Mito-FLAG with Ara-C as bolus versus continuous infusion in recurrent or refractory AML--long-term results of a prospective randomized intergroup study of the East German Study Group Hematology/Oncology (OSHO) and the Study Alliance Leukemia (SAL).

BACKGROUND: For patients with primary refractory or relapsed acute myeloid leukemia (AML), no treatment of choice has until now been defined to date. Cytarabine (Ara-C) is a key drug in the treatment of AML patients, there is still uncertainly regarding its optimal dose and infusion schedule. The aim of this study is to examine the impact of the Ara-C infusion schedule used as part of an intensive salvage regimen, in patients with relapsed or refractory AML. PATIENTS AND METHODS: A total of 252 adult patients (median age 59 years) with relapsed or refractory AML were randomly allocated to receive either Mito-FLAG with Ara-C as bolus (B) (1000 mg/m(2) over 1 h, every 12 h, days 1-5), or continuous infusion (CI) (150 mg/m(2) over 24 h, days 1-5) in combination with mitoxantrone, fludarabine, and granulocyte colony-stimulating factor (G-CSF). Autologous or allogeneic hematopoietic stem-cell transplantation was offered as consolidation therapy. Primary end point was the rate of complete remissions (CRs) after the first cycle of Mito-FLAG. RESULTS: The CR rates after Mito-FLAG (B) and Mito-FLAG (CI) were 54% and 43%, respectively (P = 0.1). There was no statistical difference between rates of grade 3/4 neutropenia, thrombocytopenia, mucositis, renal, and liver toxicity. More infections occurred, however, after Mito-FLAG (B) compared with Mito-FLAG (CI) (80% versus 69%, P = 0.01). The early death rate by day 42 was 13% in both arms. Median disease-free survival was comparable in the two arms (7.8 versus 7.1 months, P = 0.53) as was overall survival (7.1 versus 6.6 months, P = 0.53). CONCLUSION: A 5-day course of Ara-C 2 × 1000 mg/m(2) administered as bolus versus Ara-C 150 mg/m(2) administered by CI (in combination with mitoxantrone, fludarabine, and G-CSF), resulted in a nonsignificant trend in response rates in favor of Mito-FLAG (B) at the selected dose levels, but no differences in the survival outcome in relapsed or refractory AML. CLINICAL TRIAL NUMBER: LN_NN_2004_39/EudraCT number 2014-000083-18.

Real-world analysis of teclistamab in 123 RRMM patients from Germany.

Teclistamab, a B-cell maturation antigen (BCMA) × CD3 directed bispecific antibody, has shown high response rates and durable remissions in the MAJESTEC-1 trial in patients with relapsed and refractory multiple myeloma (RRMM). We retrospectively assessed efficacy and tolerability in 123 patients treated at 18 different German centers to determine whether outcome is comparable in the real-world setting. Most patients had triple-class (93%) or penta-drug (60%) refractory disease, 37% of patients had received BCMA-directed pretreatment including idecabtagene vicleucel (ide-cel) CAR-T cell therapy (21/123, 17.1%). With a follow-up of 5.5 months, we observed an overall response rate (ORR) of 59.3% and a median progression-free survival (PFS) of 8.7 months. In subgroup analyses, we found significantly lower ORR and median PFS in patients with extramedullary disease (37%/2.1 months), and/or an ISS of 3 (37%/1.3 months), and ide-cel pretreated patients (33%/1.8 months). Nonetheless, the duration of response in ide-cel pretreated patients was comparable to that of anti-BCMA naive patients. Infections and grade ≥3 cytopenias were the most frequent adverse events. In summary, we found that teclistamab exhibited a comparable efficacy and safety profile in the real-world setting as in the pivotal trial.

[Current value of quinolones in Helicobacter pylori therapy]. / Aktueller Stellenwert von Fluorchinolonen in der Helicobacter-pylori-Therapie.

