Fatty acid ethyl ester (FAEE) associated acute pancreatitis: An ex-vivo study using human pancreatic acini.

BACKGROUND & AIM: Fatty acid ethyl esters (FAEEs), are produced by non-oxidative alcohol metabolism and can cause acinar cell damage and subsequent acute pancreatitis in rodent models. Even though experimental studies have elucidated the FAEE mediated early intra-acinar events, these mechanisms have not been well studied in humans. In the present study, we evaluate the early intra-acinar events and inflammatory response in human pancreatic acinar tissues and cells in an ex-vivo model. METHODS: Experiments were conducted using normal human pancreatic tissues exposed to FAEE. Subcellular fractionation was performed on tissue homogenates and trypsin and cathepsin B activities were estimated in these fractions. Acinar cell injury was evaluated by histology and immunohistochemistry. Cytokine release from exposed acinar cells was evaluated by performing Immuno-fluorescence. Serum was collected from patients with AP within the first 72 h of symptom onset for cytokine estimation using FACS. RESULTS: We observed significant trypsin activation and acinar cell injury in FAEE treated tissue. Cathepsin B was redistributed from lysosomal to zymogen compartment at 30 min of FAEE exposure. IHC results indicated the presence of apoptosis in pancreatic tissue at 1 & 2hrs of FAEE exposure. We also observed a time dependent increase in secretion of cytokines IL-6, IL-8, TNF-α from FAEE treated acinar tissue. There was also a significant elevation in plasma cytokines in patents with alcohol associated AP within 72 h of symptom onset. CONCLUSION: Our data suggest that alcohol metabolites can cause acute acinar cell damage and subsequent cytokine release which could eventually culminant in SIRS.

ESWL for large pancreatic calculi: Report of over 5000 patients.

INTRODUCTION: The primary aim of this study was to evaluate efficacy, safety and short-term pain relief after ESWL for large pancreatic calculi in over 5000 patients at a single center. METHODS: This is a retrospective analysis of prospectively collected data. Patients with painful calculi >5 mm, located in the head, neck and body region in the MPD, who were not amenable for extraction by the standard procedure of endoscopic pancreatic sphincterotomy were subjected to ESWL using a third generation dual focus lithotripter. Patients were followed up at 6 months for outcome evaluation. RESULTS: A total of 5124 patients (66% males) were subjected to ESWL. Majority of stones (79.2%) were radiopaque. Single calculi were seen in 3851 (75.1%).The majority of stones were located in head region of MPD in 2824 (55.1%) patients. 4386 (85.5%) patients required 3 or less sessions for fragmentation and complete stone clearance was achieved in 3722 (72.6%). EPS was performed in 5022 (98%) while PD stenting was required in 3536 (69%) patients. Of the 4280 patients followed up for 6 months, 3529 (82.6%) patients were pain free. Another 512 (11.9%) patients had significant reduction in VAS score. In 229 (5.3%) there was no decrease in pain intensity. Minor and self-limiting complications were reported in 1153 (22.5%). DISCUSSION: Our study confirms the safety and efficacy and short-term pain relief of ESWL for large calculi in the MPD. In properly selected patients, this should be offered as the first line of therapy for all large MPD calculi not amenable to the standard techniques of stone extraction.

Management of achalasia cardia: Expert consensus statements.

Achalasia cardia (AC) is a frequently encountered motility disorder of the esophagus resulting from an irreversible degeneration of neurons. Treatment modalities are palliative in nature, and there is no curative treatment available for AC as of now. Significant advancements have been made in the management of AC over last decade. The introduction of high resolution manometry and per-oral endoscopic myotomy (POEM) has strengthened the diagnostic and therapeutic armamentarium of AC. High resolution manometry allows for the characterization of the type of achalasia, which in turn has important therapeutic implications. The endoscopic management of AC has been reinforced with the introduction of POEM that has been found to be highly effective and safe in palliating the symptoms in short-term to mid-term follow-up studies. POEM is less invasive than Heller's myotomy and provides the endoscopist with the opportunity of adjusting the length and orientation of esophageal myotomy according to the type of AC. The management of achalasia needs to be tailored for each patient, and the role of pneumatic balloon dilatation, POEM, or Heller's myotomy needs to be revisited. In this review, we discuss the important aspects of diagnosis as well as management of AC. The statements presented in the manuscript reflect the cumulative efforts of an expert consensus group.

