ESOPHAGEAL REFLUX DISEASE, PEPTIC ULCER AND HELICOBACTER PYLORI INFECTION – A PROSPECTIVE, CONTROLLED STUDY
Abstract
Background. A possible association of esophageal reflux disease with peptic ulcer, Helicobacter pylori infection or the results of eradication, has not been elucidated. It is an alarming fact that in developed countries the incidence of esophageal adenocarcinoma, which is associated with reflux disease, is increasing.
Aim. The aim of the study was to establish the prevalence of esophageal reflux disease after eradication of H. pylori infection in patients with hemorrhaging and nonhemorrhaging peptic ulcer of stomach or duodenum.
Patients and methods. Study was approved in 1998 by the Slovenian Medical Ethics Committee (No. 90/09/98). Prospective, controlled and randomized, carried out between 1998– 2000.The study included 80 patients (50 male and 30 female, av. age 57.5 years, SD ± 17.1, range 22–80 years) in which endoscopy confirmed hemorrhage from peptic ulcer of stomach or duodenum and HP infection. The control group was made up of 80 patients (50 male and 30 female, av. age 56.8 years, SD ± 16.8, range 19–80 years) with peptic ulcer of stomach or duodenum and H.pylori infection in the same period of time. In all cases the recommended drug combinations were used in the treatment of the infection: a proton pump inhibitor, omeprazol (4 weeks), and combination of antibiotics, claritromycin and metronidazole or with regard to the antibiogram (1 week). The therapeutic success was ascertained endoscopically four weeks after inclusion in the study. Infection eradication was confirmed by the rapid urease test and histologic investigation of the gastric mucosa. One year later, in the course of follow-up, in patients with endoscopic investigations, 24-hour pH-metry or fiberoptic spectrophotometric bilirubin determination, bilimetry, we tried to establish signs of esophageal reflux disease.
Results. Four weeks after inclusion in the study the success of infection eradication was 92.5% in the study group while in the control group reached 91.25%, p > 0.05. Endoscopic investigation performed one year after inclusion in the study revealed a recurrence of H. pylori infection in 4 patients (5%, 4/80) from the study group and in 5 (6.25%, 5/80) from the control group, p > 0.05. During endoscopy we confirmed esophagitis in 8 patients from the study group (8/76, 10.5%) and in 9 patients (9/75, 12%) from the control group, p > 0.05. The findings of the 24-hour pH-metry confirmed acid reflux in 11 patients (11/76, 14.4%) from the study group and in 10 patients (10/76, 13,1%) from the control group, p > 0.05. Fiberoptic spectrophotometric bilirubin determination showed alkaline reflux in 3 patients (3/76, 3.9%) from the study group and in one patient (1/75, 1.3%) from the control group, p > 0.05.
Conclusions. The results confirm that after eradication of H. pylori infection, esophageal reflux disease occurs significantly more often in patients with peptic ulcer of the duodenum as compared to those with peptic ulcer of the stomach. The development of complications is not affected by whether the peptic ulcer had manifested itself with complications or not.
Downloads
References
NIH Consensus conference. Helicobacter pylori in peptic ulcer disease. JAMA 1994; 272: 65–9.
Moran AP, O’Morain CA. Pathogenesis and host response in Helicobacter pylori infections. Bad Homburg: Normed Verlag, 1997: 1–262.
Malfertheiner P, Megraud F, O’Morain C et al. for the European Helicobacter pylori Study Group (EHPSG). Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. Eur J Gastroenterol Hepatol 1997; 9: 1–2.
Lee J, O’Morain CA. Consensus or confusion: a review of existing national guidelines and Helicobacter pylori related diseases. Eur J Gastroenterol Hepatol 1997; 9: 527–31.
Lam SK, Talley NJ. Helicobacter pylori consensus: Report of the 1997 Asia Pacific Consensus Conference on the management of Helicobacter pylori infection. J Gastroenterol Hepatol 1998; 13: 1–12.
Tepeš B, Križman I. Priporočila za zdravljenje okužbe z bakterijo Helicobacter pylori v Sloveniji. Zdrav Vestn 1998; 67: 159–62.
Križman I. Refluksni ezofagitis. Krka Med Farm 1996; 17: Suppl 1: 10–7.
Lee J, O’Morain C. Who should be treated for Helicobacter pylori infection? A review of consensus conferences and guidelines. Gastroenterology 1997; 113: Suppl 6: S99–106.
Labenz J, Malfertheiner P. Helicobacter pylori in gastro-oesophageal reflux disease: causal agent, independent or protective factor? Gut 1997; 41: 277–80.
Labenz J, Blum AL, Bayerdörfer E, Meining A, Stolte M, Börsch G. Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis. Gastroenterology 1997; 112: 1442–7.
Metz DC, Kroser JA. Helicobacter pylori and gastroesophageal reflux disease. Gastroenterol Clin North Am 1999; 28: 971–85.
Labenz J. Consequences of Helicobacter pylori cure in ulcer patients. Bailliere’s Clinical Gastroenterology 2000; 14: 133–45.
