Department of Cardiology, University of Aberdeen, Aberdeen, Scotland AB25 2ZN, United Kingdom. g.small@abdn.ac.uk

Pericardial diseases can be difficult to differentiate from myocardial conditions. Diagnosis can be challenging and often requires the use of different imaging modalities. Here, we describe a case which presented with common cardiac symptoms which were shown to be the result of a rare condition. A 62-year-old lady presented with left femoral artery embolism. Post-embolectomy she developed cardiac failure. Three months previously an acellular, sterile pericardial effusion had been drained. In 1993 a left mastectomy and axillary node clearance was performed for breast cancer. Adjuvant chemotherapy and radiotherapy were administered. Examination revealed a raised jugular venous pressure (JVP) with rapid Y descent and Kussmaul’s sign. CT chest and abdomen found no recurrence of breast carcinoma. Cardiac MRI demonstrated thickened pericardium. At cardiac catheterisation haemodynamic responses consistent with constrictive pericarditis were seen. Pericardiectomy was performed. Histology revealed pericardial epithelioid malignant mesothelioma. 18-FDG-PET CT post-operatively was negative in the pericardium and pleura. Chemotherapy with pemetrexed and carboplatin was given. The patient died 9 months after presentation. Radiotherapy and asbestos exposure are both associated with pericardial mesothelioma and the aetiology in this case was not clear. The condition carries a poor prognosis and is invariable fatal although newer chemotherapeutic regimens have prolonged survival times.

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Department of Oncology, St. Olavs Hospital, Trondheim University Hospital, Norway; Norwegian University of Science and Technology (NTNU), Department of Cancer Research and Molecular Medicine, Trondheim, Norway.

Soluble mesothelin-related protein (SMRP) in serum is potentially a sensitive marker of malignant mesothelioma (MM) diagnosis and progression, and may be useful as screening marker. Mesothelin expression in tumors is regarded as a sensitive marker for diagnosis and disease progression, and is a candidate prognostic marker. Levels of SMRP, CA125 and CYFRA 21-1 in pre-diagnostic (1-30 years) serum samples from 47 mesothelioma cases and 141 matched controls were analysed. Mesothelin expression in tumors was assessed. The association between biomarker level and mesothelioma risk and survival was analysed, adjusting for asbestos exposure. Survival related to tumor mesothelin expression, age, sex, histological type, location, asbestos exposure and pre-clinical SMRP was analysed. There was no significant association between biomarker levels and mesothelioma risk when analysed as continuous variables or as tertiles. Biomarker levels <10, 10-19 and >/=20 years before diagnosis were not significantly associated to mesothelioma risk. Mesothelin expressed in >50% of tumor cells was seen in 36 of 47 (77%) tumors. Mesothelin expression in <50% of tumor cells was a significant negative prognostic marker in all cases of malignant mesothelioma (median survival=6 months vs. 12 months, hazard ratio (HR)=2.49, 95%CI 1.17-5.27), and also when only epithelial mesothelioma was analysed (median=6 months vs. 14 months, HR=2.36, 95%CI 1.07-5.22). When adjusted for age and gender, the prognosis was still dismal, but non-significant (HR=1.85, 95%CI 0.85-4.05). High age (>65 years) was an independent negative prognostic factor that was related to both mesothelin expression and asbestos exposure. Mesothelioma of the epithelial type of the peritoneum had a significantly longer survival than epithelial type in pleura and was also related to mesothelin expression.

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Service de Pneumologie, Pôle Coeur-Poumons-Vaisseaux, Université Basse-Normandie, CHU de Caen, France.

Malignant pleural mesothelioma (MPM) is a rare tumour due to occupational asbestos exposure. The incidence of MPM will continue to increase until 2020-2030. The incidence reaches 100 cases/million/year in occupationally exposed populations as opposed to 1 case/million/year in the general population, leading to 800 to 1,000 cases per year in France. The molecular carcinogenesis of MPM is incompletely understood but alterations to genes NF2, c-met, WT1 RASSF and p16 have been described. These genes are involved in cell invasion and motility, cell division and apoptosis control. Histological diagnosis remains difficult and depends on immunohistochemical analysis as described by the French Mesopath group. Clinical diagnosis relies on thoracoscopy and large pleural biopsies, with increasing use of CT-PET for the evaluation of disease extent. Therapeutic strategy includes prophylactic irradiation following drainage or thoracoscopy to prevent tumour nodule development along drainage channels and puncture sites. In selected patients, extensive extra-pleural pneumonectomy can be performed with curative intent. First line chemotherapy is based on a combination of pemetrexed and cisplatin that has demonstrated an improvement in overall survival and quality of life in phase 3 trials. Antiangiogenic agents such as bevacizumab (Avastatin) may be of interest but need to be tested in phase 3 trials. The Mesothelioma Avastatin Pemetrexed Study (MAPS) is ongoing, coordinated by the French Thoracic Cancer Intergroup (IFCT).

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Department of Health Evaluation Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. jmuscat@psu.edu

Talc, like asbestos, is a silicate that has been studied in relation to cancer risk. Several studies conducted over the past 25 years found an association between perineal talc powders and ovarian cancer. The summary relative risk is about 1.3 (95% confidence intervals 1.2-1.5) and these data have been interpreted as supporting a causal role. In this review article, we discuss the chemical and morphological features of talc and asbestos, and explain why despite their similar chemical classification talc does not possess asbestos-like carcinogenic properties. The heterogeneity in the perineal dusting studies has raised important concerns over the validity of the exposure measurements, and the lack of a consistent dose-response effect limits making causal inferences. Perhaps more importantly, whereas it is unknown whether external talc dust enters the female reproductive tract, measures of internal talc exposure such as talc-dusted diaphragms and latex condoms show no relationship with ovarian cancer risk. In addition, the therapeutic use of high dose cosmetic grade talc for pleurodesis has not been shown to cause cancer in patients receiving these treatment modalities. Talc is not genotoxic. Mechanistic, pathology and animal model studies have not found evidence for a carcinogenic effect. In summary, these data collectively do not indicate that cosmetic talc causes ovarian cancer.

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Immuno-Biological Laboratories, 5-1 Aramachi, Takasaki-Shi, Gunma 370-0831, Japan.

Mesothelioma is a type of malignant tumor that most commonly arises from the pleural or peritoneal membrane and is usually associated with previous exposure to asbestos. In humans, ERC/mesothelin is expressed on the normal mesothelium and in some cancers such as mesothelioma or ovarian carcinoma. Recently, several enzyme-linked immunosorbent assay (ELISA) systems for ERC/mesothelin have been developed, the reported usefulness of which has been assessed and demonstrated as a diagnostic tool. However, the basic roles or physiological functions of, and relationship between, ERC/mesothelin and asbestos exposure-mediated carcinogenesis remain to be resolved. In order to elucidate the precise mechanism, animal models of mesothelioma are desperately needed. In this study, we consider the development of a novel specific ELISA system for not only rat N-ERC/mesothelin but also C-ERC/mesothelin, and the first data on the presence of rat ERC/mesothelin in the body fluids of rat malignant mesothelioma-bearing nude mice. The transplanted mice have revealed the higher concentrations of rat N-ERC/mesothelin in the blood and ascites than C-ERC/mesothelin. We hope these novel ELISA systems are useful in the rat model system to clarify the mechanism of asbestos-induced carcinogenesis and to develop new effective drugs for mesothelioma.

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