Gastrointestinal Disorders doi: 10.3390/gidisord8040068

Authors: Kinichi Hotta Kenichiro Imai Kazunori Takada Sayo Ito

Background: Colorectal cancer can be cured by minimally invasive therapies such as endoscopic or surgical treatment if detected at an early stage, and it is important to increase the number of cases detected as early as possible in terms of medical cost-effectiveness. The purpose of this article was to comprehensively review the current status of endoscopic diagnosis and management of early colorectal neoplasia from a Japanese perspective. Summary: Regarding diagnosis, qualitative diagnosis and depth diagnosis using advanced endoscopic imaging such as narrow-band imaging (NBI) and chromoendoscopy are important to determine the treatment strategy. As for endoscopic treatment, it is fundamental to select the appropriate treatment method according to lesion size and morphology, and the use of modified endoscopic resection for intermediate-sized lesions and endoscopic submucosal dissection for large lesions is an issue for the future. Conclusions: This narrative review article summarizes the current status of endoscopic diagnosis and treatment in Japan in comparison with Europe and the United States. In particular, we discuss the determination of treatment strategies based on detailed endoscopic diagnoses, advances in modified endoscopic mucosal resection (EMR) for intermediate-sized lesions, and the fact that, as a country that pioneered endoscopic submucosal dissection (ESD), Japan has a broader range of indications compared to Europe and the United States.

Gastrointestinal Disorders doi: 10.3390/gidisord8040067

Authors: Sri Inggriani Rio Hermawan Cosmas Rinaldi Adithya Lesmana Jessica Christanti Callistus Bruce Henfry Sulay Alexandro Wiyanda Fabianus Anugrah Pratama

Introduction: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, and many patients present with intermediate or advanced disease. Transarterial chemoembolization (TACE) is an established treatment; however, its proangiogenic effects support the use of combination therapy. Combinations of TACE with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) have shown a promising antitumor activity. The objective of this study was to describe post-treatment mRECIST response patterns of TACE alone, TACE plus lenvatinib and pembrolizumab, and TACE plus atezolizumab and bevacizumab for HCC. Methods: This multicentre retrospective, non-randomized pilot study included 25 consecutive patients with unresectable HCC treated with TACE alone (n = 10), TACE–lenvatinib–pembrolizumab (n = 7), or TACE–atezolizumab–bevacizumab (n = 8). The primary outcome was first post-treatment mRECIST response. ORR and DCR were calculated descriptively. Secondary outcomes included imaging interval, TACE exposure, repeat TACE, ALBI change, and OS, estimated using Kaplan–Meier methods. Results: Complete response, partial response, stable disease, and progressive disease occurred in 30.0%, 30.0%, 10.0%, and 30.0% after TACE alone, 14.3%, 28.6%, 57.1%, and 0% after TACE–lenvatinib–pembrolizumab, and 0%, 37.5%, 0%, and 62.5% after TACE–atezolizumab–bevacizumab. ORR/DCR were 60.0%/70.0%, 42.9%/100.0%, and 37.5%/37.5%, respectively. Median imaging intervals were 38.0, 25.0, and 20.0 months. ALBI-grade worsening occurred in 30.0%, 42.9%, and 37.5%; 1-year OS was 78.8%, 83.3%, and 50.0%, respectively. Conclusions: mRECIST response patterns were heterogeneous. Baseline liver-function imbalance, small groups, and non-randomized allocation preclude comparative efficacy inference. Larger prospective studies should standardize treatment sequencing, imaging, liver function assessment, safety monitoring, and survival evaluation.

Gastrointestinal Disorders doi: 10.3390/gidisord8040066

Authors: Mădălina Maxim Petru Radu Soroceanu Vlad Ionuț Vlăsceanu Raoul Vasile Lupușoru Alin Constantin Pînzariu Alina Onofriescu Lucian Ambrosie Bogdan-Mihnea Ciuntu Gheorghe Balan Awad Dmour Alexandru Filip Mihaela Carmen Antohie Daniel Vasile Timofte

Metabolic and bariatric surgery (MBS) represents the most effective therapeutic approach for achieving substantial and sustained weight loss and improving obesity-related comorbidities. However, the role of routine preoperative esophagogastroduodenoscopy (EGD) remains controversial, and current recommendations vary among international professional societies. Obesity is associated with a high prevalence of upper gastrointestinal disorders, including gastroesophageal reflux disease, erosive esophagitis, hiatal hernia, Barrett’s esophagus, gastritis, Helicobacter pylori infection, gastric intestinal metaplasia, and peptic ulcer disease. Importantly, clinically relevant endoscopic abnormalities may occur in asymptomatic patients, limiting the reliability of symptom-based strategies for selecting candidates for EGD. Preoperative endoscopic findings may require medical treatment, additional diagnostic investigations, endoscopic surveillance, or modification of the planned bariatric procedure. This is particularly relevant when considering sleeve gastrectomy in patients with significant reflux-related disease or Barrett’s esophagus, as well as gastric bypass procedures that may limit subsequent endoscopic access to the excluded stomach. This narrative review summarizes current evidence regarding the clinical value of preoperative EGD in MBS, with particular emphasis on relevant gastroesophageal and gastric findings, standardized endoscopic assessment, their implications for surgical decision-making, and current international recommendations.

Gastrointestinal Disorders doi: 10.3390/gidisord8040065

Authors: Sebastián Arguedas-Chacón Valeria Granados-Villalta Karla Gutiérrez-González José Moreno-Araya Esteban Zavaleta-Monestel

Background/Objectives: Celiac disease (CD) is a chronic immune-mediated disorder associated with genetic susceptibility conferred primarily by HLA-DQ2 and HLA-DQ8. Although HLA genotyping cannot confirm CD because these profiles are common in individuals without the disease, it has a complementary role in the diagnostic evaluation, particularly when compatible HLA profiles are absent. Contemporary data on the distribution of CD-associated HLA profiles in Central America remain limited. This study aimed to characterize the distribution of HLA-DQ2.2, HLA-DQ2.5, and HLA-DQ8 profiles among patients referred for CD-related genetic testing in Costa Rica and to evaluate their distribution according to biological sex and age. Methods: We retrospectively evaluated HLA-DQ2/DQ8 genotyping records from patients tested for suspected CD at Hospital Clínica Bíblica, Costa Rica, between January 2018 and August 2024. After patient-level review of 361 complete determinations from 292 unique patients, four patients with unresolved discordant repeated results were excluded, yielding a final analytical cohort of 288 patients. HLA profiles were summarized descriptively, and associations with sex and age were evaluated using Fisher’s exact test, the Mann–Whitney U test, and Pearson’s chi-square test, with Holm adjustment for multiple comparisons involving individual HLA profiles. Results: Among 288 patients, 207 (71.9%) were female, and the median age was 33 years. HLA-DQ8 was the most frequently detected CD-associated profile (31.9%; 95% CI 26.8–37.5%), whereas HLA-DQ2.2 and HLA-DQ2.5 were each detected in 19.4% (95% CI 15.3–24.4%). Overall, 59.7% of patients carried at least one of these three profiles, while 112 (38.9%; 95% CI 33.4–44.6%) had negative results for all four evaluated assay components. No statistically significant associations were identified between individual HLA profiles and biological sex after adjustment for multiple comparisons. Age did not differ according to overall HLA-profile status (p = 0.874), and HLA-profile distribution did not differ significantly across age groups (p = 0.677). Conclusions: HLA-DQ8 was the most frequently detected CD-associated HLA profile in this clinically referred Costa Rican cohort, while DQ2.2 and DQ2.5 occurred at lower and similar frequencies. No significant associations with biological sex or age were identified. These findings provide contemporary data on HLA-DQ2/DQ8 distribution in a Costa Rican clinical setting but should not be interpreted as estimates of population HLA prevalence or CD prevalence. Studies integrating HLA genotyping with clinical, serological, histological, and diagnostic outcome data are needed to establish the clinical significance of these distributions.

Gastrointestinal Disorders doi: 10.3390/gidisord8040064

Authors: Alessandro Zanasi Vincenzo Stanghellini Mario Calò Giorgio Zoli Omero Giorgi Antonio Maria Morselli-Labate

Background: Bicarbonate mineral waters have been reported to modulate biliary dynamics. Prior symptom-based data with Aqua 3 suggested digestive benefits, but objective confirmation is still lacking. Aims: We sought to evaluate the effect of Aqua 3 on gallbladder motility in fasting healthy adults, compared with an oligomineral water. Methods: In this randomized, crossover study, twenty healthy volunteers underwent two ultrasound sessions after an overnight fast and the ingestion of 500 mL of either Aqua 3 (bicarbonate-rich mineral water) or oligomineral water. Gallbladder volume was measured at baseline and after 10, 20, 30, and 60 min. Primary endpoint was the maximum observed ejection fraction. Results: Bicarbonate-rich mineral water induced a rapid increase in ejection fraction: peaking at 10 min, persisting at 20 min and attenuating by 30 min. At 60 min, gallbladder refilling exceeded baseline. Oligomineral water produced only modest early emptying at 10 min, no significant change at 20 min, and progressive refilling thereafter. Throughout the observation period, ejection fraction was significantly higher after bicarbonate than oligomineral water. Maximum observed ejection fraction was significantly greater with bicarbonate than oligomineral water, occurring most frequently at 10 min for both waters. Conclusions: Because the study compared Aqua 3 with one selected oligomineral water and the two waters differed in several chemical–physical characteristics, including bicarbonate, free CO2, calcium, magnesium, and sodium, the observed response cannot be attributed exclusively to the bicarbonate content and should be interpreted as an effect of Aqua 3. This rapid and sustained effect is potentially useful in the clinical setting to improve early phases of postprandial digestion and providing a mechanistic rationale for the previously reported digestive benefits of bicarbonate-rich mineral water. These results describe an acute physiological effect and require confirmation in larger studies, including postprandial settings and clinical populations, before therapeutic implications can be drawn.

Gastrointestinal Disorders doi: 10.3390/gidisord8040063

Authors: Catchia Hermes-Uliana Miyuki Ueno Neide Martins Moreira Juliano Yasuo Oda Marcelo Biondaro Gois

Background/Objectives: The enteric nervous system (ENS) is essential for gastrointestinal homeostasis and is vulnerable to oxidative imbalance associated with inflammatory, metabolic, and neurodegenerative disorders. However, research linking the ENS and oxidative stress has not been comprehensively mapped. This study characterized the temporal evolution, productivity patterns, collaboration networks, geographical distribution, and thematic structure of this field. Methods: Original research articles were retrieved from the Web of Science Core Collection, Scopus, and PubMed from database inception to 12 September 2026. Records were merged, deduplicated, screened, and harmonized before analysis. Bibliometrix/Biblioshiny and VOSviewer were used to assess annual production, Lotka’s and Bradford’s laws, author and journal productivity, collaboration networks, keyword co-occurrence, trend topics, thematic evolution, and thematic mapping. Results: A total of 251 original articles published between 1989 and 2026 were included. Scientific production showed an annual growth rate of 6.95%, with peaks in 2016 and 2021. Author productivity followed a Lotka-type distribution, and journal dispersion was compatible with Bradford’s law. Brazil had the largest number of corresponding-author publications, followed by the United States and China. Keyword analyses identified recurrent themes involving diabetes mellitus, inflammation, enteric glial cells, Parkinson’s disease, antioxidant mechanisms, neuroprotection, and aging. Temporal analyses indicated increasing integration of neurodegenerative, glial, and gut–brain-related topics. Conclusions: Research linking the ENS and oxidative stress has expanded and diversified over time. The field combines established metabolic and redox-oriented research with increasing attention to inflammatory, neurodegenerative, glial, and gut–brain perspectives within heterogeneous international collaboration networks.

Gastrointestinal Disorders doi: 10.3390/gidisord8040062

Authors: Hye Rin Kim Hyeon Hwa Nam Byung-Kil Choo

Background/Objectives: Reflux esophagitis (RE) is characterized by reflux-induced esophageal mucosal injury associated with inflammation and epithelial barrier disruption. Mineral-rich drinking water (MW) has attracted increasing attention because its mineral composition may exert various biological functions beyond simple hydration. However, its effects on reflux-induced esophageal injury remain unclear. Therefore, this study investigated the effects of MW in an acute experimental rat model of RE. Methods: The mineral composition of MW was analyzed before the animal experiment. During the 2-week acclimation period, the MW group received MW as drinking water, followed by an additional 1 mL oral administration 90 min before RE induction; ranitidine (40 mg/kg) was used as a pharmacological comparator. Gross esophageal lesions, histopathological alterations, gastric pH, mitogen-activated protein kinase (MAPK) phosphorylation, cyclooxygenase (COX) expression, and tight junction (TJ)-related proteins were evaluated. Results: MW significantly reduced gross esophageal lesions and was associated with less pronounced histopathological alterations. MW treatment was associated with lower phosphorylation levels of p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), lower COX-2 expression, together with higher COX-1, claudin-4, and claudin-5 expression. Gastric pH was not significantly altered by MW. Conclusions: Overall, these findings suggest that MW treatment attenuates acute reflux-induced esophageal injury and is associated with changes in inflammatory signaling and TJ-related protein expression.

Gastrointestinal Disorders doi: 10.3390/gidisord8040061

Authors: Huanlu Xu Rong Hu Ke Jiang Xiaofeng Zhang

Background: Although non-ampullary duodenal epithelial tumors (NADETs) were historically considered rare, their detection has increased with high-resolution and image-enhanced endoscopy. Endoscopic resection is the preferred organ-preserving treatment for lesions without evidence of nodal metastatic risk, but the thin, vascular duodenal wall and exposure to bile and pancreatic juice create a narrow safety margin. Methods: This structured narrative review searched PubMed/MEDLINE, Embase, Web of Science Core Collection, and the Cochrane Library through 4 August 2026 and synthesized current guidance and clinical evidence. Results: Pooled conventional endoscopic mucosal resection (CEMR) data showed 93% successful removal and 15% recurrence, whereas contemporary endoscopic submucosal dissection (ESD) data showed 98.1% en bloc resection with 8.5% intraprocedural perforation. Cold snare resection is best supported for diminutive nonmalignant lesions; CEMR or underwater EMR is appropriate for most snareable lesions ≤ 20 mm; and hot EMR remains suitable for many larger lesions without invasive features. ESD should be reserved for lesions requiring en bloc histology in expert centers; nonlifting, fibrotic, large, or closure-challenging lesions may require endoscopic full-thickness resection, laparoscopic-endoscopic cooperative surgery, or surgery. Suspected deep invasion or nodal disease requires multidisciplinary evaluation. Conclusions: Treatment should be individualized according to lesion size, morphology, invasion depth, papillary relation-ship, closure feasibility, patient fitness, and local expertise. Suspected deep invasion or nodal disease requires multidisciplinary evaluation. Complete defect closure is central to safety, and sporadic and familial adenomatous polyposis-associated disease require separate assessment.

Gastrointestinal Disorders doi: 10.3390/gidisord8040060

Authors: Faure Rodríguez-Velásquez Alejandro D. Tejada-Giraldo Andrés Montoya-Durán Laura Goez-Beltran Nicole Bonilla Daniela Riaño-Pineda Alejandra Sogamoso-Bohórquez Juan Galves-Cetina Eduardo Tuta-Quintero

Background: The development of glucagon-like peptide-1 receptor agonists (GLP-1 Ras or GLP-1) and dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonists has expanded the therapeutic options for multimodal obesity management. However, evidence regarding the integration, combination, or sequencing of these therapies with bariatric/metabolic endoscopy and bariatric/metabolic surgery has not been comprehensively synthesized. Methods: A scoping review was conducted following the methodological framework of Arksey and Levac, the recommendations of the Joanna Briggs Institute, and the PRISMA-ScR guidelines. A systematic search was performed in PubMed, Scopus, and Embase from database inception through 16 May 2026. Studies involving adults that evaluated GLP-1/GIP agonists in relation to endoscopic and/or surgical bariatric/metabolic procedures were included. Data extraction was independently performed by two reviewers, and the evidence was synthesized using descriptive and narrative analyses. Results: All 14 studies directly evaluated strategies involving the integration, combination, or sequencing of pharmacotherapy with bariatric/metabolic endoscopy and/or bariatric/metabolic surgery and therefore contributed to the primary synthesis. The reported sample sizes across the 14 included studies summed to approximately 6401 participants, with individual study sample sizes ranging from 40 to 4901 patients. Most were retrospective cohort studies (10/14; 71.4%), followed by randomized controlled trials or prospective studies (3/14; 21.4%) and comparative observational studies. GLP-1 were the most frequently evaluated pharmacological agents, particularly semaglutide (7/14; 50.0%) and liraglutide (6/14; 42.9%), whereas tirzepatide was investigated in two studies (2/14; 14.3%). Endoscopic interventions were evaluated in 11 of the 14 included studies (78.6%). The most frequently evaluated endoscopic intervention was the intragastric balloon (IGB) (4/14; 28.6%), followed by transoral outlet reduction (TORe) (1/14; 7.1%), endoscopic sleeve gastroplasty (ESG) (1/14; 7.1%), revisional ESG (R-ESG) (1/14; 7.1%), and other revisional endoscopic procedures. Conclusions: Evidence regarding integrated, combined, sequential, adjuvant, or comparative treatment strategies for obesity management remains limited and is predominantly derived from observational studies. The integration of pharmacotherapy with endoscopic and surgical interventions shows promising results; however, high-quality prospective studies and randomized clinical trials are needed to define the optimal treatment sequence and identify the patients most likely to benefit from these multimodal approaches.

Gastrointestinal Disorders doi: 10.3390/gidisord8040059

Authors: Anastasios Koulaouzidis Ramesh Arasaradnam Pablo Cortegoso Valdivia George Koulaouzidis Ervin Toth Wojciech Marlicz

European colorectal cancer screening remains largely age-defined despite changing epidemiology, heterogeneous risk, non-participation and finite colonoscopy capacity. European guidance already anticipates risk-based thresholds, intervals and test allocation; how to test these across heterogeneous health systems remains unresolved. We propose a four-decision policy and research framework, not a validated clinical protocol, addressing when screening should begin or recur, which first-line test should be offered, what result or risk trajectory should trigger escalation, and how diagnosis and treatment should be completed. Quantitative faecal immunochemical testing (FIT) should remain a principal population-based strategy and high-quality colonoscopy the confirmatory and therapeutic standard, while national programmes may differ. Previous quantitative FIT results, age, sex, family history, comorbidity and screening behaviour can be prospectively evaluated as modifiers of interval and threshold. Multitarget stool tests, blood-based cell-free DNA, microbiome or volatile-organic-compound classifiers, colon capsule endoscopy and CT colonography should address defined pathway failures rather than act as interchangeable competitors. Because evidence for risk adaptation remains modelled or observational, implementation should proceed only through prospectively governed pilots. Evaluation should prioritise sustained participation, advanced neoplasia removed, interval cancer, colonoscopy use, equity and societal cost. Risk adaptation should optimise existing workflows through prospectively validated programmatic rules, not unvetted diagnostic layers.

