Annals of Gastroenterology

A national consensus guideline on the performance and interpretation of hydrogen- and methane-based breath tests for carbohydrate malabsorption, small intestinal bacterial overgrowth, and intestinal methanogen overgrowth

2026-07-14T17:00:39+03:00

Abdominal bloating, distension, excessive gas, abdominal pain, diarrhea and constipation are common symptoms that may arise from carbohydrate malabsorption, carbohydrate intolerance, small intestinal bacterial overgrowth (SIBO), intestinal methanogen overgrowth (IMO), or disorders of gut–brain interaction. Hydrogen- and methane-based breath tests are safe, noninvasive, inexpensive and widely used, but differences in indications, patient preparation, test performance and interpretation can lead to inconsistent diagnoses and management. At the recommendation of the Israeli Gastroenterology Association, a multidisciplinary panel of adult and pediatric gastroenterologists, neurogastroenterologists, dietitians, clinical nutrition specialists and heads of gastrointestinal laboratories reviewed the literature and reached consensus during 8 meetings. This guideline provides practical standards for breath testing in adults and children. The panel recommends simultaneous measurement of hydrogen and methane, structured symptom recording during testing, standardized pretest preparation, and cautious interpretation in settings that alter anatomy or orocecal transit time. Lactulose is recommended as the preferred substrate for SIBO/IMO testing, with glucose as an acceptable alternative. Carbohydrate malabsorption
should be distinguished from intolerance by the presence or absence of typical symptoms during the test. The guideline also defines suspected hypersensitivity and highlights methane production as a cause of false-negative hydrogen-based carbohydrate tests. These recommendations are intended to harmonize breath test practice and reporting, and to support rational, test-directed treatment in adult and pediatric patients.

Keywords Breath test, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, carbohydrate malabsorption, carbohydrate intolerance

Ann Gastroenterol 2026; 39 (4): 383-389

Incidentally discovered, intentionally managed: a narrative review of the last decade’s updates on the management of neuroendocrine tumor of the appendix

2026-07-14T17:00:39+03:00

Appendiceal neuroendocrine neoplasms (aNENs) represent an increasingly recognized and heterogeneous subset of gastroenteropancreatic neuroendocrine tumors (NETs), most often identified incidentally on appendectomy specimens. Postoperative management relies on accurate risk stratification grounded in histopathological assessment and aligned with major international guidelines (WHO, ENETS), which distinguish between well-differentiated NETs (NET grades 1 to 3) and poorly differentiated neuroendocrine carcinomas. Critical prognostic
determinants shaping therapeutic decision-making include tumor size, proliferative index (Ki-67), depth of invasion—particularly mesoappendiceal involvement—and lymphovascular invasion (LVI). Consensus recommendations suggest simple appendectomy as definitive treatment for low-risk tumors (<1 cm) and right hemicolectomy for high-risk lesions (>2 cm) or those exhibiting LVI. However, the management of intermediate-sized aNENs (1.0-2.0 cm) remains the principal area of clinical uncertainty, with emerging data suggesting that appendectomy alone may be sufficient for carefully selected patients without adverse pathological factors. This review synthesizes and critically appraises the most recent evidence and international guidelines with the goal of refining current clinical practice. In particular, it provides an updated framework for individualized risk stratification, evaluates the balance between oncological benefit and procedural morbidity in determining the optimal surgical approach, and outlines evidence-based surveillance strategies to support a more consistent, risk-adapted multidisciplinary management of aNENs.

Keywords Appendiceal neuroendocrine tumor, neuroendocrine neoplasms, surgical management, right hemicolectomy, ENETS guidelines

Ann Gastroenterol 2026; 39 (4): 390-404

Granulocyte and monocyte adsorptive apheresis for ulcerative colitis: mechanisms, clinical evidence, and future perspectives

