Asia-Pacific guidelines for managing functional dyspepsia overlapping with other gastrointestinal symptoms.

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.

Long-Term Gastrointestinal Consequences are Frequent Following Sporadic Acute Infectious Diarrhea in a Tropical Country: A Prospective Cohort Study.

BACKGROUND: Postinfection irritable bowel syndrome (PI-IBS) and functional dyspepsia (PI-FD), though reported from the temperate countries, have not been studied in the tropics; PI-malabsorption syndrome (MAS), which mimics PI-IBS, is reported from the tropics. No report till date on PI-IBS excluded PI-MAS. We studied: (i) the frequency of continuing bowel dysfunction after acute gastroenteritis (AG), (ii) its predictors, and (iii) PI-MAS among patients with PI-IBS. METHODS: 345 consecutive subjects each, with AG and age- and gender-matched healthy controls were followed up 3-monthly for 12 months using a translated-validated questionnaire and functional gastrointestinal disorders (FGIDs) were diagnosed by Rome III criteria. Symptom duration >3 months but <6 months was diagnosed as chronic bowel dysfunction (CBD) and dyspeptic symptoms, respectively. MAS was diagnosed if 2/3 tests (D-xylose H2 breath test, Sudan III-stained stool microscopy, and duodenal histology) were abnormal. Fecal microbiological studies were performed in 245/345 (71%) patients. RESULTS: AG patients more often developed PI-IBS and PI-FD than controls (16.5 vs. 2.6% and 7.4 vs. 0.6%, respectively; p<0.001). Presence of FD was a risk factor for PI-IBS and IBS for PI-FD. On multivariate analysis, dyspeptic symptoms, CBD, and weight loss were the risk factors for PI-FGIDs. The frequency of PI-IBS following Vibrio cholera and other bacterial infection was comparable. Malabsorption was present among 2/23 (9%) patients with PI-IBS. CONCLUSION: FGIDs are common after AG; dyspeptic symptoms, CBD, and weight loss were risk factors for PI-FGIDs. Vibrio cholerae infection caused PI-FGID, which was never reported. About 9 % patients fulfilling the criteria for PI-IBS had PI-MAS.

Irritable bowel syndrome in Asia: Pathogenesis, natural history, epidemiology, and management.

Historically, the epidemiology of gastrointestinal diseases in Asia was different from that in Western countries. Early studies suggested a low prevalence of irritable bowel syndrome (IBS) in Asia. As the diagnosis of IBS is symptom-based and as symptom perception, expression, and interpretation are influenced by sociocultural perspectives including language, the presentation of IBS is expected to vary in different communities. Furthermore, the pathogenesis is multifactorial with psychosocial (stress, illness, behavior, and diet) and biological (infection, gut microbiota, and immune activation) variables interacting, and so, the present study can anticipate that the development of IBS will vary in different environments. In recognition of this aspect of functional gastrointestinal disorders, the recently published Rome IV documents have provided greater focus on cross-cultural factors. In this review, the present study seeks to highlight Asian perspectives by identifying historical trends and recent publications from the region and comparing these with the observations from Western societies.

Rome foundation Asian working team report: Real world treatment experience of Asian patients with functional bowel disorders.