Gastrointestinal Disorders doi: 10.3390/gidisord8040058

Authors: Fatouma Mohamed Abdoul-Latif Rohit Kumar Ali Merito Ali Filsan Omar Ali Orbisso Kabo Orbisso

Background: Crohn’s disease (CD) is a multifactorial inflammatory bowel disease (IBD) arising from interactions among genetic susceptibility, immune dysregulation, intestinal microbiota, and environmental factors. However, genetic and environmental determinants of IBD in Djibouti remain poorly characterized. Objectives: This study aimed to characterize the demographic and clinical profile of IBD and investigate the distribution and association of major (Caspase Recruitment Domain-Containing Protein 15/Nucleotide-Binding Oligomerization Domain-Containing Protein 2) CARD15/NOD2 variants with CD in a Djiboutian population. Methods: A total of 150 participants aged 18–30 years were enrolled, including 50 CD patients, 50 ulcerative colitis (UC) patients, and 50 healthy controls. Demographic, clinical, familial, lifestyle, and environmental characteristics were recorded. Genomic DNA isolated from intestinal mucosal biopsies was analyzed by PCR followed by Sanger sequencing for R702W, G908R, and 1007fs variants. Carrier and allele frequencies were assessed using odds ratios (ORs), 95% confidence intervals (CIs), and categorical statistical tests. Results: CD patients showed higher carrier frequencies of R702W (24.0%), G908R (16.0%), and 1007fs (20.0%) than controls (10.0%, 6.0%, and 8.0%, respectively). Allele-level analysis indicated increased odds for R702W (OR = 2.55), G908R (OR = 2.67), and 1007fs (OR = 2.59), although associations were not statistically significant. Abdominal pain and chronic diarrhoea predominated clinically, with greater weight loss in CD and rectal bleeding in UC. Notably, all CD participants reported a history of khat consumption before disease onset; however, the absence of an appropriate non-exposed comparison group and quantitative exposure assessment precludes inference regarding its association with CD risk. Conclusions: These findings suggest potential genetic susceptibility to CD and identify khat consumption as a hypothesis-generating environmental factor requiring further investigation.

Gastrointestinal Disorders doi: 10.3390/gidisord8030057

Authors: Moshe Argaman Chen Klechevski Aviad Gravetz Yael Ben Avraham Nadav Vaknin Rotem Horowitz Ali Safadi Ali Mousa Saida Murtaja Satea Alexandre G. Lellouch Mordechai Shimonov Eviatar Nesher Fahim Kanani

Background/Objectives: Obesity can delay kidney-transplant listing, and metabolic and bariatric surgery (MBS) may help address this barrier, but its role, timing, and procedure choice are not established for every candidate. We evaluated transplant-access outcomes, failed pathways, bariatric safety, procedure-specific considerations, and evidence relevant to pretransplant referral. Methods: PubMed/MEDLINE, Embase, and Google Scholar were searched through 6 August 2026. The review and protocol were prospectively registered in PROSPERO. Reports were mapped to access/pathway, bariatric-safety, post-transplant, and procedure/timing/pharmacokinetic/enteric-oxalate domains. Cumulative transplantation proportions were synthesized as an exploratory outcome using a restricted maximum likelihood random-effects model with Hartung–Knapp confidence intervals. Results: Forty-seven reports from 30 source clusters were included. Across 10 independent bridge cohorts (180/531 transplants), the pooled proportion over heterogeneous study-specific follow-up was 39.6% (95% CI, 28.2–52.3%; I2 = 77.4%), with a 95% prediction interval of 12.9–74.4%. This pooled estimate was descriptive and non-comparative. Adjusted observational estimates favored MBS for waitlisting, active listing, or kidney transplantation but were not pooled because their estimands and pathway structures differed. The two randomized trials had some concerns and high risk of bias, respectively, and all 23 nonrandomized comparative results were at serious or critical risk of bias. No validated treatment-effect modifier or referral prediction model was identified. Conclusions: MBS may facilitate transplant access when obesity is a principal reversible barrier. However, very-low-certainty evidence establishes neither a causal effect of MBS on transplant access nor referral criteria, an individual transplantation probability, optimal timing, or superiority of sleeve gastrectomy over gastric bypass. Referral and procedure choice should remain individualized and multidisciplinary.

Gastrointestinal Disorders doi: 10.3390/gidisord8030056

Authors: Sameer Al Awadhi Ahmad Jazzar Eyad Alakrad Osama Yousef Rahul Nathwani Sulaman Magdub Abdulla Alhassani

Background: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. Increasing recognition of EoE and advances in its diagnosis and management have highlighted the need for locally relevant, evidence-based guidance for clinical practice in the United Arab Emirates (UAE). Objectives: This study aims to develop practical, evidence-based consensus recommendations for the diagnosis and management of adult EoE tailored to the UAE healthcare setting. Methods: A modified Delphi process was conducted by the Emirates Gastroenterology and Hepatology Society (EGHS). The expert panel consisted of seven nationally recognized EoE specialists, including six gastroenterologists and one histopathologist, representing six healthcare institutions across the UAE. Six key domains were identified: (1) Definition, Pathogenesis, and Epidemiology; (2) Clinical Presentation, Natural History, and Diagnosis; (3) Management and Treatment; (4) Monitoring and Follow-up; (5) Persistent or Refractory EoE; and (6) Emergency Care. Following a comprehensive literature review, consensus statements were developed and evaluated through two rounds of voting. Consensus was predefined as ≥80% agreement, while ≥90% agreement was considered a strong recommendation. Results: Forty-seven consensus statements were developed across the six predefined domains addressing the diagnosis, treatment, monitoring, and management of refractory disease in adult patients with EoE. Conclusions: These consensus recommendations provide a practical, evidence-based framework for the diagnosis and management of adult EoE in the UAE. By integrating current evidence with expert opinion, they aim to standardize clinical practice, support high-quality patient care, and identify priorities for multidisciplinary collaboration and research in EoE across the UAE.

Gastrointestinal Disorders doi: 10.3390/gidisord8030055

Authors: Svetoslav Stoev Vesselina Yanachkova Hristina Lebanova Elina Petkova-Gueorguieva Stanislav Gueorguiev Vasil Koynarski

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030054

Authors: Yoshinori Ozono Hotaka Tamura Kazuo Kitamura Ayumu Hosokawa Yukiko Otsuki Hiroshi Hatada Naomi Uchiyama Satoshi Shimamoto Koji Igarashi Hiroshi Kawakami

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030053

Authors: Finly Septianto Ummi Maimunah

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030052

Authors: Anshoo Agarwal Sadeem Fahad Alwulayi Asayil Saleh Alanazi Ghaliah Farraj Alanzi Rawan Sawab Albanaqi Danah Naif Salem Alanzi Nada Faleh AlRuwaili Ghala Sultan Ageel Al Enezi Baraah Abu Alsel Safya E. Esmaeel Fathia Ahmed Mersal Naglaa A. Bayomy Manal S. Fawzy

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030051

Authors: Rasha Ashmawy Medhat M. Anwar Mona Nagy Elwany Ehab Kamal Khaled Abd ElAziz Kamal Sonia S. Saleh Nourelhoda E. Hassan Fayek Elkhwsky

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030050

Authors: Vaios Svolos Dimitra Eleftheria Strongylou Athanasia Vlachou Anastasia Triantafyllou Athina Samara Georgios Charmantzis Elli Zoupa Evanthia Balafa Eleni Georgakli Andreas Kapsoritakis Konstantinos Argyriou Maria Misiou Odysseas Androutsos

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030049

Authors: Aishwarya Gollamudi Prateek Mathur Harsh Tiwari Fariah Asha Haque Chanelle Benjamin Le Yu Naing Abigail Stocker Michael W. Daniels Matthew Cave Thomas L. Abell

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030048

Authors: Xhensila Pemaj Skerdi Prifti Marsela Sina Altin Hysa Adea Kocollari Sara Hoxha

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030047

Authors: Abdullah Mohammed Alshehri Mohammed Mukharrib Khaled Abdulwahab Amer Seham Marei Alqahtani

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030046

Authors: Alaa Zahalka Moshe Kamar Moshe Argaman Moran Cozin Anastasiia Iserlis Wasim Shakkur Firas Abu Akar Arckadi Isakov Fahim Kanani Catia Dayan

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030045

Authors: Mariusz Sapuła Dagny Krankowska Alicja Wiercińska-Drapało

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030044

Authors: Pier-Valerio Mari Annalisa Schifano Angela Saviano Andrea Piccioni Giacomo Costati Carmine Petruzziello Veronica Ojetti

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030043

Authors: Abdelwahap Elghezewi Yasmeen Obeidat

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030042

Authors: Vaios Svolos Anastasia Triantafyllou Maria Delliou Anna Maria Pentzerentzi Maria Misiou Elpida Galanopoulou Dimitra Eleftheria Strongylou Odysseas Androutsos

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030041

Authors: Moshe Argaman Michael Gurevich Ofir Cohen Veronika Dadaev Rotem Horowitz Shai Hoffman Yael Ben Avraham Adi Litmanovich Aviad Gravetz Eviatar Nesher Fahim Kanani

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030040

Authors: Nikos Viazis Konstantinos Mousourakis Panagiotis I. Kanellopoulos Dimitra Kozompoli Dimitra Provi Alexandra Agorogianni Vasilis Papastergiou Athanasios Soukovelos Ioanna Nefeli Mastorogianni Alexandros Skamnelos Dimitrios Christodoulou

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030039

Authors: Rebecca Einspieler Judith Pichler Wolf-Dietrich Huber Andreas Heilos Christoph Aufricht Bettina Bidmon-Fliegenschnee

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030038

Authors: Gurleen Kaur Rahul Jain Palak Grover Zarqa Yasin Karanbir Singh Bipneet Singh

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030037

Authors: Chaled Alnakib Fahim Kanani Shachar Laks Eyal Leibovitz Adam Goldstein Mohamad Jazmawi Moshe Rubin Raul Rosenthal Mordechai Shimonov

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.

Gastrointestinal Disorders doi: 10.3390/gidisord8030036

Authors: Murtaja Satea Alexandre G. Lellouch Haïzam Oubari Veronika Dadaev Rotem Horowitz Shai Hoffman Yael Ben Avraham Tobias Niederegger Karam Azem Rodolfo J. Oviedo Narmin Zoabi Eviatar Nesher Fahim Kanani

Background: Bile leaks complicate 5–25% of liver transplants and are among the most common early postoperative biliary events. Their management within the first 14 postoperative days has traditionally been framed around the timing of intervention. Objective: To evaluate whether leak characteristics and patient stability provide more consistent guidance than intervention timing for early post-transplant bile leaks. Methods: A structured narrative review using a dual-source search (AI-assisted semantic search [Elicit Plus] and PubMed/MEDLINE) was conducted. A PICO-informed (Population, Intervention, Comparator, Outcome) framework guided inclusion; two independent reviewers preformed screening, with senior adjudication, yielding 37 sources. Because “early” was defined heterogeneously—by leak onset in most studies (definitions exceeding 14 days) and by intervention timing in others—and no study compared timing within a 14-day window, quantitative pooling was not undertaken. Results: No included study directly compared intervention timing within the first 14 postoperative days. In the largest available analysis of ERCP timing, resolution and adverse event rates did not differ by whether endoscopy was performed within one day, on days two to three, or after three days; endoscopic success was consistently high (80–98%) across temporal windows. Leak type was a consistent correlate of management intensity and resolution: anastomotic leaks were associated with higher surgical-intervention rates (40% vs. 8.3% for T-tube exit-site leaks in one cohort) and lower resolution rates (58–69%) than non-anastomotic leaks (90–100%). Within endoscopic therapy, bridging stent placement—not leak location—was the strongest independent predictor of resolution, and any bile leak, irrespective of subtype, independently predicted subsequent biliary stricture (pooled adjusted OR ≈ 4). Ultra-early leaks (≤72 h), frequently technical failures, formed the one subset favoring early surgical re-exploration. Conclusions: The absence of a demonstrated timing effect reflects a lack of direct comparative data rather than proof that timing is unimportant. Leak type, patient stability, and management modality offer more consistent and actionable guidance than temporal urgency, forming the basis for a leak-stratified framework. Prospective multicenter registries with standardized timing strata and leak type stratification are needed to test whether timing independently influences outcomes.

Gastrointestinal Disorders doi: 10.3390/gidisord8030035

Authors: Marsela Sina Sara Hoxha Xhensila Pemaj Gentiana Qirjako Enkeleint A. Mechili Skerdi Prifti

Background and Aim: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease (IBD) associated with increased susceptibility to enteric infections, which may mimic or exacerbate disease flares. The C-reactive protein (CRP)-to-albumin ratio (CAR) has emerged as a simple indicator of systemic inflammation in UC. This study aimed to assess the prevalence of stool infections in active UC and to further evaluate CAR as a potential predictive marker. Methods: This retrospective study included 42 patients with active UC (Mayo score ≥ 6) from April 2024 to February 2025. Stool samples were analyzed using multiplex polymerase chain reaction (PCR) for 25 bacterial, viral, and parasitic pathogens. Serum CRP and albumin levels were measured to calculate the CAR. Patients were categorized as infected or non-infected. Logistic regression and receiver operating characteristic (ROC) analyses were performed to evaluate CAR predictive performance. Results: Enteric infections were identified in 35.7% of patients, with Escherichia coli species predominating. CAR was significantly higher in infected than in non-infected patients [0.21 (0.02–0.62) vs. 0.06 (0.02–0.15), p = 0.028]. CAR was significantly associated with enteric infection in logistic regression analysis (OR = 240.0, 95% CI 2.7–21,555.6; p = 0.017). ROC analysis yielded an AUC of 0.706, with a cut-off value of 0.669 providing 100% specificity and 40% sensitivity. Conclusions: Enteric infections are prevalent in patients with active UC. CAR may serve as a simple, rapid, and accessible adjunctive marker to identify patients who warrant further evaluation for enteric infection. Thus, it may aid in differentiating UC flares from superimposed infection.

Gastrointestinal Disorders doi: 10.3390/gidisord8030034

Authors: Agostino Fernicola Michele Santangelo Aldo Rocca Pasquale Avella Armando Calogero Felice Crocetto Luigi Ricciardelli Antonio Alvigi Andrea Paolillo Carmen De Cocinis Domenica Pignatelli Martina Sommese Antonio Grimaldi Alessio Cece Giacomo Benassai Gennaro Quarto

Background: Heller myotomy (HM) is the standard surgical treatment for achalasia. Complete muscular division while preserving mucosal integrity is essential for optimal outcomes. Indocyanine green fluorescence (ICG) imaging has recently emerged as a potential intraoperative adjunct during minimally invasive HM, although evidence remains limited and heterogeneous. Methods: A scoping review was conducted according to PRISMA-ScR recommendations. PubMed, Scopus, and Web of Science were systematically searched to identify clinical studies reporting intraoperative ICG use during laparoscopic or robotic HM. Data regarding surgical approach, fluorescence technique, intraoperative applications, and outcomes were extracted and descriptively synthesized. Results: Four clinical studies published between 2022 and 2024 were included, involving 58 patients overall, of whom 41 underwent minimally invasive HM with intraoperative ICG fluorescence assessment. Two main fluorescence strategies were identified. Intravenous ICG administration was exclusively evaluated during robotic Heller myotomy, whereas all laparoscopic studies employed intraluminal ICG instillation through a nasogastric tube. Fluorescence imaging was used to assess myotomy completeness, identify residual muscle fibers, and detect mucosal perforation. Intraluminal ICG enabled direct visualization of the mucosal tube and facilitated leak detection, whereas intravenous administration enhanced tissue contrast and identification of residual muscular bundles. No ICG-related adverse events were reported. However, the available evidence was limited to small observational series with heterogeneous protocols and inconsistent outcome reporting. Conclusions: ICG fluorescence appears technically feasible during minimally invasive HM and may support intraoperative assessment of myotomy completeness and mucosal integrity. Although early clinical experience is encouraging, the available evidence remains insufficient to support routine implementation of ICG-guided assessment during Heller myotomy, highlighting the need for standardized prospective comparative studies.

Gastrointestinal Disorders doi: 10.3390/gidisord8030033

Authors: Yohei Okawa

Background: Faecal incontinence (FI) may occur in patients with irritable bowel syndrome (IBS), particularly when loose stool, urgency, reduced warning time, fluctuating bowel habits, or constipation with retention interferes with timely defaecation. However, IBS-related FI should be distinguished from FI caused primarily by structural sphincter injury, neurological disease, advanced frailty, or other organic gastrointestinal disorders. This focused narrative review examines IBS-specific mechanisms and conservative care considerations relevant to FI risk. Methods: This article is a focused narrative review rather than a systematic review, scoping review, clinical guideline, or formal GRADE assessment. PubMed and the Ichushi-Web/Japanese Medical Abstracts Society were searched for studies published from January 2000 to June 2026. Search terms were combined and included irritable bowel syndrome with faecal/fecal incontinence, urgency, diarrhoea/diarrhea, constipation, stool form, bowel diaries, diet, FODMAP, fibre/fiber, pelvic floor rehabilitation, biofeedback, skin care, absorbent products, ultrasound, and conservative management. Studies directly addressing IBS mechanisms or symptom management, FI assessment or conservative FI care, or implementation issues relevant to IBS-related FI were deemed eligible. Results: Direct studies of FI prevention in IBS patients are scarce. The most defensible IBS-specific targets are loose stool, urgency, reduced warning time, alternating bowel habits, constipation with retention or incomplete evacuation, diet- or medication-related triggers, stress-related exacerbation, and toilet access. Broader FI evidence supports supportive measures such as skin protection, absorbent products, pelvic floor rehabilitation, biofeedback, transanal irrigation, and referral, but these measures are not IBS-specific unless they are connected to IBS-related symptom pathways. Synthesis: Evidence was organized into three categories: direct IBS evidence, general FI evidence, and indirect implementation evidence from continence-care settings. No formal certainty ratings or recommendation strengths were assigned; statements are therefore framed as clinical considerations and areas for future study rather than guideline-level recommendations. Conclusions: IBS-related FI should be discussed as a symptom-risk pathway within IBS rather than as FI in general. Available evidence suggests the value of assessing IBS subtype, stool form, urgency, triggers, warning time, and toileting circumstances before applying general FI support. Because direct preventive trials are limited, conclusions should be interpreted as practice-informing clinical considerations rather than firm recommendations.

