Imbalance in the vWF - ADAMTS13 axis exists early in acute pancreatitis and predicts persistent organ failure and pancreatic necrosis-a prospective study.

BACKGROUND: The pathophysiology of Acute Pancreatitis (AP) may be complicated by endothelial activation. von Willebrand Factor (vWF)- ADAMTS13 axis is a marker of endothelial activation. The study aimed to investigate the axis in AP, comparing it in patients with and without persistent organ failure (OF), with and without pancreatic necrosis, and correlating it with the standard severity scores (CRP, APACHE II, BISAP, SOFA, and qSOFA) METHODS: vWF-Antigen (vWF:Ag), vWF-Collagen-Binding-Assay (vWF:CBA), and ADAMTS13 activity (ADAMTS13:act) levels were measured within 5 days of symptom onset in consecutive patients (n = 98), who were admitted with a first episode of AP (Dec 2021-May 2023). RESULTS: Of the 98 patients admitted with AP, 78(79.6 %) had no or transient OF; 20(20.4 %) had persistent OF. Age was comparable (43.73 ± 15.36 vs 38.65 ± 13.69) [mean ± SD](years), and males were predominant in both groups (70.5 % vs 80 %). Patientswith persistent OF had higher vWF:CBA(%)[323(279-486.5) vs 199.5(159.1-295.75)] and lower ADAMTS13:act(%)[35.4(23.8-56.85) vs 56.35(44.1-71.9)][median (25th - 75th percentile)](P = 0.001) than those with no or transient OF. Patients with pancreatic necrosis (n = 19) had lower ADAMTS13:act(%)[42.79 ± 18.69] than those without pancreatic necrosis (n = 18) [62.49 ± 22.64] (P < 0.01). ADAMTS13:act had a negative correlation(r = -0.2), whereas vWF:Ag and vWF:CBA had a positive correlation (r = 0.2) with the standard severity scores (P < 0.05). ADAMTS13:act could predict pancreatic necrosis [AUROC-0.737, P < 0.05] and persistent OF [AUROC-0.746, P < 0.001], while vWF:CBA could predict persistent OF [AUROC- 0.73, P < 0.001]. CONCLUSION: vWF-ADAMTS13 axis helps to predict severe disease and is associated with poor outcomes in acute pancreatitis.

Pregnancy Outcomes in Patients with Early-Onset Idiopathic Chronic Pancreatitis.

BACKGROUND: Early-onset idiopathic chronic pancreatitis (EOICP) is a disease that affects young individuals. Data on pregnancy outcomes in EOICP are limited. AIM: To assess the pregnancy outcomes in patients with EOICP and the effect of pregnancy on the course of EOICP. METHODS: Patients with EOICP with disease onset before their pregnancy were recruited. Data regarding demographic variables, disease duration, pregnancy outcomes, and course of illness were noted. RESULTS: 50 patients were included in the study contributing to a total of 86 pregnancies. The mean age of onset of symptoms and at the time of delivery was 17.95 (5.71) and 23.44 (4.28) years, respectively. Gestational diabetes (GD) and gestational hypertension (GH) noted in one (1.5%) each. 3 (4.5%) pregnancies were preterm. 19 (22.1%) pregnancies did not have successful outcomes (7 (8.1%) were induced abortions). 12 (15.2%) pregnancies had spontaneous pregnancy losses. 8 (10.1%) were spontaneous abortions and 4 (5.1%) were stillbirths. Of 67 successful pregnancies, 33 (49.3%) pregnancies were delivered by LSCS. Compared to average rates of LSCS in India, this was significantly higher (21.5% vs 49.3%-p ≤ 0.001). The average birth weight was 2.87 (0.48) kg. There was one (1.5%) neonatal death. Compared to the published Indian data, there was no significant difference in the incidence of spontaneous pregnancy losses, GD, GH, preterm labor, and birth weight. Pancreatic pain was reported by 21 (42%) women in total 27 (31.4%) pregnancies. There was no difference in maternal or fetal outcomes between pregnancies with or without pancreatic pain. There were no pancreatitis-related complications reported during the pregnancies. CONCLUSION: The present study shows that mothers affected with EOICP have pregnancy outcomes similar to healthy women in India.