Endoscopic drainage of pancreatic fluid collections: Long-term outcomes in children.

BACKGROUND AND AIM: Endoscopic drainage of pancreatic fluid collections (PFC) is the standard of care in adult patients. The literature is limited in children. In the present study, we aim to evaluate the safety and long-term efficacy of endoscopic ultrasound (EUS)-guided drainage of PFC in children. METHODS: Data of all children (<18 years) with PFC who underwent EUS-guided drainage with plastic stents were analyzed retrospectively for technical feasibility, clinical efficacy and adverse events (AE). RESULTS: Thirty children (boys 22, girls 8) with PFC underwent EUS drainage (January 2013 to June 2016). Mean age of children was 13.07 ± 3.41 years (5-17 years). Majority of children had idiopathic pancreatitis (23), followed by trauma-related (6) and gallstone-related pancreatitis (1). Of 30 PFC, 13 (43.3%) and 17 (56.7%) were classified as pseudocyst and walled-off necrosis, respectively. Median size of PFC was 95 mm (61-175). EUS drainage was successfully completed in 29 children (technical success 96.7%). Clinical success was achieved in 28/30 (93.3%) children. AE included perforation (2), major bleed (1), minor bleed (2), stent migration (4) and readmission as a result of hematemesis (1). Imaging revealed disconnected pancreatic duct in nine, ductal leak in two and stricture in one child. Cystogastric stents were left in situ in children with disconnected duct. At median follow up of 829 days (150-1230), two recurrences of PFC were noticed. CONCLUSIONS: EUS-guided drainage using plastic stents is safe and effective in children with PFC. Cystogastric plastic stents can be left safely long term. However, more studies with larger sample sizes are required.

NF-κB in acute pancreatitis: Mechanisms and therapeutic potential.

The incidence of acute pancreatitis (AP) is increasing globally and mortality could be high among patients with organ failure and infected necrosis. The predominant factors responsible for the morbidity and mortality of AP are systemic inflammatory response syndrome and multiorgan dysfunction. Even though preclinical studies have shown antisecretory agents (somatostatin), antioxidants (S-adenosyl methionine [SAM], selenium), protease inhibitors, platelet activating factor inhibitor (Lexipafant), and anti-inflammatory immunomodulators (eg. prostaglandin E, indomethacin) to benefit AP in terms of reducing the severity and/or mortality, most of these agents have shown heterogeneous results in clinical studies. Several years of experimental studies have implicated nuclear factor-kappa B (NF-κB) activation as an early and central event in the progression of inflammation in AP. In this manuscript, we review the literature on the role of NF-κB in the pathogenesis of AP, its early intraacinar activation, and how it results in progression of the disease. We also discuss why anti-protease, antisecretory, and anti-inflammatory agents are unlikely to be effective in clinical acute pancreatitis. NF-κB, being a central molecule that links the initial acinar injury to systemic inflammation and perpetuate the inflammation, we propose that more studies be focussed towards targeted inhibition of NF-κB activity. Direct NF-κB inhibition strategies have already been attempted in patients with various cancers. So far, peroxisome proliferator activator receptor gamma (PPAR-γ) ligand, pyrrolidine dithiocarbamate (PDTC), proteasome inhibitor and calpain I inhibitor have been shown to have direct inhibitory effects on NF-κB activation in experimental AP.

Ameliorating effect of antioxidants and pregabalin combination in pain recurrence after ductal clearance in chronic pancreatitis: Results of a randomized, double blind, placebo-controlled trial.

