Gastrointestinal Disorders

Background: Proton pump inhibitors (PPIs) serve as efficacious therapies for acid-related conditions; nonetheless, the possibility of unwarranted prolonged usage has led to heightened focus on PPI management and suitable deprescribing practices. Investigating supportive non-pharmacological approaches after the cessation of PPIs is necessary. Objective: This single-arm pilot study evaluated the feasibility and acceptability of a structured transition from proton pump inhibitor (PPI) therapy to papaya–oat food supplementation with Caricol^®-Gastro in adults with mild-to-moderate reflux/heartburn. Changes in patient-reported symptoms during supplementation were assessed as exploratory clinical outcomes. Adults with mild-to-moderate reflux/heartburn underwent a protocol-defined PPI treatment phase, followed by PPI discontinuation and five weeks of Caricol^®-Gastro supplementation. Symptoms reported by patients were evaluated utilizing a tailored 15-item questionnaire right prior to supplementation and at Week 5. Feasibility results encompassed research finalization, compliance, fulfillment of the protocol-specified transition, and the necessity for symptom-associated PPI reinstatement. A 14-day observation period without products following the intervention evaluated the short-term incidence of symptoms after the cessation of supplementation. Results: All 39 persons who enrolled finished the trial. The average compliance with supplementation was 93.2%, and no participant ceased using Caricol^®-Gastro due to exacerbation or recurrence of reflux/heartburn symptoms, nor did any require the reinitiation of protocol-allowed PPIs during the supplementation period. The average overall symptom score diminished from 37.38 (SD 2.88) before supplementation to 24.85 (SD 4.84) by Week 5, reflecting a mean within-participant alteration of −12.54 points (95% CI: −13.54 to −11.53; p < 0.001). Throughout the 14-day observation period following the intervention without product use, 11 subjects (28.2%) exhibited no symptoms, while 28 (71.8%) experienced symptoms on at most two occasions. Conclusions: The results support the feasibility and acceptability of the protocol-defined transition from PPI therapy to papaya–oat supplementation in this selected population. The noted decreases in symptoms within participants are preliminary and, due to the lack of a controlled design, cannot be causally linked to Caricol^®-Gastro. These results advocate for additional assessment of the supplementation as a possible supporting approach after the clinically suitable cessation of PPIs in a sufficiently powered randomized controlled trial employing a validated patient-reported primary outcome. Full article

Background/Objectives: Adrenomedullin (AM) is a circulating peptide involved in tumor progression, angiogenesis, and fibrosis. However, its clinical utility as a biomarker in gastrointestinal cancers remains unclear. Methods: This single-center prospective observational study included patients with unresectable advanced gastrointestinal cancers (esophageal, gastric, colorectal, biliary tract, and pancreatic cancers) and healthy volunteers. Plasma AM levels were measured before the initiation of systemic chemotherapy in patients with cancer and at the time of enrollment in healthy volunteers. Results: In the unadjusted analyses, plasma mature and total AM levels were significantly higher in the cancer group than in healthy volunteers. Age was significantly associated with both mature and total AM levels, whereas sex did not show a significant association. After adjustment for age, between-group differences in mature and total AM levels were not statistically significant. Among patients with pancreatic cancer, plasma mature and total AM levels were significantly higher in stage IV than in stage III disease. Conclusions: Higher plasma AM levels were observed in the cancer group than in healthy controls in the unadjusted analyses; however, these differences were not statistically significant after adjustment for age. A stage-related difference was observed in pancreatic cancer. These findings should be considered hypothesis-generating and require validation in larger studies with appropriately matched control groups. Full article

