Gastroenterology[JOURNAL]
Sun
200 papers
Prognostic value of the systemic immune-inflammation index in gastrointestinal cancers treated with immune checkpoint inhibitors: a systematic review and meta-analysis.
Lu J, Feng Y, Guo K … +1 more , Pan H
BMC Gastroenterol · 2026 Jun · PMID 42343293 · Full text
BACKGROUND: Gastrointestinal (GI) cancers, including pancreatic, gastric, esophageal, colorectal, and hepatocellular carcinoma (HCC), have high mortality rates. Despite advances in immune checkpoint inhibitors (ICIs), tr...
BACKGROUND: Gastrointestinal (GI) cancers, including pancreatic, gastric, esophageal, colorectal, and hepatocellular carcinoma (HCC), have high mortality rates. Despite advances in immune checkpoint inhibitors (ICIs), treatment outcomes remain variable. Identifying reliable biomarkers, such as the systemic immune-inflammation index (SII), which combines platelet, neutrophil, and lymphocyte counts, could help optimize treatment strategies. Biologically, an elevated SII is thought to indicate a dominance of pro-tumor inflammation and a suppressed adaptive immune response, thereby potentially dampening the therapeutic efficacy of ICIs. METHODS: A systematic review was conducted of studies from Cochrane Library, Embase, and PubMed, published until August 15, 2025. This review was conducted in strict adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies involved GI cancer patients treated with ICIs, reported baseline or treatment SII data, and provided hazard ratios (HRs) for progression-free survival (PFS) or overall survival (OS). Exclusions included studies on non-GI cancers or incomplete data. RESULTS: 28 studies with 4752 patients were included. High baseline SII levels were associated with worse OS and PFS in gastric cancer (OS: HR = 2.24, 95% CI: 1.84-2.72, I = 19.4%; PFS: HR = 1.57, 95% CI: 1.35-1.83, I = 0%), HCC (OS: HR = 1.80, 95% CI: 1.47-2.21, I = 2.6%; PFS: HR = 1.60, 95% CI: 1.24-2.06, I = 53.7%), and esophageal cancer (OS: HR = 1.79, 95% CI: 1.53-2.09, I = 39.8%; PFS: HR = 1.50, 95% CI: 1.12-2.01, I = 32.6%). Baseline SII was a stronger predictor of survival than post-treatment or dynamic measurements. CONCLUSION: SII is a promising, cost-effective prognostic biomarker for GI cancer patients receiving ICIs. Elevated baseline SII predicts poorer survival, particularly in gastric cancer, HCC, and esophageal cancer. These findings highlight the potential utility of SII in patient risk stratification and clinical decision-making, thereby supporting its integration into precision oncology strategies.
Efficacy of abdominal drainage in perforated appendicitis: a retrospective single-center study using AAST grading and inverse probability treatment weighting analysis.
Wang C, Li S, Lu H … +4 more , Liu H, Yu Z, Wang S, Zhang D
BMC Gastroenterol · 2026 Jun · PMID 42343248 · Full text
BACKGROUND: While routine use of abdominal drainage in cases of perforated appendicitis is not generally recommended, there exists a paucity of evidence regarding the detailed stratification of its necessity based on var...
BACKGROUND: While routine use of abdominal drainage in cases of perforated appendicitis is not generally recommended, there exists a paucity of evidence regarding the detailed stratification of its necessity based on varying degrees of intraoperatively detected abdominal contamination. This study aimed to assess the relationship between abdominal drainage and postoperative outcomes in patients with perforated appendicitis, categorized according to AAST severity grades. METHODS: This study retrospectively included 278 patients with perforated appendicitis who underwent laparoscopic surgery between January 2021 and December 2025. Patients were classified according to the American Association for the Surgery of Trauma (AAST) grading criteria into AAST grades 3&4 (126 patients) and AAST grade 5 (152 patients). The primary outcome measured was the occurrence of surgical complications within 30 days post-surgery. Inverse probability of treatment weighting (IPTW) was employed to control for confounding variables, and E-value analysis was conducted alongside multifactorial logistic regression to evaluate the relationship between drainage and outcomes. RESULTS: In patients with AAST grade 5 appendicitis, abdominal drainage did not significantly reduce the risk of intra-abdominal abscess (aOR = 1.60, 95% CI: 0.54-4.72, P = 0.396) and may be linked to an increased risk of overall surgical complications (aOR = 2.16, 95% CI: 0.88-5.28, P = 0.091). Multifactorial logistic regression analysis indicated that drainage was an independent risk factor for surgical complications (aOR = 2.42, 95% CI: 1.02-5.77, P = 0.045). The median length of hospital stay was significantly longer in the drainage group compared to the non-drainage group (5.0 days vs. 3.0 days), as were medical costs (CNY 16,100 vs. CNY 14,100), with both comparisons yielding P < 0.001. Among patients with AAST grades 3&4 appendicitis, no statistically significant differences were observed between the drainage and non-drainage groups regarding overall complications (15.4% vs. 7.0%, P = 0.236) or intra-abdominal abscess (11.5% vs. 3.0%, P = 0.102). Furthermore, in AAST grades 3&4 patients, drainage did not significantly influence the risk of overall complications, abdominal abscesses, or other secondary outcomes (all P > 0.05). CONCLUSION: For AAST grade 5 perforated appendicitis, routine drainage fails to prevent complications and may increase risks, recovery time, and costs. Likewise, no significant benefit was observed in grades 3&4. Therefore, routine drain use is not recommended, favoring individualized intraoperative decision-making.
