Anil B. Nagar

Changing Referral Trends of Acute Pancreatitis in Children: A 12-year Single-center Analysis

Background:Acute pancreatitis is a painful inflammatory disorder known to occur in children. Recent reports, primarily on the basis of adult data, have suggested an increasing incidence. However, pediatric studies are limited. Objective:The study was performed to examine the frequency of acute pancreatitis in a pediatric population from 1994 to 2007 and to characterize etiologies by age subsets. Patients and Methods:In this retrospective study, cases of pancreatitis were identified by ICD-9 codes and subjected to inclusion criteria. Results:Two hundred and seventy-one cases of pancreatitis met inclusion criteria. Mean age of the subjects was 13.1 ± 5.6 years. The recurrence rate was 15.3%. Biliary disease was the most common etiology (32.6%). Acute pancreatitis cases evaluated at a single tertiary care center increased 53% between 1995 to 2000 and 2001 to 2006 (P < 0.02). However, when cases were normalized by all annual pediatric emergency department visits for all medical reasons, the increase was reduced to 22% and lost statistical significance (P = 0.16). The rise was not associated with a change in etiologies or body mass index (BMI). Conclusions:This is the first report demonstrating that an increase in pediatric pancreatitis may in part be due to growing referrals to tertiary care centers. The data on etiologies, particularly with regard to differing ages, may be helpful in managing children who present with acute pancreatitis.

Barrett's Surveillance Identifies Patients with Early Esophageal Adenocarcinoma

BACKGROUND Barretts surveillance for dysplasia is recommended, but few studies have documented the benefit of endoscopic surveillance for dysplasia or cancer. OBJECTIVES Using a retrospective study design, we aim to demonstrate the impact of a Barretts surveillance program on the stage of esophageal adenocarcinoma and identify factors for progression of metaplasia to cancer. SUBJECTS The Institutional Review Board at Veterans Affairs Connecticut Healthcare approved the study. We report a retrospective review of a prospectively followed Barretts cohort in a surveillance program and compared their outcome with patients with a new diagnosis of esophageal adenocarcinoma, identified at the same center between 1999 and 2005. RESULTS There were 248 patients with Barretts esophagus entered into a surveillance program from 1999 to 2005. During the surveillance period of 987 patient-years, 5 (0.5% patient-year) patients developed esophageal adenocarcinoma. During the same period, 46 patients were diagnosed with new-onset esophageal adenocarcinoma outside of our surveillance program. Only 5% of these patients had a history of gastroesophageal reflux disease. There were 248 patients who underwent a mean number of 2.7+/-1.7 upper endoscopic procedures, with 26 (10%) patients developing dysplasia. Compared with nonsurveillance, more patients had early stage of cancer in the surveillance group (P <.001). All 5 patients with cancer diagnosed from Barretts esophagus surveillance endoscopy were alive, compared with 20 of 46 (43%) patients with cancer diagnosed outside of the surveillance program. The length of Barretts segment >3 cm was found to be associated with development of dysplasia, P=.004 (odds ratio 1.2; 95% confidence interval, 1.07-1.34). CONCLUSION Patients with Barretts esophagus undergoing endoscopic surveillance benefit from early-stage cancer diagnosis. Progression to adenocarcinoma is low, but long-segment and high-grade dysplasias have an increased risk of cancer. A significant number of patients with newly diagnosed esophageal adenocarcinoma do not complain of gastroesophageal reflux disease and are therefore not investigated for Barretts esophagus nor entered into surveillance. Patients and physicians can use this information in making a decision about surveillance.

Colonoscopy surveillance after polypectomy may be extended beyond five years.

