Impact of Cytomegalovirus Infection on Short-Term Clinical Outcomes and Operative Histopathology in Infants with Biliary Atresia: A Single-Center Prospective Cohort Study.

Background: There is limited information on the impact of cytomegalovirus (CMV) infection on clinical outcomes and operative histopathology in children with biliary atresia (BA). We hypothesized that CMV infection is associated with greater histopathological damage and unfavorable short-term clinical outcomes. Materials and Methods: A prospective single-center study was conducted with effect from January 2011-July 2012 including all infants with BA who underwent surgery. Diagnosis of CMV infection was confirmed by serum immunoglobulin M (IgM) positivity or the presence of CMV-deoxyribonucleic acid (DNA) in the liver tissue. Four short-term outcome variables were observed. The cohort was divided into subgroups on the basis of seropositivity (IgM + or IgM-); the presence of CMV-DNA in the liver (polymerase chain reaction [PCR]+ or PCR-); and composite CMV groups (Group 1 - IgM+, PCR+; Group 2 - IgM+, PCR-; Group 3 -- IgM-, PCR+; and Group 4 - IgM-, PCR-). Outcomes and histopathology were compared in these subgroups. Results: A total of 32 infants with BA were operated at a mean age of 3.5 (range: 1-6) months. Serum IgM+ and PCR+ were observed in 50% and 37.5% of the patients. Unfavorable outcomes showed a significant association with IgM+ and not PCR+. Similarly, outcomes were poor for CMV Groups 1 and 2 at 1-month follow-up. Infants with IgM+ and PCR+ showed a greater degree of histopathological damage in terms of bile duct proliferation and severe bile duct fibrosis, respectively. Conclusion: In the present study, there was a high incidence of serum IgM+ (50%) and PCR+ of biopsy specimens (37.5%) in infants with BA. This CMV-infected subgroup was associated with greater histopathological damage and unfavorable short-term outcomes after surgery.

Clinical, endoscopic, and histological differentiation between celiac disease and tropical sprue: A systematic review.

BACKGROUND AND AIM: While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS. METHODS: Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis. RESULTS: Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D-xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia. CONCLUSIONS: Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests.

Prebiopsy multiparametric MRI-based risk score for predicting prostate cancer in biopsy-naive men with prostate-specific antigen between 4-10 ng/mL.

BACKGROUND: Risk calculators have traditionally utilized serum prostate-specific antigen (PSA) values in addition to clinical variables to predict the likelihood of prostate cancer (PCa). PURPOSE: To develop a prebiopsy multiparametric MRI (mpMRI)-based risk score (RS) and a statistical equation for predicting the risk of PCa in biopsy-naive men with serum PSA between 4-10 ng/mL that may help reduce unnecessary biopsies. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: In all, 137 consecutive men with PSA between 4-10 ng/mL underwent prebiopsy mpMRI (diffusion-weighted [DW]-MRI and MR spectroscopic imaging [MRSI]) during 2009-2015 were recruited for this study. FIELD STRENGTH/SEQUENCE: 1.5T (Avanto, Siemens Health Care, Erlangen, Germany); T1 -weighted, T2 -weighted, DW-MRI, and MRSI sequences were used. ASSESSMENT: All eligible patients underwent mpMRI-directed, cognitive-fusion transrectal ultrasound (TRUS)-guided biopsies. STATISTICAL TESTS: An equation model and an RS were developed using receiver operating characteristic (ROC) curve analysis and a multivariable logistic regression approach. A 10-fold crossvalidation and simulation analyses were performed to assess diagnostic performance of various combinations of mpMRI parameters. RESULTS: Of 137 patients, 32 were diagnosed with PCa on biopsy. Multivariable analysis, adjusted with positive pathology, showed apparent diffusion coefficient (ADC), metabolite ratio, and PSA as significant predictors of PCa (P < 0.05). A statistical equation was derived using these predictors. A simple 6-point mpMRI-based RS was derived for calculating the risk of PCa and it showed that it is highly predictive for PCa (odds ratio = 3.74, 95% confidence interval [CI]: 2.24-6.27, area under the curve [AUC] = 0.87). Both models (equation and RS) yielded high predictive performance (AUC ≥0.85) on validation analysis. DATA CONCLUSION: A statistical equation and a simple 6-point mpMRI-based RS can be used as a point-of-care tool to potentially help limit the number of negative biopsies in men with PSA between 4 and 10 ng/mL. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1227-1236.

