Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

Peri- and postoperative management of stage I-III Non Small Cell Lung Cancer: Which quality of care indicators are evidence-based?

Quality of care (QoC) has a central role in our health care system. The aim of this review is to present a set of evidence-based quality indicators for the surgical treatment and postoperative management of lung cancer. A search was performed through PubMed, Embase and the Cochrane library database, including English literature, published between 1980 and 2012. Search terms regarding 'lung neoplasms', 'surgical treatment' and 'quality of care' were used. Potential QoC indicators were divided into structure, process or outcome measures and a final selection was made based upon the level of evidence. High hospital volume and surgery performed by a thoracic surgeon, were identified as important structure indicators. Sleeve resection instead of pneumonectomy and the importance of treatment within a clinical care path setting were identified as evidence-based process indicators. A symptom-based follow-up regime was identified as a new QoC indicator. These indicators can be used for registration, benchmarking and ultimately quality improvement in lung cancer surgery.

Legal claims for malignant mesothelioma: dealing with all cases.

BACKGROUND: Apart of medical reasons, a definitive diagnosis of malignant mesothelioma may be required as a basis for a claim of financial compensation although a pathological source of conclusive evidence is missing. Clinical assessment of all available data is then the only option to come to a final conclusion. We evaluated the diagnostic work-up of a large cohort of Dutch patients who applied for financial compensation due to mesothelioma. We determined how often a pathological or clinical diagnosis can be made, and which factors are associated with making the final diagnosis malignant mesothelioma. METHODS: A flow diagram of the diagnostic work-up was constructed for patients that applied to the Dutch institute for asbestos victims between 2005 and 2008 (N=1498). Both pathological and clinical factors that may influence the diagnostic outcome were assessed. RESULTS: In 97 of the 1498 patients (6%) no pathologic diagnosis could be established because of an uncertain diagnosis (N=54), inadequate (N=22) or unavailable tumor samples (N=21). A final pathological diagnosis of malignant mesothelioma could most often be made when biopsy samples were available compared to those in whom only cytological material was available. In patients in who no conclusive diagnosis could be made, clinical assessment was performed. Eighty percent of patients (66/83) who were clinically assessed were considered to have mesothelioma. None of the clinical features analyzed were strongly associated with a confirmed diagnosis of malignant mesothelioma. DISCUSSION: Our study shows that only in a small number of the patients who applied no pathologic diagnosis could be obtained. Based on judgment of clinical experts in the majority of these cases a near to certain diagnosis could be made. Moreover, it is reasonable to obtain biopsy material from patients to increase the chance to obtain a confirmed diagnosis. Therefore, it is important to refer patients early for diagnostic procedures.

Malignant pleural mesothelioma: the standard of care and challenges for future management.

This review addresses the management of MPM. In an introductory section, the etiology, epidemiology, presentation, diagnosis and staging of MPM will be reviewed. The evidence was collected by a systematic analysis of the literature (2000-2009) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment - INAHTA), NIH database (USA), International Pleural Mesothelioma Program - WHOLIS (WHO Database) with the following keywords and filters: pleura, cancer, mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, palliation, supportive care, pleurodesis, review.

Anti-angiogenesis drugs in lung cancer.

In the last years much attention has been given to the implementation of the so-called targeted drugs. One of the targets of tumours is the vasculature and this has led to the development of anti-angiogenic drugs. In lung cancer the use of these drugs has resulted in both positive and negative studies. In this paper the pros and cons are presented. We hope that this information will help the physician in making a proper treatment choice.

Evaluation of (18)F-FDG PET-CT for differentiation of pulmonary pathology in an approach of outpatient fast track assessment.

INTRODUCTION: The aim of our study was to evaluate the clinical performance/ implementation of integrated F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) for differentiation of pulmonary pathology in an approach of outpatient fast track assessment. METHODS: A prospective study was performed in 114 consecutive patients with pulmonary symptoms and/or abnormal chest x-ray were referred for fast track assessment to the Netherlands Cancer Institute from March 2005 to September 2007. The presence of malignancy was evaluated in a multidisciplinary setting, including F-fluorodeoxyglucose-PET, diagnostic CT, and bronchoscopy (including biopsy), with histopathological evaluation as the reference standard. RESULTS: In 105 patients (92%), a final diagnosis was achieved. A malignancy was diagnosed in 84% of the patients; non-small cell lung cancer in 67%, small cell lung cancer in 7%, and metastases or other malignancies in 10%. Nonmalignant lesions were found in 16% of the patients. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of positive PET/CT for the presence of malignancy were 97, 56, 90, 92, and 77%, respectively. PET/CT showed unexpected M1 disease (not detected on CT) in 10% of the patients. Almost half of the patients with a malignancy were scheduled for curative treatment, of whom 29 patients for surgery and 14 patients for chemoradiotherapy. CONCLUSION: In this outpatient fast track setting, PET/CT provides valuable information for diagnosing lung cancer, with a high positive predictive value, and is useful for clinical decision making.

The value of chest computer tomography and cervical mediastinoscopy in the preoperative assessment of patients with malignant pleural mesothelioma.

BACKGROUND: Patients with localized malignant pleural mesothelioma (MPM) can be considered for surgical resection with or without additional treatment. For this approach it is imperative to select patients without mediastinal lymph node involvement. In this study cervical mediastinoscopy (CM) is compared with computer tomography (CT) scanning for its diagnostic accuracy in assessing mediastinal lymph nodes during preoperative workup. METHODS: Computer tomography scans of the chest and CM were performed in 43 patients with proven unilateral MPM. The CT scans were reviewed by one radiologist and two chest physicians. At CM the lymph node samples were taken from stations Naruke 2, 3, 4, and 7. Computer tomography and CM results were compared with final histopathologic findings obtained at thoracotomy or, if this was not performed, at CM. RESULTS: Computer tomography scanning revealed pathologic enlarged lymph nodes with a shortest diameter of at least 10 mm in 17 of 43 patients (39%). There was histopathologic evidence of lymph node metastases at CM in 11 of these patients (26%). This resulted in a sensitivity of 60% and 80%, a specificity of 71% and 100%, and a diagnostic accuracy of 67% and 93% for CT and CM, respectively. CONCLUSIONS: Cervical mediastinoscopy is a valuable diagnostic procedure for patients with MPM who are considered candidates for surgical-based therapy. Results of CM are more reliable than those obtained by CT scanning. Our data confirm results of previous studies reporting that mediastinal lymph node involvement is a frequent event in MPM.