2026-07-14T17:00:39+03:00

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease characterized by continuous mucosal erosions and ulcers in the colon. In recent years, biologics and smallmolecule agents have revolutionized UC management; however, these therapies may be limited by risks such as infections, secondary loss of response, or intolerance. Granulocyte and monocyte adsorptive apheresis (GMA), developed in Japan, offers a non-pharmacologic and selective immunomodulatory approach by removing activated myeloid cells and modulating the inflammatory milieu. In this review, we summarize the mechanisms of action of GMA, including its effects on proinflammatory cytokines and regulatory T-cell responses. We also examine the clinical evidence, from randomized controlled trials and observational studies, that supports its efficacy, particularly in steroid-dependent and elderly patients. While mucosal healing rates with GMA may be lower than those achieved with biologics, its favorable safety profile may support its use as an adjunctive or bridging strategy in selected patients. However, evidence supporting these roles remains limited and is derived mainly from observational studies. Future directions include integration with personalized medicine, biomarker development and global expansion. GMA remains a viable option in the therapeutic landscape of UC.

Keywords Ulcerative colitis, granulocyte monocyte adsorptive apheresis, Adacolumn

Ann Gastroenterol 2026; 39 (4): 405-408

Emerging endoscopic resection strategies for organ preservation in early colorectal cancer

2026-07-14T17:00:39+03:00

The management of early colorectal cancer (CRC) is increasingly debated among gastroenterologists and colorectal surgeons, driven by advances in endoscopic resection that enable curative organpreserving treatment. Conventional endoscopic mucosal resection (EMR) remains the first-line small-to-moderate sized superficial lesions, although its application is limited for larger or fibrotic polyps, because of piecemeal resection and higher recurrence rates. Modified EMR techniques, including anchoring, precutting, and underwater EMR, are widely available and achieve superior technical outcomes without compromising safety, thus broadening the indications for endoscopic resection of low-risk neoplastic lesions. Endoscopic submucosal dissection (ESD) allows en bloc resection regardless of lesion size, and provides accurate histopathological evaluation even when curative criteria are not met, though its use is constrained by its technical complexity and limited availability. For rectal lesions exhibiting features suggestive of deep submucosal invasion, endoscopic intermuscular dissection may serve as an effective endoscopic therapeutic option, as it extends the resection plane into the intermuscular space, achieving clear vertical margins while facilitating organ preservation. Endoscopic full-thickness resection, alone or combined with EMR/ESD, addresses non-lifting, fibrotic or anatomically challenging lesions throughout the colon. Together, these modalities have reshaped the therapeutic landscape of endoscopy, allowing curative and organ-sparing management of early CRCs. This review summarizes organ-preserving endoscopic approaches for early CRC, and proposes a practical algorithm for technique selection while identifying key evidence gaps and future directions.

Keywords Early colorectal cancer, endoscopic resection techniques, organ preservation, colonoscopy, invasive endoscopy

Ann Gastroenterol 2026; 39 (4): 409-423

Increased risk of de novo inflammatory bowel disease following cholecystectomy: a population-based analysis

2026-07-14T17:00:40+03:00

Background Cholecystectomy (CCY) may alter bile acid flow and gut microbiota, increasing the risk of gastrointestinal disease. Prior studies have suggested that CCY may be associated with bile acid diarrhea and microscopic colitis; however, the association with the new diagnosis of inflammatory bowel disease (IBD) remains unstudied. In this study, we evaluated whether CCY was associated with a greater risk of de novo IBD.

Methods We conducted a retrospective cohort study, analyzing data from the TriNetX network (2010-2024), using 1:1 propensity score matching between adult patients undergoing CCY and controls, based on variables that included demographics, comorbidities and medication use. The primary outcome was risk of de novo IBD. Secondary outcomes included the risk of developing ulcerative colitis (UC) or Crohn’s disease (CD). Kaplan-Meier analysis with hazard ratios (HRs) and 95% confidence intervals (CIs) was used to compare time-to-event rates.

Results Among 570,317 matched pairs, CCY was associated with a greater risk of IBD (adjusted HR [aHR] 1.29, 95%CI 1.22-1.35; P<0.001), and specifically CD (aHR 1.83, 95%CI 1.69-1.99; P<0.001), but not the risk of UC. This elevated risk persisted across both sexes and all age groups. Among patient characteristics, tobacco use was associated with the greatest additional risk of IBD post-CCY (aHR 1.43, 95%CI 1.19-1.76; P<0.001).