Ratio of Preoperative and Postoperative Serum Bilirubin Levels Predicts Early Outcome Following Biliary Atresia Surgery.

AIM: This study investigates the fall in total serum bilirubin levels within 1 week after surgery, as a marker to predict early outcome in biliary atresia (BA) patients post-Kasai portoenterostomy (KP). METHODS: The ratio of total serum bilirubin levels at the 7th postoperative day to the preoperative level (TB7/TB0) in patients undergoing KP was calculated (January 2011-July 2015). Patients were stratified after 3-months follow-up into outcome groups depending on the clinical clearance of jaundice and TB7/TB0 ratio was correlated to outcome and liver histopathological changes in these groups. RESULTS: Sixty-one patients (M:F = 44:17), median age 75 days were included. At the end of 3 months, 27 (44.39%) were anicteric while 26 (42.6%) were still clinically jaundiced. Patients with a higher median value of TB7/TB0, that is, 0.856 were more likely to have jaundice at the end of 3 months as compared to patients with a lower median value of 0.615 (P < 0.0001). A cutoff TB7/TB0 ratio >0.723 predicted the KP outcome with 84.6% sensitivity and 81.5% specificity. The difference in TB7/TB0 ratio between patients with varying severity of liver histopathological changes was also significant, namely, cholestasis (P = 0.01), hepatocellular damage (P = 0.03), portal inflammation (P = 0.04), and portal fibrosis (P = 0.02). CONCLUSIONS: The rapidity of fall in the total serum bilirubin levels within 1 week post-KP was able to predict the likely outcome in BA patients.

Evaluating clinical, dietary, and psychological risk factors for relapse of ulcerative colitis in clinical, endoscopic, and histological remission.

BACKGROUND AND AIM: The literature on possible factors that could trigger a relapse in patients with ulcerative colitis (UC) in clinical, endoscopic, and histological remission on long-term follow up is scarce. To determine the relapse rate in patients with UC in clinical, endoscopic, and histological remission and identify factors that may influence the risk of relapse. METHODS: Patients with UC in clinical, endoscopic, and histological remission were enrolled between January and July 2010 and followed up for 1 year to determine the effect of clinical, dietary, and psychological factors on relapse. Information regarding factors that may affect relapse such as infection, antibiotic, or non-steroidal anti-inflammatory drugs (NSAIDs) use and any other factor that the patient felt important and compliance with medications was obtained. RESULTS: Ninety-seven patients (59 males, mean age 39 ± 11.9 years) were followed up for a mean duration of 9 ± 2.3 months. Eighteen (18.6%) relapsed with the median time to relapse being 3.5 months. On univariate analysis, more relapsers had significantly higher NSAIDs use within 15 days of relapse, respiratory tract infection within 4 weeks, use of steroids more than once in past, higher consumption of calcium, riboflavin, and vitamin A, and lower consumption of sugars. On multivariate analysis, NSAIDs use (HR [95% CI]: 6.41 [1.88-21.9]) and intake of vitamin A (HR [95% CI]: 1.008 [1.000-1.016]) were statistically significant predictors of relapse. CONCLUSION: With a relapse rate of 18.6% over a follow up of 9 months in patients with UC in clinical, endoscopic, and histological remission, independent predictors of relapse were history of NSAIDs use within 15 days of relapse and higher intake of vitamin A.

Prevalence of Adult Celiac Disease in India: Regional Variations and Associations.

OBJECTIVES: Although celiac disease (CeD) affects 1% of people in the northern part of India, it is believed to be uncommon in the southern and northeastern parts because of significant differences in dietary pattern and ethnicity. We estimated the prevalence of CeD in these three populations. In a subset, we also investigated differences in the prevalence of HLA-DQ 2/8 allelotype and dietary grain consumption. METHODS: A total of 23,331 healthy adults were sampled from three regions of India-northern (n=6207), northeastern (n=8149), and southern (n=8973)-and screened for CeD using IgA anti-tissue transglutaminase antibody. Positive tests were reconfirmed using a second ELISA. CeD was diagnosed if the second test was positive and these participants were further investigated. A subsample of participants was tested for HLA-DQ2/-DQ8 and underwent detailed dietary evaluation. RESULTS: Age-adjusted prevalence of celiac autoantibodies was 1.23% in northern, 0.87% in northeastern, and 0.10% in southern India (P<0.0001). Prevalence of CeD and latent CeD, respectively, was 8.53/1,000 and 3.70/1,000 in northern, 4.66/1,000 and 3.92/1,000 in northeastern, and 0.11/1,000 and 1.22/1,000 in the southern part. The population prevalence of genes determining HLA-DQ2 and/or -DQ8 expression was 38.1% in northern, 31.4% in northeastern, and 36.4% in southern India. Mean daily wheat intake was highest in northern (455 g) compared with northeastern (37 g) or southern part (25 g), whereas daily rice intake showed an inverse pattern. CONCLUSIONS: CeD and latent CeD were most prevalent in northern India and were the least in southern India. The prevalence correlated with wheat intake and did not reflect differences in the genetic background.