Background: Liver abscesses represent uncommon yet potentially life-threatening infections of the hepatic parenchyma. Their imaging appearances can vary widely, and—in rare instances—may closely resemble hepatocellular carcinoma (HCC) on multimodality imaging. We report a case of pyogenic liver abscess initially misclassified as advanced HCC based on imaging characteristics meeting LI-RADS 5 criteria. Case Presentation: A 45-year-old male without known cirrhosis, viral hepatitis, or diabetes presented with right upper quadrant pain, abdominal rigidity, nausea, and vomiting. He denied alcohol use, recent dental procedures, and travel to endemic areas. Contrast-enhanced computed tomography and magnetic resonance imaging demonstrated multiple exophytic hepatic masses with arterial-phase hyperenhancement and venous/delayed washout, classified as LI-RADS 5 and initially interpreted as advanced HCC (BCLC stage C). Alpha-fetoprotein (AFP) was not elevated. Hepatitis B surface antigen and anti-HIV were non-reactive. Ultrasound-guided fine-needle aspiration biopsy yielded purulent material; histopathology confirmed chronic suppurative inflammation consistent with an abscess, with negative acid-fast bacilli staining. Cultures were sterile. The patient was treated with doripenem and metronidazole. A post-drainage complication of middle hepatic artery bleeding required urgent transcatheter embolization. The patient was subsequently discharged in stable condition. Discussion: This case illustrates a recognized but uncommon diagnostic pitfall: pyogenic liver abscesses fulfil imaging criteria for HCC. LI-RADS 5 classification carries an estimated false-positive rate of approximately 5%, and its application is technically restricted to patients with established HCC risk factors (e.g., cirrhosis, chronic hepatitis B). In non-cirrhotic patients presenting with fever, leukocytosis, and an atypical or rapidly enlarging hepatic mass, tissue confirmation is essential before committing to an oncological diagnosis. Conclusions: When a hepatic mass displays imaging features fulfilling LI-RADS 5 criteria in a non-cirrhotic patient with clinical signs of infection—including fever, leukocytosis, and elevated inflammatory markers—the possibility of a liver abscess must be actively excluded. Biopsy and percutaneous drainage are essential to avoid misdiagnosis and to enable timely, appropriate treatment. Full article

Background/Objectives: Community-level knowledge, food-label literacy, and consumer perceptions may shape the environment in which medically indicated gluten-free diets are followed. This study assessed prior exposure to the term “gluten,” ingredient-label literacy, perceived gluten-free product (GFP) cost, and purchasing behavior and intentions among adults in Arar, Saudi Arabia. Methods: A bilingual Arabic–English online cross-sectional questionnaire was administered to adult residents of Arar using non-probability convenience sampling. Categorical data were summarized as frequencies, percentages, and 95% Wilson confidence intervals. Association analyses were exploratory. Results: A total of 306 eligible adult respondents were included. Prior exposure to the term “gluten” was reported by 70.3% (95% CI: 64.8–75.3). Only 14.1% (95% CI: 10.6–18.4) reported always understanding ingredient terminology, whereas 35.0% (95% CI: 29.8–40.5) reported not understanding it. Most respondents (60.5%; 95% CI: 54.9–65.8) perceived GFPs as more expensive than standard products. Under a hypothetical scenario of improved affordability and availability, 34% indicated that they would definitely purchase GFPs regularly and 48.4% indicated that they would possibly do so. Reported acquaintance with someone with celiac disease or gluten sensitivity was associated with hypothetical purchase intention (χ² = 9.07, p = 0.011; Cramér’s V = 0.172). Conclusions: In this convenience sample, prior exposure to the term “gluten” coexisted with limited self-reported comprehension of ingredient terminology and perceived cost barriers. These descriptive findings do not establish market conditions, gluten-free diet adherence, or clinical outcomes, but identify community-level issues for future patient-based and retail-audit research. Full article

Background/Objectives: Fecal incontinence (FI) is an underrecognized complication of inflammatory bowel disease (IBD) and colorectal neoplasia that substantially impairs quality of life. This study translated, culturally adapted, and validated the Arabic Vaizey Incontinence Score while evaluating the burden of FI among Egyptian patients. Methods: In this multicenter cross-sectional study, 287 adults with histopathologically confirmed diagnoses were enrolled, including colorectal cancer/precancerous lesions (n = 54), IBD (n = 55), and other/no significant colorectal pathology (n = 178). The questionnaire underwent standardized translation and cultural adaptation. Internal consistency was assessed using McDonald’s omega. Structural validity was evaluated using exploratory factor analysis (EFA; n = 143) and confirmatory factor analysis (CFA; n = 144). Results: Patients with IBD had the greatest fecal incontinence burden, with the highest mean Vaizey score (9.24 ± 6.77) compared with patients with colorectal neoplasia (7.28 ± 6.03) and those with other or no significant colorectal pathology (6.68 ± 4.79). Continence-related quality of life was also poorest in IBD (median 8.0 [IQR 4–10] vs. 2.0 [IQR 1–3] and 2.5 [IQR 1–6]). EFA supported a two-factor solution explaining 48.1% of the variance (KMO = 0.691; Bartlett’s χ² = 298.61, p < 0.001). The inability-to-defer-defecation item showed negligible loading and was excluded. CFA confirmed a refined six-item model with excellent fit (CFI = 0.992, TLI = 0.985, RMSEA = 0.088, SRMR = 0.087). McDonald’s omega was 0.825 for Leakage Severity and Management and 0.869 for Functional Impact, with average variance exceeding 0.50 for both domains. Conclusions: The refined six-item Arabic Vaizey Incontinence Score demonstrated good reliability and construct validity. FI score was significantly higher among patients with IBD, supporting routine assessment using this validated instrument across Egyptian patients with colorectal diseases. Full article