Eradication rates in first-line Helicobacter pylori therapy have been declining over the last decades, mainly due to increasing resistance against the recommended antibiotics clarithromycin and metronidazole. Thus, there is a need to evaluate novel regimens and substances to offer effective alternative treatment strategies. New generation quinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against various Gram-positive and Gram-negative strains and are mostly well tolerated. Based on a large number of studies, quinolones have been introduced in second-line and rescue treatment and are recommended for these indications in current guidelines. Various studies have investigated alternative strategies for first-line treatment including quinolone-based regimens. In the context of increasing resistance rates of Helicobacter pylori against quinolones some risks and benefits have to be considered when using quinolones as a first-line strategy. Besides numerous studies investigating levofloxacin and moxifloxacin there are some promising results for the new substance sitafloxacin, which might overcome primary resistance of Helicobacter pylori against conventional quinolones.

Probe-based confocal laser endomicroscopy in double balloon enteroscopy.

BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) allows in-vivo assessment of the gastrointestinal mucosal architecture during ongoing endoscopy. We investigated the feasibility and safety of pCLE during double balloon enteroscopy (DBE). METHODS: DBE was performed using the Fujinon EN-450P5. pCLE (Cellvizio-GI®, Mauna Kea Technologies) was performed after intravenous injection of 5-10  mL fluorescein 1 % using a 1.8-mm probe (GastroFlex/ColoFlex Z-probe) at the deepest point of DBE insertion and in case of any pathological lesion. Primary outcome measure was technical success, defined as (i) successful advancement of the probe at the deepest DBE insertion and (ii) successful pCLE imaging of the intestinal mucosa. Secondary outcome was safety of the pCLE procedure. RESULTS: 27 DBE procedures (14 antegrade) were performed in 16 patients. The mean depth of small bowel insertion was 255  cm for antegrade and 130  cm for retrograde DBE. Technical success of pCLE was achieved in 96.3 % (antegrade 92.8 %, retrograde 100 %). One technical failure occurred (incomplete probe advancement). There were no adverse events related to the pCLE procedure. pCLE imaging of the small bowel mucosal architecture was possible in all cases. Pathological conditions within the small bowel such as loss of villi, crypt hyperplasia, advanced neoplasia, or increased blood flow due to inflammation tissue could be successful visualized. CONCLUSION: This study is the first to demonstrate successful and safe application of pCLE in the deep small bowel during double balloon enteroscopy. Further studies are needed to determine the clinical benefit of pCLE in the management of patients with small bowel diseases.

S3-guideline "helicobacter pylori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001.

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study).

To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 days 2, 16, 30), procarbazine (60 mg/m2 days 2-11) and lomustine (110 mg/m2, day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.

Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin.

BACKGROUND: The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge. AIM: To investigate the efficacy of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of H. pylori, and the correlation between cytochrome P450 2C19 (CYP2C19) polymorphisms and treatment outcome. METHODS: Patients infected with H. pylori resistant to both metronidazole and clarithromycin (n = 145) were randomized to either esomeprazole 20 mg, rifabutin 150 mg and amoxicillin 1 g, each given b.d. for 7 days (ERA), or to omeprazole 40 mg and amoxicillin 1000 mg, each given t.d.s. for 14 days (OA). Crossover therapy was offered in cases of persistent infection. CYP2C19 polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: Intention-to-treat and per-protocol eradication rates were: ERA 74% (62.4-83.6) and 78% (66.7-87.3); high-dose OA 70% (57.5-79.7) and 75% (62.5-84.5). Crossover therapy was successful in seven of 10 patients with ERA and in eight of 10 patients with OA. Premature discontinuation of treatment occurred in 2% and 5% of patients, respectively. There was only a non-significant trend to lower eradication rates in homozygous extensive metabolizers. CONCLUSIONS: Triple therapy with esomeprazole, rifabutin and amoxicillin and high-dose omeprazole/amoxicillin are comparable and effective and safe for rescue therapy of H. pylori regardless of the patient's CYP2C19 genotype.

Healing of lymphocytic gastritis after Helicobacter pylori eradication therapy--a randomized, double-blind, placebo-controlled multicentre trial.

