RSS-Feed abonnieren
DOI: 10.1055/s-2005-858257
© Karl Demeter Verlag im Georg Thieme Verlag KG Stuttgart · New York
Wirkungen von Alkohol auf den oberen Gastrointestinaltrakt und das Pankreas - Eine aktuelle Übersicht
Effects of Alcohol on the Upper Gastrointestinal Tract and the Pancreas - An Up-to-Date OverviewPublikationsverlauf
Manuskript eingetroffen: 21.11.2004
Manuskript akzeptiert: 29.3.2005
Publikationsdatum:
09. August 2005 (online)
![](https://www.thieme-connect.de/media/zfg/200508/lookinside/thumbnails/10.1055-s-2005-858257-1.jpg)
Zusammenfassung
Ösophagus, Magen und Pankreas stellen primäre Zielorgane alkoholinduzierter Erkrankungen dar. Ethanol verursacht im Ösophagus und Magen dosisabhängig Motilitätsstörungen und Mukosaläsionen, die unter akuten Bedingungen reversibel sind. Chronischer Alkoholkonsum ist mit einer deutlichen Risikosteigerung für Plattenepithelkarzinome des Ösophagus vergesellschaftet. Diese Wirkungen werden hauptsächlich durch direkten Mukosakontakt mit Ethanol oder seines Metaboliten Azetaldehyd verursacht. Einige Wirkungen von alkoholischen Getränken, beispielsweise die maximale Stimulation der Magensäuresekretion durch vergorene Alkoholika, werden durch nichtalkoholische Begleitstoffe hervorgerufen. Am exokrinen Pankreas induziert Alkohol sekretorische Veränderungen, die von der Verabreichungsart und -dauer, der zusätzlichen Gabe von Mahlzeiten, der Getränkeart oder dem basalen Sekretionszustands des Organs abhängig sind. Für die Sekretionsveränderungen sind hauptsächlich systemische und cholinerg-vagale Mechanismen verantwortlich, da das Pankreas keiner topischen Ethanolexposition unterliegt. Chronischer Alkoholabusus kann über subklinische rezidivierende Entzündungsschübe zur chronischen alkoholischen Pankreatitis führen, wobei zusätzlich genetische Prädispositionen diskutiert werden. Anders als beim kardiovaskulären System existieren bei diesen Alkoholzielorganen keine gesundheitsförderlichen moderaten Alkoholmengen. Weiterer Forschungsbedarf besteht bei der Klärung der genauen molekularen Mechanismen und möglichen genetischen Prädispositionen von Alkoholfolgeerkrankungen sowie den Wirkungen nichtalkoholischer Substanzen in alkoholischen Getränken.
Abstract
The oesophagus, stomach and pancreas are primary target organs for ethanol-related diseases. In the oesophagus and stomach, ethanol induces motility disorders and mucosal lesions that are dose-dependent and reversible under acute conditions. Chronic consumption of alcohol causes a significant increase in the risk for squamous carcinoma of the oesophagus. All of these effects are mainly caused by direct contact of alcohol or its metabolite acetaldehyde with the mucosa. Non-alcoholic components are responsible for many effects of alcoholic beverages, including the powerful stimulation of gastric acid secretion by beverages that are produced by fermentation. In the exocrine pancreas, alcohol induces secretory alterations that are mainly affected by the manner and duration of alcohol exposure, the additional administration of food, the type of beverage or the basal secretory state of the gland. Because the pancreas is not topically exposed to ethanol, these ethanol effects on pancreatic secretion are primarily caused by systemic cholinergic mechanisms of the vagus nerve. Chronic alcohol abuse may cause chronic alcoholic pancreatitis after recurrent subclinical inflammatory episodes. Genetic predispositions are believed to play an additional role in the pathomechanism of the disease. In contrast to the cardiovascular system, moderate consumption of alcoholic beverages does not have any beneficial health effects on the oesophagus, stomach or pancreas. Future research needs to define the exact molecular mechanisms and the role of different genetic predispositions for alcohol-induced diseases as well as the effects of the non-alcoholic components of alcoholic beverages.