Background/Objectives: Celiac disease (CD) is a chronic immune-mediated disorder triggered by gluten ingestion in genetically predisposed individuals with higher prevalence among first-degree relatives. Despite its hereditary risk, little is known about how parents with at least one child with CD perceive this risk in unaffected children. This study examined parental perceptions and dietary practices regarding CD prevention in unaffected children. Methods: A cross-sectional mixed-methods study was conducted in Greek parents using an online questionnaire for the quantitative component and semi-structured interviews for the qualitative. Quantitative data were analyzed using descriptive statistics and multivariable logistic regression analysis, while qualitative data were analyzed using framework analysis. Results: Although parents demonstrated high awareness of genetic risk, this was not translated into preventive dietary modifications. Belief in the role of diet as a preventive CD strategy emerged as the only significant predictor of dietary change. Diet was widely recognized as important for overall health or as a therapeutic regimen for children living with CD; however, it was not perceived as a preventive strategy for CD. Reported family barriers to adopting a healthy diet included financial constraints and limited guidance, whereas advice from healthcare professionals emerged as a key facilitator of dietary change. Conclusions: Although parents recognize the genetic risk of CD, they rarely implement dietary changes as CD preventive behavior for their unaffected children. These findings highlight the potential value of clearer dietary guidance and targeted professional support for families with children with CD and unaffected siblings. Full article

Background/Objectives: Gastroparesis is a disorder in which individuals experience dysfunctional gastric motor symptoms, but the underlying etiology is unclear. This exploratory study investigates autoimmune, inflammatory, metabolic, autonomic, and enteric (AIMAE) abnormalities in patients with gastroparesis symptoms to provide new insights into pathophysiology. The aim of this study is to further elucidate the potential associations between the different AIMAE measurements. Methods: Twenty-one patients with gastroparesis symptoms underwent a series of testing including assays for measurement of autoimmune, inflammatory, and metabolic markers; measurement of the autonomic nervous system; electrogastrography recordings; and gastric emptying measurements. Associations were evaluated using Spearman’s rank correlation with pairwise-complete observations. Benjamini–Hochberg false-discovery-rate correction was applied separately within each prespecified statistical family, with q ≤ 0.05 defining statistical significance. Results: Across 3432 planned correlations in 10 prespecified families, four associations met the false-discovery-rate threshold. DFS-70 was positively associated with C-peptide (q= 0.000330). Low-resolution EGG S1 mean amplitude was positively associated with insulin (q = 0.000172). IL-6 was inversely associated with baseline sympathetic LFa modulation (q = 0.000172) and standing sympathetic LFa modulation (q = 0.000172). Conclusions: This prospective pilot study identified strong associations among autoimmune, inflammatory, metabolic, enteric, and autonomic measurements. The findings were robust to leave-one-out analyses and generally retained their direction and magnitude after excluding participants with diabetes or a gastric electrical stimulator. However, the results of this study should be interpreted as hypothesis-generating rather than causal due to its limitations including a small cohort and incomplete confounder information. Full article

