EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT.

This consensus report of the EGILS (European Gastro-Intestinal Lymphoma Study) group includes recommendations on the management of gastric extranodal marginal zone B-cell lymphoma of MALT. They are based on data from the literature and on intensive discussions and votings of the experts during their annual meetings.

Most patients with minimal histological residuals of gastric MALT lymphoma after successful eradication of Helicobacter pylori can be managed safely by a watch and wait strategy: experience from a large international series.

BACKGROUND: Eradication of Helicobacter pylori is the established initial treatment of stage I MALT (mucosa associated lymphoid tissue) lymphoma. Patients with minimal persisting lymphoma infiltrates after successful eradication of H pylori are considered treatment failures and referred for radiation, chemotherapy, immunotherapy, or surgery. AIM: To report a watch and wait strategy in such patients. METHODS: 108 patients were selected from a larger series of patients treated at various European institutions. Their mean age was 51.6 years (25 to 82), and they were all diagnosed as having gastric marginal zone B cell lymphoma of MALT type stage I. After successful H pylori eradication and normalisation of the endoscopic findings, lymphoma infiltrates were still present histologically at 12 months (minimal histological residuals). No oncological treatment was given but the patients had regular follow up with endoscopies and multiple biopsies. FINDINGS: Based on a follow up of 42.2 months (2-144), 102 patients (94%) had a favourable disease course. Of these, 35 (32%) went into complete remission. In 67 (62%) the minimal histological residuals remained stable and no changes became evident. Local lymphoma progression was seen in four patients (5%), and one patient developed a high grade lymphoma. CONCLUSIONS: Most patients with minimal histological residuals of gastric MALT lymphoma after successful eradication of H pylori had a favourable disease course without oncological treatment. A watch and wait strategy with regular endoscopies and biopsies appears to be safe and may become the approach of choice in this situation. Longer follow up is needed to establish this definitively.

[Radiotherapy for localized gastric and orbital MALT lymphomas]. / Radiothérapie des lymphomes malins non hodgkiniens localisés de type MALT (gastriques et de la région orbitaire).

Primary gastric and orbital MALT lymphomas are both low grade (indolent) B-cell non-Hodgkin's lymphomas. Traditionally, these tumors are radiosensitive and have a good prognosis. In localized orbital and stages IE-IIE gastric MALT lymphomas without Helicobacter pylori infection or in case of persistent H. pylori infection after eradication therapy, several retrospective studies have shown that radiotherapy was an effective and well-tolerated treatment.

Problems of oral anticoagulation in an adult with homozygous protein C deficiency and late onset of thrombosis.

We describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder.

Gastrointestinal lymphoma: prevention and treatment of early lesions.

Gastrointestinal lymphomas comprise a group of distinct clinicopathological entities. Differences in lifestyle and environmental factors between countries could account for the variety in the distribution of the main subtypes: low-grade B-cell lymphomas of the mucosa-associated lymphoid tissue type, alpha-chain disease and enteropathy (coeliac disease)-associated T-cell lymphoma (EATL). The possibility of preventing these lymphomas implies a knowledge of their natural history together with an identification of potential predisposing factors. The development of the lymphoid hyperplasia and subsequently low-grade lymphoma with the possibility of high-grade transformation is a multifactorial process involving both antigenic and host-related factors. The pathogenic role of Helicobacter pylori and gluten has been demonstrated in gastric lymphoma and enteropathy-associated T-cell lymphoma respectively, while environmental factors, especially non-specific bacterial ones, may play a major role in the pathogenesis of alpha-chain disease. The most difficult task in preventing these lymphomas is the recognition of early lesions likely to regress after the removal of the exogenous stimulus.

Gastrointestinal lymphomas: the French experience of the Groupe D'etude des Lymphomes Digestifs (GELD).