Malfertheiner P, Leodolter A, Peitz U. Cure of Helicobacter pylori – associated ulcer disease through eradication. Bailliere’s Clinical Gastroenterology 2000; 14: 119–32.
Barr M, Buckley M, O’Morain C. Review article: non-steroidal anti-inflammatory drugs and Helicobacter pylori. Aliment Pharmacol Ther 2000; 14: Suppl 3: 43–7.
Vigneri S, Termini R, Savarino V, Pace F. Review article: is Helicobacter pylori status relevant in the management of GORD? Aliment Pharmacol Ther 2000; 14: Suppl 3: 31–42.
McColl KE, Dickson A, El-Nujumi A, El-Omar E, Kelman A. Symptomatic benefit 1–3 years after H. pylori eradication in ulcer patients: impact of gastroesophageal reflux disease. Am J Gastroenterol 2000; 95: 101–5.
Tepeš B. Proučevanje sprememb pri ulkusnih bolnikih po eradikaciji bakterije Helicobacter pylori. Doktorska disertacija. Ljubljana: Univerza v Ljubljani, Medicinska fakulteta, 1997: 1–146.
Tepeš B, Gubina M, Kavčič B, Košutič D, Križman I, Ihan A. Prospektivna kontrolirana študija zdravljenja bolnikov s Helicobacter pylori pozitivno ulkusno boleznijo dvanajstnika. Zdrav Vestn 1995; 64: 687–91.
Lee JP, O’Morain CA. Different management for helicobacter positive and negative patients with gastroesophageal disease. Gut 1998; 43: Suppl 1: S14–20.
Vicari JJ, Peek RM, Falk GW et al. The seroprevalence of cag A – positive Helicobacter pylori in the spektrum of gastroesophageal reflux disease. Gastroenterology 1998; 115: 50–7.
Williams MP, Pounder RE. Helicobacter pylori: From the benign to the malignant. Am J Gastroenterol 1999; 94: Suppl S: S11–6.
Kuyvenhoven JP, Veenendal RA, Vandebroucke JP. Peptic ulcer bleeding: Interaction between non-steroidal antiinflammatory drugs, Helicobacter pylori infection and the ABO blood group system. Scand J Gastroenterol 1999; 34: 1082–6.
Fallone CA, Barkun AN, Friedman G et al. Is Helicobacter pylori eradication associated with gastroesophageal reflux disease? Am J Gastroenterol 2000; 95: 914–20.
Voutilainen M, Sipponen P, Mecklin JP, Juhola M, Farkkila M. Gastroesophageal reflux disease: prevalence, clinical, endoscopic and histopathological findings in 1,128 consecutive patients referred for endoscopy due to dyspeptic and reflux symptoms. Digestion 2000; 61: 6–13.
Fallone CA, Barkun AN, Gottke MU et al. Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases. Am J Gastroenterol 2000; 95: 659–69.
Goldstein NS, Karim R. Gastric cardia inflammation and intestinal metaplasia: associations with reflux esophagitis and Helicobacter pylori. Mod Pathol 1999; 12: 1017–24.
Kilgore SP, Ormsby AH, Gramlich TL et al. The gastric cardia: fact or fiction? Am J Gastroenterol 2000; 95: 921–4.
Skok P. How efficient is endoscopic injection sclerotherapy in peptic ulcer hemorrhage? Hepatogastroenterology 1997; 15: 861–5.
Skok P. The epidemiology of hemorrhage from the upper gastrointestinal tract in the mid-nineties – has anything changed? Hepatogastroenterology 1998; 24: 2228–33.
Skok P, Križman I, Skok M. Krvaveča peptična razjeda, nesteroidna protivnetna zdravila in okužba s Helicobacter pylori – prospektivna, kontrolirana, randomizirana raziskava. Zdrav Vestn 2002; 71: 357–62.
Santolaria S, Lanas A, Benito R et al. Helicobacter pylori infection is a protective factor for bleeding gastric ulcers but not for bleeding duodenal ulcers in NSAID user. Aliment Pharmacol Ther 1999; 13: 1511–8.
Kuyvenhoven JP, Veenendal RA, Vandebroucke JP. Peptic ulcer bleeding: Interaction between non-steroidal antiinflammatory drugs, Helicobacter pylori infection and the ABO blood group system. Scand J Gastroenterol 1999; 34: 1082–6.
Tepeš B. Primerjava dveh tritirnih antimikrobnih shem zdravljenja okužbe z bakterijo Helicobacter pylori. Zdrav Vestn 2000; 69: 505–8.
Schütze K, Hentschel E, Dragosics B et al. Helicobacter pylori reinfection with identical organism: transmission by the patients’ spouses. Gut 1995; 36: 831–3.
Skok P. Vpliv izkoreninjenja bakterije Helicobacter pylori na razvoj refluksne bolezni požiralnika pri bolnikih s krvavečo peptično razjedo. Doktorska disertacija. Ljubljana: Medicinska fakulteta, 2001: 1–115.
Di Mario, Dal Bo N, Salandin S et al. The appearance of GORD in patients with duodenal ulcer after eradication of Helicobacter pylori infection: a 4 year prospective study. Gastroenterology 1998; 114: A105–5.
