ORIGINAL PAPERS DOROTA WAŚKO CZOPNIK, ELŻBIETA PONIEWIERKA. Abstract. Streszczenie

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1 ORIGINAL PAPERS Adv Clin Exp Med 2004, 13, 5, ISSN X DOROTA WAŚKO CZOPNIK, ELŻBIETA PONIEWIERKA Influence of Eradication of Helicobacter pylori Infection on Lower Esophageal Sphincter Pressure and Esophageal Corpus Manometry in Patients with Gastroesophageal Reflux Disease (GERD) Wpływ eradykacji Helicobacter pylori na ciśnienie dolnego zwieracza przełyku i motorykę trzonu przełyku u osób chorych na chorobę refluksową przełyku (GERD) Department of Gastroenterology and Hepatology, Wroclaw Medical University, Poland Abstract Background. The latest data show that H. pylori in pangastritis type infection have a beneficial influence on cour se of GERD but only antrum infection provokes GERD. Objectives. The aim of the study was to estimate the influence of H. pylori eradication on LESP and esophageal motor activity and intensity of GERD symptoms. Material and Methods. The authors examined 20 patients with GERD and H. pylori positive tests. Each patient underwent endoscopy of upper gastrointestinal tract, ph metry and manometry of esophagus and was treated with the PPI, amoxicillin and clarythromycin. After successful eradication manometry and ph metry were repeated. Pa tients were divided into 2 groups depending on infection localization: A pangastritis, B in antrum. Results. After eradication in group A significant decrease LESP was confirmed (p < 0.05) and motor activity of esophageal corpus worsened. ph metry showed increase GERD. In group B after eradication slight increase LESP was shown (p < 0.05) without influence on esophageal corpus motor activity. Patients felt better than before treat ment. In endoscopy of GI tract observed: in group A: in 3 cases (33.3%) oesophagitis, 6 (66.7%) chronic ga stritis; in group B: 1 (11.1%) oesophagitis, in 10 (88.9%) chronic gastritis. Conclusions. Obtained results show that changes of LESP after H. pylori eradication depend on the localization of infection. In patients with pangastritis H. pylori infection has protective influence and efficacious eradication may intensify GERD symptoms. Effective antrum infection treatment is beneficial in course of GERD and is connected with increased LESP after eradication (Adv Clin Exp Med 2004, 13, 5, ). Key words: gastroesophageal reflux disease, Helicobacter pylori, lower esophageal sphincter pressure, motoric activity of esophagus. Streszczenie Wprowadzenie. Ukazały się doniesienia, że zakażenie Helicobacter pylori typu pangastritis korzystnie wpływa na przebieg GERD, a obecność infekcji tylko w okolicy przedodźwiernikowej sprzyja wystąpieniu choroby. Cel pracy. Ocena wpływu eradykacji H. pylori na LESP i motorykę trzonu przełyku oraz nasilenie GERD u osób z chorobą refluksową. Materiał i metody. Badaniem objęto 20 osób chorych na GERD i potwierdzonym zakażeniem H. pylori. Każdy badany miał wykonaną endoskopię górnego odcinka przewodu pokarmowego, ocenę ph i manometrię przełyku oraz był leczony za pomocą amoksycyliny i klarytromycyny. Po leczeniu ponownie wykonano manometrię i okre ślono ph. Chorych podzielono na 2 grupy w zależności od lokalizacji zakażenia: A pangastritis, B w antrum. Wyniki. Po eradykacji u chorych z grupie A stwierdzono znaczny spadek LESP (p < 0,05) i pogorszenie motory ki trzonu, co korelowało z nasileniem GERD. W grupie B po eradykacji wykazano nieznaczny wzrost LESP (p < < 0,05) bez wpływu na motorykę trzonu przełyku i poprawę samopoczucia. W badaniu endoskopowym stwierdzo no w grupie A: u 3 osób (33,3%) zapalenie przełyku, u 6 (66,7%) gastritis chronica, w grupie B: u 1 osoby (11,1%) zapalenie przełyku, u 10 osób (88,9%) gastritis chronica.

