The host immune response plays a major role in colorectal carcinoma (CRC) progression. A mechanism of tumor immune escape might involve expression of the human leucocyte antigen (HLA)‐E/β2m on tumor cells. The inhibitory effect of HLA‐E/β2m on CD8+ cytotoxic T lymphocytes and natural killer (NK) cells is mediated by the main HLA‐E receptor CD94/NKG2A. As the pathophysiological relevance of this mechanism in CRC remains unknown, this prompted us to examine, in situ, in a series of 80 CRC (i) the HLA‐E and β2m coexpression by tumor cells, (ii) the density of CD8+, cytotoxic, CD244+ and NKP46+ intraepithelial tumor‐infiltrating lymphocyte (IEL‐TIL) and (iii) the expression of CD94/NKG2 receptor on IEL‐TIL. These data were then correlated to patient survival. We provided (i) the in situ demonstration of HLA‐E/β2m overexpression by tumor cells in 21% of CRC characterized by an overrepresentation of signet ring cell carcinomas, mucinous carcinomas and medullary carcinomas, (ii) the significant association between HLA‐E/β2m overexpression by tumor cells and increased density of CD8+ cytotoxic, CD244+ and CD94+ IEL‐TIL and (iii) finally, the unfavorable prognosis associated with HLA‐E/β2m overexpression by tumor cells. Our findings show that HLA‐E/β2m overexpression is a surrogate marker of poor prognosis and point to a novel mechanism of tumor immune escape in CRC in restraining inhibitory IEL‐TIL.

Background: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. Objective: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). Design: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. Results: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT—containing bismuth, metronidazole and tetracycline—plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. Conclusion: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. Trial registration number: NCT02328131 .

Background: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence.Material and Methods: In this prospective, multicenter, cross‐sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin‐17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference.Results: Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P = .015] and corpus AG [61.0% (95% CI 49.2; 72.0), P = .004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P = .068).Conclusion: Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.

Background: Digestive hamartomatous polyps are a rare entity. They may be sporadic (solitary Peutz-Jeghers polyp or solitary juvenile polyp) or reveal genetic predisposition like Peutz-Jeghers syndrome, juvenile polyposis or Cowden disease. Summary: Diagnosis is based on personal and family history and on clinical data including physical signs (in particular dermatological), endoscopic findings (the number of polyps) and histological features of the polyps. The risk of complications and of digestive and extra-digestive cancers may be high, especially in case of genetic predisposition syndromes, and requires multidisciplinary management of the patients (oncogenetic counseling, gastroenterologist, pathologist, dermatologist, gynecologist and endocrinologist). Endoscopic evaluation is very helpful to establish the current situation, to perform polypectomy and to allow for good histological examination of the polyps, whose degeneration has been exceptionally described. The recent development of new molecular techniques (next-generation DNA sequencing) allows for rapid multiple gene sequencing and facilitates diagnosis. Key Message: Discovery of a hamartomatous polyp requires a rigorous work-up which should be performed by a multidisciplinary team, including a genetic oncologist, experienced in this pathology. Practical Implications: The diagnostic procedure in hamartomatous polyps should be based on the number of polyps identified during endoscopy (solitary versus multiple) and on their histological characteristics. The clinical examination must search for mucosal and skin lesions. If a polyposis syndrome is identified, oncogenetic consultation is necessary in order to define screening modalities for family members, aiming at preventing cancer development. Endoscopic resection (polypectomy) of the lesions may prevent complications like bleeding and degeneration and also diminish the risk of surgery and subsequent short bowel syndrome.