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.

Gastrointestinal Disorders doi: 10.3390/gidisord7030047

Authors: Fabio Pace Antonio Maria Morselli-Labate Aladin Abu Issa Alessandro Zanasi

Background: Dyspeptic symptoms are very common in the general population, with an estimated prevalence of 14% to 41%, and the majority of patients experience symptoms without an organic cause for them (so-called functional dyspepsia). While the pathophysiology of functional dyspepsia remains elusive, the impact of functional dyspepsia on quality of life is detrimental. The treatment involves a change in lifestyle—a healthy diet and physical activity—in combination with pharmacological treatments. However, currently, there is no standard therapy for this condition, although a nutritional approach appears to be feasible and well accepted by patients. In this context, the intake of some mineral water types might be able to play an important role. Objective: The aim of the present study was to evaluate whether the regular intake of bicarbonate natural mineral water (Aqua Carpatica from source “F2 Păltiniș”) is able to positively influence the symptomatic process of dyspepsia, promoting digestion and improving the quality of life of patients. Methods: The patients enrolled in this open-label study had diagnosis of functional dyspepsia formulated in accordance with the Rome III criteria. During the 4-week study, patients had to ingest tap water at 1.5 L/day (wash-out period: 2 weeks), and in the 2-week subsequent period, they had to ingest alkaline natural mineral water at 1.5 L/day. The primary efficacy endpoint of this study includes a statistically significant improvement (p < 0.05) in the “heartburn”, “regurgitation”, and “dyspepsia” subscales and the total Reflux Disease Questionnaire’s (RDQ) score with respect to the effects of alkaline natural mineral water. As secondary endpoints, we considered statistically significant improvements (p < 0.05) in quality-of-life scores (Psychological General Well-Being Index—Short form; PGWB-S), the patient’s self-assessment of the state of efficiency of their digestion, and their sense of post-prandial fullness, as well as the use of antacids. Results: Forty-five patients were enrolled: all were Caucasian and mostly women (25, 55.6% vs. 20 men, 44.4%), and they were aged between 25 and 75 years (50.6 ± 13.5 years; mean ± SD). The results of this preliminary study show a significant improvement in functional dyspepsia symptoms—as assessed via the RDQ—and an improvement in quality of life—as assessed using the PGWB-S score—after the intake of alkaline natural mineral water. Conclusions: This preliminary study provides clinical evidence for a recommendation of alkaline natural mineral water as a symptomatic treatment of dyspepsia.

Gastrointestinal Disorders doi: 10.3390/gidisord7030046

Authors: Miltiadis K. Moutzoukis Ioannis V. Mitselos Nikoletta Karavasili Vasileios Theopistos Alexandros Skamnelos Dimitrios Sigounas Varvara Pantazi Panagiota Moschou Dimitrios K. Christodoulou

Objective: A combination of midazolam and opioid is usually used to achieve conscious sedation and analgesia during colonoscopy, but many patients may tolerate the procedure well without any sedation. This randomized trial aimed to compare the efficacy and recovery time of 3 different regimens consisting of (a) midazolam plus meperidine (b) midazolam plus fentanyl and (c) placebo. The endoscopists’ and patients’ satisfaction was assessed by an appropriate questionnaire. Methods: A total 248 consecutive, unselected patients attending outpatient colonoscopy at a University Hospital were enrolled with informed consent and were randomized to receive (a) midazolam with meperidine [group A] (b) midazolam with fentanyl [group B] or (c) placebo [group C]. Data for procedure times, perceived patient’s discomfort (using a relative patient questionnaire) and physician’s satisfaction from the procedure were collected. Patients and all endoscopy staff directly involved with the procedure except the research nurse were blinded to the regimens used. Results: The mean age of the patients was 58 ± 15 years (range 19–85 years) and 130 were males. The completion rate and time to reach cecum did not differ among the three groups. The recovery time was significantly shorter in group C (placebo, 10.4 ± 2.9 min) compared to the other groups (p < 0.000), but it was also shorter in group B (midazolam plus fentanyl, 43.0 ± 9.3 min) compared to group A (midazolam plus pethidine, 50.1 ± 9.0 min) (p = 0.001). Patients of group B (midazolam plus fentanyl) experienced less pain and discomfort than patients of group A (midazolam plus meperidine) (p = 0.02) and patients of group A experienced less pain than patients of group C (placebo). Many more patients in group B were extremely or very satisfied by the procedure(86.7%) compared to group A (59.7%) and group C (44.5%) (p = 0.001). Adverse events were mild in all groups and slightly less in group B. Conclusions: Sedation with midazolam and fentanyl was more effective, better tolerated and led to slightly faster recovery time than sedation with midazolam and meperidine. According to our findings and the literature, the most appropriate regimen for conscious sedation during colonoscopy is the combination of midazolam and fentanyl. However, both sedation regimens were proven to be effective and safe and even a significant proportion of unsedated patients could tolerate the procedure fairly well.

Gastrointestinal Disorders doi: 10.3390/gidisord7030045

Authors: HyoSung Cha JooYong Park

Background/Objectives: Health behavior management plays a critical role in improving outcomes for cancer survivors. This study aims to examine differences in health behaviors based on survival status and time since diagnosis among individuals with gastric or colorectal cancer. Methods: Data were obtained from the Korea National Health and Nutrition Examination Survey (KNHANES, 2014–2021). Among adults aged ≥40 years, 478 individuals diagnosed with gastric or colorectal cancer within the past 10 years were included. Participants were classified as current patients or survivors based on current disease status, and time since diagnosis was categorized as ≤3 years or >3 years. All analyses accounted for complex sample weights. Differences in health behaviors were evaluated using weighted t-tests and Rao–Scott chi-square tests, and weighted logistic regression was used to assess the association between time since diagnosis and current alcohol use. Results: Current alcohol consumption was significantly more prevalent in survivors (49.2%) than in current patients (29.9%) (p = 0.0002). Among current patients, those diagnosed more than three years earlier showed a higher drinking rate (40.9%) compared with those diagnosed within three years (25.4%) (p = 0.0411). In logistic regression analysis, time since diagnosis >3 years was associated with higher odds of alcohol consumption (OR = 2.32, 95% CI: 1.04–5.20), even after adjusting for age and sex. No significant differences were observed in smoking, aerobic activity, strength exercise, or walking. Conclusions: A longer time since diagnosis was associated with increased alcohol consumption in gastric and colorectal cancer patients, highlighting the need for sustained behavioral interventions during survivorship.

Gastrointestinal Disorders doi: 10.3390/gidisord7030044

Authors: Mercedes Ibáñez-García Juan Ramon Gómez-López Jean Carlo Trujillo-Díaz Pilar Concejo-Cutoli Carlos Vaquero-Puerta Juan Carlos Martín-del Olmo

Objectives: To analyze the factors associated with recurrent choledocholithiasis following endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy (BS). Methods: A retrospective, observational, and analytical cohort study was conducted. Patients who underwent ERCP with BS for benign biliary pathology and were followed for a minimum of two years were included. Demographic and clinical data were collected, including the indication for the procedure, endoscopic findings, performance and timing of cholecystectomy (before or after ERCP), and the need for repeat procedures. Episodes of choledocholithiasis were defined as those occurring at least six months after the initial ERCP. Follow-up continued until patient death, loss of follow-up, or the conclusion of the study. Results: A total of 576 patients were included, with a mean age of 71 years and an average follow-up duration of 131 months. Sixty-nine cases of recurrent choledocholithiasis were documented (11.96%). Multivariate analysis identified the following predictive factors for recurrence: age over 50 years, bile duct dilation upon initial evaluation, history of biliary surgery, cytology sampling, placement of biliary stents, repeated ERCP, biliary diversion procedures, and cholecystectomy prior to the index ERCP. Conclusions: Biliary duct dilation, advanced age, and any previous manipulation of the biliary tree are associated with an increased risk of recurrent choledocholithiasis. Cholecystectomy performed after the initial ERCP was not associated with a reduced recurrence risk.

Gastrointestinal Disorders doi: 10.3390/gidisord7030043

Authors: Emmanuel Psylinakis Nikolaos Thalassinos Aikaterini-Maria Dafouli Maria Kanaki Alexios Manidis Anastasia G. Markaki Aspasia Spyridaki

Background/Objectives: Celiac disease (CD) is an immune-mediated condition triggered by gluten ingestion in genetically predisposed individuals, requiring lifelong adherence to a strict gluten-free diet (GFD). Despite dietary compliance, many patients with CD experience impaired health-related quality of life (HRQoL). Emerging evidence suggests that dietary quality may influence HRQoL. Although the Mediterranean diet (MD) is linked to multiple health benefits, its role in CD management remains underexplored. This study aimed to investigate the relationship between MD adherence and HRQoL in adults with CD. Methods: In this cross-sectional study, adherence to the MD was assessed using the MedDiet Score. HRQoL was evaluated using the Short Form-12 (SF-12), measuring the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Results: The study enrolled 100 individuals with CD and 100 age- and sex-matched healthy controls. The mean MedDiet Score (MDS) was 30.4 ± 3.9 for patients and 30.7 ± 5.0 for controls (p = 0.709), with moderate adherence in most participants. The patients had significantly lower PCS scores (43.80 ± 4.99) compared to controls (45.45 ± 4.76; p = 0.015), while the MCS scores did not differ significantly (42.12 ± 8.05 vs. 42.79 ± 6.56; p = 0.738). In individuals with CD, the MedDiet Score was positively correlated with MCS12 (ρ = 0.302, p = 0.002), but not with PCS12 (ρ = 0.059, p = 0.562). Conclusions: Adherence to the MD is associated with better mental health outcomes in individuals with CD. Promoting a Mediterranean-style GFD may offer a holistic approach to enhancing well-being in this population.

