BACKGROUND:The most common causes for ulcero-stricturing diseases of the ileo-cecal region and colon in Southeast Asia are Crohn's disease (CD) and gastrointestinal tuberculosis (GI TB). Diagnosing these conditions is challenging because they share several clinical, endoscopic, radiological and histological features on mucosal biopsies. Therefore, there is a need to standardize the sampling, processing and interpretation of mucosal biopsies to aid clinical decision-making. METHODS:Recognizing this challenge, core subject experts nominated by the Indian Association of Pathologists and Microbiologists (IAPM), the Indian Society of Gastroenterology (ISG) and the Colitis and Crohn's Foundation, India (CCFI), collaborated to formulate comprehensive recommendations for pathologists regarding optimal biopsy protocols, histological interpretation and reporting for differentiating CD from GI TB. A structured Delphi process was followed. RESULTS:The recommendations from the core domain expert groups were based on discussions, brainstorming sessions and extensive literature reviews conducted over three virtual group meetings, multiple online voting sessions and one physical meeting involving all experts. This document is expected to standardize the practice of luminal gastroenterology by providing a ready reference for budding specialists and pathologists, thereby promoting uniformity in practice. CONCLUSION:These multi-society, evidence-based and practically applicable recommendations developed by core subject experts aim to promote uniformity and confidence in pathology reports, facilitate timely patient management and prevent complications arising from erroneous treatment.
BACKGROUND:Screening for latent tuberculosis (LTB) before initiating advanced therapy for inflammatory bowel disease (IBD) helps reduce the risk of tuberculosis (TB) development. However, there is limited data on screening practices from TB-endemic regions. AIM:To study the practices of screening for LTB and study the incidence of TB in patients with IBD on biological and small molecule inhibitors. METHODS:This retrospective multicentre study analyzed LTB screening practices in IBD patients starting advanced therapies between 2018 and 2022. We included patients who were initiated on biologics (infliximab, adalimumab, vedolizumab) or small molecule inhibitors (tofacitinib). We assessed compliance with LTB screening methods, including the tuberculin skin test, interferon-gamma release assay (IGRA), chest X-ray, and computed tomography chest, both at initiation and annually. We also evaluated the incidence of active TB and its predictors. RESULTS:Of 378 patients (mean age: 36.9 ± 14.9 years, males: 56.9%), 158 (41.8%) and 216 (57.1%) had ulcerative colitis and Crohn's disease, respectively. Advanced therapy used were anti-tumor necrosis factor in 309 (81.74%), tofacitinib in 41 (10.84%) and vedolizumab in 28 (7.40%). Standard screening and diligent screening strategy was employed in 59% and 33% of patients, respectively. Compliance with tuberculin skin test and IGRA was noted in 261 (69.04%) and 298 (78.83%) patients, respectively. Chest X-Ray and computed tomography chest were performed in 300 (79.36%) and 242 (64.02%), respectively. Annual screening in those on advanced therapy for > 1 year was performed in 27.2% (50/184). Active TB developed in 17 (4.49%); 15 (88.23%) were on anti-tumor necrosis factor. LTB was detected in 40 (10.72%), with most diagnosed on the basis of IGRA (21/40, 52.50%). Among 17 patients who developed active TB, LTB screen was negative in 12 (70.58%). CONCLUSION:Standard screening practices for LTB, prior to starting advanced therapy, remain suboptimal (< 60%) in India despite high TB endemicity.
BACKGROUND:Appropriate tapering strategy for corticosteroids in ulcerative colitis (UC) is uncertain. AIM:To compare the efficacy and safety of two steroid tapering regimens in patients with active UC. METHODS:We randomised patients with active UC with initial steroid response after 2 weeks to short (total 6 weeks) or long taper (total 10 weeks). Randomization was stratified for acute severe UC. The primary outcome was steroid-free clinical remission at 6 months. Secondary outcomes included assessment of symptomatic remission, relapse rate, endoscopic and histological scores, and safety. RESULTS:Of 94 patients (48 in long, 46 in short taper) randomised, short taper was inferior to long taper in inducing clinical remission at 6 months (RR = 2.19; CI 1.08-4.46; p = 0.02). The relapse rates were similar in the long (37%) and short taper (46%) arms (HR: 0.34; CI: 0.10-1.11; p = 0.42). The median UCEIS scores (3 vs. 2; p = 0.23) and Nancy scores [2 (IQR 0-3) vs. 1.5 (0.75-3); p = 0.4] were not different between arms. Adverse events in the long and short taper arms, such as acne (14.58% vs. 2.16%), myopathy (8.33% vs. 6.52%), skin changes (2.08% vs. 2.17%), mood changes (0% vs. 4.34%), cytopenia (0% vs. 2.17%), and headache (6.25% vs. 6.52%) were similar. CONCLUSION:A shorter taper duration of 6 weeks was inferior to a longer taper of 10 weeks in achieving clinical remission of UC at 6 months. TRIAL REGISTRATION:CTRI Number: CTRI/2021/06/034129.
