Vroeg-screening voor mesothelioom

28-10-2008

Volgens Van Meerbeeck en Hillerdal is vroeg-screening voor de ziekte mesothelioom op dit moment nog niet zinvol.
De nieuwste diagnostische scantechnieken (CT/PET) en bloedtests (SMRP-ELISA) zijn nog niet voldoende nauwkeurig. Verder is er nog geen bewijs dat vroeg-ontdekking van deze ziekte de levensduur kan verlengen of de patiënt kan genezen. Bron:
Meerbeeck, J.P. van & Hillerdal, G. (2008). Screening vor mesothelioma. More harm than good? American Journal of Respiratory and Critical Care Medicine, vol178, pp 781-82.

Overzichtsstudies asbestziekten

23-10-2008

Franse en Amerikaanse onderzoekers beschrijven in twee overzichtsartikelen de ontwikkelingen in de diagnostiek en behandeling van asbestgerelateerde ziekten, waaronder mesothelioom.

 

Greillier, L. & Astoul, P. (2008). Mesothelioma and asbestos-related pleural diseases. Respiration. 2008;76(1):1-15. 
ABSTRACT
At present, the use of asbestos is not regulated at a worldwide scale. Moreover, there is a latency period between asbestos exposure and the manifestations of asbestos-related diseases. Consequently, pulmonologists are still dealing with consequences of asbestos exposure, which mainly occur at the pleural surface. The aim of this review is to provide an overview of asbestos-related pleural diseases. We summarized the most relevant data for the diagnosis and the management of benign asbestos pleural effusions, pleural plaques, diffuse pleural thickening and rounded atelectasis. Special attention is dedicated to malignant pleural mesothelioma, given the challenging issues of this disease, the recent advances in its management and the dynamism of research in this area.

Zervos, M.D. et al. (2008). Malignant mesothelioma 2008.Curr Opin Pulm Med. 2008 Jul;14(4):303-9. 
ABSTRACT
PURPOSE OF REVIEW: Mesothelioma is an aggressive malignancy of the pleura with poor survival. There will be approximately 3000 cases of mesothelioma in the United States annually. Multimodality treatment including neoadjuvant chemotherapy in selected individuals followed by extrapleural pneumonectomy and radiation has been studied in recent trials for its effects on disease free and overall survival This review provides a general overview of malignant mesothelioma with a summary of the most significant articles from within the past year as well as from the past. RECENT FINDINGS: Areas of recent interest include the evaluation of osteopontin and mesothelin as new tumor markers for mesothelioma. New phase III trials have been performed to evaluate the use of combined chemotherapy regimens. SUMMARY: Malignant mesothelioma is a very difficult malignancy to treat. Patients with the disease usually have an occupational asbestos exposure, and in some, viral exposure with SV40. There have been many historical treatments including combinations of local control with surgery and radiation as well as attempts to prevent systemic failure with chemotherapy. Novel therapies including intrapleural chemotherapy, photodynamic therapy and hyperthermic perfusion have also been used with some success. Finally there are several attempts at immunomodulating and targeted treatments, which are in phase I/II trials.

SV40-virus veroorzaakt mesothelioom

23-10-2008

Volgens Rivera et al., is er voldoende bewijs om aan te nemen dat het simian 40 virus de ziekte mesothelioom kan veroorzaken: zowel alleen als in combinatie met asbestcontact.
Het bewijs is echter nog onvoldoende om te kunnen bepalen in welke mate het virus oorzaak is van deze ziekte. Het sv40 virus was oorspronkelijk een virus dat alleen bij apen voorkwam, maar bleek per abuis in de jaren 60 van de vorige eeuw ook in het poliovaccin te zitten.
Bron: Rivera, Z. et al. (2008). The relationship between simian virus 40 and mesothelioma. Curr Opin Pulm Med. 2008 Jul;14(4):316-21.
ABSTRACT
PURPOSE OF REVIEW:
Simian virus 40 is present in some human malignant mesotheliomas. The evidence in favor and against a pathogenic role of simian virus 40 in malignant mesothelioma is discussed in this review.
RECENT FINDINGS: When simian virus 40 is injected intracardially into hamsters, 60% develop and die of malignant mesothelioma. Moreover, some human malignant mesotheliomas contain and express simian virus 40 DNA and proteins. To date, over 50 laboratories have detected simian virus 40 in malignant mesotheliomas and in other tumors; however, the variability of the percentage of positivity led to a controversy about the role and significance of simian virus 40 in malignant mesotheliomas. Compared with other cell types, human mesothelial cells are unusually susceptible to simian virus 40-induced malignant transformation. The presence of simian virus 40 in malignant mesothelioma has been associated with the activation of specific oncogene pathways. Cocarcinogenesis between simian virus 40 and asbestos in causing malignant mesotheliomas has been demonstrated in three separate research laboratories using different experimental approaches. Epidemiological data possibly linking simian virus 40 and malignant mesothelioma is lacking owing to unattainable identification of infected from noninfected cohorts.
SUMMARY: Available evidence appears sufficient to link simian virus 40 either alone or in conjunction with asbestos in causing malignant mesotheliomas; however, it is still insufficient to speculate about the contribution of simian virus 40 to the overall incidence of malignant mesotheliomas.

