Impaired response of gastric MALT-lymphoma to Helicobacter pylorieradication in patients with autoimmune disease

Background and aims:Gastric MALT-lymphoma is thought to berelated to chronic antigenic stimulation provided by Helicobacter pylori(HP). As clonal expansion of gastric B cells not related to HP has beendemonstrated in patients with autoimmune disease (AD), we have analysedwhether AD adversely influences response of MALT-lymphoma followingHP-eradication. Patients and methods:Retrospective analysis of all patients withearly stage gastric MALT-lymphoma treated with HP-eradication was performed.The presence of AD was evaluated by personal questioning for specific symptomsand serologically by analysis of rheumatoid factor, antinuclear antibodies andthyroid autoantibodies. Results:A total of 22 patients were identified receiving onlyantibiotic treatment for initial management, and six presented with anautoimmune condition: three had Sjögren's syndrome, one polymyalgiarheumatica, one autoimmune thyroiditis along with psoriasis, and one patienthad only autoimmune thyroiditis. Successful eradication of HP was achieved inall patients, and 15 of 22 patients (68%) achieved complete responseof the lymphoma, while none out of the six patients with an autoimmunedisorder responded to HP-eradication. Conclusion:Apart from questioning the role of HP in thedevelopment of lymphoma in such patients, these results suggest that patientswith autoimmune disease might not be optimal candidates for HP-eradicationeven in case of early stage lymphoma.     

Primary multiple colonic carcinoma

Polypoid lesions of the colon are commonly accepted risk factors for the development of carcinomas of the colon. Fifty-two of 266 patients with one or more polypoid lesions of the colon showed a carcinoma in one of the polyps, 6 patients had a second carcinoma. Our study demonstrates the importance of preoperative investigation of the total colon in patients with carcinoma of the colon. Furthermore, the necessity of total exstirpation of each polypoid lesion is discussed.     

Adrenal size and function after irradiation with131I-6β-iodocholesterol in rabbits

Administration of high doses of 131I-6 beta-iodocholesterol to rabbits is followed by marked size reduction of the adrenal glands with concomitant changes of the histological structure and with a decrease of serum cortisol. Stimulation of 131I-6 beta-iodocholesterol uptake into the adrenals by additional administration of ACTH had only a minor additional effect on adrenal weight. However, with further accumulation of labeled cholesterol in the adrenals the radioactivity was reduced in blood urine, and the ovaries.     

Primary gastrointestinal non-Hodgkin's lymphomas. A retrospective clinicopathologic study of 150 cases

The records of 150 primary gastrointestinal (GI) lymphomas in adults collected from 1974 to 1982 at the Department of Pathology, University of Vienna, were reviewed. One hundred thirty-three cases of malignant lymphomas (ML) were analyzed with respect to histologic type, presenting tumor stage, and clinical course, as well as for factors influencing prognosis. The histologic type of ML as assessed by the Working Formulation and the Kiel, the Lukes and Collins, and the Rappaport classifications showed only a minor influence on prognosis. MLs of follicular center cell origin prevailed in the stomach and large cell, immunoblastic MLs prevailed in the bowel. Immunoperoxidase studies indicated a B-cell nature of GI MLs and demonstrated intracytoplasmic IgM kappa or lambda in most of the MLs of the small lymphocytic, plasmacytoid, and immunoblastic type, respectively. The 105 cases of gastric MLs represented 3.6% of all malignancies of the stomach collected during the study period. Clinical symptoms preceded the diagnosis by 4.4 months on average, and endoscopic biopsy specimens indicated malignancy in 78%. Presenting tumor stages of gastric MLs according to the Ann Arbor staging system were Stage I in 20%, Stage II in 76.2%, and Stage IV in 3.8%. The 28 cases of intestinal ML localized in the small and large bowel without any site prevalence presented with Stage I in 14%, Stage II in 82%, and Stage III in 4%. Tumor resection was performed in 90% of all cases and was followed by multiagent therapy in 53%. Radical tumor resection was obtained in 58% of the gastric MLs and only 28.6% of the intestinal MLs and was closely related to tumor stage. Statistical analysis demonstrated a significant influence of the presenting tumor stage on prognosis as expressed by the overall 2-year survival rate of 70% for Stage I versus 39% for Stage II ML. In addition, Stage II1 according to Musshoff et al. run a better course than II2 as shown by the disease-free 2-year survival rate of 49% versus 15%, respectively. Radical tumor resection was a major determinant of survival and cure of disease as exhibited by the disease-free 2-year survival rate of 57% after radical resection versus 8% after nonradical resection of ML. Finally, diffuse tumor growth and tumor penetration of the gastric wall beyond serosa decreased the survival rates.     