Background: Patients with inflammatory bowel disease (IBD) are prone to low vitamin D levels; however, data from Southeast Europe on this topic remain sparse. We measured serum 25-hydroxyvitamin D [25(OH)D] concentrations in Albanian patients with inflammatory bowel disease (IBD) to determine the prevalence of deficiency and its association with clinical disease activity. Methods: We enrolled 96 patients with IBD (82 with ulcerative colitis [UC] and 14 with Crohn’s disease [CD]) and 563 healthy controls at the University Hospital Center Mother Teresa in Tirana, Albania. Serum 25(OH)D concentrations were measured using an electrochemiluminescence immunoassay (Elecsys Vitamin D total III, Roche Diagnostics). Vitamin D levels were classified as deficient (<10 ng/mL), insufficient (10–29 ng/mL), or sufficient (≥30 ng/mL). Disease activity was scored using the Total Mayo Score (TMS) for UC and the Crohn’s Disease Activity Index (CDAI) for CD. The analysis was performed using SPSS version 26.0. Results: Patients with IBD had lower mean serum 25(OH)D concentrations than controls (18.0 ± 9.9 vs. 23.8 ± 11.1 ng/mL; p = 0.001). After adjustment for age and sex, vitamin D sufficiency (≥30 ng/mL) remained less common among patients with IBD than among healthy controls (adjusted OR, 0.494; 95% CI, 0.260–0.939; p = 0.031). Only 12 of the 96 IBD patients (12.5%) had sufficient vitamin D levels. Vitamin D insufficiency and deficiency were observed in 65.6% and 21.9% of patients, respectively. A weak inverse correlation with Total Mayo Score was observed among UC patients with complete disease activity data (r = −0.266, p = 0.044). No such correlation was observed for CDAI in patients with CD. The relationship between vitamin D and CRP was negative but did not reach significance (r = −0.213, p = 0.051). Conclusions: Low vitamin D levels are common among Albanian patients with IBD and showed a weak inverse association with disease activity in UC. Whether correcting this deficiency changes the disease course remains to be determined in prospective trials. Full article

Background: Amoxicillin–clavulanate (AC) is the antibiotic most frequently implicated in idiosyncratic drug-induced liver injury (DILI) worldwide, and it characteristically produces a cholestatic or mixed pattern in older adults. A predominantly hepatocellular presentation is distinctly less common in this age group, and reports from the Arabian Peninsula are scarce. Case presentation: A 66-year-old Saudi man developed painless, progressive jaundice after a seven-day course of oral AC (500/125 mg three times daily) prescribed for a thumb laceration. He described a similar self-limiting jaundice after the same antibiotic approximately five years earlier, an episode that was never investigated and had not been entered in his allergy record, so the drug was prescribed again unknowingly. Liver biochemistry, documented as normal four months earlier, showed alanine aminotransferase (ALT) peaking at 587 U/L (14.3 × the upper limit of normal, ULN) and aspartate aminotransferase at 335 U/L, with total bilirubin 249 µmol/L (11.9 × ULN) and a 69% conjugated fraction, whereas alkaline phosphatase (ALP) never exceeded 245 U/L (1.9 × ULN). The R-value at the ALT peak was 19.3 using the same-day ALP, and 7.6 even when the peak ALT is paired with the highest ALP recorded at any point in the illness; the pattern was therefore hepatocellular (R > 5) throughout the injury phase. Hy’s law criteria were met, although the international normalised ratio remained 1.0 and no encephalopathy developed. Peripheral eosinophilia (peak 1.05 × 10⁹/L) was documented. Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody and HIV serology were non-reactive; antinuclear, anti-smooth-muscle, anti-liver-kidney microsomal type 1 and antimitochondrial antibodies were negative and serum ceruloplasmin was normal; ultrasound with contrast-enhanced triphasic computed tomography excluded biliary obstruction and malignancy. Hepatitis A and E serology and cytomegalovirus/Epstein–Barr studies were unavailable at our institution, which we report as a limitation. AC was withdrawn and management was supportive. Liver biochemistry normalised completely over the following three months (ALT 25 U/L, ALP 103 U/L, and total bilirubin 22 µmol/L). Updated Roussel Uclaf Causality Assessment Method (RUCAM) scoring on the hepatocellular scale gave 7 points (probable); no credit was taken for the historical episode, since RUCAM requires documented enzyme re-elevation for a positive re-administration response. Conclusions: AC can cause hepatocellular, Hy’s-law-positive injury in older adults, not only the cholestatic phenotype emphasised in the literature. The decisive failure here was administrative rather than diagnostic: an adverse drug reaction that is never recorded will be repeated. Full article

