Ekkehard Bayerdörffer

Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection

Lymphoma of gastric-mucosa-associated lymphatic tissue (MALT) type has been linked to infection with Helicobacter pylori. We investigated the effect on MALT lymphoma of eradicating H pylori infection. 33 patients with primary gastric low-grade MALT lymphoma associated with H pylori gastritis were treated with omeprazole (120 mg daily) and amoxycillin (2.25 g daily) for 14 days to eradicate H pylori. In addition to histology, PCR was used to examine proliferation of monoclonal B cells before treatment and during follow-up. All patients had at least two post-treatment examinations, and all became negative for H pylori, 2 after a second treatment course. On histology, 23 (70%) patients showed complete regression and 4 (12%) partial regression of lymphoma. 6 (18%) patients had no change after cure of H pylori infection. 1 was treated with chemotherapy. Of 5 treated surgically, 4 were found to have high-grade B-cell lymphoma on histology of the resected stomach and 1 a high-grade T-cell lymphoma. PCR showed complete disappearance of monoclonal B cells after cure of H pylori infection in 13 of 16 patients investigated. During median follow-up of 1 year no relapse of MALT lymphoma occurred. Low-grade primary gastric MALT lymphoma can completely regress after eradication of H pylori infection. However, longer follow-up is needed to clarify whether the remission is lasting.

Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis

BACKGROUND & AIMS We have shown previously that cure of Helicobacter pylori infection leads to the disappearance of acid-neutralizing substances. Also, patients with ulcer after cure may gain weight. The aim of this study was to investigate whether cure of the infection increases the risk of reflux esophagitis. METHODS Patients with duodenal ulcer without reflux esophagitis at the time of Helicobacter treatment were followed up prospectively after cure of the infection (n = 244) or after diagnosis of persisting infection (n = 216). All patients underwent endoscopy at 1-year intervals or when upper gastrointestinal symptoms recurred. H. pylori infection was assessed by rapid urease test and histology. RESULTS The estimated incidence of reflux esophagitis within 3 years was 25.8% after cure of the infection and 12.9% when the infection was ongoing (P < 0.001). Patients who developed reflux esophagitis after the cure had a more severe body gastritis before cure (odds ratio, 5.5; 95% confidence interval [CI], 2.8-13.6), gained weight more frequently after cure (odds ratio, 3.2; 95% CI, 1.2-9.4), and were predominantly men (odds ratio, 3.6; 95% CI, 1.1-10.6). CONCLUSIONS A considerable proportion of patients with duodenal ulcer treated for H. pylori will develop reflux esophagitis; risk factors are male sex, severity of corpus gastritis, and weight gain.

Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I Study.

Background.Eradication of Helicobacter pylori provides potential cure in the majority of patients with peptic ulcer disease, and eradication rates of more than 90% have been reported, using omeprazole in combination with two antimicrobials. The choice of antimicrobials, dose regimen and duration of treatment have varied between studies, however, and an optimal treatment still has to be established.

The MACH2 study: Role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies

BACKGROUND & AIMS The role of omeprazole in triple therapy and the impact of Helicobacter pylori resistance on treatment outcome are not established. This study investigated the role of omeprazole and influence of primary H. pylori resistance on eradication and development of secondary resistance. METHODS Patients (n = 539) with a history of duodenal ulcer and a positive H. pylori screening test result were randomized into 4 groups. OAC group received 20 mg omeprazole, 1000 mg amoxicillin, and 500 mg clarithromycin; OMC group received 20 mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin; and AC (amoxicillin, 1000 mg, and clarithromycin, 500 mg) and MC (metronidazole, 400 mg, and clarithromycin, 250 mg) groups received no omeprazole. All doses were administered twice daily for 1 week. H. pylori status was assessed before and after therapy by 13C-urea breath test. Susceptibility testing was performed at entry and in patients with persistent infection after therapy. RESULTS Eradication (intention to treat [n = 514]/per protocol [n = 449]) was 94%/95% for OAC, 26%/25% for AC (P < 0.001), 87%/91% for OMC, and 69%/72% for MC (P < 0.001). Primary resistance was 27% for metronidazole, 3% for clarithromycin, and 0% for amoxicillin. Eradication in primary metronidazole-susceptible/-resistant strains was 95%/76% for OMC and 86%/43% for MC. Secondary metronidazole and clarithromycin resistance each developed in 12 patients: 8 treated with omeprazole and 16 without omeprazole. CONCLUSIONS Addition of omeprazole achieves high eradication rates, reduces the impact of primary resistance, and may decrease the risk of secondary resistance compared with regimens containing only two antibiotics.

