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.

Ervaringen van Britse mesothelioompatiënten

15-05-2008

Woede, schuld en verwijten zijn de eerste reacties op de fatale diagnose maligne mesothelioom. Die woede en verwijten zijn gericht op de veroorzakers van de ziekte: werkgevers en de overheid. Britse mesothelioompatiënten hebben veel behoefte aan informatie, psychosociale en emotionele steun, ook omdat ze naast hun lichamelijke lijdensweg met complexe, medische en financiële zaken te maken krijgen. Bron: Hughes, N. &amp. Arber, A. (2008). The lived experience of patients with pleural mesothelioma. International Journal of Palliative Nursing, 14, nr. 2. p. 66-71.

Hughes, N. &amp. Arber, A. (2008). The lived experience of patients with pleural mesothelioma. International Journal of Palliative Nursing, 14, nr. 2. p. 66-71.
Abstract

This paper reports on a research study of five patients diagnosed with mesothelioma. The study used a phenomenological approach to explore patients’ lived experience using in-depth interviews.
The findings identify that patients have many unmet psychosocial and emotional needs and that there was a lack of information provided to patients about specialist supportive and palliative care
services. A number of the patients found specialist supportive care by chance rather than by referral. In addition, patients were involved in complex medico-legal matters in relation to asbestos exposure, and this was an additional burden for them and their spouse or carer. A feeling of social isolation was also reported and a number of patients would welcome the opportunity to meet with
other people in the same situation as themselves. In conclusion, there is a lack of attention to the emotional needs of this group of patients, which means that supportive care resources are not
being accessed in a timely and flexible manner.

Overzichtsstudies naar ontwikkelingen in de behandeling van mesothelioom

15-05-2008

Chemotherapie is momenteel de behandeling die het meest wordt toegepast bij niet-operabele mesothelioompatienten. Het gebruik van antifolaten in combinatie met platinum geeft daarbij de grootste kans op langere overleving. Bij patienten die wel geopereerd kunnen worden biedt een combinatie van opereren, bestralen en chemo (trimodale of multimodale behandeling) de beste overlevingskansen. Er is geen standaardtherapie voor de tweedelijnsbehandeling. Bron: Fennell, D., et al. (2008). Advances in the systemic therapy of malignant pleural mesothelioma. Nature Clinical Practice, 5, 3, p. 136-147. Kaufman, A.J. &amp. Pass, H.I. (2008). Current concepts in malignant pleural mesothelioma. Expert Rev. Anticancer Ther. 8(2), 293-303.

Kaufman, A.J. &amp. Pass, H.I. (2008). Current concepts in malignant pleural mesothelioma. Expert Rev. Anticancer Ther. 8(2), 293-303.
Abstract
Malignant pleural mesothelioma (MPM) is a rare but lethal cancer associated with asbestos exposure. Worldwide, the incidence of MPM is expected to increase over the next 20 years. The molecular and genetic profiling of MPM tumors and patients, and improved understanding of the pathogenesis of MPM may lead to novel diagnostic, preventative and therapeutic strategies. Treatment options for MPM remain limited and no consensus exists at this time. Multimodality therapy that combines surgery, chemotherapy and radiation offers the best chance for long-term survival in select patients.

Fennell, D., et al. (2008). Advances in the systemic therapy of malignant pleural mesothelioma. Nature Clinical Practice, 5, 3, p. 136-147.
Abstract

Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.

Risicomodel voor longkanker

15-05-2008

Een 77-jarige man die met asbest heeft gewerkt, 45 jaar heeft gerookt, en bij wie longkanker in de familie op jonge leeftijd voorkomt, heeft bijna 10 x zoveel kans om binnen vijf jaar longkanker te krijgen als iemand met dezelfde kenmerken die nooit gerookt heeft. Cassidy et al. ontwikkelden een model waarmee geschat kan worden hoeveel kans iemand heeft binnen 5 jaar longkanker te krijgen. Meer onderzoek is nodig. Bron: Cassidy, A. et al., (2008). The LLP risk model: an individual risk prediction model for lung cancer. British Journal of Cancer, 98, 270-276.