Gastrointestinal Disorders doi: 10.3390/gidisord7030042

Authors: Zhasmina Mihaylova Stoyan Bichev Alexey Savov Maria Radanova

Background: Anti-EGFR therapy, combined with chemotherapy, represents the standard therapeutic approach for triple wild-type (KRAS/NRAS and BRAF), left-sided, microsatellite stable (MSS) metastatic colorectal cancer (mCRC). However, acquired resistance develops in approximately 50% of patients. This study evaluated the efficacy of anti-EGFR therapy re-challenge and analyzed circulating tumor DNA (ctDNA) for potential resistance mechanisms. Methods: Eleven patients with triple wild-type, MSS, HER2-negative, left-sided mCRC were included. All patients received Cetuximab with chemotherapy as the first-line treatment, with three patients subsequently receiving Cetuximab re-challenge. Twenty-one plasma samples were collected at baseline and at each response assessment for retrospective ctDNA analysis using next-generation sequencing with a 16-gene panel. Results: Genetic alterations were detected in only 14.2% of ctDNA samples. In one re-challenge patient, the KRAS: c.35G>A mutation appeared during progression. No RAS mutations were identified in four patients who progressed on first-line Cetuximab treatment. Conclusions: This preliminary study suggests that clinically based anti-EGFR re-challenge may benefit selected mCRC patients. The low detection rate of resistance-conferring mutations indicates potential alternative resistance mechanisms beyond RAS pathway alterations. Our findings, while limited by sample size and the retrospective design of ctDNA testing, contribute to the growing evidence supporting anti-EGFR re-challenge strategies in mCRC management.

Gastrointestinal Disorders doi: 10.3390/gidisord7030041

Authors: Rosario Caruso Valerio Caruso Luciana Rigoli

Background/Objectives: AllergoOncology is a new field of study that investigates the relationship between allergic inflammation and cancer. Mast cells and eosinophils are two critical players in allergy reactions, where they can interact and release bioactive granules. The electron microscope is an indispensable tool for analyzing membrane contacts and degranulation patterns in mast cells and eosinophils. The aim of the present ultrastructural study is to analyze the interactions between tumor-associated eosinophils and mast cells (TATEM) in nine cases of gastric cancer. Methods: Seventy-two gastric cancer samples were analyzed using light microscopy, and nine cases exhibiting TATEM were selected for additional examination by transmission electron microscopy. Results: In seven cases, there was direct interaction between non-activated eosinophils and mast cells demonstrating piecemeal degranulation and/or exocytosis. In cases 8 and 9, both cell types showed more advanced stages of degranulation. Mast cells exhibited either massive degranulation (anaphylactic type) or signs of recovery, while eosinophils displayed cytolysis, with or without extracellular trap formation (ETosis). The concurrent activation of both cell types may indicate a collaborative immune response that could affect tumor behavior. There was a trend toward an association with low-stage (I-II) gastric cancer in patients with TATEM, but this difference was not statistically significant (p = 0.06). Conclusions: This work is the first investigation to present ultrastructural evidence of the intimate relationship between degranulating mast cells and cytolytic eosinophils, with or without ETosis, in gastric cancer. These findings support the emerging field of AllergoOncology, which examines the role of allergy-like immune responses in tumor immunity.

Gastrointestinal Disorders doi: 10.3390/gidisord7020040

Authors: Gennaro Mazzarella Diego Coletta Edoardo Maria Muttillo Biagio Picardi Stefano Rossi Alessandro Scorsi Simona Meneghini Bruno Cirillo Gioia Brachini Marco Assenza Andrea Mingoli Irnerio Angelo Muttillo

Background: Looking for anomalies and vascular control gains a central role in colon cancer surgery. Complete mesocolic excision (CME) presents technical challenges, primarily due to the considerable variability in the arterial configuration of the right colon. The importance of understanding colonic vascular anatomy has become more prominent with the adoption of this surgical technique. The aim of this study is to systematically review the vascular anatomical variations in the superior mesenteric artery (SMA) in the setting of extended lymphadenectomy for CME in right colon cancer and to show its impact in clinical practice. Methods: A systematic review of the literature on Medline (PubMed), Web of Science (WOS), and Scopus was performed according to PRISMA guidelines. The following criteria were set for inclusion: (1) studies reporting minimally invasive (robotic, laparoscopic, and hybrid techniques) or open CME/D3 lymphadenectomy; (2) studies reporting patients with right-sided colon cancer; (3) studies reporting the description or illustration of SMA variations. The methodological quality of all included studies was evaluated using the Newcastle–Ottawa Scale (NOS). Results: After the literature search, 800 studies were recorded, 31 studies underwent full-text reviews, and 9 studies met the inclusion criteria. All studies reported vascular variations in SMA, and the total number of patients was 813. No intraoperative complications were reported. In 6.4% of patients, post-operative bleeding occurred. Conclusions: Vascular anatomical variations are not a rare entity. In experienced centers, vascular anomalies are not associated with an increase in complications, both in traditional open and minimally invasive surgery (MIS). However, in MIS, full access to central vessels and intraoperative vascular control, moderate retraction, safety maneuvers, and accurate vascular dissection are mandatory.

Gastrointestinal Disorders doi: 10.3390/gidisord7020039

Authors: Adrian Surd Rodica Muresan Carmen Iulia Ciongradi Lucia Maria Sur Lia Oxana Usatiuc Kriszta Snakovszki Camelia Munteanu Ioan Sârbu

Background and Aims: Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are rare but serious congenital anomalies requiring early surgical intervention. Over the past two decades, minimally invasive surgical (MIS) approaches—particularly thoracoscopic repair—have gained traction, aiming to reduce postoperative morbidity while maintaining surgical efficacy. Objective: This narrative review provides a comprehensive overview of the evolution and current status of MIS techniques for EA/TEF, assessing their clinical outcomes, technical challenges, and implications for patient care. Methods: A structured literature search was conducted to identify clinical studies, reviews, and reports on thoracoscopic, robotic-assisted, and endoscopic approaches to EA/TEF. Emerging adjuncts, including tissue engineering, botulinum toxin use, and magnet-assisted anastomosis, were also reviewed. Results: Thoracoscopic repair has demonstrated comparable anastomotic success rates to open surgery (approximately 85–95%) with significantly reduced rates of musculoskeletal complications, such as scoliosis and chest wall deformities (reported in less than 10% of cases, compared to up to 40% in open approaches). Robotic-assisted and endoscopic-assisted techniques have enabled improved visualization and precision in anatomically challenging cases, although their use remains limited to high-resource centers with specialized expertise. Common postoperative complications include anastomotic stricture (30–50%), gastroesophageal reflux disease (35–70%), and respiratory morbidity, necessitating long-term multidisciplinary follow-up. Recent innovations in simulation-based training and bioengineered adjuncts have facilitated safer MIS adoption in neonates. Conclusions: Minimally invasive techniques have improved the surgical management of EA/TEF, though challenges remain regarding technical complexity, training, and resource availability. Continued innovation and collaborative research are essential for advancing care and ensuring optimal outcomes for affected infants.

Gastrointestinal Disorders doi: 10.3390/gidisord7020038

Authors: Alessandro Raffaele Francesco De Leo Emanuele Cereda Thomas Foiadelli Valentina Motta Salvatore Savasta Marco Brunero Gloria Pelizzo Romano Piero Giovanni Luigi Avolio Gian Battista Parigi Giovanna Riccipetitoni Mirko Bertozzi

Background: Neurologically impaired children often face severe gastroesophageal reflux disease (GERD), feeding difficulties, and related challenges, profoundly impacting their quality of life (QoL) and that of their caregivers. Surgery is often necessary to alleviate symptoms in this population, and the success of surgical treatment, along with the achievement of clinical endpoints, must also consider the impact on QoL. The aim of this study is to evaluate the impact of fundoplication surgery on the QoL of both children and caregivers. Methods: All patients treated between 2010 and 2023 at the Pediatric Surgery Department of San Matteo Hospital in Pavia were included in the study. The modified 1996 O’Neill questionnaire was identified as a suitable model for a QoL survey. QoL assessments included caregiver-reported outcomes using validated questionnaires, focusing on physical, psychological, and social domains. Patients with a follow-up period of less than 12 months were excluded. As a secondary outcome, we evaluated the satisfaction of patients treated after 2020 who received integrated care through a multidisciplinary outpatient clinic. Results: Among the 77 patients, 42 were treated between 2010 and 2021. Of these, 16 participated in pre- and post-operative QoL evaluations, showing significant improvements in GERD resolution, feeding ease, and caregiver stress. From 2020, 35 patients benefited from a multidisciplinary approach; 12 underwent robotic fundoplication. Feeding ease scores improved significantly (mean increase from 37.5 to 84.2; p < 0.001), while caregiver stress scores decreased by 35% (p < 0.01). Conclusions: The combination of surgical and multidisciplinary interventions significantly enhances QoL for SNI children and their families. Integrated care models provide a framework for addressing complex needs and should be prioritized in clinical practice.