2 750 D. WAŚKO CZOPNIK, E. PONIEWIERKA Wnioski. Na podstawie uzyskanych wyników badań można stwierdzić, że zmiany napięcia dolnego zwieracza przełyku po eradykacji H. pylori zależą od lokalizacji zakażenia. U chorych z zakażeniem typu pangastritis infek cja H. pylori wykazuje charakter protekcyjny, a skuteczna eradykacja może w tym przypadku nasilać GERD, in fekcja natomiast okolicy antrum u chorych z GERD ma korzystny wpływ na przebieg choroby, co wiąże się ze wzrostem LESP po eradykacji (Adv Clin Exp Med 2004, 13, 5, ). Słowa kluczowe: choroba refluksowa przełyku, Helicobacter pylori, ciśnienie dolnego zwieracza przełyku, moto ryka trzonu. One of the problems raised and discussed re cently is the role of H. pylori infection in gastroe sophageal reflux disease (GERD) and its influence on the course of the disease. There have been some references showing that the patients with GERD without endoscopic changes in esophagus develop the inflammation that affects entire gastric mucosa (pangastritis) more often than the patients with GERD concomitant to esophagitis [1 4]. It is esti mated that H. pylori infection involving the whole stomach (pangastritis) plays a beneficial role in the course of GERD, probably because of increase lo wer esophageal sphincter (LES) pressure. More over, it has also an effect on decrease stomach se crection connected with atrophic gastritis. This in flammation is caused by bacterial infection and neutralizing effect of the ammonium ions, which are the products of urea degradation by bacterial urease. The effective eradication in these patients may lead to the onset of reflux disease or enforce the symptoms of existing GERD [5 7]. The simi lar effect occurs in patients with duodenal ulcera tive disease treated for the H. pylori infection. Ef fective eradication provoked development of GERD symptoms in these patients [8]. It is also claimed that the H. pylori infection affecting the antrum only contributes to the GERD symptoms development through: LES pressure decrease, role of cytotoxins and prostaglandins, role of nitrogen oxide, increase in gastric secretion, decrease in stomach dumping. Eradication in these cases may have a beneficial role on GERD course [1 4, 7, 9]. There have been some clinical studies based on the observation of the patiens who underwent successful eradication of H. pylori. In these pa tients successful treatment of the infection inten sified symptoms of the disease, which suggested a larger dose of proton pump inhibitors (PPI) to be administered [10, 11, 13]. Even though the exact mechanism of this phenomenon is still unknown, it is implied that few factors may be significant. These are: lowering of stomach secretion (with subsequent ph of gastric contents increase) caused by inflammatory and atrophic changes in stomach corpus which are provoked by chronic H. pylori infection, and ammonia production du ring the infection and intensification of alkaline duodenal reflux. Gastrin also plays a significant role in LES pressure raise. The concentration of gastrin incre ases during chronic PPI treatment. It was also no ticed that the gastrin release in patients with H. py lori infection is higher than in those without infec tion symptoms [12, 14] and successful eradication may diminish parietal cells damage and increase the number of proton pumps in single parietal cell. Thus, the GERD symptoms worsen and positive therapeutic effect requires increased PPI admini stration [3, 12]. The aim of the study was to assess the influence of the H. pylori eradication on LES pressure and esophageal corpus motoric activity as well as to estimate the changes of esophageal ph in 24 hour ph manometry in patients with GERD. The obtai ned results were compared to the control group, namely patients with GERD and without H. pylori infection. Material and Methods The research included 40 persons divided into two groups: I. Study group 20 persons, with present GERD and H. pylori infection. GERD was con firmed in physical examination and 24 hour eso phageal ph metry II. Control group 20 persons, with GERD without H. pylori infection diagnosed in physical examination and ph metry. Symptoms reported in anamnesis were taken under consideration, especially: pyrosis, sense of retrosternal burning and epigastric pain, implying diagnosis of reflux disease. H. pylori infection was assessed on the base of urease test, bacterial cul ture and histopathological examination of biopsy specimens taken from antrum and stomach corpus at endoscopy of the upper part of gastrointestinal tract. The infection was diagnosed with the use of rapid urease test by Food and Nutrition Institute in Warsaw. Patients with confirmed presence of H. pylori infection underwent eradication accord ing to the standard of three component therapy including PPI, clarythromycin and amoxycyllin. 24 hour esophageal ph metry and manometry of the esophagus including LES pressure and corpus