Schlüsselwörter
Alkohol - Ethanol - alkoholinduzierte Erkrankungen - Ösophagus - Magen - Pankreas
Key words
Alcohol - ethanol-alcohol-related diseases - oesophagus - stomach - pancreas
Literatur
- 1 Murray C J, Lopez A D. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet. 1997; 349 1269-1276
- 2 Murray C J, Lopez A D. Regional patterns of disability-free life expectancy and disability-adjusted life expectancy: global Burden of Disease Study. Lancet. 1997; 349 1347-1352
- 3 Gerke P, Hapke U, Rumpf H J. et al . Alcohol-related diseases in general hospital patients. Alcohol Alcohol. 1997; 32 179-184
- 4 Hüllinghorst R. Alkohol - Zahlen und Fakten. Singer MV, Teyssen S Alkoholfolgekrankheiten. Grundlagen - Diagnostik - Therapie Heidelberg; Springer-Verlag 1999: 32-39
- 5 Merfert-Diete C. Zahlen und Fakten in Kürze. Deutsche Hauptstelle für Suchtfragen Jahrbuch Sucht 2003 Geesthacht; Neuland-Verlag 2003: 8-17
- 6 Longnecker M P, Enger S M. Epidemiologic data on alcoholic beverage consumption and risk of cancer. Clin Chim Acta. 1996; 246 121-141
- 7 Hogan W J, Andrade de Viegas S R, Winship D H. Ethanol-induced acute esophageal motor dysfunction. J Appl Physiol. 1972; 32 755-760
- 8 Kjellen G, Tibbling L. Influence of body position, dry and water swallows, smoking, and alcohol on esophageal acid clearing. Scand J Gastroenterol. 1978; 13 283-288
- 9 Keshavarzian A, Polepalle C, Iber F L. et al . Esophageal motor disorder in alcoholics: result of alcoholism or withdrawal?. Alcohol Clin Exp Res. 1990; 14 561-567
- 10 Kaufman S E, Kaye M D. Induction of gastro-oesophageal reflux by alcohol. Gut. 1978; 19 336-338
- 11 Mayer E M, Grabowski C J, Fisher R S. Effects of graded doses of alcohol upon esophageal motor function. Gastroenterology. 1978; 75 1133-1136
- 12 Silver L S, Worner T M, Korsten M A. Esophageal function in chronic alcoholics. Am J Gastroenterol. 1986; 81 423-427
- 13 Keshavarzian A, Iber F L, Ferguson Y. Esophageal manometry and radionuclide emptying in chronic alcoholics. Gastroenterology. 1987; 92 651-657
- 14 Keshavarzian A, Polepalle C, Iber F L. et al . Secondary esophageal contractions are abnormal in chronic alcoholics. Dig Dis Sci. 1992; 37 517-522
- 15 Winship D H, Caflisch C R, Zboralske F F. et al . Deterioration of esophageal peristalsis in patients with alcoholic neuropathy. Gastroenterology. 1968; 55 173-178
- 16 Tonnesen H, Andersen J R, Christoffersen P. et al . Reflux oesophagitis in heavy drinkers. Effect of ranitidine and alginate/metoclopramide. Digestion. 1987; 38 69-73
- 17 Banciu T, Sorian E. Gastroesophageal reflux in chronic alcoholics. Endoesophageal pH determinations using Heidelberg telemetring capsule. Med Interne. 1989; 27 279-282
- 18 Chung R S, Johnson G M, Denbesten L. Effect of sodium taurocholate and ethanol on hydrogen ion absorption in rabbit esophagus. Am J Dig Dis. 1977; 22 582-588
- 19 Salo J A. Ethanol-induced mucosal injury in rabbit oesophagus. Scand J Gastroenterol. 1983; 18 713-721
- 20 Bor S, Caymaz-Bor C, Tobey N A. et al . Effect of ethanol on the structure and function of rabbit esophageal epithelium. Am J Physiol. 1998; 274 G819-826
- 21 Bor S, Bor-Caymaz C, Tobey N A. et al . Esophageal exposure to ethanol increases risk of acid damage in rabbit esophagus. Dig Dis Sci. 1999; 44 290-300
- 22 Martini G A, Wienbeck M. Does alcohol favour the development of Barret’s syndrome (endobrachy-oesophagus) (author’s transl). Dtsch Med Wochenschr. 1974; 99 434-439
- 23 Conio M, Filiberti R, Blanchi S. et al . Risk factors for Barrett’s esophagus: a case-control study. Int J Cancer. 2002; 97 225-229
- 24 Ryan P, Hetzel D J, Shearman D J. et al . Risk factors for ulcerative reflux oesophagitis: a case-control study. J Gastroenterol Hepatol. 1995; 10 306-312
- 25 Avidan B, Sonnenberg A, Schnell T G. et al . Risk factors for erosive reflux esophagitis: a case-control study. Am J Gastroenterol. 2001; 96 41-46
- 26 Avidan B, Sonnenberg A, Schnell T G. et al . Risk factors of oesophagitis in arthritic patients. Eur J Gastroenterol Hepatol. 2001; 13 1095-1099
- 27 Keshavarzian A, Urban G, Sedghi S. et al . Effect of acute ethanol on esophageal motility in cat. Alcohol Clin Exp Res. 1991; 15 116-121
- 28 Keshavarzian A, Gordon J H, Willson C. et al . Chronic ethanol feeding produces a muscarinic receptor upregulation, but not a muscarinic supersensitivity in lower esophageal sphincter muscle. J Pharmacol Exp Ther. 1992; 260 601-607