BACKGROUND: An association between Helicobacter pylori infection and lymphocytic gastritis has been postulated. AIM: To assess the long-term effect of H. pylori eradication therapy on lymphocytic gastritis in a double-blind, placebo-controlled, multicentre trial. METHODS: Patients with lymphocytic gastritis were randomized to receive either 1-week triple therapy for eradication of H. pylori or omeprazole plus placebo. Endoscopy and histology was performed at baseline and after 3 and 12 months. Patients of the omeprazole/placebo group with persistent lymphocytic gastritis after 12 months received crossover open-label triple therapy. RESULTS: Fifty-one patients were randomized. Intention-to-treat analysis revealed a trend to a higher healing rate of lymphocytic gastritis 3 months after triple therapy compared with omeprazole/placebo (83.3% vs. 57.7%, 95% CI for RR: 0.8-2.8, P = 0.06). After 12 months, the healing rate of lymphocytic gastritis was significantly higher after triple therapy compared with omeprazole/placebo (intention-to-treat 95.8% vs. 53.8%, 95% CI for RR: 1.1-3.5, P = 0.01). All patients (n = 5) who received crossover triple therapy, showed healing of lymphocytic gastritis after further 12 months. CONCLUSION: Our study demonstrates that 1-week triple therapy aiming at eradication of H. pylori leads to a complete and long-lasting resolution of lymphocytic gastritis in the majority of patients.

Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Low-grade B-cell lymphomas arising in mucosa-associated lymphoid tissue (MALT) are most frequently localized in the gastrointestinal tract. More than 90% of gastric MALT lymphomas are diagnosed in patients with chronic, Helicobacter pylori-associated gastritis. High remission rates for these lymphomas have been observed after the cure of H. pylori infection. Data are lacking, however, with regard to the duration of the remissions. To address this question of remission duration, we have followed 50 patients in whom H. pylori infections were eradicated, and we determined whether the patients in complete remission displayed evidence of residual monoclonal B cells during follow-up. METHODS: Patients were treated with amoxycillin and omeprazole for 2 weeks in an attempt to cure H. pylori infections. Follow-up included endoscopic investigations with biopsy sampling. Monoclonal B cells in biopsy specimens were detected by means of a polymerase chain reaction (PCR)-based assay. RESULTS: H. pylori infections were cured in all 50 patients. The median follow-up for the 50 patients is currently 24 months (729 days; range, 135-1411 days). Forty patients achieved complete remission of their lymphomas, but five have subsequently relapsed. The median time of continuous complete remission for the 40 patients was 15.4 months (468 days; range, 0-1198 days). Among six patients whose Iymphomas did not respond to H. pylori eradication, four revealed high-grade lymphomas upon surgery. PCR indicated the presence of monoclonal B cells during follow-up in 22 of 31 assessable patients in complete remission. CONCLUSIONS: Complete remissions of low-grade gastric MALT Iymphomas after the cure of H. pylori infection appear to be stable, although most patients display evidence of monoclonal B cells during follow-up. Whether these patients are truly cured of their Iymphomas remains to be determined.

Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial.

In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to-transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m(2) and cytarabine 1 g/m(2), days 1-5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 × 30 mg/m(2)) and melphalan (140 mg/m(2)). The median patient age was 61 years (range 40-75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia-free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32-54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40-69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML.

Long-term persistence of monoclonal B cells after cure of Helicobacter pylori infection and complete histologic remission in gastric mucosa-associated lymphoid tissue B-cell lymphoma.

PURPOSE: Cure of Helicobacter pylori infection is associated with remission induction in the majority of patients with low-grade gastric mucosa associated lymphoid tissue (MALT) lymphoma in localized stages; however, limited data exist as to whether these patients may be cured of their lymphoma. The present study was performed to investigate whether the polymerase chain reaction (PCR) for the rearranged immunoglobulin heavy chain region may be used to define "molecular" remission. PATIENTS AND METHODS: Ninety-seven patients who suffered from low-grade gastric MALT lymphoma stage I(E) were observed with central pathology and molecular biology after cure of H pylori infection. PCR was performed with the use of consensus primers for the framework regions 1, 2, and 3 and monoclonality was corroborated by sequence analysis. In selected cases, microdissection was performed to study the origin of the monoclonal B cells. RESULTS: Of the 97 patients, 77 obtained complete endoscopic and histologic remission (CR). Twenty of 44 patients with PCR monoclonality at diagnosis and with sufficient molecular follow-up displayed monoclonal bands for a median time of 20.5 months after CR (range, 0 to 50.4 months). These B cells were related to the original lymphoma clone by sequence analysis. Microdissection analysis identified basal lymphoid aggregates as the source of these monoclonal B cells. Local relapse occurred in and was observed by PCR in four patients. All four patients displayed monoclonal PCR before relapse, and three of these four showed ongoing PCR monoclonality throughout their course, indicating the persistence of malignant cells. CONCLUSION: Half of all patients with gastric MALT lymphoma show long-term PCR monoclonality up to several years after cure of H pylori infection and CR. Patients with monoclonal PCR should be observed closely, whereas long-term PCR negativity may indicate cure of the disease.

Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma.

PURPOSE: Although most patients with primary gastric low-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma experience complete endoscopic and histologic remission after the cure of Helicobacter pylori infection, in many patients, the polymerase chain reaction (PCR) still detects monoclonal B cells in the gastric mucosa. The present study asked whether the lymphoma immunoglobulin VH (IgVH) sequences remained stable in patients with gastric MALT lymphoma after H pylori eradication. PATIENTS AND METHODS: Eight patients with stage EI disease treated with H pylori eradication were analyzed before and at different time points after the cure of the infection. After the amplification of IgVH genes from DNA extracted from gastric biopsy specimens, monoclonal PCR products were cloned and multiple clones (43 to 105) were sequenced per patient. RESULTS: Mutations were detected in all lymphoma VH sequences, which suggested germinal center or postgerminal center origin of the lymphoma B cells. In five of the eight patients, clonal heterogeneity was observed at diagnosis or during follow-up. Genealogical analysis of shared and unshared mutations showed that the process of somatic mutations was ongoing after H pylori eradication in four of the five patients who showed clonal instability. Ongoing mutations were observed in three of the four patients who completely responded to H pylori eradication, but in only one of the four patients who did not respond or who partially responded. CONCLUSION: In low-grade gastric MALT lymphomas, an ongoing process of somatic hypermutation and antigen selection can be detected after the therapeutic removal of the underlying stimulus H pylori. These data point to the relevance of yet unknown antigens that drive this disease. In addition, they challenge the view that these lymphomas may be cured solely by the eradication of H pylori.

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.

Long-term follow-up of collagenous colitis after induction of clinical remission with budesonide.

BACKGROUND: Budesonide (Entocort) is effective for the treatment of collagenous colitis. AIM: To assess the long-term outcome of patients after induction of clinical remission by budesonide treatment. METHODS: Fifty-one patients with chronic diarrhoea and histologically proven collagenous colitis were enrolled in randomized, placebo-controlled crossover trial using budesonide 9 mg daily for 6 weeks. Patients in clinical remission after either initial or crossover budesonide treatment were followed using standardized questionnaires. Clinical relapse was defined as five or more loose stools/day for at least 4 consecutive days. RESULTS: A total of 33 patients achieved clinical remission (85% per-protocol). During a median follow-up of 16 months, clinical relapse occurred in 20 patients (61%), after a median time of 2 weeks (range: 1-104, mean: 10 weeks). Patient age <60 years was identified as a significant risk factor for clinical relapse (OR = 7.4, P = 0.048). Budesonide was used for treatment of clinical relapse in 80% of patients achieving clinical response in all of them. CONCLUSIONS: Budesonide is effective in the treatment of collagenous colitis. Clinical relapses may occur in a considerable number of patients, particularly in those <60 years. Treatment of clinical relapse with budesonide appears to be an effective option.

Intragastric acidity during treatment with esomeprazole 40 mg twice daily or pantoprazole 40 mg twice daily--a randomized, two-way crossover study.

