Rakesh Kalapala - Academia.edu (original) (raw)
Papers by Rakesh Kalapala
American Journal of Gastroenterology
Pediatric Obesity
SummaryObesity in paediatrics has become one of the most serious public health concerns worldwide... more SummaryObesity in paediatrics has become one of the most serious public health concerns worldwide. Paediatric obesity leads to increased adult obesity and is associated with several comorbidities, both physical and psychological. Within gastroenterology, non‐alcoholic fatty liver disease (NAFLD) is now the most common cause of paediatric liver disease and the most common cause of liver transplantation in young adults. Treatment for NAFLD largely focuses on treatment of obesity with weight loss strategies. Unfortunately, the traditional method of weight loss using multicomponent lifestyle modification (dietary changes, increased exercise and behavioural modification) has often led to disappointing results. In adult patients with obesity, treatment strategies have evolved to include bariatric surgery and, more recently, bariatric endoscopy. In paediatrics, the obesity and NAFLD epidemics will likely require this variety of treatment to address children in a personalized manner. Here, ...
Gastrointestinal Endoscopy
Endoscopy International Open
Background and study aims Percutaneous liver biopsy is traditionally done on the right lobe of th... more Background and study aims Percutaneous liver biopsy is traditionally done on the right lobe of the liver. Endoscopic ultrasound-guided liver biopsy (EUS-LB) can be performed on either the left or right lobe or as a combined bi-lobar biopsy. Earlier studies did not compare the benefit of bi-lobar biopsies to single-lobe biopsy for reaching a tissue diagnosis. The current study compared the degree of agreement of pathological diagnosis between the left lobe of the liver compared to right-lobe and with bi-lobar biopsy. Patients and methods Fifty patients fulfilling the inclusion criteria were enrolled in the study. EUS-LB with a 22G core needle was performed separately on both the liver lobes. Three pathologists, who were blinded to the site of biopsy independently reviewed the liver biopsies. Sample adequacy, safety, and concordance of pathological diagnosis between left- and right-lobe biopsy of the liver were analyzed. Results The pathological diagnosis was made in 96 % of patients....
Journal of Crohn's and Colitis
Background and Aims Lack of clinical validation and inter-observer variability are two limitation... more Background and Aims Lack of clinical validation and inter-observer variability are two limitations of endoscopic assessment and scoring of disease severity in patients with ulcerative colitis [UC]. We developed a deep learning [DL] model to improve, accelerate and automate UC detection, and predict the Mayo Endoscopic Subscore [MES] and the Ulcerative Colitis Endoscopic Index of Severity [UCEIS]. Methods A total of 134 prospective videos [1550 030 frames] were collected and those with poor quality were excluded. The frames were labelled by experts based on MES and UCEIS scores. The scored frames were used to create a preprocessing pipeline and train multiple convolutional neural networks [CNNs] with proprietary algorithms in order to filter, detect and assess all frames. These frames served as the input for the DL model, with the output being continuous scores for MES and UCEIS [and its components]. A graphical user interface was developed to support both labelling video sections an...
Journal of Clinical and Experimental Hepatology
Gastrointestinal Endoscopy
Annals of Gastroenterology, 2020
Background Acute calculous cholecystitis (ACC) is the most frequent complication of gallstones re... more Background Acute calculous cholecystitis (ACC) is the most frequent complication of gallstones requiring cholecystectomy. These patients may have coexisting choledocholithiasis. We aimed to evaluate the role of current guidelines for choledocholithiasis in patients with ACC. Methods In this retrospective study, we included all patients diagnosed with ACC between December 2018 and May 2019. These patients were substratified according to the guidelines of the American and European Societies of Gastrointestinal Endoscopy (ASGE and ESGE) as having high, intermediate, or low likelihood of choledocholithiasis, and the diagnostic performance was measured. Binomial logistic regression analysis was applied to ascertain independent risk factors for choledocholithiasis. Results A total of 173 patients with ACC, mean age (±standard deviation) 49.89±15.74 years and 60.1% male, were included. Sixty-three (36.4%) had confirmed choledocholithiasis. ASGE high likelihood criteria had sensitivity and specificity of 61.9% (95% confidence interval [CI] 48.8-73.9) and 83.4% (95%CI 75.4-90.0) for predicting choledocholithiasis. ESGE high likelihood criteria had sensitivity and specificity of 49.2% (95%CI 36.4-62.1) and 87.3% (95%CI 79.6-92.9). On logistic regression analysis, an alkaline phosphatase level above the upper limit of normal (P=0.003; odds ratio [OR] 4.26, 95%CI 1.66-10.96) and a dilated common bile duct on ultrasound (P=0.001; OR 9.97, 95%CI 4.65-21.36) were independent positive predictors for choledocholithiasis, while acute biliary pancreatitis was an independent negative predictor (P=0.030; OR 0.36, 95%CI 0.14-0.91). Conclusions The performance of the ASGE and ESGE guidelines' risk stratification criteria is inadequate in patients with ACC. We suggest the utilization of a separate predictive model for suspected choledocholithiasis in these patients.