BACKGROUND AND AIM: Information on real world treatment experiences of patients with functional bowel disorders is lacking from Asia. This study aimed to describe the medication exposure and treatment satisfaction of patients presenting to gastroenterology clinics across a sampling of Asian cities. METHODS: From March 2011 to October 2013, adult patients presenting to hospital-based gastroenterology outpatient clinics in 11 cities across Asia, who fulfilled screening criteria for any functional gastrointestinal disorder, were asked to complete a validated culturally adapted translation of the Rome III diagnostic questionnaire, a checklist of medications received in the preceding 3 months and questions on treatment satisfaction. RESULTS: A total of 1376 patients (female 755, male 621, 41.36 ± 13.25 years) comprising irritable bowel (621, 45.1%), unspecified functional bowel disorder (372, 27.8%), functional constipation (202, 14.7%), functional bloating (144, 10.5%), and functional diarrhea (56, 4.1%) completed the study. Of 1105 patients with a previous consultation, 509 (46.1%) were dissatisfied with their treatment, with ineffective treatment being the commonest reason. Satisfaction with previous consultation was lowest by diagnosis for functional constipation (29.2%), and the most bothersome symptom was straining (37.5%). Of 1046 patients who had taken medications for their gastrointestinal symptoms in the last 3 months, 793 (75.8%) had received two or more drugs. For irritable bowel syndrome patients, treatment with proton pump inhibitors and antispasmodics was recorded in 57% and 31%, with overlapping epigastric pain and heartburn predicting proton pump inhibitors use. CONCLUSIONS: More attention should be given to treatment gaps with regards to possible under-treatment with antispasmodics in irritable bowel syndrome and to critically evaluating the efficacy of constipation management.

Transforming growth factor beta 1 (TGF-ß1) modulates Epstein-Barr virus reactivation in absence of Helicobacter pylori infection in patients with gastric cancer.

BACKGROUND: Transforming growth factor-beta 1 (TGF-ß1), a multifunctional cytokine, acts as a key factor for Epstein-Barr virus (EBV) reactivation. We investigated the role of TGF-ß1 in latent and lytic stages of EBV in relation to Helicobacter pylori infection among patients with gastric cancer (GC) and peptic ulcer disease (PUD). METHOD: Gastric mucosal TGF-ß1 expression was determined in 95 EBV positive patients with gastroduodenal pathology [GC 40, PUD 19 and non-ulcer dyspepsia (NUD) 36] by quantitative real time PCR. Presence of H. pylori infection was diagnosed when either culture or any two of three tests (RUT, histopathology and specific ureA PCR) were positive. Serum level of TGF-ß1 was detected among 60 patients using ELISA. RESULTS: Mucosal TGF-ß1 mRNA expression was detected in 85 of 95 EBV positive patients and it was significantly higher in patients with GC (p=0.042). TGF-ß1 expression tended to be higher among H. pylori non-infected than infected patients (3.80±6.24 vs. 2.07±2.50, p=0.085). Both mRNA and serum level had significant association with lytic stage of EBV in absence of H. pylori infection when compared with its presence (5.21±4.00 vs. 2.29±2.89, p=0.040 and 842.00 [669.55] vs. 662.63 [628.76], p=0.049; respectively). CONCLUSION: TGF-ß1 expression was significantly associated with GC. TGF-ß1 was higher both at expression and translational levels in lytic EBV infection without H. pylori suggests that H. pylori infection might play important role in preventing EBV reactivation through attenuated TGF-ß1 expression. This might be a "wise host defense against EBV reactivation".

Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and prognosis of esophageal cancer patients in northern Indian population.

Recent genome-wide association studies (GWAS) have identified variants in phospholipase C epsilon1 (PLCE1) as novel susceptibility markers for esophageal squamous cell carcinoma (ESCC) in Chinese population. Although few studies have replicated this findings in other populations, but results are contradictory. So, we aimed to replicate association of two previously reported non-synonymous polymorphisms (rs2274223A>G and rs3765524C>T) from haplotype block 10 and evaluated a novel variant (rs7922612C>T) from haplotype block 2 of PLCE1 with susceptibility and prognosis of ESCC in northern Indian population. The genotyping of PLCE1 variants were performed in 293 histopathologically confirmed incident ESCC cases (including 177 follow-up cases) and 314 age-, gender-, and ethnicity-matched controls using PCR RFLP. All statistical analyses were performed through SPSS version 15.0. Modeling and functional prediction of two non-synonymous variants were carried out using bioinformatics tools. PLCE1 polymorphisms were not associated with susceptibility to ESCC or its clinical phenotypes (tumor location/lymph node metastasis). No interaction with environmental risk factors was found. In silico analysis suggested negligible effect on structure of PLCE1 protein due to PLCE1 rs2274223 (H1927R) and rs3765524 (T1777I) polymorphisms. Survival analysis showed PLCE1 rs7922612CT + TT genotype conferred adverse outcome to ESCC patients. Our study for the first time suggests that GWAS originated PLCE1 variants do not have independent role in susceptibility of ESCC in northern Indian population; however, a novel haplo-tagging SNP rs7922612 may modify survival outcome of ESCC patients.