BACKGROUND AND AIM: The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis. METHODS: In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2 months followed by open-label antioxidants for the next 4 months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows: complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated. RESULTS: We randomized 42 and 45 patients (mean age 29.3 years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2 months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P = 0.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P = 0.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P = 0.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P = 0.01). Needed-to-treat was 4.8. Pain reduction persisted at 6 months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P = 0.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol. CONCLUSION: Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic naïve patients with chronic calcific pancreatitis.

Peroral endoscopic myotomy for achalasia cardia: Treatment analysis and follow up of over 200 consecutive patients at a single center.

BACKGROUND AND AIM: Peroral endoscopic myotomy (POEM) is a recently introduced technique for the treatment of achalasia cardia (AC). Data regarding safety and efficacy are still emerging. We report our experience of POEM emphasizing its safety, efficacy and follow-up data. METHODS: Patients with AC (220; mean age 39 years, range 9-74 years) underwent POEM from January 2013 to August 2014 for AC. Retrospective analysis of prospectively collected data was done. POEM was carried out by the standard technique of mucosal incision, submucosal tunneling, and myotomy of the esophageal and gastric muscle bundles followed by closure of the mucosal incision by hemoclips. Eckardt score, high-resolution manometry (HRM) and timed barium esophagogram (TBE) were used to evaluate the results. Post-procedure patients were followed up. RESULTS: Technical success rate of POEM was 96%. At 1 year, clinical success rate was 92%. Mean Eckardt score was 7.2 ± 1.55 prior to POEM and 1.18 ± 0.74 after POEM (P = 0.001). There was significant improvement of esophageal emptying on TBE (38.4 ± 14.0 % vs 71.5 ± 16.1 % (P = 0.001). Pre-procedure and post-procedure mean lower esophageal sphincter pressure was 37.5 ± 14.5 mmHg and 15.2 ± 6.3 mmHg, respectively. (P = 0.001) Erosive esophagitis was seen in 16% of patients who underwent POEM. There were no major adverse events. CONCLUSIONS: Study demonstrates excellent safety profile of POEM with significant relief of symptoms, reduced pressure at HRM and improved emptying at TBE. Further prospective studies are required to compare with other treatment modalities.

Successful management of benign biliary strictures with fully covered self-expanding metal stents.

BACKGROUND & AIMS: Fully covered self-expanding metal stents (FCSEMS) are gaining acceptance for the treatment of benign biliary strictures. We performed a large prospective multinational study to study the ability to remove these stents after extended indwell and the frequency and durability of stricture resolution. METHODS: In a nonrandomized study at 13 centers in 11 countries, 187 patients with benign biliary strictures received FCSEMS. Removal was scheduled at 10-12 months for patients with chronic pancreatitis or cholecystectomy and at 4-6 months for patients who received liver transplants. The primary outcome measure was removal success, defined as either scheduled endoscopic removal of the stent with no removal-related serious adverse events or spontaneous stent passage without the need for immediate restenting. RESULTS: Endoscopic removal of FCSEMS was not performed for 10 patients because of death (from unrelated causes), withdrawal of consent, or switch to palliative treatment. For the remaining 177 patients, removal success was accomplished in 74.6% (95% confidence interval [CI], 67.5%-80.8%). Removal success was more frequent in the chronic pancreatitis group (80.5%) than in the liver transplantation (63.4%) or cholecystectomy (61.1%) groups (P = .017). FCSEMS were removed by endoscopy from all patients in whom this procedure was attempted. Stricture resolution without restenting upon FCSEMS removal occurred in 76.3% of patients (95% CI, 69.3%-82.3%). The rate of resolution was lower in patients with FCSEMS migration (odds ratio, 0.22; 95% CI, 0.11-0.46). Over a median follow-up period of 20.3 months (interquartile range, 12.9-24.3 mo), the rate of stricture recurrence was 14.8% (95% CI, 8.2%-20.9%). Stent- or removal-related serious adverse events, most often cholangitis, occurred in 27.3% of patients. There was no stent- or removal-related mortality. CONCLUSIONS: In a large prospective multinational study, removal success of FCSEMS after extended indwell and stricture resolution were achieved for approximately 75% of patients. ClincialTrials.gov number, NCT01014390.