Stratification of the aggressiveness of prostate cancer using pre-biopsy multiparametric MRI (mpMRI).

Risk stratification, based on the Gleason score (GS) of a prostate biopsy, is an important decision-making tool in prostate cancer management. As low-grade disease may not need active intervention, the ability to identify aggressive cancers on imaging could limit the need for prostate biopsies. We assessed the ability of multiparametric MRI (mpMRI) in pre-biopsy risk stratification of men with prostate cancer. One hundred and twenty men suspected to have prostate cancer underwent mpMRI (diffusion MRI and MR spectroscopic imaging) prior to biopsy. Twenty-six had cancer and were stratified into three groups based on GS: low grade (GS ≤ 6), intermediate grade (GS = 7) and high grade (GS ≥ 8). A total of 910 regions of interest (ROIs) from the peripheral zone (PZ, range 25-45) were analyzed from these 26 patients. The metabolite ratio [citrate/(choline + creatine)] and apparent diffusion coefficient (ADC) of voxels were calculated for the PZ regions corresponding to the biopsy cores and compared with histology. The median metabolite ratios for low-grade, intermediate-grade and high-grade cancer were 0.29 (range: 0.16, 0.61), 0.17 (range: 0.13, 0.32) and 0.13 (range: 0.05, 0.23), respectively (p = 0.004). The corresponding mean ADCs (×10(-3) mm(2) /s) for low-grade, intermediate-grade and high-grade cancer were 0.99 ± 0.08, 0.86 ± 0.11 and 0.69 ± 0.12, respectively (p < 0.0001). The combined ADC and metabolite ratio model showed strong discriminatory ability to differentiate subjects with GS ≤ 6 from subjects with GS ≥ 7 with an area under the curve of 94%. These data indicate that pre-biopsy mpMRI may stratify PCa aggressiveness noninvasively. As the recent literature data suggest that men with GS ≤ 6 cancer may not need radical therapy, our data may help limit the need for biopsy and allow informed decision making for clinical intervention. Copyright © 2015 John Wiley & Sons, Ltd.

Demographic profile, host, disease & viral predictive factors of response in patients with chronic hepatitis C virus infection at a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: Standard of care for chronic hepatitis C (CHC) in India is peginterferon and ribavirin (RBV). The response to treatment in real life stetting is unclear. The objectives of this study were to evaluate the demographic profile and assess the virological response and predictors of response in CHC patients. METHODS: Consecutive patients with CHC were included in this study. Detailed clinical history, risk factors, and predictive factors of response were noted. Patients were treated with peginterferon α2b (1.5 µg/kg/wk) and RBV (12 mg/kg/day) for 6 to 18 months based on response. RESULTS: A total of 211 patients were included in the analysis, mean age 40.6±12.3 yr, 144 (68%) were males and 71 (34%) had compensated cirrhosis. Commonest risk factor for acquiring CHC was previous transfusion and surgery (51%). Genotype 3 (72%) was most common followed by genotype 1 (23%). Overall sustained virologic response (SVR) was 64 per cent [95% CI 57.1%-70.4%]. The SVR was 66.5 per cent [95% CI 58.34-73.89%] for genotype 3 and 61.2 per cent [95% CI 46.23 to 74.80%] for genotype 1. Non-cirrhotics had better SVR rates compared to cirrhotics (76 vs 41%, p<0.001). On multivariate analysis, BMI ≥23 kg/m2, HOMA-IR ≥2, compliance (≤80%), and fibrosis >2 were predictors of low SVR. INTERPRETATION & CONCLUSIONS: Genotype 3 was the commonest HCV genotype. The commonest source of infection was previous transfusion and surgery. SVR rates for genotypes 3 were better than genotype 1 patients. Predictors of non-response were high BMI, insulin resistance, significant fibrosis and inadequate compliance.