- 29 Keshavarzian A, Zorub O, Sayeed M. et al . Acute ethanol inhibits calcium influxes into esophageal smooth but not striated muscle: a possible mechanism for ethanol-induced inhibition of esophageal contractility. J Pharmacol Exp Ther. 1994; 270 1057-1062
- 30 Fields J Z, Jacyno M, Wasyliw R. et al . Ethanol inhibits contractility of esophageal smooth muscle strips. Alcohol Clin Exp Res. 1995; 19 1403-1413
- 31 Keshavarzian A, Muska B, Sundaresan R. et al . Ethanol at pharmacologically relevant concentrations inhibits contractility of isolated smooth muscle cells of cat esophagus. Alcohol Clin Exp Res. 1996; 20 180-184
- 32 Keshavarzian A, Jacyno M, Urban G. et al . The role of nitric oxide in ethanol-induced gastrointestinal dysfunction. Alcohol Clin Exp Res. 1996; 20 1618-1624
- 33 Teyssen S, Singer M V. Alcohol-related diseases of the oesophagus and stomach. Best Pract Res Clin Gastroenterol. 2003; 17 557-573
- 34 Siegmund S, Spanagel R, Singer M V. Role of the brain-gut axis in alcohol-related gastrointestinal diseases - What can we learn from new animal models?. J Physiol Pharmacol. 2003; 54 (Suppl 4) 191-207
- 35 Seitz H K, Stickel F, Homann N. Pathogenetic mechanisms of upper aerodigestive tract cancer in alcoholics. Int J Cancer. 2004; 108 483-487
- 36 Salaspuro M P. Alcohol consumption and cancer of the gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2003; 17 679-694
- 37 Pöschl G, Seitz H K. Alcohol and cancer. Alcohol Alcohol. 2004; 39 155-165
- 38 Homann N, Jousimies-Somer H, Jokelainen K. et al . High acetaldehyde levels in saliva after ethanol consumption: methodological aspects and pathogenetic implications. Carcinogenesis. 1997; 18 1739-1743
- 39 Homann N, Karkkainen P, Koivisto T. et al . Effects of acetaldehyde on cell regeneration and differentiation of the upper gastrointestinal tract mucosa. J Natl Cancer Inst. 1997; 89 1692-1697
- 40 Homann N, Tillonen J, Meurman J H. et al . Increased salivary acetaldehyde levels in heavy drinkers and smokers: a microbiological approach to oral cavity cancer. Carcinogenesis. 2000; 21 663-668
- 41 Homann N, Tillonen J, Rintamaki H. et al . Poor dental status increases acetaldehyde production from ethanol in saliva: a possible link to increased oral cancer risk among heavy drinkers. Oral Oncol. 2001; 37 153-158
- 42 Fang J L, Vaca C E. Detection of DNA adducts of acetaldehyde in peripheral white blood cells of alcohol abusers. Carcinogenesis. 1997; 18 627-632
- 43 Wang M, McIntee E J, Cheng G. et al . Identification of DNA adducts of acetaldehyde. Chem Res Toxicol. 2000; 13 1149-1157
- 44 Hecht S S, McIntee E J, Wang M. New DNA adducts of crotonaldehyde and acetaldehyde. Toxicology. 2001; 166 31-36
- 45 Cheng G, Shi Y, Sturla S J. et al . Reactions of formaldehyde plus acetaldehyde with deoxyguanosine and DNA: formation of cyclic deoxyguanosine adducts and formaldehyde cross-links. Chem Res Toxicol. 2003; 16 145-152
- 46 Noori P, Hou S M. Mutational spectrum induced by acetaldehyde in the HPRT gene of human T lymphocytes resembles that in the p53 gene of esophageal cancers. Carcinogenesis. 2001; 22 1825-1830
- 47 Espina N, Lima V, Lieber C S. et al . In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O6-methylguanine transferase. Carcinogenesis. 1988; 9 761-766
- 48 Visapää J P, Götte K, Benesova M. et al . Increased cancer risk in heavy drinkers with the alcohol dehydrogenase 1C*1 allele, possibly due to salivary acetaldehyde. Gut. 2004; 53 871-876
- 49 Yokoyama A, Muramatsu T, Ohmori T. et al . Multiple primary esophageal and concurrent upper aerodigestive tract cancer and the aldehyde dehydrogenase-2 genotype of Japanese alcoholics. Cancer. 1996; 77 1986-1990
- 50 Yokoyama A, Muramatsu T, Ohmori T. et al . Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics. Carcinogenesis. 1998; 19 1383-1387
- 51 Pöschl G, Stickel F, Wang X D. et al . Alcohol and cancer: genetic and nutritional aspects. Proc Nutr Soc. 2004; 63 65-71
- 52 Blot W J. Alcohol and cancer. Cancer Res. 1992; 52 2119 s-2123 s
- 53 Tuyns A J, Pequignot G, Gignoux M. et al . Cancers of the digestive tract, alcohol and tobacco. Int J Cancer. 1982; 30 9-11
- 54 Schoenberg B S, Bailar J C 3rd, Fraumeni J F Jr. Certain mortality patterns of esophageal cancer in the United States, 1930 - 67. J Natl Cancer Inst. 1971; 46 63-73
- 55 McGlashan N D, Bradshaw E, Harington J S. Cancer of the oesophagus and the use of tobacco and alcoholic beverages in Transkei, 1975 - 6. Int J Cancer. 1982; 29 249-256
- 56 Pottern L M, Morris L E, Blot W J. et al . Esophageal cancer among black men in Washington, D.C. I. Alcohol, tobacco, and other risk factors. J Natl Cancer Inst. 1981; 67 777-783
