Hernán Quiceno

Claudin 18 isoform 2 (CLDN18.2) has emerged as a novel therapeutical target for HER2-negative, locally advanced, or metastatic gastroesophageal adenocarcinoma. However, reported prevalence rates vary widely (24–47%), underscoring the need for accurate population-specific data. This study investigates the CLDN18.2 prevalence in Spanish patients with gastroesophageal adenocarcinoma and explores its correlation with other biomarkers and clinicopathological factors. We retrospectively analyzed endoscopic biopsy samples from gastroesophageal adenocarcinoma patients across three Spanish institutions. CLDN18.2 expression was evaluated by immunohistochemistry using the Ventana CLDN18 (43-14A) assay and PS2+ scoring, with cases showing membranous 2+ or 3+ staining in ≥ 75% of tumor cells classified as positive. Clinicopathological and biomarker data were retrieved from medical records. CLDN18.2 was positive in 33% (89/270) of cases. Although histological type was not correlated with CLDN18.2 status, cases with poorly cohesive morphology exhibited heterogeneous staining, with a predominance of moderately and strongly stained cells. A weak to moderate inverse correlation was identified between signet ring cell content and CLDN18.2 staining (r = −0.29, p = 0.028). No significant differences were observed in clinical outcome. However, among patients with advanced-stage disease, CLDN18.2-positive intestinal tumors were associated with worse progression-free survival (HR 2.58, 95% CI 1.18–5.63; p = 0.029). These findings confirm a 33% prevalence of CLDN18.2 expression in the Spanish population, aligning with reports from other Western European cohorts. The significant heterogeneity in poorly cohesive cases and an inverse correlation with signet ring cell content pose diagnostic challenges for pathologists. Moreover, the association between CLDN18.2 positivity and worse progression-free survival in intestinal adenocarcinoma supports a potential role in tumor progression and metastasis, warranting further research.

Objectives: Inflammatory fibroid polyps, also known as Vanek’s tumors, are rare benign lesions of the gastrointestinal tract. Although the exact cause remains unclear, several theories suggest an association with inflammatory processes and genetic factors. This study aims to present the largest cohort of inflammatory fibroid polyp cases to date, analyzing their clinical presentation, diagnostic methods, and treatment approaches. Materials and methods: A retrospective multicentric analysis was conducted on 67 patients diagnosed with inflammatory fibroid polyps between 2013 and 2023 across four hospitals. Clinical data regarding tumor location, size, symptoms, and treatment were collected. Non-parametric statistical tests, including the chi-square test, Cramér’s V coefficient, and the Mann–Whitney U test, were used to identify association between tumor characteristics, location, and treatment outcomes. Results: The cohort included 67 patients (58.2% female, median age 60 years). The stomach was the most common tumor site (47.8%), followed by the colon (32.8%), and small intestine (10.4%). The majority of patients (73.1%) were asymptomatic, while 9% experienced intestinal obstruction, all of which were located in the small intestine. Endoscopic resection was successful in 77.6% of cases, but surgical intervention was more frequently required for tumors in the small intestine. A significant association was found between larger tumor size, emergency presentation, intestinal location, and the need for surgery. Conclusions: Inflammatory fibroid polyps are commonly managed with endoscopic resection, particularly in gastric and colonic locations. However, small intestinal tumors more often need surgical treatment, especially when presenting with complications like intestinal obstruction.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent clinical condition associated with elevated morbidity and mortality rates. Patients with MASLD treated with semaglutide, a glucagon-like peptide-1 receptor agonist, demonstrate improvement in terms of liver damage. However, the mechanisms underlaying this beneficial effect are not yet fully elucidated. We investigated the efficacy of semaglutide in halting MASLD progression using a genetic mouse model of diabesity. Leptin-receptor-deficient mice with obesity and diabetes (BKS db/db) were either untreated or administered with semaglutide for 11 weeks. Changes in food and water intake, body weight and glycemia were monitored throughout the study. Body fat composition was assessed by dual-energy X-ray absorptiometry. Upon sacrifice, serum biochemical parameters, liver morphology, lipidomic profile and liver-lipid-related pathways were evaluated. The semaglutide-treated mice exhibited lower levels of glycemia, body weight, serum markers of liver dysfunction and total and percentage of fat mass compared to untreated db/db mice without a significant reduction in food intake. Histologically, semaglutide reduced hepatic steatosis, hepatocellular ballooning and intrahepatic triglycerides. Furthermore, the treatment ameliorated the hepatic expression of de novo lipogenesis markers and modified lipid composition by increasing the amount of polyunsaturated fatty acids. The administration of semaglutide to leptin-receptor-deficient, hyperphagic and diabetic mice resulted in the amelioration of MASLD, likely independently of daily caloric intake, suggesting a direct effect of semaglutide on the liver through modulation of the lipid profile.