Gastrointestinal Disorders doi: 10.3390/gidisord7020037

Authors: Concetta Timpanaro Lorenzo Musmeci Francesco Tiralongo Pietro Valerio Foti Stefania Tamburrini Corrado Ini’ Davide Giuseppe Castiglione Rosita Comune Mariapaola Tiralongo Francesco Vacirca Stefano Palmucci Antonio Basile

Background: Acute mesenteric ischemia (AMI) is a potentially life-threatening condition that requires prompt diagnosis and treatment. The presence of air within the arterial lumen, particularly in the abdomen, is an uncommon finding with varied etiologies. This case report presents a unique instance of AMI with air in the superior mesenteric artery (SMA), highlighting the complexities in diagnosis and management. Case presentation: An 89-year-old male with a history of smoking, hypertension, dyslipidemia, and atrial fibrillation presented with chest pain and underwent coronary angiography for suspected anterior ST-elevation myocardial infarction (STEMI). Following successful thromboaspiration and admission to the coronary care unit, he developed severe abdominal pain. A contrast-enhanced computed tomography (CECT) scan revealed a thromboembolic occlusion in the SMA, along with air filling in the SMA and its branches. An endovascular thrombectomy was performed, but the patient died the next day due to complications related to AMI and metabolic acidosis. Conclusions: This case underscores the challenges in diagnosing and managing AMI, particularly when accompanied by unusual imaging findings such as air within the SMA. The presence of air in the arterial system raises questions about its origin and clinical significance in the context of AMI. Further research is needed to understand the mechanisms and implications of this rare phenomenon, which may have implications for refining diagnostic and therapeutic strategies for AMI.

Gastrointestinal Disorders doi: 10.3390/gidisord7020036

Authors: Phu Van La Diep Ngoc Nguyen Dien Minh Tran Tu Tuan Duong Minh Thanh Phuoc Tran Phuc Vinh La Minh Nhat Thanh Le Cong Phi Dang Vu Anh Doan

Synchronous colorectal cancer (SCRC) is characterized by the simultaneous occurrence of two or more primary colorectal malignancies, diagnosed either preoperatively, intraoperatively, or within six months postoperatively. The rare prevalence of SCRC makes it an uncommon scenario among colorectal malignancies. Since the majority of SCRC patients have been reported to have two concurrent malignancies, triple synchronous malignancies are extremely rare. We report the case of a 65-year-old male individual presenting with a history of abdominal pain, anemia, anorexia, and unintentional weight loss. He was diagnosed with synchronous colorectal cancer with three distinct tumors: two located in the splenic flexure and sigmoid colon, respectively, and another in the rectum that caused partial obstruction. This case highlights the importance of intraoperative evaluation and an appropriate choice of surgical intervention in colorectal cancer. The early identification and proper management of multiple colorectal cancers remain essential for better survival rates.

Gastrointestinal Disorders doi: 10.3390/gidisord7020035

Authors: Marek Vojtko Peter Banovcin Martin Duricek Jakub Hoferica Peter Liptak

The most common anorectal disorders are fecal incontinence, functional anorectal pain, and functional defecation disorders. They are often presented by overlapping symptoms with various degrees of severity. Therefore, a personalized approach to the patient is crucial for diagnosing and determining the prognosis of the disease. Biofeedback training is appropriate to consider when the motoric function disorder is known, the patient could learn voluntary control of response, and this could further lead to an improvement in the condition. Biofeedback is recommended for short-term and long-term treatment of constipation in adults and fecal incontinence in adults. It could also be considered for treatment of specific cases of anorectal pain. As office biofeedback is often time-consuming and comes with a substantially high cost, there is an emerging trend of home biofeedback administration. However, only a few significant studies have been published on this new approach. Although comprehensive data are needed to evaluate the proper strategy and development of various treatment protocols for different types of defecation disorders, home biofeedback therapy offers a potentially effective tool in the personalized treatment of defecation disorders.

Gastrointestinal Disorders doi: 10.3390/gidisord7020034

Authors: Federica Felloni Luca Costantini Michela Coccia

Background/Objectives: Oropharyngeal dysphagia (OD) is a prevalent symptom in patients with neuromuscular diseases (NMDs) and increases the risk of aspiration and malnutrition. Malnutrition is frequent in these patients and is not only related to dysphagia, but also generates a vicious circle that may result in worsening muscle atrophy and weakness. Texture modification is required to ensure safe and efficient swallowing. This study evaluates the acceptability of a ready-to-mix oral nutritional supplement (ONS) containing high-quality protein and a xanthan-based thickener in patients with OD and NMDs. Methods: This cross-sectional study includes adult patients with NMDs and OD who received a xanthan gum-based protein ONS. Patients completed a questionnaire to rate their satisfaction with the ONS. Results: Seventy-two patients were included (median age = 56 years; 51% were males). The percentage of patients with moderate-to-severe OD who rated the taste, consistency, and product quality as acceptable-to-very-satisfactory (score 3–5) were 76%, 80%, and 84%, respectively. After three months, 93% of patients continued consuming the ONS. Conclusions: Our findings support that the use of protein xanthan gum-based ONS can be as a palatable and an effective nutritional intervention, given their high satisfaction and acceptance rates among patients with NMDs and OD.

Gastrointestinal Disorders doi: 10.3390/gidisord7020033

Authors: Jakov Ivan Bucan Tamara Braut Antea Krsek Vlatka Sotosek Lara Baticic

Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that greatly influences patients’ quality of life and represents a growing public health concern. Characterized by typical and atypical symptoms, GERD encompasses a range of clinical phenotypes and is associated with complications such as erosive esophagitis and Barrett’s esophagus. This review intends to provide a thorough overview of current scientific knowledge on the etiological factors, risk determinants, and pathophysiology of GERD, while exploring diagnostic challenges and therapeutic approaches. Proton pump inhibitors (PPIs) remain the mainstay of medical therapy; however, concerns regarding their long-term safety have encouraged interest in adjunctive and alternative strategies. Emerging pharmacological agents, plant-based treatments, and integrative approaches rooted in traditional medicine offer promising modalities for enhanced management. Additionally, dietary and lifestyle modifications such as weight control, meal timing, and avoidance of trigger foods, are essential components of effective care. A multidisciplinary framework incorporating pharmacological, nutritional, and behavioral strategies is emphasized as the most reliable path toward personalized and sustainable GERD management. This review further aims to synthesize current therapeutic modalities and evolving perspectives in the treatment of GERD.

Gastrointestinal Disorders doi: 10.3390/gidisord7020032

Authors: Nicoleta Mihaela Mindrescu Cristian Guja Viorel Jinga Sorina Ispas Antoanela Curici Rucsandra Elena Danciulescu Miulescu Andreea Nelson Twakor Anca Pantea Stoian

Background: The relationship between gut microbiota and metabolic health has garnered significant attention in recent years. In this study, we aim to explore the intricate link between gut microbiota and metabolic outcomes, with a focus on lifestyle factors such as smoking, diet, and living environment. Materials and Methods: We investigated the gut microbiota and metabolic profiles of adult patients with type 2 diabetes, all receiving metformin therapy, to assess how lifestyle factors impact metabolic health. Key metabolic parameters and body composition indices were measured, alongside gut microbiota composition. Results: Our cohort included 30 patients, and we identified significant associations between smoking and adverse body composition changes, as well as dietary patterns favoring plant-based foods correlating with improved metabolic outcomes. Urban participants displayed distinct microbiota profiles and metabolic markers compared to their rural counterparts, highlighting the potential influence of environmental factors. Conclusions: The current data does not directly demonstrate a causal link between metformin usage and specific changes in gut microbiota composition. These findings align with the existing literature while providing novel insights into specific population dynamics. Future research should focus on longitudinal studies and interventions targeting the gut microbiota to further unravel its therapeutic potential.

Gastrointestinal Disorders doi: 10.3390/gidisord7020031

Authors: Angharad Vernon-Roberts Andrew S. Day

For children and adults with inflammatory bowel disease (IBD), the overarching aim of clinical management is the induction and maintenance of remission, with mucosal healing as a key target outcome [...]

Gastrointestinal Disorders doi: 10.3390/gidisord7020030

Authors: Lizeth Mejia-Ortiz Jovanny Zabaleta Jone Garai Luis Eduardo Bravo Andres Castillo

Background/Objectives: This study aimed to identify molecular variants associated with the progression of gastric precancerous lesions in a follow-up study conducted on patients from Southwestern Colombia. Methods: Whole-exome sequencing (WES) was performed on patients enrolled in the Colombian chemoprevention trial, who were classified into two groups—progression and regression—based on changes in the severity of their gastric precancerous lesions over 16 years of follow-up. The bioinformatics pipeline included steps for quality control, mapping, variant calling, filtering, and annotation. Associations between molecular variants and lesion progression were analyzed using Fisher’s exact test and the Cochran–Armitage trend test. Additionally, functional impact and pathway enrichment analyses were performed for variants that showed significant associations. Results: Thirty-eight molecular variants from thirty-seven participants were associated with the progression of gastric precancerous lesions. These variants were found in tumor suppressor genes like CDKN2A and CDK4, which are involved in cell cycle regulation and apoptosis. Additionally, variants were identified in extracellular matrix regulators such as COL23A1, LAMA2, and TNR. Other noteworthy findings included variants in FLT1, which is linked to VEGF signaling in angiogenesis, and APOB, which is involved in modulating inflammatory responses. Furthermore, alterations in genes associated with the hemostatic system, such as FGA and F5, underscored the connection between hemostasis and carcinogenesis. Conclusions: This exploratory analysis highlighted some molecular variants that may affect the function, structure, and expression of key proteins involved in cancer development, contributing to the progression of gastric precancerous lesions.