Gastrointestinal (GI) cancers remain a leading cause for global cancer-related morbidity and mortality, affecting both—men and women. Recent research highlights significant differences between the sexes in terms of incidence, development and treatment outcomes. The interplay between genetic, environmental, diet and lifestyle, and hormonal factors such as estrogen, progesterone and androgens forms a pivotal axis influencing various GI cancer development and therapeutic responses. Women’s unique vulnerability and resilience to GI cancers are influenced by differences in immune response, genetic profiles and exposure to risk factors. Site-specific evaluations show that hormonal factors can either protect or predispose women to certain cancers, often depending on life stage and hormonal status. Gender-directed approaches to prevention, screening and treatment, along with tackling psycho-social burdens and detection challenges, will significantly impact the outcomes of GI cancer in women. Further research in this area is vital to enhance outcomes and address gaps in GI cancer care for women.
Background:Gallbladder cancer (GBC) diagnosis is challenging due to overlapping imaging features. We developed and validated a multiple instance learning (MIL) model for automated GBC detection using a large-scale multi-center ultrasound dataset and benchmarked it against state-of-the-art architectures. Methods:This was a retrospective and prospective multi-center cohort study. We trained a gated attention MIL (GAIA-MIL) model on the prospective AURORA-GB dataset (August 2022-July 2024) and two public datasets. The model was evaluated on a temporally independent internal test set (August 2024-December 2024) and three retrospective external cohorts. The area under curve (AUC), sensitivity, and specificity of GAIA-MIL was compared to Clustering-constrained Attention MIL (CLAM), Dual-Stream MIL (DS-MIL), and Transformer-based MIL (TransMIL). Findings:The datasets comprised 11,012 images from 1151 patients. Cross-validation achieved a mean AUC of 0.874 (95% CI 0.846-0.902). On the internal test set (n = 97), GAIA-MIL achieved 87.7% sensitivity (78.9-95.1%), 86.2% specificity (72.4-96.9%), and an AUC of 0.883 (0.786-0.963). Pooled external validation (n = 122) showed an AUC of 0.778 (0.698-0.852). Performance varied by external center (AUCs: 0.722, 0.950, and 0.749). In comparative benchmarking, while TransMIL excelled internally (AUC 0.871), its performance degraded significantly in external validation (Pooled AUC 0.654). GAIA-MIL demonstrated superior stability, maintaining robust sensitivity (78.2%), specificity (73.4%), and AUC (0.778) pooled across all diverse external centers where complex transformers struggled. Interpretability analysis confirmed the model focused on clinically relevant features like wall thickening. Interpretation:While complex architectures like TransMIL perform well internally, GAIA-MIL offers the optimal balance of performance and generalizability for multi-center deployment. The AURORA-GB benchmark dataset is publicly released to advance research. Funding:None.
BACKGROUND:Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), poses significant diagnostic challenges, particularly in South-East Asia, where its prevalence has risen sharply. Although endoscopic biopsies and histopathological evaluations are central to IBD management, inconsistencies in sampling, processing and reporting hinder accurate and reliable diagnosis. METHODS:To address these gaps, the Indian Association of Pathologists and Microbiologists (IAPM), the Indian Society of Gastroenterology (ISG) and the Colitis and Crohn's Foundation, India, (CCFI) collaborated to formulate comprehensive guidelines. Using a structured Delphi process and expert consensus, recommendations were developed to standardize biopsy protocols, histological evaluation and reporting of mucosal biopsies and tackling critical diagnostic challenges. RESULTS:The recommendations cover biopsy sampling, optimal processing, orientation, interpretation methods, histopathological algorithms, recommendations on histological scoring, follow-up biopsies and differentiation of IBD from its mimickers based on existing literature and expert's experience. Reporting formats were suggested to ensure uniformity in practice. CONCLUSION:These evidence-based, practical recommendations aim to enhance diagnostic precision, unify practices and improve patient outcomes in IBD care, providing pathologists in resource-diverse settings with a standardized approach to gastrointestinal mucosal biopsy evaluation.
