Purpose: The pemetrexed/platinum agent combination represents the standard of care in first-line treatment for malignant pleural mesothelioma (MPM). However, there are no established indicators of responsiveness that can be used to optimize the treatment. This retrospective study aimed to assess the role of excision repair cross-complementing group-1 (ERCC1) and thymidylate synthase (TS) in tumors, and correlate expression levels and polymorphisms of these key determinants of drug activity with the outcome of MPM patients treated with carboplatin/pemetrexed in first-line setting.Experimental design: Analysis of TS and ERCC1 polymorphisms, mRNA and protein expression was done by PCR and immunohistochemistry [with the H-score (histologic score)] in tumor specimens from 126 MPM patients, including 99 carboplatin-/pemetrexed-treated patients.Results: A significant correlation between low TS protein expression and disease control (DC) to carboplatin/pemetrexed therapy (P ¼ 0.027), longer progression-free survival (PFS; P ¼ 0.017), and longer overall survival (OS; P ¼ 0.022) was found when patients were categorized according to median H-score. However, patients with the higher tertile of TS mRNA expression correlated with higher risk of developing progressive disease (P ¼ 0.022), shorter PFS (P < 0.001), and shorter OS (P < 0.001). At multivariate analysis, the higher tertile of TS mRNA level and TS H-score confirmed their independent prognostic role for DC, PFS, and OS. No significant associations were found among ERCC1 protein expression, TS and ERCC1 polymorphisms, and clinical outcome.Conclusions: In our series of carboplatin-/pemetrexed-treated MPM patients, low TS protein and mRNA levels were significantly associated to DC, improved PFS, and OS. Prospective trials for the validation of the prognostic/predictive role of TS in MPM patients treated with pemetrexed-based regimens are warranted.
Influenza vaccination is generally recommended for non-Hodgkin’s lymphoma (NHL) patients, but no data are available about the activity of this vaccine after treatment with rituximab-containing regimens. We evaluated the humoral response to the trivalent seasonal influenza vaccine in a group of NHL patients in complete remission for ≥6 mo (median, 29 mo) after treatment with rituximab-containing regimens (n = 31) compared with age-matched healthy subjects (n = 34). B cell populations and incidence of influenza-like illness were also evaluated. For each viral strain, the response was significantly lower in patients compared with controls and was particularly poor in patients treated with fludarabine-based regimens. In the patient group, the response to vaccination did not fulfill the immunogenic criteria based on the European Committee for Medicinal Products for Human Use requirements. Among the patients, CD27+ memory B cells were significantly reduced, and their reduction correlated with serum IgM levels and vaccine response. Episodes of influenza-like illness were recorded only in patients. These results showed that NHL patients treated with rituximab-containing regimens have persisting perturbations of B cell compartments and Ig synthesis and may be at particular risk for infection, even in long-standing complete remission.
Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm which may be found everywhere in the body. It is now distinguished into two forms, pleural and extrapleural, which morphologically resemble each other. Abdominal localizations are quite rare, with 10 cases only reported in bladder; rarely they can be source of paraneoplastic syndromes (i.e., hypoglycemia secondary to insulin-like growth factor). In April 2006 a 74-year-old white male presented with chills, diaphoresis and acute abdominal pain with hematuria. At admission in emergency he underwent an abdominal Xray (no pathological findings) and an ultrasound examination of the kidneys and urinary tract, which revealed a pelvic hyperechogenic neoformation measuring approximately 10×8×7 cm, compressing the bladder. Blood chemistry at admission revealed only a mild neutrophilic leucocytosis (WBC 16600, N 80%, L 11%), elevated fibrinogen and ESR, and hypoglycemia (38 mg/dL). Macro scopic hematuria was evident, while urinocolture was negative. Contrast enhanced CT scan of the abdomen and pelvic region revealed a large round neoformation dislocating the bladder, with an evident contrast-enhanced periphery and a central necrotic area. Continuous infusion of glucose 5% solution was necessary in order to maintain blood glucose levels above 50 mg/dL. The patient underwent complete surgical resection of an ovoidal mass coated by adipose tissue, with well delimited margins; histological findings were consistent with solitary fibrous tumor (SFT). Hypoglycemia resolved completely with removal of the growth. In this case report we describe a SFT growing in the bladder, a quite rare localization, which presented a unique hypoglycemia. In contrast to the majority of cases reported in the literature, the behavior of this SFT was not aggressive, and, since the patient is still alive, surgical resection was considered conclusive.
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