Gastrointestinal Disorders doi: 10.3390/gidisord8030032

Authors: Lingyu Kong Hongxin Piao

Cholangiocarcinoma (CCA) is a highly malignant tumor originating from the epithelium of the bile ducts. It has an insidious onset, is difficult to diagnose in its early stages, has a low rate of curative resection, and carries an extremely poor prognosis. Among these, intrahepatic cholangiocarcinoma (iCCA), as the most representative subtype, is a classic “immunologically cold tumor.” The response rate to single-agent immunotherapy is only 5–10%, and the mechanisms of immune resistance are complex and not yet fully elucidated. The tumor microenvironment, serving as the core site of immune resistance, forms a highly immunosuppressive network composed of cancer-associated fibroblasts, hypoxia, metabolic reprogramming, and epigenetic abnormalities; a population of immunosuppressive cells centered on tumor-associated macrophages further amplifies tolerance signals; and the gut–biliary microbiome exerts systemic immune regulation via the gut–liver axis. Based on mutant mouse models generated via tail vein injection and in-depth studies of mutations in key signaling pathways, our understanding of the mechanisms underlying iCCA’s immune resistance is deepening at both the molecular and systems levels. This article reviews the local and systemic regulatory mechanisms of immune resistance in primary iCCA, summarizes the research value of experimental and preclinical models, and reviews novel strategies such as tumor microenvironment remodeling, activation of immune cell networks, microbiome interventions, and multidimensional combination therapies. It analyzes current research bottlenecks and clinical challenges and outlines the future direction of precision immunotherapy, aiming to provide a theoretical basis and new insights for overcoming iCCA immunotherapy resistance and advancing clinical translation.

Gastrointestinal Disorders doi: 10.3390/gidisord8030031

Authors: Elina Stoffel John William Blackett Alexa Choy Dakota Ma Wynette Almeida Brad Kuo Daniela Jodorkovsky Sydney Pomenti

Background: Gastroparesis presents with frequently debilitating symptoms of nausea, vomiting, abdominal pain, bloating and early satiety, resulting in high healthcare utilization. Resilience, defined as the inherent and modifiable ability of an individual to adapt and recover positively to stress, is crucial for patients with chronic diseases but has not been studied in gastroparesis. We aimed to investigate if resilience correlates with acute care utilization and symptom severity in patients with gastroparesis. Methods: We conducted a single-center prospective observational study of patients with gastroparesis. Resilience was assessed using the 10-item Connor–Davidson Resilience scale (CD-RISC). Symptom severity was assessed through the Gastroparesis Cardinal Symptom Index (GCSI). Gastric emptying severity using scintigraphy or wireless motility capsule was categorized as mild, moderate, or severe based on consensus recommendations. Acute care utilization and hospitalizations in the last 12 months, comorbidities, medications, and demographic information were collected. Count outcomes were modeled using negative binomial regression due to overdispersion. Models were adjusted for age, sex, and symptom severity. Results: Among 40 consecutive patients (mean age 39 ± 16, 88% female), gastric emptying severity was mild in 35%, moderate in 15%, severe in 30%, and unknown in 20%. Mean resilience score was 29 ± 8 and mean GCSI was 2.96 ± 1.14. Gastroparesis symptoms did not correlate with gastric emptying severity (p = 0.5). In a linear regression model, no statistically significant correlation was observed between resilience and mean GCSI score in unadjusted or adjusted models. In negative binomial regression models, greater symptom severity was strongly associated with higher Emergency Department (ED)/urgent care visits (IRR 3.12; 95% CI 1.60–6.98; p < 0.001) and hospitalization rates (IRR 3.36; 95% CI 1.62–8.57, p = 0.006). Resilience was not a significant predictor of either (IRR 1.07; 0.95–1.22; p = 0.2 and IRR 1.02; 0.89–1.18; p = 0.7). Conclusions: Among patients with gastroparesis, no statistically significant association was detected between resilience and symptom severity, gastric emptying, or acute-care utilization after accounting for clinical and demographic factors. Symptom severity was the dominant predictor of ED visits and hospitalizations. These findings suggest that symptomatic disease burden, rather than objective gastric emptying severity, is the primary driver of acute healthcare utilization in this cohort.

Gastrointestinal Disorders doi: 10.3390/gidisord8020030

Authors: Ahmed Arafa Amira S. A. Said Tarig A. Y. Ali Ehab Elkady Doaa Mahmoud Khalil

Background: Liver cancer is a major global public health challenge, with substantial morbidity, mortality, and economic costs. Growing attention has turned to sleep-related behaviors, including daytime napping, as potential risk factors for cancer. Evidence regarding the association between daytime napping and liver cancer remains inconsistent. We, therefore, conducted a systematic review and meta-analysis to investigate this association. Methods: Several databases were searched up to 1 October 2025, for studies assessing the association between daytime napping and liver cancer. Study quality was evaluated using the Newcastle–Ottawa Scale (NOS). Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated with random-effects models. Results: Four prospective cohort studies, involving 1,281,628 participants, were included. All studies were of high methodological quality according to NOS. The pooled analysis showed a significant association between daytime napping and liver cancer risk (HR = 1.24; 95% CI: 1.07, 1.43). The results did not significantly vary by sex or region. Exploratory subgroup analyses showed similar findings across sex and region. Sensitivity analyses, performed by sequentially removing each study and recombining the remaining studies, yielded pooled HRs ranging from 1.20 to 1.29. Conclusions: Daytime napping was associated with a higher risk of liver cancer. However, residual confounding and reverse causation cannot be excluded, and whether this association reflects a causal relationship or underlying health conditions remains uncertain. Further large-scale prospective studies with detailed assessments of the frequency and duration of daytime napping are needed to confirm this association.

Gastrointestinal Disorders doi: 10.3390/gidisord8020029

Authors: Venos Saeed Abdullah Kamaran Younis M. Amin Hawraz Ibrahim M. Amin

Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic responses of the methanolic extract of T. trachycarpum using an ethanol-induced gastric ulcer model in Sprague–Dawley rats. Methods: Preliminary phytochemical screening revealed the presence of phenolics, flavonoids, terpenoids, tannins, coumarins, and glycosides. Acute oral toxicity testing demonstrated no signs of toxicity at doses up to 5 g/kg. Gastric ulceration was induced by absolute ethanol, and animals were pretreated with the extract (250 and 500 mg/kg) or omeprazole (20 mg/kg). Results: The extract significantly decreased the gastric lesion area from 258.50 ± 6.38 mm2 in the ulcer control group to 143.70 ± 0.76 mm2 and 115.50 ± 0.76 mm2, corresponding to ulcer inhibition rates of 44.41% and 55.31%. Additionally, the extract increased mucus production, maintained mucosal structure, and raised stomach pH. Biochemical analysis showed a significant increase in antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] and a reduction in malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. In addition, the extract modulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10). Blood-based ELISA analysis demonstrated increased expression of heat shock protein 70 (HSP70) and reduced Bax levels, suggesting anti-apoptotic activity. Conclusions: These findings indicate that T. trachycarpum exerts significant gastroprotective activity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting its traditional use and highlighting its potential as a natural therapeutic candidate for the management of gastric ulcers.

Gastrointestinal Disorders doi: 10.3390/gidisord8020028

Authors: Jonah C. Short-Miller Michelle Rhea Jay Jamieson Alyson Smith Jason Brumitt

Background/Objectives: Variceal bleeding (VB) is a major complication of cirrhosis, marking a progression from a compensated to a decompensated stage of the disease. Previous research has suggested that HMG-CoA reductase inhibitors, commonly called statins, may have therapeutic benefits for those living with cirrhosis, though their exact benefits and role have yet to be elucidated. This scoping review evaluates the potential role of statins in the primary prevention of variceal bleeding in patients with cirrhosis, and if there exists a difference between hydrophilic and lipophilic statins for this indication. Methods: Publications from the last 10 years with primary or secondary outcomes reporting variceal bleeding among statin users and non-users were included. A search via PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library was conducted, identifying nine studies. Results: Findings related to the benefit of statin use for the prevention of variceal bleeding were inconsistent among study designs. Retrospective studies suggest a lower incidence of VB among statin users compared to non-users. However, this finding has not been borne out in prospective studies. Conclusions: Given the conflicting findings, there is insufficient evidence at present to suggest the routine use of statins for the prevention of variceal bleeding in patients with cirrhosis.

Gastrointestinal Disorders doi: 10.3390/gidisord8020027

Authors: Saksham Kohli Anil Philip Yetunde Akande Philip Sarpong-Mensah Ibrahimkhalil-Mohamud Ibrahim Sheikh Lina George Jhalak Agrohi Hemant Mutneja

Background: Alcoholic hepatitis (AH) is associated with high short-term morbidity and mortality, but contemporary national data on hospital readmissions remain limited. Methods: Using the Nationwide Readmissions Database (2016–2022), we identified adult non-elective AH index admissions and characterized readmission burden, predictors, and outcomes using survey-weighted Cox proportional hazards and Fine-Gray competing risks models. Results: Among 121,984 weighted AH index hospitalizations, 25.0% experienced a 30-day readmission. The most common readmission diagnoses were alcoholic cirrhosis with ascites (18.9%), recurrent alcoholic hepatitis with (12.5%) and without ascites (8.9%), sepsis (11.3%), and alcohol withdrawal (5.7%). Liver-related, other/systemic, and alcohol-related non-liver diagnoses accounted for 53.6%, 36.6%, and 9.8% of 30-day readmissions. Readmissions carried higher in-hospital mortality (8.6% vs. 3.3%; aOR 2.75), longer length of stay (7.1 vs. 6.4 days), higher mean charges ($77,606 vs. $60,491), and higher liver transplantation rates (all p < 0.001). Independent predictors of 30-day readmission included age (HR 0.9954 per additional year, p < 0.001), female sex (HR 1.13), discharge against medical advice (HR 1.89), higher comorbidity burden (Category 4 HR 1.30), diabetes (HR 1.13), chronic kidney disease (HR 1.13), acute kidney injury (HR 1.23), and blood transfusion (HR 1.23). Index ICU admission was paradoxically associated with lower readmission rates (OR 0.77) but higher mortality when readmitted (OR 2.38, p < 0.001). Conclusions: One in four AH survivors experienced a 30-day readmission, predominantly liver-related and carrying nearly threefold higher in-hospital mortality. Readmission risk was concentrated among patients with high comorbidity burden, identifying high-yield targets for early risk stratification and post-discharge intervention.

Gastrointestinal Disorders doi: 10.3390/gidisord8020026

Authors: Carlo Alberto Schena Vito Laterza Marcello Covino Fausto Rosa

The gut microbiome has emerged as one of the most promising sources of non-invasive biomarkers for colorectal cancer (CRC). Over the past decade, fecal metagenomic studies have consistently identified a core CRC-associated signature enriched with oral-typical, biofilm-forming species, most notably Fusobacterium nucleatum, Parvimonas micra, Peptostreptococcus stomatis, and Bacteroides fragilis. The recent landmark pooled analysis by Piccinno et al., which combined 3741 metagenomes from 18 international cohorts, offers the most methodologically solid confirmation of this signature to date. It achieved a leave-one-dataset-out area under the curve (AUC) of around 0.85 and expanded resolution to previously unclassified species-level genome bins (SGBs) and strain-level phylogenies. In this narrative review, we critically evaluate the evidence supporting current universal CRC microbiome signatures, explore the mechanistic basis of the oral-to-gut microbial axis and the immunometabolic tumor microenvironment, and argue that increasing evidence indicates the field is nearing a point where investigating patient-level heterogeneity could be the most valuable next step. Because a strong average CRC signal has been convincingly established, an important next direction is to examine how much these signatures’ impact varies among individual patients, considering tumor molecular subtype, immune environment, metabolic profile, and host genetics. We review emerging evidence of such patient-level heterogeneity, outline analytical methods to assess it, and discuss its importance for developing microbiome-based screening, prognostics, and therapeutic strategies in CRC.

Gastrointestinal Disorders doi: 10.3390/gidisord8020025

Authors: Mario Annecchiarico Giuseppe Loiaco Claudia Cirillo Antonio Antonino Giulio Argenio Angela Romano Antonio Varricchio Francesco Carafa Pellegrino Gambardella Giovanni Aprea Giuseppe Palomba

Minimally invasive pancreas-preserving duodenal resection (MIPPDR) encompasses laparoscopic, robotic, and intentionally hybrid duodenal resections performed without pancreatic parenchymal excision, ranging from transduodenal local excision or ampullectomy to sleeve, segmental, subtotal, near-total, and total duodenectomy. This targeted narrative review was designed to provide a clinically oriented synthesis of the available literature on indications, operative strategies, platform selection, reconstruction, perioperative outcomes, oncological adequacy, and functional considerations. A structured literature search was performed in PubMed/MEDLINE, Scopus, and Web of Science up to March 2026. The review focused on minimally invasive or intentionally hybrid pancreas-preserving duodenal resections reporting operative technique, perioperative outcomes, oncological outcomes, or functional sequelae. The minimally invasive literature consisted predominantly of case reports, technical notes, video articles, and small retrospective series, with substantial heterogeneity in lesion type, anatomical location, procedure extent, reconstruction, and outcome reporting. Laparoscopy appeared most reproducible for distal, infra-papillary, and limited resections with relatively low reconstructive burden, whereas robotics appeared to offer specific technical advantages for periampullary dissection, ductal identification, and intracorporeal reconstruction. However, the available evidence was insufficient to define firm comparative indications between platforms or to demonstrate superiority of one minimally invasive approach over another. Functional outcomes, despite their central relevance to the rationale of pancreas preservation, were poorly standardized and inconsistently reported. MIPPDR was therefore interpreted as a selective pancreas-preserving strategy positioned between advanced endoscopic therapy and pancreaticoduodenectomy. Future studies should adopt anatomy-based reporting, distinguish ampullary, periampullary, and distal duodenal disease, and include standardized functional endpoints.

Gastrointestinal Disorders doi: 10.3390/gidisord8020024

Authors: Mei-Na Wang Chuan-Guo Liu Jia Pan Xiao-Gang Pang Hui-Min Liu

Background: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Intestinal barrier impairment represents a core pathogenic mechanism and a key therapeutic target for achieving mucosal healing and sustained remission. Methods: This narrative review summarizes intestinal barrier structure, disruption mechanisms, barrier-targeted therapies, and non-invasive monitoring approaches. A reproducible literature search was conducted in PubMed, Web of Science, and ClinicalTrials.gov from 2015 to 2026. Results: Barrier disruption in UC involves genetic susceptibility, proinflammatory cytokines, zonulin-mediated tight junction injury, gut microbiota dysbiosis, decreased short-chain fatty acids and secondary bile acids, impaired autophagy, and an abnormal mucin 2 (MUC2)-dependent mucus layer. Validated non-invasive monitoring tools include fecal calprotectin/lactoferrin, intestinal ultrasound, diffusion-weighted magnetic resonance imaging (MRI), and intravoxel incoherent motion (IVIM). Emerging therapies focus on tight junction stabilization, epithelial regeneration, autophagy regulation, MUC2 restoration, and microbiota modulation. Conclusions: Intestinal barrier dysfunction drives the initiation and progression of UC. Barrier-based monitoring and targeted repair strategies improve UC management. Future studies should develop personalized therapies, precise microbiota engineering, and multi-dimensional digital evaluation systems.

Gastrointestinal Disorders doi: 10.3390/gidisord8020023

Authors: Esteban Zavaleta-Monestel Yennifer Villagra-Hernandez Jeaustin Mora-Jiménez Jorge Arturo Villalobos-Madriz Carolina Rojas-Chinchilla José Andrés Castro-Gamboa Luis Guillermo Herrera-Jiménez Sebastián Arguedas-Chacón Christian Campos-Núñez

Background: Artificial intelligence (AI) has shown growing potential in the diagnosis of H. pylori infection, particularly through automated analysis of endoscopic images. Emerging studies have also explored treatment-related predictive applications, although this evidence remains limited. The aim of this systematic review was to synthesize current evidence on the use of AI in H. pylori infection, with the primary emphasis on diagnosis and secondary consideration of predictive therapeutic applications. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines through searches in PubMed, ScienceDirect, EBSCO, and the Cochrane Library, including articles published between 2020 and 2025. Six studies that employed deep learning or machine learning models, primarily convolutional neural networks and predictive classifiers, were selected. Results: Artificial intelligence models showed consistent diagnostic performance, with accuracies ranging from 79.2% to 94%, sensitivities from 62.5% to 96%, and specificities from 79.4% to 93.4%. Convolutional neural network-based systems generally demonstrated diagnostic performance comparable to or better than that of human endoscopists, particularly among less experienced operators. Limited evidence suggests a possible role for artificial intelligence in predicting treatment failure; however, this finding is based on a single included study. Conclusions: Artificial intelligence appears to be a promising complementary tool for the diagnosis of H. pylori infection, particularly in endoscopic imaging. However, evidence regarding treatment-related and resistance-related applications remains limited and indirect, and these potential uses should therefore be considered preliminary.

Gastrointestinal Disorders doi: 10.3390/gidisord8020022

Authors: Ángel Mamani-Ruelas Jani Pacheco-Aranibar Johany Sánchez Guillen Gladys Núñez-Zevallos Jhony R. Rodríguez Mamani Francis W. Jacobo-Valdivia Carlos Gámez-Bernabe Steven Criollo-Arteaga Eusebio Walter Colque Rondon Julio Cesar Bernabe-Ortiz

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Emerging evidence highlights the role of the gut microbiota in the development and progression of CRC. Microbial dysbiosis is hypothesized to contribute to chronic inflammation through a variety of mechanisms, such as the production of free radicals, which induce mutagenesis and immune dysregulation in the host, ultimately leading to diseases such as cancer. Methods: Tumor tissue samples or healthy mucosa tissue were collected for bacterial DNA extraction. The V3–V4 region of the 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Bioinformatics analysis was performed with QIIME2, including quality control, DADA2 denoising, alpha and beta diversity calculation, and taxonomic classification using the SILVA database. Results: Differences in microbial composition were observed between groups. The healthy controls exhibited high relative abundances of beneficial genera such as Faecalibacterium, Bacteroides, and Asteroleplasma, whereas the patients with CRC showed enrichment of atypical genera including Novosphingobium, Bradyrhizobium, and Undibacterium. Alpha diversity was lower in the CRC group, and clear clustering by group was observed in the beta diversity analysis. LEfSe analysis identified potential bacterial biomarkers associated with CRC at both the species and genus levels. Conclusions: The findings of this study support the hypothesis that colorectal cancer is associated with distinct alterations in gut microbiota composition, such as an increase in the Novosphingobium genus and a decrease in the Bacteroides genus. An exploratory description of these microbial profiles may aid in the development of microbiome-based diagnostic and therapeutic strategies and contribute to current knowledge of the role of the gut microbiota in CRC in southern Peru.