3 Eradication of Helicobacter Pylori in Patients with Gastroesophageal Reflux Disease 751 motor activity assessment was done in these pa tients before and after treatment. Follow up exa mination was performed 6 weeks after eradication. In endoscopy of upper part of gastrointestinal tract the assessment of degree of esophagus inflamma tion according to Savary Miller scale was made. Esophageal manometry was completed using four channel water perfusion catheter connected to the Poliphysiograph PC and computer with pro per software (Polygraph Upper GI Tract). In each patient LES pressure was measured three times. The LES pressure was normal when ranging be tween mm Hg, LES value from mm Hg pointed to moderate hypotony and decreased LES pressure was estimated when below 10 mm Hg. For ph metry, two lead antimony probes connected to Digitrapper Mark III recorder were used. The pro be was placed 5 and 15 cm above LES localized previously during esophageal manometry. Results were interpreted using computer and Polygram Word program. Four parameters were taken under consideration measured independently 5 and 15 cm above LES in ph metry: total number of acid re fluxes, time of the longest acid reflux, total ph > 4 time, demeester s index. The values mentioned above were referred to the total number of all ph metries in two examined groups. Persons included the control group (with negative results of H. pylori infection test) also underwent endoscopy of upper part of gastrointe stinal tract, esophageal manometry and ph metry. Results 20 persons with confirmed GERD and H. pylo ri infection were included to the study group: 10 ma les and 10 females aged 29 64, mean age On the basis of obtained results the study group was di vided into two subgroups. A) Patients with confirmed infection affecting the whole stomach (antrum and corpus) 9 pa tients. B) Patients with confirmed infection affecting only antrum without infection in the corpus 11 patients. In the subgroup A, in three cases (33% of the total patients) esophagitis of I degree according to Savary Miller s scale with concomitant chronic gastritis was found during endoscopy. In the remain ing part (6 patients 66%) only the presence of chronic gastritis without any changes in esophagus was stated. In the subgroup A, the esophageal manometry before eradication showed LES pressure values ran ging mm Hg (mean mm Hg). Among these, in six persons LES pressure was nor mal ( mm Hg, mean mm Hg) and there were no cases of esophagitis in endoscopy. In three cases, moderate hypotony of LES ( mm Hg, mean mm Hg) was stated and these patients presented esophagitis in gastroscopy. As far as peristalsis of esophageal corpus is concer ned, in subgroup A 8 cases (90%) showed normal peristalsis and one person presented nonspecific motoric activity disorders. After eradication, LES pressure values ranged mm Hg (mean mm Hg). In three cases (33.3%) LES pressure remained within nor mal range ( mm Hg, mean 22.2 mm Hg). 6 patients (67%) had decreased pressure, 4 patients from these had moderate LES hypotony ( mm Hg, mean mm Hg), in two cases LES pressure was significantly lowered (5 and 9.63 mm Hg, mean 7.31). Mean LES pres sure values in these group was mm Hg. 4 persons (44.5%) showed normal primary peri stalsis in esophageal corpus and 5 cases (55%) presented non specific motoric activity disorders. Statistical calculations were based on t Student test. These showed that mean LES pressure before treatment is statistically higher than the appropriate values after H. pylori infection treatment (p < 0.05) in persons with pangastritis. It explains the intensi fication of GERD symptoms in patients after eradi cation. Figure 1 shows the value of LES pressure in group with pangastritis type infection. 8 persons (88.8%) after eradication complained on heartburn, pyrosis and epigastric pain. ph me try results in these patients in comparison to ph metry before treatment were worse. Only one per son reported general feeling improvement and symptoms remission, which was parallel to ph pressure (mm Hg) ciśnienie (mm Hg) patient pacjent before eradication after eradication przed eradykacją po eradykacji Fig. 1. LES pressure before and after eradication in patients with pangastritis type infection Ryc. 1. Ciśnienie dolnego zwieracza przełyku przed i po eradykacji w grupie osób z zakażeniem typu pan gastritis