Efficacy of peroral endoscopic myotomy (POEM) in the treatment of achalasia: a systematic review and meta-analysis.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an evolving therapeutic modality for achalasia. We aim to determine efficacy of POEM for the treatment of achalasia and compare it with laparoscopic Heller's myotomy (LHM). MATERIALS AND METHODS: Systematic review and meta-analyses was conducted on 19 studies using POEM for achalasia. Pubmed, Medline, Cochrane, and Ovid databases, were searched using the terms 'achalasia', 'POEM', 'peroral endoscopic myotomy', 'per oral endoscopic myotomy', and 'per-oral endoscopic myotomy'. Reduction in Eckhart's score and lower esophageal sphincter (LES) pressure were the main outcome measures. RESULTS: A total of 1,045 patients underwent POEM in 29 studies. Ninety patients undergoing POEM was compared with 160 undergoing LHM in five studies. Nineteen and 14 studies, respectively, evaluated for Eckhart's score and LES pressure. There was significant reduction in Eckhart's score and LES pressure with effect sizes of -7.95 (p < 0.0001) and -7.28 (p < 0.0001), respectively. There was significant heterogeneity among the studies [(Q = 83.06; I (2) = 78.33 %; p < 0.0001) for Eckhart's score and (Q = 61.44; I (2) = 75.68 %; p < 0.0001) for LES pressure]. There were no differences between POEM and LHM in reduction in Eckhart's score, post-operative pain scores and analgesic requirements, length of hospital stay, adverse events, and symptomatic gastroesophageal reflux/reflux esophagitis. Operative time was significantly lower for POEM. CONCLUSIONS: POEM is effective for achalasia and has similar outcomes as LHM. Multicenter randomized trials need to be conducted to further compare the efficacy and safety of POEM between treatment naïve achalasia patients and those who failed treatment.

Treatment of pancreatic cystic neoplasm: surgery or conservative?

Pancreatic cystic neoplasms (PCNs) are a heterogeneous group of tumors with distinct biological features. These neoplasms are now being recognized more frequently owing to advances in cross-sectional imaging and increasing awareness. Guidelines for treatment of the common and clinically important PCNs frequently have been revised in view of the continuing controversies and evolving clinical data. This review summarizes the management approaches of the common and clinically important PCNs based on current evidence and guidelines.

Endoscopic therapy for chronic pancreatitis.

PURPOSE OF REVIEW: To summarize recent data on techniques, efficacy and complications of endoscopic management of chronic pancreatitis. RECENT FINDINGS: Extracorporeal shock wave lithotripsy with or without endoscopic retrograde cholangiopancreatography is the first-line treatment for large painful obstructive pancreatic duct calculi. Use of preextracorporeal shock wave lithotripsy secretin could result in better stone clearance. The first-line treatment for dominant pancreatic duct strictures is placement of a single 10-Fr polyethylene stent with planned exchanges every 3 months until 1 year. Other endoscopic approaches that have shown good efficacy include placement of simultaneous multiple plastic stents and fully covered self-expanding metallic stents. Endoscopic options to treat chronic pancreatitis-associated benign biliary strictures include single and simultaneous multiple plastic stenting and fully covered self-expanding metallic stents. The European Society of Gastrointestinal Endoscopy recommends multiple plastic stenting for such strictures, although fully covered self-expanding metallic stents should be currently used under research settings. Endoscopic ultrasonography-guided cholangiopancreatography and pancreatobiliary drainage is an evolving option for chronic pancreatitis-related ductal obstruction after failed endoscopic retrograde cholangiopancreatography. Recent data have supported the safety and efficacy of endotherapy for chronic pancreatitis in children. SUMMARY: Endotherapy is the first line of management in chronic pancreatitis with symptomatic pancreatobiliary ductal obstruction. Further studies are required in certain key areas such as use of fully covered self-expanding metallic stents for pancreatic ductal and biliary strictures and endoscopic ultrasonography-guided pancreatobiliary drainage after failed endoscopic retrograde cholangiopancreatography.