Since 1983, the French Groupe d'Etude des Lymphomes Digestifs (GELD), under the aegis of the Fondation Française de Cancérologie Digestive, has aimed to identify the different prognostic groups of the primary digestive-tract lymphomas (PDTL) and their optimal treatment. Successive multicenter studies were conducted and 91 PDTL were evaluated. A marked improvement in their prognosis was obtained by a strategy including precise histologic typing and clinical staging followed by a therapeutic approach combining initial surgical resection, whenever possible or reasonable, followed by chemotherapy adapted to the grade of malignancy and resectability of the lymphoma. The multivariate analysis indicated that the factors for good prognosis were age (< 65 yrs), gastric localisation, stage IE and radical or even incomplete surgery. However, Helicobacter pylori eradication should be the first treatment in stage IE low-grade gastric mucosa-associated lymphoid tissue (MALT) tumors. The long-term results of such medical treatment are evaluated together with the management and the place of surgery in these localised tumors. However, owing to the limited number of patients, a large international co-operative trial is needed to confirm the findings. Thirty-one cases of multiple lymphomatous polyposis were also collected and confirmed to be a distinct entity among PDTL and the gastrointestinal counterpart of the mantle-cell-zone lymphomas. High-dose radio-chemotherapy supported by auto-transplantation improved their prognosis.

Management and long-term results of surgery for localized gastric lymphomas.

BACKGROUND: High- and low-grade gastric lymphomas (GL) differ in their behavior and chemosensitivity. Surgery has to be reevaluated according to the histologic grade of malignancy. We aimed to assess the place of surgery in the management of GL and its results after long-term follow-up. METHODS: Among 54 patients with primary GL prospectively enrolled from 1984 to 1990, 45 with localized disease were studied. Primary resection was done whenever safe. All patients received chemotherapy adapted to the grade of malignancy and/or to the completeness of the resection. RESULTS: Among 18 low- and 27 high-grade GL, 35 patients had primary resections; of those, 23 were complete. The complete response rate for all patients with low- and high-grade GL was 67% and 89%, respectively. After a median follow-up of 8 years, the disease-free survival rates for low-grade GL and high-grade GL were 94% and 89%, respectively. It was better after complete resection. CONCLUSION: Complete resection is a major determinant of prolonged complete remission.

A digestive tolerance study of maltitol after occasional and regular consumption in healthy humans.

AIM: We aimed to evaluate the gastro-intestinal tolerance to an indigestible bulking sweetener containing sugar alcohol using a double-blind random cross-over study. METHOD: In order to simulate their usual pattern of consumption, 12 healthy volunteers ingested maltitol or sucrose throughout the day, either occasionally (once a week for each sugar, first period) or regularly (every day for two 9 day periods, second period). In both patterns of consumption, daily sugar doses were increased until diarrhea and/or a grade 3 (ie severe) digestive symptom occurred, at which the dose level was defined as the threshold dose (TD). RESULTS: In the first period (occasional consumption), the mean TD was 92+/-6 g with maltitol and 106+/-4 g with sucrose (P=0.059). The mean intensity of digestive symptoms was 1.1 and 1.3, respectively (P=NS). Diarrhea appeared in six and one subjects respectively (P=0.035). In the second period (regular consumption), the mean TD was 93+/-9 g with maltitol and 113+/-7 g with sucrose (P=0.008). The mean intensity of digestive symptoms was 1.7 and 1.2, respectively (P=NS). However, diarrhea appeared in eight and three subjects, respectively (P=0.04). Maltitol and sucrose TDs between the two periods were not different. CONCLUSIONS: Under our experimental conditions, in comparison to sucrose: (a) occasional or regular consumption of maltitol is not associated with severe digestive symptoms; (b) in both patterns of maltitol consumption, diarrhea frequency is higher, but it appeared only for very high doses of maltitol, much greater than those currently used; (c) maltitol does not lead to intestinal flora adaptation after a 9 day period of consumption.

Lymph node involvement revealing a lymphomatous polyposis of the gastrointestinal tract.

The digestive tract is the most frequent site of extranodal malignant lymphomas. Lymphomatous polyposis is one of them, and its prognosis is poor. It corresponds to a digestive localization of mantle cell lymphoma. In most cases it is discovered following digestive symptoms. However, in some cases this digestive malignant lymphoma may be asymptomatic. Thus complete endoscopic exploration of the digestive tract including biopsies is necessary for every patient presented with lymph node mantle cell lymphoma.

[Treatment of high malignancy lymphoma with intensive short-term chemotherapy using the MACOP-B regimen]. / Traitement des lymphomes de grande malignité par chimiothérapie courte et intensive de type MACOP-B.

We present our results of a MACOP-B regimen in a series of 46 patients with high-grade NHL. The complete remission rate was 74% for patients with advanced stage disease. The excellent tolerance allowed this regimen to be given on an outpatient basis in the majority of cases. The median follow-up for the living patients is 28 months. Although some patients received additional treatment that could influence the results, the predicted DFS (disease-free survival) at 45 months of 57% compares favorably with the best results published so far with more toxic regimens.