Gastrointestinal Disorders doi: 10.3390/gidisord8020021

Authors: Silvia Caimmi Amelia Licari Alice Di Carlo Giulia Fusi Gianluigi Marseglia Mirko Bertozzi

Background: Rome IV criteria promote a symptom-based (“positive”) diagnosis of pediatric disorders of gut–brain interaction (DGBIs). In clinical practice, however, organic gastrointestinal diseases may mimic DGBIs and lead to diagnostic revision after further evaluation. We aimed to quantify the diagnostic stability of an initial Rome IV-oriented functional diagnosis in a tertiary pediatric outpatient setting and to identify symptom phenotypes associated with a higher likelihood of later organic reclassification. Methods: We performed a single-center retrospective cohort study (2014–14 May 2021) based on outpatient chart review. Eligible patients were children and adolescents aged 0–18 years with an initial Rome IV-oriented functional diagnosis. Diagnostic reassessment was based on follow-up data, available laboratory and instrumental investigations, and/or response to exclusion therapies. Final diagnoses after reassessment were categorized as functional only, organic, or mixed. Groups were compared using Pearson’s chi-square test. Results: The cohort included 220 males (50.0%) and 220 females (50.0%), with a mean age of 8.86 ± 4.65 years. After reassessment, 343/440 (77.95%) remained functional, 73/440 (16.59%) were reclassified as organic, and 24/440 (5.45%) were classified as mixed. Final diagnosis differed by GI tract involvement (p = 0.001) and by symptom cluster (p = 0.001). Upper GI/dyspepsia-spectrum presentations showed the highest organic yield (27.03%), followed by lower abdominal pain/IBS-spectrum presentations (19.61%). Diarrhea and vomiting/cyclic vomiting each showed 16.67% organic diagnoses (mixed: 10.0% and 7.14%, respectively), whereas constipation showed the greatest diagnostic stability (98.89% functional; 1.11% organic). Functional confirmation rates were similar before and during the pandemic (77.71% vs. 78.70%; p = 0.756). Monthly case volume was higher in 2020–2021 (6.29 vs. 4.61 cases/month). Conclusions: In this tertiary cohort, about one in six children initially diagnosed with a functional disorder were later found to have an organic disease, and an additional 5% had mixed organic–functional presentations. Diagnostic revision was associated with presenting phenotype, with the highest organic yield observed in dyspepsia/upper GI presentations and the lowest in constipation. These findings support symptom-stratified evaluation and follow-up alongside Rome IV criteria.

Gastrointestinal Disorders doi: 10.3390/gidisord8020020

Authors: Armando Curto Irene Scami Giulia Gliottone Rocco G. Iamello Erica N. Lynch Andrea Galli

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disorder that, without treatment, can advance to fibrosis and cirrhosis. Although standard regimens with corticosteroids and thiopurines have significantly improved survival, many patients still experience relapses and drug-related toxicity, highlighting the urgent need for alternative strategies. Recent studies underscore AIH’s multifactorial nature, revealing intricate interactions among genetic susceptibility, environmental triggers, and dysregulated immune responses. Next-generation diagnostics, ranging from novel biomarkers to high-resolution imaging, are enhancing early detection and more precise disease classification. At the same time, multi-omics analyses and artificial-intelligence-based models are refining predictions of disease trajectory and therapeutic response. On the treatment horizon, investigational options such as targeted immunomodulators, B-cell–depleting therapies, and cell-based interventions aim to achieve durable remission while minimizing adverse effects. This review critically appraises these advances and explores how integrating epidemiological insights with cutting-edge research in pathogenesis, diagnostics, and therapy could pave the way for more personalized and effective management of AIH.

Gastrointestinal Disorders doi: 10.3390/gidisord8020019

Authors: Federico Motta Silvia Marino Patrizia Grassi Alessia Migliore Salvatore Leonardi Giovanna Russo Milena La Spina

Background: Molecular syndromic stool panels are increasingly used in paediatric diarrheal syndromes; however, interpretation of Clostridioides difficile (C. difficile) detection remains challenging because colonisation is common in younger children. We aimed to assess the frequency of C. difficile detection using a syndromic gastrointestinal panel in a paediatric tertiary-care centre and to describe the subsequent microbiological work-up and CDI-directed treatment. Methods: We conducted a retrospective single-centre study of all BioFire FilmArray Gastrointestinal (GI) panels performed at San Marco Hospital (University Hospital “G. Rodolico-San Marco”, Catania, Italy) from 1 January 2023 to 31 December 2025. Only the first C. difficile-positive result per patient was included; repeat positives within 30 days were excluded. Index-positive episodes were stratified by age (<1 year, 1 to <2 years, and ≥2 years). Data collected included co-detected pathogens, toxin A/B enzyme immunoassay (EIA) results, GeneXpert PCR findings, and CDI-directed therapy. Results: Among the 714 GI panels performed during the study period, 112 (15.7%) were positive for C. difficile. After exclusion of repeat positives, 91 index-positive episodes were analysed. Median age was 1.0 years (IQR 0.75–4.0), and 48/91 cases (52.7%) occurred in children younger than two years. Toxin A/B EIA was positive in 11/82 tested episodes (13.4%), whereas GeneXpert tcdB was positive in 75/84 episodes (89.3%). Co-detection of at least one additional enteric pathogen occurred in 40/91 cases (44.0%). CDI-directed therapy was administered in 9/91 episodes (9.9%), mainly in children aged ≥2 years. Conclusions: Detection of C. difficile by syndromic molecular panels was relatively frequent in our paediatric cohort but rarely associated with toxin positivity or the need for specific treatment. These findings suggest that many positive Nucleic Acid Amplification Test (NAAT) results may represent colonisation rather than true infection, particularly in younger children. Careful clinical interpretation of syndromic panel results is therefore essential to avoid overdiagnosis and unnecessary antimicrobial therapy.

Gastrointestinal Disorders doi: 10.3390/gidisord8020018

Authors: Hana Jazvo Bogdan Crnokrak Slobodan Todorovic Jasna Gacic Igor Nadj Borislav Toskovic

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT). This study aims to report the experience in the surgical treatment of GIST patients, evaluate the prognostic factors and discuss some controversial issues regarding the significance of microscopically margin-negative resection in GIST patients and the importance of tumor rupture during intraoperative surgical manipulation. Methods: Fifty-four GIST patients with primary disease without metastasis were admitted and treated during the past 15 years. Patients initially presenting with metastatic lesions and those who underwent adjuvant systemic therapy prior to surgical treatment were excluded from the study. Results: The median patient follow-up was 84 weeks. The 5-year overall survival was 34.34% and disease-free survival (DFS) was 35.37%. The median DFS was 244 weeks. In multivariate analysis, survival was affected by a high mitotic rate, resection margin status and the tumor rupture occurrence. Tumor size and tumor location did not show an impact. Conclusions: Surgical resection remains the mainstay of GIST treatment. Mitotic rate, resection margin status, and the occurrence of tumor rupture were predicators for DFS in patients presenting with primary disease. Recurrence of disease after resection was predominantly intra-abdominal and involved the original tumor size and the liver.

Gastrointestinal Disorders doi: 10.3390/gidisord8020017

Authors: Catarina Costa Maria Manuela Estevinho Pedro Mesquita Rita Ferreira Pedro Vilela Teixeira João Santos Ana Ponte Rolando Pinho

Background: The optimal bowel preparation regimen for a small bowel capsule endoscopy (SBCE) remains uncertain. The PrepRICE clinical trial showed that the administration of purgatives after the capsule reached the duodenum improved the mucosal visualization and diagnostic yield. However, it was limited to patients with suspected mid-gastrointestinal bleeding who met strict inclusion criteria. This work aims to report real-life results after the implementation of the new protocol and to compare them with those of the PrepRICE trial. Methods: A prospective analysis was performed on all consecutive patients who underwent an SBCE between December of 2024 and December of 2025. The quality of the small bowel visualization (QSBV), gastric transit time (GTT), small bowel transit time (SBTT), adequate visualization rate, and complete examination rate were assessed. The QSBV was evaluated according to the Brotz quantitative scale. Results: A total of 188 patients were included (52.1% male; median age 56 years [IQR 30]). The median Brotz scale scores were 9 (IQR 1), 9 (IQR 1), 8 (IQR 2), and 8 (IQR 1) in the first, second, and third terciles and overall, respectively (compared to 9, 9, 9, 9 in PrepRICE, p < 0.001). No significant differences were found in the complete examination rate (96.8% vs. 99%, p = 0.43), adequate visualization rate (91.3% vs. 92.0%, p = 0.68), GTT and SBTT. Conclusions: The real-life results were good and similar to those of the original study, with a high rate of complete examination and adequate visualization, with slightly weaker QSBV compared to that reported in the periprocedural group in the PrepRICE study yet still superior to the preprocedural groups.

Gastrointestinal Disorders doi: 10.3390/gidisord8020016

Authors: Agostino Fernicola Giuseppe Scognamiglio Viviana Verlingieri Luigi Ricciardelli Andrea Paolillo Veronika Dadaev Moshe Argaman Yael Ben Avraham Felice Crocetto Armando Calogero Antonio Alvigi Alessio Cece Fahim Kanani

Background: Kartagener syndrome (KS) is a rare subset of primary ciliary dyskinesia characterized by the triad of situs viscerum inversus (SVI), chronic sinusitis, and bronchiectasis. Laparoscopic cholecystectomy (LC) in patients with SVI is technically demanding because of mirror-image anatomy, while evidence supporting the use of indocyanine green (ICG) fluorescence in this setting is scarce. Case Presentation: We report the case of a 25-year-old woman with KS and SVI totalis who underwent elective LC for symptomatic cholelithiasis. The procedure was performed using a mirror American approach with four trocars and near-infrared ICG fluorescence cholangiography. ICG enabled real-time visualization of biliary anatomy and facilitated intraoperative orientation. The procedure was completed laparoscopically without intraoperative or postoperative complications, and the postoperative course was uneventful. Methods: A non-systematic narrative review of the literature was conducted to identify reported cases of LC in patients with SVI, including cases associated with KS. Studies published between 1991 and 2025 were retrieved from PubMed, Web of Science, Scopus, and Embase. Data were descriptively summarized, focusing on surgical technique, trocar placement, and reported use of ICG fluorescence. Results: A total of 143 articles were included. Most cases involved isolated SVI, while KS was reported only in a minority of patients. The mirror American technique and four-trocar configuration were the most frequently adopted approaches. Only three cases, including the present report, described the use of ICG fluorescence during LC in patients with SVI or KS. Conclusions: LC in patients with SVI is feasible but technically demanding. ICG fluorescence may assist intraoperative biliary orientation in complex anatomical settings; however, current evidence is extremely limited and should be considered hypothesis-generating only.

Gastrointestinal Disorders doi: 10.3390/gidisord8010015

Authors: Pedro Mesquita Rolando Pinho João Carlos Silva João Correia Catarina Costa Pedro Teixeira Rita Ferreira Ana Ponte Teresa Freitas

Background/Objectives: Acute severe ulcerative colitis (ASUC) affects up to one quarter of patients with ulcerative colitis and carries a substantial risk of colectomy. Early recognition of the need for escalation beyond intravenous (IV) corticosteroids is essential, yet most indices—such as the Oxford criteria—require reassessment on day 3, delaying rescue therapy. The ASUC score, based on admission albumin, C-reactive protein (CRP), endoscopic severity (Ulcerative Colitis Endoscopic Index of Severity, UCEIS), and pre-admission steroid use, was recently proposed to predict early escalation at admission. This study aimed to externally validate the ASUC score and compare its performance with established indices. Methods: We performed a single-center retrospective validation study including consecutive ASUC admissions (2015–2024). The primary outcome was escalation beyond IV steroids, defined as medical rescue therapy with infliximab or ciclosporin and/or colectomy during the index hospitalization. As a sensitivity analysis providing a more specific estimate of IV corticosteroid non-response, we repeated analyses restricting the outcome to medical rescue therapy alone. The model performance was assessed for discrimination (AUC and bootstrap-corrected 2000 resamples), calibration (intercept, slope, and Brier score), and clinical utility (decision-curve analysis). Comparator indices included Albumin-CRP-Endoscopy score (ACE), Admission Model for Acute Severe Colitis (ADMIT-ASC), Oxford Day 3, Lindgren, and Edinburgh. Predefined subgroup analyses (exploratory and underpowered) evaluated infection and biologic exposure. Results: Ninety-one admissions were included overall. The primary validation was performed in the infection-free cohort (n = 77), and infected cases (n = 14) were analyzed separately. In the infection-free cohort, 17/77 (22.1%) required escalation beyond IV steroids during the index hospitalization (medical rescue therapy and/or colectomy), and 5/91 (5.5%) underwent colectomy within 90 days. The ASUC score showed excellent discrimination (Area under the receiver-operating characteristic curve [AUC] 0.89, 95% Confidence Interval [CI] 0.81–0.95), good calibration (intercept 0.26, slope 1.29), and net clinical benefit across 30–50% thresholds. In the rescue-only sensitivity analysis, discrimination remained high (AUC 0.86, 95% CI 0.77–0.94). At a cut-off of ≥2, sensitivity 94% and specificity 78% outperformed other indices (AUC 0.62–0.83). Exploratory subgroup analyses were imprecise due to small sample sizes; discrimination was lower in the infected-only subgroup (AUC 0.71), and estimates in biologic-experienced patients were unstable because of severe imbalance. Conclusions: The ASUC score accurately identified patients likely to require escalation beyond IV steroids on the day of admission, outperforming or matching established day-3 indices. Its simplicity and reliability support its integration into early ASUC management to expedite rescue therapy and potentially improve outcomes.

Gastrointestinal Disorders doi: 10.3390/gidisord8010014

Authors: Sarah Hoeck Thuy Ngan Tran

Background: Flanders (Belgium) offers a fecal immunochemical test (FIT) biennially to citizens aged 50–74 years, but uptake is suboptimal (~50%). This study evaluated the impact of a second e-reminder on FIT uptake. Methods: We conducted a quasi-experimental study comparing FIT uptake in individuals who received a first e-reminder during June 2023–May 2024 and a second e-reminder five weeks later (intervention cohort) with those who received a first e-reminder in June 2021–May 2022 without a second reminder (historical control). The study outcome was FIT uptake within one year after the first e-reminder. Analyses were stratified by screening history (regular vs. irregular participants). Results: The study population consisted of 54,734 regular (27,522 control and 27,212 intervention); and 18,492 irregular participants (8565 control and 9927 intervention). Median age was slightly lower in the intervention group (regular: 57 vs. 59 years; irregular: 62 vs. 64 years). Gender distribution was balanced (≈50% men). Regular participants receiving a second e-reminder had 80% higher probability of participation than controls (OR 1.80; 95% CI 1.73–1.86; p < 0.0001); with uptake increasing from 29.5% to 43.7%. Irregular participants with a second e-reminder had a 91% higher probability of participation compared with no second e-reminder (OR 1.91; 95% CI 1.74–2.09; p < 0.0001), with uptake increasing from 9.4% to 18.4%. Conclusions: A second e-reminder significantly increased FIT uptake among both regular and irregular participants in the Flemish colorectal cancer screening program. These findings support its use as a low-cost strategy to improve population-level screening participation.

Gastrointestinal Disorders doi: 10.3390/gidisord8010013

Authors: Daniele Balducci Marta Mosca Sabrina Monaco Susanna Faenza Stefano Fabiani Fabio Cortellini Nicola Cesaro Gianpiero Stefanelli Salvatore Paba Maddalena Pecchini Michele Montori Marco Valvano

Background: Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions that affect the gastrointestinal tract. Since the initial approval of infliximab (IFX), a monoclonal antibody targeting TNF-α, numerous novel therapeutic targets have been identified, and many new therapies have been approved for the treatment of IBD. Methods: We conducted a narrative review of the literature using major biomedical databases, including EMBASE, Scopus, PubMed, CENTRAL, and ClinicalTrials.gov (last search date: 10 December 2025). Results: This review summarizes the current evidence on therapies approved for IBD (both CD and UC) and provides an overview of investigational agents currently being evaluated in ongoing phase II and III clinical trials. Conclusions: Moderate optimism arises from the expanding array of therapeutic targets under investigation and from emerging treatment strategies. However, only through a deeper understanding of the pathophysiological mechanisms underlying IBD will substantial improvements in treatment outcomes be achieved for conditions that continue to impose a significant burden on patients’ quality of life.

Gastrointestinal Disorders doi: 10.3390/gidisord8010012

Authors: Nebojsa Manojlovic Ivana Tufegdzic Elizabeta Ristanović Nemanja Rancic Stevan Manojlovic

Background/Objectives: Helicobacter pylori infection induces a systemic humoral immune response that reflects both bacterial virulence and host immune regulation. While anti-H. pylori IgG is widely used as a marker of infection, its ability to predict the topographic distribution and biological activity of gastritis is limited. The objective of this study was to evaluate whether the relative predominance of systemic IgG versus IgA antibodies, IgG subclasses, and antigen-specific IgG reactivity could better reflect the features and topography of gastric inflammation. Methods: A total of 123 patients with dyspeptic symptoms, confirmed H. pylori infection, and histologically verified gastritis were included. Anti-H. pylori IgG and IgA levels were measured by ELISA, IgG1 and IgG2 subclasses by subclass-specific assays, and antigen-specific IgG reactivity (CagA, VacA, UreB66, 30 kDa, and UreA 26 kDa) by Western blot. Histopathological parameters of the antral and corpus mucosa were graded according to the updated Sydney system. Receiver operating characteristic (ROC) analysis and univariate and multivariate logistic regression were applied to identify predictors of gastritis topography. Results: Anti-H. pylori IgG levels correlated with the grade and activity of inflammation in the antrum, whereas IgA correlated with inflammatory parameters in the corpus. IgG1 and IgG2 showed limited associations with antral inflammatory activity. IgA showed the best diagnostic performance for pangastritis/corpus-predominant gastritis, while IgG2 best identified antrum-predominant gastritis. The combined serological profile defined as IgG > IgA together with 30 kDa antigen positivity was independently associated with antrum-predominant gastritis in multivariate analysis (OR 2.516; 95% CI 1.004–6.308). Conclusions: The systemic balance between IgG and IgA responses reflects the topographic distribution of H. pylori-associated gastritis. IgG predominance combined with 30 kDa antigen seropositivity represents an independent serological predictor of antrum-predominant gastritis and may improve non-invasive stratification of gastric inflammation.

