Amit Raina

Evaluation and Management of Autoimmune Pancreatitis: Experience at a Large US Center

OBJECTIVES:Autoimmune pancreatitis (AIP) is increasingly recognized as a form of chronic pancreatitis. Systematic evaluation and management of AIP in the United States is reported only from one center. Our aim was to review the evaluation and management of AIP at a large tertiary center.METHODS:We retrospectively reviewed information on demographics, clinical presentation, laboratory and imaging findings, extrapancreatic involvement, treatment response, and recurrence in 26 patients with AIP treated at the University of Pittsburgh Medical Center from 1998 to 2007.RESULTS:The median age at presentation was 62.5 years (range: 23–86), 65% were men, and 88% were Caucasians. The most common presentation included new-onset mild abdominal pain (65%), jaundice (62%), and weight loss (42%). Pancreatic mass, enlargement, or prominence on imaging was present in 85% of the patients. Serum IgG4 (immunoglobulin-4) was elevated (>140 mg/dl) in 44% (8/18) at presentation. The most common extrapancreatic finding was extrapancreatic/intrahepatic biliary strictures (35%). Peri-pancreatic vascular complications were noted in 23% of the patients. Six patients underwent partial or complete pancreatectomy. Partial or complete response was observed for initial steroid treatment in 19 patients and for methotrexate in 1 patient. Recurrences were common, especially in patients with extrapancreatic manifestations, and usually responded to a combination of steroids and azathioprine. Any one of the commonly used diagnostic criteria (Mayo Clinics HISORt criteria, the Japanese Pancreas Society criteria, Korean diagnostic criteria) was fulfilled in 85% of cases.CONCLUSIONS:In this second major US series, we confirm several findings previously reported in AIP. Our study highlights the presence of vascular complications in a subset of patients with AIP. The current diagnostic criteria may not identify all AIP patients.

Serum Immunoglobulin G Fraction 4 Levels in Pancreatic Cancer : Elevations Not Associated With Autoimmune Pancreatitis

CONTEXT Autoimmune pancreatitis is an uncommon, inflammatory disease of the pancreas that presents with clinical features, such as painless jaundice and a pancreatic mass, similar to those caused by pancreatic cancer. Patients with autoimmune pancreatitis frequently have elevated serum immunoglobulin G fraction 4 (IgG4) levels, and their pancreatic tissue may show IgG4-positive plasma cell infiltration. It is imperative to differentiate autoimmune pancreatitis from pancreatic cancer because autoimmune pancreatitis typically responds to corticosteroid treatment. A previous Japanese study reported that serum IgG4 greater than 135 mg/dL was 97% specific and 95% sensitive in predicting autoimmune pancreatitis. OBJECTIVE To prospectively measure serum IgG4 levels in pancreatic cancer patients to ascertain whether increased levels might be present in this North American population. DESIGN We collected blood samples and phenotypic information on 71 consecutive pancreatic cancer patients and 103 healthy controls who visited our clinics between October 2004 and April 2006. IgG4 levels were determined using a single radial immunodiffusion assay. A serum IgG4 level greater than 135 mg/dL was considered elevated. RESULTS Five cancer patients had IgG4 elevation, with a mean serum IgG4 level of 160.8 mg/dL. None of our cancer patients with plasma IgG4 elevation demonstrated evidence of autoimmune pancreatitis. One control subject demonstrated elevated serum IgG4 unrelated to identified etiology. CONCLUSIONS As many as 7% of patients with pancreatic cancer have serum IgG4 levels above 135 mg/dL. In patients with pancreatic mass lesions and suspicion of cancer, an IgG4 level measuring between 135 and 200 mg/dL should be interpreted cautiously and not accepted as diagnostic of autoimmune pancreatitis without further evaluation.