Gastrointestinal Disorders doi: 10.3390/gidisord7020029

Authors: Apostolis Papaefthymiou Nasar Aslam Benjamin Norton Andrea Telese Charles Murray Alberto Murino Gavin Johnson Roberto Simons-Linares Rehan Haidry

Background: The increasing availability of gastrointestinal (GI) interventions has raised the need to treat luminal defects. Endoscopic suturing (ES) is a minimally invasive technique that is used for a wide range of indications. This retrospective cohort study aimed to evaluate the performance of ES in treating upper GI defects. Materials and Methods: Data from a tertiary centre were collected for patients undergoing ES to treat upper GI defects. The primary outcome was long-term outcomes, defined as the successful sutures deployment. Secondary outcomes included technical success, immediate clinical success (confirmation of closure at the time of the procedure), recurrence, and complications. Descriptive statistics and x2 test were used to calculate the rates of the outcomes and assess any link between independent variables and results. Results: Forty-two procedures were performed on 25 patients between 2018 and 2023. The mean age was 55 (±16.2) years, and 56% were female. The long-term clinical success rate was 69.6% (16/23), the technical success rate was 88.1% (37/42), and the immediate clinical success rate was 91.9% (34/37), with only two (4.8%) adverse events. The overall recurrence rate was 61.8% (21/34). Technical success was higher in the esophagus (92.3%), and stomach (100%) (p = 0.002), and immediate clinical success was more likely in patients with leaks (88.9%) or fistula (95.2%) compared to perforation (50%; p = 0.005). Conclusions: ES demonstrated high rates of technical and immediate clinical success for defect closure in the upper GI tract, with low rates of complications. The benefit is most prominently seen among patients with leaks and fistulas in the stomach and esophagus.

Gastrointestinal Disorders doi: 10.3390/gidisord7020028

Authors: Ana Jagodic Antea Krsek Lou Marie Salomé Schleicher Lara Baticic

Microbiome dysbiosis—an imbalance in gut microbial communities—has emerged as a critical factor in the pathogenesis of neurological disorders, particularly Alzheimer’s and Parkinson’s diseases. This review examines the role of gut microbiota in neurodegeneration, emphasizing how dysbiosis disrupts gut–brain communication through mechanisms such as impaired gut permeability, systemic inflammation, and neuroinflammation. The gastrointestinal and central nervous systems interact bidirectionally, with microbial metabolites like short-chain fatty acids playing a pivotal role in maintaining gut and brain health. Dysbiotic shifts in microbial composition can compromise the blood–brain barrier, enabling inflammatory molecules to alter brain biochemistry and potentially accelerate neurodegenerative processes. Additionally, this review explores therapeutic strategies—including probiotics, prebiotics, and dietary modifications—designed to restore microbial balance, reduce neuroinflammation, and slow disease progression. Further research is essential to refine microbiome-targeted therapies and fully elucidate their potential in managing neurodegenerative diseases.

Gastrointestinal Disorders doi: 10.3390/gidisord7020027

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

Background: Single-Anastomosis Duodenoileostomy with Sleeve Gastrectomy (SADI-S) has been reported as both a safe and effective surgical procedure. However, these findings have not been directly compared to those of more established and less complex procedures, such as Sleeve Gastrectomy (SG), which remains the most commonly performed technique in Metabolic and Bariatric Surgery (MBS). Objective: This study aimed to assess and contrast the intraoperative and postoperative outcomes between patients who underwent SADI-S and those who underwent SG. Methods: A systematic review and meta-analysis were performed and registered under PROSPERO with the ID CRD42024532504. A comprehensive search strategy was executed on 15 April 2024, covering PubMed, Embase, Cochrane Library, Scopus, Web of Science, and Science Direct from the first reports to March 2024. The search strategy incorporated relevant keywords, including: “SADI-S” OR “Single Anastomosis Duodenal-Ileal bypass” and “Sleeve Gastrectomy”. We included studies comparing adult patients (≥18 years old) undergoing SADI-S and SG, reporting at least one clinical outcome of interest. Results: Five studies published between 2019 and 2023, comprising 3593 patients, were included. Of these, 461 patients (12.8%) underwent SADI-S, while 3132 (87.2%) underwent SG. The mean patient age was 42.96 years, with 89.6% female participants. Patients undergoing SADI-S had a significantly higher Body Mass Index (BMI) than those undergoing SG (Mean: 49.73 ± 8.10 vs. 45.64 ± 7.84; Mean Difference [MD]: 3.83, 95% CI: 0.52–7.14; p = 0.02) and an increased risk of hypertension (OR: 1.38, 95% CI: 1.04–1.84; p = 0.03). SADI-S also resulted in longer operative times (125.63 ± 51.91 min vs. 49.67 ± 26.07 min; MD: 65.97 min, 95% CI: 61.71–70.25; p < 0.001) and length of hospital stay (2.30 ± 2.76 days vs. 1.21 ± 0.81 days; MD: 1.03 days, 95% CI: 0.70–1.37; p < 0.001). Moreover, patients who underwent SADI-S demonstrated a significantly higher risk of postoperative complications, such as readmissions and reinterventions (OR: 3.17, 95% CI: 2.15–4.67; p < 0.001), and experienced greater excess weight loss (MD: 12.42%, 95% CI: 0.92–23.92; p = 0.03). No significant differences were observed between the groups regarding age, sex, or the prevalence of obstructive sleep apnea (OSA). Conclusions: SADI-S appears to be a promising surgical technique for facilitating substantial weight loss in individuals with severe obesity. Given the higher risk of postoperative complications associated with SADI-S, careful evaluation and personalized decision-making for patient selection and education are essential to optimize clinical and safety outcomes.

Gastrointestinal Disorders doi: 10.3390/gidisord7020026

Authors: Deborah Jael Herrera Daiane Maria Seibert Karen Feyen Marlon van Loo Guido Van Hal Wessel van de Veerdonk

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. While screening tools such as the fecal immunochemical test (FIT) aid in early detection, they do not provide insights into individual risk factors or strategies for primary prevention. This study aimed to develop and internally validate an interpretable machine learning-based model that estimates an individual’s probability of developing CRC using readily available clinical and lifestyle factors. Methods: We analyzed data from 154,887 adults, aged 55–74 years, who participated in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A risk prediction model was built using the Light Gradient Boosting Machine (LightGBM) algorithm. To translate these findings into clinical practice, we implemented the model into a risk estimator that categorizes individuals as average, increased, or high risk, highlighting modifiable risk factors to support patient–clinician discussions on lifestyle changes. Results: The LightGBM model incorporated 12 predictive variables, with age, weight, and smoking history identified as the strongest CRC risk factors, while heart medication use appeared to have a potentially protective effect. The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.726 (95% confidence interval [CI]: 0.698–0.753), correctly distinguishing high-risk from average-risk individuals 73 out of 100 times. Conclusions: Our findings suggest that this model could support clinicians and individuals considering screening by guiding informed decision making and facilitating patient–clinician discussions on CRC prevention through personalized lifestyle modifications. However, before clinical implementation, external validation is needed to ensure its reliability across diverse populations and confirm its effectiveness in real-world healthcare settings.

Gastrointestinal Disorders doi: 10.3390/gidisord7010025

Authors: Yash R. Shah Ernesto Calderon-Martinez Dushyant Singh Dahiya Saurabh Chandan Manesh Kumar Gangwani Mihir Shah Hassam Ali Amir H. Sohail Sumant Inamdar Rashmi Advani

Background and Aims: Endoscopic clipping is the standard method for mucosotomy closure in per-oral endoscopic myotomy (POEM) and gastric per-oral endoscopic myotomy (G-POEM). Concerns remain regarding potential leaks and long-term complications. This meta-analysis compares the technical success rates and outcomes of endoscopic clipping and suturing for mucosotomy closure in E-POEM/G-POEM. Methods: A systematic search of databases for studies comparing endoscopic clipping and suturing in E-POEM/G-POEM was conducted. The primary outcomes were technical success rates, and the secondary outcomes were cost, procedure time, and complications. Meta-analyses and sensitivity analysis were performed. Results: Three studies with a total of 91 patients were included. The technical success rates were similar between suturing and clipping, with a success rate of 100% (48/48) for suturing and 94.4% (41/43) for clipping (odds ratio 1.03, 95% confidence interval 0.89–1.19, p = 0.50). There was no significant difference in procedure time between the two methods (SMD −0.73; CI: −1.70 to 0.23; p = 0.13). The cost of suturing was higher on average (mean: $1751, range: $873–$2353) compared to clipping (mean: $898, range: $703–$1083), but the difference was not statistically significant (SMD 1.85, CI −5.05 to 1.35, p = 0.25) with high heterogeneity. Complications for clipping and suturing were also comparable. Conclusions: Both endoscopic clipping and suturing achieve successful mucosotomy closure in E-POEM/G-POEM without any significant difference in the cost and the time between the two closure methods. Further investigation with larger, randomized, controlled trials are necessary to determine their roles in routine practice.