Bile Culture May Guide Antibiotic Stewardship in Acute Bacterial Cholangitis.

BACKGROUND: Bile cultures are often sent with blood cultures in patients with acute bacterial cholangitis. AIMS: To assess the yield of blood and bile cultures in patients with cholangitis and the clinical utility of bile cultures in guiding therapy. METHODS: All patients diagnosed with cholangitis, based on the Tokyo 2013/2018 guidelines were recruited retrospectively over ten years. The clinical and investigation details were recorded. The results of bile and blood cultures including antibiotic sensitivity patterns were noted. The concordance of microorganisms grown in blood and bile cultures and their sensitivity pattern were assessed. RESULTS: A total of 1063 patients with cholangitis were included. Their mean age was 52.7 ± 14 years and 65.4% were males. Blood cultures were positive in 372 (35%) patients. Bile culture was performed in 384 patients with 84.4% being positive, which was significantly higher than the yield of blood culture (p < 0.001). Polymicrobial growth was more in bile (59.3%) than in blood cultures (13.5%, p < 0.001). E.coli, Klebsiella, Enterococcus and Pseudomonas were the four most common organisms isolated from both blood and bile. Extended spectrum betalactamase producing organisms were isolated in 57.7% and 58.8% of positive blood and bile cultures, respectively. Among 127 patients with both blood and bile cultures positive, complete or partial concordance of organisms was noted in about 90%. CONCLUSION: Bile and blood cultures have a similar microbial profile in most patients with cholangitis. As bile cultures have a significantly higher yield than blood cultures, they could effectively guide antimicrobial therapy, especially in those with negative blood cultures.

A Simple Pre-endoscopy Score for Predicting Risk of Malignancy in Patients with Dyspepsia: A 5-Year Prospective Study.

BACKGROUND: The guidelines for performing endoscopy in dyspeptic patients based on clinical parameters alone have shown variable performance, and there is a need for better prediction tools. AIM: We aimed to prospectively develop and validate a simple clinical-cum-laboratory test-based scoring model to identify dyspeptic patients with high risk of upper gastrointestinal malignancy (UGIM). METHODS: Adult patients with dyspeptic symptoms were prospectively recruited over 5 years. Clinical details including alarm features were recorded, and blood tests for hemoglobin and albumin were done before endoscopy. The presence of UGIM was the primary outcome. Risk factors for UGIM were assessed, and based on the OR of significant factors, a predictive scoring model was constructed. ROC curve was plotted to identify optimal cutoff score. The model was validated using bootstrapping technique. RESULTS: The study included 2324 patients (41.9 ± 12.8 years; 33.4% females). UGIM was noted in 6.8% patients. The final model had following five positive predictors for UGIM-age > 40 years (OR 3.3, score 1); albumin ≤ 3.5 g% (OR 3.4, score 1); Hb ≤ 11 g% (OR 3.3, score 1); alarm features (OR 5.98, score 2); recent onset of symptoms (OR 8.7, score 3). ROC curve had an impressive AUC of 0.9 (0.88-0.93), and a score of 2 had 92.5% sensitivity in predicting UGIM. Validation by bootstrapping showed zero bias, which further strengthened our model. CONCLUSION: This simple clinical-cum-laboratory test-based model performed very well in identifying dyspeptic patients at risk of UGIM. This can serve as a useful decision-making tool for referral for endoscopy.

Addition of second-line steroid sparing immunosuppressants like mycophenolate mofetil improves outcome of Immunoglobulin G4-related disease (IgG4-RD): a series from a tertiary care teaching hospital in South India.