Prognostic nutritional index as a predictor of ursodeoxycholic acid response in primary biliary cholangitis: a retrospective study.
Zheng M, Lei H, He H … +7 more , Huang Y, Zhu H, Lin H, Fu W, Tai W, Wang Y, Yang J
BMC Gastroenterol · 2026 Jun · PMID 42343243 · Full text
BACKGROUND: Primary Biliary Cholangitis (PBC) is an autoimmune hepatic disorder characterized by the progressive destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) remains the primary treatment modality;...
BACKGROUND: Primary Biliary Cholangitis (PBC) is an autoimmune hepatic disorder characterized by the progressive destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) remains the primary treatment modality; however, a subset of patients exhibits non-responsiveness to UDCA therapy. The objective of this study is to investigate the association between the Prognostic Nutritional Index (PNI) and UDCA treatment non-responsiveness in individuals diagnosed with PBC. METHODS: This retrospective study encompassed PBC patients who received UDCA therapy (13-15 mg/kg) from June 1, 2014, to December 31, 2021. The criterion for UDCA non-response was defined as an alkaline phosphatase (ALP) level exceeding 1.67 times the upper limit of normal (ULN) after 12 months of UDCA therapy. Logistic regression analysis was utilized to examine the relationship between baseline PNI and response to UDCA. The stableness of the findings was assessed through both unadjusted and adjusted models. RESULTS: The study included 241 patients with PBC (mean age 55.80 ± 11.694 years; 210 (87.1%) females). During the 12-month clinical follow-up, 83 patients exhibited non-responsiveness to UDCA, corresponding to a non-response rate of 34.44%. Univariate binary logistic regression analysis indicated that factors such as alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bile acid, total cholesterol, neutrophils, and PNI were associated with UDCA non-responsiveness (p < 0.05). Multivariate regression analysis showed that lower baseline PNI was associated with UDCA non-response (odds ratio [OR]: 0.882, 95% confidence interval [CI]: 0.825-0.943, p < 0.001). PNI showed modest discriminatory ability for UDCA non-response, with an AUROC of 0.664 in the overall cohort and 0.676 in non-cirrhotic patients. Based on the Youden index, the optimal PNI cut-off value was 49.03. CONCLUSIONS: Lower baseline PNI was associated with inadequate biochemical response to UDCA in patients with PBC and may serve as a supportive risk stratification marker. However, its modest discriminatory performance and retrospective design limit its standalone clinical application. Further prospective validation is needed.
Association of IL-10 promoter and IL-12 gene polymorphisms with the risk of symptomatic Helicobacter pylori infection.
Karami P, Mokari S, Alikhani MY … +7 more , Kazemi S, Mirzaei M, Soltanian A, Ahmadyousefi M, Dehdar F, Haghi AR, Azizi E
BMC Gastroenterol · 2026 Jun · PMID 42343242 · Full text
BACKGROUND: The host's immune response to Helicobacter pylori (H. pylori) infection is largely determined by its cytokine profile. Genetic variations within crucial immunomodulatory genes, including those for interleukin...
BACKGROUND: The host's immune response to Helicobacter pylori (H. pylori) infection is largely determined by its cytokine profile. Genetic variations within crucial immunomodulatory genes, including those for interleukin-10 (IL-10) and interleukin-12 (IL-12), are thought to influence an individual's vulnerability to the infection and its clinical consequences by modifying cytokine production. Nonetheless, research data derived from diverse human populations continue to show inconsistent results. AIM: This case-control analysis sought to examine a potential link between symptomatic H. pylori infection susceptibility in an Iranian population and specific genetic variants in the IL-10 (-1082G > A, -819 C > T) and IL-12 (+ 1188 A > C) genes. METHODS: In this investigation, 68 individuals with confirmed symptomatic H. pylori infection diagnosed by a positive rapid urease test and elevated anti-H. pylori IgG levels exceeding 90 ng/ml via ELISA were enrolled alongside 68 healthy controls. The control group was carefully matched to the patient group based on age, sex, and ethnic background. Genotyping for the IL-10 (-1082G > A, -819 C > T) and IL-12 (+ 1188 A > C) polymorphisms was conducted using the Amplification Refractory Mutation System-PCR (ARMS-PCR) method. To evaluate associations, the distribution of genotypes and alleles between the groups was contrasted using logistic regression, applying additive, dominant, and recessive inheritance models. The strength of any association was expressed as odds ratios (ORs) accompanied by 95% confidence intervals (CIs). RESULTS: The analysis revealed no statistically significant correlations linking the investigated IL-10 and IL-12 gene variants to an increased predisposition for H. pylori infection. A notable methodological observation was the deviation from Hardy-Weinberg equilibrium (HWE) across all studied polymorphisms in the control group. Regarding the IL-10 -1082G > A locus, the AA genotype was associated with a marginally elevated risk estimate; however, this finding was not statistically significant (OR = 3.45, 95% CI: 0.29-41.36; p = 0.327). Likewise, for the IL-12 + 1188 A > C polymorphism, the CC genotype, while more prevalent in the patient cohort, also demonstrated no significant association with infection risk (OR = 1.43, 95% CI: 0.42-4.87; p = 0.567). CONCLUSION: This investigation did not establish a significant link between the specific IL-10 and IL-12 gene variants analyzed and susceptibility to symptomatic H. pylori infection in the studied population. Although minor genetic associations were noted, they lacked statistical significance. Future research with larger sample sizes is required to validate these results and to investigate additional genetic determinants that may affect infection risk.