Levensverwachting

02-10-2008

Moshammer en Neuberger concluderen dat de verslechtering van de conditie van de longen een betere voorspeller is van de levensverwachting is dan de kennis over de hoeveelheid asbest waaraan iemand is blootgesteld. Volgens Christensen et al. is er een relatie tussen het aantal asbestvezels dat in de longen aangetroffen wordt en de levensverwachting van een mesothelioompatiënt.
Bron: Moshammer, H. & Neuberger, M. (2008). Lung function predicts survival in a cohort of asbestos cement workers. Int Arch Occup Environ Health. 2008 Apr 12. ABSTRACT

PURPOSE: To study the predictive power of respiratory screening examinations a cohort of asbestos workers was followed from active work in an asbestos cement plant until death.

METHODS: From a cohort with data on individual exposure since first employment 309 workers who had a preventive medical examination in 1989/1990 were observed until death or the end of 2006. The impact of asbestos exposure (fibre years) and of smoking history on lung function was examined by linear regression, on specific causes of death and total mortality by Cox regression. The prognostic value of lung function, chest X-ray, and various clinical findings regarding total mortality was also examined by Cox regression.

RESULTS: Lung function proved to be the best predictor of survival apart from current smoking. Depending on the lung function variable an impairment by the interquartile range resulted in a hazard ratio of 1.5-1.6 while for current smokers it was 2.3. An increase of 70 fibre years (interquartile range) led to a hazard ratio of only 1.1. Lung function was influenced by asbestos exposure, current (but not former) smoking, and by pathological X-ray findings. The risk for pleural mesothelioma was dominated by time since first exposure to crocydolite in the pipe factory while the risk for bronchial cancer increased with smoking and total fibre years. An unexpected finding was an increase of gastric cancer in asbestos cement workers.

CONCLUSION: Lung function decrease predicts risk of premature death better than exposure history and regular spirometry should therefore be offered as primary screening to all former asbestos workers. In workers with a history of high cumulative exposure or rapid lung function decrease or radiological signs (diffuse pleural thickening or small irregular opacities) more sensitive techniques (high resolution computer tomography) need to be applied. All smokers with a history of asbestos exposure should be given free smoking cessation therapy to prevent premature death and lung cancer in particular.

Bron: Christensen, B.C. et. al. (2008). Asbestos burden predicts survival in pleural mesothelioma. Environmental  Health Perspectives, Jun;116(6):723-6.

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rapidly fatal asbestos-associated malignancy with a median survival time of <1 year following diagnosis. Treatment strategy is determined in part using known prognostic factors. OBJECTIVE: The aim of this study was to examine the relationship between asbestos exposure and survival outcome in MPM in an effort to advance the understanding of the contribution of asbestos exposure to MPM prognosis. Methods: We studied incident cases of MPM patients enrolled through the International Mesothelioma Program at Brigham and Women's Hospital in Boston, Massachusetts, using survival follow-up, self-reported asbestos exposure (n=128), and a subset of cases (n=80) with quantitative asbestos fiber burden measures. Results: Consistent with the established literature, we found independent, significant associations between male sex and reduced survival (p<0.04), as well as between nonepithelioid tumor histology and reduced survival (p<0.02). Although self-reported exposure to asbestos was not predictive of survival among our cases, stratifying quantitative asbestos fiber burden [number of asbestos bodies per gram of lung (wet weight)] into groups of low (0-99 asbestos bodies), moderate (100-1,099), and high fiber burden (>1,099), suggested a survival duration association among these groups (p=0.06). After adjusting for covariates in a Cox model, we found that patients with a low asbestos burden had a 3-fold elevated risk of death compared to patients with a moderate fiber burden [95% confidence interval (CI), 0.95-9.5; p=0.06], and patients with a high asbestos burden had a 4.8-fold elevated risk of death (95% CI, 1.5-15.0; p<0.01) versus those with moderate exposure. Conclusion: Our data suggest that patient survival is associated with asbestos fiber burden in MPM and is perhaps modified by susceptibility.