Gastroenterology, 2018
Introduction: Chronic pancreatitis (CP) is characterized by pain, exocrine insufficiency and diab... more Introduction: Chronic pancreatitis (CP) is characterized by pain, exocrine insufficiency and diabetes. Studies evaluating the impact of endotherapy and surgery on diabetes in CP have yielded divergent results. In this study, we evaluate the risks of diabetes and effect of pancreatic ductal clearance on its development in patients with CP. Methods: A database was generated between 1 st Aug. 2011 to 31 st July 2012 wherein consecutive patients with CP who visited the Pancreas Clinic were enrolled and prospectively followed. Details pertaining to patient demography, disease onset, progression, morphology (imaging), and treatment received were recorded after verifying from the available documents. After recording relevant available data, the patients were subjected to 6-mthly follow-up, during which all data are being prospectively recorded. Follow-up of patients who could not visit the hospital physically was done via a structured telephone interview. Patients without complete data and those who were lost to follow-up were excluded from the study. In the current study, data until June 2017 are being reported. For categorical variables, Fischer's exact or the Chi square test was performed as appropriate; while Student's 't' or the Mann Whitney U test was conducted for continuous variables. Step forward binary logistic regression was performed to identify disease related factors that imparted independent risk of development of diabetes. The Kaplan-Meier survival analysis and Cox proportional hazards model were used to compare the diabetes free interval since onset of CP symptoms and to calculate the HR (95% confidence interval [CI]). A two-tailed 'p' value of <0.05 was considered statistically significant. Results: 644 patients were enrolled into the database, of which 137 were excluded in this study. 507 patients were analyzed; of which 312 (61.5%) had idiopathic CP. 283 (55.8%) patients underwent ductal clearance (ESWL with ERCP 232, drainage surgery 27 and ESWL followed by surgery 24), while 190 (37.5%) patients developed diabetes. The mean (SD) duration between onset of CP symptoms and ductal clearance was 3.4 (3.2)yrs. Alcohol intake & presence of pancreatic ductal calculi were independently associated with the development of diabetes (OR [95% CI] of 2.01 [1.16-3.47], p=0.03 and 2.04 [1.38-3.01], p<0.0001 respectively) (Table 1). Kaplan-Meier estimate for diabetes free patients was significantly higher in the patients who underwent ductal clearance in the idiopathic CP group (p=0.001 by Log rank test), with a Hazard ratio (HR [95% CI]) of 2.01 (1.3-3.0), p=0.002. This was not significantly different for patients with non-idiopathic (alcohol+/smoking) CP (Fig. 1). Discussion: Pancreatic ductal calculi increase the risk of diabetes in CP. Early ductal clearance of stones could delay the development of diabetes in patients with idiopathic CP.
Journal of Gastroenterology and Hepatology, 2020
Introduction: Even though ductal interventions in chronic pancreatitis (CP) is known to improve p... more Introduction: Even though ductal interventions in chronic pancreatitis (CP) is known to improve pain, its impact on diabetes is unclear. In this cohort study, we evaluated the impact of ductal interventions on diabetes in these patients. Methods: Consecutive patients with CP visiting the Pancreas Clinic between 1 st August 2011 and 31 st July 2012 were enrolled and followed till December 2018. Detailed clinical, laboratory, imaging, and treatment data were recorded at enrollment and follow-up. Patients were followed 6-monthly through hospital visit and/or telephonic interview. Risk factors for diabetes were evaluated using logistic regression. The impact of ductal interventions on diabetes was evaluated using Kaplan Meier survival analyses and Cox Proportional Hazard. Results: 644 patients were enrolled of which 137 were excluded. 326 (64.3%) patients had idiopathic CP. 283 (55.8%) patients underwent ductal intervention. The cumulative incidence of diabetes was 57.9%. Median duration between symptom onset and ductal intervention were similar irrespective of diabetes [2.6 (0.6-6.0) vs 3.0 (1.0-5.5) yrs; p=0.69]. Alcohol intake and pancreatic ductal calculi were independent risk factors for diabetes (OR [95% CI] of 2.05 (1.18-3.55), p=0.01 and 2.05 (1.28-3.28), p=0.003 respectively). Kaplan Meier analyses revealed that diabetes free interval-was significantly longer in patients undergoing ductal interventions, predominantly in those with idiopathic CP with obstructive ductal calculi [HR (95%CI) 0.39 (0.28-0.55); p< 0.0001]. There were no differences in glycemic status in patients with non-idiopathic CP and those with preexisting diabetes. Discussion: Early ductal intervention could delay development of diabetes in patients with idiopathic CP with obstructive ductal calculi.