Intermittent Directly Observed Therapy for Abdominal Tuberculosis: A Multicenter Randomized Controlled Trial Comparing 6 Months Versus 9 Months of Therapy.

BACKGROUND: The duration of treatment of gastrointestinal tuberculosis continues to be a matter of debate. The World Health Organization advocates intermittent directly observed short-course therapy (DOTs), but there is a lack of data of its efficacy in abdominal tuberculosis. We therefore conducted a multicenter randomized controlled trial to compare 6 months and 9 months of antituberculosis therapy using DOTs. METHODS: One hundred ninety-seven patients with abdominal tuberculosis (gastrointestinal, 154; peritoneal, 40; mixed, 3) were randomized to receive 6 months (n = 104) or 9 months (n = 93) of antituberculosis therapy using intermittent directly observed therapy. Patients were followed up 1 year after completion of treatment to assess recurrence. Patients were evaluated for primary endpoint (complete clinical response, partial response, and no response) and secondary endpoint (recurrence of the disease at the end of 1 year of follow-up). RESULTS: Baseline characteristics were similar between the 2 randomized groups. There was no difference between the 6-month group and 9-month group in the complete clinical response rate on per-protocol analysis (91.5% vs 90.8%; P = .88) or intent-to-treat analysis (75% vs 75.8%; P = .89). Only 1 patient in the 9-month group and no patients in the 6-month group had recurrence of disease. Side effects occurred in 21 (21.3%) and 16 (18.2%) patients in the 6-month and 9-month groups, respectively. CONCLUSIONS: There was no difference in efficacy of antituberculosis therapy delivered for either 6 months or 9 months in either gastrointestinal or peritoneal tuberculosis, confirming the efficacy of intermittent directly observed therapy. CLINICAL TRIALS REGISTRATION: NCT01124929.

Metabolic abnormalities of gastrointestinal mucosa in celiac disease: An in vitro proton nuclear magnetic resonance spectroscopy study.

BACKGROUND AND AIM: Celiac disease (CeD) is a common autoimmune disorder in which ingestion of gluten and related proteins leads to inflammation in the small intestine. Although the histological findings in CeD are characteristic, they are not specific. In this study, proton nuclear magnetic resonance (NMR) spectroscopy was used to investigate the differences in metabolic profile of duodenal mucosal biopsies of patients with CeD and controls to find out the biomarker/s of villous atrophy. METHODS: Duodenal mucosal biopsies were collected from 29 CeD patients (mean age 26.2 ± 10.8 years) and 17 controls (mean age 34.1 ± 11.1 years) and were subjected to proton NMR spectroscopy following perchloric acid extraction. Assignment of metabolite resonances was carried out and their concentrations were determined. For comparison between the groups unpaired t-test/Wilcoxon rank sum test was used. Partial least squares-discriminant analysis was performed to study the clustering behavior of the samples from CeD patients and controls using the Unscrambler 10.2 software. RESULTS: Partial least squares-discriminant analysis clearly differentiated CeD patients from controls. Significantly higher concentrations of isoleucine, leucine, aspartate, succinate, and pyruvate, and lower concentration of glycerophosphocholine, were observed in the duodenal mucosa of CeD patients compared with controls. The results suggest abnormalities in glycolysis, Krebs cycle (energy deficiency), and amino acid metabolism, which may affect the biosynthetic pathways and consequently contribute to villous atrophy. CONCLUSIONS: NMR spectroscopy with multivariate analysis of duodenal mucosal biopsies revealed a characteristic metabolic profile in CeD patients. The work provided an insight in determining biomarker/s for villous atrophy and diagnosis of CeD patients.

Coeliac disease in patients with short stature: A tertiary care centre experience.

BACKGROUND: We aimed to determine the prevalence of coeliac disease among children with short stature at a tertiary care centre and to define the predictors for coeliac disease, if any, in them. METHODS: In this retrospective study, we reviewed the case records of children and adolescents with growth retardation attending the Paediatric Endocrinology Clinic from January 2008 to June 2011. All patients underwent the multi-tier stratified diagnostic protocol for complete evaluation of short stature. Coeliac disease was screened using IgA-anti-tissue transglutaminase antibody. The diagnosis of coeliac disease was made on the basis of the modified European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. RESULTS: Of 432 patients (238 boys) who presented with short stature, 72 (16.7%) had physiological, while 360 (83.3%) had pathological causes. Endocrine causes were growth hormone deficiency (86 patients, 19.9%), hypopituitarism (31, 7.2%), hypothyroidism (22, 5.1%) and others (7, 1.6%). The systemic causes were: coeliac disease (47, 10.9%), haematological diseases (14, 3.2%), renal diseases (11, 2.5%) and others (24, 5.6%). Chronic diarrhoea (OR 15.7, 95% CI 7.8-31.5) and anaemia (OR 4.9, 95% CI 1.9-12.7]) were significant predictors for coeliac disease in patients with short stature. There was a definite response to gluten-free diet in them and the mean (SD) growth velocity measured over at least 6 months of gluten-free diet was 8.1 (3.0) cm/year. CONCLUSION: Nearly 11% of patients presenting with short stature have coeliac disease. In these patients chronic diarrhoea and anaemia were significant predictors of coeliac disease.