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease. This disease may be associated with elevated serum and tissue IgG4 levels. Early treatment prevents fibrosis and organ damage. We retrospectively studied the clinicopathologic correlation and outcome of treatment in IgG4-RD. This single-center retrospective study was done using electronic records of patients subjected to assay of serum IgG4 levels in our laboratory by nephelometry. There were 473 patients with suspected IgG4-RD. Of them, 41 patients fulfilled comprehensive diagnostic criteria for IgG4-RD and 432 had diseases other than IgG4-RD. Clinical and histopathological data including tissue IgG4/IgG ratio, other relevant laboratory findings as well as management data of 41 patients with IgG4-RD were analyzed. There were 29 males and 12 females with mean age of 44.1 ± 2.19 years. Thirteen patients had definite, 19 had probable and 9 had possible IgG4-RD. Male predominance, multiple organ involvement and IgG4 responder Index were significantly higher in definite IgG4-RD as compared to probable and possible IgG4-RD. Serum IgG4 level was elevated in 37 patients (90.2%). Glucocorticoids were used in 35 patients (85.4%) and second-line immunosuppressive agent in 23 patients (65.7%). Of the 21 patients on follow-up, 19 (90.7%) had clinical improvement at the first follow-up visit. Nine (90%) out of the ten patients who were assessed by IgG4 responder index, also had shown improved score with treatment. Patients with IgG4-RD in our series showed favorable responses to treatment with glucocorticoids and addition of steroid sparing immunosuppressive agents (mainly mycophenolate mofetil) helped successful tapering of steroids, while maintaining the improvement.

Does COX1 gene polymorphism (A842G/C50T) influence peptic ulcer bleeding in Indian patients?.

This is a pilot study to test the hypothesis that polymorphisms that may be linked to cyclooxygenase production may affect the likelihood and the nature of bleeding in patients with ulcer disease. Of the two polymorphism that have previously been studied for links we chose the A842G polymorphims. Of the 50 patients with ulcer bleeding who were studied, 8 had a heterozygous polymorphisms and 42 had the normal configuration. On comparing these two groups. there were no significant differences in clinical presentation except that there was a tendency to have less gastric ulcers among those with the A842G/C50T polymorphism. Based on these studies we need to undertake a larger studies comparing these groups with those with ulcers without GI bleeding and those without ulcers

Comparison of the diagnostic yield of rapid versus non-rapid onsite evaluation in endoscopic ultrasound-guided fine-needle aspiration cytology of solid pancreatic lesions.

Background: The role of rapid on-site evaluation (ROSE) for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions is debatable. In this study, we aimed to compare the diagnostic yield of ROSE vs. non-ROSE in solid pancreatic lesions. Methods: This retrospective single-center study included patients undergoing EUS-FNA of solid pancreatic lesions from 2019-2021. Patients with cystic lesions, those undergoing fine-needle core biopsy, those undergoing repeat procedures, and patients with non-diagnostic smears with less than 6-month follow up were excluded. The diagnostic yield, need for repeat procedures and number of passes required with and without ROSE were analyzed in these patients. Results: Of the 111 patients included, 56 underwent ROSE. The majority of lesions were malignant in both groups (79.6% ROSE vs. 75% non-ROSE). The diagnostic yield was 96.4% in the ROSE group and 94.5% in the non-ROSE group. Repeat samples were needed in 1 ROSE and 2 non-ROSE patients. The median number of passes made was significantly fewer in the ROSE group (3.5, interquartile range - 3,4) compared with the non-ROSE group (4, interquartile range - 3,5) P=0.01. However, the frequency of procedure-related complications was similar in both groups. Conclusion: The utilization of ROSE during EUS-FNA of solid pancreatic lesions does not affect the diagnostic yield or the need for repeat samples, but reduces the number of passes needed for acquiring samples.

A novel frameshift mutation in TRPV6 is associated with hereditary pancreatitis.