Clinical utility of the revised Atlanta classification of acute pancreatitis in a prospective cohort: have all loose ends been tied?

BACKGROUND AND AIM: Revision of the Atlanta classification for acute pancreatitis (AP) was long awaited. The Revised Atlanta Classification has been recently proposed. In this study, we aim to prospectively evaluate and validate the clinical utility of the new definitions. PATIENT AND METHODS: 163 consecutive patients with AP were followed till death/6 mths after discharge. AP was categorized as mild (MAP) (no local complication[LC] and organ failure[OF]), moderate (MSAP)(transient OF and/or local/systemic complication but no persistent OF) and severe (SAP) AP (persistent OF). LC included acute peripancreatic fluid collections, pseudocyst, acute necrotic collection, walled-off necrosis, gastric outlet dysfunction, splenic/portal vein thrombosis, and colonic necrosis. Baseline characteristics (age/gender/hematocrit/BUN/SIRS/BISAP) and outcomes (total hospital stay/need for ICU care/ICU days/primary infected (peri)pancreatic necrosis[IN]/in-hospital death) were compared. RESULTS: 43 (26.4%) patients had ANP, 87 (53.4%) patients had MAP, 58 (35.6%) MSAP and 18 (11.04%) SAP. Among the baseline characteristics, BISAP score was significantly higher in MSAP compared to MAP [1.6 (1.5-2.01) vs 1.2 (1.9-2.4); p = 0.002]; and BUN was significantly higher in SAP compared to MSAP[64.9 (50.7-79.1) vs 24.9 (20.7-29.1); p < 0.0001]. All outcomes except mortality were significantly higher in MSAP compared to MAP. Need for ICU care (83.3%vs43.1%; p = 0.01), total ICU days[7.9 (4.8-10.9) vs 3.5 (2.7-5.1); p = 0.04] and mortality (38.9%vs1.7%; p = 0.0002) was significantly more in SAP compared to MSAP. 8/18 (44.4%) patients had POF within seven days of disease onset (early OF). This was associated with 37.5% of total in-hospital mortality. Patients with MSAP who had primary IN (n = 10) had similar outcomes as SAP. CONCLUSIONS: This study prospectively validates the clinical utility of the Revised Atlanta definitions of AP. However, MSAP patients with primary infected necrosis may behave as SAP. Furthermore, patients with early severe acute pancreatitis (early OF) could represent a subgroup that needs to be dealt with separately in classification systems.

ERCP in the management of pancreatic diseases in children.

