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Gastrointest. Disord., Volume 8, Issue 3 (September 2026) – 11 articles

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28 pages, 4592 KB  
Systematic Review
Spontaneous Bile Duct Perforation in Children: A Systematic Review of 209 Cases and Practical Diagnostic and Management Considerations
by Moshe Argaman, Michael Gurevich, Ofir Cohen, Veronika Dadaev, Rotem Horowitz, Shai Hoffman, Yael Ben Avraham, Adi Litmanovich, Aviad Gravetz, Eviatar Nesher and Fahim Kanani
Gastrointest. Disord. 2026, 8(3), 41; https://doi.org/10.3390/gidisord8030041 - 5 Aug 2026
Viewed by 195
Abstract
Background/Objectives: Pediatric spontaneous or non-traumatic extrahepatic bile duct perforation (SBDP) is a rare cause of bile ascites and biliary peritonitis. We aimed to characterize presentation, diagnosis, management, outcomes, and summarize practical management considerations. Methods: A systematic review was performed in accordance with PRISMA [...] Read more.
Background/Objectives: Pediatric spontaneous or non-traumatic extrahepatic bile duct perforation (SBDP) is a rare cause of bile ascites and biliary peritonitis. We aimed to characterize presentation, diagnosis, management, outcomes, and summarize practical management considerations. Methods: A systematic review was performed in accordance with PRISMA 2020, we searched PubMed/MEDLINE, EMBASE, and Google Scholar from inception to February 2026, and completed backward citation tracking in June 2026. We included pediatric SBDP cases and excluded traumatic, iatrogenic, isolated gallbladder, and perforated choledochal cyst cases. Case-level data were extracted when available, and exploratory subgroup analyses were performed by age and management approach. Results: A total of 139 studies reported 208 cases; with one institutional case, final cohort of 209 patients. Median age was 3.0 months (IQR, 1.15–15.0; n = 174), and 70.5% of patients were ≤1 year old (124/176). Bilious ascites or bile-stained fluid was confirmed in 95.2%. The cystic duct–CHD/CBD junction was the most frequently reported site (82/180, 45.5%), and biliary anomalies were reported in 39.7% (83/209). A step-up initial management was used in 60.3% and immediate surgery in 38.8%. Reported survival was 97.0% (197/203), although publication bias limits interpretation. Clinical complications and reinterventions were reported in 75/198 (37.9%) and 66/209 (31.6%), respectively. Conclusions: Pediatric SBDP is age-dependent and anatomy-driven; infants more often presented with cholestatic-ascitic features, whereas older children more often had acute-abdominal features. Bilious ascites is an important diagnostic clue. Management should prioritize stabilization and source control, followed by anatomical definition and selective reconstruction. Full article
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15 pages, 1184 KB  
Article
Effect of a Sequential Butyrate–Probiotic Administration on Symptoms and Stool Consistency in Patients with Irritable Bowel Syndrome: A Randomized Controlled Study
by Nikos Viazis, Konstantinos Mousourakis, Panagiotis I. Kanellopoulos, Dimitra Kozompoli, Dimitra Provi, Alexandra Agorogianni, Vasilis Papastergiou, Athanasios Soukovelos, Ioanna Nefeli Mastorogianni, Alexandros Skamnelos and Dimitrios Christodoulou
Gastrointest. Disord. 2026, 8(3), 40; https://doi.org/10.3390/gidisord8030040 - 4 Aug 2026
Viewed by 141
Abstract
Background: Dysbiosis, mucosal inflammation and increased intestinal permeability have been implicated in the pathophysiology of irritable bowel syndrome (IBS). Objective: To evaluate the effectiveness of a sequential butyrate–probiotic administration in reducing symptoms and improving stool consistency in patients with diarrhea-predominant (IBS-D) [...] Read more.