Gastrointestinal Endoscopy, 2020
Background: Therapeutic endoscopy plays a major role in the management of upper gastrointestinal ... more Background: Therapeutic endoscopy plays a major role in the management of upper gastrointestinal (UGI) post-surgical leaks, with multiple endoscopic techniques being available. However, no definite consensus exists on most appropriate therapeutic approach, as well as data is scarce regarding clinical success and safety. Aim: Evaluate endoscopic therapy results on the management of UGI post-surgical leaks regarding number and order of therapies performed, as well as safety, clinical success and long-term follow-up. Methods: Multicenter, international, retrospective study from 10 centers of consecutive patients who underwent endoscopic treatment of UGI post-surgical leaks. Results: 206 patients (50.5% male) were included, with a median age of 54 years (range 18-81). Previous surgery most often performed was sleeve gastrectomy (38.8%), followed by total gastrectomy (21.8%), Ivor-Lewis esophagectomy (15.0%) and gastric bypass (10.7%). Median time from surgery to beginning of endoscopic treatment was 16 days (range 0-2405). Global leak closure was observed in 187 patients (90.8%). Endoscopic closure was achieved in 165 patients (80.1%), after a median follow-up of 52 days (range 0-693). In 8 patients (3.9%) in whom leak closure was not achieved, a stent was left-in-place, without evidence of leak persistence during follow-up. Fourteen patients (6.8%) underwent surgery after endoscopic treatment failure, and leak closure was possible in 12 of them. One patient underwent radiological leak closure and one patient had spontaneous closure. Most commonly performed first-line endoscopic treatment was SEMS placement [average ranking (AR) 5.5], followed by over-the-scope clips (AR 5.3), endoscopic vacuum therapy (AR 5.1) and endoscopic internal drainage (AR 5.1). Multimodal therapeutic endoscopy was necessary in 40.8% of patients (nZ84; median number of different therapies: 2; range 1-6). The median total number of endoscopic procedures performed per patient were 3 (range 1-26). The success-rate of leak closure was 41.3% (85/206) with the first endoscopic technique, 44.3% (47/106) with the second technique, 35.6% (16/45) with the third technique, 59.1% (13/22) with the fourth technique, 80.0% (4/5) with the fifth technique. In one patient that underwent 6 different endoscopic techniques, endoscopic closure was not possible. The global rate of at least one endoscopic therapy-related adverse event (AE) was 39.3% (nZ81; one AE: nZ60; two AEs: nZ21), being severe in 10 patients (4.9%). Leak-related mortality rate was 11.6% (nZ24). Median follow-up since beginning of endoscopic therapy was 303 days (range 2-2801). Conclusion: Multimodal therapeutic endoscopy, despite time-consuming, allows leak closure in a significant proportion of patients, with a low rate of associated severe-AEs.
Gastrointestinal Endoscopy, 2022
With great interest, we read the study comparing preoperative, intraoperative, and follow-up func... more With great interest, we read the study comparing preoperative, intraoperative, and follow-up functional luminal imaging probe measurements in patients undergoing myotomy for achalasia cardia. 1 In that study, the esophagogastric junction distensibility index (EGJ-DI) was measured at 4 time points (preoperative, induction, postmyotomy, and follow-up) in patients undergoing peroral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM). The authors concluded that the preoperative and induction mean EGJ-DIs were similar, with a significant increase in DI after POEM. At the 12month follow-up visit, there was a decrease in DI as compared with the postmyotomy value, although it was higher than preoperative values. These values at 4 different time points were compared by use of a paired t test. However, the paired t test should be used to compare continuous variables at 2 different time points. 2 For comparison of more than 2 mean scores at different time points, repeated-measures analysis of variance (ANOVA) should be performed. 3 The application of a paired t test to such data multiple times increases type 1 errors in multiples of 5% for each comparison. A Greenhouse-Geisser correction should be used if sphericity assumption is violated. Pairwise comparisons should be analyzed with a Bonferroni post hoc test, to find out which 2 specific means are statistically different. If overall ANOVA is not statistically significant, then a pairwise comparison should not be performed. The authors should use repeated-measures ANOVA for analysis of mean EGJ-DI at 4 different time points.
Meta Gene, 2021
Background Mortality due to COVID-19 caused by SARS-CoV-2 infection varies among populations. Fun... more Background Mortality due to COVID-19 caused by SARS-CoV-2 infection varies among populations. Functional relevance of genetic variations in Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2), two crucial host factors for viral entry, might explain some of this variation. Methods In this comparative study in Indian subjects, we recruited 510 COVID-19 patients and retrieved DNA from 520 controls from a repository. Associations between variants in ACE2 and TMPRSS2 with disease severity were identified by whole exome sequencing (WES, n = 20) and targeted genotyping (n = 1010). Molecular dynamic simulations (MDS) were performed to explore functional relevance of the variants. Cleavage of spike glycoprotein by wild and variant TMPRSS2 was determined in HEK293T cells. Potential effects of confounders on the association between genotype and disease severity were tested (Mantel-Haenszel test). Results WES identified deleterious variant in TMPRSS2 (rs12329760, G > A, p. V160M). The minor allele frequency (MAF) was 0·27 in controls, 0·31 in asymptomatic, 0·21 in mild-to-moderately affected and 0·19 in severely affected COVID-19 patients. Risk of severity increased with decreasing MAF: Asymptomatic: Odds ratio-0·69 (95% CI–0·52–0·93; p = 0·01); mild-to-moderate: Odds ratio-1·89 (95% CI–1·22–2.92;p = 0·004) and severe: Odds ratio-1·79 (95% CI–1·11–2.88;p = 0·01). No confounding effect of diabetes and hypertension were observed on the risk of developing severe COVID-19 disease with respect to genotype. MDS revealed decreased stability of TMPRSS2 with 160 M variant. Spike glycoprotein cleavage by TMPRSS2 reduced ~2·4-fold in cells expressing 160 M variant. Conclusion We demonstrate association of TMPRSS2 variant rs12329760 with decreased disease severity in COVID-19 patients from India.