Introduction: Hereditary pancreatitis (HP) is a rare debilitating disease with incompletely understood etio-pathophysiology. The reduced penetrance of genes such as PRSS1 associated with hereditary pancreatitis indicates a role for novel inherited factors. Methods: We performed whole-exome sequencing of three affected members of an Indian family (Father, Son, and Daughter) with chronic pancreatitis and compared variants with those seen in the unaffected mother. Results: We identified a novel frameshift mutation in exon 11 of TRPV6 (c.1474_1475delGT; p.V492Tfs*136), a calcium channel, in the patients. Functional characterization of this mutant TRPV6 following heterologous expression revealed that it was defective in calcium uptake. Induction of pancreatitis in mice induced Trpv6 expression, indicating that higher expression levels of the mutant protein and consequent dysregulation of calcium levels in patients with chronic pancreatitis could aggravate the disease. Discussion: We report a novel frameshift mutation in TRPV6 in an Indian family with HP that renders the mutant protein inactive. Our results emphasize the need to expand the list of genes used currently for evaluating patients with hereditary pancreatitis.

Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn's disease in Indian.

BACKGROUND: Multiple genetic risk factors for Crohn's disease (CD) have been identified. However, these observations are not consistent across different populations. The protein tyrosine phosphate non-receptor type 2 (PTPN2) gene plays a role in various aspects of host defense including epithelial barrier function, autophagy, and innate and adaptive immune response. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) have been associated with risk of CD in Western countries. AIM: To evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population. METHODS: We conducted a prospective case-control study. Patients with CD were recruited, and their clinical and investigation details were noted. Controls were patients without organic gastrointestinal disease or other comorbid illnesses. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) were assessed. DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers. The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism. The frequency of alleles was determined. The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences. RESULTS: A total of 108 patients with CD (mean age 37.5 ± 12.7 years, females 42.6%) and 100 controls (mean age 39.9 ± 13.5 years, females 37%) were recruited. For the single nucleotide polymorphism (SNP) rs7234029, the overall frequency of G variant genotype (AG or GG) was noted to be significantly lower in the cases compared to controls (35.2% vs 50%, P = 0.05). For the SNP rs2542151, the overall frequency of G variant genotype (GT or GG) was noted to be similar in cases compared to controls (43.6% vs 47%, P = 0.73). There were no significant differences in minor allele (G) frequency for both polymorphisms between the cases and controls. Both the SNPs had no significant association with age of onset of illness, gender, disease location, disease behaviour, perianal disease, or extraintestinal manifestations of CD. CONCLUSION: Unlike observation form the West, polymorphisms in the PTPN2 gene (rs7234029 and rs2542151) are not associated with an increased risk of developing CD in Indian patients.

Prevalence of serological markers of hepatitis B in inflammatory bowel disease - Experience from a tertiary care centre in South India.

Inflammatory bowel disease patients are at risk of hepatitis B infection. Data on this prevalence from South Asia are limited. We conducted a prospective study comprising of 76 inflammatory bowel disease patients between October 2013 and August 2014. Prevalence of hepatitis B surface antigen in inflammatory bowel disease, ulcerative colitis and Crohn's disease patients were 2.6%, 2.4% and 3% respectively and that of markers of hepatitis B exposure (hepatitis B surface antigen /hepatitis B core antibody) were 11.8%, 14.3% and 9.1% respectively. Risk factors found significantly more common in those positive for viral markers compared to those negative were age, non-inflammatory bowel disease related surgery and hospital admission. Only 7(9.2%) had completed hepatitis B vaccination. There is a need to create awareness among physicians regarding the importance of hepatitis B screening and vaccination in inflammatory bowel disease patients.

Self-expanding metal stent in esophageal perforations and anastomotic leaks.