- 57 Brown L M, Blot W J, Schuman S H. et al . Environmental factors and high risk of esophageal cancer among men in coastal South Carolina. J Natl Cancer Inst. 1988; 80 1620-1625
- 58 Longnecker M P. Alcohol consumption and risk of cancer in humans: an overview. Alcohol. 1995; 12 87-96
- 59 Launoy G, Milan C, Day N E. et al . Oesophageal cancer in France: potential importance of hot alcoholic drinks. Int J Cancer. 1997; 71 917-923
- 60 Launoy G, Milan C, Day N E. et al . Diet and squamous-cell cancer of the oesophagus: a French multicentre case-control study. Int J Cancer. 1998; 76 7-12
- 61 Rothman K J. The proportion of cancer attributable to alcohol consumption. Prev Med. 1980; 9 174-179
- 62 Alcohol drinking . Epidemiological studies of cancer in humans. IARC Monogr Eval Carcinog Risks Hum. 1988; 44 153-250
- 63 Kato I, Nomura A M, Stemmermann G N. et al . Prospective study of the association of alcohol with cancer of the upper aerodigestive tract and other sites. Cancer Causes Control. 1992; 3 145-151
- 64 Chyou P H, Nomura A M, Stemmermann G N. Diet, alcohol, smoking and cancer of the upper aerodigestive tract: a prospective study among Hawaii Japanese men. Int J Cancer. 1995; 60 616-621
- 65 Boeing H. Alcohol and risk of cancer of the upper gastrointestinal tract: first analysis of the EPIC data. IARC Sci Publ. 2002; 156 151-154
- 66 Tuyns A J, Pequignot G, Jensen O M. Esophageal cancer in Ille-et-Vilaine in relation to levels of alcohol and tobacco consumption. Risks are multiplying. Bull Cancer. 1977; 64 45-60
- 67 Singer M V, Leffmann C, Eysselein V E. et al . Action of ethanol and some alcoholic beverages on gastric acid secretion and release of gastrin in humans. Gastroenterology. 1987; 93 1247-1254
- 68 Singer M V, Eysselein V, Goebell H. Beer and wine but not whisky and pure ethanol do stimulate release of gastrin in humans. Digestion. 1983; 26 73-79
- 69 Singer M V, Teyssen S, Eysselein V E. Action of beer and its ingredients on gastric acid secretion and release of gastrin in humans. Gastroenterology. 1991; 101 935-942
- 70 Chari S, Teyssen S, Singer M V. Alcohol and gastric acid secretion in humans. Gut. 1993; 34 843-847
- 71 Chari S T, Teyssen S, Singer M V. What controls should be used in studies of acute effects of alcohol and alcoholic beverages on the stomach and the pancreas?. Scand J Gastroenterol. 1993; 28 289-295
- 72 Teyssen S, Singer M V. Alkohol und Magen. Singer MV, Teyssen S Alkohol und Alkoholfolgekrankheiten. Grundlagen - Diagnostik - Therapie Heidelberg; Springer-Verlag 1999: 168-187
- 73 Singer M V. Effect of ethanol and alcoholic beverages on the gastrointestinal tract in humans. Rom J Gastroenterol. 2002; 11 197-204
- 74 Teyssen S, Gonzalez-Calero G, Schimiczek M. et al . Maleic acid and succinic acid in fermented alcoholic beverages are the stimulants of gastric acid secretion. J Clin Invest. 1999; 103 707-713
- 75 Teyssen S, Lenzing T, Gonzalez-Calero G. et al . Alcoholic beverages produced by alcoholic fermentation but not by distillation are powerful stimulants of gastric acid secretion in humans. Gut. 1997; 40 49-56
- 76 Davenport H W. Ethanol damage to canine oxyntic glandular mucosa. Proc Soc Exp Biol Med. 1967; 126 657-662
- 77 Davenport H W. Gastric mucosal hemorrhage in dogs. Effects of acid, aspirin, and alcohol. Gastroenterology. 1969; 56 439-449
- 78 Kvietys P R, Twohig B, Danzell J. et al . Ethanol-induced injury to the rat gastric mucosa. Role of neutrophils and xanthine oxidase-derived radicals. Gastroenterology. 1990; 98 909-920
- 79 Szabo S, Trier J S, Brown A. et al . Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology. 1985; 88 228-236
- 80 Ferraz J G, Tigley A W, Appleyard C B. et al . TNF-alpha contributes to the pathogenesis of ethanol-induced gastric damage in cirrhotic rats. Am J Physiol. 1997; 272 G809-814
- 81 Morales R E, Johnson B R, Szabo S. Endothelin induces vascular and mucosal lesions, enhances the injury by HCl/ethanol, and the antibody exerts gastroprotection. Faseb J. 1992; 6 2354-2360
- 82 Masuda E, Kawano S, Nagano K. et al . Effect of intravascular ethanol on modulation of gastric mucosal integrity: possible role of endothelin-1. Am J Physiol. 1992; 262 G785-790
- 83 Masuda E, Kawano S, Nagano K. et al . Role of endogenous endothelin in pathogenesis of ethanol-induced gastric mucosal injury in rats. Am J Physiol. 1993; 265 G474-481
- 84 Iaquinto G, Giardullo N, Taccone W. et al . Role of endogenous endothelin-1 in ethanol-induced gastric mucosal damage in humans. Dig Dis Sci. 2003; 48 663-669
- 85 Gottfried E B, Korsten M A, Lieber C S. Alcohol-induced gastric and duodenal lesions in man. Am J Gastroenterol. 1978; 70 587-592
- 86 Laine L, Weinstein W M. Histology of alcoholic hemorrhagic „gastritis”: a prospective evaluation. Gastroenterology. 1988; 94 1254-1262
- 87 Knoll M R, Kölbel C B, Teyssen S. et al . Action of pure ethanol and some alcoholic beverages on the gastric mucosa in healthy humans: a descriptive endoscopic study. Endoscopy. 1998; 30 293-301
- 88 Sarfeh I J, Tabak C, Eugene J. et al . Clinical significance of erosive gastritis in patients with alcoholic liver disease and upper gastrointestinal hemorrhage. Ann Surg. 1981; 194 149-151
- 89 Uppal R, Lateef S K, Korsten M A. et al . Chronic alcoholic gastritis. Roles of alcohol and Helicobacter pylori. Arch Intern Med. 1991; 151 760-764
- 90 Kapzan B, Neumann P, Heilmann K L. Alcohol consumption and chronic gastritis. Leber Magen Darm. 1985; 15 14-18
- 91 Roberts D M. Chronic gastritis, alcohol, and non-ulcer dyspepsia. Gut. 1972; 13 768-774
- 92 Dinoso V P Jr, Chey W Y, Braverman S P. et al . Gastric secretion and gastric mucosal morphology in chronic alcoholics. Arch Intern Med. 1972; 130 715-719
- 93 Cheli R, Giacosa A, Marenco G. et al . Chronic gastritis and alcohol. Z Gastroenterol. 1981; 19 459-463
- 94 Segawa K, Nakazawa S, Tsukamoto Y. et al . Chronic alcohol abuse leads to gastric atrophy and decreased gastric secretory capacity: a histological and physiological study. Am J Gastroenterol. 1988; 83 373-379
- 95 Potet F, Florent C, Benhamou E. et al . Chronic gastritis: prevalence in the French population. CIRIG. Gastroenterol Clin Biol. 1993; 17 103-108
- 96 Pateron D, Fabre M, Ink O. et al . Effect of alcohol and cirrhosis on the presence of Helicobacter pylori in the gastric mucosa. Gastroenterol Clin Biol. 1990; 14 555-560
- 97 Battaglia G, Di Mario F, Pasini M. et al . Helicobacter pylori infection, cigarette smoking and alcohol consumption. A histological and clinical study on 286 subjects. Ital J Gastroenterol. 1993; 25 419-424
- 98 Brenner H, Rothenbacher D, Bode G. et al . Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study. Bmj. 1997; 315 1489-1492
- 99 Brenner H, Bode G, Adler G. et al . Alcohol as a gastric disinfectant? The complex relationship between alcohol consumption and current Helicobacter pylori infection. Epidemiology. 2001; 12 209-214
- 100 Tursi A, Cammarota G, Papa A. et al . Effect of adequate alcohol intake, with or without cigarette smoking, on the risk of Helicobacter pylori infection. Hepatogastroenterology. 1998; 45 1892-1895
- 101 Murray L J, Lane A J, Harvey I M. et al . Inverse relationship between alcohol consumption and active Helicobacter pylori infection: the Bristol Helicobacter project. Am J Gastroenterol. 2002; 97 2750-2755
- 102 Baena J M, Lopez C, Hidalgo A. et al . Relation between alcohol consumption and the success of Helicobacter pylori eradication therapy using omeprazole, clarithromycin and amoxicillin for 1 week. Eur J Gastroenterol Hepatol. 2002; 14 291-296
- 103 Suzuki H, Mori M, Seto K. et al . Ethanol intake preceding Helicobacter pylori inoculation promotes gastric mucosal inflammation in Mongolian gerbils. J Gastroenterol Hepatol. 1999; 14 1062-1069
- 104 Paffenbarger R S Jr, Wing A L, Hyde R T. Chronic disease in former college students; 13. Early precursors of peptic ulcer. Am J Epidemiol. 1974; 100 307-315
- 105 Friedman G D, Siegelaub A B, Seltzer C C. Cigarettes, alcohol, coffee and peptic ulcer. N Engl J Med. 1974; 290 469-473
- 106 Kato I, Nomura A M, Stemmermann G N. et al . A prospective study of gastric and duodenal ulcer and its relation to smoking, alcohol, and diet. Am J Epidemiol. 1992; 135 521-530
- 107 Johnsen R, Forde O H, Straume B. et al . Aetiology of peptic ulcer: a prospective population study in Norway. J Epidemiol Community Health. 1994; 48 156-160
- 108 Piper D W, Nasiry R, McIntosh J. et al . Smoking, alcohol, analgesics, and chronic duodenal ulcerp. A controlled study of habits before first symptoms and before diagnosis. Scand J Gastroenterol. 1984; 19 1015-1021
- 109 Franke A, Teyssen S, Harder H. et al . Effect of ethanol and some alcoholic beverages on gastric emptying in humans. Scand J Gastroenterol. 2004; 39 638-644
- 110 Cooke A R. The stimultaneous emptying and absorption of ethanol from the human stomach. Am J Dig Dis. 1970; 15 449-454
- 111 Kaufman S E, Kaye M D. Effect of ethanol upon gastric emptying. Gut. 1979; 20 688-692
- 112 Pfeiffer A, Hogl B, Kaess H. Effect of ethanol and commonly ingested alcoholic beverages on gastric emptying and gastrointestinal transit. Clin Investig. 1992; 70 487-491
- 113 Moore J G, Christian P E, Datz F L. et al . Effect of wine on gastric emptying in humans. Gastroenterology. 1981; 81 1072-1075
- 114 Izbeki F, Wittmann T, Jancso G. et al . Inhibition of gastric emptying and small intestinal transit by ethanol is mediated by capsaicin-sensitive afferent nerves. Naunyn Schmiedebergs Arch Pharmacol. 2002; 365 17-21
- 115 Izbeki F, Wittmann T, Csati S. et al . The mechanisms of the inhibitory effect of ethanol on gastric emptying involve type A CCK receptors. Regul Pept. 2004; 117 101-105
- 116 Jian R, Cortot A, Ducrot F. et al . Effect of ethanol ingestion on postprandial gastric emptying and secretion, biliopancreatic secretions, and duodenal absorption in man. Dig Dis Sci. 1986; 31 604-614
- 117 Barboriak J J, Meade R C. Effect of alcohol on gastric emptying in man. Am J Clin Nutr. 1970; 23 1151-1153
- 118 Franke A, Nakchbandi I A, Schneider A. et al . The effect of ethanol and alcoholic beverages on gastric emptying of solid meals in humans. Alcohol Alcohol. 2004; In Press;
- 119 Keshavarzian A, Iber F L, Greer P. et al . Gastric emptying of solid meal in male chronic alcoholics. Alcohol Clin Exp Res. 1986; 10 432-435
- 120 Wegener M, Schaffstein J, Dilger U. et al . Gastrointestinal transit of solid-liquid meal in chronic alcoholics. Dig Dis Sci. 1991; 36 917-923
- 121 Crew K D, Neugut A I. Epidemiology of upper gastrointestinal malignancies. Semin Oncol. 2004; 31 450-464
- 122 Pollack E S, Nomura A M, Heilbrun L K. et al . Prospective study of alcohol consumption and cancer. N Engl J Med. 1984; 310 617-621
- 123 Jedrychowski W, Boeing H, Wahrendorf J. et al . Vodka consumption, tobacco smoking and risk of gastric cancer in Poland. Int J Epidemiol. 1993; 22 606-613
- 124 Falcao J M, Dias J A, Miranda A C. et al . Red wine consumption and gastric cancer in Portugal: a case-control study. Eur J Cancer Prev. 1994; 3 269-276
- 125 Boeing H. Epidemiological research in stomach cancer: progress over the last ten years. J Cancer Res Clin Oncol. 1991; 117 133-143
- 126 Niebergall-Roth E, Harder H, Singer M V. A review: acute and chronic effects of ethanol and alcoholic beverages on the pancreatic exocrine secretion in vivo and in vitro. Alcohol Clin Exp Res. 1998; 22 1570-1583
- 127 Demol P, Singer M V, Hotz J. et al . Action of intragastric ethanol on pancreatic exocrine secretion in relation to the interdigestive gastrointestinal motility in humans. Arch Int Physiol Biochim. 1986; 94 251-259
- 128 Demol P, Singer M V, Hotz J. et al . Different actions of intravenous ethanol on basal (= interdigestive) secretion of gastric acid, pancreatic enzymes and bile acids and gastrointestinal motility in man. Alcohol Alcohol. 1985; 20 19-26
- 129 Kölbel C B, Singer M V, Möhle T. et al . Action of intravenous ethanol and atropine on the secretion of gastric acid, pancreatic enzymes, and bile acids and the motility of the upper gastrointestinal tract in nonalcoholic humans. Pancreas. 1986; 1 211-218
- 130 Mott C, Sarles H, Tiscornia O. et al . Inhibitory action of alcohol on human exocrine pancreatic secretion. Am J Dig Dis. 1972; 17 902-910
- 131 Marin G A, Ward N L, Fischer R. Effect of ethanol on pancreatic and biliary secretions in humans. Am J Dig Dis. 1973; 18 825-833
- 132 Hajnal F, Flores M C, Valenzuela J E. Effect of alcohol and alcoholic beverages on nonstimulated pancreatic secretion in humans. Pancreas. 1989; 4 486-491
- 133 Chari S T, Harder H, Teyssen S. et al . Effect of beer, yeast-fermented glucose, and ethanol on pancreatic enzyme secretion in healthy human subjects. Dig Dis Sci. 1996; 41 1216-1224
- 134 Tiscornia O, Gullo L, Sarles H. The inhibition of canine exocrine pancreatic secretion by intravenous ethanol. Digestion. 1973; 9 231-240
- 135 Sarles H, Tiscornia O, Palasciano G. et al . Effects of chronic intragastric ethanol administration on canine exocrine pancreatic secretion. Scand J Gastroenterol. 1973; 8 85-96
- 136 Tachibana I, Okabayashi Y, Akiyama T. et al . Ethanol inhibits CCK-induced enzyme secretion by affecting calcium-pump activity in isolated rat pancreatic acini. Pancreas. 1996; 13 316-323
- 137 Planche N E, Palasciano G, Meullenet J. et al . Effects of intravenous alcohol on pancreatic and biliary secretion in man. Dig Dis Sci. 1982; 27 449-453
