Long-term outcome following Helicobacter pylori eradication in a retrospective study of 105 patients with localized gastric marginal zone B-cell lymphoma of MALT type.

BACKGROUND: Treatment aimed at eradicating Helicobacter pylori infection results in lymphoma remission in most localized gastric mucosa-associated lymphoid tissue (MALT) lymphomas. The aim of this survey is to investigate the long-term effect of this therapeutic approach in a large series of patients. METHODS: One hundred and five patients with localized gastric MALT lymphoma were initially treated only with H. pylori eradication regimens. Lymphoma responses were graded using the Wotherspoon score. RESULTS: Helicobacter pylori, detected by histology in 81% of cases, was eradicated in all positive patients. Histological regression of the lymphoma was achieved in 78 of 102 assessable patients [76%, 95% confidence interval (CI): 67% to 84%] with complete remission (score 0-2) in 66 and partial remission (score 3) in 12. At a median follow-up time of 6.3 years, histological remission was consistently confirmed in 33 of 74 assessable patients, while 25 had score fluctuations (from 0 to 4) and 13 presented a lymphoma relapse (score 5). Only one patient had a distant progression. Transformation to a large-cell lymphoma was seen in two cases. The 5- and 10-year overall survival is 92% (95% CI: 84% to 96%) and 83% (95% CI: 70% to 91%), respectively. Only one patient died of lymphoma after transformation to a high-grade lymphoma. CONCLUSIONS: Helicobacter pylori eradication resulted in complete lymphoma remission in the majority of cases. Long-term clinical disease control was achieved in most patients. A watch and wait policy appears to be safe in patients with minimal residual disease or histological-only local relapse.

A multicenter study of treatment of primary CNS lymphoma.

OBJECTIVE: To characterize the therapeutic variables correlated to outcome in 370 patients with primary CNS lymphoma. METHODS: Planned treatment was radiotherapy (RT) in 98 patients, chemotherapy (CHT) in 32, RT followed by CHT in 36, and CHT followed by RT in 197 patients. High-dose methotrexate (HD-MTX; 1 to 8 g/m2) was used in 169 patients and intrathecal CHT in 109. RESULTS: One hundred sixteen patients are alive (median follow-up 24 months), with a 2-year overall survival of 37%. Patients treated with CHT followed by RT had improved survival with respect to patients treated with RT alone. Patients receiving HD-MTX-based primary CHT survived longer than those treated with other drugs. HD-MTX associated with other cytostatics, in particular HD-cytarabine, produced better results than HD-MTX alone. No correlation between MTX dose and survival was found. In patients receiving HD-MTX, consolidation RT or intrathecal CHT did not improve survival. Age, performance status, lactate dehydrogenase serum level, CSF protein level, site of disease, and use of HD-MTX were all predictors of survival. CONCLUSIONS: Combination CHT-RT is superior to RT alone. Patients treated with primary CHT containing HD-MTX exhibited improved survival. In these patients, the addition of HD-cytarabine was associated with a better survival, whereas intrathecal CHT was not correlated to outcome. RT may be unnecessary in patients achieving complete remission after receiving HD-MTX-based primary CHT.

Protothecosis in an HIV-positive patient.

This is the first report of localized tendosynovial human protothecosis in an HIV-positive host. The lesion appeared as a nodule in the extensor face of the thumb. A simple excision was performed, and histology confirmed numerous granulomas, some with central fibrinoid necrosis. Enormous numbers of prototheca were found in periodic acid-Schiff and Gömöri methenamine silver strains, evidencing endosporulation with diagnostic morula- or daisy-like sporangia. The presence of prototheca species was confirmed by direct immunofluorescence with the specific conjugate. The cellular response estimated by the relative number of polymorphonuclear leukocytes, lymphocytes, and plasma cells was minimal, although granuloma formation was unaffected. The infective agents were found either extracellular or harbored by macrophages and giant cells.

Overexpression of NAD(P)H:quinone oxidoreductase 1 in human reproductive system.

NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a two-electron reductase that efficiently bioactivates compounds of the quinone family, such as mitomycin C. The observation that DTD is overexpressed in many cancerous tissues compared to normal tissues has provided us with a potentially selective target that can be exploited in the design of novel anticancer agents. Because of the relative lack of information on the cell-specific expression of DTD, the purpose of this study was to perform a body mapping of its normal distribution. Tissue samples from various components of the human reproductive system were analyzed by immunohistochemistry. We found strong expression of this enzyme in testicular stromal cells (Leydig cells) and in the epithelium of epididymis, ductuli efferentes, and Fallopian tube. These results suggest that DTD-bioactivated quinones could be responsible for a selective toxicity on these components of the reproductive system and cause clinical problems due to testosterone deficiency and infertility. This observation needs to be investigated in preclinical evaluation of new anticancer quinones and in patients treated with these compounds. (J Histochem Cytochem 49:1187-1188, 2001)

Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin.