BACKGROUND: Patients with severe or complicated reflux disease may require higher than standard doses of a proton pump inhibitor for sufficient acid suppression. AIM: To test the hypothesis that esomeprazole 40 mg twice daily is superior to pantoprazole 40 mg twice daily in lowering intragastric acidity. METHODS: In a randomized, single-blinded, two-way crossover study, healthy subjects received esomeprazole 40 mg twice daily or pantoprazole 40 mg twice daily orally for five consecutive days. Continuous ambulatory 24-h intragastric pH was recorded on day 5 of each treatment. RESULTS: Thirty subjects were analysed. Esomeprazole provided significantly higher intragastric pH-values over the 24-h period [median intragastric pH 6.4 for esomeprazole and 5.1 for pantoprazole (P < 0.00005)]. Intragastric pH > 4 was maintained for 21.1 h with esomeprazole and 16.8 h with pantoprazole (P < 0.0001). An intragastric pH > 4 for more than 16 h was achieved in 96.7 and 56.7% of subjects, respectively (P = 0.0002). During night-time the proportion of time with intragastric pH > 4 was 85.4% with esomeprazole and 63.6% with pantoprazole (P = 0.0001). Nocturnal acid break through occurred less frequently on esomeprazole. CONCLUSIONS: Esomeprazole 40 mg twice daily provides better and more consistent intragastric acid control than pantoprazole 40 mg twice daily.

Atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach: a reality or merely an hypothesis?

The results of recent investigations have suggested that the old hypothesis of an atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach needs to be qualified. The most common cause of intestinal metaplasia is Helicobacter pylori gastritis. The consequence of this intestinal metaplasia is focal atrophy. Helicobacter pylori infection may also trigger an autoimmune gastritis of the corpus mucosa, with atrophy and intestinal metaplasia. Most intestinal metaplasias are only 'paracancerous' but not 'precancerous' lesions. Diffuse gastric carcinomas, such as the signet ring cell carcinoma, arise independently of intestinal metaplasia. Histogenetically, numerous carcinomas of the stomach are primarily of the gastric type, and may secondarily change into the intestinal type.High-grade intra-epithelial neoplasias (dysplasias) detected during the biopsy-based diagnostic work-up appear to be a marker for carcinoma and must, therefore, be removed endoscopically. The detection of intestinal metaplasia in routinely obtained biopsy material is subject to sampling error and is, therefore, not a suitable marker for an increased risk of a gastric carcinoma developing. As an alternative, the concept of gastritis of the carcinoma phenotype, which is more frequently found in early gastric carcinomas and in the relatives of gastric carcinoma patients, has been developed. In this concept, the diffuse parameters of grade and activity of the gastritis in the antrum and corpus, which are independent of sampling error, are subjected to a comparative analysis. A risk gastritis of the carcinoma phenotype is diagnosed when the grade and activity of the gastritis in the corpus are at least equally as pronounced as in the antrum. Currently, this concept is being tested in a prospective ongoing study. Future studies must show whether, and if so which, immunohistochemical or molecular-genetically detectable changes can be applied as risk markers in the diagnostic work-up. Helicobacter pylori eradication probably does not lead to complete regression of the intestinal metaplasia and ensuing focal atrophy. However, eradication of H. pylori does lead to the normalization of changes that can lead to mutations of the stem cells of the gastric mucosa (free radicals, nitric oxide, cell proliferation and vitamin C secretion).

Differing degree and distribution of gastritis in Helicobacter pylori-associated diseases.

Infection with Helicobacter pylori (H. pylori) causes gastritis, and may be associated with gastric and duodenal ulcers and also with such malignant diseases as MALT lymphoma and gastric carcinoma. In order to determine whether there are differences in the degree and distribution of gastritis, each patient with H. pylori gastritis only (n = 50) was matched for sex and age with four patients, one each with H. pylori-associated duodenal ulcer, gastric ulcer, gastric carcinoma or MALT lymphoma. From each patient, two biopsies were taken from the antrum and two from the corpus for histopathological examination of H. pylori gastritis. The median summed gastritis score decreases in the following order: antrum: gastric ulcer > duodenal ulcer > gastritis alone > carcinoma > MALT lymphoma, and corpus: gastric ulcer > carcinoma > MALT lymphoma > gastritis alone and duodenal ulcer. We conclude that the degree and distribution of H. pylori gastritis differs significantly among H. pylori-associated diseases. These differences may explain some of the underlying pathomechanisms associated with H. pylori infection.

Gastric MALT lymphoma and its relationship to Helicobacter pylori infection: management and pathogenesis of the disease.