- 138 Rinderknecht H, Renner I G, Koyama H H. Lysosomal enzymes in pure pancreatic juice from normal healthy volunteers and chronic alcoholics. Dig Dis Sci. 1979; 24 180-186
- 139 Rinderknecht H, Renner I G, Carmack C. Trypsinogen variants in pancreatic juice of healthy volunteers, chronic alcoholics, and patients with pancreatitis and cancer of the pancreas. Gut. 1979; 20 886-891
- 140 Sahel J, Sarles H. Modifications of pure human pancreatic juice induced by chronic alcohol consumption. Dig Dis Sci. 1979; 24 897-905
- 141 Renner I G, Rinderknecht H, Valenzuela J E. et al . Studies of pure pancreatic secretions in chronic alcoholic subjects without pancreatic insufficiency. Scand J Gastroenterol. 1980; 15 241-244
- 142 Sarles H. Chronic calcifying pancreatitis-chronic alcoholic pancreatitis. Gastroenterology. 1974; 66 604-616
- 143 Sarles H, Laugier R. Alcoholic pancreatitis. Clin Gastroenterol. 1981; 10 401-415
- 144 Singh M. Effect of chronic ethanol feeding on pancreatic enzyme secretion in rats in vitro. Dig Dis Sci. 1983; 28 117-123
- 145 Schmidt D N, Sarles H, Devaux M A. Early increased pancreatic secretory capacity during alcohol adaptation in the dog. Scand J Gastroenterol. 1982; 17 49-55
- 146 Schmidt D N, Devaux M A, Biedzinski T M. et al . Disappearance of an inhibitory factor of exocrine pancreas secretion in chronic alcoholic dogs. Scand J Gastroenterol. 1982; 17 761-768
- 147 Schmidt D N, Devaux M A, Biedzinski T M. et al . Cholinergic stimulation and inhibition of pancreatic secretion in alcohol-adapted dogs. Scand J Gastroenterol. 1983; 18 425-431
- 148 Schmidt D N, Johnson C D, Devaux M A. et al . Vagal influence on exocrine pancreas of alcohol-fed and of normal dogs. Eur J Clin Invest. 1984; 14 111-115
- 149 Singer M V, Müller M K. Epidemiologie, Ätiologie und Pathogenese der chronischen Pankreatitis. Mössner JG, Adler G, Fölsch UR, Singer MV Erkrankungen des exkretorischen Pankreas Jena; Fischer-Verlag 1995: 313-324
- 150 Sarles H. The geographical distribution of chronic pancreatitis. Johnson CD, Imrie CW Pancreatic disease. Progress and prospects Heidelberg, New York; Springer-Verlag 1991: 177-184
- 151 Hanck C, Singer M V. Does acute alcoholic pancreatitis exist without preexisting chronic pancreatitis?. Scand J Gastroenterol. 1997; 32 625-626
- 152 Nordback I, Jaakkola M, Iovanna J L. et al . Increased serum pancreatitis associated protein (PAP) concentration after longterm alcohol consumption: further evidence for regular subclinical pancreatic damage after heavy drinking?. Gut. 1995; 36 117-120
- 153 Migliori M, Manca M, Santini D. et al . Does acute alcoholic pancreatitis precede the chronic form or is the opposite true? A histological study. J Clin Gastroenterol. 2004; 38 272-275
- 154 Etemad B, Whitcomb D C. Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology. 2001; 120 682-707
- 155 Hanck C, Schneider A, Whitcomb D C. Genetic polymorphisms in alcoholic pancreatitis. Best Pract Res Clin Gastroenterol. 2003; 17 613-623
- 156 Whitcomb D C. Genetic predisposition to alcoholic chronic pancreatitis. Pancreas. 2003; 27 321-326
- 157 Apte M V, Wilson J S. Alcohol-induced pancreatic injury. Best Pract Res Clin Gastroenterol. 2003; 17 593-612
- 158 Tierney S, Qian Z, Lipsett P A. et al . Ethanol inhibits sphincter of Oddi motility. J Gastrointest Surg. 1998; 2 356-362
- 159 Coelho J C, Moody F G, Senninger N. et al . Effects of gastrointestinal hormones on Oddi’s sphincter and duodenal myoelectric activity and pancreatobiliary pressure. Studies in the opossum. Arch Surg. 1985; 120 1060-1064
- 160 Becker J M, Sharp S W. Effect of alcohol on cyclical myoelectric activity of the opossum sphincter of Oddi. J Surg Res. 1985; 38 343-349
- 161 Sarles H. Alcoholism and pancreatitis. Scand J Gastroenterol. 1971; 6 193-198
- 162 Sarles H, Tiscornia O. Ethanol and chronic calcifying pancreatitis. Med Clin North Am. 1974; 58 1333-1346
- 163 Pandol S J, Periskic S, Gukovsky I. et al . Ethanol diet increases the sensitivity of rats to pancreatitis induced by cholecystokinin octapeptide. Gastroenterology. 1999; 117 706-716
- 164 Gukovsky I, Reyes C N, Vaquero E C. et al . Curcumin ameliorates ethanol and nonethanol experimental pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2003; 284 G85-95
- 165 Gukovskaya A S, Mouria M, Gukovsky I. et al . Ethanol metabolism and transcription factor activation in pancreatic acinar cells in rats. Gastroenterology. 2002; 122 106-118
- 166 Deng X, Wang L, Elm M S. et al . Chronic alcohol consumption accelerates fibrosis in response to cerulein-induced pancreatitis in rats. Am J Pathol. 2005; 166 93-106