Gastrointestinal Disorders doi: 10.3390/gidisord7010024

Authors: Veronica Vitali Giulia Fusi Alessandro Raffaele Maria Ruffoli Simonetta Mencherini Carmine Noviello Gian Battista Parigi Mirko Bertozzi

Background: Meckel’s diverticulum on the mesenteric side has been reported only as case reports in the literature and presents a diagnostic challenge, with ultimate recognition often taking place intraoperatively. We describe a case series of children with mesenteric Meckel’s diverticulum (MMD) treated at our institution, along with the results of a systematic review of the literature. Methods: Our experience on MMD was analyzed along with a systematic literature review performed according to PRISMA criteria. We identified studies published from 1941 to 2023 from PubMed, EMBASE, SCOPUS, and WOS. Search terms were variations of “Meckel”, “diverticulum”, and “mesenteric”. Inclusion criteria were patients < 18 years of age and articles written in English. Results: A total of three cases of MMD were observed and treated in our hospital. The mean age was 7.6 years. The most common symptoms were rectal bleeding and abdominal pain. Diagnostic workup included ultrasound and both upper and lower endoscopy. Surgery was performed by the laparoscopy-assisted technique. One case had to be reoperated due to postoperative intestinal occlusion. The mean length of hospital stay was 9.3 days. The literature search yielded 795 citations; out of the 590 papers remaining after the exclusion of 205 duplications, only 15 papers matched the inclusion criteria and were included and analyzed. Conclusions: MMD remains a rare and elusive pathology, sharing with its normal counterpart symptoms and signs. In our experience, and in the more recent literature, laparoscopy-assisted surgery appears safe and effective both for final diagnosis and definitive treatment.

Gastrointestinal Disorders doi: 10.3390/gidisord7010023

Authors: Teodora Spataru Ana Stemate Marina Cozma Alexandru Fleschiu Remus Popescu Lucian Negreanu

Background: Disability and poor quality of life are frequently reported by patients with inflammatory bowel diseases (IBDs). There is an increased interest in the use and development of self-administered questionnaires of patient-reported outcomes including depression symptoms, potentially allowing easier and even remote monitoring of health status and permitting treatment adjustments. Aim: We noticed a significant overlap in some of the parameters evaluated by Beck’s Depression Inventory and the IBD Disk, which led to the idea that the IBD Disk might be a useful and easy-to-use tool to assess the mental state and quality of life of patients with IBD. Our objective was to validate the IBD Disk in measuring depression symptoms, as well as the correlation between IBD Disk scores and patient background and disease activity. Methods: Patients included in this study were asked to complete Beck’s Depression Inventory (BDI) and the IBD Disk. The resulting scores of BDI and IBD Disk were compared and both questionnaires were corelated with the patients’ background and disease activity. Results: Eighty-two patients with IBD, age 43.11 +/− 13.07, 63.4% male, 61.0% with Crohn’s disease and 39.0% with Ulcerative Colitis, were included. The total scores of BDI and IBD Disk significantly correlated (rs(80) = 0.951, p < 0.001), as well as the overlapping questions. Disease remission was associated with lower total scores in both questionnaires (BDI and IBD Disk) (rs(80) = 0.559, p < 0.016; rs(80) = 0.951, p < 0.005, respectively). Conclusions: Our findings suggest that IBD Disk is a useful and easy-to-use tool for screening for depression symptoms and establishing the quality of life of IBD patients. We encourage its routine use in patients during IBD care and follow-up.

Gastrointestinal Disorders doi: 10.3390/gidisord7010022

Authors: Martin Tobi Fadi Antaki MaryAnn Rambus Jason Hellman James Hatfield Suzanne Fligiel Benita McVicker

Background: The perspective of inflammatory bowel disease (IBD) has changed radically since the first decade of the 21st century, and the formerly monolithic components of IBD, ulcerative colitis (UC), and Crohn’s disease (CD) have undergone a fundamental convergence, with realization that there is likely an element of shared pathogenesis. The ground shift began with genomic revelation but with the current emergence of the innate immune system (InImS) as a key player, allowing for improved understanding of the associations between the immune underpinnings of IBD. Methods: Using unique ferritin/fecal p87 (FERAD) or using colonoscopic effluent as denominator (FEREFF) and other ratios to test this hypothesis, we prospectively enrolled 2185 patients with increased risk of colorectal cancer, of whom 31 had UC and 18 CD, with 2136 controls and brought to bear in a convenient measure for the InImS, the FERAD ratio. The FERAD, FEREFF, and NLR ratios have been shown to be effective measures of the InImS in COVID-19 and various cancers. p87 is expressed in gut Paneth cells known to modulate the microbiome by secretion of alpha-defensins, a natural antibiotic. Other related parameters were also evaluated. Results: There was no significant difference between the FERAD ratio in UC and CD. However, differences between IBD entities and controls were substantial. Conclusions: InImS settings in IBD are similar between CD and UC. p87 tissue immunohistochemistry (IHC) is also shared. Other InImS markers, such as the absolute neutrophil/lymphocyte ratio, are also confluent between the two IBD forms.

Gastrointestinal Disorders doi: 10.3390/gidisord7010021

Authors: Lilian Camaño Carballo Alejandro Ernesto Lorenzo Hidalgo Paola Andrea Romero Riaño Alejandro Martínez-Rodríguez Daniela Alejandra Loaiza Martínez

Background: Helicobacter pylori infection, overweight, and obesity are global health concerns. This bacterium is involved in the pathophysiology of chronic gastritis and gastric cancer. Additionally, overweight and obesity, associated with unhealthy eating habits and sedentary lifestyles, cause alterations in the gut microbiota that facilitate gastric colonization by Helicobacter pylori. Moreover, individuals with obesity tend to consume low-quality foods due to episodes of anxiety and exhibit elevated insulin levels, which may promote the development of gastric neoplasms. Studies conducted in Latin America have found that over 50% of participants are infected with Helicobacter pylori, a situation similar to that reported in Ecuador, where the prevalence of overweight and obesity in individuals aged 19 to 59 years reached 64.58% in 2018. Both health issues are influenced by the high consumption of processed foods or those prepared under inadequate hygiene conditions. Methods: In this context, this research aimed to correlate the body composition of university students with the prevalence of Helicobacter pylori. An observational, cross-sectional, and descriptive study was conducted with 57 Nursing, Medicine, and Psychology students from Universidad Indoamérica, Ambato campus, during 2024. Fecal samples were analyzed to detect the presence of the bacterium, and anthropometric measurements were taken to establish a possible relationship between these parameters. Results: Of the 57 students who participated, 54.39% tested positive for Helicobacter pylori. However, the presence of the bacteria did not show any relationship with body composition parameters such as fat mass, lean mass, BMI, weight, height, or age. Conclusions: The study found no evidence of a connection between Helicobacter pylori infection and anthropometric parameters in this university population. However, the high incidence of infections highlights the importance of promoting the consumption of safe food and ensuring timely diagnosis and treatment.

Gastrointestinal Disorders doi: 10.3390/gidisord7010020

Authors: Francesco Tiralongo Davide Giuseppe Castiglione Rosita Comune Stefano Palmucci Chandra Bortolotto Fiore De Simone Filomena Pezzullo Giovanni Ferrandino Giacomo Sica Paolo Ricci Mariano Scaglione Antonio Basile Stefania Tamburrini

Background: Cystic artery bleeding (CAB) is a rare but potentially life-threatening condition. Its etiologies span iatrogenic trauma, inflammatory diseases, and trauma, often presenting variably as hemoperitoneum, upper gastrointestinal bleeding, or hemorrhagic shock. The clinical heterogeneity of CAB complicates its diagnosis, necessitating a high index of suspicion and reliance on imaging modalities, particularly computed tomography (CT), for accurate identification of bleeding sources and differentiation from other causes of abdominal pain. Methods: This pictorial essay highlights key imaging findings in CAB and pseudoaneurysms, emphasizing the role of ultrasound, CT, and digital subtraction angiography (DSA) in diagnosis and management planning. Additionally, a systematic review of transcatheter arterial embolization (TAE) is presented, consolidating data from 64 studies encompassing 90 patients. Results: The review evaluates patient demographics, etiologies, clinical presentations, and procedural outcomes, underscoring TAE’s high efficacy and safety as a first-line treatment. Conclusions: The findings reinforce the importance of early diagnosis and tailored intervention strategies to optimize outcomes in CAB management.

Gastrointestinal Disorders doi: 10.3390/gidisord7010019

Authors: Mariya Armova Martina Stefanova Nikolova Petar Martinov Draganov Petya Valentinova Peneva Jean Marc Sabaté Javier Santos

Background/Objectives: Natural compounds represent novel promising alternative treatments for functional gastrointestinal disorders. This multicenter, double-blind, randomized, placebo-controlled, crossover study aimed to evaluate the efficacy and safety of xyloglucan, pea protein, and chia seed powder (XP + CS) in irritable bowel syndrome with constipation (IBS-C). Methods: Sixty patients received twice-daily XP + CS or placebo for 28 days. Following a 28-day washout period, patients switched to the alternative treatment for another 28 days. Efficacy was evaluated using the Bristol Stool Form Scale; a seven-point Likert scale for abdominal pain, bloating, and discomfort; a Visual Analogue Scale for IBS symptom severity; the quality of life (QoL)-IBS questionnaire; Sickness Impact Profile (SIP) score; and serum zonulin concentrations. Adverse events were monitored throughout the study. Results: Compared to the placebo, XP + CS significantly improved stool consistency (p = 0.04 and p < 0.001 at days 15 and 28, respectively), IBS symptoms (p < 0.001 at day 15), QoL (p < 0.001 from day 15 on), and nearly all SIP domains (p < 0.001 at all time-points). Additionally, XP + CS treatment restored serum zonulin concentrations to within normal ranges by day 15. No serious adverse events were reported. Conclusions: This study provides evidence supporting the efficacy and safety of XP + CS in managing IBS-C symptoms.