Long-Term Follow-Up of Gastric MALT Lymphoma After Helicobacter Pylori Eradication

PURPOSE Cure of infection induces remissions in most patients with early stage Helicobacter pylori- (Hp) positive gastric MALT (mucosa-associated lymphoid tissue) lymphoma (GML). We tracked the long-term stability of remissions in this prospective, multicenter trial. PATIENTS AND METHODS In 120 patients with stage I(1E) disease, we performed sequential endoscopic-bioptic follow-up after Hp eradication and polymerase chain reaction of the rearranged immunoglobulin heavy chain gene. The status of t(11;18) was assessed in 65 patients. RESULTS Median follow-up was 75 months (range, one to 116). Five-year survival was 90%. Eighty percent of patients (96 of 120) achieved complete histologic remission (CR). Eighty percent of CRs are in continuous complete histologic remission (CCR). Three percent of CR patients (three of 96) relapsed and were referred for alternative treatment. Seventeen percent of CR patients (16 of 96) showed histologic residual disease (RD) during follow-up; a watch-and-wait strategy was applied, and all entered into a second CR. After a median follow-up of 63 months, 14 of 52 analyzed patients reaching CR showed ongoing B-cell monoclonality. Fifteen percent of GMLs were t(11;18) positive. Both t(11;18) and ongoing monoclonality were associated with a significantly higher risk for no response or relapse (P =.004, P =.007), but also present in patients in CCR. Early gastric cancer was diagnosed in three cases during follow-up. CONCLUSION Cure of Hp infection results in CCR in most patients. Histologic RD, B-cell monoclonality, and t(11;18) were present in a considerable number of CR patients. A watch-and-wait strategy is justified when close follow-up is guaranteed.

Helicobacter heilmannii–associated primary gastric low-grade MALT lymphoma: Complete remission after curing the infection

BACKGROUND & AIMS Cure of Helicobacter pylori infection may lead to complete remission of associated low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in stage EI. This study investigated whether Helicobacter heilmannii infection-associated primary gastric MALT lymphoma will regress after cure of the infection. METHODS H. heilmannii-induced gastritis was diagnosed histologically, by a new specific immunoglobulin G enzyme-linked immunosorbent assay, and with 16S ribosomal RNA amplification and sequencing in 5 consecutive patients with primary gastric MALT lymphoma clinical stage EI. Patients received 40 mg omeprazole and 750 mg amoxicillin 3 times per day for 14 days. Polymerase chain reaction (PCR) was used to detect rearrangement of immunoglobulin heavy-chain genes before treatment and during follow-up. RESULTS Five patients (3 men, 2 women; mean age, 65 years; range, 42-79 years) were studied. H. pylori was not detected by culture, histology, serology, or PCR. Treatment resulted in the cure of H. heilmannii infection in each case and complete histological and endoscopic remission of the tumors. Three of 5 patients showed monoclonal B cells before treatment, 2 of whom remained PCR positive. Within a median follow-up period of 24 months, no relapse of the lymphoma or reinfection with H. heilmannii occurred. CONCLUSIONS These data suggest that gastric MALT lymphoma may arise in patients with H. heilmannii infection. Cure of this infection may lead to complete remission of the MALT lymphoma.

Difference in expression of Helicobacter pylori gastritis in antrum and body.

