Bielański, Władysław

Bobrzyński, Andrzej

Budzyński, Andrzej

Bęben, Piotr

Konturek, Stanisław

Płonka, Małgorzata

Medical Science Monitor

English

Jagiellonian Univeristy Repository

WWW.MEDSCI MONIT.COMClinical ResearchSignature: Med Sci Monit, 2002; 8(8): CR554-557PMID: 12165741CR554Incidence of complications of peptic ulcers in patientswith Helicobacter pylori (Hp) infection and/or NSAIDuse in the era of Hp eradicationAndrzej Bobrzyński1 b, Piotr Bęben1 b, Andrzej Budzyński1 b, Władysław Bielański2 b, Małgorzata Płonka2 c, Stanisław J. Konturek2 a1 2nd Department of Surgery, Jagiellonian University College of Medicine, Cracow, Poland2 Department of Clinical Physiology, Jagiellonian University College of Medicine, Cracow, PolandSummaryBackground: Hp and NSAID are considered as major pathogens in peptic ulcerations and their complica-tions but little is known about the incidence of ulcers and their complications following wide-spread use of Hp eradication. The aims of the study were: 1) to analyze incidence of ulcersand their complications, bleeding and perforations at time when the Hp eradication has beenused in ulcer therapy, and 2) to assess the impact of Hp infection and NSAID use on the inci-dence of ulcers and complications.Material/Methods: From 1996 to 2001, 381 patients with complications of peptic ulcers were admitted to theemergency surgery, including 273 patients with bleeding ulcers and 108 with perforations outof a sample of 6515 dyspeptic patients examined with upper endoscopy and 13C-urea breathtest (UBT).Results: The rate of ulcer bleeding and perforations, remained relatively constant throughout thestudy period. NSAID use in that group increased form 15.8% in 1999 to 19.4% in 2001. Theincidence of Hp in patients with complications assessed by UBT or CLO was 76.7%, while theincidence of Hp in 7920 patients ranged form 72.8% in 1996 to 53.8% in 2001. There were1940 (29.7%) patients with duodenal and/or gastric ulcer diagnosed by upper gastroscopy.The decline in the prevalence of peptic ulcer from about 44% to 8% occurred over the sametime. A slight increase in the number of ulcer resulting from NSAID use was observed so wasthe number of ulcers without Hp or NSAID (idiopathic).Conclusions: Despite decreased Hp prevalence, the incidence of ulcers complications remained unchangedprobably due to increased use of NSAID and the appearance of idiopathic ulcers.key words: Helicobacter pylori • non-steroidal anti-inflammatory drugs • gastric hemorrhage • perforation •idiopathic ulcersFull-text PDF: http://www.MedSciMonit.com/pub/vol_8/no_8/2918.pdfWord count: 1487Tables: —Figures: 3References: 16Received: 2001.12.09Accepted: 2002.06.06Published: 2002.08.07Author’s address: Prof Dr Stanisław J. Konturek, Department of Physiology, College of Medicine, Jagiellonian University, Grzegorzecka 16, 31-531 Cracow, PolandAuthors’ Contribution:A Study DesignB Data CollectionC Statistical AnalysisD Data InterpretationE Manuscript PreparationF Literature SearchG Funds CollectionCRCR555Med Sci Monit, 2002; 8(8): CR554-557 Bobrzyński A et al – Incidence of complications of peptic ulcers in patients…BACKGROUNDPeptic ulcer hemorrhage and perforation remainimportant emergency situations. Although the crucialrole of H. pylori infection in the pathogenesis of ulcerhas been generally accepted [1,2], its association withulcer complications is less clear. A strong argument forthe etiological role of H. pylori in ulcerogenesis is the factthat eradication of this germ prevents the ulcer recur-rence but it is less clear whether this therapy alsodecreases the ulcer complications such as hemorrhageand perforation [3–9]. Despite the marked progressover last 20 years in diagnosis and treatment of ulcerpatients, especially the widespread use of the Hp eradi-cation therapy, the mortality rate caused by hemor-rhage and perforation worldwide is relatively stable andaverages, respectively about 10 and 7% [3–5].The gross upper gastrointestinal bleeding is the mostcommon complication of peptic ulcer disease. Growingawareness of the role of H. pylori infection in theetiopathology of upper gastrointestinal