Correlation of pre- and post-operative liver function, duct diameter at porta hepatis, and portal fibrosis with surgical outcomes in biliary atresia.

BACKGROUND AND AIMS: Extrahepatic biliary atresia is one of the most challenging conditions in pediatric surgery. The definition of prognostic factors is controversial. Surgical outcomes after bilioenteric drainage procedures are variable. This study attempts to correlate the pre- and post-operative liver histology with clinical factors in order to define early predictors of success. MATERIALS AND METHODS: Twenty consecutive patients, treated by Kasai's portoenterostomy (KP) over a 3 years period were included in this study. Tissue obtained from the porta hepatis was analyzed for duct size using an optical micrometer and was categorized into three types: I-No demonstrable ducts; II - <50 µ; III - >50 µ. Pre- and post-operative liver biopsy was analyzed for architectural changes and fibrosis; hepatic fibrosis was quantified using existing criteria. Pre- and post-operative liver function tests (LFTs) were also done. Surgical outcomes were defined as: (A) Disappearance of jaundice within 3 months; (B) initial disappearance of jaundice with recurrence by 6 months and (C) persistence of jaundice. Duct diameters, fibrosis score, and LFT were correlated with age and clinical outcomes. RESULTS: The surgical outcomes were: A-6 patients (30%), B-6 patients (30%), C-8 patients (40%). The duct size at the porta was I-3 patients, II-11 patients, and III-4 patients (tissue was not available in 2 cases). The change in total serum bilirubin (mg%) from pre- to post-operative period was 13.6 ± 3.9 (Group A), 4.6 ± 2.8 (Group B), and 3.4 ± 3.9 (group C) (P < 0.001) and direct and indirect fractions followed a similar trend; the changes in liver enzymes were not significant. The changes in hepatic histopathological changes (ballooning of hepatocytes, giant cells, cholestasis, portal tract infiltration, ductular proliferation, lobular necrosis, and fibrosis) were also not significant but there was a definite trend in the change in fibrosis -1.500 ± 1.643 (Group A), 0.667 ± 2.582 (Group B), and 1.500 ± 1.852 (Group C) - reduction of fibrosis with good results and progression of fibrosis with poor results. CONCLUSIONS: Following KP, jaundice persisted in 40% patients; it disappeared in 60% patients but reappeared in half of these patients 6 months postoperatively. The duct size at the porta hepatis did not correlate with age or surgical outcome. Serum bilirubin showed the best correlation with surgical outcome. Postoperative changes in hepatic fibrosis seem to have some bearing on surgical outcomes-progressive fibrosis is a poor prognostic factor.

Sequential occurrence of preneoplastic lesions and accumulation of loss of heterozygosity in patients with gallbladder stones suggest causal association with gallbladder cancer.

BACKGROUND: Causal association of gallbladder stones with gallbladder cancer (GBC) is not yet well established. OBJECTIVE: To study the frequency of occurrence of preneoplastic histological lesions and loss of heterozygosity (LOH) of tumor suppressor genes in patients with gallstones. METHODS: All consecutive patients with gallstones undergoing cholecystectomy from 2007-2011 were included prospectively. Histological examination of the gallbladder specimens was done for preneoplastic lesions. LOH at 8 loci, that is 3p12, 3p14.2, 5q21, 9p21, 9q, 13q, 17p13, and 18q for tumor suppressor genes (DUTT1, FHIT, APC, p16, FCMD, RB1, p53, and DCC genes) that are associated with GBC was tested from microdissected preneoplastic lesions using microsatellite markers. These LOH were also tested in 30 GBC specimens. RESULTS: Of the 350 gallbladder specimens from gallstone patients, hyperplasia was found in 32%, metaplasia in 47.8%, dysplasia in 15.7%, and carcinoma in situ in 0.6%. Hyperplasia, metaplasia, and dysplasia alone were found in 11.7%, 24.6%, and 1.4% of patients, respectively. A combination of hyperplasia and dysplasia, metaplasia and dysplasia, and hyperplasia, metaplasia, and dysplasia was found in 3.4%, 6.3%, and 4.3% of patients, respectively. LOH was present in 2.1% to 47.8% of all the preneoplastic lesions at different loci. Fractional allelic loss was significantly higher in those with dysplasia compared with other preneoplastic lesions (0.31 vs 0.22; P = 0.042). No preneoplastic lesion or LOH was found in normal gallbladders. CONCLUSIONS: Patients with gallstones had a high frequency of preneoplastic lesions and accumulation of LOH at various tumor suppressor genes, suggesting a possible causal association of gallstones with GBC.