Gastrointestinal Disorders doi: 10.3390/gidisord8010011

Authors: Valerio Caruso Luciana Rigoli Rosario Caruso

Background: Perineural invasion (PNI) is a recognized pathway for cancer spread and is associated with poor outcomes in gastric cancer. However, the initial morphological characteristics of tumor–nerve interactions in early gastric cancer, particularly at the ultrastructural level, remain insufficiently defined. Case Presentation: We report a case of a 49-year-old man diagnosed with type IIc early gastric cancer. Histological examination revealed a combined poorly cohesive carcinoma (PCC)-NOS/signet-ring cell (SRC) histotype. Tumor invasion reached the middle third of the submucosa and was accompanied by a mature desmoplastic reaction, with metastases identified in two perigastric lymph nodes (pT1bN1M0). Transmission electron microscopy (TEM) revealed unmyelinated nerve fibers embedded within the submucosal desmoplastic stroma, in close proximity to infiltrating neoplastic cells. Several tumor cells exhibited cytoplasmic projections ranging from single extensions to multiple prominent pseudopods, resulting in an amoeboid morphology. Notably, an unmyelinated nerve process was observed within a cytoplasmic invagination of an individual tumor cell. Conclusions: Taken together, these ultrastructural findings provide novel and previously undescribed morphological evidence of a specific interaction between amoeboid tumor cells and peripheral unmyelinated nerve fibers within the submucosal desmoplastic stroma of early gastric cancer. The biological and clinical significance of this interaction in the early stages of perineural invasion warrants further investigation.

Gastrointestinal Disorders doi: 10.3390/gidisord8010010

Authors: Jianlong Chen Huanlu Xu Yiwen Feng Hongzhang Shen

Chronic atrophic gastritis (CAG) is a key precursor in the Correa cascade leading to gastric cancer and is driven by long-standing Helicobacter pylori infection, autoimmune reactions, environmental exposures, and persistent inflammation. Emerging evidence indicates that mild to moderate atrophy and part of intestinal metaplasia exhibit a degree of reversibility when etiological eradication, microenvironmental optimization, and regenerative stimulation are achieved. This review summarizes recent advances in the pathological basis, evaluation systems, therapeutic mechanisms, and clinical management strategies of CAG. Reversibility is closely related to residual glandular reserve, stem-cell plasticity, and effective mitigation of chronic inflammation. Current assessment tools integrate OLGA/OLGIM histological staging, high-quality endoscopy with AI assistance, and serological biomarkers. Fundamental interventions include early H. pylori eradication, mucosal protective agents, micronutrients, and small-molecule drugs targeting inflammation, oxidative stress, and epithelial regeneration. Novel strategies such as mesenchymal stem cells, exosomes, and focal endoscopic therapies demonstrate regenerative potential in preclinical studies. Traditional Chinese medicine provides multi-target regulation of inflammation, apoptosis, microecology, and stem-cell-related pathways, contributing to histological improvement. Contemporary guidelines emphasize early eradication, risk-stratified surveillance, and comprehensive intervention. Future directions focus on unified evaluation criteria, long-term prospective studies, multimodal combination regimens, and integration of AI-based risk modeling to achieve precise, cancer-preventive CAG management.

Gastrointestinal Disorders doi: 10.3390/gidisord8010009

Authors: Abdulrahman Adel Hawari Shaly Mohammed Aljedaani Hanan Ismail Wasaya Arwa Alsharif Abdulaziz Alsharif Reem Mohammed Rara Aseel Alomari Sara Abdullah Magboul Salma Ismail Daffa

Background/Objectives: Iron-deficiency anemia (IDA) is a common condition in children and is frequently attributed to nutritional causes. However, gastrointestinal (GI) pathology may be present even in the absence of overt GI symptoms. The diagnostic value of endoscopic evaluation in asymptomatic pediatric patients with IDA remains debated. This systematic review aimed to synthesize available evidence on endoscopic and histologic findings in asymptomatic children with IDA and to assess their clinical implications. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines, and the protocol was registered in PROSPERO. MEDLINE (via PubMed) and Scopus were searched for studies involving children and adolescents (0–18 years) with confirmed iron-deficiency anemia and no gastrointestinal symptoms who underwent endoscopic evaluation. Results: Six studies met the inclusion criteria, comprising a total of 455 pediatric patients. Upper GI endoscopy was the most commonly performed procedure. Clinically significant findings were frequently identified, including histologic features consistent with celiac disease, Helicobacter pylori-associated gastritis, and chronic inflammatory gastric changes. Histologic abnormalities were often present despite minimal or absent macroscopic endoscopic findings. The diagnostic yield of endoscopy was particularly high in older children and adolescents and in those with severe or refractory IDA. Conclusions: This systematic review demonstrates that asymptomatic children with IDA may harbor significant GI pathology detectable by endoscopic and histologic evaluation. These findings support the consideration of targeted endoscopic assessments in selected pediatric patients with unexplained or persistent IDA, even in the absence of GI symptoms.

Gastrointestinal Disorders doi: 10.3390/gidisord8010008

Authors: Joanna Michalina Jurek Zuzanna Jakimowicz Runyang Su Kexin Shi Yiqiao Qin

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations.

Gastrointestinal Disorders doi: 10.3390/gidisord8010007

Authors: Teodora Radu Speranța Iacob Ioana Manea Liliana Gheorghe

Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular carcinoma (HCC), but decline with fibrosis progression in end-stage liver disease (ESLD). CCL5 has also been linked to atherosclerosis. This study aimed to evaluate serum CCL5 levels in ESLD patients listed for liver transplantation (LT) and to assess their potential role as markers of cardiovascular (CV) risk and portal hypertension. Methods: We conducted an observational cohort study. Between 2019 and 2022, patients with ESLD evaluated for LT were enrolled. Data on liver pathology, CV risk, and laboratory parameters were collected. Serum CCL5 concentrations were measured using Sigma Aldrich® CCL5 ELISA kits (MilliporeSigma, St. Louis, MO, USA). The database was analyzed with IBM® SPSS® Statistics version 20 (Chicago, IL, USA). Results: Overall, 46 patients were included, 50% with viral hepatitis and 28.3% with alcohol-related liver disease. HCC was present in 37% of cases. The median CV risk scores (CAD_LT = 7, mCAD_LT = 7, CAR_OLT = 18) placed the population at moderate CV risk. Serum CCL5 levels did not vary significantly between viral vs. non-viral cirrhosis (5511.8 vs. 6272.5 pg/mL, p = 0.15) and were not influenced by the presence of HCC (6098.4 vs. 5771.3 pg/mL, p = 0.55). We did not detect a correlation with MELD score (p = 0.21) or CV risk scores (CAD_LT: p = 0.58; mCAD_LT: p = 0.70; CAR_OLT: p = 0.22). Patients with thrombocytopenia (<100,000/µL, 54.3%) or a history of esophageal variceal ligation had lower CCL5 levels (5170.9 vs. 6750.8 pg/mL, p = 0.002 and 4252.0 vs. 6237.5 pg/mL, p = 0.003, respectively). Similarly, patients with a history of previous variceal bleeding and spontaneous bacterial peritonitis (SBP) had lower levels of CCL5 (4373.8 vs. 6119.9 pg/mL, p = 0.02 and 3404.3 vs. 6606.7 pg/mL, p = 0.01, respectively). We found a negative correlation between CCL5 and QTc interval duration (τ = −0.216, p = 0.037), left ventricle size (LV: τ = −0.235, p = 0.027), and pulmonary artery pressure (RV/RA gradient: τ = −0.225, p = 0.03). CCL5 correlated positively with the inflammatory markers C-reactive protein (CRP) (τ = 0.246, p = 0.018) and fibrinogen (r = 0.216, p = 0.04). Conclusions: In liver transplant candidates, serum CCL5 is not associated with cardiovascular risk scores or coronary atherosclerotic burden, but is inversely associated with clinical markers of portal hypertension severity. These findings suggest that CCL5 may serve as a potential non-invasive surrogate marker of portal hypertension rather than a cardiovascular risk biomarker in ESLD.

Gastrointestinal Disorders doi: 10.3390/gidisord8010006

Authors: Raffaele Borghini Francesco Borghini Alessia Spagnuolo Agnese Borghini Giovanni Borghini

Transanal Irrigation (TAI) and Colon Hydrotherapy (CHT) represent emerging therapeutic options that may complement first-line interventions or serve as rescue treatments for chronic constipation and fecal incontinence. Their clinical utility depends on patient characteristics, specific therapeutic goals, device features, and probe type, as well as the procedural setting. This review presents the various pathophysiological contexts in which these techniques can be applied, analyzing their specific characteristics and potential pros and cons. Moreover, these interventions are also considered within a Psycho-Neuro-Endocrino-Immunological (PNEI) framework, given the potential influence of intestinal function and microbiota modulation on the bidirectional communication pathways linking the enteric nervous system, neuroendocrine regulation, immune activity, and global patient well-being. Since there is not yet enough scientific data on this topic, future research should prioritize randomized controlled trials comparing these techniques with other standard treatments (e.g., laxatives or dietary fiber) in defined patient populations. Longitudinal studies will also be essential to clarify long-term safety, potential effects on microbiota, and both risks and benefits. Standardization of technical procedures also remains a critical need, especially regarding professional competencies, operating parameters (e.g., instilled volumes and pressure ranges), and reproducible protocols. Moreover, future investigations should incorporate objective outcome measures, as colonic transit time, stool form and frequency, indices of inflammation or intestinal wall integrity, and changes to microbiome composition. In conclusion, TAI and CHT have the potential to serve as important interventions for the treatment and prevention of chronic constipation and intestinal dysbiosis, as well as their broader systemic correlates, in the setting of bio-integrated medicine.

Gastrointestinal Disorders doi: 10.3390/gidisord8010005

Authors: Agostino Fernicola Murtaja Satea Fahim Kanani Federico Maria Mongardini Jesus Enrique Guarecuco Castillo Alfonso Santangelo Felice Crocetto Armando Calogero José Maria Zepeda Torres Aniello Zoretti Luigi Ricciardelli Michele Santangelo Salvatore Tolone

Background: Esophageal achalasia increasingly affects elderly patients, in whom frailty and comorbidity complicate management and heighten procedural risk. Minimally invasive Heller–Dor myotomy remains the reference surgical treatment, while the advent of robotics has renewed interest in its potential advantages. Whether these refinements translate into meaningful benefits for older adults remains unclear. This gap is clinically significant given the distinct physiological vulnerabilities of older adults. Methods: A narrative review of the literature was conducted to examine current evidence on robotic Heller–Dor myotomy for achalasia, with specific focus on its applicability in elderly and frail patients. Comparative studies between robotic and laparoscopic approaches were analyzed and integrated with available data on achalasia management in older individuals. Results: Robotic Heller–Dor myotomy demonstrates equivalent efficacy to laparoscopic surgery, with reduced mucosal perforation rates, improved ergonomics, and comparable operative times once the learning curve is achieved. However, no published series has specifically analyzed outcomes in geriatric cohorts. Available evidence from laparoscopic studies confirms that surgery remains safe and effective in geriatric patients, suggesting that the precision of robotics could potentially further enhance safety and recovery in this subgroup. Conclusions: Robotic Heller–Dor myotomy represents a promising evolution of minimally invasive therapy for achalasia, potentially aligning technological refinements with the physiological needs of older adults. Prospective studies incorporating frailty assessment, patient-centered outcomes, and cost analyses are required to determine its true value and guide evidence-based use in the aging population.

Gastrointestinal Disorders doi: 10.3390/gidisord8010004

Authors: Angharad Vernon-Roberts Francesca Musto Marina Aloi Nerissa Bowcock Daniel A. Lemberg Andrew S. Day

Background/Objectives: Children with inflammatory bowel disease (IBD) are managed with multi-modal treatment strategies, including non-clinical components such as the development of self-management skills. Assessment tools have been developed to quantify such traits, and parents may be asked to provide proxy reports on behalf of their child. The aim of this study was for child/parent dyads to complete a self-management skills assessment tool [IBD-STAR] to assess the agreement level between reports. Methods: Children aged ≥10 years with IBD, and one parent/caregiver, were recruited from three tertiary care centers in New Zealand, Australia, and Italy [translated version]. IBD-STAR is scored as completing skills independently [score = 2], with help [score = 1], or not at all [score = 0]. Individual agreement was assessed as a proportion of the maximum agreement on items, category agreement as inter-rater reliability using Gwets AC1 coefficient, and aggregate agreement as a Bland–Altman plot and correlations between child/parent percentage scores. Results: Fifty child/parent dyads participated; child mean age of 14.5 years (±2.4), 31 (62%) female, and 31 (62%) had Crohn’s disease and 19 (38%) ulcerative colitis. At the individual level, the mean proportional agreement was 0.70 (±0.15), equating to complete agreement on ≥12 IBD-STAR items. Category agreement was in the range of 44–94% for items, parents were more likely to underestimate self-management skills, and inter-rater reliability ranged from poor to very good for items, and ‘good’ overall. Aggregate agreement showed high correlation between child/parent % scores (R 0.77, p < 0.001, CI 0.63 to 0.87), and 47 (94%) of the pairs had % scores within two standard deviations of each other. No level of agreement was associated with any independent variable. Conclusions: Parental proxy reports of self-management skills using IBD-STAR had acceptable agreement. The trend towards parental underestimation should be considered when child self-report cannot be assessed.

Gastrointestinal Disorders doi: 10.3390/gidisord8010003

Authors: Rayan Alataa Mohamed Farag Priscilla Lajara Hallal Patel Harish

Mushroom coffee—blends of coffee with “functional” mushroom powders—has surged in popularity, yet its hemostatic effects are poorly appreciated in perioperative care. We report a postoperative hemorrhage likely potentiated by a commercial mushroom coffee. A 62-year-old man with HIV, hepatitis C, and insulin-treated diabetes underwent colostomy reversal. On postoperative day 9, he developed brisk bleeding at the colonic anastomosis requiring angiography and embolization. Recurrent hemorrhage prompted a detailed supplement history, revealing daily use of mushroom coffee for two months preoperatively. The product’s labeled ingredients include an organic mushroom blend of cordyceps, lion’s mane (Hericium), reishi (Ganoderma), shiitake, turkey tail, and king trumpet, combined with arabica coffee, MCT oil, and coconut milk. Several constituents—reishi, cordyceps, lion’s mane, and chaga (Inonotus obliquus, used in some mushroom blends)—have published antiplatelet or antithrombotic activity in vitro and/or in vivo. After counseling, the patient discontinued mushroom coffee; no further bleeding occurred, and he recovered without additional intervention. This case highlights a clinically important but underrecognized risk: mushroom-based beverages can exert antiplatelet effects comparable to herbal supplements traditionally flagged in preoperative screening. We recommend that preoperative medication reconciliation explicitly query mushroom coffees and “adaptogenic” blends and that such products be held similarly to other agents with antiplatelet properties. Greater awareness among surgeons, anesthesiologists, and internists is needed as functional foods proliferate. Controlled studies are warranted to quantify bleeding risk from multi-mushroom products and to inform evidence-based perioperative guidance

Gastrointestinal Disorders doi: 10.3390/gidisord8010002

Authors: Natale Calomino Engjell Kelmendi Gianmario Edoardo Poto Ludovico Carbone Matteo Zanchetta Daniele Marrelli

Pigment gallstones represent a heterogeneous group of concretions, classically divided into black and brown types, whose morphology and microstructure offer critical clues about their underlying pathogenesis. Gallstone formation (lithogenesis) is a complex process triggered when the physicochemical equilibrium of bile is disrupted. Background/Objectives: The spicules observed on the surface of certain black pigment gallstones have traditionally been attributed to the branching capacity of cross-linked bilirubin polymers. However, a growing body of experimental and spectroscopic evidence suggests that inorganic calcium salts, particularly calcium carbonate and calcium phosphate, play a central role in the formation of the distinctive spiculated or “coral-like” architecture. Materials and Methods: In our study, we examined a case series of 1350 consecutive patients with gallstone disease, identifying 81 patients who presented with solitary black pigment stones. We systematically explored the association between high calcium content, specifically calcium carbonate, and the occurrence of spiculated morphology. Our analyses demonstrated a robust correlation between an elevated concentration of calcium carbonate and the presence of well-defined spicules. Results: These results support the hypothesis that mineral elements, rather than organic bilirubin polymers, act as crucial determinants of the peculiar crystalline structure observed in a significant subset of pigment stones. Spiculated stones, due to their small size and sharp projections, have a higher likelihood of migrating, increasing the risk of potentially life-threatening complications, such as acute cholangitis and gallstone pancreatitis. Conclusions: Our findings, consistent with recent advanced crystallographic analyses, underscore the importance of considering mineral composition in the diagnosis and management of cholelithiasis. Understanding the factors that drive calcium carbonate precipitation is essential for developing new preventive and therapeutic strategies, aiming to modulate bile chemistry and reduce the risk of calcium-driven lithogenesis.

Gastrointestinal Disorders doi: 10.3390/gidisord8010001

Authors: Jan Finderle Valentin Silvano Schleicher Lou Marie Salome Schleicher Antea Krsek Tamara Braut Lara Baticic

The gut microbiota plays a fundamental role in human physiology by influencing metabolism, immunity, and neuroendocrine communication. Growing evidence suggests that physical exercise modulates gut microbial composition; however, study findings remain inconsistent due to variations in design, training type, and population characteristics. This review summarizes current research on how different forms, intensities, and frequencies of exercise shape the gut microbiota and discusses their implications for athlete health and performance. Moderate and sustained physical activity generally promotes higher microbial diversity, increases short-chain fatty acid (SCFA)-producing bacteria, and enhances gut barrier integrity. Endurance training, particularly long-term, is most consistently associated with beneficial microbial shifts, including increases in Prevotella, Akkermansia, and Faecalibacterium. In contrast, excessive or high-intensity endurance exercise was shown to cause dysbiosis, inflammation, and greater intestinal permeability. Resistance training appears to induce milder changes but was shown to improve mucin synthesis and butyrate production, especially in older adults. Exercise frequency also plays a role, with regular daily training enriching metabolic pathways linked to gut and systemic health. Overall, the impact of exercise on the gut microbiota depends on the type, intensity, and duration of activity. Balanced, moderate exercise combined with a healthy diet emerges as the most effective strategy to enhance microbial diversity, reduce inflammation, and support overall performance and well-being in athletes.