diseases resultedin the major change in the treatment regimens and thewidespread use of its eradication also during the emer-gency bleeding [10].NSAID, similarly to H. pylori, also may cause damage tothe gastric mucosa and peptic ulcers. These ulcerogensindependently and significantly increase the risk of pep-tic ulcer and ulcer bleeding. H. pylori infection andNSAID seem to cause the majority of bleeding ulcersfrom gastrointestinal tract. Much controversy, however,surrounds the interaction of H. pylori infection and useof NSAID on gastro-duodenal mucosa [10–14]. Theseverity of dyspeptic symptoms appears worse in infec-ted drug users [14]. More ulcers were found in H. pyloripositive than H. pylori negative users of NSAID [12].The complex interaction between H. pylori and NSAIDimplies that it is over simplistic to conclude that theirrelationship is independent, synergistic or antagonisticwithout considering the influence of other factors [13]such as previous exposure to NSAID, a history of ulcercomplication, concurrent use of acid-suppressant thera-py, and the difference between gastrotoxicity of varioustypes of NSAID. Current evidence suggests that H.pylori may contribute to an increased risk of ulcer deve-lopment and its bleeding in patients who are about tostart NSAID treatment [14], whereas NSAID probablyaccount for the majority of ulcer disease in patients whoare already taking long-term NSAID [12]. Based on themeta-analysis of numerous clinical trials, it has beenconcluded that eradication of H. pylori infection reducesthe risk of ulcers for patients starting long-term NSAIDtreatment [12].The aim of this study was an attempt to analyze the inci-dence of complications of peptic ulcer disease such ashemorrhage and perforation, in the years 1996–2001 inlarge samples of dyspeptic patients who consecutivelyappeared in our H. pylori University Center for diagno-sis and treatment of dyspeptic symptoms. The questionhas been risen how these two ulcerogens – the H. pyloriand the NSAID have influenced the incidence of com-plications of peptic ulcer disease.MATERIAL AND METHODSAnalysis of emergency admissions for complication ofpeptic ulcer was carried out in the 2nd Department ofSurgery, College of Medicine of Jagiellonian University,Cracow between 1996 and 2001. Endoscopic and intra-operative findings were analyzed and data from patienthistory with special attention to NSAID use werereviewed. The prevalence of H. pylori infection amongin patients with bleeding was assessed by capsulatedmini-dose 13C-urea breath test (UBT), while in thosewith perforation, a biopsy sample of antral mucosa wastaken during open or laparoscopic surgery by rapidurease test using CLO test (Delta West Pty Ltd, Bentley,Australia).Concomitantly the data of the Institute of Physiology,Collegium Medicum of Jagiellonian University, Cracow,where UBT is routinely performed, were analyzed asdescribed before [15]. Among all dyspeptic patientsfrom that group incidence of peptic ulcer disease anduse of NSAID were assessed.During study period, 381 patients with complications ofpeptic ulcers were admitted to our Department ofSurgery and this encompasses 273 patients with bleed-ing ulcer and 108 patients with perforated ulcer. In thesame period, 7920 patients with dyspeptic symptomswere subjected to UBT. No side-effects following theupper endoscopy or swallowing the capsule with 13C-urea (38 mg/capsule) were recorded in our patients withulcer complication or in controls without complications.Out of these dyspeptic patients, 6515 were subjected toupper endoscopy and most of patients with ulcer com-plications originated from the dyspeptic patients withgastro-duodenal ulcerations. The study was approvedby the Jagiellonian University Ethical Research Commit-tee (KE/99/02/B/271).RESULTSThe ratio of women to men was like 1:2 in patients withbleeding gastric ulcer patients and this was similar tothat in non-bleeding gastric ulcer and in healthy con-trols.The rate of complications of peptic ulcer, namely bleed-ing and perforations, remained relatively constantthroughout the 6 yr study period (Fig. 1).The reported rate of NSAID use in that