Recent Advances In the Pathology of Alcoholic Myopathy

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Victor R. Preedy and Junko Adachi. The presentations were (1) Alcoholic myopathy: Past, present and future, by Timothy J. Peters and Victor R. Preedy; (2) Protein adducts in the type I and II fiber-predominant muscles of the ethanol-fed rat, by Simon Worrall, Seppo Parkkila, and Onni Niemela; (3) Hydroperoxides and changes in alcoholic myopathy, by Junko Adachi, Migiwa Asamo, and Yasuhino Ueno; and (4) A close association between testicular atrophy, muscle atrophy, and the increase in protein catabolism after chronic ethanol administration, by Kunihiko Takeda, Masayoshi Yamauchi, Kazuhiko Sakamoto, Masaru Takagi, Hisato Nakajima, and Gotaro Toda.     

Acute Alcoholic Pancreatitis in the Rat

Pancreatic lesions have been produced in rats by the injection of different solutions into the pancreatic duct system. Alcoholic bile (bile containing about 1.5 mg per cent alcohol) caused more extensive lesions (hemorrhagic necrosis) than normal bile. Alcohol (0.5 per cent), on the contrary, gave the same type of lesions as did saline (interstitial edema only). Alcohol intake thus appears to potentiate the injurious effect of bile on the pancreas. It is suggested that this may be an important factor in the production of acute pancreatitis in alcoholism in man.     

Cecal Perforation in Alcoholic Pancreatitis

A 51-YEar old male with alcoholic pancreatitis progressed to bowel inflammation and cecal perforation. Colonic complications of pancreatitis include fistula, stenosis, necrosis and perforation. The pathogenesis of these entities is discussed and the literature regarding colonic complications is reviewed. Although it is uncommon, bowel involvement in pancreatitis is potentially lethal and may necessitate surgery in an otherwise medically managed illness.     

Immunological Changes of Mild Acute Pancreatitis in Late-Stage Alcoholic Chronic Pancreatitis

The exact immunological mechanisms underlyingalcoholic chronic pancreatitis are unclear. Toinvestigate the role of the tumor necrosis factor (TNF)receptor pathway the serum levels of TNF-,soluble TNF receptors-p55/-p75, and CRP were determinedby ELISA in 34 patients with late-stage alcoholicchronic pancreatitis and 28 controls. The diseaseactivity (Balthazar scoring system) of acutepancreatitis on the background of late-stage chronicpancreatitis correlated with an increase of functionallyactive TNF receptor-p55/-p75 serum levels. Unstimulatedperipheral blood mononuclear cells are one source of soluble TNF receptors and demonstrated asystemic leukocyte activation. The marked enhancement ofsoluble TNF receptors suggests that alcoholic chronicpancreatitis may be characterized by transient peaks of in situ TNF- productionpreceding a long-lasting release of soluble TNFreceptors. The data demonstrate immunological changescharacteristic of acute pancreatitis in late-stagealcoholic chronic pancreatitis.     

Chronic Alcoholic Pancreatitis with Pancreas Divisum

The mechanism for the onset of chronic alcoholic pancre-atitis(CAP) involves many unresolved questions. We (1,2) have succeeded in creating an animal model of CAPby inducing mild stenosis of the pancreatic duct in experi-mentalanimals given alcohol. The CAP seen in this modelis akin to that seen in humans. This means that pancreaticduct-related factors play an important role in the onset ofCAP.     

CFTR Polymorphisms in Patients with Alcoholic Chronic Pancreatitis

Introduction: Pancreas susceptibility to alcohol is variable and only 5–10% of chronic alcohol abusers develop chronic pancreatitis; the role of genetic factors in this process is unknown. The CFTR gene encodes a protein that acts on epithelial cells and plays a key role in normal exocrine pancreatic function. Methods: This study investigated the frequency of polymorphisms in intron 8 of the CFTR gene in patients with alcoholic chronic pancreatitis. Three groups of patients were studied: group A - 68 adult alcoholics with a diagnosis of chronic pancreatitis; group B - 68 adult alcoholics without pancreatic disease or liver cirrhosis and group C - 104 healthy nonalcoholic adults. Results: T5/T7 genotype was more frequent in group A (11.8%) than in group B (2.9%) (p = 0.0481), and there was no statistical difference when groups A and C (5.8%) were compared (p = 0.1317). The haplotype combination (TG)10-T7/(TG)11-T7 was more frequent in groups B (23.5%) and C (20.2%) than in group A (7.3%) (p = 0.0080 and 0.0162). Conclusion: There are differences when these three groups are compared and individuals with T5/T7 genotype might have a greater risk of developing chronic pancreatitis when they become chronic alcoholics.     

Advances in Alcoholic Liver Disease

Alcoholic liver disease (ALD) remains a leading cause of death from liver disease in the United States. In studies from the Veterans Administration, patients with cirrhosis and superimposed alcoholic hepatitis had greater than 60% mortality over a 4-year period, with most of those deaths occurring in the first month. Thus, the prognosis for this disease is more ominous than for many common types of cancer (eg, breast, prostate, and colon). Moreover, ALD imposes a significant economic burden from lost wages, health care costs, and lost productivity. Unfortunately, there is still no Food and Drug Administration–approved or widely accepted drug therapy for any stage of ALD. Thus, a pressing need exists for a more detailed understanding of mechanisms of liver injury. This article reviews recent advances in mechanisms and therapy related to five major areas of direct relevance to ALD: oxidative stress; gut-liver axis and cytokine signaling; malnutrition; fibrin/clotting; and stellate cell activation/fibrosis. We also review why therapies related to these mechanisms have performed well in experimental animals and in vitro systems, but have not necessarily translated into effective therapy for humans with ALD.     