Background: Dysbiosis, mucosal inflammation and increased intestinal permeability have been implicated in the pathophysiology of irritable bowel syndrome (IBS). Objective: To evaluate the effectiveness of a sequential butyrate–probiotic administration in reducing symptoms and improving stool consistency in patients with diarrhea-predominant (IBS-D) or mixed-type IBS (IBS-M). Methods: Two hundred adult patients were allocated to intervention (n = 105) or control (n = 95). The intervention group received ColonLife formulation (Εuro-Pharma S.r.l., Torino—Italy), consisting of two distinct capsules: the first containing butyric acid and grapefruit seed extract, and the second containing microencapsulated probiotic strains together with fructooligosaccharides (FOSs). Symptom severity, quality of life and stool consistency (Bristol Stool Scale) were assessed at baseline and three follow-up visits. Results: Baseline characteristics were comparable between groups (p > 0.05). Diarrhea severity decreased significantly in the intervention group (3.78 ± 1.01 to 3.31 ± 1.21; Δ − 0.47) compared with minimal change in controls (3.71 ± 1.05 to 3.62 ± 1.14; Δ − 0.08; p = 0.015). Stool consistency improved more in the intervention group (−1.18 ± 1.46 vs. −0.64 ± 1.41; p = 0.028), with normal stools increasing from 1.0% to 65.7% versus 4.2% to 36.8% in controls (p < 0.001). The degree of change in pain scores was similar between the two groups (p > 0.05). The degree of reduction in bloating scores was also similar between groups (p > 0.05). Quality of life improved in both groups (intervention: +0.68 ± 1.43; control: +0.71 ± 1.64; both p < 0.01), with no significant difference between groups (p > 0.05). Conclusions: Sequential butyrate–probiotic administration significantly improves diarrhea, stool consistency and gastrointestinal symptoms in IBS-D and IBS-M, supporting its role as a microbiota-targeted treatment. Full article
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8 pages, 222 KB  
Brief Report
Orodispersible Budesonide Tablets in Pediatric Patients with Eosinophilic Esophagitis—A Viennese Experience
by Rebecca Einspieler, Judith Pichler, Wolf-Dietrich Huber, Andreas Heilos, Christoph Aufricht and Bettina Bidmon-Fliegenschnee
Gastrointest. Disord. 2026, 8(3), 39; https://doi.org/10.3390/gidisord8030039 - 31 Jul 2026
Viewed by 170
Abstract
Background: Orodispersible budesonide tablets (OBTs, Jorveza) are approved by the EMA as a therapy option in eosinophilic esophagitis (EoE) in adults. However, data on their use in pediatric patients remain limited and no approved pediatric OBT formulation is currently available in Europe. Therefore, [...] Read more.
Background: Orodispersible budesonide tablets (OBTs, Jorveza) are approved by the EMA as a therapy option in eosinophilic esophagitis (EoE) in adults. However, data on their use in pediatric patients remain limited and no approved pediatric OBT formulation is currently available in Europe. Therefore, real-world data on off-label use of OBTs in children is needed. Methods: We retrospectively analyzed data on the off-label use of OBTs in eight children (five girls) at a median age of 10.5 years (ranging from 5 to 14). Clinical, histological and safety outcomes were assessed descriptively. Results: Treatment with OBTs was associated with clinical improvement and a reduction in eosinophil counts. Specifically, the median eosinophil count decreased from 38.5 (ranging from 20 to 100) to 0 (ranging from 0 to 20) eosinophils per high-power field. Histological remission, defined as <15 eosinophils per high-power field, was achieved in six of eight patients (75%). Clinical remission was reached in seven of eight patients (87.5%). No severe side effects could be detected. Conclusions: OBTs showed promising clinical and histological responses in this small retrospective pediatric case series. However, larger prospective studies are required before efficacy and safety can be established. Further clinical studies are needed to assess whether OBTs could become an approved pediatric therapy. Full article
(This article belongs to the Special Issue Feature Papers in Gastrointestinal Disorders in 2025–2026)
16 pages, 992 KB  
Review
Systematic Review of Malignancy Risk with Biologic, Advanced Small-Molecule, and Thiopurine Therapies for Inflammatory Bowel Disease
by Gurleen Kaur, Rahul Jain, Palak Grover, Zarqa Yasin, Karanbir Singh and Bipneet Singh
Gastrointest. Disord. 2026, 8(3), 38; https://doi.org/10.3390/gidisord8030038 - 28 Jul 2026
Viewed by 237
Abstract
Patients with inflammatory bowel disease (IBD) often require long-term immunosuppressive or advanced therapy, raising concerns about treatment-associated malignancy risk. This systematic review evaluated malignancy outcomes associated with biologic, advanced small-molecule, and thiopurine therapies in adults with IBD. PubMed, Embase, the Cochrane Library, and [...] Read more.