Primary cutaneous B-cell lymphomas have been associated with Borrelia burgdorferi, the spirochete responsible for Lyme disease. Recently, cutaneous marginal zone B-cell lymphoma has been proposed as a distinct clinical-pathological entity. We report a case of primary cutaneous marginal zone lymphoma, associated with B burgdorferi infection. Polymerase chain reaction (PCR) amplification of the third complementarity determining region (CDR3) of the immunoglobulin heavy chain gene showed the presence of a monoclonal lymphoproliferation, therefore strengthening the histological diagnosis of a malignant process. B burgdorfer-specific hbb gene sequences were detected by PCR in the lymphoma tissue at diagnosis but not after antibiotic treatment. A nearly complete clinical and histological regression was observed after B burgdorferi eradication, with immunohistochemistry studies showing disappearance of plasma cell differentiation and a marked decline in the number of CD3+ T cells and Ki-67+ cells. Our case confirms the link between B burgdorferi and some cutaneous lymphomas. The disappearance of the microorganism accompanied by the unequivocal decrease of most indicators of active T- and B-cell immune response strongly supported a pathogenetic role for B burgdorferi in sustaining an antigen-driven development and growth of this cutaneous marginal zone lymphoma. Antibiotic therapy (analogous to Helicobacter pylori infection in gastric MALT lymphoma) might be helpful with the aim of averting or at least deferring the indication for more aggressive treatment.

Treatment and prognosis of centrocytic (mantle cell) lymphoma: a retrospective analysis of twenty-six patients treated in one institution.

We retrospectively attempted to analyse prognostic factors in a group of 26 patients with centrocytic lymphomas (CCL) treated from 1979 to 1991 (representing 7% of all cases of NHL diagnosed in our institution during that period). Ten of the patients were females and 16 males, and their median age at diagnosis was 69 years (range 38-85). The majority of patients (77%) had advanced disease (Ann Arbor stage III-IV) at presentation. Twenty-two patients (85%) had good performance status (0-1 ECOG). B-symptoms were present in 10 cases. Most patients (87%) presented with generalized adenopathies. Bone marrow involvement was observed in 12 patients (46%) and Waldeyer's ring involvement in 5 (4 of them with stage I-II). In 5 cases the liver was involved and 3 pts had gastrointestinal localizations; 15 patients had more than 2 sites of disease: LDH elevation was observed in 8/24 pts. Fourteen patients (54%) received single-agent chlorambucil (3 pts) or CVP (11 pts). Eleven patients were treated with ADM-containing regimens (7 with CHOP or M-ACOD and 4 with 3rd generation regimens). One patient had radiotherapy alone. The complete response (CR) rate was 50% (13/26); 8 patients relapsed with a median time to progression of 19 months, and only 3 responded to salvage treatment. The median overall survival was 33 months, with fewer than 40% of patients surviving longer than 3 years. At univariate analysis the use of ADM-containing regimens seems significantly correlated with the CR rate (p = 0.047), the failure-free survival (p = 0.023), and the overall survival (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Clonality assessment in blood of patients with mantle cell lymphoma.

The presence of circulating neoplastic cells at diagnosis was assessed in the blood of patients presenting with mantle cell lymphoma (MCL) to determine the feasibility of a diagnostic molecular assay. Blood samples from 16 patients with pathologically reviewed MCL were analysed for the t(11;14)(q13;q32) translocation by the polymerase chain reaction (PCR): 7 (44%) were found positive. The remaining cases were examined by PCR for the presence of circulating neoplastic B-cells by amplifying the third complementarity region (CDR3) of immunoglobulin heavy chain genes and the immunoglobulin light kappa chain deletion rearrangements. A further 7 (44%) patients showed the presence of clonal lymphoma cells, leaving only 2 (12%) of cases negative for circulating lymphomatous cells. This study suggests that there is a high incidence of lymphoma cells in the blood of patients presenting with MCL. PCR for these clonal cells may be diagnostically useful.

Primary mediastinal large B-cell lymphoma (PMLCL): the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) patients and bulky disease in 10 (37%). All patients were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year TTP and OS were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. In conclusion our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular lymphoma entity should be evaluated in prospective randomized trials.