Gastrointestinal Disorders doi: 10.3390/gidisord7040079

Authors: Vlad Alexandru Ionescu Alice Elena Ciontu Gabriel Ianu Ianuș Vlad Buica Ancuța Năstac Ioana-Alexandra Baban Alexandru Barbu Loredana-Crista Tiucă Ninel Iacobus Antonie Gina Gheorghe Camelia Cristina Diaconu

Celiac disease (CeD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals, with a heterogeneous clinical spectrum spanning classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical forms. We synthesize contemporary epidemiology, immunopathogenesis, and the updated 2025 European Society for the Study of Coeliac Disease diagnostic framework. Adaptive responses to deamidated gliadin peptides presented by human leukocyte antigen (HLA)-DQ2/DQ8, together with interleukin-15-driven activation of intraepithelial lymphocytes (IELs), culminate in villous atrophy, crypt hyperplasia, and increased IELs. Serology centered on tissue transglutaminase immunoglobulin A (tTG-IgA) with total immunoglobulin A assessment remains first-line, complemented by standardized duodenal sampling (≥4 distal + 2 bulb biopsies) and selective HLA typing. The guidelines conditionally endorse a no-biopsy pathway for adults <45 years with tTG-IgA ≥10× upper limit of normal confirmed on a second sample, emphasizing shared decision-making and exclusion of red flags. We delineate differential diagnoses (tropical sprue, Crohn’s disease, common variable immunodeficiency, small intestinal bacterial overgrowth) and contrast CeD with non-celiac gluten sensitivity, which lacks villous atrophy, disease-specific serology, and HLA association. Emerging tools (immunohistochemistry, CD3/CD8/γδ IELs, video capsule endoscopy, confocal laser endomicroscopy) and the limitations of salivary/fecal assays are reviewed. Early detection improves quality of life and reduces healthcare utilization. Future directions include artificial intelligence-assisted imaging, molecular immunophenotyping, and non-dietary therapeutics.

Gastrointestinal Disorders doi: 10.3390/gidisord7040078

Authors: Aqsa Shoaib Mariam Shahabi Reyan Hussain Shaikh Mian Muinuddin Jamshed Syed Usama Ashraf Faryal Jahangir Faqeeha Arif Soha Ali Syed Adeel Hassan Waqas Rasheed Tooba Jabeen Fatima Mansoor Suhaira Khalid Abubaker Khan

Background: Inflammatory bowel disease (IBD) is associated with systemic inflammation and potential cardiovascular complications. This meta-analysis evaluates long-term cardiovascular risks in IBD. Methods: Electronic databases were searched for studies examining cardiovascular, cerebrovascular, and thromboembolic risks in IBD. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results: Fifty-three studies comprising 1,406,773 patients were analyzed. IBD was linked to increased risk of ischemic heart disease (aHR 1.25; p = 0.001) myocardial infarction (aHR 1.25; p = 0.01), acute coronary syndrome (aHR 1.43; p < 0.00001), heart failure (aHR 1.24; p < 0.00001), atrial fibrillation (aHR 1.20; p < 0.00001), and stroke (aHR 1.13; p < 0.00001). Elevated risks were also observed for peripheral arterial disease (aHR 1.41; p < 0.00001), diabetes mellitus (aHR 1.40; p < 0.00001), venous thromboembolism (aHR 1.98; p < 0.00001), deep vein thrombosis (aHR 2.85; p = 0.0004), and pulmonary embolism (aHR 1.98; p = 0.03). Importantly, IBD was associated with increased cardiovascular (aHR 1.14; p = 0.03) and all-cause mortality (aHR 1.53; p < 0.00001). Conclusions: IBD patients face higher risk for adverse cardiovascular outcomes, thromboembolic disease, and mortality, necessitating early cardiovascular risk assessment and targeted interventions in this population.

Gastrointestinal Disorders doi: 10.3390/gidisord7040077

Authors: Imran Mohammad Md. Rizwan Ansari Mohammed Sarosh Khan Md. Nadeem Bari Mohammad Azhar Kamal Muhammad Musthafa Poyil

The gut microbiota has emerged as a critical immune–metabolic interface, orchestrating a complex network of interactions that extend well beyond digestion. This highly diverse community of bacteria, viruses, archaea, and eukaryotic microbes modulates host immunometabolism, metabolic reprogramming, and systemic inflammatory responses, thereby shaping human health and disease trajectories. Dysbiosis, or disruption of microbial homeostasis, has been implicated in inflammatory bowel disease, cardiometabolic disorders, neurodegeneration, dermatological conditions, and tumorigenesis. Through the biosynthesis of short-chain fatty acids (SCFAs), bile acid derivatives, tryptophan metabolites, and microbial-derived indoles, the gut microbiota regulates epigenetic programming, barrier integrity, and host–microbe cross-talk, thereby influencing disease onset and progression. In oncology, specific microbial taxa and oncomicrobiotics (cancer-modulating microbes) are increasingly recognized as key determinants of immune checkpoint inhibitor (ICI) responsiveness, chemotherapeutic efficacy, and resistance mechanisms. Microbiota-targeted strategies such as fecal microbiota transplantation (FMT), precision probiotics, prebiotics, synbiotics, and engineered microbial consortia are being explored to recalibrate microbial networks and enhance therapeutic outcomes. At the systems level, the integration of multi-omics platforms (metagenomics, transcriptomics, proteomics, and metabolomics) combined with network analysis and machine learning-based predictive modeling is advancing personalized medicine by linking microbial signatures to clinical phenotypes. Despite remarkable progress, challenges remain, including the standardization of microbiome therapeutics, longitudinal monitoring of host–microbe interactions, and the establishment of robust ethical and regulatory frameworks for clinical translation. Future directions should prioritize understanding the causal mechanisms of microbial metabolites in immunometabolic regulation, exploring microbial niche engineering, and developing precision microbiome editing technologies (CRISPR, synthetic biology).

Gastrointestinal Disorders doi: 10.3390/gidisord7040076

Authors: Franco Roviello Eleonora Andreucci Ludovico Carbone Natale Calomino Stefania Piccioni Lucia Bobbio Riccardo Piagnerelli Andrea Fontani Daniele Marrelli

Background: Indocyanine green (ICG)-guided surgery is an emerging technique to enhance intraoperative visualization of nodes and tumor location. However, there is no uniform protocol regarding the optimal timing, dosage, or injection site for ICG in colorectal cancer surgery. We assess the feasibility of ICG injection at the anorectal junction immediately before surgery to safely identify the inferior mesenteric artery (IMA). Methods: This was a prospective study involving robotic left hemicolectomy or anterior resection of the rectum for primary colorectal cancer in 2024 in a single center. A total of 10–20 mg was injected into the anorectal submucosa at four quadrants circumferentially using an anoscope immediately before robot docking. Results: In this first study, ICG allowed us to identify the IMA in 84.6% of 26 patients (mean age 66.5 years; BMI 26.7 kg/m2), without intraoperative medical and surgical complications. Elevated BMI correlated with failure of IMA detection (r = −0.77, p < 0.001), despite high ICG doses trending toward improved vascular visualization (p = 0.097). A mean of 22 lymph nodes was harvested after ICG injection, with yields unaffected by the quality of IMA visualization. Conclusions: Submucosal injection of ICG is a feasible and easily adoptable option for early identification of the IMA, thereby preventing major vascular injuries, particularly in patients with challenging anatomy. A standardized protocol was implemented to improve reliability.

Gastrointestinal Disorders doi: 10.3390/gidisord7040075

Authors: Michele Montori Daniele Balducci Francesco Martini Marco Valvano Andrea Sorge Maria Eva Argenziano Enrico Palmeri Giuseppe Tarantino Marco Marzioni Antonio Benedetti Luca Maroni

Unresectable extrahepatic cholangiocarcinoma remains a challenging malignancy with limited therapeutic options and poor prognosis. In this setting, effective and durable biliary drainage is crucial to prevent cholangitis, allow timely initiation and maintenance of systemic therapy, and ultimately improve survival. Endobiliary radiofrequency ablation (RFA) has emerged as a promising adjunct to biliary stenting, aimed at delaying tumor ingrowth and prolonging stent patency through localized thermal ablation of malignant tissue. Several studies have reported longer stent patency and, in some cases, improved survival with RFA plus stenting compared with stenting alone. However, the literature remains heterogeneous, and recent high-quality trials have yielded conflicting results, highlighting the need for further standardization of technique and patient selection. This narrative review summarizes the current evidence on the role of endobiliary RFA in unresectable cholangiocarcinoma, with particular emphasis on mechanism of action, endoscopic technique and oncologic outcomes.

Gastrointestinal Disorders doi: 10.3390/gidisord7040074

Authors: Saša Rink Sabina Škrgat Matevž Harlander Polona Mlakar

Background: Hypereosinophilia, defined as a peripheral blood eosinophil count greater than 1.5 × 109/L, can arise from allergic, infectious, autoimmune, or malignant conditions. In solid tumors, it is rare and most often linked to mucin-secreting carcinomas, while on extremely rare occasions, it accompanies signet ring cell carcinoma, a highly aggressive form of adenocarcinoma. Case Presentation: A 64-year-old woman presented with dyspnea and hypereosinophilia (2.9 × 109/L). She was admitted with suspected eosinophilic pneumonia, but extensive testing was inconclusive. After bone marrow biopsy, her condition deteriorated; histology revealed metastatic signet ring cell carcinoma. PET/CT showed skeletal metastases without apparent local recurrence, although colonoscopy could not be performed to definitively rule it out. Retrospective review uncovered a 2 mm rectal polyp with signet ring cell carcinoma (SRCC) removed two years earlier. Peripheral eosinophilia progressively increased from 0.16 × 109/L ten months earlier to a peak of 4.29 × 109/L one month prior to admission. She died four weeks after discharge. Conclusions: To the best of our knowledge, this case represents one of the smallest reported primary colorectal SRCC lesions (2 mm) presenting with disseminated disease and paraneoplastic hypereosinophilia as the first diagnostic clue. Monitoring peripheral blood eosinophil counts may provide additional insight into disease activity and prognosis in solid tumors.

Gastrointestinal Disorders doi: 10.3390/gidisord7040073

Authors: Yeisson Rivero-Moreno Alba Zevallos Samantha Redden-Chirinos Víctor Bolivar-Marín Dayanna Silva-Martinez Aman Goyal Arturo Estrada Rebeca Domínguez-Profeta Diego Camacho Sjaak Pouwels Wah Yang Luigi Marano Adel Abou-Mrad Rodolfo J. Oviedo

In the original publication [...]

Gastrointestinal Disorders doi: 10.3390/gidisord7040072

Authors: Alireza FakhriRavari Minh Hien Chau Nguyen

Akkermansia muciniphila—a mucus-resident commensal—has emerged as a promising target at the interface of metabolism, barrier function, and immunity. Observational human studies link higher intestinal abundance of A. muciniphila with healthier adiposity and glycemic profiles, while preclinical experiments demonstrate causal benefits on adiposity, insulin resistance, gut-barrier integrity, and inflammatory tone. These effects are attributed to mucus-layer reinforcement, reduced intestinal permeability and endotoxemia, production of short-chain fatty acids, and host signaling by defined bacterial components. In a randomized proof-of-concept trial in overweight/obese insulin-resistant adults, pasteurized A. muciniphila was safe and well-tolerated and improved insulin sensitivity and total cholesterol versus placebo; live cells showed directionally favorable but non-significant trends. A separate multicenter randomized trial of a five-strain consortium that included A. muciniphila improved post-prandial glucose and HbA1c in type 2 diabetes, supporting translational potential while underscoring the need for strain-resolved studies. Evidence for liver and cardiovascular benefits is strong in animals (e.g., MASLD and atherosclerosis models) but remains preliminary in humans. Inter-individual response heterogeneity—potentially influenced by baseline Akkermansia levels and gut-barrier status—highlights the value of personalized, microbiome-guided approaches. Larger, longer clinical studies are now warranted to define optimal dosing and formulation (live vs. pasteurized), durability, safety across populations, and impacts on hard outcomes (clinically meaningful weight change, glycemic endpoints, and cardiometabolic events). Overall, A. muciniphila represents a promising microbial adjunct for metabolic health with a plausible path from postbiotic concepts to clinical application, pending confirmatory trials.

Gastrointestinal Disorders doi: 10.3390/gidisord7040071

Authors: Marcia Baiocchi Amaral Danielle Elisiane Lorenzini Ana Letícia Missio de Oliveira Anthony John Onwuegbuzie Letícia Flores Trindade Michelle Mariah Malkiewiez Darlisom Sousa Ferreira Luana Amaral Alpirez Adriane Cristina Bernat Kolankiewicz

Objective: To identify facilitating and hindering factors for implementing a care transition strategy for adult patients undergoing elective colorectal cancer surgery, within a primary health care (PHC) context, addressing gaps in the literature on implementation challenges and contextual factors influencing such strategies. Methods: This complex mixed methods study combined a randomized clinical trial (RCT) and a qualitative component within an Implementation Research framework. The RCT enrolled adult patients with colorectal cancer, while the qualitative phase included a multilevel sample of participants. Iterative data integration occurred throughout the planning, implementation, and evaluation phases. The intervention was assessed using the RE-AIM (Reach, Efficacy, Adoption, Implementation, Maintenance) framework. Statistical analyses were conducted using IBM SPSS Statistics 22.0, applying descriptive and inferential methods. Results: Our findings revealed that the adoption of the intervention was satisfactory; however, Reach, Efficacy, and Implementation were not achieved. Facilitating factors included recognition of the potential of the care transition strategy to improve patient outcomes, and the intervention’s feasibility, replicability, and low cost. The main hindering factors identified included poor communication between care levels, inadequate material resources, and high workload. Integration of qualitative insights helped explain the limited quantitative impact, highlighting contextual challenges during the COVID-19 pandemic. Conclusions: The care transition strategy was well accepted by participants and health care providers, demonstrating potential to strengthen continuity of care between hospital and PHC services. Nonetheless, significant organizational and resource-related barriers hindered its effectiveness. Future studies are required to adapt transitional care models to overcome communication gaps, optimize resource allocation, and enhance implementation in similar settings.

Gastrointestinal Disorders doi: 10.3390/gidisord7040070

Authors: Anna Laura Maiozzi Filomena Botta Silvia Maccioni Livia Stanga Lucretia Marin-Bancila Ciprian Ilie Rosca Anca Dinu Abhinav Sharma Nilima Rajpal Kundnani

Background: Varicose veins (VVs) are an overlying manifestation of chronic venous disease, commonly occurring in the lower extremities. While typically linked to primary venous insufficiency, they can occasionally be secondary to systemic disease, e.g., malignancies, by various mechanisms such as tumor compression, hypercoagulability, and paraneoplastic syndromes. Bilateral varicose veins, as a presenting symptom of gastric cancer, are extremely rare and poorly documented. Materials and Methods: A comprehensive literature search was conducted to identify reports and studies linking varicose veins and malignancies, with particular focus on gastric cancer. The search was performed using the PubMed, Scopus, and Web of Science databases covering the last 13 years. Results: Literature Review: A review of the literature in the past decade identified publications, mostly case reports, describing associations between varicose-like venous changes and malignancies such as gastric, pancreatic, hepatic, and small-bowel tumors. The predominant mechanisms reported were inferior vena cava obstruction, tumor-related thrombosis, and paraneoplastic migratory superficial thrombophlebitis (Trousseau’s syndrome). Only a few cases involved gastric cancer as the primary site, with venous changes often being the first clinical sign. There is limited experience with gastric cancer that presents alongside bilateral collateral or varicose veins initially. Apart from the various reports having malignancies and varicose veins we also describe the case of a 50-year-old man who had extended history of bilateral lower-limb varicose veins. Severe, unexplained anaemia without obvious bleeding was discovered during examination. A biopsy verified a gastric adenocarcinoma, while upper gastrointestinal endoscopy revealed an ulcerated mass on the stomach’s greater curvature. Peritoneal dissemination was discovered with additional staging. A palliative subtotal gastrectomy was carried out because of the patient’s ongoing anaemia and suspected chronic bleeding caused by the tumour. The venous symptoms preceded any gastrointestinal issues. Conclusions: Although uncommon, malignancy should be considered in the differential diagnosis for atypical or rapidly progressing bilateral varicose veins, especially when accompanied by systemic symptoms or lab results such as unexplained anemia. Increased suspicion may lead to earlier cancer detection in some patients.

Gastrointestinal Disorders doi: 10.3390/gidisord7040069

Authors: Sergiu Dorin Matei Ramona Nicoleta Suciu Tiberia Ilias Cristian Hocopan Ovidiu Frățilă

This review conducts a bibliometric analysis of scientific literature on antibiotic resistance in Helicobacter pylori (H. Pylori), aiming to map scientific production, identify trends and key themes, analyze collaboration models, and highlight research gaps to inform research priorities and guide public health policies, amidst the growing challenge of multidrug resistance affecting treatment success. Background/Objectives: H. Pylori infection is usually contracted during childhood and often becomes chronic and asymptomatic in 80–90% of cases. Eradication requires complex treatments involving proton pump inhibitors and multiple antibiotics, but success rates have declined due to increased antibiotic resistance caused by genetic mutations, efflux mechanisms, altered membrane permeability, and biofilm formation. Reports indicate an alarming increase in multidrug resistance, affecting the effectiveness of treatments. Methods: The bibliometric analysis was performed using the Web of Science Core Collection (WoS) database, which provides comprehensive bibliographic data. Filters were applied for articles in English, reducing the set to 39,879 papers. The analysis was performed using the VOSviewer program (v1.6.20) to visualize co-author networks, citations, and keyword co-occurrence, and Microsoft Excel for processing and organization. Results: Editorial Trends: Over the last decade (2016–2025), interest in this topic has increased, with over 4000 publications annually in 2020, although a slight decline was observed in 2023. Leading Contributors: China is the most prolific author, followed by the USA and Japan. Cited Articles and Key Publications: Articles by prominent authors are frequently cited in 2022 and 2023, indicating their high relevance. Bibliographic Coupling Analysis: This revealed three main thematic clusters centered around research by specific authors. Keyword Analysis: A total of 57,462 terms were identified, of which 5292 appeared at least five times; “Helicobacter pylori” was the most frequent, followed by “infection” and “eradication.” Visualized terms highlight central areas of interest, such as “risk,” “cancer,” and “resistance”. Conclusions: This bibliometric analysis underscores a rising research focus on H. pylori antibiotic resistance, with recent publications providing essential clinical guidelines and epidemiological insights into the infection’s global impact. China leads in contributions, followed by the US and Japan. Significant articles by notable authors received many citations, emphasizing their significance.