Patients with inflammatory bowel disease (IBD) often require long-term immunosuppressive or advanced therapy, raising concerns about treatment-associated malignancy risk. This systematic review evaluated malignancy outcomes associated with biologic, advanced small-molecule, and thiopurine therapies in adults with IBD. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception through June 2025, with supplementary screening of Google Scholar and reference lists. Eligible primary studies included randomized controlled trials and prospective or retrospective cohort studies evaluating malignancy outcomes. Thiopurines were included because they remain clinically important comparators and are central to combination-therapy risk. The Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool were used for observational studies and randomized trials, respectively. Because of substantial clinical and methodological heterogeneity, we did not perform a de novo meta-analysis; pooled estimates from previously published meta-analyses are reported only as contextual evidence. Twenty-eight studies met the inclusion criteria. Thiopurines showed the most consistent malignancy associations, including lymphoma, non-melanoma skin cancer (NMSC), acute myeloid leukemia/myelodysplastic syndrome, and urinary tract cancer. Anti-tumor necrosis factor (anti-TNF) monotherapy was not associated with a clear increase in overall cancer incidence, although a modest lymphoma signal was reported in some datasets. Combination anti-TNF plus thiopurine therapy showed the strongest lymphoma signal. Current evidence has not demonstrated an increased malignancy risk with vedolizumab or ustekinumab, including in available cohorts of patients with prior malignancy; however, confidence is limited by observational designs, small event numbers, heterogeneous cancer histories, and limited follow-up. IBD-specific data for Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators remain comparatively immature, and long-term surveillance is required. Overall, treatment decisions should integrate absolute baseline risk, age, smoking, prior malignancy, prior NMSC, Epstein–Barr virus-related risk, disease-related cancer risk, and cumulative immunosuppressive exposure. Full article
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17 pages, 872 KB  
Article
Anatomical Reconstruction After Metabolic Bariatric Surgery (MBS): Indications and Biochemical Responses in Post-Bariatric Hyperinsulinemic Hypoglycemia Patients—A Single-Center Case Series
by Chaled Alnakib, Fahim Kanani, Shachar Laks, Eyal Leibovitz, Adam Goldstein, Mohamad Jazmawi, Moshe Rubin, Raul Rosenthal and Mordechai Shimonov
Gastrointest. Disord. 2026, 8(3), 37; https://doi.org/10.3390/gidisord8030037 - 27 Jul 2026
Viewed by 216
Abstract
Introduction: Anatomical gastrointestinal reconstruction following metabolic bariatric surgery (MBS) is a revisional procedure used for refractory complications, including malnutrition, intractable reflux, recurrent marginal ulcer disease, and post-bariatric hyperinsulinemic hypoglycemia (PBHH). Objective: This study aims to describe the indications, perioperative outcomes, and short-term results [...] Read more.
Introduction: Anatomical gastrointestinal reconstruction following metabolic bariatric surgery (MBS) is a revisional procedure used for refractory complications, including malnutrition, intractable reflux, recurrent marginal ulcer disease, and post-bariatric hyperinsulinemic hypoglycemia (PBHH). Objective: This study aims to describe the indications, perioperative outcomes, and short-term results of laparoscopic anatomical reconstruction in a single-center series, focusing on patients with PBHH. Methods: We retrospectively reviewed 11 consecutive patients who underwent reconstruction following MBS at a single tertiary center. Perioperative outcomes, weight changes, and biochemical responses to standardized dual-modality (oral and intravenous) glucose suppression testing were analyzed. Results: Between 2018 and 2025, 11 patients completed laparoscopic anatomical reconstruction. The anatomy immediately preceding reconstruction was OAGB in nine patients (81.8%) and RYGB in two (18.2%). The indications overlapped; the most common were severe malnutrition (n = 9), marginal ulcer disease (n = 6), and PBHH (n = 4; three biochemically confirmed, one clinically diagnosed). Ten of eleven procedures (90.9%) were completed laparoscopically, with no 30-day Clavien–Dindo grade III–IV complications. Among the four PBHH patients, symptomatic resolution was achieved in all four, with residual asymptomatic biochemical hypoglycemia in one. Weight gain occurred in 10 of the 11 patients (mean 8.1 ± 4.9 kg) at a median follow-up of 7 months (IQR 3–12). Conclusions: In this preliminary series, laparoscopic anatomical reconstruction was feasible, though the small sample precludes conclusions regarding safety. Incretin hormones were not measured; the mechanistic contribution of restored foregut anatomy is inferred from prior literature rather than demonstrated here. Standardized dual-modality glucose suppression testing was central to patient selection and to documenting the biochemical response. Full article