Conclusions Prior CCY is associated with a greater risk of CD but not UC. These findings support the need for a low threshold to think about CD in patients with gastrointestinal symptoms after CCY.

Keywords Inflammatory bowel disease, cholecystectomy, bile acids, diarrhea

Ann Gastroenterol 2026; 39 (4): 424-429

The effect of pembrolizumab on the healing of colonic anastomosis: a pre-clinical study in Wistar rats

2026-07-14T17:00:40+03:00

Background Pembrolizumab is a monoclonal antibody that targets the programmed cell death-1 (PD-1) protein. Blocking this pathway alters T-cell activity, and has been approved for the treatment of several malignancies, including microsatellite instability-high (MSI-H) and mismatch repair-deficient (dMMR) colorectal cancers. The aim of this study was to evaluate the effect of pembrolizumab on colonic anastomotic healing in a rat model.

Methods Sixty male Wistar rats were randomly divided into 2 groups of 30: a control group, and an experimental group receiving pembrolizumab. Each group was further divided into 3 subgroups of 10 rats, sacrificed on postoperative day (POD) 3, 7 or 14. All animals underwent laparotomy, a 1-centimeter segmental colectomy, and an end-to-end colonic anastomosis. Postmortem evaluation included measuring anastomotic bursting pressure, tissue hydroxyproline levels, and histopathological assessment.

Results Statistically significant differences in bursting pressure (P=0.019) and rupture site (P=0.033) were observed between the groups on POD 7. Tissue hydroxyproline levels were significantly lower in the pembrolizumab-treated subgroups on POD 7 (P=0.003), and POD 14 (P=0.001). Histopathological analysis demonstrated significant differences on POD 3, in neovascularization (P=0.026), fibroblast ingrowth (P=0.005), and collagen deposition (P=0.030), suggesting impaired inflammatory-phase healing.

Conclusions This experimental study suggests that a high single dose of pembrolizumab may negatively affect colonic anastomotic healing in rats. Further studies are necessary to determine the safety of intestinal anastomosis in both emergency and elective clinical settings.

Keywords Pembrolizumab, immune checkpoint inhibitors, healing, anastomosis, colorectal cancer

Ann Gastroenterol 2026; 39 (4): 430-437

Comparative outcomes and characteristics of biliary, alcoholic and drug-induced pancreatitis based on the National Inpatient Sample (2016-2021)

2026-07-14T17:00:40+03:00

Background Pancreatitis outcomes vary significantly depending on etiology. We compared biliary, alcoholic and drug-induced pancreatitis, focusing on mortality, complications and healthcare resource utilization to inform etiology-specific management strategies.

Methods A nationwide retrospective analysis was conducted using the National Inpatient Sample (NIS) database from 2016-2021. Patients with biliary, alcoholic and drug-induced pancreatitis were identified using International Classification of Diseases, 10th Revision (ICD-10) codes. Logistic regression models were used to compare mortality, complications and healthcare utilization, with biliary pancreatitis as the reference. Adjusted odds ratios (aORs) and regression coefficients were calculated.

Results A total of 287,050 biliary, 451,730 alcoholic, and 27,465 drug-induced pancreatitis hospitalizations were identified. Patients with alcoholic pancreatitis were younger and predominantly male, while those with drug-induced pancreatitis had higher comorbidity burdens, including diabetes, dyslipidemia and hypertension. Mortality was higher in alcoholic pancreatitis (aOR 1.19, 95% confidence interval [CI] 1.06-1.41; P=0.05), whereas drug-induced pancreatitis showed no significant difference. Alcoholic pancreatitis was associated with greater odds of pseudocyst formation (aOR 3.54, 95%CI 3.32-3.79), bleeding (aOR 1.52, 95%CI 1.41-1.63), and mechanical ventilation (aOR 2.06, 95%CI 1.84-2.31), all with P<0.001. In contrast, drug-induced pancreatitis was linked to lower odds of bleeding (aOR 0.69, 95%CI 0.57-0.84; P<0.001) and percutaneous drainage (aOR 0.23, 95%CI 0.09-0.63; P=0.004). Both alcoholic and drug-induced pancreatitis had shorter hospital stays and lower total charges compared with biliary pancreatitis.