Gastrointestinal Disorders doi: 10.3390/gidisord7040068

Authors: Samia Chatterjee Ananda Vardhan Hebbani Khajamohiddin Syed

The gut microbiota greatly influences host physiology, including immune regulation, metabolic balance, and brain health. Aging is associated with alterations in the gut microbiome, including reduced microbial diversity and increased pro-inflammatory bacteria, which are linked to age-related decline and chronic diseases. This review examines the impact of the gut microbiota on key indicators of aging, including cellular senescence, mitochondrial dysfunction, alterations in gene expression, and immune system modifications. It also examines microbiome-related diseases associated with aging, including neurodegeneration, cardiovascular issues, metabolic syndrome, and frailty. Additionally, it highlights evidence-based methods to restore a youthful microbial profile. New findings suggest that certain microbial substances, including short-chain fatty acids, urolithins, and bile acids, play a role in regulating inflammation, maintaining barrier integrity, and influencing metabolism. Age-related diseases are often associated with molecular pathways driven by an imbalance in the gut microbiome. Various intervention strategies, from dietary changes and probiotics to personalized nutrition and fecal microbiota transplantation, have shown promise in reversing signs of microbial aging and improving health outcomes in both lab and human studies. Overall, the gut microbiome serves as both a marker and a regulator of healthy aging. Treatments that restore microbial balance offer hopeful ways to extend healthy living. Future studies should focus on developing long-term, multifaceted, and personalized methods to identify causal pathways and enhance microbiota-based strategies for various aging populations.

Gastrointestinal Disorders doi: 10.3390/gidisord7040067

Authors: Vaios Svolos Anastasia Triantafyllou Georgios Charmantzis Maria Delliou Maria-Nikoletta Nanti Melina Moustaka Eleni Bakasieta Evanthia Balafa Dimitra Eleftheria Strongylou Odysseas Androutsos

Background/Objectives: Despite the growing understanding of the relationship between the genome and nutrition, clearly defined and evidence-based clinical guidelines remain insufficient. The objective of this review was to identify and compile all available European guidelines related to the impact of genetic predisposition on nutritional recommendations in the field of gastroenterology. Methods: A review of guidelines and position papers issued by four European organisations [the European Crohn’s and Colitis Organisation (ECCO), the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), the European Society for Clinical Nutrition and Metabolism (ESPEN), and United European Gastroenterology (UEG)] was conducted for the past ten years. Results: Out of 5196 recommendations and statements extracted from 124 manuscripts, only 13 highlighted a link between genetic predisposition and dietary factors in clinical gastroenterology. From the available guidelines, there is no clear trend indicating an increased focus on genetic background and its association with nutrition in recent years. Conclusions: There is a critical opportunity for European organisations to develop an evidence-based information framework, guided by clinical protocols, in order to integrate the large volume of genetic data into clinical practice and personalised care of individuals with gastrointestinal disorders.

Gastrointestinal Disorders doi: 10.3390/gidisord7040066

Authors: Vlad Buică Ancuța Năstac Gina Gheorghe Teodor Florin Georgescu Camelia Cristina Diaconu Vlad Alexandru Ionescu

Background: Colorectal cancer (CRC) represents one of the leading causes of cancer-related morbidity and mortality globally. Although national screening programs in Europe and the United States have demonstrated success in reducing incidence and death rates among populations aged 50 and above, a concerning increase in early-onset colorectal cancer (EOCRC), defined as diagnosis before age 50, has emerged. Methods: This paper is a narrative literature review comparing American and European CRC screening guidelines. A comprehensive search was conducted using the PubMed database with emphasis on publications from the past ten years. Results: The United States has adapted more swiftly to EOCRC trends by lowering the recommended screening age to 45, supported by modeling studies showing life-years gained and improved cost-effectiveness. In contrast, European programs remain largely organized and cost-efficient but predominantly initiate screening at age 50, potentially missing high-risk younger adults. EOCRC appears to demonstrate unique molecular and pathological features compared to late-onset CRC. Participation and adherence to screening also vary significantly between regions and modalities, with colonoscopy remaining the gold standard but less scalable than fecal immunochemical tests. Conclusions: The rising incidence of EOCRC calls for a reassessment of CRC screening policies. While the European model emphasizes equity and structure, its slower responsiveness to epidemiological changes may lead to late detection in younger cohorts. The American model’s earlier screening age addresses emerging trends but faces challenges in implementation equity. A hybrid approach may provide the optimal management, balancing public health benefit with system sustainability.

Gastrointestinal Disorders doi: 10.3390/gidisord7040065

Authors: Pedro Mesquita Rolando Pinho João Carlos Silva Catarina Costa Pedro Teixeira Rita Ferreira Liliana Santos Ana Ponte Teresa Freitas

Background/Objectives: Superficial gastric neoplasms, including dysplasia and early adenocarcinoma, are increasingly managed by endoscopic submucosal dissection (ESD). Preoperative assessment relies on endoscopic forceps biopsy (EFB), despite its limited ability to predict final histology. The diagnostic value of repeat biopsy, the influence of the endoscopy setting where biopsies were taken, and the clinical relevance of histologic discrepancies remain incompletely defined. Methods: We conducted a retrospective, single-center study of 270 superficial gastric lesions resected by ESD between 2015 and 2024. Histologic concordance between EFB and ESD was evaluated, including comparisons between initial and repeated biopsies, and between community- and hospital-based settings. Multivariable models identified predictors of histologic discrepancy and assessed the impact of underestimation on curative resection. The association between biopsy repetition and submucosal fibrosis was also explored. Results: Histologic concordance between EFB and ESD was 54.1%, with underestimation in 41.1% and severe underestimation in 8.9%. Repeat biopsy improved concordance from 39.3% to 60.7% (p = 0.007) and increased adenocarcinoma sensitivity from 12.5% to 56.3%, without increasing submucosal fibrosis. Hospital-based biopsies outperformed community-based ones across all diagnostic metrics. In multivariable analysis, older age and larger lesion size were independent predictors of discrepancy. Histologic underestimation was independently associated with a lower likelihood of curative resection (OR = 0.148; p = 0.003), although only six lesions ultimately exceeded formal ESD criteria due to undetected high-risk features. Conclusions: EFB frequently underestimates histological severity in superficial gastric neoplasia. Repeat biopsy and centralized evaluation significantly improve diagnostic accuracy without increasing procedural risk. However, the role of biopsy lies primarily in excluding high-risk features rather than providing definitive staging. In this context, ESD serves not only as curative therapy but also as a key diagnostic step for accurate staging and treatment planning.

Gastrointestinal Disorders doi: 10.3390/gidisord7040064

Authors: Agostino Fernicola Armando Calogero Felice Crocetto Giacomo Capece Guido Bocchino Michele Santangelo

Background: Achalasia is a rare primary esophageal motility disorder characterized by impaired lower esophageal sphincter relaxation and progressive loss of peristalsis. Although its pathogenesis remains incompletely understood, autoimmune mechanisms have been repeatedly proposed. Thyroid disorders, particularly autoimmune thyroiditis and Graves’ disease, have been reported as frequent comorbidities, suggesting a shared autoimmune background. Methods: We conducted a narrative review of PubMed, Scopus, and Web of Science from January 2005 to August 2025. Eligible studies included observational cohorts, case–control analyses, and case reports describing thyroid disease in achalasia. Mechanistic and immunological studies relevant to thyroid autoimmunity were also considered. Data were synthesized narratively and summarized in tables and figures. Results: Despite heterogeneity, evidence consistently indicates an increased prevalence of thyroid disease in achalasia. Early reports described dysfunction in up to one quarter of cases, while Romero-Hernández et al. demonstrated a threefold higher risk of autoimmune thyroid disease. Multicenter data confirmed thyroid autoimmunity in about one fifth of patients. Although thyroid disease did not alter short-term procedural outcomes, unrecognized dysfunction may complicate postoperative evaluation. Immunological findings, including human leukocyte antigen (HLA) susceptibility and lymphocytic infiltration of myenteric plexus, further support a shared autoimmune predisposition. Conclusions: Thyroid disorders, particularly autoimmune hypothyroidism, are more common in achalasia than in the general population. Although the evidence remains limited, the consistent signal suggests a non-random association. Early recognition may improve patient management, while prospective multicenter studies are needed to clarify causality and to determine whether achalasia should be considered part of a broader autoimmune spectrum.

Gastrointestinal Disorders doi: 10.3390/gidisord7040063

Authors: Sjaak Pouwels Alex Mwangi Michail Koutentakis Moises Mendoza Sanskruti Rathod Santosh Parajuli Saurabh Singhal Uresha Lakshani Wah Yang Kahei Au Safwan Taha

Background: Over the years, surgical techniques have evolved, resulting in an abundance of available procedures in the armamentarium of metabolic and bariatric surgeons, and the technology has also advanced in a similar way. Significant steps have been made in stapling technology especially, introducing artificial intelligence (AI) in optimizing this technology for better treatment outcomes. The introduction of AI in stapling technology showed a decrease in potential stapling complications not only in MBS, but also in other (surgical) specialties. Areas Covered: This review will cover the general principles of stapling in surgery, but with an emphasis on both the technical and anatomical considerations. We will also discuss the mechanisms of staplers and potential safety hazards. Finally, we will focus on how AI is integrated in stapling technology, potential pros and cons, and areas for future development of stapling technology and the integration of AI. Conclusions: In metabolic and bariatric surgery, stapling is a technical procedure that requires a comprehensive understanding of the anatomical and physiological characteristics of the target tissue. Variability in tissue thickness, vascularity, elasticity, and mechanical load, compounded by patient-specific factors and intraoperative dynamics, demands constant vigilance and adaptability from the surgeon. The integration of AI and digital technologies offers potential improvements in refining this process. By providing real-time feedback on tissue properties and supporting intraoperative decision-making, these tools can assist surgeons in optimizing staple-line integrity and minimizing complications. The ongoing combination of surgical expertise with intelligent technology may contribute to advancing precision stapling in metabolic and bariatric surgery.

Gastrointestinal Disorders doi: 10.3390/gidisord7040062

Authors: Michael Enwere Edward Irobi Adamu Onu Emmanuel Davies Gbadebo Ogungbade Omowunmi Omoniwa Charles Omale Mercy Neufeld Victoria Chime Ada Ezeogu Dung-Gwom Pam Stephen Terkaa Atim Laurens Holmes

Background: The human gut microbiome—a diverse ecosystem of trillions of microorganisms—plays an essential role in metabolic, immune, and neurological regulation. However, modern lifestyle factors such as antibiotic overuse, cesarean delivery, reduced breastfeeding, processed and high-sodium diets, alcohol intake, smoking, and exposure to environmental toxins (e.g., glyphosate) significantly reduce microbial diversity. Loss of keystone species like Bifidobacterium infantis (B. infantis) and Lactobacillus reuteri (L. reuteri) contributes to gut dysbiosis, which has been implicated in chronic metabolic, autoimmune, cardiovascular, and neurodegenerative conditions. Materials and Methods: This Qualitative Systematic Review (QualSR) synthesized data from over 547 studies involving human participants and standardized microbiome analysis techniques, including 16S rRNA sequencing and metagenomics. Studies were reviewed for microbial composition, immune and metabolic biomarkers, and clinical outcomes related to microbiome restoration strategies. Results: Multiple cohort studies have consistently reported a 40–60% reduction in microbial diversity among Western populations compared to traditional societies, particularly affecting short-chain fatty acid (SCFA)-producing bacteria. Supplementation with B. infantis is associated with a significant reduction in systemic inflammation—including a 50% decrease in C-reactive protein (CRP) and reduced tumor necrosis factor-alpha (TNF-α) levels—alongside increases in regulatory T cells and anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-β1). L. reuteri demonstrates immunomodulatory and neurobehavioral benefits in preclinical models, while both probiotics enhance epithelial barrier integrity in a strain- and context-specific manner. In murine colitis, B. infantis increases ZO-1 expression by ~35%, and L. reuteri improves occludin and claudin-1 localization, suggesting that keystone restoration strengthens barrier function through tight-junction modulation. Conclusions: Together, these findings support keystone species restoration with B. infantis and L. reuteri as a promising adjunctive strategy to reduce systemic inflammation, reinforce gut barrier integrity, and modulate gut–brain axis (GBA) signaling, indicating translational potential in metabolic and neuroimmune disorders. Future research should emphasize personalized microbiome profiling, long-term outcomes, and transgenerational effects of early-life microbial disruption.

Gastrointestinal Disorders doi: 10.3390/gidisord7040061

Authors: Sarah Hoeck Thuy Ngan Tran

Background: Timely diagnostic colonoscopy (DC) after a positive fecal immunochemical test (FIT+) is essential for effective colorectal cancer (CRC) screening. In Flanders, 16% of FIT+ participants in 2022 had no DC in the 24 months following the FIT+ result. This study evaluated the impact of a failsafe reminder letter—sent 24 months after a FIT+ result without registered correct follow-up—on DC completion and identified factors associated with correct follow-up. Methods: We included all individuals in the Flemish CRC screening program who had a FIT+ result between 2017 and 2019 and later received a failsafe letter due to lacking correct follow-up within 24 months. Correct follow-up was defined as a complete colonoscopy, virtual colonoscopy, or cancer diagnosis. We calculated the proportion of individuals completing correct follow-up within 24 months of the letter. Multivariable logistic regression examined associations between odds of correct follow-up and individual and area-level characteristics. Results: Of the 7175 individuals who received a failsafe letter, 16.1% completed correct follow-up within 24 months. Individuals aged 70–74 had significantly lower odds of correct follow-up than those aged 60–64 (odd ratio (OR) = 0.59; 95% confidence interval (CI): 0.48–0.72). Living in areas with a higher proportion of young adults in higher education was associated with higher odds of correct follow-up (OR = 1.041; 95% CI: 1.002–1.080). Conclusions: The failsafe letter modestly improved follow-up among a hard-to-reach group. Older age and lower area-level educational attainment were linked to reduced odds of correct follow-up. Targeted efforts are needed to improve DC completion in these subgroups.

Gastrointestinal Disorders doi: 10.3390/gidisord7040060

Authors: Cesare Tosetti Alessandra Belvedere Massimo Berardino Luciano Bertolusso Rosanna Cantarini Francesco Carofiglio Floriana Di Bella Daniele Franchi Andrea Furnari Alessandro Marturano Tecla Mastronuzzi Roberto Barone Giuseppe Disclafani Silvia Dubini Marco Prastaro Riccardo Scoglio Alessandro Rossi Ignazio Grattagliano

Background/Objectives: The role of the intestinal microbiota in gastroenterological diseases has gained increasing relevance in general medicine. The study aimed to evaluate the knowledge and awareness of Italian general practitioners regarding gut microbiota, as well as the clinical applications of probiotics and prebiotics. Methods: The survey research involved 457 Italian general practitioners, who anonymously filled an online structured questionnaire. Results: Most respondents identified antibiotics, diet, gastrointestinal infections, and stress as factors that can modulate the gut microbiota, while a smaller proportion recognized the role of physical activity. A comparable number acknowledged the influence of obesity, smoking, and immunosuppressant drugs. Although most participants correctly defined probiotics, the concept of prebiotics was less widely understood. Probiotics were primarily prescribed for irritable bowel syndrome, suspected dysbiosis, or during antibiotic therapy, and only a portion of physicians reported routinely combining them with prebiotics. The selection of probiotic strains was mainly based on personal experience, while fecal microbiota analysis was seldom used in clinical practice. Conclusions: These findings provide an updated snapshot of current knowledge and practices regarding the microbiota in Italian general medicine and highlight critical gaps, particularly in the understanding of prebiotics and less recognized modulatory factors.

Gastrointestinal Disorders doi: 10.3390/gidisord7040059

Authors: Giuseppe Blando Arianna Toscano Anna Viola Laura Patanè Sabrina Verachtert Carmela Morace Giovanni Squadrito Giuseppe Mandraffino Angela Alibrandi Walter Fries Giuseppe Costantino

Background: Patients with ulcerative colitis (UC) and Crohn’s disease (CD) have an increased cardiovascular risk (CVR). The aim of the present study was to stratify the CVR of patients with UC and CD according to the most recent guidelines via carotid ultrasound (US) to detect subclinical atherosclerotic disease. Methods: Demographic and disease-related data of consecutive patients with IBD were prospectively collected along with information on blood pressure, body mass index, lipid profile, and concomitant medications. CVR was stratified at inclusion according to the most recent version of Systematic Coronary Risk Evaluation 2 (SCORE2) and re-stratified after carotid US when subclinical atherosclerotic disease was detected. Results: A total of 166 patients aged ≥ 40 years with IBD were included. Before carotid US evaluation, 43.4% of patients with IBD were at moderate risk, 40.3% at high risk, and 16.3% at very high risk. With carotid US, subclinical atherosclerosis was diagnosed in 48% of patients, leading to CVR re-stratification from moderate to high in 18% of patients and from high to very high in 4% of patients. The only predictive factor for re-stratification was failure with more than two biologics (p = 0.047; OR 2.187, 95% CI: 1.004–4.741). Conclusions: CVR is considerably prevalent in patients with IBD. Carotid US may help to re-classify CVR and should be considered as a risk modifier in patients at intermediate risk. Screening for CVD risk factors should be recommended in IBD.

Gastrointestinal Disorders doi: 10.3390/gidisord7030058

Authors: Charlotte Silvestre Julien Antih Baptiste Perrier Lucas Fabrega Florence Bichon Patrick Poucheret

Background: Inflammatory bowel disease (IBD) represents significant health challenges on a global scale, primarily encompassing Crohn’s disease and ulcerative colitis. These conditions are characterized by cycles of relapse and remission. Current treatment options, including conventional chemical therapies and biologics such as anti-Tumor Necrosis Factor α (anti-TNFα), anti-integrin, anti-interleukins 12 (IL-12) or 23 (IL-23) agents, Janus Kinase (JAK) inhibitors, and sphingosine-1-phosphate (S1p) receptor modulators, provide symptomatic relief but do not offer a cure. These therapies are associated with both localized and systemic adverse effects, necessitating careful patient monitoring. Probiotics and prebiotics have been investigated for their potential to enhance gut microbiota diversity, which may assist in managing IBD. However, their efficacy in preventing disease flares remains limited. Recent advances in drug delivery systems, including pressure-based and pH-sensitive formulations, aim at enhancing localized treatment efficacy while minimizing adverse effects. Additionally, a pharmacogenomic approach could improve treatment personalization, optimize therapeutic outcomes, and enhance patients’ quality of life by addressing mental health needs and ensuring comprehensive follow-up care. Despite increased awareness and education among healthcare providers regarding IBD, there is still a need for clearer guidance on available treatment options. Objective: This review aims at providing deeper understanding of IBD management strategies, ultimately striving to improve the quality of care for individuals affected by this disease.