Epidemiology of Disorders of the Gut-Brain Interaction: An Appraisal of the Rome IV Criteria and Beyond.

Disorders of the gut-brain interaction (DGBIs) are presently classified into mutually exclusive anatomical area-related symptom-based categories according to the Rome IV criteria. The pathophysiology of visceral nociception, which contributes to the wide range of symptoms of DGBIs, involves complex psychobiological processes arising from the bidirectional interactions of multiple systems at the gut and brain levels, which affect symptom expression and illness behaviors. The attitude toward an illness and expression of pain and bowel habit vary across cultures with variable interpretation based on sociocultural beliefs, which may not tally with the medical definitions. Thus, psychological factors impact DGBI definitions, their severity and health care utilization. Due to the poor localization and multisegment referral of visceral pain, the anatomical site of pain may not correspond to the affected segment, and there may be a variable degree of overlap among symptoms. The somewhat restrictively defined Rome IV criteria assume one-to-one correlation of symptoms with underlying pathophysiology and ignore overlapping DGBIs, nonstandardized symptom categories, and change or shift in category over time. The microorganic nature of DGBIs resulting from systemic, metabolic or motility disorders, gut dysbiosis and inflammation are not addressed in the Rome IV criteria. Although there is a multidimensional clinical profile that does address these factors, it is not followed rigorously in practice. Threshold changes for diagnostic criteria or addition/deletion of symptoms leads to wide variation among different DGBI criteria resulting in uncertain comparability of results. Although the Rome IV criteria are excellent for research studies and therapeutic trials in homogenous populations, further improvement is needed for their wider applicability in clinical practice.

Determinants, profile and outcomes of hepatitis A virus-associated severe acute liver injury in adults.

BACKGROUND AND OBJECTIVES: Hepatitis A virus (HAV)-related hepatitis is witnessing an epidemiological transition with increasing trends in adults. While uncomplicated hepatitis remains common, evidence suggests it to be a growing cause for acute liver failure (ALF). In between the two extremes exists severe acute liver injury (s-ALI) which has a propensity to transition to ALF. We aimed at describing the clinical profile of patients with HAV-related s-ALI and identifying potential predictors of progression to ALF. METHODS: This was a single-center retrospective analysis of adult patients admitted with HAV-related s-ALI between April 2022 and December 2023. Demographic and laboratory parameters were compared between patients with only s-ALI and those with ALF. Predictors of progression from s-ALI to ALF were identified using logistic regression. RESULTS: Forty-three patients satisfied criteria of s-ALI, of which 33 (76.7%) had only s-ALI, while 10 (23.3%) had ALF. Patients with s-ALI had lesser leukocytosis (6.3 ± 3 vs. 13.2 ± 4.8), less incidence of acute kidney injury (9.1% vs. 40%) and lower model for end-stage liver disease (MELD) (20 [18-24.5] vs. 31.5 [26-42]), arterial lactate (2.1 [1.3-3.1] vs. 6.3 [5.2-8.0]), arterial ammonia (94 [72-118] vs. 299 [188-573]), procalcitonin (0.5 [0.28-1.25] vs. 3.2 [1.2-6.1]) and ferritin (482 [213-1633] vs. 5186 [1341-11,053]) compared to HAV-ALF (p < 0.05 for all). Three patients (9.09%) with s-ALI progressed to ALF of whom one (3%) died. Baseline ammonia levels (unadjusted odds ratio [OR] 1.03 [1.01-1.06]) and leukocyte count (OR 1.00 [1.00-1.01]) tended to be associated with ALF progression, although none was significant after multi-variable adjustment. Ammonia levels had an area under receiver operating curve of 0.816 (0.64-0.93) (p = 0.009) (cut-off of 144 µmol/L). Additional comorbidities did not impact overall outcomes. CONCLUSION: HAV presents as s-ALI in young adults, with almost one in 10 progressing to ALF. Baseline ammonia may be an important predictor of progression even in s-ALI, but mandates larger well-designed studies.