Issues associated with the emergence of coeliac disease in the Asia­Pacific region: a working party report of the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology.

BACKGROUND AND AIM: Once thought to be uncommon in Asia, coeliac disease (CD) is now being increasingly recognized in Asia­Pacific region. In many Asian nations, CD is still considered to be either nonexistent or very rare. In recognition of such heterogeneity of knowledge and awareness, the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology commissioned a working party to address the key issues in emergence of CD in Asia. METHODS: A working group consisting of members from Asia­Pacific region, Europe, North America, and South America reviewed relevant existing literature with focus on those issues specific to Asia­Pacific region both in terms of what exists and what needs to be done. RESULTS: The working group identified the gaps in epidemiology, diagnosis, and management of CD in Asian­Pacific region and recommended the following: to establish prevalence of CD across region, increase in awareness about CD among physicians and patients, and recognition of atypical manifestations of CD. The challenges such as variability in performance of serological tests, lack of population-specific cut-offs values for a positive test, need for expert dietitians for proper counseling and supervision of patients, need for gluten-free infrastructure in food supply and creation of patient advocacy organizations were also emphasized. CONCLUSIONS: Although absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years or decades. It is thus appropriate that medical community across the Asia­Pacific region define extent of problem and get prepared to handle impending epidemic of CD.

Correlation between intestinal stem cell niche changes and small bowel crypt failure in patients with treatment-naïve celiac disease.

OBJECTIVES: We hypothesized that crypt failure in the small bowel results in villous flattening in patients with celiac disease (CeD). We investigated whether alterations in the stem cell niche (ISC) are responsible for this phenomenon. MATERIALS AND METHODS: We included 92 duodenal (D2/3) biopsies from treatment-naive patients of CeD and 37 controls. All underwent screening for serum anti-tissue transglutaminase and endoscopic upper small bowel biopsy. Immunohistochemical markers were used to investigate ISC niche alterations, including LGR5 for crypt basal cells (CBC), Bmi1 for position 4+ cells, ß-Defensin for Paneth cells, R-spondin1 as WNT activator, transcription factor-4 as WNT transcription factor, BMP receptor1A as WNT inhibitor, fibronectin-1 as periepithelial stromal cell marker, H2AX as apoptosis marker, and Ki67 as proliferation marker. We also analyzed IgA anti-tTG2 antibody deposits by using dual-color immunofluorescence staining. RESULTS: We found that in biopsies from patients with treatment-naive CeD with modified Marsh grade 3a-3c changes, the epithelial H2AX apoptotic index was upregulated than in controls. LGR5+ crypt basal cells were upregulated in all modified Marsh grades compared to controls. However, the Ki67 proliferation index, expressions of WNT-activator RSPO1, and position-4 cell marker Bmi1 did not significantly alter in patients' biopsies as compared to controls ( P = 0.001). We also observed depletion of pericrypt stromal fibronectin-1 in patients with CeD compared to controls. In addition, we identified IgA anti-TG2 antibody deposits in pericrypt stroma. CONCLUSIONS: Our data suggests that ISC niche failure is a plausible hypothesis for villous flattening in patients with CeD, resulting from pericrypt IgA anti-TG2 antibody complex-mediated stromal depletion.

Microscopic colitis in children with chronic diarrhea.