Conclusions Alcoholic pancreatitis is associated with higher mortality and complication rates, while drug-induced pancreatitis demonstrates fewer complications but greater comorbidity. These findings highlight the importance of etiology-based management in optimizing pancreatitis outcomes.

Keywords Pancreatitis, biliary, alcoholic, drug-induced, outcomes

Ann Gastroenterol 2026; 39 (4): 438-445

Prior bariatric surgery and better short-term outcomes in acute pancreatitis: a multicenter propensity-matched analysis

2026-07-14T17:00:40+03:00

Background Obesity is associated with an increased risk of severe acute pancreatitis (AP). Bariatric surgery is known to improve comorbidities and reduce systemic inflammatory burden. We aimed to evaluate whether a history of bariatric surgery is associated with differences in shortterm clinical outcomes among patients hospitalized with AP.

Methods Retrospective study using the TriNetX research network, including adults aged 18 years or older who were hospitalized with AP. Patients with chronic pancreatitis, pancreatic malignancy or cystic pancreatic disease were excluded. Study cohorts were defined based on the presence or absence of prior bariatric surgery performed at least 1 year before the AP admission. Cohorts were matched 1:1 using propensity scores. The primary outcome was 30-day all-cause mortality. Secondary outcomes were acute kidney injury (AKI), need for hemodialysis, endotracheal intubation, vasopressor use, elevations in inflammatory markers, and pancreatitis-related procedures, such as endoscopic retrograde cholangiopancreatography (ERCP) with stent placement, cholecystectomy, and pancreatic debridement.

Results After matching, both cohorts included 4024 patients. Bariatric patients had significantly lower 30-day mortality (1.9% vs. 2.6%; relative risk [RR] 0.71, 95% confidence interval [CI] 0.53-0.95; P=0.021), less AKI (0.8% vs. 1.5%; RR 0.54, 95%CI 0.35-0.82; P=0.003), and less hemodialysis (0.5% vs. 0.9%; RR 0.54, 95%CI 0.31-0.93; P=0.025). ERCP with stent placement was less frequent in the bariatric group (1.0% vs. 1.6%; RR 0.60, 95%CI 0.40-0.89; P=0.011). Other secondary outcomes did not differ significantly between groups.

Conclusions Bariatric surgery was associated with better short-term outcomes in AP. This included lower mortality and renal complications, possibly via metabolic and inflammatory effects.

Keywords Acute pancreatitis, bariatric, obesity, mortality

Ann Gastroenterol 2026; 39 (4): 446-451

Effect of GLP-1 receptor agonists on upper gastrointestinal endoscopy outcomes: a systematic review and meta-analysis

2026-07-14T17:00:40+03:00

Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying, raising concerns about potential aspiration risk during upper gastrointestinal (GI) endoscopy. We conducted a systematic review and meta-analysis to evaluate the effect of GLP-1 RA therapy on procedural outcomes in patients undergoing upper GI endoscopy.

Methods We searched Medline and Cochrane library up to July 2025 without restrictions. Eligible studies evaluated patients undergoing upper GI endoscopy, comparing those taking GLP-1 RAs with those who were not. Outcomes of interest were the incidence of retained gastric contents (RGC), bronchopulmonary aspiration, and procedure discontinuation. Pooled estimates are expressed as odds ratios (ORs) with 95% confidence intervals (CIs), using a random-effects metaanalysis with inverse variance weighting.

Results Twenty-four observational studies, predominantly retrospective, met the inclusion criteria: these comprised 184,707 participants, of whom 59,095 were taking GLP-1 RAs. Mean age was 58.7 years, 48.8% were women, and 51.2% had type 2 diabetes. Use of GLP-1 RAs was associated with higher rates of RGC (OR 4.82, 95%CI 3.66-6.35) and procedure discontinuation (OR 3.93, 95%CI 2.42-6.39) compared with control treatment. In contrast, the incidence of aspiration events was similar between groups (OR 1.1, 95%CI 0.84-1.48). Results remained consistent in a sensitivity analysis based on propensity score matching to control for confounders.