4 752 D. WAŚKO CZOPNIK, E. PONIEWIERKA Table 1. Mean ph metry values in patients with GERD and pangastritis before eradication Tabela 1. Średnie wartości wskaźników ph metrii u pa cjentów chorych na GERD i pangastritis przed eradykacją Total number of refluxes (Całkowita liczba refluksów) (22.27) (31.42) Time of longest reflux event (Czas trwania najdłuższego (4.9) (8.97) reluksu) Total ph < 4 time (Całkowity czas PH < 4) (1.15) (2.73) DeMeester s index (Wskaźnik DeMeestera) (4.4) (8.94) Table 2. Mean ph metry values in patients with GERD and pangastritis after eradication Tabela 2. Średnie wartości wskaźników ph metrii u pa cjentów chorych na GERD i pangastritis po eradykacji Total number of refluxes (Całkowita liczba refluksów) (42.28) (79.71) Time of longest reflux event (Czas trwania najdłuższego (2.89) (11.8) Total ph < 4 time (Całkowity czas PH < 4) (2.04) (5.4) DeMeester s index (Wskaźnik DeMeestera) (8.06) (41.18) metry results improvement and significant LES pressure increase. In patients with H. pylori infection affecting the whole stomach before eradication, ph metry presented results which mean values are enclosed in table 1 (Tab. 1), whereas Table 2 presents mean parameters of 24 hour assessment of ph metry after eradication (Tab. 2). In the group of H. pylo ri infection in the antrum and no infection in sto mach corpus (group B) 10 persons (91%) reported relief of ailments after eradication. Only one per son complained of symptoms like: pyrosis, chest pain, regurgitations and meteorismus. These per sons presented normal LES pressure (20.75 mm Hg before eradication and mm Hg after treat ment), whereas ph metry results after eradication showed significant increase in the number of pa thologic acid reflux to the esophagus. During endoscopy of upper gastrointestinal tract in this group one case of esophagitis of I de gree in Savary Miller scale was found, other exa mined patients showed only chronic gastritis with out any esophageal mucosa changes. In the manometry examination before H. pylori eradication 6 persons (64.5%) presented normal LES pressure ( mm Hg; mean mm Hg), and in 5 cases (45.5%) moderate LES hypotony ( mm Hg; mean mm Hg) was stated. Mean LES pressure value in this group was mm Hg. As far as esophageal corpus is concerned 8 cases (82%) presented normal primary peristalsis, while 2 persons showed non specific motoric activi ty disorders. Figure 2 shows the value of LES pres sure in patients with H. pylori infection in antrum. All the patients in this group presented slight ly increase in LES pressure (p < 0.05) after eradi cation, while mean values of LES pressure were higher then before therapy. However, in 8 cases (73%) the values were normal ( mm Hg; mean mm Hg) and in three persons (27%) moderate LES hypotony ( mm Hg; mean 16.8 mm Hg) was stated. Mean LES pressure va lues in this group of patients was mm Hg. As far as esophageal corpus is concerned 9 pa tients (82%) presented normal primary peristalsis, meanwhile 2 persons showed non specific motoric activity disorders. ph metry results before eradi cation are placed in Table 3, while after H. pylori infection treatment in Table 4. Improvement of ph metry records in this group was connected with subjective decrease in GERD symptoms in tensity in examined patients. 20 persons were assessed in the control group (12 males and 8 females aged 25 73; mean 50.05). pressure (mm Hg) ciśnienie (mm Hg) before treatment przed leczeniem after treatment po leczeniu patient pacjent Fig. 2. LES pressure before and after eradication in patients with H. pylori in antrum infection Ryc. 2. Ciśnienie dolnego zwieracza przełyku przed i po eradykacji u pacjentów z H. pylori tylko w antrum