Association between total body water and the risk of gastrointestinal symptoms: evidence from NHANES and Mendelian randomization analyses.
Li YB, Zheng ZW, Zuo M
BMC Gastroenterol · 2026 Jun · PMID 42343231 · Full text
BACKGROUND: Total body water (TBW) is an important indicator of fluid homeostasis and is closely related to various metabolic and chronic diseases. However, the relationship between TBW and gastrointestinal symptoms (sto...
BACKGROUND: Total body water (TBW) is an important indicator of fluid homeostasis and is closely related to various metabolic and chronic diseases. However, the relationship between TBW and gastrointestinal symptoms (stomach or intestinal illness, SII) remains unclear. Most previous studies were observational and lacked causal inference. This study, based on data from the National Health and Nutrition Examination Survey (NHANES, 2001-2018) and combined with two-sample Mendelian randomization (MR), explored the nonlinear relationship and potential causal association between TBW and gastrointestinal symptoms from both epidemiological and genetic perspectives. METHODS: Using cross-sectional data from the NHANES (2001-2018), logistic regression, restricted cubic spline (RCS), and subgroup analyses were performed to explore the association between TBW and gastrointestinal symptoms. A two-sample MR study was subsequently conducted using genome-wide association study (GWAS) summary statistics to determine the causal relationship between body water mass (BWM) and gastrointestinal or abdominal diseases. RESULTS: From the NHANES, 36,043 participants aged ≥ 20 years were included. Baseline analysis revealed a significant difference in TBW between participants with and without gastrointestinal symptoms. Logistic regression confirmed that the association between TBW and gastrointestinal symptoms was robust across models. RCS analysis suggested a potential nonlinear pattern, although formal testing did not support significant nonlinearity (P = 0.551). Within the range of 24.9-38.5 L, TBW was associated with lower odds of gastrointestinal symptoms (odds ratio (OR) < 1), whereas values above 38.5 L were associated with higher odds (OR > 1). In subgroup analysis, the high-TBW group (> 38.5 L) was associated with increased risk, whereas the low-TBW group (< 38.5 L) showed a protective association. CONCLUSION: There is a potential nonlinear relationship between TBW and the risk of gastrointestinal symptoms. However, as TBW is strongly correlated with body size and adiposity, the associations may be largely driven by obesity-related factors rather than by water balance. MR analysis provided suggestive evidence supporting a causal association between TBW and gastrointestinal or abdominal diseases. Maintaining an appropriate water balance may help reduce gastrointestinal symptoms, but these findings should be interpreted with caution, and further studies incorporating comprehensive body composition measures are needed.
Endoscopic incision and debridement for presumed delayed postoperative anastomotic submucosal abscess of the rectum: a case report.
Zhou HH, Xu JP, Yuan S … +4 more , Ma YM, Shi SL, Zhang W, Li RQ
BMC Gastroenterol · 2026 Jun · PMID 42337720 · Full text
BACKGROUND: Anastomotic lesions after colorectal cancer surgery are uncommon and usually signify tumor recurrence or early complications. Delayed submucosal abscess occurring several years after curative resection is ext...
BACKGROUND: Anastomotic lesions after colorectal cancer surgery are uncommon and usually signify tumor recurrence or early complications. Delayed submucosal abscess occurring several years after curative resection is extremely rare. Due to the lack of specific clinical manifestations, imaging studies may mimic tumors or other subepithelial lesions, making the diagnosis challenging. Moreover, such lesions are located deep within the intestinal wall at the anastomotic site, which further complicates their management. Herein, we report a rare case of presumed delayed postoperative anastomotic submucosal abscess of the rectum successfully treated by endoscopic incision and debridement, highlighting diagnostic pitfalls and therapeutic feasibility. CASE DESCRIPTION: A 43-year-old woman presented with an incidentally discovered submucosal mass at the rectal anastomotic site during routine surveillance colonoscopy, eight years following laparoscopic low anterior resection for rectal cancer. She was completely asymptomatic (no abdominal pain or distension) with unremarkable laboratory findings, including normal tumor markers. Endoscopic ultrasound (EUS) revealed a slightly hyperechoic solid lesion originating from the submucosa, measuring approximately 1.61 cm × 0.81 cm, with relatively clear borders and heterogeneous internal echoes. Given the diagnostic uncertainty and the lesion's deep intramural location, endoscopic treatment was undertaken for both diagnostic and therapeutic purposes. The procedure involved a longitudinal incision through the muscularis propria at the central part of the lesion elevation, which unexpectedly revealed a sinus cavity containing purulent fluid and yellow plaque-like solid material, suggesting the presence of a chronic abscess. The cavity was irrigated, and the defect was closed with clips. Post-procedure EUS confirmed complete resolution of the mass, and the patient recovered uneventfully without complications. CONCLUSIONS: This case shows that a presumed delayed anastomotic submucosal abscess, although rare, should be considered in the differential diagnosis of mass-like lesions occurring years after rectal cancer surgery. However, in the absence of microbiological and pathological confirmation, the exact nature of the lesion remains uncertain. Alternative explanations, including a chronic postoperative cavity, anastomotic sinus formation, implantation cyst, or other benign postoperative changes, cannot be completely excluded. Nevertheless, endoscopic incision and debridement may represent a safe, minimally invasive diagnostic and therapeutic option in selected cases of presumed postoperative abscess.