Gastrointestinal Disorders doi: 10.3390/gidisord7030057

Authors: Mina Guirgis Michael Sala Ranesh Palan Han Beh Sharie Apikatoa Omar Zubair Paul Moroz

Introduction: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal early chemotherapy (HIPEC) has gained traction as a viable treatment option for patients with colorectal cancer peritoneal metastases (CRC-PM). Refinements have been made to patient selection and choice of HIPEC agent. We report outcomes with respect to peritoneal disease volume (peritoneal cancer index, PCI) and HIPEC agent for patients treated at the Western Australian Peritonectomy Service (WAPS) in the ten years from December 2013. Methods: A retrospective statistical analysis assessing the factors affecting survival outcomes of patients with CRC-PM who received CRS with HIPEC was performed, with particular focus on disease volume and HIPEC agent (Mitomycin C and Oxaliplatin). Results: 89 patients with CRC-PM were treated with CRS-HIPEC with a median overall survival (OS) of 58 months, 5-year OS of 48% and disease-free survival (DFS) of 20%. PCI <10 (n = 57) had OS and DFS of 60% and 29%, compared to 23% and 0% for PCI ≥ 10 (n = 32); HR = 2.9, p = 0.002. Three-year OS and DFS for treatment with Oxaliplatin HIPEC (n = 40) were 61% and 41%, which was not significantly different from 71% and 34% with Mitomycin C HIPEC (n = 49); HR = 1.5, p = 0.3. Conclusions: CRS/HIPEC should continue to evolve into the standard of care for carefully selected patients with CRC-PM as almost half of all selected patients survive to at least five years; in particular patients with low-volume disease (PCI < 10) can benefit greatly with a 60% five-year OS and 29% five-year DFS with low morbidity. The choice of HIPEC agent, Oxaliplatin or Mitomycin C, remains uncertain.

Gastrointestinal Disorders doi: 10.3390/gidisord7030056

Authors: Laith Alrubaiy Ahmed El-Sayed Diya Kapila Abisoye Akintimehin Papakas Wijeyendram

Colorectal cancer (CRC) is a significant public health issue, representing one of the greatest causes of both cancer diagnosis and mortality globally. While the incidence is highest in high-income countries, it is rising across the world, including in the Middle East and North Africa (MENA) region. Many countries have implemented national screening programmes to reduce the burden of CRC, utilising mostly stool tests and colonoscopy, but this has yet to occur across most MENA countries. Uptake of screening opportunities is generally poor. System-level barriers to establishing screening programmes include cost constraints and limited screening infrastructure. Patient-level barriers include embarrassment, fear of a cancer diagnosis, and limited awareness/education. Screening programmes across the MENA region would likely reduce the CRC incidence. These barriers must be overcome through patient education and government action to ensure appropriate patient uptake. This study aims to examine CRC screening practices across MENA, identify key barriers, and propose solutions for sustainable CRC management in the region, through a narrative review and expert input from the Middle East and North Africa Colorectal Cancer (MENA-CRC) Screening and Prevention collaborators.

Gastrointestinal Disorders doi: 10.3390/gidisord7030055

Authors: Mina Guirgis Parveen Kumar Jason Laurens Brijesh Madhok

Background: Spontaneous intragastric balloon hyperinflation (SIBH) is a rare and concerning complication of intragastric balloons (IGBs). The mechanisms underlying SIBH remain unclear. This systematic review aims to synthesise the current evidence regarding the clinical presentation, management, complications, and hypothesised aetiologies of SIBH. Methods: A comprehensive literature search was conducted using PubMed, EMBASE, MEDLINE, and Ebsco databases. Studies reporting on cases of SIBH were identified and reviewed. Data points were extracted on patient presentation, management strategies, complications, outcomes, and proposed mechanisms. Results: Eighteen publications describing 29 patients with SIBH were included. The most common clinical presentation was gastric outlet obstruction (86%). Emergency endoscopy was required in 96% of cases, with balloon removal performed in 82%. Reported complications included acute pancreatitis and mucosal erosions; however, neither long-term morbidity nor mortality was observed. Microbial colonisation was hypothesised as the underlying cause in 62% of publications, supported by culture findings from balloon contents in 90% of cases, most commonly isolating gas-producing organisms such as Candida (80%) and anaerobic bacteria (40%). Conclusions: SIBH most frequently presents with gastric outlet obstruction and typically necessitates emergency endoscopic intervention. Gas-producing microbial colonisation of the balloon is the predominant hypothesised aetiology. Preventive strategies targeting microbial colonisation may be crucial in reducing the incidence of SIBH.

Gastrointestinal Disorders doi: 10.3390/gidisord7030054

Authors: Elizaveta Makarova Tatyana Gabrusskaya Ekaterina Kharitonova Natalia Ulanova Natalia Volkova Maria Revnova Dmitri Ivanov Mikhail Kostik

Background: Children with inflammatory bowel disease (IBD) are at heightened risk for vaccine-preventable infections because of underlying immune dysregulation and long-term immunosuppressive therapy. Despite published guidelines affirming vaccine safety, real-world coverage remains suboptimal. It is a pilot, single-country survey designed to explore baseline knowledge and practices regarding vaccination in paediatric IBD within a specific local healthcare context. Objective: The objective of this study is to evaluate the knowledge, attitudes, and practices of paediatric gastroenterologists (PGs) regarding the immunisation of children with IBD. Methods: We conducted an exploratory pilot, cross-sectional survey of paediatric gastroenterologists in Russia, focusing on immunisation knowledge and practical barriers in routine care. A cross-sectional, anonymous online survey was distributed to PGs nationwide between January 2022 and April 2022. The online questionnaire explored demographic characteristics, awareness of international recommendations, perceptions of vaccine safety at various disease and treatment stages, and routine vaccination practices. Responses were analysed with non-parametric statistics (α = 0.05). In a parallel prospective cohort, the vaccination certificates of 98 paediatric IBD patients (January 2022–April 2023) were audited to quantify real-world coverage. Results: Fifty-one PGs completed the survey. Forty-one per cent agreed that vaccines do not provoke IBD flares, while 17.6% considered live vaccines acceptable during immunosuppressive remission. Nearly one-third (32%) did not personally oversee immunisation, and 18% occasionally discouraged vaccination during therapy. Only 35.3% deemed baseline serology essential before starting immunosuppression; 46.5% supported antibody checks immediately prior to vaccination. The certificate audit revealed a full schedule completion rate of 66.3% for measles–mumps–rubella and 74.2% for hepatitis B, contrasting with parental reports of 82.3% complete coverage. Conclusions: Knowledge gaps, limited guideline awareness, and parental concerns contribute to suboptimal vaccination of paediatric IBD patients. Targeted educational initiatives, clearer shared-care pathways, and routine certificate audits are needed to close the coverage gap and reduce infection-related morbidity. Findings are hypothesis-generating and reflect local practice; as a pilot study, results should be interpreted with caution and may not generalise beyond similar settings.

Gastrointestinal Disorders doi: 10.3390/gidisord7030053

Authors: Tareq Alsaleh Prachi Mann John George

Background: Magnetically controlled capsule endoscopy (MCCE) has shown promise in upper gastrointestinal evaluation and is a potentially less invasive alternative to esophagogastroduodenoscopy (EGD). We performed a systematic review and meta-analysis aiming to measure its diagnostic performance compared to EGD for esophageal varices. Methods: Our protocol was registered on PROSPERO (CRD420251081967). A systematic search of multiple databases was conducted through July 2025 for studies assessing the diagnostic performance of MCCE compared to EGD for EV. The primary outcomes were sensitivity and specificity. Secondary outcomes included the area under the curve (AUC), likelihood ratios, diagnostic odds ratio, and safety. Pooled effect estimates were calculated using a random effects model and expressed as proportions with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic. Results: Five prospective studies with 795 patients (68.8% male, mean age of 55.1) were included. The pooled sensitivity and specificity were 87.1% (95% CI: 68.5–95.4) and 95.2% (95% CI: 88.4–98.1), respectively, with an AUC of 0.97. Following subgroup analysis of cirrhotic patients, pooled sensitivity and specificity were 96.0% (95% CI: 93.6–97.5; I2 = 43%) and 95.2% (95% CI: 84.2–98.6; I2 = 88.4%), respectively. Furthermore, MCCE use with detachable strings increased sensitivity to 96% (95% CI: 93.7–97.5; I2 = 0%) and specificity to 96.3% (95% CI: 87.2–99.0; I2 = 76.8%). Only four adverse events occurred across the five studies. Conclusions: Our meta-analysis demonstrated the high sensitivity, specificity, and diagnostic accuracy of MCCE, along with a favorable safety profile. Further large-scale trials are needed to validate our findings.

Gastrointestinal Disorders doi: 10.3390/gidisord7030052

Authors: Silpa Choday Tamer Zahdeh Paul Kang Justin Reynolds Robert Wong

Background: Alcohol-associated liver disease (AALD) represents significant health burdens worldwide. This study aims to provide a comprehensive overview of the AALD outcomes that were incompletely understood. Methods: The current study utilizes data from the National Health and Nutrition and Examination Survey (NHANES) from 2011–2020, using a stratified, multistage probability cluster design. AALD in the NHANES was defined using clinical laboratory data and self-reported alcohol use, among which fibrosis-4 score of >2.67. Analysis is conducted using weighted, logistic, and Cox linear regression. Results: The initial sample included 23,206 participants aged 20 and older, with recorded cardiovascular status and AST/ALT levels. Participants reporting AALD had a higher percentage of college degrees (p < 0.001) and were more likely to be daily smokers. Asians exhibited the highest rates of AALD compared to other demographics (p < 0.001). The prevalence in private insurance is significantly greater than Medicaid, but the usage trends have been increasing in Medicaid. The trends of advanced fibrosis have been increasing in blacks and Asians, while they have been decreasing among whites and Mexicans. Those with AALD also had higher mean systolic and diastolic blood pressure, as well as elevated fasting glucose levels (p < 0.001). The mortality rate among AALD participants with heart diseases was 25%, compared to 3% among those without (p < 0.001). After adjusting for potential confounding variables, no statistically significant associations were found between AALD status and HF or CAD. However, a clinically significant increase in the odds of stroke was observed within the AALD group (p < 0.001). Conclusions: Our findings indicate Asians have the highest rates of AALD. The trends of advanced fibrosis have been increasing in blacks and Asians. There is an increased prevalence of AALD with heart diseases and a significant increase in mortality with stroke.

Gastrointestinal Disorders doi: 10.3390/gidisord7030051

Authors: Alexandra Dinu Mariana Aşchie Mariana Deacu Anca Chisoi Manuela Enciu Oana Cojocaru Sabina E. Vlad

Background/Objectives: The 2019 WHO classification redefined high-grade gastrointestinal neuroendocrine neoplasms (GI NENs), encompassing not only poorly differentiated neuroendocrine carcinomas (NECs), but also well-differentiated grade 3 neuroendocrine tumors (NETs G3). Since both subtypes share a Ki-67 index > 20%, distinguishing them based solely on morphology is challenging. Prior studies have shown TP53 alterations in NECs but not in NETs. This study aimed to evaluate clinico-morphological parameters and the immunohistochemical (IHC) expression of p53 in high-grade GI NENs to identify relevant correlations. Methods: Tumors were stratified by Ki-67 index into two groups: >20–50% and >50%. p53 IHC expression was assessed as “wild-type” (1–20% positive tumor cells) or “non-wild-type” (absence or >20% positivity). Correlations were analyzed between Ki-67, p53 status, and various pathological features. Results: Significant correlations were found between the Ki-67 index and maximum tumor size, pT stage, lymphovascular invasion, perineural infiltration, and diagnostic classification. Similarly, p53 immunohistochemical status was significantly associated with lymphovascular invasion, lymph node metastasis, and tumor classification (NET G3 versus NEC, including NEC components of MiNENs). Conclusions: The findings support the value of Ki-67 and p53 as complementary biomarkers in the pathological evaluation of high-grade GI NENs. Their significant associations with key morphological parameters support their utility in differentiating NETs G3 from NECs, particularly in cases showing overlapping histological features. The immunohistochemical profile of p53 may serve as a useful diagnostic adjunct in routine practice.

Gastrointestinal Disorders doi: 10.3390/gidisord7030050

Authors: Sanda Pletikosić Tončić Marko Tončić Sanja Bradić

Background/Objectives: Irritable bowel syndrome (IBS) is a common disorder of brain–gut interaction characterized by abdominal pain and altered bowel habits. While stress and anxiety are known to exacerbate IBS symptoms, less is understood about how these factors interact on a daily timescale. This study aimed to clarify the relationship between daily stress and abdominal pain in IBS and to examine whether trait anxiety moderates this association. Methods: Forty-nine IBS patients completed daily assessments of stress and abdominal pain over a 14-day period. Participants rated abdominal pain three times daily and reported daily stress levels across seven life domains each evening. Trait anxiety was assessed at baseline using the STAI-T. Results: Hierarchical linear modeling was used to analyze within-person and between-person effects. An increase in between-person stress was associated with increased probability of abdominal pain among individuals with low-to-moderate trait anxiety, while this was not observed in patients with high trait anxiety. Even though within-person (day-to-day) stress variations had an impact on pain probability, the effects of between-person variations were multiple times greater. Conclusions: These findings suggest that the interplay between stress and anxiety in IBS might not be uniform. High trait anxiety may, under certain conditions, attenuate rather than amplify the link between stress and pain, possibly pointing to a more dynamic relationship.

Gastrointestinal Disorders doi: 10.3390/gidisord7030049

Authors: Hiroshi Yasuda Tadateru Maehata Yoshinori Sato Hirofumi Kiyokawa Masaki Kato Yusuke Nakamoto Takumi Komatsu Keisuke Tateishi

Objectives: To investigate the real-world outcomes of a population-based gastric cancer (GC) screening program in Kawasaki City, a major urban area with a growing aging population and relatively high screening participation rates. Methods: Between December 2012 and 2021, a total of 337,842 citizens in Kawasaki City underwent population-based GC screening, leading to the detection of 1087 GC cases. Esophageal cancer (EC) has been recorded since 2016, with 236 cases detected. To evaluate the short- and long-term clinical outcomes of screening-detected GC and EC, we conducted a retrospective study using the electronic medical records of patients treated at our hospital, a high-volume institution for GC and EC treatment in the city. As a control group, we included 34 GC and EC cases diagnosed based on symptoms at our hospital in 2018. Results: Among the 1087 GC cases detected through population-based screening, 102 cases treated at our hospital were included in the analysis. Of them, 91 patients (89%) were diagnosed with early-stage GC. All screening-detected GC cases underwent either surgery (27 cases) or endoscopic submucosal dissection (75 cases). The five-year survival rates for GC were 90% in males and 86% in females. Eighteen EC cases were also included in the study. The five-year survival rate for screening-detected advanced GC was 70.0%, while for screening-detected EC, it was 100%. Both survival rates were significantly higher than those for symptom-diagnosed GC (30.0%) and EC (40.8%). Conclusions: The prognosis of GC and EC detected through population-based endoscopic screening is significantly better than that of cancers diagnosed based on symptoms. This underscores the effectiveness of endoscopic screening as a valuable tool for the early detection of upper gastrointestinal tract cancers.

Gastrointestinal Disorders doi: 10.3390/gidisord7030048

Authors: Martin Tobi Donald Bradley Fadi Antaki MaryAnn Rambus Noreen F. Rossi James Hatfield Suzanne Fligiel Benita McVicker

Background: The number of women veterans has been rising steadily since the Gulf War and many assume the functions of their male counterparts. Women face unique obstacles in their service, and it is imperative that differences in physiology not be overlooked so as to provide better and appropriate care to our women in uniform. Despite this influx and incorporation of female talent, dedicated reports contrasting female and male veterans are rare, outside of specific psychological studies. We therefore attempt to contrast gut constituents, absorption, innate immune system, and nutritional differences to provide a comprehensive account of similarities and differences between female and male veterans, from our single-center perspective, as this has not been carried out previously. Herein, we obtained a detailed roster of commonly used biomedical tests and some novel entities to detect differences between female and male veterans. The objective of this study was to detect differences in the innate immune system and other ancillary test results to seek differences that may impact the health of female and male veterans differently. Methods: To contrast biochemical and sociomedical parameters in female and male veterans, we studied the data collected on 450 female veterans and contrasted them to a group of approximately 1642 males, sequentially from 1995 to 2022, all selected because of above-average risk for CRC. As part of this colorectal cancer (CRC) screening cross-sectional and longitudinal study, we also collected stool, urine, saliva, and serum specimens. We used ELISA testing to detect stool p87 shedding by the Adnab-9 monoclonal and urinary organ-specific antigen using the BAC18.1 monoclonal. We used the FERAD ratio (blood ferritin/fecal p87), a measure of the innate immune system to gauge the activity of the innate immune system (InImS) by dividing the denominator p87 (10% N-linked glycoprotein detected by ELISA) into the ferritin level (the enumerator, a common lab test to assess anemia). FERAD ratios have not been performed elsewhere despite past Adnab-9 commercial availability so we have had to auto-cite our published data where appropriate. Results: Many differences between female and males were detected. The most impressive differences were those of the InImS where males clearly had the higher numbers (54,957 ± 120,095) in contrast to a much lower level in females (28,621 ± 66,869), which was highly significantly different (p < 0.004). Mortality was higher in males than females (49.4% vs. 24.1%; OR 3.08 [2.40–3.94]; p < 0.0001). Stool p87, which is secreted by Paneth cells and may have a protective function, was lower in males (0.044 ± 0.083) but higher in females (0.063 ± 0.116; p < 0.031). Immunohistochemistry of the Paneth cell-fixed p87 antigen was also higher in females (in the descending colon and rectum). In contrast, male ferritin levels were significantly higher (206.3 ± 255.9 vs. 141.1 ± 211.00 ng/mL; p < 0.0006). Females were less likely to be diabetic (29.4 vs. 37.3%; OR 0.7 [0.55–0.90]; p < 0.006). Females were also more likely to use NSAIDs (14.7 vs. 10.7%, OR 1.08 [1.08–2.00]; p < 0.015). Females also had borderline less GI bleeding by fecal immune tests (FITs), with 13.2% as opposed to 18.2% in males (OR 0.68 [0.46–1.01]; p = 0.057), but were less inclined to have available flexible sigmoidoscopy (OR 0.68 [0.53–0.89]; p < 0.004). Females also had more GI symptomatology, a higher rate of smoking, and were significantly younger than their male counterparts. Conclusions: This study shows significant differences with multiple parameters in female and male veterans.