BACKGROUND AND AIMS: Placement of self-expanding metal stents (SEMS) has emerged as a minimally invasive treatment option for esophageal perforation and leaks. The aim of our study was to assess the role of SEMS for the management of benign esophageal diseases such as perforations and anastomotic leaks. METHODS: All patients (n = 26) who underwent SEMS placement for esophageal perforation and anastomotic leaks between May 2012 and February 2019 were included. Data were analyzed in relation to the indications, type of stent used, complications, and outcomes. RESULTS: Indications for stent placement included anastomotic leaks 65% (n = 17) and perforations 35% (n = 9). Fully covered SEMS (FCSEMS) was placed in 25 patients, and in 1, partially covered SEMS (PCSEMS) was placed. Stent placement was successful in all the patients (n = 26). Four patients did not report for follow-up after stenting. Among the patients on follow-up, 91% (20/22) had healing of the mucosal defect. Stent-related complications were seen in 5 (23%) patients and included stent migration [3], reactive hyperplasia [1] and stricture [1]. CONCLUSION: Covered stent placement for a duration of 8 weeks is technically safe and clinically effective as a first-line procedure for bridging and healing benign esophageal perforation and leaks.

Acoustic radiation force impulse imaging of pancreas in patients with early onset idiopathic recurrent acute pancreatitis.

BACKGROUND AND AIMS: Patients with recurrent acute pancreatitis (RAP) may progress to chronic pancreatitis (CP). A critical step in this progression is the development of fibrosis. Elastography has been used to assess degree of fibrosis by measurement of shear wave velocity (SWV). The aim of this study was to measure the stiffness of pancreas as a surrogate for pancreatic fibrosis in patients with RAP and compare it with a group of individuals without any history of pancreatic disorders. MATERIAL AND METHODS: Using acoustic radiation force impulse (ARFI) imaging SWV was calculated in 31 patients with idiopathic RAP having disease onset ≤30 years. A control group of 31 individuals with no history pancreatic disorder and no features of CP on endosonography was selected for comparison. ARFI imaging was done by a single radiologist who was blinded to the cases and controls RESULTS:: Mean age of patients with RAP was 24.8 (SD 9.86) years, disease duration was 3.45 (interquartile range 1-5) years, mean number of episodes 4.9 (SD 2.72). There was a significant difference in SWV between patients (1.27 ± 0.50 m/s) and controls (1.00 ± 0.17 m/s) (P = 0.001)). There was a positive correlation between SWV and number of pain episodes (P = 0.026) and negative correlation with BMI (P = 0.002). CONCLUSION: SWV was high in patients with RAP indicating a stiff pancreas. The stiffness increases with the number of episodes of pancreatitis.

Immediate and long-term outcome of corrosive ingestion.

BACKGROUND: Corrosive ingestion (CI) has short- and long-term consequences. The aim of this study was to assess the outcome of mucosal injury grade ≥ 2A. METHODS: Consecutive patients between January 2008 and January 2015 who presented within 48 h of CI were included. Details of substance ingested, intent, symptoms, injury grade at endoscopy, and treatment were obtained by a review of medical records. Patients aged less than 15 years or injury grade less than 2A were excluded. Patients were followed up using a structured symptom-based questionnaire and barium swallow. RESULTS: A total of 112 patients were admitted with CI during the study period. Eighty-two patients were included in the study. There was no relationship between the presence of symptoms or oral mucosal injury and the grades of gastrointestinal mucosal injury. Grades 2B and 3A were the most common grades of mucosal injury. Five patients died at index hospitalization. Patients were followed up for a median period of 31 months (6-72) during which 11 patients were lost to follow up. During follow up, 2 patients with high-grade injury died as a consequence of CI and 4 died of unrelated causes. Sixteen (26.6%) patients remained symptomatic. Forty-three patients underwent barium swallow. Esophageal stricture was identified in 11 patients, gastric stricture in 8, and combined esophageal and gastric in 2. High-grade esophageal mucosal injury was associated with a high risk of stricture formation (p = 0.02). CONCLUSIONS: CI is associated with high immediate and long-term morbidity and mortality.

Endoscopic ultrasonography in pediatric patients--Experience from a tertiary care center in India.