Gastrointestinal Endoscopy, 2018
recorded. Data were compared to baseline by Wilcoxon test. Results: TIF was performed in 50 pts a... more recorded. Data were compared to baseline by Wilcoxon test. Results: TIF was performed in 50 pts and successful in 49 pts (one case of intra-procedural pneumothorax). Only one delayed pneumothorax occurred. Four pts underwent surgical fundoplication for TIF inefficacy during the first year after TIF, while three pts underwent surgery between 3 and 5 years after TIF. All pts completed the 3 and 5 years clinical follow-up (45 and 41 pts respectively), while twenty-eight and fourteen pts completed the 7 and 10 years clinical follow-up. Over the 10-year follow-up the mean GERD-HRQL score was significantly reduced compared with the pre-TIF score (46AE19). The reduction was significant at 2 years (18AE13, p<0.01) and scores were maintained similar at 3 years (19AE14, p<0.01); between 3 and 5 years there was a further slight reduction of mean scores (19AE14, p<0.01 ; 10AE7, p<0.01), while at 7 and 10 years the score did not substantially change (10AE8, p<0.01 ; 10AE6, p<0.01), compared with 5-year data. Overall, GERD-HRQL score appeared substantially unchanged between 2 and 10 years after TIF procedure. The percentages of pts who stopped or halved PPI therapy 3, 5, 7 and 10 years after TIF were 84.4%, 73.5%, 83.3%, and 91.7%, respectively; this rate remained substantially stable and similar to that at 2 years (87.8%). Conclusions: TIF using Esophyx 2.0 device achieved a significant GERD-HRQL score improvement compared to baseline and lasting elimination of daily dependence on PPI in about 73-91% of pts for up to ten years, and thus seems an effective therapeutic option for selected symptomatic GERD pts, with a hiatal hernia not longer than 2 cm, who refuse lifelong medical therapy or surgery or are intolerant to PPI.
Gastrointestinal Endoscopy, 2017
Background: Both pancreatic stent (PS) placement and rectal administration of nonsteroidal anti-i... more Background: Both pancreatic stent (PS) placement and rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) were proved to be effective in preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). Although the efficacies of these treatments have been compared by a post hoc analysis 1) and network meta-analysis 2) , they have not been compared directly. The aim of this study
Gastrointestinal Endoscopy, 2019
GERD-X, an endoscopic full thickness plication device, is a novel minimally invasive endoscopic d... more GERD-X, an endoscopic full thickness plication device, is a novel minimally invasive endoscopic device for the treatment of patients with chronic GERD. With this endoscopic device, transmural sutures are applied at the gastroesophageal junction (GEJ), leading to the reconstruction of the gastric cardia and thereby accentuating the valvular mechanism to prevent reflux. In this RCT, we evaluated the (1) technical success (2) safety and efficacy of GERD-X over the short term period for management of patients with chronic GERD well controlled on PPI therapy. Methods: Patients with symptomatic GERD on PPI therapy for at least 6 months and documented pathological reflux on 24-h pH impedance monitoring were randomized to GERD-X versus a sham procedure in a ratio of 1:1. Technical success was defined as the successful application of at least 2 transmural sutures at the GEJ. Clinical success was defined as an improvement in the GERD-HRQL total score by >50% at 3 months. Complications in both groups were noted. At 3 months, outcomes were compared between the treatment and sham group using Mann Whitney U test. Results: 67 patients with prospectively enrolled in this RCT. Baseline characteristics of GERD-X (nZ37) and Sham (nZ30) groups were comparable. Technical success was achieved in all patients (100%) in the GERD-X group. At 3 months, the proportion of patients achieving clinical success i.e. >50% improvement in GERD-HRQL total score was significantly higher in the GERD-X group compared to the sham group [58% vs. 30%; pZ0.021]. In addition, there was a significant reduction in GERD-HRQL heartburn score at 3 months from baseline in GERD-X [14(10-21) vs. 5 (0-12); pZ<0.001] compared to sham [8 (0-50) vs. 5.2 (0-11); pZ0.931]. Mild chest pain and self-limiting pleuritis were reported in 2 patients after GERD-X. At 3 months, 40% of patients in the treatment group vs 27% of patients in the sham group were off PPI therapy. Conclusion: Results from this prospective randomized controlled trial show that Endoscopic full thickness plication is a safe and efficacious technique. There is a significant improvement in the GERD symptoms and health related quality of life over short term follow up. Long term results are awaited.
Case Reports in Clinical Medicine, 2017
A 55-year-old man presented with intermittent colicky abdominal pain for few months. The severity... more A 55-year-old man presented with intermittent colicky abdominal pain for few months. The severity of pain increased over last 3–4 weeks. Physical examination revealed lump over right iliac and lumbar region. Colonoscopy showed a large polyp occupying almost entire lumen of colon extending from terminal ileum to hepatic flexure of colon. Contrast enhanced computed tomography (CT) of abdomen confirmed the findings of colonoscopy and revealed a large polyp arising from ileum and occupying the entire lumen of ascending colon resulting in ileocolic intussusception. As endoscopic resection was rendered unsafe due to limited working space, the patient underwent surgery and giant polyp was removed. Histopathology and immunohistochemistry of the polyp showed features of Inflammatory Fibroid Polyp (IFP). IFPs are rare benign tumors with varied presentations and should be considered in such cases where gigantic polyps are encountered during imaging (colonoscopy or radiological imaging). Smalle...