5 Eradication of Helicobacter Pylori in Patients with Gastroesophageal Reflux Disease 753 In the endoscopic examination of the upper part of gastrointestinal tract in 8 persons (40%) esophagitis was found: 6 persons had esophagitis of I degree in Savary Miller scale with concomitant chronic gasti tis, in two persons erosions of esophagus (III degree) were stated. Remaining 12 persons (60%) of the control group did not present any changes in esopha geal and gastric mucosa. The specimens from antrum and corpus of sto mach were taken during gastroscopy. The material was tested using urease test, bacterial cultures and histopathological examination towards H. pylori infection. In all the tests in this group no H. pylori infection was determined. In manometric examination LES pressure valu es ranged between 5.9 and 35.4 mm Hg; mean Table 3. Mean ph metry values in patients with GERD and H. pylori infection in antrum before eradication Tabela 3. Średnie wartości parametrów ph metrii u pa cjentów chorych na GERD i zakażeniem H. pylori w an trum przed eradykacją Total number of refluxes (Całkowita liczba refluksów) (105.08) (67.72) Time of longest reflux event (Czas trwania najdłuższego (6.38) (14.59) Total ph > 4 time (Całkowity czas PH < 4) (7.16) (10.44) DeMeester s index (Wskaźnik DeMeestera) (27.25) (37.06) Table 4. Mean ph metry values in patients with GERD and H. pylori infection in antrum after eradication Tabela 4. Średnie wartości parametrów ph metrii u pa cjentów chorych na GERD i zakażeniem H. pylori w an trum po eradykacji Total number of refluxes (Całkowita liczba refluksów) (76.9) (75.37) Time of longest reflux event (Czas trwania najdłuższego (7.31) (9.32) Total ph > 4 time ,76 (Całkowity czas PH < 4) (5.93) (7.36) DeMeester s index ,17 (Wskaźnik DeMeestera) (9.24) (16.86) 19.3 mm Hg. 50% of this group presented normal LES pressure ( mm Hg; mean mm Hg); in 8 persons (40%) moderate LES hypotony (13,4 18,3 mm Hg; mean mm Hg) and in two persons (10%) lowered LES values (5 and 9 mm Hg; mean 7.29 mm Hg). As far as eso phageal corpus is concerned 11 patients (55%) pre sented normal primary peristalsis, while 9 persons (45%) showed non specific motoric activity disor ders. Motoric activity disorders occurred in two pa tients with lowered LES pressure values, in three pa tients with moderate hypotony and three with nor mal LES pressure. Table 5 contains mean values of 24 hour ph metry examination in this group. Table 6 arranges all the results of manometric examinations in stu dy group compared to control group before and after eradication. Discussion Achieved results agree with available refe rences in worldwide literature, confirming the in fluence of effective H. pylori eradication and in fluence on esophageal corpus motoric activity and lower esophageal sphincter pressure. In presented study it was shown that patients with pangastritis type infection develop decrease in LES pressure and more frequent occurrence of motoric activity disorders after eradication, while slight increase in LES pressure was observed in patients with infection in antrum [3, 5, 8]. Esopha geal motoric activity in these patients remained unchanged before and after eradication. Patients from the group with pangastritis showed intensification of GERD symptoms in ph Tabela 5. Średnie wartości parametrów ph metrii u pa cjentów chorych na GERD bez zakażenia H. pylori Table 5. Mean ph metry values in H. pylori negative pa tients with GERD Total number of refluxes (Całkowita liczba refluksów) (39.47) (64.65) Time of longest reflux event (Czas trwania najdłuższego (5.82) (18.13) Total ph > 4 time (Całkowity czas PH < 4) (2.33) (6.14) DeMeester s index (Wskaźnik DeMeestera) (4.9) (23.9)

6 754 D. WAŚKO CZOPNIK, E. PONIEWIERKA Table 6. Manometry results in study group before and after eradication and in control group (mean values arrangement) Tabela 6. Wyniki badania manometrycznego przełyku przed i po eradykacji w grupie badanej i kontrolnej (wartości średnie) Study group Control group (Grupa badana) (Grupa kontrolna) SD pangastritis antrum before eradication after eradication before eradication after eradication (przed eradykacją) (po eradykacji) (przed eradykacją) (po eradykacji) LES (mm Hg) (6.7) (6.14) (5.59) (6.4) (7.66) Corpus 8 normal 4 normal 9 normal 9 normal 11 normal (Trzon) 1 NSMAD 5 NSMAD 2 NSMAD 2 NSMAD 9 NSMAD NSMAD non specific motoric activity disorder. NSMAD nieswoiste zaburzenia motoryki. metry in the form of increase all the ph metry re sults needed for reflux disease diagnosis. The au thors suggest that it may be connected with lowe ring in LES pressure and enhancing of disease symptoms in the study group. In the study group with H. pylori infection in an trum the authors observed minor increase in LES pressure and normal primary motoric activity after the therapy. 