Conclusions GLP-1 RA therapy is associated with a greater incidence of RGC and higher rates of endoscopy termination, but not with a higher risk of aspiration. Adjusting the fasting duration, rather than routinely discontinuing GLP-1 RAs, may represent a reasonable management approach.

Keywords Upper gastrointestinal endoscopy, glucagon-like peptide-1 receptor agonists, systematic review, meta-analysis

Ann Gastroenterol 2026; 39 (4): 452-463

Solid pseudopapillary epithelial neoplasm of the pancreas: an audit of 29 cases operated in a tertiary Indian centre

2026-07-14T17:00:41+03:00

Background Solid pseudopapillary epithelial neoplasm (SPEN) of the pancreas is an indolent tumor of rare occurrence seen predominantly in young females in the 2nd to 4th decade. These tumors tend to grow large, producing a mass effect, or may show local invasiveness.

Method This is a retrospective analysis of a prospectively maintained database of SPEN cases operated at a tertiary care hospital in India from 2011-2023.

Results The cohort consisted of 29 patients with a male: female ratio of 1:8.6, and a median age of 24 years. The majority of the lesions were in the body and tail of the pancreas (65.5%). Mean tumor diameter was 6.1±1.9 cm. Pancreatic resection (9 distal pancreatectomies, 7 Whipple’spancreatic oduodenectomies, 2 central pancreatectomies) was undertaken in the majority of cases (62.1%), while 11 patients (37.9%) underwent enucleation. Additional resections included splenectomy (n=4), segmental colonic resection (n=2), and 1 non-anatomical liver wedge resection for solitary liver metastasis. Mean operative time and blood loss were 222.1±106.1 min and 115.5±85.9 mL, respectively. Minor complications were seen in 7 (24.1%) patients, while 1 patient had a major complication. At a median follow up of 37 months, 28 (96.6%) patients were alive, 1 of whom had local recurrence.

Conclusions SPEN represents an indolent, low-grade malignant tumor that is reasonably diagnosed preoperatively by cross-sectional imaging. The majority of cases are cured by surgical resection, the extent of which is dictated by the location of the tumor and its relation to surrounding structures. Excellent outcomes, both short- and long-term, can be achieved.

Keywords Solid pseudopapillary epithelial neoplasm, pancreatic resection, enucleation

Ann Gastroenterol 2026; 39 (4): 464-470

Blood eosinophilia in patients with inflammatory bowel disease losing response to biologics

2026-07-14T17:00:41+03:00

Background Emerging data suggest that blood eosinophilia may be linked to inflammatory bowel disease (IBD) activity and biologic treatment failure. This study assessed the occurrence of eosinophilia in IBD patients experiencing biologic failure.

Methods This was a single-center retrospective study of IBD patients treated with infliximab (IFX) or vedolizumab (VDZ) between 2017 and 2023. Demographics, disease characteristics, disease activity, treatment modifications, together with data on blood eosinophilia and persistent blood eosinophilia, were recorded at 1-year follow up following treatment initiation with biologics. The outcomes were rate of biologic failure, hospitalizations, and surgery at 1 year. Uni- and multivariate analyses were performed to identify factors associated with these outcomes.

Results The study included 154 patients, 96 with Crohn’s disease (CD) (62.3%) and 58 with ulcerative colitis (UC) (37.7%). The occurrence of blood eosinophilia was observed in 22% of patients over 1 year of followup. In univariate analysis, factors associated with biologic failure included previous biologic exposure (P<0.001), baseline immunosuppressants (P=0.009), baseline perinuclear antineutrophil cytoplasmic antibody (P=0.041), and blood eosinophilia (P=0.037). Blood eosinophilia was associated with a higher risk of VDZ failure (odds ratio [OR] 2.81, 95% confidence interval [CI] 1.01-8.10; P=0.047) and was more frequently observed in patients with CD than in UC (OR 2.97, 95%CI 1.05-8.91; P=0.040). Multivariate analysis confirmed the association of blood eosinophilia and biologic failure (OR 2.65, 95%CI 1.08-6.65; P=0.034).