Background and Objectives: Anastomotic leak after left-sided colectomy has not declined despite refinements in technique and patient selection, prompting interest in whether local reinforcement might influence the clinical course of leaks that occur rather than their occurrence. We describe the feasibility and safety of Hemopatch serosal reinforcement of stapled colocolic anastomoses in elective left colectomy, and the distribution of leak grades observed under two reinforcement practices in routine use. Materials and Methods: A retrospective single-centre cohort of consecutive elective left colectomies was observed (January 2013–December 2024). Reinforcement technique followed the operating surgeon’s routine practice and was therefore completely confounded with surgeon and department; the study was not designed to isolate a device effect, and no causal or comparative-effectiveness inference is drawn. Leaks were graded by the ISREC classification. Balance was quantified with standardised mean differences (SMD) and proportions with exact 95% confidence intervals; a penalised (Firth) logistic model is reported as exploratory. Results: Ninety-four patients were analysed (28 Hemopatch, 66 s-line suture). Reinforcement was applied as intended in all 28 Hemopatch cases (100%, 95% CI 87.7–100). The Hemopatch group was older (median 76.5 vs. 68 years; SMD 0.89), with further imbalance in both directions. Anastomotic leak occurred in 14.3% (95% CI 4.0–32.7) versus 13.6% (6.4–24.3); the exploratory model was uninformative (OR 1.20, 95% CI 0.32–4.48). Leak grades were distributed differently, with no Hemopatch leak requiring reoperation (0%, 95% CI 0–12.3) versus four (6.1%, 1.7–14.8) and radiologically detected leaks more frequent with Hemopatch; all intervals overlapped substantially. Length of stay (median 9 vs. 6.5 days), readmission (35.7% vs. 11.3%) and two reoperative small-bowel obstructions occurred in the Hemopatch group. Conclusions: Hemopatch serosal reinforcement was technically feasible. Leak occurrence was similar between practices; leak grades differed in distribution, with reoperation for leak absent in the Hemopatch group. As reinforcement was confounded with surgeon and department, these differences describe two practices rather than a device effect. Longer stay and higher readmission require prospective safety capture; two adhesive obstructions occurred in the Hemopatch group, with operative findings in both remote from the reinforcement site. Prospective cluster-adjusted evaluation is required before any efficacy claim. Full article

Sexually transmitted infections (STIs) are common and probably underreported causes of proctitis and colitis. Bacterial (chlamydia, gonorrhoea, syphilis, Mycoplasma genitalium), viral (herpes simplex virus, mpox), and amoebic (Entamoeba histolytica) pathogens can cause inflammatory proctitis or colitis, which, depending on the pathogen, can mimic inflammatory bowel disease both on endoscopy and histopathology. Rectal and colonic masses are uncommon, but important manifestations of these infections, especially with chlamydia, syphilis, and E. histolytica. Testing for HIV is important in this context, since it allows for the inclusion of opportunistic pathogens into the differential diagnosis. Chronic diarrhoea can be a feature of chronic HIV infection. Enteric pathogens, such as Salmonella spp., Shigella spp., or Campylobacter spp., can be transmitted during sex, especially during oral–anal contact (“rimming”). The most common STI, human papillomavirus, is not associated with colitis, but is important because of its causal association with genital warts and anal cancer. Full article

Background: Gastrointestinal (GI) bleeding is a recognised complication of long-term antithrombotic therapy. Whereas the overall bleeding risk associated with direct oral anticoagulants (DOACs) and low-dose aspirin has been extensively characterised, the anatomical distribution of bleeding lesions between these two pharmacological classes remains incompletely defined. Methods: We retrospectively analysed all consecutive adult patients admitted to the Emergency Department of San Carlo di Nancy Hospital (Rome, Italy) between January 2022 and March 2025 with a clinical diagnosis of acute GI bleeding. Patients were categorised as DOAC monotherapy or aspirin (ASA) monotherapy at presentation. The primary endpoint was the site of bleeding (upper vs. lower GI tract) by drug group. Secondary endpoints included site of bleeding by specific DOAC molecule and indicators of clinical severity (haemoglobin at admission, transfusion requirement, melena, hematochezia). Logistic and linear regression models were adjusted for age and sex. Because the number of transfused units is count data with a right-skewed distribution, the corresponding linear-regression estimate is reported as an exploratory approximation and interpreted with caution. As adjustment was limited to age and sex, all adjusted estimates are associative rather than causal and do not represent an independent effect of drug class. Results: The merged cohort comprised 316 patients; the head-to-head analysis included 179 patients on monotherapy (DOAC n = 100, ASA n = 79). Upper GI bleeding (UGIB) was equally distributed between groups (55% vs. 54%; OR 1.02, 95% CI 0.57–1.85; p = 1.00), whereas identified lower GI bleeding (LGIB) was numerically less frequent in DOAC monotherapy (34% vs. 49%; OR 0.53, 95% CI 0.29–0.97; p = 0.047), an association that was attenuated and no longer significant after adjustment for age and sex (p = 0.076). Restricting to patients who underwent oesophagogastroduodenoscopy (EGDS), the diagnostic yield was substantially lower in DOAC monotherapy (72% vs. 91%; adjusted OR 0.25, 95% CI 0.08–0.79; p = 0.018). DOAC-treated patients presented with lower haemoglobin (7.9 ± 2.4 vs. 9.3 ± 2.9 g/dL; adjusted β = −1.32 g/dL, p = 0.002) and required transfusion more frequently (68% vs. 49%; adjusted OR 2.50, 95% CI 1.29–4.83; p = 0.007). No statistically significant differences were detected among the four DOAC molecules for site of bleeding or specific lesion, although this analysis was substantially underpowered. Conclusions: In a real-world emergency cohort, DOAC and ASA monotherapy were associated with a comparable proportion of upper GI bleeding, while identified LGIB was numerically less frequent in DOAC users. DOAC users presented with lower haemoglobin and more frequently required transfusion, despite a lower diagnostic yield at EGDS. Among the four DOAC molecules, no significant differences emerged. In sensitivity analyses, the lower identified-LGIB frequency and the higher transfusion burden in DOAC users were attenuated and no longer statistically significant when the analysis was restricted to fully evaluated patients or when count-based and comorbidity-adjusted models were applied. Further studies are warranted to clarify the anatomical distribution of bleeding sources in DOAC users with negative initial endoscopy. Full article