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14 pages, 972 KB  
Review
Leak-Stratified Management of Early Bile Leaks After Liver Transplantation: A Narrative Review of Leak Characteristics, Patient Stability, and the Limited Evidence on Intervention Timing in the First 14 Postoperative Days
by Murtaja Satea, Alexandre G. Lellouch, Haïzam Oubari, Veronika Dadaev, Rotem Horowitz, Shai Hoffman, Yael Ben Avraham, Tobias Niederegger, Karam Azem, Rodolfo J. Oviedo, Narmin Zoabi, Eviatar Nesher and Fahim Kanani
Gastrointest. Disord. 2026, 8(3), 36; https://doi.org/10.3390/gidisord8030036 - 21 Jul 2026
Viewed by 368
Abstract
Background: Bile leaks complicate 5–25% of liver transplants and are among the most common early postoperative biliary events. Their management within the first 14 postoperative days has traditionally been framed around the timing of intervention. Objective: To evaluate whether leak characteristics and patient [...] Read more.
Background: Bile leaks complicate 5–25% of liver transplants and are among the most common early postoperative biliary events. Their management within the first 14 postoperative days has traditionally been framed around the timing of intervention. Objective: To evaluate whether leak characteristics and patient stability provide more consistent guidance than intervention timing for early post-transplant bile leaks. Methods: A structured narrative review using a dual-source search (AI-assisted semantic search [Elicit Plus] and PubMed/MEDLINE) was conducted. A PICO-informed (Population, Intervention, Comparator, Outcome) framework guided inclusion; two independent reviewers preformed screening, with senior adjudication, yielding 37 sources. Because “early” was defined heterogeneously—by leak onset in most studies (definitions exceeding 14 days) and by intervention timing in others—and no study compared timing within a 14-day window, quantitative pooling was not undertaken. Results: No included study directly compared intervention timing within the first 14 postoperative days. In the largest available analysis of ERCP timing, resolution and adverse event rates did not differ by whether endoscopy was performed within one day, on days two to three, or after three days; endoscopic success was consistently high (80–98%) across temporal windows. Leak type was a consistent correlate of management intensity and resolution: anastomotic leaks were associated with higher surgical-intervention rates (40% vs. 8.3% for T-tube exit-site leaks in one cohort) and lower resolution rates (58–69%) than non-anastomotic leaks (90–100%). Within endoscopic therapy, bridging stent placement—not leak location—was the strongest independent predictor of resolution, and any bile leak, irrespective of subtype, independently predicted subsequent biliary stricture (pooled adjusted OR ≈ 4). Ultra-early leaks (≤72 h), frequently technical failures, formed the one subset favoring early surgical re-exploration. Conclusions: The absence of a demonstrated timing effect reflects a lack of direct comparative data rather than proof that timing is unimportant. Leak type, patient stability, and management modality offer more consistent and actionable guidance than temporal urgency, forming the basis for a leak-stratified framework. Prospective multicenter registries with standardized timing strata and leak type stratification are needed to test whether timing independently influences outcomes. Full article
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12 pages, 600 KB  
Article
Enteric Infections in Relapsing Ulcerative Colitis Patients in Albania: The Predictive Value of CRP/Albumin Ratio
by Marsela Sina, Sara Hoxha, Xhensila Pemaj, Gentiana Qirjako, Enkeleint A. Mechili and Skerdi Prifti
Gastrointest. Disord. 2026, 8(3), 35; https://doi.org/10.3390/gidisord8030035 - 6 Jul 2026
Viewed by 319
Abstract
Background and Aim: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease (IBD) associated with increased susceptibility to enteric infections, which may mimic or exacerbate disease flares. The C-reactive protein (CRP)-to-albumin ratio (CAR) has emerged as a simple indicator of systemic inflammation [...] Read more.