Gastrointestinal malignant lymphomas of the mucosa-associated lymphoid tissue: factors relevant to prognosis.

Three hundred seven cases (244 gastric, 63 intestinal) of primary gastrointestinal non-Hodgkin's lymphoma (NHL) in stages EI and EII, according to a modified Ann Arbor system, were examined retrospectively. The histological classification for mucosa-associated lymphoid tissue-derived lymphomas was applied. Gastric NHLs (male-female ratio, 0.97; mean age, 64.5 years) were stage EI in 51% and stage EII in 49% of cases. Histological grade of malignancy was low in 41% and high in 59% of cases; all NHLs were B-cell type. Tumors were radically resected in 87%, and overall 2-, 5-, and 10-year survival rates were 61%, 55%, and 46%, respectively. Early lymphomas (substage EI1) had best prognosis (5- and 10-year survival rates, 90% and 70%, respectively). Intestinal NHLs (male-female ratio, 1.1; mean age, 54.4 years) were stage EI in 30% and stage EII in 70% of cases. Histology was low grade in 21% and high grade in 79%, and all but 11 cases were B-cell type. In 58% of cases, radical tumor resection resulted in overall 2- and 5-year survival rates of 44% and 24%, respectively. Major prognosticators for survival in gastric location were low-grade histology, low depth of infiltration, and low stage and radical resectability of lymphoma; all factors were strictly intercorrelated. In intestinal site, radical tumor resectability was highly significant for survival. Cumulative proportion of relapses after 5 years was higher in intestinal than in gastric sites (44% vs. 22%). In conclusion, primary gastrointestinal tract NHLs may represent an entity with respect to characteristic histological features, focal tumor growth, and potential cure by radical resection. Because of late relapses, clinical follow-up is needed.     

Blood groups Lewis(b) and ABH expression in gastric mucosa: lack of inter-relation with Helicobacter pylori colonisation and occurrence of gastric MALT lymphoma.

BACKGROUND: Blood group Lewis(b) antigens mediate Helicobacter pylori attachment to gastric mucosa with attachment being particularly strong in subjects with ABH blood group O. AIMS: To determine whether H pylori colonisation or the occurrence of gastric mucosa associated lymphoid tissue (MALT) lymphomas might be related to gastric Lewis(b) expression or occurrence of particular ABH blood groups on gastric mucosa. PATIENTS: Gastric resection specimens from 89 cases with gastric MALT lymphoma and gastric mucosal biopsy specimens from 95 patients undergoing upper endoscopy due to upper gastrointestinal complaints, including five cases with gastric MALT lymphoma, were studied. METHODS: H pylori was visualised with the Warthin-Starry stain. Immunostaining (Lewis(b), Lewis(a), A, B) was performed by applying a three step immunoperoxidase technique and indirect immunofluorescence staining on formalin fixed and paraffin wax embedded tissue. In 40 patients red blood cell Lewis phenotype and ABH blood groups were additionally determined by haemagglutination assay. RESULTS: Gastric surface epithelial cells showed an immunoreactivity to blood groups A, B, and AB in 80 (43.5%), 22 (12%), and 11 (6%) cases respectively and no immunoreactivity to any of these blood group substances (blood group O) in 71 (38.5%) patients. Lewis(b) expression of all gastric surface epithelial cells (secretor status) was found in 130 (70.7%) cases. Lewis(a) expression of all gastric surface epithelial cells (non-secretor status) was found in 36 (19.6%) cases, secretor status remained unclassified in 18 (9.8%) patients. Colonisation with H pylori was found in 134 (72.8%) cases. The occurrence of H pylori was neither significantly associated with secretor status nor with certain ABH blood groups. The infiltration of gastric mucosa with MALT lymphoma was highly significantly associated with H pylori colonisation (p < 0.0003) but neither with secretor status nor with certain ABH blood groups. There was no inter-relation between secretor status or ABH blood groups and type, stage, grade of, and survival after MALT lymphoma. CONCLUSION: This study failed to show an inter-relation between secretor status or particular ABH blood groups and either H pylori infection or the occurrence of gastric MALT lymphomas.     

