Improved survival with combined chemo-radiotherapy in primary central nervous system lymphoma

Primary CNS lymphoma [PCNSL] is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long term disease control or prolonged survival. We retrospectively analyzed data on the effect of adding high-dose methotrexate [HDMTX] prior to whole brain irradiation [WBI]. All patients with PCNSL diagnosed and managed during 1991-2004 were identified and demographic characteristics, prognostic factors, treatment and outcome were reviewed. Of 62 patients, 10 were excluded [4 had WBI < 40 Gy and 6 had no treatment]. Radiation alone was considered curative with a dose > 40 Gy. Combined modality therapy included 3-4 cycles of HDMTX [3g/m2] followed by WBI. Of 52 patients analyzed for outcome, 36 had WBI [dose > 40 Gy], 16 received 3-4 cycles of HDMTX followed by WBI [combined modality therapy [CMT]]. Median age was 48.2 years; 42 years in the CMT group, 51 years in WBI. Patient characteristics were comparable between two groups except for higher multifocal tumor in the CMT group [92% vs. x22%, P=.029]. Median follow up was 12.83 +/- 6.4 months. The hazard ration for an event was 0.64 [95% CI, 0.52-0.98] and for death 0.58 [95% CI, 0.48-0.92], both in favor of CMT. Univariate regression analysis using one-way analyses of variance [ANOVA] and multivariate Cox regression analysis for prognostic factors including age [< 60 vs. >60], ECOG PS [0-2 vs. 3-4], extent of surgery [biopsy vs. debulking], solitary vs multifocal tumor and dose of radiation therapy [>50Gy vs. >50 Gy] failed to identify any prognostic factor. This retrospecitive comparison supports phase II trial results that indicate that high-dose methotrexate followed by WBI in PCNSL improves outcome

Biological markers in Helicobacter pylori-associated gastritis and carcinoma : the value of a scoring system

Background: Helicobacter pylori-associated gastritis has been linked to the pathogenesis of gastric adenocarcinoma [GA], especially when associated with intestinal metaplasia [IM] and atypia/dysplasia [A/D]. We examined p53 expression, ploidy and proliferative activity and assessed H. pylori infection in relationship to IM and/or A/D in cases of gastritis not associated with GA and in cases of GA

Methods: We examined 53 gastric biopsies from patients with gastritis not associated with GA, including patients with gastritis not associated with IM and/or A/D [n=35] and with gastritis associated with IM and/or A/D [n=21]. Thirty-six distal gastrectomy specimens from patients with GA constituted a third group of patients. A scoring system that encompassed the presence or absence of H. pylori, degree of gastritis, IM and/or A/D, p53, MIB-1 proliferative index [MPI] and ploidy was estimated in the cases of gastritis and in cancer-associated mucosa [CAM] and the adenocarcinoma from patients with GA

Results: Patients with GA had a higher median age than those with gastritis without IM and more were males [ratio, 2.2:1]. H. pylori was detected in 75% [40/53] of gastritis specimens and in 55% [20/36] of GA cases. There was a statistically significant difference between the incidence of gastritis without IM and/or A/D and CAM [P=0.01]. p53 expression was seen in 67% of cases [14/21] of gastritis with IM and/or A/D and in only 5% [2 cases] of gastritis without IM [P=0.0005]. A statistically significant difference in MPI was seen between CAM and GA [P=0.01] and gastritis without IM and/or A/D and gastritis with IM [P=0.004]. Cases of gastritis without IM and/or A/D had a median score of 8 while cases of gastritis with IM and/or A/D had a median score of 12 [P=0.0003]. CAM had a median score of 13, which was significantly different than gastritis without IM and/or A/D [P=0.0003]

Conclusion: The presence of IM and/or A/D can be used in H. pylori-associated gastritis as a starting point to further investigate high-risk lesions. Those showing p53 expression, high proliferative activity and aneuploidy require closer follow up and perhaps additional biopsies. Although aneuploidy is commonly seen in GA, its presence in cases of gastritis as an isolated finding should not indicate a high-risk lesion