BACKGROUND: ERCP experience in pancreatic disorders in children is limited. OBJECTIVE: This study evaluated the utility and efficacy of ERCP in children with pancreatic diseases at a tertiary care referral center. PATIENTS AND SETTINGS: Consecutive patients 18 years of age and younger who underwent ERCP for pancreatic diseases from January 2010 to June 2011 were identified. Indications, findings, interventions, adverse events, and outcomes were recorded. RESULTS: A total of 221 ERCPs were performed in 172 children (102 boys, mean ± standard deviation age 13.8 ± 3.2 years, 157 therapeutic). A total of 143 children (83.1%) had chronic pancreatitis (CP), 19 (11%) had recurrent acute pancreatitis (RAP), and 10 (5.8%) had acute pancreatitis (AP). Indications included pain (153, 89.4%), pancreatic fistula (11, 6.3%), symptomatic pseudocyst (4, 2.3%), and jaundice (3, 1.7%). In chronic pancreatitis patients, findings included a dilated and irregular main pancreatic duct (92, 64.3%), pancreatic duct (PD) calculi (76, 53%), dominant PD stricture (23, 16%), PD leak (7, 4.9%), pancreas divisum (35, 24.5%), and common bile duct (CBD) stricture (3, 2%). Therapeutic procedures included major papilla sphincterotomy (93, 65%), minor papilla sphincterotomy (32, 22.3%), PD stenting (77, 53.8%), and CBD stenting (3, 2.2%). PD stones larger than 5 mm were retrieved endoscopically after 57 extracorporeal shock wave lithotripsy sessions in 50 patients (34.9%). In patients with RAP, 6 (31.5%) had complete and 1 partial pancreas divisum. All underwent minor papillotomy. In patients with AP, 4 (40%) had stenting for PD leak, 2 (20%) underwent CBD clearance for biliary pancreatitis, and 4 (40%) had transpapillary pseudocyst drainage. During 13 ± 4.7 months (range 6-22 months) of follow-up, improvement of symptoms was seen in 143 of 172 (83%) patients. Procedure-related adverse events were seen in 8 (4.7%) patients. LIMITATIONS: Retrospective study. CONCLUSION: ERCP is a safe therapeutic option for pancreatic disorders in children.

Different gastric mucosa and CagA status of patients in India and Japan infected with Helicobacter pylori.

BACKGROUND AND AIM: Despite similar incidence of Helicobacter pylori infection, the frequency of gastric cancer is sevenfold higher in Japan than in India. The objective of this work was to define differences in H. pylori-induced gastritis and to identify the bacterial virulence factors involved. MATERIALS AND METHODS: We prospectively enrolled 353 consecutive patients who underwent endoscopy and received three gastric biopsies in Tokyo, Japan, and Hyderabad, India. Immunohistochemistry against H. pylori and East Asian CagA and hematoxylin-eosin and Giemsa stain were used to examine gastric mucosal biopsy specimens. Histological scores were assessed in accordance with the updated Sydney System. Subjects with H. pylori infection were matched by age and sex to compare histopathology and bacterial virulence. RESULTS: Sixty patients infected with H. pylori were prospectively selected. Median histological scores for neutrophil and mononuclear cell infiltration and for atrophy were significantly higher in Japan than in India (neutrophils 4.0 vs 3.0, p < 0.01; mononuclear cells 5.0 vs 4.5, p = 0.03; atrophy 3.0 vs 2.0, p < 0.01, respectively). Scores for H. pylori density and intestinal metaplasia were also higher in Japan, albeit without statistical significance (H. pylori 5.0 vs 3.0, p = 0.08; intestinal metaplasia 0.0 vs 0.0, p = 0.08). Prevalence of East Asian CagA-positive H. pylori was significantly higher in Japan (73.3 vs 0.0 %, p < 0.01). CONCLUSION: The significantly higher prevalence of histologically severe gastritis and East Asian CagA in patients from Japan with H. pylori infection may be involved in the pathogenesis of gastric cancer.

Clinical evaluation of a prototype multi-bending peroral direct cholangioscope.

BACKGROUND: Although peroral direct cholangioscopy (PDCS) is emerging as an alternative to traditional mother-daughter cholangioscopy, it is associated with high failure rates. The aim of the present study was to evaluate the ability to insert and carry out interventions using a prototype multi-bending PDCS. PATIENTS AND METHODS: Prospective, observational clinical feasibility study was done in 41 patients with a variety of biliary diseases. A multi-bending PDCS prototype was inserted using a free-hand technique, a guidewire alone, or with a 5-Fr diameter anchoring balloon. Diagnostic and therapeutic procedures were carried out. RESULTS: The free-hand direct insertion technique failed in all attempted cases (n = 7). Of the remaining 34 cases, successful rate of PDCS insertion into the distal bile duct was achieved by passing the PDCS over a guidewire alone (n = 6) and/or with a guidewire plus anchoring balloon (n = 28) for an overall successrate of 88.2% (30/34). In 13 (92.9%) patients without an underlying biliary stricture, PDCS insertion proximal to the bifurcation was possible. In 25 cases, biliary interventions were attempted including biopsy (n = 13), stone removal (n = 6), stent removal (n = 1), and intraductal electrohydraulic lithotripsy (n = 2) and were successful in 22 (88%). Other than two patients with procedure-related cholangitis with a mild grade of severity, no complications were observed. CONCLUSIONS: Using a novel multi-bending prototype peroral direct cholangioscope, cholangioscopy had a high diagnostic and therapeutic success rate only when passed over a guidewire and anchoring balloon but not with the free-hand insertion technique. Comparative studies of direct cholangioscopy are warranted.