Helicobacter pylori and gastric cancer: current status of the Austrian-Czech-German gastric cancer prevention trial (PRISMA-Study)

AIM To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease.METHODS It is a prospective, randomized,double-blind, placebo-controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacterpylori gastritis are randomized to receive a 7-day course of omeprazole 2 × 20 mg,clarithromycin 2 × 500 mg, and amoxicillin 2 ×lg for 7 days, or omeprazole2 × 20mg plusplacebo. Follow - up endoscopy is scheduled 3months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, anddeath.RESULTS Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus-dominant type of H.pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (n -- 86), H. pylori infection infection was cured in 88.9% of patients. Currently, thecumulative follow-up time is 3046 months (253.8patient-years, median follow-up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three(1.8%) patients reached study endpoints other than gastric cancer.CONCLUSION Among men between 55 and 65years of age, the gastric cancer phenotype of H.pylori gastritis appears to be more common than expected. Further follow- up and continuing recruitment are necessary to fulfil the main aim of the study.     

Chemotherapy for the treatment of patients with primary high grade gastric B-cell lymphoma of modified Ann Arbor Stages IE and IIE

BACKGROUND: Surgical intervention and combined modality treatment including radiation and chemotherapy have been studied widely in patients with high grade gastric B-cell lymphoma, whereas to the authors' knowledge the role of chemotherapy alone in patients with localized disease has not been investigated extensively. METHODS: Twenty-five consecutive patients with primary high grade gastric B-cell lymphoma of localized modified Ann Arbor Stages IE and IIE were studied prospectively at the study institution. Patients age < 75 years (n = 17; age range, 41-75 years) were given a standard regimen comprised of doxorubicin, cyclophosphamide, vincristine, and prednisone (CHOP), whereas patients age > 75 years (n = 8; age range, 82-93 years) were treated at a reduced dose. Restaging was performed after 3 and 6 cycles, followed by every 3 months for the first 2 years, and every 6 months thereafter. RESULTS: A total of 123 cycles were administered to the study patients, with the median number of 6 cycles per patient (range, 1-9 cycles). At a median follow-up of 24 months (range, 1.5-87+ months), 22 patients were alive without evidence of disease and 3 patients had died (1 patient death was treatment-related). Twenty-four patients who were considered evaluable achieved a complete remission, 21 patients after 3 cycles and the remaining 3 patients after 6 cycles of treatment. Side effects generally were manageable, with only one patient requiring premature discontinuation of treatment due to protracted thrombocytopenia after three courses of therapy, and tolerance was not different between the two age groups. No recurrences were observed at last follow-up. CONCLUSIONS: The authors believe that chemotherapy using the CHOP regimen is highly effective in the treatment of patients with localized primary high grade gastric lymphoma.     

Importance of extensive staging in patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma

Lymphoma of the mucosa-associated lymphoid tissue (MALT) type usually arises in MALT acquired through chronic antigenic stimulation triggered by persistent infection and/or autoimmune processes. Due to specific ligand-receptor interactions between lymphoid cells and high-endothelial venules of MALT, both normal and neoplastic lymphoid cells display a pronounced homing tendency to MALT throughout the body. In the case of neoplastic disease these homing properties may be responsible for lymphoma dissemination among various MALT-sites. According to this concept, we have standardized staging procedures in all patients diagnosed with MALT-type lymphoma. All patients with MALT-type lymphoma underwent standardized staging procedures before treatment. Staging included ophthalmologic examination, otolaryngologic investigation, gastroscopy with multiple biopsies, endosonography of the upper gastrointestinal tract, enteroclysis, colonoscopy, computed tomography of thorax and abdomen and bone marrow biopsy. Biopsy was performed in all lesions suggestive for lymphomatous involvement, and evaluation of all biopsy specimens was performed by a reference pathologist. 35 consecutive patients with histologically verified MALT-type lymphoma were admitted to our department. Twenty-four patients (68%) had primary involvement of the stomach, five (15%) had lymphoma of the ocular adnexa, three (8.5%) had lymphoma of the parotid, and three (8,5%) of the lung. Lymph-node involvement corresponding to stage EII disease was found in 13 patients (37%), only one patient with primary gastric lymphoma had local and supradiaphragmatic lymph-node involvement (stage EIII). Bone marrow biopsies were negative in all patients. Overall, eight of 35 patients (23%) had simultaneous biopsy-proven involvement of two MALT-sites: one patient each had lymphoma of parotid and lacrimal gland, conjunctiva and hypopharynx, conjunctiva and skin, lacrimal gland and lung, stomach and colon, and stomach and lung. The remaining two patients had bilateral parotideal lymphoma. Staging work-up was negative for lymph-node involvement in all of these eight patients. The importance of extensive staging in MALT-type lymphoma is emphasized by the demonstration of multiorgan involvement in almost a quarter of patients. In addition, our data suggest that extra-gastrointestinal MALT-type lymphoma more frequently occurs simultaneously at different anatomic sites than MALT-type lymphoma involving the GI-tract.