Varanasi RV, Fantry GT, Wilson KT et al. Protective role of Helicobacter pylori infection in gastroesophageal reflux disease. Gastroenterology 1998; 114: A322–2.
Carlsson R, Bate C, Dent J et al. Does H. pylori infection influence the response to treatment with acid inhibition in patients with gastroesophageal reflux disease (GERD). Scand J Gastroenterol 1997; 32: Suppl 2: 56–6.
El-Serag HB, Sonnenberg A, Jamal A et al. Chronic corpus gastritis is protective against erosive esophagitis. Gastroenterology 1998; 114: A113–3.
Befrits R, Granstrom M, Rylander M et al. Helicobacter pylori in 205 consecutive endoscopy patients. Scand J Infect Dis 1993; 24: 185–91.
Ohara S, Sekine H, Iijima K et al. Gastric mucosal atrophy and prevalence of Helicobacter pylori in reflux esophagi tis of the elderly. Jpn J Gastroenterol 1996; 93: 235–9.
Haruma K, Mihara M, Kawaguchi H et al. Low prevalence of Helicobacter pylori infection in patients with reflux esophagitis. Gastroenterology 1996; 110: A130–0.
Tzathas C, Amperiadis P, Kourtessas D et al. The role of Helicobacter pylori infection in the development of reflux esophagitis. Gastroenterology 1998; 114: A314–4.
Boixeda D, Gisbert JP, Canton R et al. Is there any association between Helicobacter pylori infection and peptic esophagitis. Med Clin 1995; 105: 774–7.
Newton M, Bryan R, Burnham WR et al. Evaluation of Helicobacter pylori in reflux oesophagitis and Barrett’s oesophagus. Gut 1997; 40: 9–13.
Liston R, Pitt MA, Banerjee AK. Reflux esophagitis and Helicobacter pylori infection in elderly patients. Postgrad Med J 1996; 72: 221–3.
O’Connor HJ, Cunnane K. Helicobacter pylori and gastroesophageal reflux disease – a prospective study. Ir J Med Sci 1994; 163: 369–73.
Kuipers EJ, Lundell L, Klinkenberg-Knoll EC et al. Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. N Engl J Med 1996; 334: 1018–22.
Sekiguchi T, Shirota T, Horikoshi T et al. Helicobacter pylori infection and severity of reflux esophagitis. Gastroenterology 1996; 110: A755–5.
Cargill G, Atlan P, Tudor D et al. Association of Helicobacter pylori and reflux esophagitis in symptomatic children. Gastroenterology 1996; 106: A59–9.
Francual S, Lamy PH, Quintrec YL et al. Helicobacter pylori: Has it a part in the lesion of gastroesophageal reflux. J Infect Dis 1990; 162: 1414–4.
Grebenev AL. Helicobacter pylori and reflux esophagitis. Am J Gastroenterol 1994; 89: A1372–2.
Galimov O, Fyodorov S, Nurtdinov M et al. Helicobacter pylori in esophageal reflux. Gut 1996; 39: Suppl 3: A193–3.
Skok P, Križman I, Skok M. H. pylori eradication in bleeding peptic ulcer – a prospective, controlled study. Hepatogastroenterology 2001; 48: Suppl 1: 173–3.
Skok P, Križman I, Čeranič D, Skok M. Reflux disease and Helicobacter pylori eradication – a prospective, controlled study. Gut 2001; 49: Suppl III: 1147–7.
Skok P, Križman I, Skok M. Endoscopy, 24-hour pH-metry and bilimetry in reflux esophagitis – results of a prospective, controlled study. Gut 2002; 51: Suppl III: A230–0.
Kocijančič B, Ivanuša M. Gastroezofagealna refluksna bolezen pri odraslih. Zdrav Vestn 2000; 69: 531–6.
Pleterski G, Ivanuša M, Drinovec J, Mrhar A. Epidemiološka ocena pogostnosti gastroezofagealne refluksne bolezni za Slovenijo. Zdrav Vestn 2002; 71: 379–84.
The Author transfers to the Publisher (Zdravniški vestnik/Slovenian Medical Journal) all economic copyrights following form Article 22 of the Slovene Copyright and Related Rights Act (ZASP), including the right of reproduction, the right of distribution, the rental right, the right of public performance, the right of public transmission, the right of public communication by means of phonograms and videograms, the right of public presentation, the right of broadcasting, the right of rebroadcasting, the right of secondary broadcasting, the right of communication to the public, the right of transformation, the right of audiovisual adaptation and all other rights of the author according to ZASP.
The aforementioned rights are transferred non-exclusively, for an unlimited number of editions, for the term of the statutory
The Author can make use of his work himself or transfer subjective rights to others only after 3 months from date of first publishing in the journal Zdravniški vestnik/Slovenian Medical Journal.
The Publisher (Zdravniški vestnik/Slovenian Medical Journal) has the right to transfer the rights, acquired parties without explicit consent of the Author.
The Author consents that the Article be published under the Creative Commons BY-NC 4.0 (attribution-non-commercial) or comparable licence.
