Age, PS, LDH serum level, CSF protein concentration, and involvement of deep structures of the brain were independent predictors of survival. A prognostic score including these five parameters seems advisable in distinguishing different risk groups in PCNSL patients. The proposed score and its relevance in therapeutic decision deserve to be validated in further studies.

SummaryWell-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 ¼ 0AE02). 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.

This study focuses on the development of fibrosis of the liver of cattle with Fasciola hepatica infection, correlating with the intensity of infection. Animals with an established diagnosis of chronic F. hepatica infection were identified in a slaughterhouse in Lima, Peru. The study included 24 fresh cattle livers from infected animals and two uninfected controls. Tissues were stored at 4 degrees C for approximately 8 h after which they were brought to a necropsy room and examined. Between 9 and 12 biopsies were randomly obtained from each liver. Histological staining of formalin-fixed liver sections with haematoxylin and eosin (H & E) and Masson's trichrome were performed. Liver samples were examined using a pathology protocol that included 30 items. Histopathologically, 16 out of 30 liver specimens (67.6%) showed diffuse fibrotic lesions (cirrhosis) with a mean number of Fasciola of 116 +/- 30 (range 4-435). Pathological data were matched to number of adult parasites and presence of cirrhosis after being reviewed by two independent pathologists. There was concordance between the two pathologists (K = 0.72). The group with cirrhosis showed an average of 116 +/- 30 adult parasites whereas the group not showing cirrhosis contained 56 +/- 28 flukes (P = 0.2). To measure how number of flukes and diagnosis of cirrhosis are related we used Kendall's tau-b coefficient; the correlation was +0.296 (P = 0.04). Receiver Operating Characteristic (ROC) curve results showed that the best point was 38 parasite adults, which had 93.8% sensitivity and 75% specificity. We conclude that as the number of F. hepatica adult forms increases, the likelihood of developing liver fibrosis will also increase in cattle.

Purpose: This phase II trial of pemetrexed explored potential correlations between treatment outcome (antitumor activity) and molecular target expression. Experimental Design: Chemonaïve patients with advanced breast cancer received up to three cycles of pemetrexed 500 mg/m 2 (10-minute i.v. infusion) on day 1 of a 21-day cycle, with folic acid and vitamin B 12 supplementation. Tumors were surgically removed after the last cycle of pemetrexed as clinically indicated. Biopsies were taken at baseline, 24 hours after infusion in cycle 1, and after cycle 3. Results: Sixty-one women (median age, 46 years; range, 32-72 years) were treated and were evaluable for response. Objective response rate was 31%. Simple logistic regression suggested a potential relationship between mRNA expression of thymidylate synthase (TS) and pemetrexed response (P = 0.103). Based on threshold analysis, patients with ''low'' baseline TS (V71) were more likely to respond to pemetrexed than patients with ''high'' baseline TS (>71). Expression of baseline dihydrofolate reductase and glycinamide ribonucleotide formyl transferase tended to be higher in responders but this association was not significant (P > 0.311). TS expression increased significantly between baseline and biopsy 2 (P = 0.004) and dropped to near baseline levels at biopsy 3. Conversely, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase decreased after pemetrexed chemotherapy. Conclusions: Our results suggest a potential association between ''low''pretreatmentTS expression levels and response to pemetrexed chemotherapy. Future trials examining expression levels of other genes important to the folate pathway and/or breast cancer may identify a more robust multigene profile that can better predict response to this novel antifolate.

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