24 hour ph metry findings indicate the improvement of basic values, which is confirmed by decrease in subjective general feeling of the patient. Achieved data correspond with Labenz obse rvations [3] who on the basis of available literature suggests that there are many possible mechanisms which may influence on relations between the pre sence and localization of H. pylori infection and intensification of reflux disease. It was also stated that in patients with GERD infection occurs in an trum which is probably connected with the greater exposure to the acidic content of the stomach. In flammation of stomach mucosa due to H. pylori contributes to the secretion of many mediators, cy tokines and nitric oxide, which may affect the LES pressure and in the same time provoke GERD. H. pylori stimulates increased synthesis of prosta glandins, which in connection with inflammation mediators may affect efferent nerve endings of va gus nerve and thus decrease LES pressure and above all provoke transient LES relaxations, which incline esophageal reflux. Labenz [3, 8], ba sing on his own observations, found that patients with pangastritis type infection and GERD deve lop esophagitis scarcely which was frequently re ported after successful eradication of H. pylori. Among described patients with H. pylori infection affecting the whole stomach the authors found three patients of esophagitis of I Savary Miller de gree, while in the group of patients with infection in antrum in one case. In control H. pylori ne gative group esophagus inflammatory changes was found during endoscopy in 8 patients (40%), including 6 with esophagitis of I degree and 2 with III degree. The authors confirm more frequent pre sence of esophagitis in GERD without H. pylori patients which may confirm protective character of the inflammation in the course of GERD. It may be connected with the increased gastrin concentra tion affecting LES pressure. The relationship men tioned above was widely documented in available literature. Labenz [3, 8] claims that patients with duode nal ulcer and H. pylori infection who underwent eradication in the past developed symptoms of eso phageal reflux disease. He suggested additional risk factors apart from the pangastitis to be sex (male) and obesity. Fallone [6] in his studies con firms Labenz s suggestions that the effective eradi cations causes GERD symptoms and these patients have esophagitis assessed by endoscopy more fre quently, but he did not find any relation between body mass, nutrition habits and infection spot. He based his conclusions on the randomized studies carried out on 87 patients eradicated due to duode nal ulcer. The group was divided into 2 subgroups: effectively and non effectively treated because of H. pylori infection. At the end of 12 month obser vation period, effectively eradicated persons repor ted ailments characteristic for GERD. Esophagitis was more frequently found in endoscopy in these patients than in ineffectively treated patients. El Serag confirmed protective character of pangastritis type infection. He examined 302 pa tients, among whom 154 had endoscopic signs of esophagitis. In these patients he showed minor in crease in H. pylori infection, mainly in antrum. The examined persons without esophagitis pre sented intensified chronic gastritis dependent on H. pylori presence. Holtman [14] provides one more argument that the presence of H. pylori in course of GERD is an advantage. In his research, Holtman proved that pa tients with GERD and H. pylori infection respond