Background and Aim: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease (IBD) associated with increased susceptibility to enteric infections, which may mimic or exacerbate disease flares. The C-reactive protein (CRP)-to-albumin ratio (CAR) has emerged as a simple indicator of systemic inflammation in UC. This study aimed to assess the prevalence of stool infections in active UC and to further evaluate CAR as a potential predictive marker. Methods: This retrospective study included 42 patients with active UC (Mayo score ≥ 6) from April 2024 to February 2025. Stool samples were analyzed using multiplex polymerase chain reaction (PCR) for 25 bacterial, viral, and parasitic pathogens. Serum CRP and albumin levels were measured to calculate the CAR. Patients were categorized as infected or non-infected. Logistic regression and receiver operating characteristic (ROC) analyses were performed to evaluate CAR predictive performance. Results: Enteric infections were identified in 35.7% of patients, with Escherichia coli species predominating. CAR was significantly higher in infected than in non-infected patients [0.21 (0.02–0.62) vs. 0.06 (0.02–0.15), p = 0.028]. CAR was significantly associated with enteric infection in logistic regression analysis (OR = 240.0, 95% CI 2.7–21,555.6; p = 0.017). ROC analysis yielded an AUC of 0.706, with a cut-off value of 0.669 providing 100% specificity and 40% sensitivity. Conclusions: Enteric infections are prevalent in patients with active UC. CAR may serve as a simple, rapid, and accessible adjunctive marker to identify patients who warrant further evaluation for enteric infection. Thus, it may aid in differentiating UC flares from superimposed infection. Full article
(This article belongs to the Special Issue Feature Papers in Gastrointestinal Disorders in 2025–2026)
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15 pages, 1944 KB  
Review
Indocyanine Green Fluorescence During Heller Dor Myotomy for Achalasia: Techniques, Intraoperative Applications, and Evidence Gaps—A Scoping Review
by Agostino Fernicola, Michele Santangelo, Aldo Rocca, Pasquale Avella, Armando Calogero, Felice Crocetto, Luigi Ricciardelli, Antonio Alvigi, Andrea Paolillo, Carmen De Cocinis, Domenica Pignatelli, Martina Sommese, Antonio Grimaldi, Alessio Cece, Giacomo Benassai and Gennaro Quarto
Gastrointest. Disord. 2026, 8(3), 34; https://doi.org/10.3390/gidisord8030034 - 6 Jul 2026
Viewed by 360
Abstract
Background: Heller myotomy (HM) is the standard surgical treatment for achalasia. Complete muscular division while preserving mucosal integrity is essential for optimal outcomes. Indocyanine green fluorescence (ICG) imaging has recently emerged as a potential intraoperative adjunct during minimally invasive HM, although evidence remains [...] Read more.
Background: Heller myotomy (HM) is the standard surgical treatment for achalasia. Complete muscular division while preserving mucosal integrity is essential for optimal outcomes. Indocyanine green fluorescence (ICG) imaging has recently emerged as a potential intraoperative adjunct during minimally invasive HM, although evidence remains limited and heterogeneous. Methods: A scoping review was conducted according to PRISMA-ScR recommendations. PubMed, Scopus, and Web of Science were systematically searched to identify clinical studies reporting intraoperative ICG use during laparoscopic or robotic HM. Data regarding surgical approach, fluorescence technique, intraoperative applications, and outcomes were extracted and descriptively synthesized. Results: Four clinical studies published between 2022 and 2024 were included, involving 58 patients overall, of whom 41 underwent minimally invasive HM with intraoperative ICG fluorescence assessment. Two main fluorescence strategies were identified. Intravenous ICG administration was exclusively evaluated during robotic Heller myotomy, whereas all laparoscopic studies employed intraluminal ICG instillation through a nasogastric tube. Fluorescence imaging was used to assess myotomy completeness, identify residual muscle fibers, and detect mucosal perforation. Intraluminal ICG enabled direct visualization of the mucosal tube and facilitated leak detection, whereas intravenous administration enhanced tissue contrast and identification of residual muscular bundles. No ICG-related adverse events were reported. However, the available evidence was limited to small observational series with heterogeneous protocols and inconsistent outcome reporting. Conclusions: ICG fluorescence appears technically feasible during minimally invasive HM and may support intraoperative assessment of myotomy completeness and mucosal integrity. Although early clinical experience is encouraging, the available evidence remains insufficient to support routine implementation of ICG-guided assessment during Heller myotomy, highlighting the need for standardized prospective comparative studies. Full article
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13 pages, 284 KB  
Review
IBS-Related Faecal Incontinence: A Focused Narrative Review of Mechanisms, Evidence, and Conservative Care Considerations
by Yohei Okawa
Gastrointest. Disord. 2026, 8(3), 33; https://doi.org/10.3390/gidisord8030033 - 29 Jun 2026
Viewed by 622
Abstract
Background: Faecal incontinence (FI) may occur in patients with irritable bowel syndrome (IBS), particularly when loose stool, urgency, reduced warning time, fluctuating bowel habits, or constipation with retention interferes with timely defaecation. However, IBS-related FI should be distinguished from FI caused primarily by [...] Read more.