OBJECTIVE: The aim of the present study was to study microscopic colitis (MC) in children with special reference to its role in chronic diarrhea and changes in mucosal biopsies. METHODS: A total of 100 consecutive children ages 3 to 12 years, with nonbloody diarrhea (passage of ≥3 loose stools per day) of >12 weeks' duration were screened and 26 were enrolled in the study in which no specific etiology could be found and colonoscopy did not reveal any mucosal abnormality. Colonic biopsies were evaluated for the presence of lymphocytic colitis or collagenous colitis and those with the characteristic changes were defined to have MC (group A). Colonic biopsies from patients with MC were compared with biopsies from patients with chronic diarrhea but no evidence of MC (group B). One hundred children ages 3 to 12 years with bleeding per rectum were screened and colonic biopsies from 45 patients (group C) who had colonic mucosal changes but no vascular or polyp lesion were compared with patients with MC. RESULTS: Of the 26 patients with chronic diarrhea, MC was found in 5 (3 lymphocytic colitis and 2 collagenous colitis). Significantly higher polymorphonuclear infiltration was seen in group A as compared with group B (13.8 [5.4-20.6] vs 7.2 [0-19.6]; P = 0.03) or group C (13.8 [5.4-20.6] vs 4 [0-13.4]; P = 0.007). Intraepithelial lymphocytes (12 [4-32] vs 4 [0-24]; P = 0.008) and basement membrane thickening (3.5 [2.9-10.6] vs 2.5 [1.6-5.86]; P = 0.008) were also significantly higher in group A as compared with group C. CONCLUSIONS: MC was found to be present in children with nonbloody chronic diarrhea in children. Further multicentric studies may provide adequate data on its prevalence.

Pancreatic Mass Characterization Using IVIM-DKI MRI and Machine Learning-Based Multi-Parametric Texture Analysis.

Non-invasive characterization of pancreatic masses aids in the management of pancreatic lesions. Intravoxel incoherent motion-diffusion kurtosis imaging (IVIM-DKI) and machine learning-based texture analysis was used to differentiate pancreatic masses such as pancreatic ductal adenocarcinoma (PDAC), pancreatic neuroendocrine tumor (pNET), solid pseudopapillary epithelial neoplasm (SPEN), and mass-forming chronic pancreatitis (MFCP). A total of forty-eight biopsy-proven patients with pancreatic masses were recruited and classified into pNET (n = 13), MFCP (n = 6), SPEN (n = 4), and PDAC (n = 25) groups. All patients were scanned for IVIM-DKI sequences acquired with 14 b-values (0 to 2500 s/mm2) on a 1.5T MRI. An IVIM-DKI model with a 3D total variation (TV) penalty function was implemented to estimate the precise IVIM-DKI parametric maps. Texture analysis (TA) of the apparent diffusion coefficient (ADC) and IVIM-DKI parametric map was performed and reduced using the chi-square test. These features were fed to an artificial neural network (ANN) for characterization of pancreatic mass subtypes and validated by 5-fold cross-validation. Receiver operator characteristics (ROC) analyses were used to compute the area under curve (AUC). Perfusion fraction (f) was significantly higher (p < 0.05) in pNET than PDAC. The f showed better diagnostic performance for PDAC vs. MFCP with AUC:0.77. Both pseudo-diffusion coefficient (D*) and f for PDAC vs. pNET showed an AUC of 0.73. ADC and diffusion coefficient (D) showed good diagnostic performance for pNET vs. MFCP with AUC: 0.79 and 0.76, respectively. In the TA of PDAC vs. non-PDAC, f and combined IVIM-DKI parameters showed high accuracy ≥ 84.3% and AUC ≥ 0.84. Mean f and combined IVIM-DKI parameters estimated that the IVIM-DKI model with TV texture features has the potential to be helpful in characterizing pancreatic masses.

Novel Scoring Systems and Age-Based Hepatic Shear Wave Stiffness Cut-Offs for Improving Sonographic Diagnosis of Biliary Atresia.