Objectives Colonoscopy surveillance interval data longer than 5 years are limited. We examined adenoma yield to identify factors that predict appropriate intervals for postpolypectomy surveillance greater than 5 years, including risk of advanced adenoma recurrence. Methods We identified patients with and without adenomas on an index colonoscopy who returned at 5 to 10 years for a follow-up colonoscopy. Multivariate logistic regression was used to identify variables that predict finding an adenoma on follow-up colonoscopy. Results Three hundred ninety-nine patients were identified with a follow-up colonoscopy at an interval of >5 years. Irrespective of surveillance interval, adenoma incidence occurred in 116 patients (29.1%) with 25 (6%) having advanced adenomas. Patients with nonadvanced adenomas on index colonoscopy had a similar risk of advanced adenoma on follow-up colonoscopy at 5 years versus 6 to 10 years, 5% versus 6.2% (P=0.39). The risk of advanced adenoma at 5 and 6 to 10 years in patients with a negative index colonoscopy was 7% versus 3.6% (P=0.15). Patients with an advanced adenoma at index colonoscopy had the highest rate of advanced adenoma detection at 5 years at 26%. Proximal polyp location (odds ratio 12.4, confidence interval 2.7-56.7) predicted advanced adenoma occurrence at 5 years. Conclusions Postpolypectomy colonoscopy intervals can be extended beyond 5 years in patients with nonadvanced adenomas. Our findings also support a rescreening interval of 5 to 10 years in patients with a negative index colonoscopy. Patients with an index advanced adenoma are at highest risk for recurrent advanced adenoma and should have repeat colonoscopy before a 5 years interval.

Ethanol Exposure Depletes Hepatic Pigment Epithelium-Derived Factor, a Novel Lipid Regulator

BACKGROUND & AIMS Ethanol abuse can lead to hepatic steatosis and evolve into cirrhosis and hepatocellular carcinoma. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein that is expressed by hepatocytes. Proteomic, experimental, and clinical studies implicate PEDFs role in lipid regulation. Because matrix metalloproteinase (MMP)-2/9 activity regulates PEDF levels, we investigated whether PEDF degradation by MMPs has a permissive role in ethanol-induced hepatic steatosis. METHODS PEDF levels were examined in liver biopsy specimens from patients with ethanol-induced steatosis. Hepatic PEDF levels and MMP activity were assessed in 2 animal models of ethanol feeding (rats on an alcohol-containing liquid diet and mice given intragastric infusion of ethanol). The consequences of PEDF depletion in the liver were examined in PEDF-null mice. RESULTS Liver biopsy samples from patients with ethanol-induced steatosis had reduced PEDF levels, compared with normal liver samples. Ethanol-fed animals had histologic steatosis and increased liver triglyceride content (P< .05), as well as reduced levels of hepatic PEDF and increased MMP-2/9 activity. Ethanol-exposed hepatic lysates degraded PEDF in a MMP-2/9-dependent manner, and liver sections demonstrated abundant MMP-2/9 activity in situ. Addition of recombinant PEDF to PEDF-null hepatocytes, reduced their triglyceride content. CONCLUSIONS Ethanol exposure leads to marked loss of hepatic PEDF in human livers and in 2 animal models of ethanol feeding. Loss of PEDF contributes to the accumulation of lipids in ethanol-induced hepatic steatosis.

Multi-center colonoscopy quality measurement utilizing natural language processing

Background:An accurate system for tracking of colonoscopy quality and surveillance intervals could improve the effectiveness and cost-effectiveness of colorectal cancer (CRC) screening and surveillance. The purpose of this study was to create and test such a system across multiple institutions utilizing natural language processing (NLP).Methods:From 42,569 colonoscopies with pathology records from 13 centers, we randomly sampled 750 paired reports. We trained (n=250) and tested (n=500) an NLP-based program with 19 measurements that encompass colonoscopy quality measures and surveillance interval determination, using blinded, paired, annotated expert manual review as the reference standard. The remaining 41,819 nonannotated documents were processed through the NLP system without manual review to assess performance consistency. The primary outcome was system accuracy across the 19 measures.Results:A total of 176 (23.5%) documents with 252 (1.8%) discrepant content points resulted from paired annotation. Error rate within the 500 test documents was 31.2% for NLP and 25.4% for the paired annotators (P=0.001). At the content point level within the test set, the error rate was 3.5% for NLP and 1.9% for the paired annotators (P=0.04). When eight vaguely worded documents were removed, 125 of 492 (25.4%) were incorrect by NLP and 104 of 492 (21.1%) by the initial annotator (P=0.07). Rates of pathologic findings calculated from NLP were similar to those calculated by annotation for the majority of measurements. Test set accuracy was 99.6% for CRC, 95% for advanced adenoma, 94.6% for nonadvanced adenoma, 99.8% for advanced sessile serrated polyps, 99.2% for nonadvanced sessile serrated polyps, 96.8% for large hyperplastic polyps, and 96.0% for small hyperplastic polyps. Lesion location showed high accuracy (87.0–99.8%). Accuracy for number of adenomas was 92%.Conclusions:NLP can accurately report adenoma detection rate and the components for determining guideline-adherent colonoscopy surveillance intervals across multiple sites that utilize different methods for reporting colonoscopy findings.