17-Beta-Hydroxysteroid Dehydrogenase 13 Loss of Function Does Not Confer Protection to Nonalcoholic Fatty Liver Disease in Indian Population.

Background: A splice variant in HSD17B13 gene is demonstrated to protect against nonalcoholic fatty liver disease (NAFLD), and mitigate the effect of Patatin-like phospholipase domain-containing 3 (PNPLA3-I148M). It is being explored as a putative drug target and in polygenic risk scores. Based on whole exome sequencing (WES) in our cohort of biopsy proven NAFLD and limited data on the variant in our ethnicity, we sought to explore its role. Methods: This is a cross-sectional study that recruited 1,020 individuals with ultrasound/biopsy-confirmed NAFLD and matched controls. Liver enzymes and lipid profiles were estimated (Beckman coulter LX750/DXH800); WES was performed in NAFLD patients and controls (Illumina; HiSeqX); HSD17B13-A-INS/I148M-PNPLA3 variants were genotyped (sequencing/qR T-PCR); HSD17B13 protein expression was estimated (immunohistochemistry); the Student's t-test/Mann-Whitney U/Chi-square test and odds ratio (95% confidence interval) were used. Results: There was no significant difference (Odds ratio = 0.76; 95% CI -0.57 to 1.03; P = 0.76) in the frequency of the rs72613567-A-INS between controls and patients (17.8% vs. 14.4%). No difference in the ALT (Alanine transaminase; 72.24 ± 65.13 vs. 73.70 ± 60.06; P = 0.51) and AST levels (Aspartate aminotransferase; 60.72 ± 55.59 vs. 61.63 ± 60.33; P = 0.91) between HSD17B13-wild and variant carriers were noted. Significantly elevated liver enzymes were seen in PNPLA3-148-variant/HSD17B13-wild compared with PNPLA3-148-variant/HSD17B13-variant (90.44 ± 59.0 vs. 112.32 ± 61.78; P = 0.02). No difference in steatosis (P = 0.51) between HSD17B13-wild and variant carriers was noted. No other variants in the intron-exon boundaries were identified. Although, protein expression differences were noted between wild and variant carriers, no difference in the extent of steatosis was seen. Conclusion: Our study reports lack of association of the splice variant with reduced risk of NAFLD, and mitigating the effect of PNPLA3 variant. Ethnicity-based validation must be carried out before including it in assessing protection against NAFLD.

Application of machine-learning model to optimize colonic adenoma detection in India.

AIMS: There is limited data on the prevalence and risk factors of colonic adenoma from the Indian sub-continent. We aimed at developing a machine-learning model to optimize colonic adenoma detection in a prospective cohort. METHODS: All consecutive adult patients undergoing diagnostic colonoscopy were enrolled between October 2020 and November 2022. Patients with a high risk of colonic adenoma were excluded. The predictive model was developed using the gradient-boosting machine (GBM)-learning method. The GBM model was optimized further by adjusting the learning rate and the number of trees and 10-fold cross-validation. RESULTS: Total 10,320 patients (mean age 45.18 ± 14.82 years; 69% men) were included in the study. In the overall population, 1152 (11.2%) patients had at least one adenoma. In patients with age > 50 years, hospital-based adenoma prevalence was 19.5% (808/4144). The area under the receiver operating curve (AUC) (SD) of the logistic regression model was 72.55% (4.91), while the AUCs for deep learning, decision tree, random forest and gradient-boosted tree model were 76.25% (4.22%), 65.95% (4.01%), 79.38% (4.91%) and 84.76% (2.86%), respectively. After model optimization and cross-validation, the AUC of the gradient-boosted tree model has increased to 92.2% (1.1%). CONCLUSIONS: Machine-learning models may predict colorectal adenoma more accurately than logistic regression. A machine-learning model may help optimize the use of colonoscopy to prevent colorectal cancers. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT04512729).