groupincreased form 15.8% in 1999 to 19.4% in 2001 yr. TheH. pylori prevalence in patients with complications ofpeptic ulcer assessed by UBT or CLO test was 76.7%and this was not significantly different from that detec-ted in non-bleeding gastric ulcer patients (75%) but sig-nificantly higher than that in control healthy subjects(60%).In 7920 of dyspeptic patients that underwent UBT theincidence of H. pylori infection decreased from 72.8% in1996 to 53.8% in 2001 (Fig. 2). Among 6515 of dyspep-tic patients who were submitted to upper endoscopythere were 1940 (29.7%) patients with gastric ulcerand/or duodenal ulcers. A significant decline in theprevalence of peptic ulcer was noted from 43.7% at1996 to only 7.7% at 2001 yr. At the same period aslight increase in the number of ulcers resulting fromthe NSAIDs use was observed (from 2.2% to 4.1%). Thenumber of ulcers without H. pylori and NSAID (idio-pathic ulcers) also increased especially at 2000 and 2001yr so the ratio of idiopathic ulcers to total number ofulcers significantly increased during this period (Fig. 3).DISCUSSIONThis study demonstrates that during last 6 years the H.pylori prevalence detected by UBT in Polish populationshows significant decrease from nearly 73% at 1996 to54% at 2001. Similarly the percent of dyspeptic patientswith peptic ulcerations also showed remarkable declinefrom 43.7% at 1996 to only 7.7% in 2001. At the sametime, the ratio of non-H. pylori, non-NSAID or idiopa-thic ulcers increased from about 20% at 1996 to about30% in 2000-2001.The significant fall in H. pylori prevalence in our popu-lation is closely and probably causally correlated withthe decline in the occurrence of peptic ulcerations [13]possibly due to the improvement of living standards andwidespread use of eradication of H. pylori in the treat-ment of peptic ulcerations.CR556Med Sci Monit, 2002; 8(8): CR554-557Clinical ResearchComplications of peptic ulcer020406080100n-of complicationsbleeding 52 58 38 31 49 45perforations 18 27 13 22 10 181996 1997 1998 1999 2000 2001Figure 1. Emergency admissions for complications of peptic ulcer(1999–2001).Figure 3. Occurrence of gastroduodenal ulcers in dyspeptic patients with endoscopy (1996–2001). Total N = 6515, total number of ulcers =1940.72,8 70,964,7 6555,5 53,8020406080Hp prevalence, [%]N  2060          1506          1507           1367          932           548 yr. 1996           1997          1998           1999         2000          2001 Figure 2. Prevalence of H. pylori infection detected by UBT in dyspep-tic patients (1996–2001). N = 7920The major finding of this report is that despite thedecline in the H. pylori prevalence in our society and theremarkable decline in the occurrence of peptic ulcera-tions during last 6 years, the rate of ulcer complicationssuch as hemorrhages and perforations recorded in theemergency surgery, serving for the south part ofPoland, was virtually unchanged during the same time.One of the possible reasons for the sustained rate ofupper gastrointestinal bleeding could be an increaseduse of NSAID available in this country without prescrip-tion and sold under various names without warning ofthe possible side-effects. Another explanation for therelatively high incidence of ulcer complications is thatthey may concern mostly non-H. pylori, non-NSAIDulcers (idiopathic), whose rate was found in this study toincrease during last 6 years. Similar rise in the rate ofidiopathic ulcerations was recently reported by Xia et al.[16] showing that about 14% among 1153 duodenalulcer patients had this type of ulcerations. Such ulcersmay represent serious problem due to ulcer complica-tions such as bleeding or perforation despite the lack ofH. pylori infection and NSAID use. Further studies areneeded to establish whether these idiopathic ulcerationstend to be accompanied by increased rate of complica-tions such as hemorrhage or perforation.The results of this study are at variance with the recentreport of Huang et al [12] based on meta-analysis of 16multicenter trials showing that; 1) the H. pylori infectionacts synergistically with NSAID in promoting gastro-duodenal ulcerations, and 2) that peptic ulcers do notdevelop in patients without H. pylori infection or NSAIDuse. Our finding that relatively large proportion ofulcer patients were neither infected with H. pylori norused NSAID militates against the notion of Huang et al.