Nola Olsen

Increasing incidence of malignant mesothelioma after exposure to asbestos during home maintenance and renovation.

Objective: To determine trends in incidence of malignant mesothelioma (MM) caused by exposure to asbestos during home maintenance and renovation.

A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit

Aims: Cytological diagnosis of malignant pleural mesothelioma (MPM) is controversial, but has been used in our institution for over 30 years. To assess the role of effusion cytology in mesothelioma diagnosis we conducted an audit of pleural fluid cytology results over a 20 year period (1988–2007). Methods: Pleural samples were received from 6285 patients; data linkage with Western Australian Cancer and Mesothelioma Registries demonstrated that 815 of these patients had a diagnosis of MPM. Cytological examination of a pleural effusion specimen had been performed in 517 (63%) of these 815 patients. Results: Definitive cytological diagnosis of MPM was made in 377/517 cases, resulting in an ‘absolute’ sensitivity of 73%. An additional 66 patients were diagnosed as atypical/suspicious, resulting in a ‘complete’ sensitivity of 86%. If only biopsy/necropsy proven cases are considered, the absolute sensitivity is 68% and the complete sensitivity is 82%. There were no false positive diagnoses of malignancy; two patients with metastatic adenocarcinoma were initially diagnosed as MPM, prior to the availability of specific mesothelial markers, resulting in a positive predictive value of 99%. Conclusions: Effusion cytology is an inexpensive, minimally invasive procedure which should be included in the diagnostic work-up of cases of suspected MPM.

Postmortem Findings of Malignant Pleural Mesothelioma A Two-Center Study of 318 Patients

BACKGROUND Malignant pleural mesothelioma (MPM) is an incurable cancer with a rising incidence. MPM is often perceived as a locally invasive cancer, and the exact cause of death is poorly understood.This two-center study describes the anatomic features of patients with MPM at postmortem. METHODS The Western Australia Mesothelioma Registry (Australia) and Coroner’s Office reports from the Avon region (England) were interrogated for the postmortem records of confirmed mesothelioma cases. RESULTS Postmortem records of 318 patients with pleural mesothelioma (169 from Western Australia and 149 from Avon) were identified. Most patients (91.5%) were men (mean age, 68.4 ± 11.5 years), and MPM was right-sided in 55.3%. Extrapleural dissemination of tumor was found in 87.7% of cases and lymph node involvement in 53.3%. Tumor dissemination in extra thoracicsites was common (55.4% of patients), and almost all organs were involved, including liver(31.9%), spleen (10.8%), thyroid (6.9%), and the brain (3.0%). Pulmonary emboli were found in 6% of cases and considered as directly contributing to death in 13 patients (4.1%). The precise cause of death could only be determined in 63 (19.8%) cases even after postmortem. The BMI was significantly lower in cases that had no identifiable anatomic cause of death at postmortem(18.8 ± 4.3 vs 21.0 ± 4.7, P = .034). CONCLUSIONS In this largest, to our knowledge, postmortem series on MPM, extrathoracic dissemination of mesothelioma was common and often under recognized. No anatomic cause of death was identified in the majority of patients even at autopsy, raising the possibility of physiologic and metabolic causes of death.

Original ResearchDisorders of the PleuraPostmortem Findings of Malignant Pleural Mesothelioma: A Two-Center Study of 318 Patients

BACKGROUND Malignant pleural mesothelioma (MPM) is an incurable cancer with a rising incidence. MPM is often perceived as a locally invasive cancer, and the exact cause of death is poorly understood.This two-center study describes the anatomic features of patients with MPM at postmortem. METHODS The Western Australia Mesothelioma Registry (Australia) and Coroner’s Office reports from the Avon region (England) were interrogated for the postmortem records of confirmed mesothelioma cases. RESULTS Postmortem records of 318 patients with pleural mesothelioma (169 from Western Australia and 149 from Avon) were identified. Most patients (91.5%) were men (mean age, 68.4 ± 11.5 years), and MPM was right-sided in 55.3%. Extrapleural dissemination of tumor was found in 87.7% of cases and lymph node involvement in 53.3%. Tumor dissemination in extra thoracicsites was common (55.4% of patients), and almost all organs were involved, including liver(31.9%), spleen (10.8%), thyroid (6.9%), and the brain (3.0%). Pulmonary emboli were found in 6% of cases and considered as directly contributing to death in 13 patients (4.1%). The precise cause of death could only be determined in 63 (19.8%) cases even after postmortem. The BMI was significantly lower in cases that had no identifiable anatomic cause of death at postmortem(18.8 ± 4.3 vs 21.0 ± 4.7, P = .034). CONCLUSIONS In this largest, to our knowledge, postmortem series on MPM, extrathoracic dissemination of mesothelioma was common and often under recognized. No anatomic cause of death was identified in the majority of patients even at autopsy, raising the possibility of physiologic and metabolic causes of death.