Seven hundred seventy biopsy specimens obtained from 10 different sites in stomachs of 77 patients were examined for the presence of active chronic gastritis (ACG) and Helicobacter pylori to investigate the characteristics of gastritis in the antrum and body. Forty-eight patients with ACG at one or more sites were all H. pylori positive. H. pylori was not found in 20 patients who had chronic gastritis with no activity or in 9 patients who had histologically normal mucosa. In patients with ACG in at least one biopsy site, a strong positive topographic association between H. pylori colonization and ACG was seen in the Warthin-Starry stain. The frequency of H. pylori colonization was similar in the antrum and body. However, the incidence of ACG declined significantly proximal to the borderline between the antrum and body (P less than 0.001). The average grade of gastritis at the individual biopsy sites was distributed evenly throughout the antrum but decreased markedly in the body (P less than 0.0001). In the same manner, the average grade of H. pylori colonization decreased in the body (P less than 0.0027). The grade of H. pylori colonization in the individual biopsy specimens was closely related to the grade of gastritis (r = 0.51); also, the grade of neutrophil infiltration was related to the grade of gastritis (r = 0.79). A good correlation existed between the grade of H. pylori colonization and the grade of neutrophil infiltration (r = 0.70). The results of this study show a different expression of H. pylori gastritis in the antrum and body, which is the main subtype of chronic type B gastritis. The close topographic and graded association between the presence of H. pylori and the activity and grade of gastritis lend further support to the major pathogenic role of H. pylori in active chronic gastritis. The different expression of gastritis in antrum and body is suggested to be increased reactivity of the antral mucosa to the infection, possibly on the basis of an enhanced immunologic response to H. pylori in this region.

Helicobacter and gastric MALT lymphoma.

Helicobacter pylori infection is a pre-MALT lymphoma condition. H pylori eradication leads to complete remission in 80% of low grade stage E1 lymphomas, with a yearly recurrence rate of approximately 5%. The possibility for complete remission in high grade lymphomas needs to be investigated in prospective studies. In addition, the significance of persistent B cell monoclonality (stable disease? danger of relapse? regression of monoclonality?) needs to be investigated in follow up studies.

Increased Serum Deoxycholic Acid Levels in Men With Colorectal Adenomas

BACKGROUND Epidemiological and animal studies have suggested that the secondary bile acid deoxycholic acid is cocarcinogenic in colorectal cancer, but this hypothesis was not confirmed by case-control studies investigating fecal bile acids. METHODS Individual serum bile acid concentrations were investigated in 25 men and 25 women with colorectal adenomas and in an equal number of age- and sex-matched controls by gas-liquid chromatography. RESULTS Deoxycholic acid levels were significantly higher in the sera of men with colorectal adenomas (1.70 +/- 0.59 vs. 1.16 +/- 0.39 mumol/L, P < 0.0005) and in a combined analysis of both sexes (1.47 +/- 0.78 vs. 1.08 +/- 0.39 mumol/L, P < 0.0025). Six- and 12-month follow-up measurements of deoxycholic acid concentrations in a subgroup of 22 men and 17 women showed higher serum levels in men with adenomas, indicating that measurement of deoxycholic acid concentration may be a reliable parameter to investigate its pathogenetic role in colonic neoplasia. CONCLUSIONS The data of this study support the hypothesis that deoxycholic acid may play a role in the pathogenesis of colorectal cancer.

Complete Remission of Primary High-Grade B-Cell Gastric Lymphoma After Cure of Helicobacter pylori Infection

PURPOSE Treatment of low-grade gastric mucosa-associated lymphoid tissue lymphoma by eradication of Helicobacter pylori is reported to result in complete lymphoma remission in approximately 75% of cases. The effect that cure of the infection has on the course of a primary high-grade gastric lymphoma is largely uncertain. The aim of this study was to report the effect of cure of H pylori infection exerted in patients with high-grade B-cell gastric lymphoma. PATIENTS AND METHODS Eight patients (4 males and 4 females; age range, 26 to 85 years) with H pylori infection and high-grade lymphoma received eradication therapy before planned treatment. The effect of H pylori eradication on the course of high-grade lymphoma was assessed by analysis of surgical specimens (n = 2) or endoscopic biopsies (n = 6). RESULTS H pylori eradication was successful in all patients and led to complete remission of the lymphoma in seven patients. One patient has experienced partial remission. Two patients were referred to surgery, one of whom (stage II(1E)) had lymph node involvement, and the histologic work-up of the resected stomach revealed residual infiltrates of a low-grade lymphoma, which prompted consolidation chemotherapy. In one patient (initially stage I(1E)), abdominal lymphoma developed 6 months after eradication therapy, which regressed completely after chemotherapy. In four patients, no further treatment was given. Six patients continue in complete remission (range, 6 to 66 months). CONCLUSION Primary high-grade B-cell gastric lymphoma in stages I(E) through II(E1) associated with H pylori may regress completely after successful cure of the infection. Prospective trials are needed to investigate this treatment in larger numbers of patients.