Een medisch wonder

01-08-2008

Een 46-jarige Australische vrouw is zwanger geworden kort nadat zij door haar artsen genezen was verklaard van de ziekte mesothelioom.
Inmiddels is zij vijf maanden zwanger. Volgens deskundigen behoort zij tot de ‘derde golf’ van asbestslachtoffers in Australië; mensen die als kind in een omgeving speelden waar met asbest werd gewerkt. Bron: The Age, 26 juli 2008.

Aantal asbestvezels in longen voorspelt overleving mesothelioom

24-06-2008

Er is een relatie tussen het aantal asbestvezels dat in de longen aangetroffen wordt en de levensverwachting van een mesothelioompatiënt.

Dat concluderen Amerikaanse onderzoekers na onderzoek bij 80 mesothelioompatiënten. Deze relatie wordt waarschijnlijk wel beïnvloed door de aanleg/gevoeligheid van de patiënt. Andere factoren die de levensverwachting beïnvloeden zijn het geslacht en het type tumor.

Bron: Christensen, B.C. et. al. (2008). Asbestos burden predicts survival in pleural mesothelioma. Environmental  Health Perspectives, Jun;116(6):723-6.

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rapidly fatal asbestos-associated malignancy with a median survival time of <1 year following diagnosis. Treatment strategy is determined in part using known prognostic factors. OBJECTIVE: The aim of this study was to examine the relationship between asbestos exposure and survival outcome in MPM in an effort to advance the understanding of the contribution of asbestos exposure to MPM prognosis. Methods: We studied incident cases of MPM patients enrolled through the International Mesothelioma Program at Brigham and Women's Hospital in Boston, Massachusetts, using survival follow-up, self-reported asbestos exposure (n=128), and a subset of cases (n=80) with quantitative asbestos fiber burden measures. Results: Consistent with the established literature, we found independent, significant associations between male sex and reduced survival (p<0.04), as well as between nonepithelioid tumor histology and reduced survival (p<0.02). Although self-reported exposure to asbestos was not predictive of survival among our cases, stratifying quantitative asbestos fiber burden [number of asbestos bodies per gram of lung (wet weight)] into groups of low (0-99 asbestos bodies), moderate (100-1,099), and high fiber burden (>1,099), suggested a survival duration association among these groups (p=0.06). After adjusting for covariates in a Cox model, we found that patients with a low asbestos burden had a 3-fold elevated risk of death compared to patients with a moderate fiber burden [95% confidence interval (CI), 0.95-9.5; p=0.06], and patients with a high asbestos burden had a 4.8-fold elevated risk of death (95% CI, 1.5-15.0; p<0.01) versus those with moderate exposure. Conclusion: Our data suggest that patient survival is associated with asbestos fiber burden in MPM and is perhaps modified by susceptibility.

Multimodale behandeling bij mesothelioom

11-06-2008

Mesothelioompatiënten die in aanmerking komen voor operatieve verwijdering van de tumor hebben, volgens chirurg en oncoloog dr. Robert Cameron van de Universiteit van Californië. (UCLA), de meeste baat bij een multimodale behandeling. Deze behandeling bestaat uit een operatie, bestraling en chemotherapie. Patiënten zouden hierover zowel advies moeten vragen aan een thoracaal chirurg als aan een oncoloog. Bron: www.mesothel.com, 21 mei 2008. Meer http://www.mesothel.com/