Background: Faecal incontinence (FI) may occur in patients with irritable bowel syndrome (IBS), particularly when loose stool, urgency, reduced warning time, fluctuating bowel habits, or constipation with retention interferes with timely defaecation. However, IBS-related FI should be distinguished from FI caused primarily by structural sphincter injury, neurological disease, advanced frailty, or other organic gastrointestinal disorders. This focused narrative review examines IBS-specific mechanisms and conservative care considerations relevant to FI risk. Methods: This article is a focused narrative review rather than a systematic review, scoping review, clinical guideline, or formal GRADE assessment. PubMed and the Ichushi-Web/Japanese Medical Abstracts Society were searched for studies published from January 2000 to June 2026. Search terms were combined and included irritable bowel syndrome with faecal/fecal incontinence, urgency, diarrhoea/diarrhea, constipation, stool form, bowel diaries, diet, FODMAP, fibre/fiber, pelvic floor rehabilitation, biofeedback, skin care, absorbent products, ultrasound, and conservative management. Studies directly addressing IBS mechanisms or symptom management, FI assessment or conservative FI care, or implementation issues relevant to IBS-related FI were deemed eligible. Results: Direct studies of FI prevention in IBS patients are scarce. The most defensible IBS-specific targets are loose stool, urgency, reduced warning time, alternating bowel habits, constipation with retention or incomplete evacuation, diet- or medication-related triggers, stress-related exacerbation, and toilet access. Broader FI evidence supports supportive measures such as skin protection, absorbent products, pelvic floor rehabilitation, biofeedback, transanal irrigation, and referral, but these measures are not IBS-specific unless they are connected to IBS-related symptom pathways. Synthesis: Evidence was organized into three categories: direct IBS evidence, general FI evidence, and indirect implementation evidence from continence-care settings. No formal certainty ratings or recommendation strengths were assigned; statements are therefore framed as clinical considerations and areas for future study rather than guideline-level recommendations. Conclusions: IBS-related FI should be discussed as a symptom-risk pathway within IBS rather than as FI in general. Available evidence suggests the value of assessing IBS subtype, stool form, urgency, triggers, warning time, and toileting circumstances before applying general FI support. Because direct preventive trials are limited, conclusions should be interpreted as practice-informing clinical considerations rather than firm recommendations. Full article
28 pages, 2237 KB  
Review
Multidimensional Regulatory Networks of Immune Resistance in Intrahepatic Cholangiocarcinoma: Synergistic Mechanisms of Tumor Microenvironment, Immune Cells, and Microbiota, and Novel Therapeutic Strategies
by Lingyu Kong and Hongxin Piao
Gastrointest. Disord. 2026, 8(3), 32; https://doi.org/10.3390/gidisord8030032 - 29 Jun 2026
Viewed by 665
Abstract
Cholangiocarcinoma (CCA) is a highly malignant tumor originating from the epithelium of the bile ducts. It has an insidious onset, is difficult to diagnose in its early stages, has a low rate of curative resection, and carries an extremely poor prognosis. Among these, [...] Read more.