Alpha-gal syndrome (AGS) is a tick-induced, IgE-mediated hypersensitivity to the oligosaccharide galactose-α-1,3-galactose (α-gal), which is expressed on glycoproteins and glycolipids of non-primate mammals but absent in humans. Gastrointestinal (GI) symptoms dominate the clinical presentation in a substantial proportion of patients yet remain systematically under-recognized, frequently being attributed to irritable bowel syndrome (IBS), non-celiac gluten sensitivity (NCGS), or lactose intolerance. This narrative review synthesizes the current evidence on the epidemiology, GI and systemic phenotype, immunological mechanisms, diagnostic strategies, management approaches, quality-of-life burden, and multi-level public health interventions for AGS, and it identifies critical knowledge gaps as of 2026. We searched PubMed/MEDLINE, Embase, and Web of Science from database inception through 31 March 2026, and synthesized the evidence narratively in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA). GI symptoms occur in 47–69% of patients with AGS, with abdominal pain (58%), diarrhea (42%), nausea (39%), and vomiting (31%) as the cardinal manifestations. A characteristic 2–6 h delay between the ingestion of mammalian-derived food and symptom onset—explained by the glycolipid–chylomicron delivery mechanism—drives diagnostic confusion with functional GI disorders. Among 295,400 tested individuals in the United States, 30.5% were α-gal IgE positive, and an estimated 96,000–450,000 Americans were affected between 2010 and 2022. Despite this burden, 42% of U.S. healthcare providers had never heard of AGS. Strict avoidance of mammalian meat improves symptoms in 53–86% of adherent patients, although the condition carries a meaningful risk of anaphylaxis even among GI-predominant presenters. AGS is a prevalent, frequently misdiagnosed, and clinically morbid condition whose GI phenotype lies squarely within the gastroenterologist’s domain. A coordinated response that integrates clinician education, institutional diagnostic algorithms, and national surveillance infrastructure is urgently needed. Full article

Background: Coeliac disease (CD) is a highly heritable autoimmune disease. Given the high risk among first-degree relatives, early screening and prevention are essential, yet clinical guidelines vary. This review analyzed clinical practice guidelines issued by leading European, British, and North American organisations over a 12-year period (2014–2026) regarding genetic screening and lifestyle/dietary prevention strategies. Methods: A systematic search was conducted across official databases of prominent societies (ESSCD, UEG, ESPEN, NASPGHAN, AGA, ESPGHAN, WGO, BSG, ACG) for English-language guidelines and position papers. Extracted statements addressing genetic testing (HLA-DQ2/DQ8) and early-life risk-modifying strategies were coded into three thematic domains: (1) genetic predisposition, (2) lifestyle prevention or (3) both. Results: Eleven manuscripts yielded 399 statements, categorized into genetic predisposition (n = 23, 5.8%), lifestyle prevention (n = 30, 7.5%) and integrated approaches (n = 2, 0.5%), with the remainder (n = 344, 86.2%) addressing unrelated clinical topics. Universal consensus confirmed the high negative predictive value of HLA-DQ2/DQ8 testing to rule out CD, whereas dietary strategies (breastfeeding duration and timing of gluten introduction) showed no protective effect. ESPGHAN exclusively provided evidence regarding early-life high-risk genotypes and concluded that risk-stratified dietary guidance based on specific HLA profiles remains currently unsupported. Conclusions: Current CD guidelines demonstrate substantial international consensus regarding the role of genetic testing in disease exclusion and risk stratification. However, recommendations integrating genetic susceptibility with preventive lifestyle interventions remain scarce. Future research should focus on generating robust evidence to support precision prevention approaches and facilitate the harmonization of international guidelines. Full article