7 Eradication of Helicobacter Pylori in Patients with Gastroesophageal Reflux Disease 755 to therapy better than those without infection. 917 patients with endoscopically confirmed eso phagitis of Savary Miller II and III degree were di vided into two groups: H. pylori positive and nega tive. Both groups were administered the same doses of pantoprazole. Gastroscopy was performed again after 4 weeks of the therapy to estimate the presence of esophagitis. Remission of GERD symptoms and inflammatory changes in esophagus was much fas ter in H. pylori positive patients than in negative ones and it did not require increasing drug doses. Comparing presented results in control group (GERD without signs of H. pylori infection) and study group the authors found similar intensity of GERD in ph metry in control group as in patients with pangastritis after eradication. Average values of LES pressure in these patients are lower after the therapy in comparison to control group. In the group of patients with infection in antrum the treatment of H. pylori contributed to slight in crease of LES pressure with no effect on motoric activity of esophagus. It resulted in decrease in clini cal symptoms reported by patients, which is also pa rallel to results of ph metry examination [4, 7]. Achieved results confirm the hypothesis of protective influence of H. pylori infection affec ting the whole stomach mucosa in the course of gastroesophageal reflux disease. It contributes to the increase in LES pressure and effective eradica tion of H. pylori may enhance disease symptoms. The infection involving only antrum promotes the onset of GERD symptoms due to decrease in LES pressure. Thus, the eradication in the men tioned examples may be profitable in the course of GERD [7, 9]. References [1] O Connor HJ: H. pylori and gastro oesophageal reflux disease: clinical implications and management. Aliment Pharmacol Ther 1999, 13, [2] Lee JM, O Morain CA: Different management for Helicobacter pylori positive and negative patients with ga stroesophageal reflux disease? Gut 1998, 43, Suppl. 1, S14 S20. [3] Labenz J, Malfertheiner P: Helicobacter pylori in gastroesophageal reflux disease: casual agent, independent or protective factor? Gut 1997, 41, [4] Nowak A, Marek T: Szczególne zagadnienia terapeutyczne: rola zakażenia Helicobacter pylori w chorobie re fluksowej przełyku. W: Poradnik klinicysty, postępowanie w chorobie refluksowej przełyku. Red: Misiewicz JJ. Via Medica, Gdańsk 2000, wyd. I, [5] El Serag HB, Sonnenberg A, Jamal MM, Inadomi JM, Crooks LA, Feddersen RM: Corpus gastritis is pro tective against reflux oesophagitis. Gut 1999, 45, [6] Fallone CA, Barkun AN, Friedman G, Mayrand S, Loo V, Beech R, Best L, Joseph L: Is Helicobacter pylo ri eradication associated with gastroesophageal reflux disease? Am J Gastroenterol 2000, 95, [7] Dzieniszewski J: Znaczenie infekcji Helicobacter pylori w chorobie refluksowej przełyku. W: VII Warszawskie Spo tkania Gastroenterologiczne. Red. Bartnik W, Habior A, Przytulski K, Rupiński M. Goldprint, Warszawa 2000, [8] Labenz J, Blum AL, Bayerdorffer E, Meining A, Stolte M, Borsch G: Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis. Gastroenterology 1997, 112, [9] Quinta MG: Helicobacter pylori and gastroesophageal reflux disease. Curr Opin Gastroenterol 1998, 14, Suppl. 1, S53 S55. [10] Labenz J, Tillenburg B, Peitz U, Verdu E, Stolte M, Borsch G, Blum AL: Efficiacy of omeprazol one year after cure of Helicobacter pylori infection in duodenal ulcer patients. Am J Gastroenterol 1997, 92, [11] Jansen J, Klikenberg Knol EC, Meuwissen SG, De Brune IW, Festen HP, Snel P, Luckers AE, Biemond L, Lamers CB: Effect of long term treatment with omeprazole on serum gastrin and serum group A and C pepsinogens in patients with reflux esophagitis. Gastroenterology 1990, 99, [12] Lambert JR, Midolo P, Prichard PJ: Helicobacter pylori infection causes hypergastrinaemia during omeprazol therapy. Gut 1995, Suppl., A59. [13] Klikenberg Knol EC, Festen HP, Jansen JB, Russel EG, Lin SK: Long term treatment with omeprazole for re fractory reflux esophagitis: Efficacy and safety. Ann Intern Med 1994, 121, [14] Holtman G, Cain C, Malfertheiner P, Lamers CB, Nelis F, Snel P, Luckers A, Dekkers CP, Havu N, Mellwissen SG: Gastric Helicobacter pylori infection accelerates healing of reflux esophagitis during treatment with proton pomp inhibitor pantoprazole. Gastroenterology 1999, 117, Address for correspondence: Dorota Waśko Czopnik Department of Gastroenterology and Hepatology Wroclaw Medical University ul. J. Poniatowskiego Wrocław Received: Revised: Accepted: Praca wpłynęła do Redakcji: r. Po recenzji: r. Zaakceptowano do druku: r.