Primary mediastinal large B-cell lymphoma: the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) and bulky disease in 10 (37%) patients. All were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 received more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year time to progression (TTP) and overall survival (OS) were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. Our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular type of lymphoma should now be evaluated in prospective randomized trials.

Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma.

The purpose of this paper is to report the clinical characteristics and treatment outcome following different therapeutic approaches in a large series of patients with primary low-grade MALT lymphoma of the stomach. A total of ninety-three patients (median age 63 years) were reviewed. The patients were treated by different modalities (local treatment alone, combined treatment, chemotherapy, antibiotics alone); seven patients refused any treatment. The antibiotic-treated group of patients was prospectively followed with regular endoscopic biopsies, and their responses were histologically evaluated. The 5-years projected overall survival is 82% (95% C.I.; 67%-91%) in the series as a whole. Second tumors were observed in 21.5% of the patients in this series (95% CI 14%v to 31%). There was no apparent difference in overall survival and event-free survival between patients who received different treatments. In the antibiotic-treated group histologic regression of MALT lymphoma was documented in 67% of patients (95% CI 51% to 80%). In conclusion the indolent nature of the disease justifies a conservative approach. The use of antibiotics as first-line therapy may avert or at least postpone the indication for surgical resection in the majority of patients.

Angiotropic (intravascular) large cell lymphoma: case report and short discussion of the literature.

We report a case of angiotropic (intravascular) large B-cell lymphoma in an 84-year-old woman who underwent diagnostic procedures for progressive, painful induration of the legs. Physical examination and imaging studies revealed only widespread telangiectasias and significant panniculities-like lymphedema of the legs, with no masses or lymphadenopathies. The patient achieved a complete clinical remission after the first three cycles of polychemotherapy. Although angiotropic lymphoma is a rare entity with polymorphic clinical presentations, its early diagnosis appears very important since it may be curable with appropriate chemotherapy regimens.

[Prevalence of hysterectomy and cancer of the uterus in the population of Tessin canton]. / Prévalence de l'hystérectomie et cancer de l'utérus dans la population du canton du Tessin.

The study presents an analysis of the prevalence of hysterectomy during the year 1982 in Canton Ticino, where the rate (507) per 100'000 women is double that found in the West Midlands area of Great Britain (P less than 0,001). No statisticaly significant difference is found in the mortality rate or morbidity rate for tumour of the cervix and body of the uterus.

[Lymphocytic gastritis]. / Gastrite à lymphocytes.

Lymphocytic gastritis is characterised by an accumulation of lymphocytes in the epithelium of the gastric mucosa. This form accounts for 4.5% of chronic B-gastritis and manifests itself by dyspepsia, anorexia and weight loss. The course is benign, as 12 of 19 patients recovered within 24 to 36 months in Haot's studies. Macroscopically it appears with nodules, erosions, thickened mucosal folds, or diffuse varioliform pattern. The gastric corpus is preferentially involved. The etiology is unknown. Some authors have hypothesized an abnormal immune response to a local antigen, i.e. Campylobacter pylori.

Reactive perivascular T-cell infiltrate predicts survival in primary central nervous system B-cell lymphomas.

Well-established histopathological prognostic factors are lacking in primary central nervous system (CNS) lymphomas (PCNSL). The present study investigated the presence and prognostic role of tumour necrosis (TN) and reactive perivascular T-cell infiltrate (RPVI), defined as a rim of small reactive T-lymphocytes occurring alone or located between the vascular wall and large neoplastic cells, in tumour samples from 100 immunocompetent patients with PCNSL. World Health Organization histotypes of the patients were: 96 diffuse large B-cell lymphomas, two Burkitt-like lymphomas, one anaplastic large T-cell lymphoma and one unclassified B-cell lymphoma. TN was observed in 24 (24%) cases and RPVI in 26 (36%) of 73 assessable cases. Patients with RPVI-positive lesions exhibited a significantly better overall survival (OS) than patients with RPVI-negative lymphoma, particularly among patients treated with high-dose methotrexate-based chemotherapy (3-year OS: 59 +/- 14% vs. 42 +/- 9%, P = 0.02). By contrast, the presence of TN did not demonstrate prognostic significance. Multivariate analysis confirmed an independent association between RPVI and survival. In conclusion, the presence of RPVI is independently associated with survival in PCNSL. This parameter can be easily and routinely assessed at diagnosis on histopathological specimens.