[Digestive lymphomatous polyposis]. / Polypose lymphomateuse digestive.

We report 7 prospectively followed cases of lymphomatous polyposis of the gastrointestinal tract. They were characterized by multiple polypoid lesions affecting several segments of the gastrointestinal tract always involving the colon and the rectum. An ileocecal mass was present in 4 cases. Regional lymph node involvement was constant. Peripheral lymphadenopathy was frequent (5 cases out of 7), as was other extra-digestive extension to the bone marrow (4 cases out of 7) and cavum (3 cases out of 7). The histopathological aspect was that of a small cleaved cells (working formulation) or centrocytic (Kiel classification) non-Hodgkin's lymphoma. The peculiar morphology and phenotype of the tumoral B-lymphocytes suggest their possible follicle marginal zone origin. Lymphomatous polyposis bore a rapidly fatal prognosis in every case (mean survival 20 months). This study of seven patients together with the 20 well-documented cases of the literature confirms the existence of lymphomatous polyposis as a distinctive clinicopathological entity among gastrointestinal non-Hodgkin's lymphoma.

[Role of percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis]. / Place de la gastrostomie endoscopique percutanée dans la sclérose latérale amyotrophique.

Percutaneous endoscopic gastrostomy (PEG) is an enteral nutritional assistance technique using a simple device compatible with conventional feeding and thus enabling the patient to be integrated into his or her social and familial surroundings. This inexpensive device is quickly and easily inserted under local anaesthesia. It causes little morbidity and virtually no mortality and has many advantages for patients with amyotrophic lateral sclerosis (ALS). We report the results of PEG in 28 ALS patients with bulbar involvement. Three of these patients developed minor complications during 6 consecutive months of PEG-assisted nutrition (2 had periostomial infection, 1 had mild haematemesis). There were no major complications, and mortality directly ascribable to PEG was nil. All patients put on weight or had their weight stabilized, and GEP was well accepted in all cases.

[MALT gastric lymphomas]. / Les lymphomes gastriques du MALT.

INTRODUCTION: The stomach is the most common site involved in primary gastrointestinal lymphoma. Gastric lymphoma originates from the mucosa-associated lymphoïd tissue so called MALT. It comprises a group of distinctive clinicopathological entities which are important to consider for clinical management. CURRENT KNOWLEDGE AND KEY POINTS: In recent years, new diagnostic tools and new treatment strategies have improved the overall prognosis. One of the most exciting recent discoveries is the hypothesis that an infection by a bacterium, Helicobacter pylori has a decisive role in gastric lymphoma. FUTURE PROSPECTS AND PROJECTS: Recent advances, essentially due to molecular biology and cytogenetic studies may emerge with the understanding of pathogenesis and new prognostic factors of these different types of gastric lymphomas. It is the aim of our oncoming studies together with the evaluation of the new therapeutic options such as radiotherapy and monoclonal antibodies in prospective studies.

[Gastric lymphoma]. / Lymphome gastrique.

The stomach is the most common site involved in primary gastrointestinal lymphoma. Gastric lymphoma originates from the mucosa-associated lymphoid tissue so called MALT. It comprises a group of distinctive clinicopathological entities which are important to take in account for clinical behavior. In recent years, new diagnostic tools and modern modes of treatment have improved their overall prognosis. One of the most exciting recent discoveries is the hypothesis that an infection by a bacterium. Helicobacter pylori has a decisive role in gastric lymphoma.

Differential expression of NF-kappaB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism.

Mucosa-associated lymphoid tissue (MALT) lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the nuclear factor (NF)-kappaB pathway. Gastric MALT lymphomas harboring such translocations usually do not respond to Helicobacter pylori eradication, while most of those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 21 MALT lymphomas (13 translocation-positive, 8 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-kappaB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions have shown that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-kappaB target genes, particularly toll like receptor (TLR)6, chemokine, CC motif, receptor (CCR)2, cluster of differentiation (CD)69 and B-cell CLL/lymphoma (BCL)2, while translocation-negative cases were featured by active inflammatory and immune responses, such as interleukin-8, CD86, CD28 and inducible T-cell costimulator (ICOS). Separate analyses of the genes differentially expressed between translocation-positive and -negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10-mediated NF-kappaB activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors.