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Perforated Peptic Ulcer in Estonia: Epidemiology, Risk Factors and Relations with Helicobacter Pylori

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Perforated Peptic Ulcer in Estonia: Epidemiology, Risk Factors and Relations with Helicobacter Pylori DISSERTATIONES MEDICINAE UNIVERSITATIS TARTUENSIS 80 PERFORATED PEPTIC ULCER IN ESTONIA: EPIDEMIOLOGY, RISK FACTORS AND RELATIONS WITH HELICOBACTER PYLORI TOOMAS SILLAKIVI TARTU 2003 DISSERTATIONES MEDICINAE UNIVERSITATIS TARTUENSIS 80 DISSERTATIONES MEDICINAE UNIVERSITATIS TARTUENSIS 80 PERFORATED PEPTIC ULCER IN ESTONIA: EPIDEMIOLOGY, RISK FACTORS AND RELATIONS WITH HELICOBACTER PYLORI TOOMAS SILLAKIVI TARTU UNIVERSITY PRESS Department of Surgery, University of Tartu, Tartu, Estonia The dissertation was accepted for commencement of the degree of Doctor of Medical Sciences on January 15, 2003 by the Council of the Faculty of Medi­ cine, University of Tartu Opponents: Rando Truve, Dr Med, Central Hospital of Western Tallinn Tamara Vorobjova, Dr Med, Institute of General and Molecular Biology, University of Tartu Commencement: March 26, 2003 The publication of this dissertation is granted by the University of Tartu © Toomas Sillakivi, 2003 Tartu Ülikooli Kirjastus Tiigi 78, Tartu 50410 Tellimus nr. 70 CONTENTS LIST OF ORIGINAL PUBLICATIONS THAT THE PRESENT THESIS IS BASED O N ................................................................................................... 7 ABBREVATIONS............................................................................................. 8 1. INTRODUCTION ......................................................................................... 9 2. REVIEW OF THE LITERATURE ............................................................ 11 2.1. Epidemiology of P P U .......................................................................... 11 2.2. Risk factors related to PPU development .......................................... 12 2.3. Treatment strategies in PPU and risk factors for mortality............. 13 2.4. H. pylori and P P U ................................................................................. 14 2.4.1. Prevalence of H. pylori infection in PPU patients ............... 15 2.4.2. H. pylori genotypes................................................................... 15 2.4.3. Eradication of H. pylori ........................................................... 17 2.4.4. Failure of H. pylori eradication............................................... 18 3. AIMS OF THE STUDY ............................................................................... 20 4. PATIENTS AND M ETHODS..................................................................... 21 4.1. Subjects................................................................................................. 21 4.1.1. Retrospective study of the epidemiology of PPU in Tartu county in 1981-2000 ............................................................... 22 4.1.2. Retrospective study evaluating the risk factors for morta­ lity in perforated peptic ulcer patients in Tartu county in 1978-97 ..................................................................................... 23 4.1.3. Multicentral international prospective studies in 1994-96 (MEDWIS A 70, Germany) and in 1997 (Copernicus AAP 555, East Europe). Comparison of East European and Ger­ man PPU patients, evaluation of the risk factors for comp­ lications and mortality ............................................................. 23 4.1.4. Prospective study conducted at Tartu University Clinic in 1997-1999: possible reasons for high PPU incidence in Estonian patients, H. pylori strains and postoperative era­ dication therapy in PPU patients............................................. 24 4.1.5. Prospective study conducted Tartu University in 1995— 2000: H. pylori in patients with different gastric diseases ... 24 4.2. Definitions and terminology: PPU, classification of ulcer loca­ tions, ulcerogenic drugs, operations and mortality ......................... 24 4.3. Determination of H. pylori infection in the gastric mucosa........... 25 4.3.1. Use of histological method ...................................................... 25 4.3.2. Use of PCR method .................................................................. 25 4.4.Eradication regimens for H. p ylo ri...................................................... 26 4.5.Statistical analysis ................................................................................. 27 2 5 5. RESULTS .............................................................................................................28 5.1. Epidemilogy of PPU in Tartu county in 1981-2000.............................28 5.2. Comparison of East European and German PPU patients: epide­ miology, treatment strategies and outcome...................................... ......28 5.3. Evaluation of risk factors for complications and mortality in PPU patients .................................................................................................. ......29 5.4. Characteristics of PPU patients in a prospective study, possible reasons for high PPU incidence in Estonian patients............................30 5.5. H. pylori in PPU patients ..........................................................................31 5.5.1. H. pylori infection rates in PPU patients .....................................31 5.5.2. Evaluation of different H. pylori strains in Estonian and Russian patients ........................................................................ ......31 5.5.3. Results of H. pylori eradication in PPU patients ................. ......32 5.6. H. pylori in patients with different gastric diseases: perforated peptic ulcer, peptic ulcer disease and chronic gastritis .........................32 6. DISCUSSION.....................................................................................................34 6.1. Epidemiology of PPU in Tartu county in 1981-2000 ...........................34 6.2. Comparison of East European and German PPU patients: epi­ demiology, treatment strategies and outcom e........................................35 6.3. Evaluation of the risk factors for complications and mortality in PPU patients................................................................................................37 6.4. Characteristics of PPU patients in a prospective study: possible reasons for high PPU incidence in the patients......................................38 6.5. H. pylori in PPU patients ..........................................................................40 6.5.1. Evaluation of different H. pylori strains in Estonian and Russian PPU patients............................................................... ......40 6.5.2. Results of H. pylori eradication in PPU patients ................. ......42 6.6. H. pylori in patients with different gastric diseases: perforated peptic ulcer, uncomplicated peptic ulcer disease and chronic gastritis.................................................................................................. ......43 7. CONCLUSIONS .................................................................................................44 8. REFERENCES ....................................................................................................45 SUMMARY IN ESTONIAN .......................................................................... ......56 ACKNOWLEDGEMENTS....................................................................................60 PUBLICATIONS............................................................................................... ......61 6 LIST OF ORIGINAL PUBLICATIONS THAT THE PRESENT THESIS IS BASED ON I Sillakivi T, Lang A, Soplepmann J, Tein A, Peetsalu A. Incidence of perforated peptic ulcer correlated with suicide rate in Estonia in 1981- 2000. Proceedings of the Eurosurgery 2002. Monduzzi Editore. Lisbon (Portugal), June 5-7, 2002: 199-204. II Sillakivi T, Lang A, Tein A, Peetsalu A. Evaluation of risk factors for mortality in surgically treated perforated peptic ulcer. Hepato-Gastro- enterol 2000; 47: 1765-1768. III Sillakivi T, Yang Q, Peetsalu A, Ohmann C. Perforated peptic ulcer: Is there a difference between Eastern Europe and Germany? Langenbeck’s Arch Surg 2000; 385: 344-349. IV Sillakivi T, Aro H, Ustav M, Peetsalu M, Peetsalu A, Mikelsaar M. Diversity of Helicobacter pylori genotypes among Estonian and Russian patients with perforated peptic ulcer, living in Southern Estonia. FEMS Microbiol Letters 2001; 195: 29-33. V Sillakivi T, Peetsalu M, Mikelsaar M, Peetsalu A. An Attempt for Helico­ bacter pylori Eradication with Intravenous Clarithromycin in Perforated Peptic Ulcer Patients. Scand J Gastroenterol 2001; 36: 1119-1120. VI Andreson H, Lõivukene К, Sillakivi T, Maaroos H-I, Ustav M, Peetsalu A, Mikelsaar M. Association of cagA and vac A genotypes of Helico­ bacter pylori with gastric diseases in Estonia. J Clin Microbiol 2002; 40: 298-300. VII Sillakivi T, Peetsalu A. Perforeerunud peptilise haavandi riskifaktorid. Eesti Arst 2000; 12: 718-722. VIII Sillakivi T, Peetsalu M, Mikelsaar M, Peetsalu A. Helicobacter pylori eradikatsioon perforeerunud peptilise haavandiga haigetel. Eesti Arst 2001; 1: 8- 11. 7 ABBREVATIONS PPU perforated peptic ulcer DU duodenal ulcer GU gastric ulcer PUD peptic ulcer disease CG chronic gastritis H. pylori Helicobacter pylori N SA ® Nonsteroidal Antiinflammatory Drugs PCR Polymerase Chain Reaction vacA vacuolating cytotoxin gene A cagA cytotoxin associated gene A PPI proton pump inhibitor CI confidence interval OR Odds ratio 1. INTRODUCTION Peptic ulcer is naturally a chronic disease with frequent exacerbations which can last 20-30 years (Penston, 1990). The pathology of gastric ulcer was first described by Creuveilhier in 1835 (Creuveilhier,
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