Biliary tract cancers: French national clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACABi, ACHBPT).

Introduction: This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org).

Cholangiocarcinoma: what are the options in all comers and how has the advent of molecular profiling opened the way to personalised medicine ?

Cholangiocarcinoma is a deadly cancer comprising very heterogenous subtypes with a limited therapeutic arsenal in all comers. However, recent significant advances were made with immunotherapy in the first-line treatment of advanced cholangiocarcinoma, with the addition of durvalumab to cisplatin-gemcitabine chemotherapy showing a survival benefit. In the second line setting, only FOLFOX (5FU/folinic acid-oxaliplatin) is validated by a phase 3 trial, yet with a very modest benefit on survival; new options using 5FU with nanoliposomal-irinotecan may emerge in the next few years.

A Promising Biomarker and Therapeutic Target in Patients with Advanced PDAC: The Stromal Protein βig-h3.

With an overall survival rate of 2-9% at 5 years, pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related deaths in the industrialized world and is predicted to become the second by 2030. Owing to often late diagnosis and rare actionable molecular alterations, PDAC has not yet benefited from the recent therapeutic advances that immune checkpoint inhibitors (ICI) have provided in other cancer types, except in specific subgroups of patients presenting with tumors with high mutational burden (TMB) or microsatellite instability (MSI). The tumor microenvironment (TME) plays a substantial role in therapeutic resistance by facilitating immune evasion.

Hyperprogressive Disease After Combined Anti-PD-L1 and Anti-CTLA-4 Immunotherapy for MSI-H/dMMR Gastric Cancer: A Case Report.

Immune checkpoint inhibitors (ICI) have been developed in gastric adenocarcinomas and approved in first-line metastatic setting (in combination with chemotherapy) as well as in pretreated patients. Microsatellite instability-high (MSI-H) tumors are predicted to derive high benefit from ICI but data in gastric locations are limited. Here, we describe the case of a 68-year old patient with stage IV MSI-H gastric adenocarcinoma, referred to our center to receive immunotherapy after failure of standard of care (surgery with perioperative platin-based chemotherapy and paclitaxel plus ramucirumab at disease progression).

Immune checkpoint inhibitor sensitivity of DNA repair deficient tumors.

Faithful DNA replication is necessary to maintain genome stability and implicates a complex network with several pathways depending on DNA damage type: homologous repair, nonhomologous end joining, base excision repair, nucleotide excision repair and mismatch repair. Alteration in components of DNA repair machinery led to DNA damage accumulation and potentially carcinogenesis. Preclinical data suggest sensitivity to immune checkpoint inhibitors in tumors with DNA repair deficiency.

Role of FOLFIRINOX and chemoradiotherapy in locally advanced and borderline resectable pancreatic adenocarcinoma: update of the AGEO cohort.

Background: FOLFIRINOX has shown promising results in locally advanced (LAPA) or borderline resectable (BRPA) pancreatic adenocarcinoma. We report here a cohort of patients treated with this regimen from the AGEO group.

Methods: This is a retrospective multicentre study.

Adrenal gland as a sanctuary site for immunotherapy in patients with microsatellite instability-high metastatic colorectal cancer.

Metastatic colorectal cancers (mCRC) harboring microsatellite instability (MSI) are sensitive to immune checkpoint inhibitors (ICIs), but the mechanisms of resistance to ICIs remain unclear. Dissociated responses in patients with ICI-treated cancer suggest that certain organs may serve as sanctuary sites due to the tumor microenvironment. This case series describes five patients with ICI-treated MSI mCRC with disease progression limited to the adrenal glands.

Neutrophil Heterogeneity in Cancer: From Biology to Therapies.

Neutrophils have been extensively described in the pathophysiology of autoimmune and infectious diseases. Accumulating evidence also suggests the important role of neutrophils in cancer progression through their interaction with cancer and immune cells in blood and in the tumor microenvironment (TME). Most studies have described neutrophils as key drivers of cancer progression, due to their involvement in various tumor promoting functions including proliferation, aggressiveness, and dissemination, as well as in immune suppression.

Long-Term Survivors in Metastatic Pancreatic Ductal Adenocarcinoma: A Retrospective and Matched Pair Analysis.

Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is an aggressive malignancy with a median overall survival (OS) of between 8 and 11 months. However, a significant number of patients experience a longer survival, more than 18 months. The aim of this study was to describe the "long-term survivor" population and to evaluate clinical and pathological factors that might affect survival.

Primary malignant melanoma of the esophagus, treated with immunotherapy: a case report.

Primary malignant melanoma of the esophagus is rare, accounting for less than 0.1-0.2% of all esophageal malignancies.

Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: a multicenter AGEO study.

Introduction: Trastuzumab in combination with platinum-based chemotherapy is the standard first-line regimen in HER2-positive advanced gastric cancer. However, there are very few data concerning efficacy of continuing trastuzumab beyond first-line progression.

Methods: This retrospective multicenter study included all consecutive patients with HER2-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received a second-line of chemotherapy with or without trastuzumab after progression on platinum-based chemotherapy plus trastuzumab.

Use of gemcitabine as a second-line treatment following chemotherapy with folfirinox for metastatic pancreatic adenocarcinoma.

There is a lack of prospective data about second-line treatments for metastatic pancreatic ductal adenocarcinoma patients. This is partially due to recent changes in first-line chemotherapy treatments. Despite this dearth of information, 50.

Obscure bleeding colonic duplication responds to proton pump inhibitor therapy.

We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding. Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years previously. An emergency abdominal computed tomography scan, gastroscopy and colonoscopy, performed after hemodynamic stabilization, were considered normal.

Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors.

Cancer immunosurveillance relies on effector/memory tumor-infiltrating CD8(+) T cells with a T-helper cell 1 (TH1) profile. Evidence for a natural killer (NK) cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells as well as by indirect immunostimulatory effects on T and NK cells.

Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors.

The natural killer (NK) cell receptor NKp30 is involved in the recognition of tumor and dendritic cells (DCs). Here we describe the influence of three NKp30 splice variants on the prognosis of gastrointestinal sarcoma (GIST), a malignancy that expresses NKp30 ligands and that is treated with NK-stimulatory KIT tyrosine kinase inhibitors. Healthy individuals and those with GIST show distinct patterns of transcription of functionally different NKp30 isoforms.