Pleurodesis outcome in malignant pleural mesothelioma

Few data exist on the pleurodesis outcome in patients with malignant pleural mesothelioma (MPM). A retrospective review of the Western Australian Mesothelioma Registry over 5 years revealed 390 evaluable patients. Only a subset of patients (42.3%) underwent pleurodesis, surgically (n=78) or by bedside instillation of sclerosants (n=87). Surgical pleurodesis showed no advantages over bedside pleurodesis in efficacy (32% vs 31% failures requiring further drainage, p=0.98), patient survival (p=0.52) or total time spent in hospital from procedure till death (p=0.36). No clinical, biochemical or radiographic parameters tested adequately predict pleurodesis outcome.

Effects of asbestos and smoking on the levels and rates of change of lung function in a crocidolite exposed cohort in Western Australia

Background: Increased rates of death from asbestos related diseases have been reported in former workers and residents exposed to crocidolite (blue asbestos) at Wittenoom, Western Australia. Exposure to asbestos is associated with reduced static lung volumes, gas transfer and lung compliance, and a restrictive ventilatory abnormality. Methods: The effects of crocidolite exposure and smoking history on levels and rates of change of lung function were evaluated using a linear mixed model. Lung function was measured as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC. Results: Cumulative doses of asbestos and the presence of radiographic asbestosis were associated with lower levels of FEV1 and FVC and a steeper decline during the period of observation. Subjects exposed to asbestos at a younger age had lower levels of FEV1 and FVC. Current smokers had lower levels and a steeper decline in lung function than never smokers. No significant interactions between crocidolite exposure and smoking on the levels or rates of change of lung function were found. Conclusions: The deleterious effects of crocidolite exposure on lung function persist in this population, despite asbestos exposure having ceased more than 30 years ago. No significant interactions were found in this population between asbestos and smoking at the first visit or longitudinally.

Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia

Clustering of cases of malignant mesothelioma within families has often been observed, but disentangling genetic and exposure effects has not been done. Former workers and residents exposed to crocidolite at Wittenoom, Western Australia, where many families shared exposure to asbestos, have had high rates of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma in relatives, after allowance for common exposure to crocidolite. More than 11,000 former asbestos workers and residents from Wittenoom have been followed up in cancer and death registries. Levels of exposure for all members of the Wittenoom cohorts have been estimated previously. Relationships between family members of all mesothelioma cases were established from questionnaires, birth and death certificates. Expected numbers of cases of mesothelioma were estimated by fitting a Weibull survival model to all data, based on time from first asbestos exposure, duration and intensity of exposure and age. For each family group, the earliest case was considered the index case. Predicted risk was estimated for each subject from the time of diagnosis of the index case. Familial risk ratios were estimated by dividing observed cases by the sum of risks of all same degree relatives of index cases. There were 369 family groups with at least one case of mesothelioma and a further 25 cases of mesothelioma among relatives in the same families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95% confidence interval [CI] = 1.3–2.9, p = 0.002). These findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers.

Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma

Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility. BAP1 gene somatic mutations and allelic loss are common in mesothelioma and recently a BAP1 cancer syndrome was described in which affected individuals and families had an increased risk of cancer of multiple types, including MM. To determine if BAP1 mutations could underlie any of the sporadic mesothelioma cases in our cohort of patients, we performed targeted deep sequencing of the BAP1 exome on the IonTorrent Proton sequencer in 115 unrelated MM cases. No exonic germline BAP1 mutations of known functional significance were observed, further supporting the notion that sporadic germline BAP1 mutations are not relevant to the genetic susceptibility of MM.

Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma.

Rationale. The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain. Objectives. To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM. Methods and Measurements. Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined. Results. 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy. Conclusions. A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis.

Retinol supplementation and mesothelioma incidence in workers earlier exposed to blue asbestos (Crocidolite) at Wittenoom, Western Australia

Owing to the high rates of malignant mesothelioma in workers exposed to crocidolite earlier at Wittenoom and evidence of protection against cancer by vitamin A, a population-based cancer prevention programme providing retinol supplements (25 000 IU/day) was commenced in 1990. The former workers at Wittenoom known to be alive and living in Western Australia in June 1990 constitute the study population. The participants were classified into two groups: those who received supplemental retinol (intervention group) and those who received none (comparison group). The relative rate of mesothelioma for those receiving retinol was estimated using Cox regression, adjusting for cumulative asbestos exposure and age at first exposure to asbestos. Nine hundred and twenty-eight former Wittenoom workers received retinol at some stage of the programme, whereas 1471 workers never received retinol (comparison group). Those who received retinol were younger, had a greater exposure to asbestos and smoked less than the comparison group. There were 65 cases of mesothelioma in the retinol group and 88 in the comparison group. After adjustment, the hazard ratio was 0.99 (95% confidence interval=0.70–1.41). This result did not alter when the participants who received only retinol once or those who received β-carotene earlier were excluded from the analysis. In conclusion, this study provides little support for possible preventive effects of retinol against mesothelioma in workers exposed to blue asbestos.