Gastrointestinal Disorders doi: 10.3390/gidisord7010018

Authors: Niki Markou Doxa Papakonstantinou

Background/Objectives: Individuals with Crohn’s disease often experience challenges at work and are confronted with the decision of whether to disclose their health status in their workplace. This study explores the disclosure of Crohn’s disease in the workplace and the factors influencing their choices among individuals in Greece. Methods: The study examined how demographic characteristics affected the disclosure of a non-visible disability, the reasons behind the disclosure, and the associated experiences. Results: The sample consisted of 152 individuals with Crohn’s disease. Although 52.6% of participants had disclosed their condition, the results show that factors like health benefits, the impact of COVID-19, and necessary workplace accommodations influenced disclosure decisions. On the other hand, 47.3% chose not to disclose their condition, the predominant reason being the fear of being fired or not being hired. Conclusions: The findings imply that workplace cultures and policies that foster inclusive, supportive environments are necessary to allow employees with non-visible disabilities to request the accommodations they require without worrying about the consequences. Future research could focus on a deeper understanding of the disclosure issues for people with Crohn’s disease and other non-visible disabilities.

Gastrointestinal Disorders doi: 10.3390/gidisord7010017

Authors: Hoang Tran Viet Tuan Huynh Minh Nhan Vu Truong Anh Huynh Thi Phuong Bich-Uyen Nguyen Hao Chung The Cong Phi Dang Linh Truong Nguyen Uy

Background/Objective: Hirschsprung-associated enterocolitis (HAEC) can occur before and after surgery, increasing the complication rates, hospital stay, and treatment costs. This study aims to determine the incidence of preoperative and postoperative Hirschsprung-associated enterocolitis HAEC and the related risk factors. Methods: This study is a prospective cohort study of Hirschsprung’s disease patients under 16 years of age at two Children’s Hospitals in Ho Chi Minh City, Vietnam from December 2022 to June 2024. The postoperative follow-up is 12 months. Results: We enrolled 84 pediatric patients, with a male-to-female ratio of 5.4/1 and an average age of 7.2 ± 1.07 months. Of the patients, 25% had preoperative enterocolitis at the time of admission. Statistical analysis revealed that risk factors for preoperative enterocolitis at admission included a history of enterocolitis (p = 0.024), low weight in hospital (p = 0.001), and lack of preoperative treatment (p = 0.01). Postoperative enterocolitis occurred in 14 patients (16.7%) at an average of 4.03 months postoperatively. Multiple logistic regression of postoperative enterocolitis was associated with a history of preoperative enterocolitis (p < 0.001), anastomotic stricture (p = 0.002), and the length of the aganglionic segment (p = 0.031). No statistically significant association was found between the surgical method and the risk of postoperative enterocolitis. Conclusions: A history of preoperative enterocolitis, low weight, and anastomotic stricture are significant risk factors for postoperative enterocolitis in patients with Hirschsprung’s disease. Therefore, preoperative medical treatment is recommended for the patients who have not yet undergone a definitive surgical procedure.

Gastrointestinal Disorders doi: 10.3390/gidisord7010016

Authors: Hannah DeGonza Sarah Laurenzano Janna Galinato Rasha Elmaoued Razan Alkhouri Ricardo Orlando Castillo Rajmohan Dharmaraj

Metabolic bone disease (MBD) is a known complication of short bowel syndrome (SBS), with a high prevalence in both pediatric and adult populations. MBD includes various conditions that disrupt skeletal homeostasis, such as rickets, osteomalacia, and osteoporosis. The pathogenesis of MBD is multifactorial, regardless of the underlying cause of SBS. When MBD is suspected, it is important to conduct laboratory evaluations to guide proper diagnosis and treatment. Dual-energy X-ray absorptiometry (DXA) is the preferred imaging modality for assessing MBD in routine clinical care. Early and accurate diagnosis and treatment of MBD in pediatric patients with SBS are essential to support growth and development and prevent fractures and metabolic complications. Using the best evidence available, this article aims to review the pathophysiology, diagnosis, and current management of MBD in pediatric patients with SBS.

Gastrointestinal Disorders doi: 10.3390/gidisord7010015

Authors: Patrick Campbell Michael Solomon Cherry Koh Peter Lee Kirk Austin Lilian Whitehead Neil Pillinger Sascha Karunaratne Daniel Steffens

Introduction: Pelvic cancers present significant health challenges and often require aggressive treatment strategies. Pelvic exenteration, which involves the resection of multiple pelvic organs, is currently the only curative option for advanced or recurrent pelvic malignancies. Due to its extensive nature, it carries a high risk for postoperative complications and extended hospital stays. Current evidence suggest that improved preoperative fitness is associated with better postoperative outcomes. This study explored the relationship between preoperative self-reported physical activity levels and surgical outcomes following pelvic exenteration. Methods: This retrospective cohort study included consecutive adult patients undergoing pelvic exenteration at Royal Prince Alfred Hospital between May 2017 and December 2023. Eligible participants completed the International Physical Activity Questionnaire—Short Form (IPAQ-SF) preoperatively. Primary outcomes included postoperative morbidity, length of hospital stay, and survival. Univariate and multivariate logistic regression analyses explored the association between preoperative physical activity and postoperative outcomes. Results: A total of 256 participants were included, of which 115 (44.9%) were classified as active. Active patients experienced fewer postoperative complications (p = 0.047) and shorter hospital stays (p = 0.007), compared to inactive participants. There was no significant association between preoperative physical activity levels and survival outcomes (p = 0.749). Younger age, preoperative physical activity level, and advanced primary malignancy were significantly associated with fewer complications and shorter hospital stays. Conclusions: Higher levels of preoperative physical activity is associated with fewer postoperative complications and shorter hospital stays in patients undergoing pelvic exenteration. These findings support the potential benefits of incorporating prehabilitation programs to improve surgical outcomes and reduce healthcare costs.

Gastrointestinal Disorders doi: 10.3390/gidisord7010014

Authors: Jacob J. Gries Bing Chen Steven M. Ney Idorenyin Udoeyo Duane E. Deivert

Introduction: Primary colorectal lymphoma (PCL) is a very rare disease with limited information regarding its macroscopic features. This retrospective descriptive study aims to identify the macroscopic characteristics of PCL and explore treatment trends and outcomes with respect to histopathologic subtypes. Methods: This IRB-approved study from a large academic medical center identified 66 patients with colorectal lymphoma from 1998 to 2022 from a tumor registry. Thirty-four patients met the inclusion criteria of having PCL with available endoscopic data. The macroscopic features of each lesion were identified. Treatment trends and outcomes were examined at the patient level. Data were described using frequency and percentages for categorical characteristics and the median and interquatile range (IQR) for continuous outcomes. Results: A total of 77 PCL lesions were identified. Most were identified on screening or surveillance colonoscopies or colonoscopies performed after abnormal imaging (61.8%). Diffuse large B cell lymphoma (DLBCL) had the highest prevalence (N = 24), followed by follicular lymphoma (n = 21), mantle cell (n = 16), mucosa-associated lymphoid tissue (MALT) (n = 14), then Burkitt’s (n = 2). More mantle cell (93.8%) and follicular (90.5%) lymphomas were sessile. More MALT lymphomas were ulcerated (71.4%). A higher proportion of follicular (76.2%) and mantle cell (71.4%) lymphomas were diminutive (≤5 mm). More MALT (78.6%), DLBCL (75.0%), and Burkitt’s (100%) were large (≥20 mm). More lesions were found in the sigmoid colon (26.0%), followed by the rectum (22.1%), transverse colon (18.2%), cecum (18.2%), descending colon (10.4%), and ascending colon (5.2%). Overall, most underwent immunotherapy (61.3%) and did not have radiation therapy (81.3%), endoscopic resection (75.0%), and surgery (68.8%). Patients with DLBCL demonstrated higher rates of chemotherapy (70.6%), immunotherapy (87.5%), and remission after intervention (52.9%). Conclusions: Primary colorectal lymphomas display distinct macroscopic features and appear in different locations depending on the histopathologic subtype. Most cases are identified at early stages on screening colonoscopies and demonstrate a 75% two-year survival rate.