A Toxic-Metabolic Hypothesis of Pathogenesis of Alcoholic Pancreatitis

Rejecting the big duct hypothesis of alcoholic pancreatitis, a toxic-metabolic hypothesis, in which the acinar cells and ductular system participate, is offered instead. This hypothesis explains the latent period from alcoholism inception to clinical signs of pancreatitis and clarifies the secretory changes at various stages of the disorder.     

胆源性和酒精性慢性胰腺炎临床特点分析

背景：慢性胰腺炎作为一种常见疾病已引起广泛关注．但对其病因分布以及不同类型慢性胰腺炎的临床特征尚不十分明了。目的：了解慢性胰腺炎的临床特征，分析胆源性与酒精性慢性胰腺炎的异同。方法：回顾性分析武汉协和医院1991年1月～2005年12月收治的119例慢性胰腺炎患者的病因构成、临床表现和常规实验室检查结果。结果：本组119例慢性胰腺炎中，最常见的病因为胆系疾病和长期饮酒，分别占37．0％和18．5％。临床表现多样化，常见的除腹痛外，还包括上腹不适、腹胀、消化不良等。除与胆道梗阻相关的黄疸和相应生化改变外，胆源性胰腺炎与酒精性胰腺炎的其他临床表现无明显差异。胆源性胰腺炎的中性粒细胞计数和天冬氨酸氨基转移酶（AST）水平更高。结论：胆系疾病和长期饮酒是本组慢性胰腺炎的主要病因。单从症状和体征难以直接判断慢性胰腺炎的病因，淤胆相关指标以及中性粒细胞计数和AST水平对鉴别胆源性与酒精性胰腺炎有一定临床价值。     

酒精性肝病的流行病学和预后

酒精性肝病(ALD)是酒精滥用的主要医学并发症之一。在西方，酒精是肝硬化的主要病因。摄入过量的酒精可导致不同类型的肝损害，约三分之二的重度嗜酒者出现脂肪肝、肝纤维化和肝硬化等，但仍有约三分之一的重度嗜酒者不发生肝损害，其确切原因不明。酒精性肝病的高发病率与低廉的酒精消费水平有     

Susceptibility Factors and Cellular Mechanisms Underlying Alcoholic Pancreatitis

Alcohol is a major cause of acute and chronic pancreatitis. There have been some recent advances in the understanding of the mechanisms underlying alcoholic pancreatitis, which include perturbation in mitochondrial function and autophagy and ectopic exocytosis, with some of these cellular events involving membrane fusion soluble N-ethylmaleimide–sensitive factor receptor protein receptor proteins. Although new insights have been unraveled recently, the precise mechanisms remain complex, and their finer details have yet to be established. The overall pathophysiology of pancreatitis involves not only the pancreatic acinar cells but also the stellate cells and duct cells. Why only some are more susceptible to pancreatitis and with increased severity, while others are not, would suggest that there may be undefined protective factors or mechanisms that enhance recovery and regeneration after injury. Furthermore, there are confounding influences of lifestyle factors such as smoking and diet, and genetic background. Whereas alcohol and smoking cessation and a generally healthy lifestyle are intuitively the advice given to these patients afflicted with alcoholic pancreatitis in order to reduce disease recurrence and progression, there is as yet no specific treatment. A more complete understanding of the pathogenesis of pancreatitis from which novel therapeutic targets could be identified will have a great impact, particularly with the stubbornly high fatality (>30%) of severe pancreatitis. This review focuses on the susceptibility factors and underlying cellular mechanisms of alcohol injury on the exocrine pancreas.     

Recent Advances in the Diagnosis and Management of Autoimmune Pancreatitis: Similarities and Differences in Japan and Korea

Two subtypes (types 1 and 2) of autoimmune pancreatitis (AIP) are currently recognized. Type 1 AIP is related to immunoglobulin G4 (lymphoplasmacytic sclerosing pancreatitis), and type 2 AIP is characterized by neutrophilic infiltration into the epithelium of the pancreatic duct (idiopathic duct-centric pancreatitis). Although type 2 AIP is sometimes observed in the United States and Europe, most cases of AIP in Japan and Korea are type 1. The international consensus diagnostic criteria for AIP were created to be applicable worldwide and to distinguish between the two types of AIP. AIP is diagnosed based on the presence of at least one of the five cardinal features (i.e., imaging, serology, other organ involvement, histology, and response to steroid therapy). Oral steroids are the standard therapy for AIP, but immunomodulatory drugs or rituximab have been successfully used for patients with relapsed AIP in the United States and Europe. Generally, the clinical manifestations and demography of AIP are similar between Japan and Korea. However, there are differences in some aspects of the disease, including the proportion of other organ involvement, the prevalence of type 2 AIP, diagnostic criteria and maintenance therapy between the two countries.