Cassidy, A. et al., (2008). The LLP risk model: an individual risk prediction model for lung cancer. British Journal of Cancer, 98, 270-276.
Abstract
Using a model-based approach, we estimated the probability that an individual, with a specified combination of risk factors, would develop lung cancer within a 5-year period. Data from 579 lung cancer cases and 1157 age- and sex-matched population-based controls were available for this analysis. Significant risk factors were fitted into multivariate conditional logistic regression models. The final multivariate model was combined with age standardised lung cancer incidence data to calculate absolute risk estimates. Combinations of lifestyle risk factors were modelled to create risk profiles. For example, a 77-year-old male non-smoker, with a family history of lung cancer (early onset) and occupational exposure to asbestos has an absolute risk of 3.17% (95% CI, 1.67&ndash.5.95). Choosing a 2.5% cutoff to trigger increased surveillance, gave a sensitivity of 0.62 and specificity of 0.70, while a 6.0% cutoff gave a sensitivity of 0.34 and specificity of 0.90. A 10-fold cross validation produced an AUC statistic of 0.70, indicating good discrimination. If independent validation studies confirm these results, the LLP risk models&rsquo. application as the first stage in an early detection strategy is a logical evolution in patient care.

Libby vermiculiet schadelijk door amfibool asbest

15-05-2008

Bij veel mensen die vóór 1980 in een vermiculietfabriek in Libby, Montana hebben gewerkt zijn afwijkingen aan de longen te zien, zoals pleurale verdikking. Ook lage blootstellingsniveaus kunnen longafwijkingen veroorzaken. Oorzaak zijn de amfibool asbestvezels die in de vermiculietmijn voorkwamen.Bron: Rohs, A.M. e..a. (2008).

Lockey, J.E., (2008). Low-level fiber-induced radiographic changes caused by Libby vermiculite: a 25-year follow-up study. American Journal of Respiratory and Critical Care Medicine, Mar 15.177(6):630-7.

ABSTRACT
RATIONALE:
From 1921 to 1990, vermiculite ore from Libby, Montana, was shipped worldwide for commercial and residential use. A 1980 study of a manufacturing facility using Libby vermiculite was the first to demonstrate a small but significant prevalence of pleural chest radiographic changes associated with amphibole fibers contained in the ore. OBJECTIVES: This follow-up study of the original cohort evaluated the extent of radiographic changes and cumulative fiber exposure (CFE) 25 years after cessation of exposure. METHODS: From the original cohort of 513 workers, 431 (84%) were living and available for participation and exposure reconstruction. Of these, 280 (65%) completed both chest radiographs and interviews. Primary outcomes were pleural and/or interstitial changes. MEASUREMENTS AND MAIN RESULTS: Pleural and interstitial changes were demonstrated in 80 (28.7%) and 8 (2.9%) participants, respectively. Of those participants with low lifetime CFE of less than 2.21 fiber/cc-years, 42 (20%) had pleural changes. A significant (P &lt. 0.001) exposure-response relationship of pleural changes with CFE was demonstrated, ranging from 7.1 to 54.3% from the lowest to highest exposure quartile. Removal of individuals with commercial asbestos exposure did not alter this trend. CONCLUSIONS: This study indicates that exposure within an industrial process to Libby vermiculite ore is associated with pleural thickening at low lifetime CFE levels. The propensity of the Libby amphibole fibers to dramatically increase the prevalence of pleural changes 25 years after cessation of exposure at low CFE levels is a concern in view of the wide national distribution of this ore for commercial and residential use.

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/

Operatieve behandeling bij mesothelioom

03-04-2008

Mesothelioompatiënten die een operatie ondergaan waarbij de zieke long, het aangetaste vlies, hartzakje en middenrif worden verwijderd hebben meer complicaties dan andere patënten maar leven gemiddeld vijf maanden langer. Bron: Schipper, P.H. et al., (2008). Surgery for malignant pleural mesothelioma. Ann. Thorac. Surg.. 85:257-64.