Conclusion Blood eosinophilia was independently associated with biologic failure at 1 year in IBD patients and may represent a risk-stratifying biomarker.

Keywords Blood eosinophilia, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, biologics

Ann Gastroenterol 2026; 39 (4): 471-479

Nonconventional dysplasia in ulcerative colitis: a clinicopathological study of 694 patients

2026-07-14T17:00:41+03:00

Background Ulcerative colitis (UC) carries an increased risk of colorectal carcinoma (CRC) through the inflammation–dysplasia–carcinoma sequence. Recently, several nonconventional dysplastic subtypes have been recognized, often lacking classical features and posing diagnostic challenges.

Method This retrospective study evaluated dysplasia frequency and patterns in UC patients using archival colonoscopic biopsy specimens from the Pathology Laboratory at Ain Shams University Hospitals between 2020 and 2024.

Results A total of 694 patients with histologically confirmed UC were included. For each patient, 1 representative colonoscopic biopsy was evaluated: the most recent biopsy from the most distal colonic site when multiple biopsies were available. This specimen was reviewed histologically, regardless of whether dysplasia had previously or concurrently been diagnosed at another site. Based on this standardized approach, 203 of the 694 patients (29.3%) were found to have dysplasia, including 88 patients (43.3%) with conventional dysplasia and 115 patients (56.7%) with nonconventional dysplasia. The most common nonconventional subtype was dysplasia with increased Paneth cell differentiation (48.7%), followed by hypermucinous dysplasia (19.1%), crypt cell dysplasia (18.3%), goblet cell-deficient dysplasia (11.3%), and serrated dysplasia variants (2.6%). Over 87% of nonconventional dysplastic lesions presented endoscopically with flat/ invisible appearance; however, serrated dysplasia subtypes represented an exception, as all serrated lesions in our cohort were polypoid. Patients with nonconventional dysplasia were significantly younger (median 29.5 vs. 35 years for conventional dysplasia, P=0.015).

Conclusions Nonconventional dysplasia is frequent in UC, and often presents endoscopically with flat/invisible appearance. Pathologists should recognize and report these subtypes to improve surveillance accuracy.

Keywords Ulcerative colitis, dysplasia, nonconventional dysplasia

Ann Gastroenterol 2026; 39 (4): 480-486

Impact of p53 mutations on the synergistic effects of metformin and radiation on colorectal cancer cells

2026-07-14T17:00:41+03:00

Background Metformin has been reported to be effective as an adjunctive therapy in cancer treatment. In this study, the synergistic effects of metformin and radiotherapy were investigated in colorectal cancer cell lines and colorectal cancer organoids, as were the underlying mechanisms.

Methods This was an experimental study conducted in vitro. Cell proliferation was investigated in vitro after treatment of colorectal cancer cell lines with metformin and radiation. Western blotting was used to analyse treatment-induced changes in p53 expression. The combination index for metformin and irradiation was calculated. Organoids were generated via genomic analysis of colorectal cancer cells from surgical specimens from patients with colorectal cancer. Responses of colorectal cancer organoids with and without p53 mutations to metformin and radiation were compared. Organoids cultured from human colorectal cancer and cell lines were used.

Results In experiments using the colorectal cancer cell lines HCT116 and Lovo, which are p53 wild type cells, the combination treatment of metformin and irradiation appeared to have a synergistic effect. In HCT116 and Lovo cells, metformin treatment increased TP53 expression. No synergistic effect of metformin treatment and irradiation was demonstrated in WiDr and SW620 cells, which contain p53 mutations. Measurements of cell proliferation rates in colorectal cancer organoids also confirmed a similar trend in p53 wild-type organoids and those with p53 mutations.

Conclusion Mutations in the p53 gene in colorectal cancer cells may influence the synergistic effect of metformin and radiotherapy.

Keywords Colorectal cancer, metformin, radiation, organoid, p53

Ann Gastroenterol 2026; 39 (4): 487-494

Immune-mediated diarrhea with normal investigations: the importance of diagnostic stratification and small-bowel assessment

2026-07-14T17:00:41+03:00

Authors’ reply

2026-07-14T17:00:42+03:00