Early Jejunal Feeding Initiation and Clinical Outcomes in Patients with Severe Acute Pancreatitis

BACKGROUND Compared with parenteral nutrition, enteral nutrition reduces infectious complications and mortality in patients with severe acute pancreatitis (SAP). This study used clinical outcomes to investigate the association between time to initiation of distal jejunal feeding (DJF) and time to achievement of goal enteral feeding with clinical outcomes. METHODS A retrospective chart review was performed on all patients with SAP admitted to the medical intensive care unit (ICU) during a 1-year period. Collected data included demographic information, body mass index (BMI; kg/m(2)), Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission, time of onset of DJF, time to goal feeding, ICU length of stay, and mortality. RESULTS Time to starting DJF was longer in nonsurvivors (n = 4) than in survivors (n = 12) (17 vs 7 days, P < .05). All nonsurvivors had BMI >30 kg/m(2) (50% had BMI > 50 kg/m(2)). ICU length of stay was significantly associated with achievement of goal feeding. Three patients never reached goal feeding and spent 45.3 ± 19.6 days in the ICU; 7 patients reached goal feeding within 3 days of initiating DJF and spent 18 ± 1.7 days in the ICU; and 4 patients reached goal feeding within 3 days and spent 10.5 ± 3.5 days in the ICU. APACHE II scores were not significantly different among the 3 groups (16.7 ± 1.5, 12 ± 0.7, and 16.2 ± 1.2, respectively, P > .05). CONCLUSIONS Early initiation of DJF in the ICU was associated with reduced mortality in this cohort of patients with SAP. Early achievement of jejunal feeding goal early was associated with a shorter ICU length of stay, irrespective of the severity of SAP.

Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways

Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is characterized by a distinct metabolic phenotype spanning multiple pathways. Metabolomics profiling revealed a panel of biomarkers for disease prognosis, and future studies are planned to validate these findings in larger cohorts of patients with severe AAH.

Enteral Feeding Patients With Gastric Outlet Obstruction

Patients with upper gastrointestinal obstructions were previously managed with gastric decompression and parenteral feeding. The authors present their experience in 50 patients with obstructions chiefly due to complicated severe acute (n = 31) or chronic cystic pancreatitis (n = 11) using a double-lumen nasogastric decompression and jejunal feeding tube system (NGJ) held in place with a nasal bridle that passes through the obstructed gastroduodenal segments, allowing distal jejunal feeding, and at the same time decompresses the stomach to prevent vomiting and aspiration. The tip of the jejunal tube was placed approximately 40 cm down the jejunum to maintain pancreatic rest. Duration of feeding ranged from 1-145 days (median 25 days); 19 patients were discharged home with tube feeds. Only 1 patient could not tolerate feeding and needed to be converted to parenteral feeding. Average tube life was 14 days, with replacement being needed most commonly for kinking or clogging of the jejunal tube (56%) or accidental dislodgement (24%). The obstruction resolved spontaneously in 60%, allowing resumption of normal eating. Of the patients with severe acute pancreatitis or pancreatic pseudocysts, pancreatic rest resulted in resolution of the disease without surgery in 87%, and need for surgery in the remainder was put off for 31-76 days. Seven patients died predominantly of complications of acute pancreatitis between 1 and 31 days. In conclusion, NGJ feeding provides a relatively safe conservative management for critically ill patients with upper gastrointestinal obstructions, reducing the need for surgery and parenteral feeding.

Mucosal IgG4 cell infiltration in ulcerative colitis is linked to disease activity and primary sclerosing cholangitis.

Background:The distribution of IgG4 plasma cells in colonic mucosa, its significance, and relation to disease activity in patients with inflammatory bowel disease (IBD) is unclear. We systematically evaluated IgG4 cell distribution in colonic mucosal biopsies of patients with IBD and correlated histological findings with disease pattern and mucosal inflammation. Methods:We reviewed clinical records and pathology specimens of 54 randomly selected patients with IBD (13 Crohns colitis: 7 active, 6 inactive; 18 ulcerative colitis [UC]: 10 active, 8 inactive; 23 UC with primary sclerosing cholangitis: 11 active colitis, 12 inactive colitis), and 11 controls (3 nonspecific diarrhea, 8 collagenous/lymphocytic colitis) who had colonoscopy and biopsies performed at our institution from April 2003 to July 2010. Immunostains for IgG4 were performed on archived rectal biopsies. Presence of >10 IgG4 cells per high-power field (×40 field) on microscopic evaluation was considered significant. Results:Overall, significant IgG4 plasma cell infiltration was seen in 24% of patients compared with none of the controls (P = 0.05). Within IBD groups, significant infiltration was limited to patients with UC with active colitis (30%), primary sclerosing cholangitis with inactive (25%) and active (64%) colitis. In contrast, patients with Crohns colitis, UC with inactive colitis, and controls had rare IgG4 plasma cells. No correlation was observed between the number of IgG4 cells and degree of active inflammation. In 4 patients with UC and primary sclerosing cholangitis who had more than 1 colonoscopy and biopsies, the number of IgG4 cells fluctuated without correlation with colonic disease activity. Conclusions:IgG4 plasma cells are significantly increased in a subset of patients with IBD suggesting the possibility of a B-cell–mediated mechanism in these patients.