Comparison of proton vs. photon radiotherapy for liver cancer: a meta-analysis.
He H, Yan Y, Zhang Y
BMC Gastroenterol · 2026 Jun · PMID 42337418 · Full text
OBJECTIVE: To systematically evaluate the efficacy and safety of proton beam radiotherapy (PBT) compared with photon radiotherapy in the treatment of hepatocellular carcinoma (HCC), thereby providing evidence-based guida...
OBJECTIVE: To systematically evaluate the efficacy and safety of proton beam radiotherapy (PBT) compared with photon radiotherapy in the treatment of hepatocellular carcinoma (HCC), thereby providing evidence-based guidance for clinical decision-making in radiotherapy modality selection. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, and EMBASE databases was conducted to identify clinical studies comparing PBT with photon radiotherapy for HCC. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and the certainty of evidence was evaluated using the GRADE system. Meta-analysis was performed using Review Manager 5.4. The primary outcomes assessed were overall survival (OS), radiation-induced liver injury (RILD), and non-classical RILD. RESULTS: Four retrospective cohort studies were included. Meta-analysis results indicated that the PBT group had a hazard ratio for OS of 0.45 (95% CI: 0.34-0.60, P < 0.00001). However, moderate heterogeneity was observed for this outcome (I² = 48%), accompanied by significant publication bias, resulting in a low certainty of evidence. Conversely, PBT significantly reduced the risk of RILD (OR = 0.26, 95% CI: 0.15-0.46, P < 0.00001) and non-classical RILD (OR = 0.27, 95% CI: 0.15-0.47, P < 0.00001). Both outcomes demonstrated no heterogeneity (I² = 0%) and no significant publication bias, yielding a moderate certainty of evidence. The number needed to treat to prevent one case of liver injury was approximately five. CONCLUSION: Compared with photon radiotherapy, PBT offers a clear advantage in reducing the risk of RILD and non-classical RILD in patients with HCC. However, the potential benefit of PBT in improving OS remains inconclusive due to limitations related to study design and publication bias, resulting in a low level of evidence. Clinical selection of radiotherapy modalities should be individualized based on patients' liver function reserve, tumor characteristics, and medical conditions. Large-scale, multicenter prospective studies are warranted to further validate the long-term survival benefits of PBT.
Epithelial FOXP3 Orchestrates O-Glycosylated IL6 Secretion to Drive Pancreatic Fibrocarcinogenesis.
Gong R, Wang J, Ren M … +20 more , Zhang W, Ping S, Jing Y, Lei K, Yu Q, Ma L, Gao C, Zhao C, Fu S, Xing Y, Xue J, Wang J, Sun H, Chen J, Zhang S, Liu M, Zhao T, Saluja A, Yang Z, Ren H
Gastroenterology · 2026 Jun · PMID 42336167 · Publisher ↗
BACKGROUND & AIMS: Pancreatic fibrosis characterizes pancreatic ductal adenocarcinoma, driving therapeutic resistance and organ failure. However, the mechanisms initiating fibrosis during early preneoplastic stages remai...
BACKGROUND & AIMS: Pancreatic fibrosis characterizes pancreatic ductal adenocarcinoma, driving therapeutic resistance and organ failure. However, the mechanisms initiating fibrosis during early preneoplastic stages remain unclear. We investigated the role of the transcription factor FOXP3, unexpectedly identified within the epithelial cells of precancerous lesions. METHODS: Using human tissues and genetically engineered mouse models, we analyzed FOXP3 expression in premalignant lesions. We used epithelial-specific FOXP3 knockout and knockin strategies to determine its functional impact on fibrogenesis and neoplasia progression. Mechanistic studies included chromatin immunoprecipitation, glycomic analyses, and signaling assays. The therapeutic potential of a fasting-mimicking diet was assessed in vivo. RESULTS: FOXP3 was consistently expressed in the epithelial compartment of human and murine precancerous pancreases. Epithelial-specific deletion of FOXP3 attenuated pancreatic fibrosis and delayed neoplasia, whereas its knockin induced spontaneous stromal activation and accelerated pancreatic intraepithelial neoplasia progression. Epithelial FOXP3 transactivated the glycosyltransferase GALNT1. GALNT1, in turn, mediated O-glycosylation of IL6 at threonine 165, essential for its rapid secretion. Secreted glycosylated IL6 engaged the gp130 receptor on pancreatic stellate cells, triggering a self-reinforcing MAPK/ERK signaling cascade that propagated stromal activation and established a feed-forward loop for fibrotic expansion. A threonine 165A mutation in IL6 abolished gp130 binding and pancreatic stellate cell activation. A fasting-mimicking diet suppressed the epithelial FOXP3/GALNT1 axis, inhibited IL6 glycosylation, and markedly ameliorated pancreatic fibrosis. CONCLUSIONS: Our study establishes epithelial-derived FOXP3 as a crucial regulator of early pancreatic fibrocarcinogenesis, driving a glycosylation-dependent amplification loop for IL6 signaling, orchestrating sustained stromal activation. This pathway represents a promising target for intercepting pancreatic fibrosis and carcinogenesis at its origin.
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Rudbaek JJ, Jess T, Ottosson F
Gastroenterology · 2026 Jun · PMID 42336166 · Publisher ↗
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Methodological Considerations on Neonatal Metabolomics and Future Inflammatory Bowel Disease.
Wang Y
Gastroenterology · 2026 Jun · PMID 42336165 · Publisher ↗
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Proactive Fecal Calprotectin Home Monitoring in Ulcerative Colitis: Results of a Prospective Randomized Control Trial.