Gastrointestinal Disorders doi: 10.3390/gidisord7010013

Authors: Elisa Perestrelo João Pedro Dinis Ana Pereira Sandra F. Martins

Background: Surgery in periampullary cancers (PAC) is associated with high morbimortality rates. There are multiple scores used to predict surgical risk. This study aims to identify a possible correlation between POSSUM, P-POSSUM, E-PASS, and mE-PASS scores and morbimortality in patients operated on for PAC. Methods: POSSUM, P-POSSUM, E-PASS, and mE-PASS were calculated for patients operated for PAC in Hospital de Braga between 1 January 2011 and 31 August 2021. The calibration and discrimination of scores were analyzed by comparing the predicted mortality and morbidity with the observed one and by evaluating the Receiver Operating Characteristic (ROC) curve, respectively. Results: The study included 58 patients. The most frequent location was the ampulla of Vater (AVC) (43.10%), and the most frequent stage was IIb (48.28%). The postoperative mortality and morbidity observed at 30 days were 3.45% and 37.93%, respectively. P-POSSUM (O:E 0.45), POSSUM (O:E 0.16), and E-PASS (O:E 0.03) overestimated mortality, and mE-PASS underestimated it (O:E 1.89). In most subgroups, both POSSUM scores showed the best calibration. CRS and E-PASS showed the highest discriminative ability for mortality (AUC 0.982). In the pancreatic head carcinoma subgroup, the SSS showed better calibration for morbidity. The operative score had the best discrimination for the CAV subgroup (AUC 0.767) and for stage IIb (AUC 0.900). No scale showed discriminative ability in overall morbidity. Conclusions: POSSUM and P-POSSUM obtained the best calibration regarding subgroup mortality. E-PASS and CRS showed the highest discrimination for mortality, and the operative score showed the greatest discrimination for morbidity in the subgroups.

Gastrointestinal Disorders doi: 10.3390/gidisord7010012

Authors: Yohei Okawa

The purpose of this study was to propose a new diagnostic approach using ultrasound imaging equipment. Many patients suffer from constipation, and medical professionals have difficulty providing treatment and care. The prevalence of constipation increases with age, and this condition strongly impacts the quality of life. Herein, a new diagnostic approach using ultrasound imaging equipment was examined. The study design was a narrative review, and the authors discussed existing knowledge, challenges, and prospects based on previous research. References were obtained by searching PubMed and Centralblatt für die gesammte Medicine. Most of the papers were published in English. Papers with scientific knowledge that has already been published in academic journals were extracted from these documents. No restrictions were placed on the publication date, sample size, study design, or age of subjects, and only published papers reporting scientific knowledge and consensus were cited. As a result, we suggest that this approach classifies the state of fecal retention in the rectum into three patterns. If ultrasound imaging indicates that the rectum is free of feces, there is no need to administer an enema. If hard stool is found, dissection can be performed to prevent complications such as severe intestinal perforation due to subsequent administration of laxatives. If ultrasound imaging reveals normal stool in the rectum, inducing defecation with suppositories may enable treatment for constipation.

Gastrointestinal Disorders doi: 10.3390/gidisord7010011

Authors: Luana Alexandrescu Ionut Eduard Iordache Alina Mihaela Stanigut Laura Maria Condur Doina Ecaterina Tofolean Razvan Catalin Popescu Andreea Nelson Twakor Eugen Dumitru Andrei Dumitru Cristina Tocia Alexandra Herlo Ionut Tiberiu Tofolean

Background: Chronic constipation is a well-recognized complication which is caused by hard and/or infrequent defecation. According to estimates, constipation presents as a chronic illness affecting 16% of adults globally, who deal with insufficient bowel movements that cause discomfort, bloating, or a sensation of incomplete bowel. Objectives: This review looks at the many local and systemic factors that contribute to the pathogenesis of the causative, including dietary habits, genetic factors, colon function and absorption, social and economic factors, lifestyle, and biological and drug factors. Results: Appropriate diagnostic and management modalities are the cornerstone in the management of patients with chronic constipation. However, there are still controversies regarding the timing of these diagnostic and management approaches. This condition is common and reduces the quality of life of patients and represents a burden on any healthcare system. In clinical practice, it remains problematic, as physicians are most of the time indecisive on which therapy to administer and at what time. Conclusions: Constipation management is a new topic that was introduced over a decade ago and the purpose of this study is to shed some light onto the practice, problems and modern day techniques that can be used to treat constipation in patients, primarily through behavioural, conservative, medical, and surgical means. Additionally, this particular management is to be used in conjunction with an algorithm designed to enhance and support clinical practice.

Gastrointestinal Disorders doi: 10.3390/gidisord7010010

Authors: Juan Carlos Martín-del Olmo Cristina López-Mestanza Jean Carlo Trujillo Díaz Carlos Vaquero-Puerta Pilar Concejo-Cutoli Juan Ramón Gómez-López

Background/Objectives: Gastric cancer is a major global health concern and a leading cause of cancer-related death. While surgical resection remains the cornerstone of curative treatment, postoperative morbidity and mortality are significant issues. This study aimed to identify factors associated with postoperative morbidity and mortality in patients undergoing laparoscopic gastrectomy for gastric adenocarcinoma. Results: The median age was 73 years. Eighteen total gastrectomies (15%) and eighty-eight subtotal gastrectomies (66.6%) were performed. Major complications (Clavien-Dindo ≥ III) occurred in 22.3% of patients, and the hospital mortality rate was 7.5%. Independent predictors of morbidity included anemia (OR 2.49, p = 0.047), extended lymphadenectomy (OR 5.09, p = 0.002), and conversion to open surgery (OR 9.40, p = 0.031). Coagulopathy was a significant predictor of mortality (OR 5.01, p = 0.049). Methods: A retrospective, single-center observational study was conducted on 120 patients who underwent laparoscopic surgery between January 2004 and December 2022. Preoperative assessments included endoscopy, imaging, and staging according to the TNM classification. Risk factors were analyzed using univariate and multivariate logistic regression. Conclusions: Laparoscopic gastrectomy is a technically challenging procedure with substantial risks of morbidity and mortality. Identifying modifiable risk factors, such as anemia and coagulopathy, provides opportunities for improved outcomes through preoperative prehabilitation and optimized patient selection.

Gastrointestinal Disorders doi: 10.3390/gidisord7010009

Authors: Adina Ioana Mihele Harrie Toms John Nicoleta Negrut Anca Ferician Paula Marian Felicia Manole

Background/Objectives: The gut–liver axis is bidirectional and influences the body’s homeostasis. Pathologies such as metabolic dysfunction-associated steatotic liver (MASL) can have detrimental effects on the human microbiome, with multiple systemic effects. Furthermore, the geographical particularities of the intestinal microbiome may influence liver disease. The study’s outcome was to identify dysbiosis in a group of patients with MASL from the western region of Romania. Methods: The NGS shotgun genomic sequencing (WGS metagenomics) method was used to identify bacteria in fecal samples. The data were analyzed using IBM SPSS Statistics software [version 29.0.2.0 (20)]. Results: Out of the 122 MASL patients included in the study, 43 (35.24%) exhibited low alpha diversity. In the subgroup with a normal biodiversity index, approximately half were identified with a Firmicutes/Bacteroidetes ratio below the lower reference value, while the remaining patients presented dysbiosis based on decreased concentrations of Proteobacteria and Prevotella, considered among the most relevant species supporting dysbiosis. A higher prevalence of Prevotella species (15.99 ± 13.65%) was identified in the study cohort. Conclusions: The present study demonstrates that patients with MASL from the western region of Romania exhibit criteria for intestinal dysbiosis, namely reduced bacterial diversity, along with significant alterations in populations of Firmicutes, Bacteroidetes, Proteobacteria, and Prevotella. Together, these findings suggest a possible influence of geo-cultural factors on the intestinal microbiome, highlighting the need for regionally adapted therapeutic interventions to support liver health.

Gastrointestinal Disorders doi: 10.3390/gidisord7010008

Authors: Vlad Alexandru Ionescu Gina Gheorghe Teodor Florin Georgescu Vlad Buica Mihai-Stefan Catanescu Iris-Andreea Cercel Beatrice Budeanu Mihail Budan Ancuta Nastac Ninel Iacobus Antonie Daniel O. Costache Raluca Simona Costache Nicolae Bacalbasa Loredana-Crista Tiuca Camelia Cristina Diaconu

Despite many advances in the management of patients with colorectal cancer, this malignancy remains the second leading cause of cancer death worldwide. One of the keys to improve the prognosis of these patients is diagnosis in early stages, making them eligible for curative surgical treatment. Cutaneous paraneoplastic syndromes can enhance the diagnostic management of these patients. The time elapsed from the appearance of skin lesions to the appearance of the first digestive symptoms can reach up to a decade. Thus, comprehensive paraclinical evaluation and the monitoring of patients with specific skin lesions play an important role in detecting an underlying cancer. Given these findings, it is imperative to increase the awareness of cutaneous paraneoplastic syndromes among patients and medical professionals. Additionally, the investigation of the mechanisms that elucidate this pathogenic link has the potential to result in the identification of novel therapeutic targets.

Gastrointestinal Disorders doi: 10.3390/gidisord7010007

Authors: Muneer Oladipupo Yaqub Aashika Jain Chinedu Eucharia Joseph Lekshmi K. Edison

The human microbiome, a complex ecosystem of microorganisms residing in and on the body, plays a pivotal role in the regulation of a wide range of physiological processes, including digestion, immune responses, and metabolic functions. In recent years, the rapidly growing field of microbiome-driven therapeutics has garnered significant attention owing to its potential to revolutionize healthcare. This review explores the evolving landscape of microbiome-based therapies, with a particular focus on the gut microbiome and its implications for both gut health and precision medicine. We highlight recent advances in understanding how microbial communities influence disease pathogenesis and treatment outcomes, spanning conditions such as inflammatory bowel disease (IBD), metabolic disorders, neurological diseases, and even cancer. This article also discusses emerging therapeutic strategies, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and microbial-based drugs, as well as the challenges associated with their clinical implementation. Additionally, we examined how the integration of microbiome profiling and metagenomic data is advancing the field of precision medicine, paving the way for personalized and effective treatments. This review serves as a comprehensive resource that synthesizes current knowledge, identifies key gaps in microbiome research, and offers insights into the future direction of microbiome-driven therapeutics, thus providing a valuable framework for clinicians, researchers, and policymakers seeking to harness the potential of microbiomes to advance personalized healthcare solutions.