Airway observations during upper endoscopy predicting obstructive sleep apnea

Background This pilot study examined airway characteristics during upper endoscopy to determine who is at high risk for obstructive sleep apnea. Methods Patients undergoing routine upper endoscopy were divided into 2 groups according to the Berlin Questionnaire (high and low risk for sleep disordered breathing). Patients underwent routine upper endoscopy using propofol sedation. The airway was then evaluated for no, partial, or complete collapse at the levels of the palate/uvula/tonsils, the tongue base, the hypopharynx, and the larynx. They were given a score of 0 for no collapse, 1 for partial collapse, and 2 for complete collapse. The score for each of these levels was added to give a total score or severity index. The larynx was also evaluated for lateral pharyngeal collapse (minimal, up to 50%, >50%, or 100%). Results We found that patients with a partial obstruction at the level of the palate/uvula/tonsils, tongue base, hypopharynx, or larynx, or complete obstruction at any level more often had a positive Berlin questionnaire. Patients with a positive Berlin questionnaire were more often of increased weight (mean 197 vs 175 lbs, P=0.19), increased body mass index (31.2 vs 27.42 kg/m2, P=0.11), increased neck circumference (36.7 vs 34.7 cm, P=0.23), and had a higher total airway score (2.61 vs 1.67, P=0.09). Conclusions The results of our pilot study represent preliminary data regarding the use of upper endoscopy as a potential tool to evaluate patients for obstructive sleep apnea.

591b Natural History After Acute Necrotizing Pancreatitis (NP): A Large U.S. Tertiary Care Experience

Background Most studies of acute necrotizing pancreatitis (ANP) focus on short-term outcomes. We evaluated long-term survival and outcomes following ANP.

Successful management of a very large common hepatic duct stone in a patient with pancreaticoduodenectomy by use of cholangioscopy and electrohydraulic lithotripsy

re 1. A, Large filling defect in common hepatic duct on MRCP. B, Dilated intrahepatic ducts on MRCP. C, Unsuccessful attempt at removal of stone extraction balloon. D, Electrohydraulic lithotripsy probe could not be lined up with a large fragment of the stone due to the stone’s location. E, Use hincterotome to guide the electrohydraulic lithotripsy probe. F, Electrohydraulic lithotripsy. G, Two stents placed after second ERCP. H, Removal of fragments with extraction balloon. I, No residual stone on occlusion cholangiogram at the end of the third ERCP.

An Unusual Case of Obstructive Jaundice Owing to an Extrabiliary Mass

Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, East Carolina University, Greenville, North Carolina; Department of Pathology and Laboratory Medicine, East Carolina University, Greenville, North Carolina 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 Question: A 79-year-old African American man with history of morbid obesity and metabolic syndrome presented with darkening urine, itching, and yellow discoloration of the eyes. He denied having abdominal pain, weight loss, or fever. On physical examination, his vital signs were normal. He had marked scleral icterus and normal abdominal examination. His total bilirubin was 18.3 mg/dL (direct bilirubin, 16.1 mg/dL); alkaline phosphatase, 693 U/L; aspartate aminotransferase, 137 U/L; and alanine aminotransferase, 89 U/L. Abdominal computed tomography showed intrahepatic and extrahepatic ductal dilation and gallbladder distension. A large mass involving distal stomach and duodenum with compression of the distal common bile duct (CBD) was noted (Figure A). Endoscopic ultrasound with fine needle aspiration and cytology was performed (Figure B). Endoscopic ultrasound imaging demonstrated a large mass occupying the submucosa of the antrum and proximal duodenum (Figure C). What is the most likely cause of this patient’s jaundice? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. 99 100 101 102 103 104 105 Conflicts of interest The authors disclose no conflicts.