Evaluation of common genetic variants in pre-microRNA in susceptibility and prognosis of esophageal cancer.

Genetic variants in micro-RNAs (miRNA) have been shown to affect progression, diagnosis, and prognosis of various malignancies; however, their role in esophageal squamous cell carcinoma (ESCC) susceptibility is controversial. Therefore, we aimed to determine role of common genetic variants in cancer related pre-miRNA in susceptibility and survival outcome of north Indian ESCC patients. We genotyped four common polymorphisms in pre-miRNA: mir-196a-2C>T, mir-146aG>C, mir-499T>C, and mir-423C>A in 289 incident ESCC cases (including 153 follow-up cases) and 309 controls using PCR/PCR RFLP-based methods. Binary logistic regression was applied for risk estimation, while Kaplan-Meier and Cox Regression tests were performed for survival analysis. We observed that none of the pre-miRNA genetic variants were associated with ESCC or its clinical phenotypes independently, however, combined risk genotypes of four pre-miRNA polymorphisms increased risk of ESCC in dose-response manner (Ptrend = 0.011). Specifically, patients with 2-4 risk genotypes of pre-miRNA polymorphisms had 1.4-fold higher risk of ESCC compared to patients with 0-1 risk genotypes (OR = 1.43, 95% CI = 1.02-1.09, P-value = 0.037). The risk was more pronounced in ESCC cases with upper-third esophageal tumors. Moreover, cumulative but not independent effect of risk genotypes of pre-miRNA polymorphisms was observed on survival outcome of ESCC patients. Cases with 2-4 risk genotypes had significantly lower median survival (11.60 vs. 30.2 months) and 2.3-fold greater hazard of death compared to patients with 0-1 risk genotypes. In conclusion, the four studied common pre-miRNA polymorphisms cumulatively affect susceptibility and survival of ESCC patients in north Indian population. © 2012 Wiley Periodicals, Inc.

Modification of risk, but not survival of esophageal cancer patients by esophageal cancer-related gene 1 Arg290Gln polymorphism: a case-control study and meta-analysis.

BACKGROUND AND AIM: Esophageal cancer-related gene 1 (ECRG1) is a novel tumor suppressor gene known to affect matrix remodeling, cell growth, and differentiation. Previous studies in high incidence geographical regions of esophageal cancer (EC) have shown association of ECRG1 Arg290Gln polymorphism with risk of esophageal squamous cell carcinoma (ESCC); however, role of this variant in low incidence region is missing. So, we aimed to evaluate association of ECRG1 Arg290Gln with susceptibility and prognosis of EC patients in low-risk north Indian population. METHODS: The genotyping of ECRG1 Arg290Gln polymorphism was done in 310 incident EC cases (including 179 follow up cases) and 310 healthy controls through polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis applied were binary logistic regression for risk estimation and Kaplan-Meier/log-rank test for survival analysis. Meta-analysis of published studies, exploring role of ECRG1 polymorphism in ESCC risk, was carried out using MIX 2.0 software. RESULTS: ECRG1 Arg290Gln polymorphism significantly conferred 1.8-fold increased risk of EC in dominant model (odds ratio = 1.78, 95% confidence interval = 1.27-2.49, P = 0.001). Stratification based on clinical phenotypes showed pronounced risk in cases with ESCC histopathology and middle/lower third tumor locations. No significant interaction with environmental risk factors was observed. Meta-analysis also showed significant association of ECRG1 Arg290Gln polymorphism with risk of ESCC. Kaplan-Meier and Cox regression tests suggested that ECRG1 polymorphism did not modulate survival outcome of ESCC patients. CONCLUSIONS: ECRG1 Arg290Gln polymorphism significantly affects the susceptibility but not the prognosis of ESCC patients in low-risk north Indian population.

Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship.

Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.

Role of p53 and p73 genes polymorphisms in susceptibility to esophageal cancer: a case control study in a northern Indian population.

Genetic variants in p53 and in its homologue p73 may modulate Esophageal Cancer (EC) risk because they are supposed to influence cell cycle progression, apoptosis and DNA repair. Therefore, we aimed to evaluate the association of p53 intron3 16 bp duplication and p73 G4C14-to-A4T14 polymorphisms with susceptibility to EC in a northern Indian population in 255 EC patients and 255 age and sex matched healthy controls. We found that p53 intron3 16 bp duplication polymorphism was not associated with EC and its clinical characteristics. However, p73 G4C14-to-A4T14 polymorphism was associated with significant higher risk of EC (OR = 1.74, 95% CI = 1.16-2.60, P = 0.007) in an allele dose-dependent manner (P(trend) = 0.0047). Stratification of subjects on the basis of clinical characteristics showed that p73 AT genotype carriers were at significant increased risk of developing esophageal squamous cell carcinoma (OR = 1.78, 95% CI = 1.18-2.67, P = 0.006) at middle third tumor location (OR = 1.87, 95% CI = 1.18-2.97, P = 0.007) with lymph node metastasis (OR = 1.77, 95% CI = 1.04-3.02, P = 0.035). No interaction with environmental risk factors was observed with any of the studied polymorphisms. In summary, p73 G4C14-to-A4T14 polymorphism but not the p53 intron3 16 bp duplication polymorphism is associated with EC and its clinical characteristics in northern Indian population.

Asian consensus report on functional dyspepsia.

BACKGROUND AND AIM: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared with the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. METHODS: Consensus team members were selected from Asian experts and consensus development was carried out by using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using a keypad voting system. A grade of evidence and strength of recommendation were applied to each statement according to the method of the GRADE Working Group. RESULTS: Twenty-nine consensus statements were finalized, including seven for definition and diagnosis, five for epidemiology, nine for pathophysiology, and eight for management. Algorithms for diagnosis and management of functional dyspepsia were added. CONCLUSIONS: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.

Analysis of p53, K-ras gene mutation & Helicobacter pylori infection in patients with gastric cancer & peptic ulcer disease at a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: Mutations in the oncogene and tumour suppressor genes play an important role in carcinogenesis. We investigated the association of p53 and K-ras gene mutation and Helicobacter pylori infection in patients with gastric cancer (GC) and peptic ulcer disease (PUD) attending a tertiary care hospital in north India. METHODS: In total, 348 adult patients [62 GC, 45 PUD and 241 non-ulcer dyspepsia (NUD)] who underwent an upper gastrointestinal endoscopy were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR. Mutation in the exon 5-8 of p53 gene was analyzed by PCR-single stranded conformational polymorphism (SSCP) and confirmed by sequence analysis. K-ras gene codon 12 mutation was analyzed by PCR-based restriction fragment length polymorphism. RESULTS: Overall p53 gene mutation was found in 4.6 per cent of the study population, and its distribution in GC, PUD and NUD was 21, 4.4 and 0.4 per cent, respectively. p53 gene mutation was significantly higher in patients with GC than PUD (P<0.05) and NUD (P<0.001). No difference in p53 gene mutation was observed between H. pylori infected and non-infected individuals. K-ras gene mutation was absent in all the patients. INTERPRETATION & CONCLUSIONS: Our results show that p53 gene mutation may be associated with gastric carcinogenesis independent to H. pylori infection and absence of K-ras gene mutation questions its role in the pathogenesis of GC and PUD in Indian patients.