We read with great interest the trial by Singh et al. comparing double-dose versus standard-dose hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) [1]. This study from India is particularly timely: HBV prevalence remains high in low socio-demographic index countries where IBD incidence is rising [2]. As immunosuppressive therapy can trigger HBV reactivation with potentially fatal consequences [3], optimising vaccination strategies is paramount. The findings are compelling: double-dose vaccination achieved significantly higher adequate immune response (88.4% vs. 55.6%) and effective immune response (69.8% vs. 46.7%) rates as compared to standard dose. By using an identical schedule for both arms, Singh et al. elegantly isolate the effect of antigen dose on immunogenicity, extending earlier observations [4]. The benefit was most pronounced in patients on immunosuppressive therapy—precisely the population where anti-TNF agents and immunomodulators consistently attenuate vaccine responses [5, 6]. These results carry important practical implications. Guidelines recommend HBV vaccination for all seronegative IBD patients, ideally before initiating immunosuppression [7]. However, the standard regimen achieves seroprotection in only approximately 61% of IBD patients versus over 95% in healthy individuals [8]. The double-dose strategy offers an accessible solution using widely available vaccines, particularly relevant where newer adjuvanted formulations may be unavailable. Several questions merit further investigation. The durability of enhanced responses remains unknown. Given the predominantly ulcerative colitis population and limited representation of patients on biologics, validation in broader IBD cohorts is warranted. Comparative trials with adjuvanted vaccines such as Heplisav-B [9] and studies addressing non-responders through revaccination strategies would help define optimal approaches for different patient subgroups [10]. Singh et al. provide valuable evidence that a simple dose modification can meaningfully improve HBV vaccine immunogenicity in IBD. We should consider incorporating this approach into preventive care protocols, particularly for patients on or anticipating immunosuppressive therapy. Luisa Bertin: conceptualization, investigation, writing – original draft. Edoardo Vincenzo Savarino: conceptualization, investigation, writing – review and editing, project administration. The authors have nothing to report. Edoardo Vincenzo Savarino has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr. Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, MayolyBiohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots and Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, DiademaFarmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestle, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda and Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco and Zeta Farmaceutici. Luisa Bertin has served as speaker for Edra SPA, Takeda. This article is linked to Singh et al. papers. To view these article, visit https://doi.org/10.1111/apt.70470 and https://doi.org/10.1111/apt.70603. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Background: Clostridioides difficile infection (CDI) is well-recognised as a cause of flare in inflammatory bowel disease (IBD). Objectives: To prospectively evaluate CDI as a cause of flare in moderate-to-severe ulcerative colitis (UC) and perform a region-specific systematic review to evaluate the role of CDI in IBD patients in South Asia. Design: A single-centre prospective observational study followed by a region-specific systematic review. Data sources and methods: The observational study was conducted between December 2024 and December 2025 and included patients with moderate-to-severe UC flares. Triple testing using Stool glutamate dehydrogenase (GDH), an enzyme immunoassay (EIA) for toxin A/B, and polymerase chain reaction (PCR) testing was performed. A literature search in PubMed, Embase, and Scopus was conducted on 5th December 2025 to identify relevant studies from South Asia. Information on the study population (IBD type, age, gender, disease activity), the testing method, and the outcomes of CDI testing were extracted. The pooled prevalence of CDI was estimated using a random-effects model. The risk of Bias was assessed using Joanna Briggs’ tool. Results: Of the 101 patients with active UC, 59 had acute severe UC. Six patients tested positive for GDH, whereas only one tested positive for EIA and PCR. A total of 13 studies reporting on 1267 patients were included in the systematic review. Pooled prevalence of CDI was 0.06 (0.03–0.11, I 2 = 80.8%). Subgroup analyses were performed by testing method, study type, and region. However, there was persistent statistical heterogeneity. Funnel plot and Egger’s test suggested the presence of publication bias. Conclusion: Our observational study shows a low prevalence of CDI as a cause of UC flares. The findings of the systematic review suggest high variability in the CDI positivity across South Asia. These differences were not fully explained by the method of testing, the type of study, or the geographic location of the study.