Background/Objectives: Pediatric spontaneous or non-traumatic extrahepatic bile duct perforation (SBDP) is a rare cause of bile ascites and biliary peritonitis. We aimed to characterize presentation, diagnosis, management, outcomes, and summarize practical management considerations. Methods: A systematic review was performed in accordance with PRISMA 2020, we searched PubMed/MEDLINE, EMBASE, and Google Scholar from inception to February 2026, and completed backward citation tracking in June 2026. We included pediatric SBDP cases and excluded traumatic, iatrogenic, isolated gallbladder, and perforated choledochal cyst cases. Case-level data were extracted when available, and exploratory subgroup analyses were performed by age and management approach. Results: A total of 139 studies reported 208 cases; with one institutional case, final cohort of 209 patients. Median age was 3.0 months (IQR, 1.15–15.0; n = 174), and 70.5% of patients were ≤1 year old (124/176). Bilious ascites or bile-stained fluid was confirmed in 95.2%. The cystic duct–CHD/CBD junction was the most frequently reported site (82/180, 45.5%), and biliary anomalies were reported in 39.7% (83/209). A step-up initial management was used in 60.3% and immediate surgery in 38.8%. Reported survival was 97.0% (197/203), although publication bias limits interpretation. Clinical complications and reinterventions were reported in 75/198 (37.9%) and 66/209 (31.6%), respectively. Conclusions: Pediatric SBDP is age-dependent and anatomy-driven; infants more often presented with cholestatic-ascitic features, whereas older children more often had acute-abdominal features. Bilious ascites is an important diagnostic clue. Management should prioritize stabilization and source control, followed by anatomical definition and selective reconstruction. Full article

Background: Dysbiosis, mucosal inflammation and increased intestinal permeability have been implicated in the pathophysiology of irritable bowel syndrome (IBS). Objective: To evaluate the effectiveness of a sequential butyrate–probiotic administration in reducing symptoms and improving stool consistency in patients with diarrhea-predominant (IBS-D) or mixed-type IBS (IBS-M). Methods: Two hundred adult patients were allocated to intervention (n = 105) or control (n = 95). The intervention group received ColonLife formulation (Εuro-Pharma S.r.l., Torino—Italy), consisting of two distinct capsules: the first containing butyric acid and grapefruit seed extract, and the second containing microencapsulated probiotic strains together with fructooligosaccharides (FOSs). Symptom severity, quality of life and stool consistency (Bristol Stool Scale) were assessed at baseline and three follow-up visits. Results: Baseline characteristics were comparable between groups (p > 0.05). Diarrhea severity decreased significantly in the intervention group (3.78 ± 1.01 to 3.31 ± 1.21; Δ − 0.47) compared with minimal change in controls (3.71 ± 1.05 to 3.62 ± 1.14; Δ − 0.08; p = 0.015). Stool consistency improved more in the intervention group (−1.18 ± 1.46 vs. −0.64 ± 1.41; p = 0.028), with normal stools increasing from 1.0% to 65.7% versus 4.2% to 36.8% in controls (p < 0.001). The degree of change in pain scores was similar between the two groups (p > 0.05). The degree of reduction in bloating scores was also similar between groups (p > 0.05). Quality of life improved in both groups (intervention: +0.68 ± 1.43; control: +0.71 ± 1.64; both p < 0.01), with no significant difference between groups (p > 0.05). Conclusions: Sequential butyrate–probiotic administration significantly improves diarrhea, stool consistency and gastrointestinal symptoms in IBS-D and IBS-M, supporting its role as a microbiota-targeted treatment. Full article