Role of survivin gene promoter polymorphism (-31G>C) in susceptibility and survival of esophageal cancer in northern India.

BACKGROUND AND AIM: Survivin is an upregulated inhibitor of apoptosis protein in esophageal cancer (EC), and a promoter region polymorphism (-31G>C) in the survivin gene has been reported as a modulator of gene expression. We aim to explore the role of survivin -31G>C polymorphism in susceptibility and survival of EC patients in northern Indian population. MATERIALS AND METHODS: A case-control study was performed in 500 subjects (250 EC patients and 250 controls), and genotyping was done by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. RESULTS: Survivin CC genotype was found to be significantly associated with EC susceptibility [odds ratio (OR) = 2.29; 95% confidence interval (CI) = 1.27-4.14; P = 0.006], particularly in males (OR = 4.91; 95% CI = 2.19-11.02; P = 0.0001) having squamous cell carcinoma (SCC) histopathology (OR = 2.4; 95% CI = 1.36-4.21; P = 0.002) at middle third esophagus location (OR = 2.60; 95% CI = 1.40-4.82; P = 0.002). Patients carrying CC genotype were found to have higher susceptibility to lymph node metastasis (OR = 2.82; 95% CI = 1.46-5.48; P = 0.002). However, on survival analysis, no prognostic role of survivin -31G>C polymorphism was detected. In case-only analysis, no gene-environment interaction was observed. CONCLUSION: Survivin promoter region polymorphism (-31G>C) is associated with susceptibility and clinical characteristics but not prognosis of esophageal cancer in northern Indian population.

CASP8 -652 6N del and CASP8 IVS12-19G>A gene polymorphisms and susceptibility/prognosis of ESCC: a case control study in northern Indian population.

BACKGROUND: Caspase8 influences carcinogenesis through regulation of apoptosis, hyperproliferation, and metastasis. Role of genetic variations in caspase8 has been explored in various cancers; however, their predictive and prognostic role in esophageal cancer is poorly understood. METHODS: We investigated the association of two potential caspase8 polymorphisms: CASP8 -652 6N del and CASP8 IVS12-19 G>A polymorphisms with susceptibility and survival of 259 esophageal squamous cell carcinoma (ESCC) cases and 259 cancer-free controls from northern Indian population using PCR/PCR RFLP method. RESULTS: CASP8 IVS12-19 AA genotype was found to be associated with significant increased risk of ESCC (odds ratio (OR) 3.28, 95% confidence interval (CI) 1.04-10.29) specifically in male subjects (OR 3.71, 95% CI 1.01-13.35) with lower third tumor anatomical location (OR 6.00, 95% CI 1.60-22.55). Kaplan-Meier and Cox Regression analysis showed lower median survival (7.13 months vs. 25.21 months) and greater hazard of death (HR 3.40, 95% CI 1.38-7.90) with CASP8 IVS12-19 AA genotype in ESCC cases compared to IVS12-19 GG genotype. However, no association of CASP8 -652 6N del polymorphism with susceptibility and prognosis of ESCC was observed. CONCLUSION: CASP8 IVS12-19 G>A but not CASP8 -652 6N del polymorphism may modulate risk of ESCC and its survival outcome in northern Indian population.

Best practices of handling, processing, and interpretation of small intestinal biopsies for the diagnosis and management of celiac disease: A joint consensus of Indian association of pathologists and microbiologists and Indian society of gastroenterology.