Giardia duodenalis is a major intestinal protozoan parasite responsible for over 200 million infections annually worldwide. The gut microbiota influences parasite colonization, disease outcome, and host immune responses. In this context, the present study aimed to evaluate Th17-associated cytokine levels during Giardia duodenalis infection. This study evaluated the influence of gut microbiota modulation during Giardia duodenalis infection by analyzing Th17-related cytokines (IL-17 A, IL-17 F, IL-22, IL-23, and IL-10) in antibiotic pre-treated, Lactobacillus pre-treated, and untreated Giardia-infected mice. Serum cytokine profiles were also assessed in Giardia-infected patients to examine their association with clinical severity. Mice were divided into antibiotic pre-treated, probiotic (Lactobacillus) pre-treated, and untreated groups prior to Giardia infection. Animals were sacrificed on day 0 and on days 3, 7, and 14 post-infection. Th17 cytokines were quantified by ELISA, parasite burden was determined by RT-PCR, and intestinal pathology was assessed by hematoxylin and eosin staining. Additionally, 60 Giardia positive patients were clinically evaluated using the Vesikari scoring system and classified as mild and moderate to severe symptoms. Serum Th17 cytokines were measured by ELISA. Giardiasis increased both pro and anti-inflammatory cytokines in untreated mice and antibiotic pre-treatment exacerbated giardiasis, resulting in increased parasite load, heightened inflammatory cytokine responses, and severe intestinal mucosal damage. In contrast, probiotic pre-treatment induced an early and regulated cytokine response, reduced parasite burden, promoted mucosal healing, and facilitated faster recovery. Clinically, patients with moderate to severe disease exhibited elevated IL-17 A, IL-17 F, IL-23, and IL-10 levels, whereas higher IL-22 levels were associated with mild symptoms, suggesting a protective role. Antibiotic-induced dysbiosis aggravates giardiasis, while probiotic modulation of gut microbiota enhances protective immunity and reduces disease severity, highlighting probiotics as potential preventive and therapeutic agents.
Giardia duodenalis is a common intestinal parasite that infects children and adults worldwide. Of its eight known assemblages (A-H), assemblages A and B are the predominant genotypes infecting humans. The infection ranges from asymptomatic to chronic diarrhea, but whether disease severity depends on parasite strain or host factors remains unclear. This study analyzed Giardia isolates from non-Inflammatory Bowel Disease (non-IBD) and Inflammatory Bowel Disease (IBD) patients at PGIMER, Chandigarh, to explore link between assemblage type and symptom severity. A total of 180 non-IBD and 80 IBD patients were enrolled categorized into mild, moderate, and severe groups based on symptom severity scores. Detection was done by microscopy and nested PCR, followed by assemblage specific conventional and real-time PCR. The present study revealed that among non-IBD patients, 20 cases were identified as assemblage A, 25 as assemblage B, and 2 as mixed assemblages. Among IBD patients, 4 cases each were classified as assemblage A and assemblage B. Assemblage B predominated in the severe symptom group among non-IBD patients. In IBD patients, a possible association of assemblage A with severe symptoms was observed, although this finding remains preliminary due to the limited sample size. In non-IBD cases, assemblage A was frequent in females and B in males, while in IBD cases, assemblage A dominated in males and B showed equal distribution. This study reveals novel association between Giardia assemblages and symptom severity, highlighting the value of assemblage-level detection for better diagnosis and treatment, and the role of host factors in disease outcome.
Percutaneous transhepatic biliary drainage (PTBD) is a standard palliative intervention for malignant obstructive jaundice, yet 60–75
Perianal fistulizing Crohn’s disease (PFCD) presents significant challenges due to its complex nature and severe impact on patients’ quality of life. Several factors contribute to its complexity, including the anatomical intricacies, chronic and recurrent course, heightened risk of infection and the need for multifaceted treatment strategies. Recognizing these challenges, the Colitis and Crohn’s Foundation (India) (CCF[I]) deemed it essential to release a clinical guidance on PFCD. This update, developed through a structured literature review and national expert consensus meeting, integrates the latest research, standardizes treatment protocols, aims to improve patient outcomes and addresses persisting challenges, while also serving as a valuable educational resource for healthcare professionals.