Rosenfeld G, Narula N, Leung Y … +18 more , Afif W, Williams AJ, Huang V, Singh H, McCurdy JD, Jairath V, Lam M, Loomes DE, Zezos P, Stewart M, Ma C, Ropeleski M, Ancheta-Schmit M, Tavakoli P, Bone JN, Lewis JD, Colombel JF, Bressler B
Gastroenterology · 2026 Jun · PMID 42336164 · Publisher ↗
BACKGROUND & AIMS: Elevated fecal calprotectin (FC), a biomarker of intestinal inflammation, can be detected 3 months before symptomatic flare in patients with ulcerative colitis (UC). We hypothesized that proactive home...
BACKGROUND & AIMS: Elevated fecal calprotectin (FC), a biomarker of intestinal inflammation, can be detected 3 months before symptomatic flare in patients with ulcerative colitis (UC). We hypothesized that proactive home-based FC monitoring would prevent symptomatic flares in patients with UC in remission. METHODS: This prospective, multicenter clinical trial randomized adults with a modified partial Mayo score ≤2 and no rectal bleeding to standard care or FC testing every 2 months for 18 months or until symptomatic flare. Confirmatory FC testing was performed within 2 weeks for FC ≥250 μg/g; change in therapy was at physician discretion. Primary end point was time to symptomatic flare. Secondary end points included health care use, medication use, and quality of life. RESULTS: The trial enrolled 716 patients; 308 in the control arm and 303 in the intervention arm were analyzed. Mean age was 42 years, and 47% were men. Distribution of disease extent was similar in both arms, and 45% were on advanced therapy. Symptomatic flare occurred in 32% in both arms; median time to flare was not reached. There was no difference in risk for symptomatic flare overall (hazard ratio, 1.05; 95% confidence interval, 0.79-1.40), by disease extent, or advanced therapy use. Flare frequency was lower among the 88 who changed therapy after confirmatory elevated FC (49% vs 55%), but flare risk was not different. There were no differences in secondary end points. CONCLUSIONS: Our results suggest that proactive home-based FC monitoring without protocolized escalation does not prevent symptomatic flares. Additional studies are needed to define the optimal use of FC monitoring and the benefit of early intervention. CLINICALTRIALS: gov number: NCT03549988.
BIRC3 (Encoding Cellular Inhibitor of Apoptosis Protein 2) Variants Result in Dysregulated Receptor-Interacting Protein Kinase 1 Signaling Leading to Increased Epithelial Cell Death and Are Associated With Monogenic Crohn's Disease.
Li Q, Nambu R, Yaqiang H … +44 more , Shen X, Argmann C, Guan R, Janssen E, Le Voyer T, Warner N, Yu DD, Guo J, Long K, Ouahed J, Field M, Collen L, Bibus J, Illig D, Rohlfs M, Yu Z, Yang S, Li W, Platt CD, Comella PH, Jordan D, Suárez-Fariñas M, Alosaimi MF, Peters LA, Rosain J, Fieschi C, Puel A, Hsieh EWY, Naito T, Zeng Z, Rodríguez-Belvís MV, Palomino L, Küster P, Li D, Klein C, Snapper SB, Casanova JL, Geha R, Hoffenberg E, McGovern DPB, Schadt E, Kotlarz D, Li D, Muise AM
Gastroenterology · 2026 Jun · PMID 42335979 · Publisher ↗
BACKGROUND & AIMS: Tumor necrosis factor (TNF) is a key driver of intestinal epithelial inflammation. The baculoviral inhibitor of apoptosis protein repeat-containing 3 (BIRC3) gene encodes the cellular inhibitor of apop...
BACKGROUND & AIMS: Tumor necrosis factor (TNF) is a key driver of intestinal epithelial inflammation. The baculoviral inhibitor of apoptosis protein repeat-containing 3 (BIRC3) gene encodes the cellular inhibitor of apoptosis protein 2 (cIAP2), a known regulator of TNF signaling. Although genetic variants in components of the TNF signaling pathway have been reported, no human BIRC3 variants have been previously identified. METHODS: We screened exomes obtained from Crohn's disease (CD) patients from multiple centers for BIRC3 variants. We used cellular, mouse organoids, induced pluripotent stem cells-derived intestinal organoids, knock-in and knockout mouse models, and knockout zebrafish, as well as transcriptome analysis of various samples to determine pathogenicity of BIRC3 variants. RESULTS: Rare and damaging BIRC3 variants were identified in 14 patients from 10 unrelated families with CD diagnosed between infancy and adulthood. Functional studies showed that BIRC3 deficiency caused impaired receptor-interacting protein kinase 1 (RIPK1) ubiquitylation, leading to RIPK1 autophosphorylation resulting in increased epithelial cell death. The p.H312Y cIAP2 variant identified in both our index and in another independent patient was mislocalizaed, and a knock-in mouse model of this BIRC3 variant (cIAP2) had exacerbation of chemically induced colitis, whereas ciap1 zebrafish developed spontaneous colitis. Transcriptome analysis of mice organoids and zebrafish showed that BIRC3 deficiency led to inappropriate sustained activation of TNF-responsiveness genes in the absence of stimuli. Small molecule pharmacologic inhibition of RIPK1 or caspases attenuated intestinal inflammation in BIRC3-deficient intestinal organoids and cIAP2 mice. CONCLUSIONS: We establish BIRC3 deficiency as a cause of monogenic CD in both pediatric- and adult-onset patients and identify RIPK1 as a therapeutic target.