Chronic Helicobacter pylori infection is strongly associated with the development of primary gastric B cell lymphoma of MALT-type. Therapeutic decisions in primary gastric MALT lymphomas, e.g., the choice for gastric surgery or stomach-conserving treatments in the form of radio-, chemo-, or eradication therapy, should be based on an accurate histopathological diagnosis, grading and clinical staging. Primary gastric low-grade MALT-NHLs in an early clinical stage associated with H. pylori infection were shown to respond with complete remission in approximately 77% of cases upon successful cure of the infection as only treatment modality. The effect of curing H. pylori infection on the course of a high-grade gastric MALT lymphoma is largely uncertain but preliminary results indicate a possible benefit for patients with high-grade MALT lymphoma upon eradication therapy. Concerning the pathogenetic mechanisms of lymphomagenesis, there are many questions to be addressed in the near future. In general, it is still unclear what the exact mechanisms are which lead to the malignant transformation of a reactive infiltrate. Is there a molecular-genetic or immunological point of no return? What is the biological significance of the immunoglobulin rearrangement detected with PCR? The wave of new data each year about the role of H. pylori in gastric MALT lymphoma might help that many of these questions addressed above might be answered within the next years.

Eradication of Helicobacter pylori and stability of remissions in low-grade gastric B-cell lymphomas of the mucosa-associated lymphoid tissue: results of an ongoing multicenter trial.

The normal human stomach is devoid of any organized lymphatic tissue. Acquisition of mucosa-associated lymphatoid tissue (MALT) in the stomach is considered to be a direct consequence of chronic infection with Helicobacter pylori. Thus, MALT appears to be part of the host defense against the pathogen H. pylori. Consequently, lymphomas arising from gastric MALT may be seen as an end point of a clonal evolution starting from the infection. Cumulative data from several studies show that eradication of H. pylori induces complete histologic remissions in about 70%-80% of the patients. Here we present data of an extended analysis of an ongoing multicenter trial. Eighty-four patients with low-grade gastric MALT lymphoma in stage EI were treated using a dual regimen to eradicate H. pylori. Complete remission was observed in 68 (81%) patients; a partial remission was found in seven (8%) patients. In contrast, nine (11%) patients revealed "no change" and were referred for alternative treatment strategies. The majority of these cases were found to harbor high-grade lymphomas in deeper mucosal areas. Polymerase chain reaction (PCR) performed on the VDJ rearrangements of the immunoglobulin heavy chain yielded monoclonal bands in 50 of 65 analyzed patients (77%) at diagnosis. Interestingly, in patients analyzed during follow up after achieving complete histologic remission, ongoing PCR monoclonality was found in 19 of 39 eligible patients (49%). Several patients who developed local relapse of the lymphoma were found in the group with ongoing PCR monoclonality. Together with data from the literature, these results suggest that the majority of low-grade gastric MALT lymphomas in stage EI respond to eradication of H. pylori. Longer follow-up investigations are necessary to determine whether remissions really indicate a cure from the disease and to elucidate whether PCR monoclonality after complete histological remission is predictive of increased relapse rate.

Development of early gastric cancer 4 and 5 years after complete remission of Helicobacter pylori associated gastric low grade marginal zone B cell lymphoma of MALT type.

AIM: To report 3 of 120 patients on the German MALT lymphoma trial with H. pylori associated gastric MALT lymphoma who developed early gastric cancer 4 and 5 years, after complete lymphoma remission following cure of H. pylori infection. PATIENTS AND RESULTS: Three patients (two men, 74 and 70 years; one women, 77 years) with H. pylori-associated low-grade MALT lymphoma achieved complete lymphoma remission after being cured. Surveillance endoscopies were performed twice a year in accordance to the protocol. Four years after complete lymphoma remission in two patients, and after 5 years in the other, early gastric adenocarcinoma of the mucosa-type, type IIa and type IIc, respectively, was detected, which were completely removed by endoscopic mucosa resection. In one patient, the gastric cancer was diagnosed at the same location as the previous MALT lymphoma, in the other patients it was detected at different sites of the stomach distant from location of the previous MALT lymphoma. The patients were H. pylori negative during the whole follow-up time. CONCLUSION: These findings strengthen the importance of regular Long-term follow-up endoscopies in patients with complete remission of gastric MALT lymphoma after cure of H. pylori infection. Furthermore, gastric adenocarcinoma may develop despite eradication of H. pylori.