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by complex interactions between genetics, environment, and the gut microbiota, with rising incidence in developing nations. India, currently in stage 2 of the IBD epidemiological transition, reports one of the highest case burdens in Southeast Asia. While gut microbial dysbiosis is implicated in UC pathogenesis, most studies have focused on fecal microbiota, with limited exploration of the mucosa-associated microbiome (MAM), which resides in close contact with the intestinal epithelium. This study aimed to characterize microbial signatures relevant to UC pathogenesis in Indian patients, where high fecal–oral transmission and infection rates may uniquely shape microbial dynamics. The microbiomes of colonic mucosal biopsies were characterized from 30 patients with established UC (inflamed areas) and 30 non-IBD controls (normal mucosa). DNA was extracted using a mechanical–chemical lysis protocol followed by kit-based purification. V3–V4 region of 16S rRNA gene was sequenced on the Illumina MiSeq platform (2 × 300 bp). Data were processed using the DADA2 pipeline, followed by taxonomic assignment with the SILVA database. Diversity analyses (alpha and beta), phylum-level comparisons, LEfSe-based biomarker discovery, species-level differential abundance testing, and Spearman correlation-based co-occurrence network analysis were conducted to assess the microbial communities in UC. UC samples showed significantly altered beta diversity across all taxonomic levels and a notably elevated Firmicutes-to-Bacteroidota ratio (mean 1.91). Enrichment of Firmicutes and Desulfobacterota, alongside reduction of Fusobacteriota, Actinobacteriota, Patescibacteria, and Spirochaetota, characterized the UC microbiome. LEfSe revealed UC-associated families such as Campylobacteraceae, Lachnospiraceae, and Cardiobacteriaceae, while Porphyromonadaceae, Spirochaetaceae, and Actinomycetaceae were enriched in controls. At the species level, pathobionts including Bacteroides fragilis, Parabacteroides goldsteinii, Escherichia sp., and Campylobacter concisus were elevated in UC, whereas health-associated commensals like Streptococcus infantis, Capnocytophaga spp., and Lactobacillus casei were reduced. Network analysis revealed strong positive correlations among pro-inflammatory taxa in UC, indicating tightly clustered microbial communities potentially driving mucosal inflammation. Our findings highlight distinct mucosal bacterial signatures in Indian patients with UC, marked by enrichment of pro-inflammatory pathobionts, depletion of beneficial commensals, and an increased Firmicutes-to-Bacteroidota ratio. These results underscore the importance of region-specific MAM profiling and support the integration of microbial signatures into personalized treatment strategies for UC.
Although more women are entering gastroenterology and related fields (GI practice) in India, gender gaps remain in training, leadership and career growth. This Indian Society of Gastroenterology-Women in GI Forum (ISG-WGF) study examines the challenges women face in GI and hepatology and suggests practical steps to improve equity and inclusion. A structured, online questionnaire was disseminated to 4140 members of the ISG, including trainees and practising gastroenterologists. The questionnaire assessed six domains: socio-demographic data, GI training experiences, family support, current GI practice, work-life balance and gender-related career trajectory in men and women GI professionals. Of 185 respondents (response rate 4.5
Background: Pancreatic cancer is one of the most aggressive cancers, with poor survival rates. Endoscopic ultrasound (EUS) is a key diagnostic modality, but its effectiveness is constrained by operator subjectivity. This study evaluates a Vision Transformer-based deep learning segmentation model for pancreatic tumors. Methods: A segmentation model using the USFM framework with a Vision Transformer backbone was trained and validated with 17,367 EUS images (from two public datasets) in 5-fold cross-validation. The model was tested on an independent dataset of 350 EUS images from another public dataset, manually segmented by radiologists. Preprocessing included grayscale conversion, cropping, and resizing to 512x512 pixels. Metrics included Dice similarity coefficient (DSC), intersection over union (IoU), sensitivity, specificity, and accuracy. Results: In 5-fold cross-validation, the model achieved a mean DSC of 0.651 +/- 0.738, IoU of 0.579 +/- 0.658, sensitivity of 69.8
Mycotoxin contamination represents a major public health and economic burden worldwide. Aflatoxins, particularly aflatoxin B1, are the most detrimental for human health. In this review, we discuss the sources of exposure and geographic distribution. The prevalence of aflatoxin–albumin/lysine adduct detection in humans varies dramatically across the world, from 0% reported in two European studies to up to 100% reported in studies from parts of Africa and Asia. We also summarize the disease outcomes that aflatoxins are associated with in humans. We focus particularly on cancer outcomes, which aflatoxins can cause through mutagenic DNA adducts, oxidative stress, mitochondrial dysfunction, immune effects, and epigenetic changes. Synergy with hepatitis B virus and potentially with other mycotoxins can also increase risk. Minimization of aflatoxin exposure requires an integrative approach, beginning at the farm level and continuing through pre-harvest, post-harvest, storage, and the consumer level. New developments in technology, such as electrochemical biosensors and artificial intelligence algorithms, are being piloted and could help improve detection and decontamination efforts. Further, new tests for aflatoxin exposure in humans (e.g., blood spot assays) could assist biomonitoring efforts. Despite regulatory standards in most countries for the maximum allowable level of aflatoxins in food products and animal feed, exposure remains high in many parts of the world and might be increasing even in countries with historically low exposure. Integration of these tools in a One Health framework is essential to reduce the current and future burden of aflatoxin-related disease.