Cholangiocarcinoma (CCA) is a highly malignant tumor originating from the epithelium of the bile ducts. It has an insidious onset, is difficult to diagnose in its early stages, has a low rate of curative resection, and carries an extremely poor prognosis. Among these, intrahepatic cholangiocarcinoma (iCCA), as the most representative subtype, is a classic “immunologically cold tumor.” The response rate to single-agent immunotherapy is only 5–10%, and the mechanisms of immune resistance are complex and not yet fully elucidated. The tumor microenvironment, serving as the core site of immune resistance, forms a highly immunosuppressive network composed of cancer-associated fibroblasts, hypoxia, metabolic reprogramming, and epigenetic abnormalities; a population of immunosuppressive cells centered on tumor-associated macrophages further amplifies tolerance signals; and the gut–biliary microbiome exerts systemic immune regulation via the gut–liver axis. Based on mutant mouse models generated via tail vein injection and in-depth studies of mutations in key signaling pathways, our understanding of the mechanisms underlying iCCA’s immune resistance is deepening at both the molecular and systems levels. This article reviews the local and systemic regulatory mechanisms of immune resistance in primary iCCA, summarizes the research value of experimental and preclinical models, and reviews novel strategies such as tumor microenvironment remodeling, activation of immune cell networks, microbiome interventions, and multidimensional combination therapies. It analyzes current research bottlenecks and clinical challenges and outlines the future direction of precision immunotherapy, aiming to provide a theoretical basis and new insights for overcoming iCCA immunotherapy resistance and advancing clinical translation. Full article
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13 pages, 685 KB  
Article
Resilience in Gastroparesis Is Not Associated with Symptom Severity or Healthcare Utilization: An Exploratory Pilot Analysis
by Elina Stoffel, John William Blackett, Alexa Choy, Dakota Ma, Wynette Almeida, Brad Kuo, Daniela Jodorkovsky and Sydney Pomenti
Gastrointest. Disord. 2026, 8(3), 31; https://doi.org/10.3390/gidisord8030031 - 24 Jun 2026
Viewed by 385
Abstract
Background: Gastroparesis presents with frequently debilitating symptoms of nausea, vomiting, abdominal pain, bloating and early satiety, resulting in high healthcare utilization. Resilience, defined as the inherent and modifiable ability of an individual to adapt and recover positively to stress, is crucial for [...] Read more.
Background: Gastroparesis presents with frequently debilitating symptoms of nausea, vomiting, abdominal pain, bloating and early satiety, resulting in high healthcare utilization. Resilience, defined as the inherent and modifiable ability of an individual to adapt and recover positively to stress, is crucial for patients with chronic diseases but has not been studied in gastroparesis. We aimed to investigate if resilience correlates with acute care utilization and symptom severity in patients with gastroparesis. Methods: We conducted a single-center prospective observational study of patients with gastroparesis. Resilience was assessed using the 10-item Connor–Davidson Resilience scale (CD-RISC). Symptom severity was assessed through the Gastroparesis Cardinal Symptom Index (GCSI). Gastric emptying severity using scintigraphy or wireless motility capsule was categorized as mild, moderate, or severe based on consensus recommendations. Acute care utilization and hospitalizations in the last 12 months, comorbidities, medications, and demographic information were collected. Count outcomes were modeled using negative binomial regression due to overdispersion. Models were adjusted for age, sex, and symptom severity. Results: Among 40 consecutive patients (mean age 39 ± 16, 88% female), gastric emptying severity was mild in 35%, moderate in 15%, severe in 30%, and unknown in 20%. Mean resilience score was 29 ± 8 and mean GCSI was 2.96 ± 1.14. Gastroparesis symptoms did not correlate with gastric emptying severity (p = 0.5). In a linear regression model, no statistically significant correlation was observed between resilience and mean GCSI score in unadjusted or adjusted models. In negative binomial regression models, greater symptom severity was strongly associated with higher Emergency Department (ED)/urgent care visits (IRR 3.12; 95% CI 1.60–6.98; p < 0.001) and hospitalization rates (IRR 3.36; 95% CI 1.62–8.57, p = 0.006). Resilience was not a significant predictor of either (IRR 1.07; 0.95–1.22; p = 0.2 and IRR 1.02; 0.89–1.18; p = 0.7). Conclusions: Among patients with gastroparesis, no statistically significant association was detected between resilience and symptom severity, gastric emptying, or acute-care utilization after accounting for clinical and demographic factors. Symptom severity was the dominant predictor of ED visits and hospitalizations. These findings suggest that symptomatic disease burden, rather than objective gastric emptying severity, is the primary driver of acute healthcare utilization in this cohort. Full article
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