OBJECTIVES: To make sonographic evaluation for biliary atresia (BA) more objective and reproducible using scoring systems, and evaluate hepatic shear wave elastography (SWE) as an adjunct in sonographic diagnosis of BA. METHODS: Sixty-four infants with cholestatic jaundice were enrolled between June 2016 and March 2018 in this prospective observational cohort study. Sonography and SWE was performed with SuperSonic Aixplorer system. Novel scoring systems were developed incorporating established sonographic parameters and hepatic stiffness values and analysed using SPSS software. RESULTS: Of the 18 patients confirmed as BA, 3 were misdiagnosed on conventional sonography (16.7%) as non-BA. Gall bladder (GB) wall irregularity and fasting GB length were the most accurate (93.8%) and most specific (97.8%) individual parameters, respectively. A significant difference was noted in the triangular cord (TC) thickness of BA and non-BA infants (p <0.001), with a high specificity of 95.6% for a 4 mm cut-off value for a positive TC sign. Comparison of hepatic SWE stiffness among age-matched groups of BA and non-BA showed significant differences (≤60 d: p = 0.003; >60 d: p <0.001) but with a reduced accuracy (93.8%). Diagnostic accuracy of greyscale scoring system (96.9%), greyscale + elastography scoring system in ≤60 d (94.4%) and >60 d (97.8%) were better than that of conventional sonographic diagnosis (93.8%). CONCLUSIONS: Grey scale scoring system improves the accuracy of sonographic diagnosis of BA without any additional cost or time penalty along with making it universally reproducible. SWE has only an adjunctive role, if any, in the sonographic diagnosis of BA.

Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn's disease: a randomized controlled trial.

BACKGROUND: Increased intestinal permeability (IP) has been implicated in the etiopathogenesis, disease activity and relapse of Crohn's disease (CD). Glutamine, the major fuel for the enterocytes, may improve IP. AIM: We evaluated the effect of oral glutamine on IP and intestinal morphology in patients with CD. METHODS: In a randomized controlled trial, consecutive patients with CD in remission phase with an abnormal IP were randomized to a glutamine group (GG) or active control group (ACG) and were given oral glutamine or whey protein, respectively, as 0.5 g/kg ideal body weight/day for 2 months. IP was assessed by the lactulose mannitol excretion ratio (LMR) in urine, and morphometry was performed by computerized image analysis system. RESULTS: Patients (age 34.5 ± 10.5 years; 20 males) were assigned to the GG (n = 15) or ACG (n = 15). Fourteen patients in each group completed the trial. The LMR [median (range)] in GG and ACG at 2 months was 0.029 (0.006-0.090) and 0.033 (0.009-0.077), respectively, with P = 0.6133. IP normalized in 8 (57.1%) patients in each group (P = 1.000). The villous crypt ratio (VCR) [mean (SD)] in GG and ACG at 2 months was 2.68 (1.02) and 2.49 (0.67), respectively, (P = 0.347). At the end of 2 months LMR improved significantly in GG from 0.071 (0.041-0.254) to 0.029 (0.006-0.090) (P = 0.0012) and in ACG from 0.067 (0.040-0.136) to 0.033 (0.009-0.077) (P = 0.0063). VCR improved in the GG from 2.33 (0.77) to 2.68 (1.02) (P = 0.001), and in ACG from 2.26 (0.57) to 2.49 (0.67) (P = 0.009). CONCLUSIONS: Intestinal permeability and morphology improved significantly in both glutamine and ACG.

Role of Whole body PET/CT and Examination under anesthesia with multi-site biopsy in evaluating CUP.

To evaluate the role of 18FDG-WBPET-CT, Examination under anesthesia (EUA), and multiple-site biopsy in detecting the occult site in head & neck carcinoma of unknown primary (HN-CUP). In this prospective study, 22 patients with diagnosed CUP, after a thorough outpatient endoscopic evaluation of upper airway and radiological evaluation (CT/MRI) that ruled out a primary lesion were included. These patients subsequently underwent whole-body PET-CT and EUA. Based on the presence of suspicious findings ( +) or their absence (-) on 18FDG-WBPET-CT (P) and EUA (E), we divided the patients into 5 groups: P-E-, P-E + , P + E-, P + E + , and P + or E + . All these patients underwent bilateral palatine tonsillectomy, bilateral nasopharyngeal biopsy, and ipsilateral lingual tonsillectomy for identification of occult primary. Out of 22 patients, the primary could be detected in 4 patients (18%) after the workup (three in the oropharynx and one in the hypopharynx, all ipsilateral). 18FDG-PET-CT suspected primaries in 7 patients; biopsy was positive for three (sensitivity-75%, specificity-77%, PPV-43%, NPV-93%). Out of 5 patients, who had suspicious findings on EUA, 3 of the biopsies revealed malignancy (sensitivity-75%, specificity-88%, PPV-60%, NPV-94%). Both PET-CT and EUA when combined, yield a NPV of 100% if both are negative and PPV of 100% when both are positive for suspicious findings. No primary was identified in the absence of a suspicion by PET-CT or EUA. Without a suspicion on 18FDG-WBPET-CT and EUA, there is a limited role of multiple-site biopsies in patients of HN-CUP.