- 167 Foitzik T, Hotz H G, Hot B. et al . Endothelin-1 mediates the alcohol-induced reduction of pancreatic capillary blood flow. J Gastrointest Surg. 1998; 2 379-384
- 168 Schilling M K, Redaelli C, Reber P U. et al . Microcirculation in chronic alcoholic pancreatitis: a laser Doppler flow study. Pancreas. 1999; 19 21-25
- 169 Harvey M H, Wedgwood K R, Austin J A. et al . Pancreatic duct pressure, duct permeability and acute pancreatitis. Br J Surg. 1989; 76 859-862
- 170 Wedgwood K R, Adler G, Kern H. et al . Effects of oral agents on pancreatic duct permeability. A model of acute alcoholic pancreatitis. Dig Dis Sci. 1986; 31 1081-1088
- 171 Shrikhande S V, Martignoni M E, Shrikhande M. et al . Comparison of histological features and inflammatory cell reaction in alcoholic, idiopathic and tropical chronic pancreatitis. Br J Surg. 2003; 90 1565-1572
- 172 Friess H, Büchler M W, Mueller C. et al . Immunopathogenesis of chronic pancreatitis. Gastroenterology. 1998; 115 1018-1022
- 173 Hunger R E, Mueller C, Z’Graggen K. et al . Cytotoxic cells are activated in cellular infiltrates of alcoholic chronic pancreatitis. Gastroenterology. 1997; 112 1656-1663
- 174 Hanck C, Rossol S, Böcker U. et al . Presence of plasma endotoxin is correlated with tumour necrosis factor receptor levels and disease activity in alcoholic cirrhosis. Alcohol Alcohol. 1998; 33 606-608
- 175 Hanck C, Rossol S, Singer M V. Immunological changes of mild acute pancreatitis in late-stage alcoholic chronic pancreatitis. Dig Dis Sci. 1999; 44 1768-1773
- 176 Pedersen N, Larsen S, Seidelin J B. et al . Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis. Scand J Gastroenterol. 2004; 39 277-282
- 177 Bachem M G, Schneider E, Gross H. et al . Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology. 1998; 115 421-432
- 178 Apte M V, Haber P S, Applegate T L. et al . Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture. Gut. 1998; 43 128-133
- 179 Mews P, Phillips P, Fahmy R. et al . Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis. Gut. 2002; 50 535-541
- 180 Apte M V, Wilson J S. Stellate cell activation in alcoholic pancreatitis. Pancreas. 2003; 27 316-320
- 181 Teich N, Mossner J, Keim V. Screening for mutations of the cationic trypsinogen gene: are they of relevance in chronic alcoholic pancreatitis?. Gut. 1999; 44 413-416
- 182 Monaghan K G, Jackson C E, KuKuruga D L. et al . Mutation analysis of the cystic fibrosis and cationic trypsinogen genes in patients with alcohol-related pancreatitis. Am J Med Genet. 2000; 94 120-124
- 183 Truninger K, Kock J, Wirth H P. et al . Trypsinogen gene mutations in patients with chronic or recurrent acute pancreatitis. Pancreas. 2001; 22 18-23
- 184 Threadgold J, Greenhalf W, Ellis I. et al . The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease. Gut. 2002; 50 675-681
- 185 Drenth J P, te Morsche R, Jansen J B. Mutations in serine protease inhibitor Kazal type 1 are strongly associated with chronic pancreatitis. Gut. 2002; 50 687-692
- 186 Schneider A, Pfützer R H, Barmada M M. et al . Limited contribution of the SPINK1 N34S mutation to the risk and severity of alcoholic chronic pancreatitis: a report from the United States. Dig Dis Sci. 2003; 48 1110-1115
- 187 Chari S T, Forßmann K, Singer M V. Alkohol und Pankreaskarzinom. Singer MV, Teyssen S Alkohol und Alkoholfolgekrankheiten. Grundlagen - Diagnostik - Therapie Heidelberg; Springer-Verlag 1999: 220-225
- 188 Lowenfels A B, Maisonneuve P, Cavallini G. et al . Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993; 328 1433-1437
- 189 Whitcomb D C, Pogue-Geile K. Pancreatitis as a risk for pancreatic cancer. Gastroenterol Clin North Am. 2002; 31 663-678
- 190 Zografos G N, Bean A G, Bowles M. et al . Chronic pancreatitis and neoplasia: correlation or coincidence. HPB Surg. 1997; 10 235-239
- 191 Talamini G, Falconi M, Bassi C. et al . Incidence of cancer in the course of chronic pancreatitis. Am J Gastroenterol. 1999; 94 1253-1260
- 192 Talamini G, Bassi C, Falconi M. et al . Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer. Dig Dis Sci. 1999; 44 1303-1311
Prof. Dr. med. Dr. h. c. M. V. Singer
II. Medizinische Universitätsklinik (Gastroenterologie/Hepatologie/Infektionskrankheiten), Fakultät für Klinische Medizin der Universität Heidelberg, Universitätsklinikum Mannheim
Theodor-Kutzer-Ufer 1-3
68135 Mannheim
Telefon: 06 21/3 83-32 84
Fax: 06 21/3 83-38 05
eMail: manfred.v.singer@med.ma.uni-heidelberg.de