American Journal of Gastroenterology
Pediatric Obesity
SummaryObesity in paediatrics has become one of the most serious public health concerns worldwide... more SummaryObesity in paediatrics has become one of the most serious public health concerns worldwide. Paediatric obesity leads to increased adult obesity and is associated with several comorbidities, both physical and psychological. Within gastroenterology, non‐alcoholic fatty liver disease (NAFLD) is now the most common cause of paediatric liver disease and the most common cause of liver transplantation in young adults. Treatment for NAFLD largely focuses on treatment of obesity with weight loss strategies. Unfortunately, the traditional method of weight loss using multicomponent lifestyle modification (dietary changes, increased exercise and behavioural modification) has often led to disappointing results. In adult patients with obesity, treatment strategies have evolved to include bariatric surgery and, more recently, bariatric endoscopy. In paediatrics, the obesity and NAFLD epidemics will likely require this variety of treatment to address children in a personalized manner. Here, ...
Gastrointestinal Endoscopy
Endoscopy International Open
Background and study aims Percutaneous liver biopsy is traditionally done on the right lobe of th... more Background and study aims Percutaneous liver biopsy is traditionally done on the right lobe of the liver. Endoscopic ultrasound-guided liver biopsy (EUS-LB) can be performed on either the left or right lobe or as a combined bi-lobar biopsy. Earlier studies did not compare the benefit of bi-lobar biopsies to single-lobe biopsy for reaching a tissue diagnosis. The current study compared the degree of agreement of pathological diagnosis between the left lobe of the liver compared to right-lobe and with bi-lobar biopsy. Patients and methods Fifty patients fulfilling the inclusion criteria were enrolled in the study. EUS-LB with a 22G core needle was performed separately on both the liver lobes. Three pathologists, who were blinded to the site of biopsy independently reviewed the liver biopsies. Sample adequacy, safety, and concordance of pathological diagnosis between left- and right-lobe biopsy of the liver were analyzed. Results The pathological diagnosis was made in 96 % of patients....
Journal of Crohn's and Colitis
Background and Aims Lack of clinical validation and inter-observer variability are two limitation... more Background and Aims Lack of clinical validation and inter-observer variability are two limitations of endoscopic assessment and scoring of disease severity in patients with ulcerative colitis [UC]. We developed a deep learning [DL] model to improve, accelerate and automate UC detection, and predict the Mayo Endoscopic Subscore [MES] and the Ulcerative Colitis Endoscopic Index of Severity [UCEIS]. Methods A total of 134 prospective videos [1550 030 frames] were collected and those with poor quality were excluded. The frames were labelled by experts based on MES and UCEIS scores. The scored frames were used to create a preprocessing pipeline and train multiple convolutional neural networks [CNNs] with proprietary algorithms in order to filter, detect and assess all frames. These frames served as the input for the DL model, with the output being continuous scores for MES and UCEIS [and its components]. A graphical user interface was developed to support both labelling video sections an...
Journal of Clinical and Experimental Hepatology
Gastrointestinal Endoscopy
Annals of Gastroenterology, 2020
Background Acute calculous cholecystitis (ACC) is the most frequent complication of gallstones re... more Background Acute calculous cholecystitis (ACC) is the most frequent complication of gallstones requiring cholecystectomy. These patients may have coexisting choledocholithiasis. We aimed to evaluate the role of current guidelines for choledocholithiasis in patients with ACC. Methods In this retrospective study, we included all patients diagnosed with ACC between December 2018 and May 2019. These patients were substratified according to the guidelines of the American and European Societies of Gastrointestinal Endoscopy (ASGE and ESGE) as having high, intermediate, or low likelihood of choledocholithiasis, and the diagnostic performance was measured. Binomial logistic regression analysis was applied to ascertain independent risk factors for choledocholithiasis. Results A total of 173 patients with ACC, mean age (±standard deviation) 49.89±15.74 years and 60.1% male, were included. Sixty-three (36.4%) had confirmed choledocholithiasis. ASGE high likelihood criteria had sensitivity and specificity of 61.9% (95% confidence interval [CI] 48.8-73.9) and 83.4% (95%CI 75.4-90.0) for predicting choledocholithiasis. ESGE high likelihood criteria had sensitivity and specificity of 49.2% (95%CI 36.4-62.1) and 87.3% (95%CI 79.6-92.9). On logistic regression analysis, an alkaline phosphatase level above the upper limit of normal (P=0.003; odds ratio [OR] 4.26, 95%CI 1.66-10.96) and a dilated common bile duct on ultrasound (P=0.001; OR 9.97, 95%CI 4.65-21.36) were independent positive predictors for choledocholithiasis, while acute biliary pancreatitis was an independent negative predictor (P=0.030; OR 0.36, 95%CI 0.14-0.91). Conclusions The performance of the ASGE and ESGE guidelines' risk stratification criteria is inadequate in patients with ACC. We suggest the utilization of a separate predictive model for suspected choledocholithiasis in these patients.
