Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a significant percentage of germline pathogenic variants (GPVs). Unlike in the United States, routine universal genetic testing is not performed in Europe. The aim of the study is to evaluate the diagnostic yield of germline genetic testing in all patients with PDAC. Methods: Individuals with newly diagnosed PDAC from three Spanish hospitals were enrolled, regardless of family history. Thirteen known susceptibility genes for PDAC were studied using a multigene panel or whole-exome sequencing. Results: One hundred seventy-nine PDAC patients underwent genetic testing. Fourteen (7.8%) had a GPV or likely pathogenic variant In the genes studied: six in ATM, six in BRCA2, one in PALB2, and one in TP53. Of these, seven (50%) did not meet the clinical criteria for genetic study and would have been classified as sporadic PDAC. Presenting with a personal history of any other neoplasm was associated with some GPV, with an odds ratio (OR) of 3.5 (1.1–11.5). A family history of PDAC and breast cancer was also associated with some GPV, with oRs of 3.7 (1.08–13.6) and 8.5 (2.6–26.6), respectively. None of the patients over 60 years without a relevant family history of malignancies presented a GPV associated with PDAC. Conclusions: In our PDAC cohort, a noteworthy number of GPVs were identified, and half of these patients would have been classified as sporadic based solely on clinical criteria. Genetic testing should always be considered, particularly in patients under 60 years or those with a history of other malignancies, especially where economic resources need optimization.

Background/Objectives: Gastric cancer (GC) remains a leading cause of cancer mortality worldwide. While most cases are sporadic, approximately 10% show familial clustering with only a minority explained by known hereditary syndromes. The remaining, termed familial non-hereditary gastric cancer (FNHGC), lack a defined high-penetrance germline mutation. This review aims to summarize current knowledge regarding the diagnosis, risk factors, molecular characteristics and management of FNHGC. Methods: A comprehensive narrative review of the literature was conducted focusing on epidemiologic, molecular and clinical studies addressing families with multiple GC cases but no identified germline mutation. Results: The etiology of FNHGC is multifactorial, and H. pylori, with its related chronic gastritis, is probably the key driver. Familial clustering likely occurs when combined with other elements such as genetic polymorphisms, shared exposures to risk factors or even epigenetic phenomena. Molecular profiling reveals distinct patterns in familial tumors such as more frequent microsatellite instability; somatic CDH1 promoter hypermethylation; and recurrent somatic mutations in TP53, RHOA and DNA repair genes. Current management focuses on genetic testing to rule out hereditary syndromes, endoscopic surveillance and mitigation of risk factors, with eradication of H. pylori paramount. Conclusions: FNHGC represents a distinct subgroup of GC characterized by a multifactorial etiology related to exposure to risk factors and genetic susceptibility although significant gaps remain in fully explaining the condition. Ongoing research holds promise to provide tools for better detection and prevention in order to reduce the burden of GC in familial settings.

La MIG constituye una de las principales lesiones premalignas implicadas en la secuencia de carcinogénesis del adenocarcinoma gástrico de tipo intestinal descrita por Correa. Su identificación representa uno de los pilares de la prevención secundaria del cáncer gástrico, al permitir seleccionar a los pacientes con mayor riesgo de progresión y establecer programas de vigilancia individualizados. En los últimos años se han producido avances relevantes en la comprensión fisiopatológica de la metaplasia intestinal y en las técnicas de diagnóstico endoscópico. Entre los avances más destacados se encuentran la cromoendoscopia virtual, la clasificación EGGIM, los sistemas histológicos OLGA y OLGIM, y la incorporación progresiva de la inteligencia artificial. Las guías clínicas actuales han reforzado el papel de la endoscopia de alta calidad, la estratificación individual del riesgo y la erradicación sistemática de Helicobacter pylori. Esta revisión resume la evidencia más reciente sobre epidemiología, fisiopatología, clasificación, diagnóstico, estratificación del riesgo y manejo clínico de la MIG, comparando las principales guías internacionales e incorporando las perspectivas de la inteligencia artificial aplicada a la endoscopia digestiva.

Preliminary evidence suggests that patients with Enterococcus faecalis bacteremia and infective endocarditis, particularly those without an identifiable source, may have an increased prevalence of colorectal neoplasia. Whether systematic colonoscopy should be recommended in this population remains unresolved. EnteroColonus is a multicenter, prospective, observational matched cohort study that will recruit adults aged 50 years or older with E. faecalis bacteremia and/or infective endocarditis from 22 Spanish centers, together with asymptomatic controls undergoing colorectal cancer screening. Cases will be stratified into E. faecalis bacteremia/endocarditis of unknown origin (EFBEUO) and with suspected source (EFBESS). Planned sample size is 414 participants: 276 cases and 138 matched controls. Core procedures include colonoscopy, histopathology, clinical and microbiological phenotyping, fecal microbiome profiling by shotgun metagenomics, detection of E. faecalis genetic material in colorectal biopsy specimens using 16S sequencing and species-specific qPCR, and whole-genome, SNP, and phylogenetic analyses of clinical isolates. The primary endpoint is the detection of colorectal neoplasia by colonoscopy/histopathology in EFBEUO compared with EFBESS and matched screening controls. Secondary endpoints include microbiome profiles, biopsy positivity for E. faecalis, genomic traits of bloodstream isolates, mortality, relapse/recurrence, and development of a colorectal neoplasia risk score. This protocol is designed to clarify which patients with E. faecalis bloodstream infection might benefit from systematic colonoscopy evaluation and to explore host-microbe mechanisms underlying the observed association with colorectal neoplasia.