[12] and the reason for this discrepancy is not known.Furthermore, according to our results based on relative-ly large sample of ulcer patients (about 6000 patients)examined in one unit in Poland, the H. pylori infectionactually reduced the risk of NSAID-induced gastro-duo-denal ulcerations [13].CONCLUSIONSIn summary, this study provides first evidence in Polandthat both the H. pylori infection and peptic ulcerationsdecline in recent years, while the ulcer complicationssuch as hemorrhages and perforations remain at thesame level possibly due to increased use of NSAID andthe occurrence of idiopathic ulcers.REFERENCES:1. Marshall BJ: Helicobacter pylori. Am J Gastroenterol, 1994; 89:116-1282. Konturek PC, Bielanski W, Konturek SJ et al: Helicobacter pyloriassociated gastric pathology. J Physiol Pharmacol, 1999; 50: 211-2253. Elta GH: Approach to the patient with gross gastrointestinal bleed-ing. [In:] Textbook of Gastroenterology. Yamada T. eds, J B Lippi-cott Company, Philadelphia, 1995: 6714. Gilbert DA: Epidemiology of upper gastrointestinal bleeding. Gas-trointest Endosc, 1990; 36: 8-135. Richardson CT: Gastric ulcer. [In:] Gastrointestinal Disease. Patho-physiology, Diagnosis, Management. Sleisenger MH, Fordtran JS,eds, WB Saunders, 19896. Hopkins RJ, Girardi LS, Turney EA: Relationship between Heli-cobacter pylori eradication and reduced duodenal and gastric ulcerrecurrence: a review. Gastroenterology, 1996; 110: 12447 Graham DY, Hepps KS, Ramirez FC et al: Treatment of Helicobac-ter pylori reduces the rate of rebleeding in peptic ulcer disease.Scand J Gastroenterol, 1993; 28: 939-9428. Labenz J, Borsch G: Role of Helicobacter pylori eradication in theprevention of peptic ulcer bleeding relapse. Digestion, 1994; 55:19-239. Jaspersen D, Koerner T, Schorr W et al: Helicobacter pylori eradi-cation reduces the rate of rebleeding in ulcer hemorrhage. Gas-trointest Endosc, 1995; 41: 5-710. Winiarski M, Bielanski W, Plonka M et al: The usefulness of capsu-lated 13C-urea breath test in diagnosis of Helicobacter pylori inpatients with upper gastrointestinal bleeding. Dig Liver Dis, (inpress)11. Hawkey CJ, Tulassay Z, Szczepanski L et al: Randomized con-trolled trial of Helicobacter pylori eradivcation in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Heli-cobacter eradication for lesion prevention Lancet, 1998; 352: 1016-102112. Huang JQ, Sridhar S, Hunt RH: Role of Helicobacter pylori infec-tion and noin-steroidal anti-inflammatory drugs in peptic ulcer di-sease: a meta-analysis. Lancet, 2002; 359: 14-2213. Pawlik T, Konturek PC, Konturek JW et al: Impact of Helicobacterpylori and non-steroidal anti-inflammatory drugs on gastric ulcero-genesis in experimental animals and humans. Eur J Phramacol,2002 (in press)14. Chan FK, To KF, Wu JC et al: Eradication of Helicobacyter pyloriand risk of peptic ulcers in patients starting long-term treatmentwith non-steroidal anti-inflammatory drugs: a randomized trial.Lancet, 2002; 359: 3-415. Bielanski W, Konturek SJ: New approach to 13C-urea breath test:capsule-based modification with low-dose of 13C-urea in the diag-nosis of Helicobacter pylori infection. J Physiol Pharmacol, 1996:47(3): 545-55316. Xia HH, Wong BC, Wong KW et al: Clinical and endoscopic chara-cteristics of non-Helicobacter pylori, non-NSAID duodenal ulcers: a long term prospective study. Aliment Pharmacol Thert, 2001; 15:1875-1882CR557Med Sci Monit, 2002; 8(8): CR554-557 Bobrzyński A et al – Incidence of complications of peptic ulcers in patients…CR

Incidence of complications of peptic ulcers in patients with "Helicobacter pylori" (Hp) infection and/or NSAID use in the era of Hp eradication

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Incidence of complications of peptic ulcers in patients with "Helicobacter pylori" (Hp) infection and/or NSAID use in the era of Hp eradication

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