Gastroenterology, 2018
Introduction: Chronic pancreatitis (CP) is characterized by pain, exocrine insufficiency and diab... more Introduction: Chronic pancreatitis (CP) is characterized by pain, exocrine insufficiency and diabetes. Studies evaluating the impact of endotherapy and surgery on diabetes in CP have yielded divergent results. In this study, we evaluate the risks of diabetes and effect of pancreatic ductal clearance on its development in patients with CP. Methods: A database was generated between 1 st Aug. 2011 to 31 st July 2012 wherein consecutive patients with CP who visited the Pancreas Clinic were enrolled and prospectively followed. Details pertaining to patient demography, disease onset, progression, morphology (imaging), and treatment received were recorded after verifying from the available documents. After recording relevant available data, the patients were subjected to 6-mthly follow-up, during which all data are being prospectively recorded. Follow-up of patients who could not visit the hospital physically was done via a structured telephone interview. Patients without complete data and those who were lost to follow-up were excluded from the study. In the current study, data until June 2017 are being reported. For categorical variables, Fischer's exact or the Chi square test was performed as appropriate; while Student's 't' or the Mann Whitney U test was conducted for continuous variables. Step forward binary logistic regression was performed to identify disease related factors that imparted independent risk of development of diabetes. The Kaplan-Meier survival analysis and Cox proportional hazards model were used to compare the diabetes free interval since onset of CP symptoms and to calculate the HR (95% confidence interval [CI]). A two-tailed 'p' value of <0.05 was considered statistically significant. Results: 644 patients were enrolled into the database, of which 137 were excluded in this study. 507 patients were analyzed; of which 312 (61.5%) had idiopathic CP. 283 (55.8%) patients underwent ductal clearance (ESWL with ERCP 232, drainage surgery 27 and ESWL followed by surgery 24), while 190 (37.5%) patients developed diabetes. The mean (SD) duration between onset of CP symptoms and ductal clearance was 3.4 (3.2)yrs. Alcohol intake & presence of pancreatic ductal calculi were independently associated with the development of diabetes (OR [95% CI] of 2.01 [1.16-3.47], p=0.03 and 2.04 [1.38-3.01], p<0.0001 respectively) (Table 1). Kaplan-Meier estimate for diabetes free patients was significantly higher in the patients who underwent ductal clearance in the idiopathic CP group (p=0.001 by Log rank test), with a Hazard ratio (HR [95% CI]) of 2.01 (1.3-3.0), p=0.002. This was not significantly different for patients with non-idiopathic (alcohol+/smoking) CP (Fig. 1). Discussion: Pancreatic ductal calculi increase the risk of diabetes in CP. Early ductal clearance of stones could delay the development of diabetes in patients with idiopathic CP.
Journal of Gastroenterology and Hepatology, 2020
Introduction: Even though ductal interventions in chronic pancreatitis (CP) is known to improve p... more Introduction: Even though ductal interventions in chronic pancreatitis (CP) is known to improve pain, its impact on diabetes is unclear. In this cohort study, we evaluated the impact of ductal interventions on diabetes in these patients. Methods: Consecutive patients with CP visiting the Pancreas Clinic between 1 st August 2011 and 31 st July 2012 were enrolled and followed till December 2018. Detailed clinical, laboratory, imaging, and treatment data were recorded at enrollment and follow-up. Patients were followed 6-monthly through hospital visit and/or telephonic interview. Risk factors for diabetes were evaluated using logistic regression. The impact of ductal interventions on diabetes was evaluated using Kaplan Meier survival analyses and Cox Proportional Hazard. Results: 644 patients were enrolled of which 137 were excluded. 326 (64.3%) patients had idiopathic CP. 283 (55.8%) patients underwent ductal intervention. The cumulative incidence of diabetes was 57.9%. Median duration between symptom onset and ductal intervention were similar irrespective of diabetes [2.6 (0.6-6.0) vs 3.0 (1.0-5.5) yrs; p=0.69]. Alcohol intake and pancreatic ductal calculi were independent risk factors for diabetes (OR [95% CI] of 2.05 (1.18-3.55), p=0.01 and 2.05 (1.28-3.28), p=0.003 respectively). Kaplan Meier analyses revealed that diabetes free interval-was significantly longer in patients undergoing ductal interventions, predominantly in those with idiopathic CP with obstructive ductal calculi [HR (95%CI) 0.39 (0.28-0.55); p< 0.0001]. There were no differences in glycemic status in patients with non-idiopathic CP and those with preexisting diabetes. Discussion: Early ductal intervention could delay development of diabetes in patients with idiopathic CP with obstructive ductal calculi.