Helicobacter pylori-related gastric outlet obstruction: is there a role for medical treatment?

The role of Helicobacter pylori in the pathogenesis of duodenal and gastric ulcer and ulcer recurrence is widely known. Bleeding, perforation, and gastric outlet obstruction represent the most serious, potentially life-threatening complications of ulcer disease. At present, the effect of H. pylori eradication on complicated ulcer disease has not been fully established. Case reports exist on the resolution of gastric outlet obstruction after eradication of H. pylori. We report the first case of H. pylori-related gastric outlet obstruction successfully treated with parenteral antibiotics.

Bleeding from a duodenal varix: a unique case of variceal hemostasis achieved using EUS-guided placement of an embolization coil and cyanoacrylate.

We report a case of a bleeding duodenal varix demonstrating excellent hemostasis achieved by endoscopic ultrasound (EUS)-directed placement of an embolization coil followed by cyanoacrylate. A 31-year-old man with decompensated Child’s class C cirrhosis presented with hematemesis. An initial endoscopy revealed an actively bleeding duodenal varix. Subsequent attempt at hemostasis with ethanolamine oleate injection failed. A later attempt at hemostasis involving EUS-guided placement of an embolization coil followed by cyanoacrylate injection into the varix was successful. We reviewed the literature involving the treatment of bleeding ectopic varices and conclude that EUS provides a unique and advantageous modality for achieving variceal hemostasis of duodenal varices in patients who are not candidates for transjugular intrahepatic portosystemic shunt.

Successful Multimodality Endoscopic Treatment of Gastric Outlet Obstruction Caused by an Impacted Gallstone (Bouveret's Syndrome)

Bouverets syndrome is a rare condition of gastric outlet obstruction resulting from the migration of a gallstone through a choledochoduodenal fistula. Due to the large size of these stones and the difficult location in which they become impacted, endoscopic treatment is unsuccessful and most patients require surgery. We report the case of an elderly male who presented with nausea and hematemesis, and was found on CT scan and endoscopy to have an obstructing gallstone in his duodenal bulb. After several endoscopic sessions and the use of multiple instruments including a Holmium: YAG laser and electrohydraulic lithotripter, fragmentation and endoscopic removal of the stone were successful. We believe this to be the first case of Bouverets syndrome successfully treated by endoscopy alone in the United States. We describe the difficulties encountered which necessitated varied and innovative therapeutic techniques.

Long-Term PPI Use: Balancing Potential Harms and Documented Benefits

Concerns about the possible side effects of proton pump inhibitors (PPIs) have been raised since their introduction in the 1980s, including gastric carcinoids, gastric carcinoma, decreased absorption of minerals (e.g., iron, calcium) and vitamin B-12, fractures, enteric infections (e.g., C. difficile), pneumonia, hypomagnesemia, and cardiovascular events (1). This year studies reporting associations with chronic kidney disease (CKD) and dementia had widespread media coverage (2, 3), prompting renewed concern and many questions from patients and physicians regarding long-term PPI use.

Epidemiology and Pathophysiology of Acute Pancreatitis

Acute pancreatitis (AP) is an acute inflammatory process of the pancreas with variable involvement of the pancreas, regional tissues around the pancreas, or remote organ systems. The clinical course may range from mild discomfort with minimal pancreatic inflammation to severe necrotizing pancreatitis, complicated by multiorgan system failure and death. The most common etiologies are gallstones and alcohol abuse. The natural history is dependent on the degree of inflammation and necrosis. Following an acute attack, there is usually complete recovery of function if the offending agent is identified and removed. The pathogenesis of AP involves discrete intracellular events that prematurely activate intra-acinar zymogen granules and generate the release of proinflammatory and proapoptotic mediators. Understanding the natural history and specific roles of these cytokines may help develop therapies that can alter the course of severe pancreatitis and decrease its complications.