Development and reliability of a questionnaire to assess the dietary knowledge of Italian adult and elderly population: the QCAI (Questionario delle Conoscenze Alimentari Italiano).
Rondanelli M, Barrile GC, Gasparri C … +2 more , Moroni A, Perna S
Minerva Gastroenterol (Torino) · 2026 Jun · PMID 42333419 · Publisher ↗
BACKGROUND: Reliable tools to quantify nutrition knowledge are crucial for planning education and prevention. We developed the Questionario delle Conoscenze Alimentari Italiano (QCAI) for Italian adults and assessed its...
BACKGROUND: Reliable tools to quantify nutrition knowledge are crucial for planning education and prevention. We developed the Questionario delle Conoscenze Alimentari Italiano (QCAI) for Italian adults and assessed its reliability. METHODS: A convenience sample of 165 participants (18-89 years; 70.9% women) completed a self-administered, 69-item questionnaire organized into four content sections (experts' recommendations; nutrient content of foods; healthy choices; meal frequency and labels) plus demographics. Participants completed the questionnaire at baseline (T0) and again after seven days (T1) under identical conditions. Internal consistency was evaluated with Cronbach's alpha (and KR-20 for dichotomous items). Temporal stability was assessed with intraclass correlation coefficients (ICC<inf>(2,1)</inf>) for section and total scores, Cohen's kappa (κ) for items, and Bland-Altman analysis. RESULTS: Total-scale internal consistency was acceptable (Cronbach's α=0.757 for available items), but domain-level α values were heterogeneous and in some sections low (α: 0.307-0.638), indicating limited coherence of some subscales. Test-retest stability for the total score was moderate (ICC<inf>(2,1)</inf>=0.62), and 64.29% of items showed at least moderate agreement (κ≥0.40). Age-stratified analyses showed no linear trend in the total score across groups (18-39, 40-59, ≥60; P<inf>trend</inf>=0.26). CONCLUSIONS: QCAI is a low-cost instrument that shows moderate temporal stability and acceptable reliability for the total score in Italian adults. However, the low internal consistency observed in some domains limits the interpretability of section scores and highlights the need for item refinement and formal validation (content, construct, and criterion validity) against established measures before routine clinical or public-health use.
Progressive growth of a small gallbladder polyp diagnosed as intracholecystic papillary neoplasm: a case report.
Yokotani Y, Nakahata Y, Okuyama H … +7 more , Mukai R, Nagano J, Sakamoto N, Obora A, Murakami Y, Kojima T, Yagi N
BMC Gastroenterol · 2026 Jun · PMID 42332607 · Full text
Intracholecystic papillary neoplasm (ICPN) is a rare premalignant lesion of the gallbladder, and its natural history remains incompletely understood. We report a case of ICPN presenting as a small gallbladder polyp with...
Intracholecystic papillary neoplasm (ICPN) is a rare premalignant lesion of the gallbladder, and its natural history remains incompletely understood. We report a case of ICPN presenting as a small gallbladder polyp with progressive growth. A 56-year-old woman was found to have a gallbladder polyp measuring 7.6 mm, which increased to 11.2 mm over 2 years and 8 months. Contrast-enhanced computed tomography demonstrated a papillary lesion with enhancement. Laparoscopic cholecystectomy was performed. Histopathological examination revealed pyloric gland-type ICPN with low-grade dysplasia without invasive carcinoma. Immunohistochemical analysis showed positivity for MUC6 and MUC5AC, supporting gastric-type differentiation. No recurrence has been observed during postoperative follow-up.This case suggests that progressive growth, papillary morphology, and enhancement characteristics may indicate neoplastic potential even in gallbladder polyps initially measuring < 10 mm, suggesting the importance of careful follow-up and timely surgical intervention.
Differential diagnosis of solitary rectal ulcer syndrome and early rectal cancer via endorectal ultrasound: a retrospective matched case-control study.
Yi H, Liu X, Chen L … +2 more , Chen J, Liu G
BMC Gastroenterol · 2026 Jun · PMID 42332586 · Full text
BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is a rare chronic rectal disease with nonspecific symptoms and endoscopic findings that overlap with rectal cancer, leading to misdiagnosis in up to 64%. Biopsy is often...
BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is a rare chronic rectal disease with nonspecific symptoms and endoscopic findings that overlap with rectal cancer, leading to misdiagnosis in up to 64%. Biopsy is often limited by insufficient depth. Data on the use of endorectal ultrasound (ERUS) for differentiating SRUS from early rectal cancer (ERC) are scarce. Thus, this study aims to identify ERUS features that differentiate SRUS from ERC (T1 and T2 stages). METHODS: Twenty-nine patients who were pathologically diagnosed with SRUS between 2015 and 2024 were enrolled, whereas ERC patients were randomly selected at a 1:1 ratio and matched based on sex and lesion-to-anal verge distance. The ERUS features and clinical information of the two groups were compared via t tests, Wilcoxon rank sum tests or chi-square tests. Predictive factors for SRUS were analyzed via univariable and multivariable logistic regression. Diagnostic performance was assessed using ROC curves. RESULTS: SRUS patients were younger and presented with constipation more frequently than ERC patients did (P < 0.001 and P = 0.013, respectively). Compared with ERC lesions, SRUS lesions were more frequently located in the anterior rectal wall (44.83% vs. 13.79%, P = 0.044), were longer (median: 37 mm vs. 26 mm, P = 0.002), and had greater rectal circumferential involvement (41.38% vs. 13.79%, P = 0.019). Similarly, rectal wall thickening with preserved layer stratification and anarchic vascularization were more frequently observed in the SRUS group (79.31% vs. 13.79% and 96.55% vs. 65.52%, respectively; both P < 0.05). Multivariable logistic regression revealed that age (OR:0.87; 95% CI:0.78-0.97; P = 0.014), rectal wall thickening with preserved layer stratification (OR: <0.001, 95% CI: 0.00-0.36, P = 0.015) and > 50% circumferential involvement (OR: 97.04, 95% CI: 1.32-7,134.40, P = 0.037) were independent factors for differentiating between SRUS and ERC. The area under the curve (AUC) was 0.815, 0.638, 0.828, and 0.933 for age, circumferential involvement, layer stratification, and their combination, respectively, in the diagnosis of SRUS. CONCLUSION: ERUS features, including anterior wall location, longer lesions, > 50% circumferential involvement, rectal wall thickening with preserved layer stratification, and anarchic vascularization, are typical ERUS findings of SRUS. Younger patient age, preserved layer stratification and > 50% circumferential involvement are particularly valuable for differential diagnosis between SRUS and ERC.
Curative treatment is feasible for recurrent hepatocellular carcinoma regardless of recurrence pattern after hepatitis C virus eradication with interferon-free direct-acting antiviral therapy.
Hagiwara S, Matsubara T, Omaru N … +10 more , Okai N, Komeda Y, Ueshima K, Minami Y, Takita M, Morita M, Chishina H, Yoshida A, Nishida N, Kudo M
BMC Gastroenterol · 2026 Jun · PMID 42332568 · Full text
BACKGROUND: Interferon (IFN)-free direct-acting antivirals (DAAs) have significantly improved hepatitis C virus (HCV) elimination rates. However, new-onset or recurrence of hepatocellular carcinoma (HCC) remains common e...
BACKGROUND: Interferon (IFN)-free direct-acting antivirals (DAAs) have significantly improved hepatitis C virus (HCV) elimination rates. However, new-onset or recurrence of hepatocellular carcinoma (HCC) remains common even after achieving sustained virological response (SVR). This study investigated the clinical significance and treatability of HCC recurrence patterns after SVR, which have not been fully explored yet. METHODS: We retrospectively analyzed the risk factors for HCC development in 279 patients with HCV-associated chronic liver disease who achieved SVR with DAA therapy after July 2014. Twenty-eight patients with HCC recurrence after SVR were classified by the type of recurrence (intrahepatic metastasis, hypervascularization, and de novo). Correlation between tumor markers (alpha-fetoprotein and des-γ-carboxy prothrombin) at the time of previous HCC and at the time of recurrence was examined. RESULTS: Thirty-three patients (11.8%) developed HCC after SVR. Multivariate analysis revealed that a history of HCC was the only independent risk factor for HCC development after SVR (hazard ratio 14.4, P < 0.001). Among the 28 patients with HCC recurrence, intrahepatic metastasis was observed in eight (29%), hypervascularization in seven (25%), and de novo recurrence in six (21%) patients. At the time of recurrence, 27 patients (96%) had Barcelona clinic liver cancer stage 0/A disease. Curative treatment was possible in 27 patients (96%). CONCLUSIONS: HCC recurrence after SVR was detected early, regardless of the recurrence pattern, allowing for the selection of curative treatment. In the DAA era, HCC recurrence after SVR in patients with a history of HCC could be appropriately managed through strict follow-up.
Which fluid resuscitation strategy is associated with shorter length of stay in mild acute pancreatitis? Interaction between crystalloid type and administration rate.
Bozkurt E, Saglam O, Sarı A … +1 more , Ay M
BMC Gastroenterol · 2026 Jun · PMID 42324501 · Full text
BACKGROUND: While fluid resuscitation is the cornerstone of acute pancreatitis (AP) management, uncertainty remains regarding the optimal crystalloid selection and administration rate. This study assessed the independent...
BACKGROUND: While fluid resuscitation is the cornerstone of acute pancreatitis (AP) management, uncertainty remains regarding the optimal crystalloid selection and administration rate. This study assessed the independent and interactive associations of crystalloid type and resuscitation rate with clinical outcomes in mild AP. METHODS: This single-center, retrospective cohort study (2018-2024) included 204 patients hospitalized with mild AP. Patients were categorized by crystalloid type (Lactated Ringer's (LR), normal saline (NS), Isolyte S, or dextrose-containing solutions) and resuscitation rate (aggressive, moderate, minimal, or low). The primary endpoint was length of stay (LOS). Multivariable linear regression and analyses stratified by Bedside Index for Severity in Acute Pancreatitis (BISAP) score were performed to assess main associations and interactions. RESULTS: LR and NS were associated with comparable hospital stays, with no significant difference in LOS (P = 0.24). Both were associated with significantly shorter LOS than Isolyte S and dextrose (p < 0.001). A significant interaction occurred between fluid type and resuscitation rate: LR and NS at moderate-to-aggressive rates yielded the shortest stays, whereas Isolyte S and dextrose at low rates yielded the longest. In multivariable analysis, fluid type, resuscitation rate, BISAP score, age, and hypertension were independent predictors of LOS (R² = 0.739). These associations remained consistent across severity subgroups. CONCLUSIONS: In mild AP, LR and NS showed comparable outcomes, both of which were associated with shorter hospital stays than Isolyte S and dextrose. The significant interaction between fluid type and rate suggests that crystalloid composition and infusion rate may need to be considered jointly when optimizing resuscitation. NS appears to be a reasonable alternative when LR availability is limited.