BACKGROUND AND AIMS: Although endoscopic ultrasound (EUS) is used in the management of various gastrointestinal (GI) diseases in adults, data on its role in children is limited. This study evaluated the indications, safety, and impact of EUS in children. METHODS: Records of children (<18 years age) who underwent EUS between January 2006 and September 2014 were reviewed retrospectively and analyzed. RESULTS: One hundred and twenty-one children (70 males, 51 females) aged 15.2 ± 2.9 years (mean ± SD) underwent 123 diagnostic (including fine needle aspiration cytology (FNAC) in 7) and 2 therapeutic EUS procedures. Conscious sedation was used in 81 procedures (65%) and general anesthesia in 44 (35%). The pancreaticobiliary system was evaluated in 114 (118 procedures), mediastinum in 5, and stomach in 2 patients. EUS diagnosed chronic pancreatitis (21 patients), pancreatic necrosis (1), splenic artery pseudoaneurysm (1), gastric varix (1), pseudocysts (3), insulinomas (2), other pancreatic masses (2), choledocholithiasis (2), choledochal cysts (2), portal biliopathy (1), esophageal leiomyoma (1), gastric neuroendocrine tumor (NET) (1), and GI stromal tumor in stomach (1). EUS-guided FNAC was positive in four of seven patients (two had tuberculosis, one pancreatic solid pseudopapillary tumor, and one gastric NET). Three patients had minor adverse events. EUS had a positive clinical impact in 43 (35.5%) patients. CONCLUSIONS: EUS is feasible and safe in children. It provides valuable information that helps in their clinical management.

Pancreatic exocrine insufficiency: Comparing fecal elastase 1 with 72-h stool for fecal fat estimation.

INTRODUCTION: Identification of pancreatic exocrine insufficiency (PEI) is important in the management of chronic pancreatitis. The 72-h stool for fecal fat estimation (FFE) has long been considered a gold standard indirect test for the diagnosis of PEI. However, the test is cumbersome for both patients and laboratory personnel alike. In this study, we aimed to assess fecal elastase 1 (FE1) as an alternate to FFE for the diagnosis of PEI. METHODS: In all, 87 consecutive patients diagnosed with chronic pancreatitis were included in this study. FFE and FE1 estimation was done for all the patients. For FE1, two cutoffs (<100 and <200 µg) were selected to define pancreatic exocrine insufficiency. The sensitivity, specificity, and positive and negative predictive values for the two cutoffs were estimated. Kappa statistics was used to assess degree of agreement between both tests. RESULTS: All patients completed the study and were included in the analysis. The sensitivity, specificity, and positive and negative predictive value and PABAK (prevalence and bias adjusted kappa) for FE1 <100 µg was 84.9, 47.6, 83.6, 50, and 0.52, respectively. For FE1 <200 µg, it was 90.9, 9.5, 75.95, 25, and 0.43, respectively. CONCLUSION: FE1 is a sensitive test; however, it does not have a good agreement with FFE. FE1 may be used as screening test for PEI in patients with chronic pancreatitis.

Hypogammaglobulinemia-associated gastrointestinal disease--a case series.

Hypogammaglobulinemia, a form of primary immunodeficiency, is an uncommon condition. Gastrointestinal (GI) symptoms may be the only presentation. A series of 22 patients who presented with GI symptoms and were diagnosed with hypogammaglobulinemia is presented. Chronic diarrhea was the presentation in majority (90.9 %) of patients. Malabsorption was identified in 87.5 % of patients followed by weight loss (59.0 %), abdominal pain (27.2 %), and oral ulcers (4.5 %). The median duration of symptoms prior to diagnosis was 4 years, range being 6 months to 23 years. Evaluation revealed opportunistic infections including Giardia lamblia in 31.8 % and Cryptosporidium parvum, Isospora belli, Cytomegalovirus and Aeromonas in 4.5 % each. Serum globulins were low in all patients. Duodenal biopsy showed paucity of plasma cells in 45 %, villous atrophy in 35 % and nodular lymphoid hyperplasia in 30 % patients. Though uncommon, hypogammaglobulinemia is associated with GI disease. The possibility of a primary immunodeficiency should be considered in patients presenting with GI symptoms and low serum globulin.