Mesothelioma and the Modalities of Aggressive Surgery Radiotherapy and Chemotherapy

Another study is called, "The palliative benefits of MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in patients with malignant Mesothelioma" by E. Andreopoulou, P. J. Ross, M. E. R. O'Brien*, H. E. R. Ford, K. Priest, T. Eisen, A. Norton, S. Ashley and I. E. Smith - Oxford Journals Medicine Annals of OncologyVolume15, Issue9Pp. 1406-1412.  Here is an excerpt: "Abstract - Background: With the rising incidence of malignant mesothelioma (MM), it is important to optimise treatment to control symptoms, maintain quality of life and, if possible, prolong life. We have analysed prospectively collected data to evaluate a frequently used palliative chemotherapy regimen. Patients and methods: Between October 1986 and May 2002 all patients with inoperable pleural mesothelioma were considered for treatment with MVP (mitomycin C 8 mg/m2 every 6 weeks, vinblastine 6 mg/m2 every 3 weeks and cisplatin 50 mg/m2 every 3 weeks) chemotherapy. Symptoms were assessed by physician assessment at baseline and after each cycle of chemotherapy.

Results: One hundred and fifty patients were treated with MVP for mesothelioma. Forty-three per cent had a performance status (PS) 2 or worse. The response rate was 15.3%, with 68.6% having stable disease. Sixty-nine per cent reported an improvement in symptoms; in particular there were good responses for pain (71%), cough (62%) and dyspnoea (50%). The most common grade 3/4 toxicity was neutropenia (22%). Median overall survival was 7 months, with 1-year survival 31% and 2-year survival 11%. Median survival for patients with PS 0/1 was 10 months, and was 6 months for patients with PS 2/3. Poor prognostic factors in univariate analysis included poor PS, weight loss, mixed or sarcomatoid histology, low haemoglobin and high white blood cell count. Excluding pathological subtype, the prognostic significance of poor PS and weight loss were retained in multivariate analysis. Conclusions: Palliation of symptoms in MM is achievable with current cisplatin-based treatments.

One interesting study is called, "Effects of glycosaminoglycans on proliferation of epithelial and fibroblast human malignant mesothelioma cells: a structure–function relationship" by Christopher Potten, Zbigniew Darzynkiewicz, Kohsuke Sasaki, A. Syrokou, G. Tzanakakis, T. Tsegenidis, A. Hjerpe, N. K. Karamanos - Cell Proliferation Volume 32, Issue 2-3, pages 85–99, April 1999.  Here is an excerpt: "Abstract. Proteoglycans interact with other effective macromolecules regulating a variety of cellular events via their glycosaminoglycan (GAG) chains. The effects of all known glycosaminoglycans (GAGs) produced by normal cells and tissues on the proliferation of two human malignant mesothelioma cell lines, one with fibroblast-like morphology and the other with epithelial differentiation – both able to produce hyaluronan (HA), galactosaminoglycans (GalAGs) and heparan sulphate (HS) containing proteoglycans – have been studied. Cell proliferation was assessed by measuring [3H]thymidine incorporation and cell number. GalAGs, i.e. chondroitin sulphates (CSs) and dermatan sulphate (DS), strongly stimulate the proliferation of fibroblast-like cells in a dose-dependent manner (170–250% at 100 μg/ml), independently of their sulphation pattern. In epithelial cells, however, only DS stimulates cell proliferation. The effects of CSs on proliferation of epithelial cells are not depended on their sulphation pattern. Thus, CSs either with -[GlcA-GalNAc-(-6-O-SO3−)]- or -[GlcA-GalNAc-(-4-O-SO3−]- as the commonest unit, had no significant effect. l-Iduronic acid (IdoA)-rich heparin and fast-moving HS (fm-HS), a HS fraction with a heparin-like structure, had significant antiproliferative effects on mesothelioma cells of both types (30–70% at 1.0 μg/ml and 85–90% at 100 μg/ml, respectively). GlcA-rich HS, however, had no significant effects. HA inhibits only the proliferation of fibroblast-like cells by 25% at 50 and 100 μg/ml. Keratan sulphate suppresses cell proliferation (10–30%) in both cell lines. In the view of these findings, a structure–function relationship of GAGs on cell proliferation of the two human malignant mesothelioma cell lines is discussed. Other factors, such as chain conformation and geometry, as well as interactions of growth factors with GAGs, possibly involved in the regulation of cell proliferation, are also discussed."

Another study is called, "Ectopic thymoma mimicking diffuse pleural mesothelioma: A case report" - Volume 29, Issue 4, Pages 409-410 (April 1998) by Hiroaki Fushimi, MD, Yoshiro Tanio, MD, Kiyoshi Kotoh, MD.  Here is an excerpt: "Abstract - A case of ectopic thymoma of the pleura with a particular growth pattern mimicking diffuse pleural mesothelioma is reported.  Diagnostic imaging showed that the pleural tumor encased the entire left lung. The specimen biopsied from the tumor was composed of lymphocytes and epithelial cells, consistent with the mixed type of thymoma. The autopsy found no evidence of a mediastinal tumor. An involuted thymus was found in the parietal pleural tissue adhered to the apex of the left lung. The thymoma was thought to originate from the ectopic thymic tissue in the parietal pleura, as a lesion independent from the primary mediastinal thymoma, and spread along the pleura like diffuse mesothelioma.

Conclusion: The results of our study have shown that fatal pulmonary toxicities were associated with radiation to the contralateral lung. V20 was the only independent determinant for risk of PRD or non–cancer-related death. The mean V20 of the non-PRD patients was considerably lower than that accepted during standard thoracic radiotherapy, implying that the V20 should be kept as low as possible after extrapleural pneumonectomy.

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