New endoscopic "scissors" to treat Zenker's diverticulum (with video).

BACKGROUND: Zenker's diverticulum (ZD) is a rare disorder but is associated with significant morbidity. Cricopharyngeal (CP) myotomy is the mainstay of treatment, and various flexible endoscopic techniques have been used for division of the septum. However, there is a constant need for improvement in accessories. OBJECTIVE: To evaluate the safety and effectiveness of a new electrocautery endoscopic scissor for CP myotomy in patients with symptomatic ZD. DESIGN: Observational human study. SETTING: Tertiary-care hospital. PATIENTS: This study involved 3 patients with symptomatic ZD. INTERVENTION: Flexible endoscopic CP myotomy was performed by using a novel scissors-type grasping device. CP myotomy involved 4 steps: (1) opening of the forceps, (2) grasping the muscle fiber, (3) closure of the forceps with application of gentle traction, and (4) dissection of muscle fibers by using cutting current. Intraprocedural bleeding was controlled with the same instrument by grasping vessels and applying coagulation current. MAIN OUTCOME MEASUREMENTS: Overall feasibility and performance, procedure time to achieve complete CP myotomy. RESULTS: CP myotomy was successfully performed in all patients. Mean procedure time was 10.6 minutes. There were no major adverse events. Minor intraprocedure bleeding occurred in 1 patient. LIMITATIONS: Single arm, limited number of patients. CONCLUSION: The new instrument has potential advantages in comparison with standard instruments used for CP myotomy. The advantages of this new technique are better control of cutting and hemostatic abilities.

Granulomas of intestinal tuberculosis and Crohn's disease can be differentiated by CD73 cell surface marker expression: a pilot study.

BACKGROUND: Intestinal tuberculosis (ITB) and Crohn's disease are similar granulomatous disorders. Granulomas are present in both and difficult to differentiate on histopathology alone. A recent study demonstrated recruitment of mesenchymal cells (MSCs) at the periphery of granulomas in lymph node tuberculosis which suppressed T cell responses. We hypothesized that granulomas of ITB would also recruit MSCs to evade host immune response. AIM: The purpose of this study was to demonstrate MSC markers in granulomas of ITB and evaluate whether distribution of MSC markers could differentiate between granulomas of Crohn's and ITB. METHODS: We initially retrospectively enrolled 17 patients with confirmed ITB (8) or Crohn's (9) with granulomas on histopathology. Tissues were evaluated by immunofluorescence for MSC markers CD29, CD90, CD73 and absence of haematopoietic markers CD31, CD34, CD45 and CD14. Double-staining was done to confirm presence of MSCs. Subsequently, 23 postoperative specimens of Crohn's (18) and ITB (5) were analyzed for validation. RESULTS: Overall, 27 Crohn's and 13 ITB cases were assessed. CD29 and CD90 positive cells were noted around both ITB and Crohn's granulomas. MSC marker CD73 was expressed around the granulomas of ITB alone and was completely absent in the Crohn's. The subsequent assessment of granulomas in postoperative specimens of Crohn's and ITB also showed similar results. CONCLUSION: Granulomas of ITB and Crohn's disease can be differentiated by CD73 MSC surface marker expression. The differential CD73 expression around ITB granuloma indicates that Mycobacterium tuberculosis evades host immunity by recruiting MSCs with CD73 expression. MSCs with increased CD73 expression could be the future for therapeutic intervention in Crohn's.