A Search for Acute Necrotic Pancreatitis in Early Stages of Alcoholic Chronic Pancreatitis Lucio Gullo, MD, Riccardo Casadei, MD, Marina Migliori, MD, Marco Manca, MS, Luciana Bastagli, MD, Raffaele Pezzilli, MD, and Donatella Santini, MD Objectives: Various investigators believe that alcoholic chronic pancreatitis is the result of recurrent episodes of acute necrotic pancreatitis. The aim of this work is to study pancreatic histology in early stages of the disease to search for evidence of these acute episodes. Study: Of about 650 patients with alcoholic pancreatitis seen during the 30-year period from 1972 to 2002, 45 underwent surgery for this disease, all within 2 years of clinical onset. Of these 45, tissue samples adequate for study were obtained from 42, and this was the study material. Tissue samples were prepared for histologic examination by standard procedures. Results: Areas of pancreatic necrosis were seen in tissue samples of only three (7%) of the 42 patients, and in all three cases chronic lesions were also present. No evidence of localized scarring that could be attributed to prior episodes of focal necrotic pancreatitis was found. A typical feature was the patchy distribution of the lesions in largely normal pancreatic tissue. The main lesions observed were perilobular and intralobular fibrosis, dilation of acini and ducts, and protein plugs in dilated ducts surrounded by periductal fibrosis. Conclusions: This study shows that, in the early stages of alcoholic chronic pancreatitis, signs of acute necrotic pancrea- titis are very infrequent and, when present, they are associated with chronic lesions. These findings suggest that alcoholic pancreatitis begins as a chronic disease. Key Words: pancreatitis acute, necrotizing, pancreatitis, alco- holic, early diagnosis, pathology (J Clin Gastroenterol 2006;40:435–439) D espite considerable progress toward an understand- ing of chronic pancreatitis, its pathogenesis con- tinues to be debated, in particular, whether it is a chronic disease from the start 1–9 or if it begins as acute necrotic pancreatitis, recurs, and eventually develops into a chronic form of the disease. 10–15 In recent years, various authors 10–15 have sustained the latter hypothesis, which had initially been proposed by Comfort et al 16 in 1944 but then was largely abandoned. Lately, renewed support has been given to this theory by Whitcomb et al, 17 who identified a mutation of the gene for cationic trypsinogen on chromosome 7 of patients with hereditary pancreatitis and hypothesized that this mutation is responsible for development of this disease. According to these investi- gators, hereditary pancreatitis starts with an episode of acute necrotic pancreatitis that, after repeated bouts, eventually becomes chronic. Whitcomb et al 18,19 subsequently extended this theory to explain the pathogenesis of the other forms of chronic pancreatitis, including the alcoholic form. We believe that this question could be clarified by histological study of the pancreas to search for evidence of diffuse or focal acute necrotizing pancreatitis in the initial stages of the disease. Over the years we have acquired vast experience with the pancreatic histology of alcoholic pancreatitis from patients who have undergone surgery for treatment of this disease. In this article we present these findings, limiting the study to those who had surgical intervention within 2 years of clinical onset of the pancreatitis. Our working premise is that if the disease begins as an attack of acute necrotizing pancreatitis and progresses as these attacks recur, there should be histologic evidence of these acute inflammatory processes. PATIENTS AND METHODS During the period from 1972 to 2002, one of us (LG) saw more than 650 patients with alcoholic chronic pancreatitis, about half of whom underwent surgery for this disease. The 45 who had the surgery within 2 years of clinical onset composed the study group for this article. Of these 45 subjects, four had surgery within 6 months of the first painful attack, 14 had it between 7 and 12 months, and 27 had it between 12 and 24 months. Relief of very frequent (three or four times per month) or persistent intense abdominal pain was the most common reason for the surgery. Of the study subjects, 43 were male and two, female; average age at the time of surgery was 42 years (range, 25–52 years). All drank wine as the primary Copyright r 2006 by Lippincott Williams & Wilkins Received for publication October 26, 2005; accepted January 19, 2006. From the Institutes of Internal Medicine, General Surgery, and Pathology, University of Bologna, St. Orsola Hospital, Bologna, Italy. Reprints: Prof. Lucio Gullo, Institute of Internal Medicine, Pad. 11, St. Orsola Hospital, Via Massarenti 9, 40138 Bologna, Italy (e-mail: gullo@med.unibo.it). LIVER,PANCREAS, AND BILIARY TRACT:CLINICAL RESEARCH J Clin Gastroenterol  Volume 40, Number 5, May/June 2006 435