Gastrointestinal Endoscopy, 2020
Background: Therapeutic endoscopy plays a major role in the management of upper gastrointestinal ... more Background: Therapeutic endoscopy plays a major role in the management of upper gastrointestinal (UGI) post-surgical leaks, with multiple endoscopic techniques being available. However, no definite consensus exists on most appropriate therapeutic approach, as well as data is scarce regarding clinical success and safety. Aim: Evaluate endoscopic therapy results on the management of UGI post-surgical leaks regarding number and order of therapies performed, as well as safety, clinical success and long-term follow-up. Methods: Multicenter, international, retrospective study from 10 centers of consecutive patients who underwent endoscopic treatment of UGI post-surgical leaks. Results: 206 patients (50.5% male) were included, with a median age of 54 years (range 18-81). Previous surgery most often performed was sleeve gastrectomy (38.8%), followed by total gastrectomy (21.8%), Ivor-Lewis esophagectomy (15.0%) and gastric bypass (10.7%). Median time from surgery to beginning of endoscopic treatment was 16 days (range 0-2405). Global leak closure was observed in 187 patients (90.8%). Endoscopic closure was achieved in 165 patients (80.1%), after a median follow-up of 52 days (range 0-693). In 8 patients (3.9%) in whom leak closure was not achieved, a stent was left-in-place, without evidence of leak persistence during follow-up. Fourteen patients (6.8%) underwent surgery after endoscopic treatment failure, and leak closure was possible in 12 of them. One patient underwent radiological leak closure and one patient had spontaneous closure. Most commonly performed first-line endoscopic treatment was SEMS placement [average ranking (AR) 5.5], followed by over-the-scope clips (AR 5.3), endoscopic vacuum therapy (AR 5.1) and endoscopic internal drainage (AR 5.1). Multimodal therapeutic endoscopy was necessary in 40.8% of patients (nZ84; median number of different therapies: 2; range 1-6). The median total number of endoscopic procedures performed per patient were 3 (range 1-26). The success-rate of leak closure was 41.3% (85/206) with the first endoscopic technique, 44.3% (47/106) with the second technique, 35.6% (16/45) with the third technique, 59.1% (13/22) with the fourth technique, 80.0% (4/5) with the fifth technique. In one patient that underwent 6 different endoscopic techniques, endoscopic closure was not possible. The global rate of at least one endoscopic therapy-related adverse event (AE) was 39.3% (nZ81; one AE: nZ60; two AEs: nZ21), being severe in 10 patients (4.9%). Leak-related mortality rate was 11.6% (nZ24). Median follow-up since beginning of endoscopic therapy was 303 days (range 2-2801). Conclusion: Multimodal therapeutic endoscopy, despite time-consuming, allows leak closure in a significant proportion of patients, with a low rate of associated severe-AEs.
Gastrointestinal Endoscopy, 2022
With great interest, we read the study comparing preoperative, intraoperative, and follow-up func... more With great interest, we read the study comparing preoperative, intraoperative, and follow-up functional luminal imaging probe measurements in patients undergoing myotomy for achalasia cardia. 1 In that study, the esophagogastric junction distensibility index (EGJ-DI) was measured at 4 time points (preoperative, induction, postmyotomy, and follow-up) in patients undergoing peroral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM). The authors concluded that the preoperative and induction mean EGJ-DIs were similar, with a significant increase in DI after POEM. At the 12month follow-up visit, there was a decrease in DI as compared with the postmyotomy value, although it was higher than preoperative values. These values at 4 different time points were compared by use of a paired t test. However, the paired t test should be used to compare continuous variables at 2 different time points. 2 For comparison of more than 2 mean scores at different time points, repeated-measures analysis of variance (ANOVA) should be performed. 3 The application of a paired t test to such data multiple times increases type 1 errors in multiples of 5% for each comparison. A Greenhouse-Geisser correction should be used if sphericity assumption is violated. Pairwise comparisons should be analyzed with a Bonferroni post hoc test, to find out which 2 specific means are statistically different. If overall ANOVA is not statistically significant, then a pairwise comparison should not be performed. The authors should use repeated-measures ANOVA for analysis of mean EGJ-DI at 4 different time points.
Meta Gene, 2021
Background Mortality due to COVID-19 caused by SARS-CoV-2 infection varies among populations. Fun... more Background Mortality due to COVID-19 caused by SARS-CoV-2 infection varies among populations. Functional relevance of genetic variations in Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2), two crucial host factors for viral entry, might explain some of this variation. Methods In this comparative study in Indian subjects, we recruited 510 COVID-19 patients and retrieved DNA from 520 controls from a repository. Associations between variants in ACE2 and TMPRSS2 with disease severity were identified by whole exome sequencing (WES, n = 20) and targeted genotyping (n = 1010). Molecular dynamic simulations (MDS) were performed to explore functional relevance of the variants. Cleavage of spike glycoprotein by wild and variant TMPRSS2 was determined in HEK293T cells. Potential effects of confounders on the association between genotype and disease severity were tested (Mantel-Haenszel test). Results WES identified deleterious variant in TMPRSS2 (rs12329760, G > A, p. V160M). The minor allele frequency (MAF) was 0·27 in controls, 0·31 in asymptomatic, 0·21 in mild-to-moderately affected and 0·19 in severely affected COVID-19 patients. Risk of severity increased with decreasing MAF: Asymptomatic: Odds ratio-0·69 (95% CI–0·52–0·93; p = 0·01); mild-to-moderate: Odds ratio-1·89 (95% CI–1·22–2.92;p = 0·004) and severe: Odds ratio-1·79 (95% CI–1·11–2.88;p = 0·01). No confounding effect of diabetes and hypertension were observed on the risk of developing severe COVID-19 disease with respect to genotype. MDS revealed decreased stability of TMPRSS2 with 160 M variant. Spike glycoprotein cleavage by TMPRSS2 reduced ~2·4-fold in cells expressing 160 M variant. Conclusion We demonstrate association of TMPRSS2 variant rs12329760 with decreased disease severity in COVID-19 patients from India.