The Indian Association of Pathologists and Microbiologists (IAPM) and Indian Society of Gastroenterology (ISG) decided to make a joint consensus recommendation for handling, processing, and interpretation of SI biopsies for the diagnosis and management of celiac disease (CD) recognizing the inhomogeneous practice of biopsy sampling, orientation, processing, and interpretation. A modified Delphi process was used to develop this consensus document containing a total of 42 statements and recommendations, which were generated by sharing the document draft, incorporating expert's opinion, followed by three cycles of electronic voting as well as a full-day face-to-face virtual ZOOM meeting and review of supporting literature. Of the 42 statements, 7 statements are on small intestinal (SI) biopsy in suspected patients of CD, site and the number of biopsies; 7 on handling, fixative, orientation, processing, and sectioning in pathology laboratories; 2 on histological orientation; 13 statements on histological interpretation and histological grading; 3 on the assessment of follow-up biopsies; 2 statements on gluten-free diet (GFD)-nonresponsive CD; 4 on challenges in the diagnosis of CD; 2 statements each on pathology reporting protocol and training and infrastructure in this area. The goal of this guideline document is to formulate a uniform protocol agreed upon both by the experienced pathologists and gastroenterologists to standardize the practice, improve the yield of small bowel biopsy interpretation, patients' compliance, overall management in CD, and generate unified data for patient care and research in the related field.

Evaluation of MTHFR677C>T polymorphism in prediction and prognosis of esophageal squamous cell carcinoma: a case-control study in a northern Indian population.

Early diagnosis and better prognosis of esophageal squamous cell carcinoma (ESCC) is still a challenge. Besides environmental risk factors, nutritional deficiencies have an established role in pathogenesis of ESCC. Folate deficiency and functional polymorphisms in folate metabolizing genes such as methylene tetrahydrofolate reductase (MTHFR) 677C>T may have oncogenic role through disruption of normal DNA methylation pattern, synthesis, and impaired DNA repair. MTHFR677C>T or A222V (rs1801133) polymorphism has conflicting role in susceptibility to ESCC among different populations. Thus, we aimed to study the role of MTHFR677C>T polymorphism in susceptibility, survival, and interaction with environmental risk factors in ESCC patients from a northern Indian population. A case control study was performed in 208 ESCC incident cases (including 114 follow-up cases) and 223 healthy controls, and genotyping was done by PCR-RFLP. Our results show no significant association of MTHFR677C>T polymorphism with ESCC, tumor locations, or gender of subjects. However, we found a trend of decreased risk of ESCC due to interaction of MTHFR677CT genotype with smoking and alcohol intake. Kaplan Meier, and Cox regression survival analysis showed no prognostic impact of MTHFR677C>T polymorphism in ESCC patients. In conclusion, MTHFR677C>T polymorphism does not seem to have significant role either in susceptibility or survival of ESCC in a northern Indian population.

Asian consensus on irritable bowel syndrome.

BACKGROUND AND AIMS: Many of the ideas on irritable bowel syndrome (IBS) are derived from studies conducted in Western societies. Their relevance to Asian societies has not been critically examined. Our objectives were to bring to attention important data from Asian studies, articulate the experience and views of our Asian experts, and provide a relevant guide on this poorly understood condition for doctors and scientists working in Asia. METHODS: A multinational group of physicians from Asia with special interest in IBS raised statements on IBS pertaining to symptoms, diagnosis, epidemiology, infection, pathophysiology, motility, management, and diet. A modified Delphi approach was employed to present and grade the quality of evidence, and determine the level of agreement. RESULTS: We observed that bloating and symptoms associated with meals were prominent complaints among our IBS patients. In the majority of our countries, we did not observe a female predominance. In some Asian populations, the intestinal transit times in healthy and IBS patients appear to be faster than those reported in the West. High consultation rates were observed, particularly in the more affluent countries. There was only weak evidence to support the perception that psychological distress determines health-care seeking. Dietary factors, in particular, chili consumption and the high prevalence of lactose malabsorption, were perceived to be aggravating factors, but the evidence was weak. CONCLUSIONS: This detailed compilation of studies from different parts of Asia, draws attention to Asian patients' experiences of IBS.