Real-world outcomes of tumour necrosis factor inhibitor (TNFi) cyclers versus mechanism-of-action switchers among ulcerative colitis patients who failed first-line TNFi.
Upadhyay N, Ketkar A, Mert C … +8 more , Wallem A, Baygani SK, Beyene TJ, Fisher DA, Quimbo T, Perez RA, Grabner M, Chapman JC
BMC Gastroenterol · 2026 Jun · PMID 42323583 · Full text
BACKGROUND: We compared real-world outcomes among patients with ulcerative colitis (UC) prescribed second-line tumour necrosis factor inhibitor (TNFi) versus non-TNFi therapy after a first-line TNFi. METHODS: We included...
BACKGROUND: We compared real-world outcomes among patients with ulcerative colitis (UC) prescribed second-line tumour necrosis factor inhibitor (TNFi) versus non-TNFi therapy after a first-line TNFi. METHODS: We included adults with ≥ 2 claims for UC and ≥ 1 medical or pharmacy claim for a UC-approved TNFi as first-line therapy between 1 January 2015 and 30 June 2022 from the Healthcare Integrated Research Database. Second-line therapy was identified by one or more claims for a different TNFi or non-TNFi. The primary outcome was inadequate response, a composite of at least one of switch/add alternative advanced therapy, augment with conventional therapy, dose escalation, glucocorticoid intensification, UC-related hospitalisation, or UC-related surgery. We used multivariable logistic regression with trimmed inverse probability treatment weighting (IPTW) to calculate adjusted odds of inadequate response with second-line TNFi versus non-TNFi. RESULTS: Among 921 IPTW-weighted patients (second-line TNFi, n = 281; non-TNFi, n = 640), 62% of the TNFi cohort versus 49% non-TNFi had inadequate response (chi-square p = 0.001; odds ratio [95% CI], 1.76 [1.31-2.37], p < 0.001). Mean/median time to inadequate response among patients with inadequate response within 1 year was 139/125 days (TNFi) and 150/130 days (non-TNFi). The most common criterion for inadequate response was addition of new conventional therapy (35% second-line TNFi vs. 25% non-TNFi, p < 0.01); switch to or addition of alternative advanced therapy (30% vs. 15%, p < 0.01), and dose increase of oral glucocorticoids (14% vs. 9%, p < 0.05) were also significantly more common among patients in the TNFi cohort than the non-TNFi cohort. Total healthcare costs were modestly higher in the TNFi cohort. CONCLUSIONS: These results suggest that patients with UC have higher odds of inadequate response with a second TNFi versus non-TNFi after a first TNFi failure. Switching to an alternate mechanism of action for second-line therapy yielded better clinical outcomes.
Corrigendum.
Gastroenterology · 2026 Jun · PMID 42322318 · Publisher ↗
Abstract loading — click title to view on PubMed.
Insomnia screening protocol and postoperative outcomes among patients with gastrointestinal cancer: a propensity score-matched analysis.
Shen M, Hang W, Zhang L
BMC Gastroenterol · 2026 Jun · PMID 42321624 · Full text
PURPOSE: The occurrence of insomnia was prevalent in patients with gastrointestinal cancers (GICs). This study aimed to evaluate the effectiveness of perioperative insomnia screening for early detection and treatment amo...
PURPOSE: The occurrence of insomnia was prevalent in patients with gastrointestinal cancers (GICs). This study aimed to evaluate the effectiveness of perioperative insomnia screening for early detection and treatment among these patients. METHODS: A retrospective analysis was performed using prospectively collected data from 438 patients who underwent insomnia screening using the Insomnia Severity Index (ISI), followed by specialized treatments. Propensity-score matching was conducted at a 1:1 ratio to control for potential confounding factors. Primary endpoint was the reduction in ISI scores at 1 week postoperatively. Secondary outcomes included postoperative analgesics, gastrointestinal function, Multidimensional Fatigue Inventory (MFI), Hospital Anxiety and Depression scale (HADS) and European Quality of Life Five-dimension (EQ-5D) scores. RESULTS: There were 29.9% of patients with a mean ISI score of 8.19 ± 1.32 in the screening cohort at postoperative 1-week, which was lower than the control cohort with a mean difference (MD) of 9.77 (95% confidence interval (CI): 8.56-10.90 (p < 0.001). Significant differences were observed in the mean scores of MFI (MD = 23.67 (95%CI: 14.07-33.26), p < 0.001 for 1-week and 27.05 (95%CI: 17.19-36.89), p < 0.001 for 3-month) and HADS (MD = 17.62 (95%CI: 11.32-23.92), p < 0.001 for 1-week and 14.59 (95%CI: 9.63-19.54), p < 0.001) between cohorts. The screening cohort demonstrated better outcomes compared to the control cohort in postoperative analgesic consumption (p = 0.012) and time to first flatus (p = 0.022)/defecation (p < 0.001). Patients undergoing screening exhibited significantly greater improvements in EQ-5D scores over time compared to controls (all p < 0.001). Infectious complications were fewer in screening cohort than controls. CONCLUSIONS: The introduce of screening combined with specialized treatments for insomnia in patients with GICs effectively reduced sleep disturbances, resulting in significantly faster operative recovery and greater improvements in patients' psychological distress and quality of life within a 3-month follow-up.
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