Gastrointestinal Disorders doi: 10.3390/gidisord7010006

Authors: Luigi Santacroce Skender Topi Concetta Cafiero Raffaele Palmirotta Emilio Jirillo

Helicobacter pylori (H.p.) is a Gram-negative bacterium endowed with gastric tropism. H.p. infection is widely spread throughout the world, accounting for various pathologies, such as peptic ulcer, gastric cancer, mucosa-associated lymphoid tissue lymphoma, and extra-gastric manifestations. This bacterium possesses several virulence factors, e.g., lipopolysaccharides (LPS), the toxins CagA and VacA, and adhesins, which elicit a robust immune response during the initial phase of the infection. Of note, the lipid A moiety of the LPS exhibits a lower endotoxic potency than that of other LPSs, thus facilitating infection through a mechanism of immune escape. H.p. colonization of the gastric mucosa induces an initial protective immune response with innate immune cells, e.g., neutrophils, monocytes, and macrophages, which engulf and kill bacteria. Moreover, the same cells, along with gastric epithelial cells, secrete cytokines and chemokines, which recruit T cells [T helper (h)1 and Th17 cells] to the site of infection, thus leading to H.p. eradication. In a large subset of individuals, the perturbation of such an immune equilibrium leads to a harmful response, with an expansion of T regulatory (TREG) cells, which suppress the protective immune response. In fact, TREG cells, via the production of interleukin (IL)-10, downregulate Th1- and Th17-related cytokines, thus allowing H.p. survival and the perpetuation of inflammation. As far as the humoral immune response is concerned, B cells, upon H.p. stimulation, produce autoreactive antibodies, and IgG anti-Lex antibodies are harmful to the gastric mucosa. In this review, the structure and function of H.p. antigenic components and immune mechanisms elicited by this bacterium will be described in relation to gastric damage.

Gastrointestinal Disorders doi: 10.3390/gidisord7010005

Authors: Sebastián Eustaquio Martín Pérez Hakim Al Lal Abdel Lah Nelson Hernández García Umabel Aaron Reyes Carreño Isidro Miguel Martín Pérez

Nociplastic pain, commonly observed in conditions such as Fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome, arises from altered central pain processing and involves complex mechanisms, including interactions between the gut–brain axis and immune dysregulation. Conventional therapies often fail to address this type of pain effectively, leading to interest in alternative approaches such as fecal microbiota transplantation. This technique has been proposed to restore gut microbial balance and modulate systemic inflammation, neuroinflammation, and neurotransmitter signaling. This systematic review, conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and registered in the International Prospective Register of Systematic Reviews (CRD42024611939), evaluated 13 studies with n = 409 participants, including clinical trials, case reports, and retrospective analyses. A quality assessment was performed using appraisal tools such as Cochrane RoB 2, ROBINS-I, NOS, and CARE. The results suggest that fecal microbiota transplantation may reduce pain intensity and improve fatigue and quality of life, particularly in patients with Fibromyalgia and irritable bowel syndrome. However, outcomes for Chronic Fatigue Syndrome and psoriatic arthritis were inconsistent and limited by methodological flaws, small sample sizes, and variability in protocols and donor selection. Although adverse events were minimal, the current evidence is insufficient to support widespread clinical use. High-quality, standardized studies are needed to confirm the efficacy of fecal microbiota transplantation. Until then, its application should remain experimental and interpreted with caution.

Gastrointestinal Disorders doi: 10.3390/gidisord7010004

Authors: Tugba Kose Paul A. Sharp Gladys O. Latunde-Dada

Background/Objectives: Pancreatic cancer is a common gastrointestinal cancer with high risk of mortality. Currently, the therapeutic strategies for pancreatic cancers are surgery, chemotherapy, and radiotherapy, none of which are effective treatments. Ferroptosis is a new form of cell death that is iron (Fe)-dependent and characterized by lipid peroxidation, which is a new approach for treatment of pancreatic cancer. Therefore, this study was dedicated to investigating the effect of erastin and Ras-selective lethal small molecule 3 (RLS3) as ferroptosis inducers as well as focusing on the antioxidant effects of two natural products, curcumin and (−)-epigallocatechin-3-gallate (EGCG), against ferroptosis. Methods: PANC1 cells were treated with 20 μmol/L curcumin or EGCG and then exposed to 20 μmol/L erastin. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, Reactive Oxygen Species (ROS) were measured by dihydrodichlorofluorescein (H2DCF) cell-permeant probe, Fe levels were determined by inductively coupled plasma mass spectrometry (ICP-MS), and glutathione (GSH), lipid peroxidation, Western blot, and mRNA were assayed with commercially available kits. Results: Curcumin and EGCG enhanced cell viability in erastin-treated PANC1 cells in a dose-and time-dependent manner. Erastin-treated PANC1 cells exhibited the elevated levels of GSH depletion, ROS productions, and lipid peroxidation while curcumin reversed the erastin-induced ferroptotic effects. The treatment of erastin-induced PANC1 cells with curcumin increased the GPX4 mRNA gene and protein levels. Also, curcumin decreased the FTH1 mRNA gene levels as a strong Fe chelator. Conclusions: In conclusion, this study shows that erastin can be potentially a therapeutic strategy for treatment of cancer cells. Additionally, curcumin might play an antioxidant role at the specific concentrations, potentially mitigating ferroptosis in cells.

Gastrointestinal Disorders doi: 10.3390/gidisord7010003

Authors: Jennifer Wilbrink Mark van Avesaat Arnold Stronkhorst Freddy Troost Carel W le Roux Ad Masclee

Objective: The regulation of food intake is disturbed in obesity, possibly resulting from alterations in gut peptide secretion. We hypothesize that obesity is associated with attenuated systemic and tissue concentrations of the gut peptides PYY and GLP-1. Methods: A prospective single-center study in which we included 13 individuals with obesity (BMI 39.5 ± 2.8 kg/m2) and 11 lean individuals as controls (BMI 20.7 ± 1.2 kg/m2) matched for age and gender. We measured: (1) tissue concentrations and mRNA expression of GLP-1 and PYY in ileal and colonic biopsies taken during routine colonoscopy and (2) plasma concentrations of PYY and GLP-1 in response to a meal in the same group. Results: Plasma GLP-1 and PYY responses did not differ between individuals with obesity and lean controls. Neither were tissue concentrations and mRNA expression of both peptides different between both groups. Conclusions: Systemic and local PYY and GLP-1 concentrations in individuals with obesity do not differ from those in lean subjects.

Gastrointestinal Disorders doi: 10.3390/gidisord7010002

Authors: Yash R. Shah Carensa Cezar Heena Khan Sumant Inamdar Mauricio Garcia Saenz De Sicilia Matthew G. Deneke Mary K. Rude

Background: The rise in bariatric surgeries, particularly Roux-en-Y gastric bypass (RYGB), has added complexity to diagnostic evaluations in post-transplant patients. Case Presentation: We present a rare case of metastatic jejunal adenocarcinoma in the biliopancreatic limb of a patient with a history of RYGB, diagnosed three months after simultaneous liver–kidney transplantation. Despite multiple advanced imaging modalities, the primary malignancy eluded detection during pre-transplant evaluation. The patient developed progressive anemia and persistent liver enzyme elevation, which led to a comprehensive diagnostic workup. After failed initial endoscopic and radiological attempts, a multifaceted approach combining PET-CT, targeted open liver biopsy, and repeat endoscopy via a G-tube site enabled the discovery of a 5 cm partially obstructing jejunal mass. Histopathological analysis confirmed moderately differentiated adenocarcinoma. Conclusions: This case underscores the challenges in diagnosing gastrointestinal malignancies in patients with altered anatomy, particularly following RYGB. It highlights the need for modified cancer screening protocols before organ transplantation, especially for those with complex post-surgical gastrointestinal anatomy, to prevent the development of metastatic disease post-transplant. Further research is warranted to refine screening strategies and improve early malignancy detection in this high-risk population.

Gastrointestinal Disorders doi: 10.3390/gidisord7010001

Authors: Taina Hudson Claudia Phen Isabel Rojas Shlomi Cohen Warren Hyer Thomas Attard

Hereditary polyposis syndromes are rare but potentially devastating conditions which require multidisciplinary care from an early age. Societal guidelines, which ideally combine expert opinions and medical evidence, serve as the framework for disease diagnosis, surveillance and treatment. However, there is a significant underrepresentation of pediatric gastroenterology input in guideline formulation, and additionally, recommendations can vary significantly between societies, which can have a moderate-to-high clinical impact on patient care. This paper aims to summarize key differences in management based on societal guidelines and identify some of the factors which may contribute to divergence in care in hereditary polyposis syndromes in pediatric patients. The authors review the literature underlying the divergence in recommendations and attempt to reconcile these differences with a closer consideration of the pediatric population, considering the available evidence. This review highlights the need to harmonize recommendations across subspecialties and professional societies and sheds light on the significant underrepresentation of pediatric gastroenterology input in guideline formulation. Given the poor-quality evidence underlying many societal guidelines and the lack of pediatric gastroenterology representation in guideline formulation in these rare syndromes, there is a need for collaborative, multicenter, registry-based studies to refine and improve care standards.