Gastrointestinal Endoscopy, 2018
recorded. Data were compared to baseline by Wilcoxon test. Results: TIF was performed in 50 pts a... more recorded. Data were compared to baseline by Wilcoxon test. Results: TIF was performed in 50 pts and successful in 49 pts (one case of intra-procedural pneumothorax). Only one delayed pneumothorax occurred. Four pts underwent surgical fundoplication for TIF inefficacy during the first year after TIF, while three pts underwent surgery between 3 and 5 years after TIF. All pts completed the 3 and 5 years clinical follow-up (45 and 41 pts respectively), while twenty-eight and fourteen pts completed the 7 and 10 years clinical follow-up. Over the 10-year follow-up the mean GERD-HRQL score was significantly reduced compared with the pre-TIF score (46AE19). The reduction was significant at 2 years (18AE13, p<0.01) and scores were maintained similar at 3 years (19AE14, p<0.01); between 3 and 5 years there was a further slight reduction of mean scores (19AE14, p<0.01 ; 10AE7, p<0.01), while at 7 and 10 years the score did not substantially change (10AE8, p<0.01 ; 10AE6, p<0.01), compared with 5-year data. Overall, GERD-HRQL score appeared substantially unchanged between 2 and 10 years after TIF procedure. The percentages of pts who stopped or halved PPI therapy 3, 5, 7 and 10 years after TIF were 84.4%, 73.5%, 83.3%, and 91.7%, respectively; this rate remained substantially stable and similar to that at 2 years (87.8%). Conclusions: TIF using Esophyx 2.0 device achieved a significant GERD-HRQL score improvement compared to baseline and lasting elimination of daily dependence on PPI in about 73-91% of pts for up to ten years, and thus seems an effective therapeutic option for selected symptomatic GERD pts, with a hiatal hernia not longer than 2 cm, who refuse lifelong medical therapy or surgery or are intolerant to PPI.
Gastrointestinal Endoscopy, 2017
Background: Both pancreatic stent (PS) placement and rectal administration of nonsteroidal anti-i... more Background: Both pancreatic stent (PS) placement and rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) were proved to be effective in preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). Although the efficacies of these treatments have been compared by a post hoc analysis 1) and network meta-analysis 2) , they have not been compared directly. The aim of this study
Gastrointestinal Endoscopy, 2019
GERD-X, an endoscopic full thickness plication device, is a novel minimally invasive endoscopic d... more GERD-X, an endoscopic full thickness plication device, is a novel minimally invasive endoscopic device for the treatment of patients with chronic GERD. With this endoscopic device, transmural sutures are applied at the gastroesophageal junction (GEJ), leading to the reconstruction of the gastric cardia and thereby accentuating the valvular mechanism to prevent reflux. In this RCT, we evaluated the (1) technical success (2) safety and efficacy of GERD-X over the short term period for management of patients with chronic GERD well controlled on PPI therapy. Methods: Patients with symptomatic GERD on PPI therapy for at least 6 months and documented pathological reflux on 24-h pH impedance monitoring were randomized to GERD-X versus a sham procedure in a ratio of 1:1. Technical success was defined as the successful application of at least 2 transmural sutures at the GEJ. Clinical success was defined as an improvement in the GERD-HRQL total score by >50% at 3 months. Complications in both groups were noted. At 3 months, outcomes were compared between the treatment and sham group using Mann Whitney U test. Results: 67 patients with prospectively enrolled in this RCT. Baseline characteristics of GERD-X (nZ37) and Sham (nZ30) groups were comparable. Technical success was achieved in all patients (100%) in the GERD-X group. At 3 months, the proportion of patients achieving clinical success i.e. >50% improvement in GERD-HRQL total score was significantly higher in the GERD-X group compared to the sham group [58% vs. 30%; pZ0.021]. In addition, there was a significant reduction in GERD-HRQL heartburn score at 3 months from baseline in GERD-X [14(10-21) vs. 5 (0-12); pZ<0.001] compared to sham [8 (0-50) vs. 5.2 (0-11); pZ0.931]. Mild chest pain and self-limiting pleuritis were reported in 2 patients after GERD-X. At 3 months, 40% of patients in the treatment group vs 27% of patients in the sham group were off PPI therapy. Conclusion: Results from this prospective randomized controlled trial show that Endoscopic full thickness plication is a safe and efficacious technique. There is a significant improvement in the GERD symptoms and health related quality of life over short term follow up. Long term results are awaited.
Case Reports in Clinical Medicine, 2017
A 55-year-old man presented with intermittent colicky abdominal pain for few months. The severity... more A 55-year-old man presented with intermittent colicky abdominal pain for few months. The severity of pain increased over last 3–4 weeks. Physical examination revealed lump over right iliac and lumbar region. Colonoscopy showed a large polyp occupying almost entire lumen of colon extending from terminal ileum to hepatic flexure of colon. Contrast enhanced computed tomography (CT) of abdomen confirmed the findings of colonoscopy and revealed a large polyp arising from ileum and occupying the entire lumen of ascending colon resulting in ileocolic intussusception. As endoscopic resection was rendered unsafe due to limited working space, the patient underwent surgery and giant polyp was removed. Histopathology and immunohistochemistry of the polyp showed features of Inflammatory Fibroid Polyp (IFP). IFPs are rare benign tumors with varied presentations and should be considered in such cases where gigantic polyps are encountered during imaging (colonoscopy or radiological imaging). Smalle...