Background: Orodispersible budesonide tablets (OBTs, Jorveza) are approved by the EMA as a therapy option in eosinophilic esophagitis (EoE) in adults. However, data on their use in pediatric patients remain limited and no approved pediatric OBT formulation is currently available in Europe. Therefore, real-world data on off-label use of OBTs in children is needed. Methods: We retrospectively analyzed data on the off-label use of OBTs in eight children (five girls) at a median age of 10.5 years (ranging from 5 to 14). Clinical, histological and safety outcomes were assessed descriptively. Results: Treatment with OBTs was associated with clinical improvement and a reduction in eosinophil counts. Specifically, the median eosinophil count decreased from 38.5 (ranging from 20 to 100) to 0 (ranging from 0 to 20) eosinophils per high-power field. Histological remission, defined as <15 eosinophils per high-power field, was achieved in six of eight patients (75%). Clinical remission was reached in seven of eight patients (87.5%). No severe side effects could be detected. Conclusions: OBTs showed promising clinical and histological responses in this small retrospective pediatric case series. However, larger prospective studies are required before efficacy and safety can be established. Further clinical studies are needed to assess whether OBTs could become an approved pediatric therapy. Full article

Patients with inflammatory bowel disease (IBD) often require long-term immunosuppressive or advanced therapy, raising concerns about treatment-associated malignancy risk. This systematic review evaluated malignancy outcomes associated with biologic, advanced small-molecule, and thiopurine therapies in adults with IBD. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception through June 2025, with supplementary screening of Google Scholar and reference lists. Eligible primary studies included randomized controlled trials and prospective or retrospective cohort studies evaluating malignancy outcomes. Thiopurines were included because they remain clinically important comparators and are central to combination-therapy risk. The Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool were used for observational studies and randomized trials, respectively. Because of substantial clinical and methodological heterogeneity, we did not perform a de novo meta-analysis; pooled estimates from previously published meta-analyses are reported only as contextual evidence. Twenty-eight studies met the inclusion criteria. Thiopurines showed the most consistent malignancy associations, including lymphoma, non-melanoma skin cancer (NMSC), acute myeloid leukemia/myelodysplastic syndrome, and urinary tract cancer. Anti-tumor necrosis factor (anti-TNF) monotherapy was not associated with a clear increase in overall cancer incidence, although a modest lymphoma signal was reported in some datasets. Combination anti-TNF plus thiopurine therapy showed the strongest lymphoma signal. Current evidence has not demonstrated an increased malignancy risk with vedolizumab or ustekinumab, including in available cohorts of patients with prior malignancy; however, confidence is limited by observational designs, small event numbers, heterogeneous cancer histories, and limited follow-up. IBD-specific data for Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators remain comparatively immature, and long-term surveillance is required. Overall, treatment decisions should integrate absolute baseline risk, age, smoking, prior malignancy, prior NMSC, Epstein–Barr virus-related risk, disease-related cancer risk, and cumulative immunosuppressive exposure. Full article

Introduction: Anatomical gastrointestinal reconstruction following metabolic bariatric surgery (MBS) is a revisional procedure used for refractory complications, including malnutrition, intractable reflux, recurrent marginal ulcer disease, and post-bariatric hyperinsulinemic hypoglycemia (PBHH). Objective: This study aims to describe the indications, perioperative outcomes, and short-term results of laparoscopic anatomical reconstruction in a single-center series, focusing on patients with PBHH. Methods: We retrospectively reviewed 11 consecutive patients who underwent reconstruction following MBS at a single tertiary center. Perioperative outcomes, weight changes, and biochemical responses to standardized dual-modality (oral and intravenous) glucose suppression testing were analyzed. Results: Between 2018 and 2025, 11 patients completed laparoscopic anatomical reconstruction. The anatomy immediately preceding reconstruction was OAGB in nine patients (81.8%) and RYGB in two (18.2%). The indications overlapped; the most common were severe malnutrition (n = 9), marginal ulcer disease (n = 6), and PBHH (n = 4; three biochemically confirmed, one clinically diagnosed). Ten of eleven procedures (90.9%) were completed laparoscopically, with no 30-day Clavien–Dindo grade III–IV complications. Among the four PBHH patients, symptomatic resolution was achieved in all four, with residual asymptomatic biochemical hypoglycemia in one. Weight gain occurred in 10 of the 11 patients (mean 8.1 ± 4.9 kg) at a median follow-up of 7 months (IQR 3–12). Conclusions: In this preliminary series, laparoscopic anatomical reconstruction was feasible, though the small sample precludes conclusions regarding safety. Incretin hormones were not measured; the mechanistic contribution of restored foregut anatomy is inferred from prior literature rather than demonstrated here. Standardized dual-modality glucose suppression testing was central to patient selection and to documenting the biochemical response. Full article