Nanobuisjes net als asbest

31-05-2008

Koolstof nanobuisjes, een van de belangrijkste nieuwe moleculen in de nanotechnologie, kunnen in het buikvlies van muizen een ontstekingsreactie veroorzaken die lijkt op het beginstadium van mesothelioom. Dat blijkt uit een studie die deze week is gepubliceerd in het tijdschrift Nature Nanotechnology. Volgens Ken Donaldson (universiteit van Edinburgh), één van de auteurs, is het te vroeg om te concluderen dat mensen die in contact komen met nanobuisjes daar ook echt kanker van kunnen krijgen. De muizen kregen de nanobuisjes namelijk ingespoten in hun buikvlies. Om het risico voor mensen te bepalen moet vast staan hoeveel nanobuisjes mensen inademen en of die moleculen in het long- of buikvlies terecht kunnen komen. Nanobuisjes bestaan uit koolstofatomen die op een speciale manier met elkaar zijn verbonden. Ze worden al jaren verwerkt in consumentenproducten als tennisrackets, schokbestendige fietssturen en auto-onderdelen. Bron: NRC en kennislink, 22 mei 2008. Meer http://www.kennislink.nl/

Twijfels over effecten chemotherapie bij mesothelioom

31-05-2008

Een studie in het medische tijdschrift Lancet meldt dat honderden mesothelioompatiënten van een groep van 409 geen baat hadden bij een chemokuur met mitomycin, vinblastine en cisplatine. Behandeling met vinorelbine verdient echter nader onderzoek. Bron: BBC news, 15 mei. Muers, M.F., et. al. (2008). Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet 2008. 371:1685-94. Meer http://news.bbc.co.uk/

Muers, M.F., et. al. (2008). Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet 2008. 371:1685-94.
BACKGROUND:
Malignant pleural mesothelioma is almost always fatal, and few treatment options are available. Although active symptom control (ASC) has been recommended for the management of this disease, no consensus exists for the role of chemotherapy. We investigated whether the addition of chemotherapy to ASC improved survival and quality of life. METHODS: 409 patients with malignant pleural mesothelioma, from 76 centres in the UK and two in Australia, were randomly assigned to ASC alone (treatment could include steroids, analgesic drugs, bronchodilators, palliative radiotherapy [n=136]). to ASC plus MVP (four cycles of mitomycin 6 mg/m2, vinblastine 6 mg/m2, and cisplatin 50 mg/m2 every 3 weeks [n=137]). or to ASC plus vinorelbine (one injection of vinorelbine 30 mg/m2 every week for 12 weeks [n=136]). Randomisation was done by minimisation, with stratification for WHO performance status, histology, and centre. Follow-up was every 3 weeks to 21 weeks after randomisation, and every 8 weeks thereafter. Because of slow accrual, the two chemotherapy groups were combined and compared with ASC alone for the primary outcome of overall survival. Analysis was by intention to treat. This study is registered, number ISRCTN54469112. FINDINGS: At the time of analysis, 393 (96%) patients had died (ASC 132 [97%], ASC plus MVP 132 [96%], ASC plus vinorelbine 129 [95%]). Compared with ASC alone, we noted a small, non-significant survival benefit for ASC plus chemotherapy (hazard ratio [HR] 0.89 [95% CI 0.72-1.10]. p=0.29). Median survival was 7.6 months in the ASC alone group and 8.5 months in the ASC plus chemotherapy group. Exploratory analyses suggested a survival advantage for ASC plus vinorelbine compared with ASC alone (HR 0.80 [0.63-1.02]. p=0.08), with a median survival of 9.5 months. There was no evidence of a survival benefit with ASC plus MVP (HR 0.99 [0.78-1.27]. p=0.95). We observed no between-group differences in four predefined quality-of-life subscales (physical functioning, pain, dyspnoea, and global health status) at any of the assessments in the first 6 months. INTERPRETATION: The addition of chemotherapy to ASC offers no significant benefits in terms of overall survival or quality of life. However, exploratory analyses suggested that vinorelbine merits further investigation.

VS: oprichting online databank voor mesothelioom

15-05-2008

Sinds mei is in de VS de eerste elektronische databank voor mesothelioom online toegankelijk voor onderzoekers. De “National Mesothelioma Virtual Bank” bevat kenmerken van 900 monsters van mesothelioomweefsel van 600 patiënten. De databank is ondergebracht bij de Mesothelioma Applied Research Foundation (MARF), een non-profit stichting waarin nabestaanden, artsen, juristen en onderzoekers samenwerken in de strijd tegen mesothelioom. Bron: MARF, 13 mei 2008. Meer http://www.mesotissue.org/