8 and 79.6, respectively)., Conclusion: CRP levels between POD3 and 7 are the best predictors of postoperative IC after CRS/HIPEC. The presence of postoperative IC should be suspected in patients with CRP higher than 140 mg/L, 90 mg/L or 100 mg/L on PODs 3, 5 or 7., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Immune checkpoint inhibitors have failed in treating metastatic colorectal cancer (mCRC) patients except those with dMMR/MSI tumors. However, until very recently we had only non-comparative promising data in this population with anti-programmed cell death 1/ programmed cell death ligand 1 (PD1/PD-L1) antibodies alone or combined with anti- cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies. This comparative phase II trial (NCT03186326), conducted in more than 100 centers in France, will include dMMR/MSI mCRC patients with progression after a first-line treatment with chemotherapy ± targeted therapies, to evaluate efficacy and safety of the anti-PDL1 Avelumab versus a standard second-line treatment. Main inclusion criteria were patients aged 18 to 75 years, ECOG performance status ≤2, dMMR/MSI mCRC and failure of a standard first-line regimen. Patient will be randomised to receive Avelumab 10 mg/kg versus standard second-line doublet chemotherapy plus a targeted agent according to tumor RAS status. Patients will be followed for 4 years. A gain of 5 months in median PFS is expected in favour of the Avelumab arm (12 vs 7 months; HR=0.58). Secondary endpoints include objective response rate, overall survival, quality of life and toxicity. In addition, circulating tumour DNA and microbiota will be explored to test their potential prognostic and predictive values. The study was opened in March 2018., Competing Interests: Declaration of Competing Interest JT has received honoraria for speaker or advisory role from Sanofi, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, Lilly, Astra Zeneca and MSD. LE has received honoraria for speaker or advisory role Servier, Merck Serono, Amgen. PLP is a consultant/advisory board member for Merck Serono, Astrazeneca Amgen, Boehringer Ingelheim, Biocartis, Roche, Bristol-Myers Squibb, Pierre Fabre, Servierand MSD. CL has served in a consulting/advisory role and or received honoraria for, Amgen, Pierre Fabre, Novartis, AAA. FE has received honoraria for speaker and/or advisory role from Ipsen, Merck, Bayer, Sanofi and Servier. OB has received honoraria for speaker and/or advisory role from Merck KGaA, Roche Genentech, Bayer, Astra-Zeneca, Grunenthal, MSD, Amgen, Servier, and Pierre Fabre, TA has served in a consulting/advisory role and/or received honoraria from Amgen, Bristol-Myers Squibb, Chugai, Clovis, Halliodx, MSD, Pierre Fabre, Roche/Ventana, Sanofi, Servier and has received travel, accommodations, and expenses from Roche/Ventana, MSD Oncology, and Bristol-Myers Squibb. DT has served in a consulting/advisory role and/or received honoraria from Amgen, Bristol-Myers Squibb, MSD Oncology, Roche/Ventana, Sanofi, Servier, Novartis, Merck Serono and Astra Zeneca. HP has served in a consulting/advisory role and/or received honoraria from Amgen, Sanofi, Servier, Merck Serono and Roche. SK has received honoraria for speaker and/or advisory role from Amgen, Ipsen, MSD, Pfizer, Sanofi, and Servier. EB, JFE, JB, MC and FD have nothing to disclose. CT has received honoraria for speaker or advisory role from Merck, Sanofi, MSD, Ipsen, Amgen, Servier, and Bristol-Myers Squibb. This research was financially supported by Merck Santé S.A.S., an affiliate of Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: This document is a summary of the French Intergroup guidelines regarding the management of gastrointestinal stromal tumours (GISTs) updated in December 2018., Design: This collaborative work summarizes clinical practice recommendations (guidelines) on the management of GISTs. It is based on recent literature review, ESMO recommendations and expert opinions., Results: The diagnosis of GIST is based on histological examination and immunohistochemistry with markers KIT and DOG-1. Each case must be discussed within a multidisciplinary team. Complete surgical resection tumour, avoiding peroperative perforation, is the potentially curative treatment of localized GISTs. The estimation of the recurrence risk is essential, or adjuvant treatment,and follow-up adaptation. Genotyping (KIT and PDGFRA) of all but very low-risk GISTs is recommended. The nature of mutation has a prognostic value and predictive influence on drug efficacy. Imatinib, a tyrosine-kinase inhibitor, is the standard adjuvant treatment after R0 resection of a GIST with a high risk of recurrence, and the first line therapy for advanced GISTs. Suninitib and regorafenib are respectively the second- and third-line standard treatments for advanced GISTs., Conclusion: Guidelines for management of GISTs are continuously evolving and need to be regularly updated. This constant progress is made possible through clinical and translational research., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m 2  q3w) to cisplatin (75 mg/m 2  q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated., Aim: GASTFOX study is a randomized phase III trial comparing FOLFOX alone or with docetaxel at 50 mg/m 2 (TFOX regimen) in first-line treatment for advanced gastric cancer. In both arms, cycle is repeated every 2 weeks until disease progression or unacceptable toxicity., Materials and Methods: Main eligibility criteria: histologically proven locally advanced or metastatic gastric or esogastric junction adenocarcinoma, HER negative status, measurable disease, ECOG performance status 0 or 1, and adequate renal, hepatic and bone marrow functions., Results: The primary endpoint is radiological/clinical progression-free survival (PFS). A difference of 2 months for the median PFS in favor of TFOX is expected (HR = 0.73) Based on a two-sided α risk of 5% and a power of 90%, 454 events are required to show this difference. Secondary endpoints included overall survival, overall response rate, safety, quality of life and the therapeutic index., Conclusion: This study is planned to include 506 patients to demonstrate the superiority of TFOX over FOLFOX in first-line advanced gastric cancer treatment (NCT03006432)., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

In this randomized, double-blind, placebo-controlled study comparing gemcitabine+tipifarnib (G+t) or gemcitabine+placebo (G+p) in patients with pancreatic cancer, the primary endpoint of time to deterioration (TTD) was based primarily on patient-reported outcomes. Deterioration was defined as death or worsening of disease-related symptoms, based on patient-reported outcomes of pain intensity and analgesic use in a daily diary, plus investigator-rated weekly performance status. Secondary endpoints included survival and safety. Two hundred and forty-four patients were treated for a total of 4780 weeks, during which the diary was completed daily. Overall, the completion of the diary was found to be feasible: patients completed approximately 95% of scheduled diary entries. Baseline characteristics were well balanced between the two treatment arms. The primary endpoint of TTD was not significantly different between the G+t arm (69 days) and the G+p arm (91 days, P=0.40). Survival was not significantly different between the G+t arm (202 days) and the G+p arm (221 days, P=0.66). The combination of G+t had an acceptable toxicity profile, with primarily neutropenia and thrombocytopenia. Methodologically, measurement of patient-reported outcomes is feasible and useful in assessing the effect of anti-cancer therapy in pancreatic cancer if comprehensive initial and ongoing training is provided to all people involved, including not only the patients but also the study personnel.

We report a case with neurologic symptoms which occurred after iterative radiologic examinations of the gastrointestinal tract with barium sulphate, which were related to a barium encephalopathy. Suspected by the presence of barium in the blood, a systematic intoxication was occurred without any evidence for a gut or a vascular leak. This case raises the question about a possible extraluminal diffusion of such a heavy metal, given orally, in normal conditions of use.