Schipper, P.H. et al., (2008). Surgery for malignant pleural mesothelioma. Ann. Thorac. Surg.. 85:257-64.
Abstract
Background.
Malignant pleural mesothelioma is a rare, aggressive, and deadly malignancy. Despite increasing incidence, no treatment modality is accepted standard of care. This report analyzes our experience with surgical management of mesothelioma.
Methods. All patients with surgery for mesothelioma from January 1985 through December 2003 were retrospectively reviewed.
Results. There were 285 patients with a median age of 66 years (range, 26 to 91 years). One hundred forty-six patients (51%) had biopsy only, 73 (26%) had extrapleural pneumonectomy, 34 (12%) had subtotal parietal pleurectomy, 22 (8%) underwent exploration without resection, and 10 (3%) had total pleurectomy. Histopathology was epithelial, nonepithelial, and unclassified in 134, 108, and 43 patients, respectively. Twenty patients were stage IA, 82 patients were stage IB, 24 patients were stage II, 75 patients were stage III, 60 patients were stage IV, and 24 patients were of unknown stage. Fifty-three patients (19%) had chemotherapy alone, 16 (5.6%) had radiation alone, and 42 (14.7%) had both. Thirty-day operative mortality was 6.3% and was not significantly associated with the operative procedure (p 0.79). Fifty-one percent of extrapleural pneumonectomy patients had major complications, significantly greater than patients having any other procedure (p &lt. 0.001). Median follow-up was 11 months (range, 0 to 7 years). Overall median survival was 10.7 months. however, for patients having extrapleural pneumonectomy, median survival was 16 months. One-, 2-, and 3-year survival after extrapleural pneumonectomy was 61%, 25%, and 14%, respectively.
Conclusions. Extrapleural pneumonectomy can be performed
with similar 30-day mortality as other procedures for malignant pleural mesothelioma with a median survival better than subtotal pleurectomy, exploration without resection, and biopsy alone. However, extrapleural pneumonectomy has significant morbidity and a 3-year survival of only 14%.

De gevaren van amosiet asbest in Zuid Afrika

15-02-2008

Amosiet asbest veroorzaakt zowel niet-kwaadaardige als kwaadaardige asbestziekten. Het is echter minder schadelijk dan het blauwe crocidoliet asbest. In Zuid Afrika zijn de meeste mijnwerkers zowel aan amosiet- als aan crocidoliet-asbest blootgesteld. Bron: Murray, J. &amp. Nelson, G., (2007). Health effects of amosite mining and milling in South Africa. Regul. Toxicol. Pharmacol. (2007), doi:10.1016/j.yrtph.2007.09.011.

Murray, J. &amp. Nelson, G., (2007). Health effects of amosite mining and milling in South Africa. Regul. Toxicol. Pharmacol. (2007), doi:10.1016/j.yrtph.2007.09.011.

This study focuses on the amosite mining region in South Africa and associated health effects, compared to other mined asbestos fiber types. Historically, dust and fiber levels were high in the amosite mills and mines, and many miners and members of the surrounding communities were exposed to the fibers. Research has shown that amosite produces both benign and malignant disease. Nevertheless, the mesotheliomagenic potential of amosite is several fold lower than crocidolite. The risk of disease associated with amosite exposure is difficult to quantify. Reasons for this include the scarcity of available information, including fiber measurements, and case ascertainment, as well as the juxtaposition of the amosite and crocidolite asbestos seams in South Africa.

Latentietijd mesothelioom steeds langer

31-01-2008

De tijd tussen het eerste moment van asbestblootstelling en het moment waarop de ziekte mesothelioom wordt vastgesteld wordt steeds langer en is nu al gemiddeld 45 jaar. Bij werkgerelateerde blootstelling is de latentietijd gemiddeld korter dan bij mensen die via asbest in het milieu de ziekte opgelopen hebben. Dit concluderen Italiaanse onderzoekers na analyse van gegevens van 2544 patiënten die tussen 1993 en 2001 mesothelioom kregen. Bron: Marinaccio, A. et al.,(2007). Analysis of latency time and its determinants in asbestos related malignant mesothelioma cases of the Italian register. European Journal of Cancer. Dec.43(18):2722-8.

Marinaccio, A. et al.,(2007). Analysis of latency time and its determinants in asbestos related malignant mesothelioma cases of the Italian register. European Journal of Cancer. Dec.43(18):2722-8.

Italy was an important producer of raw asbestos until 1992 (when it was banned) and it is now experiencing severe public health consequences due to large-scale industrial use of asbestos in shipbuilding and repair, asbestos-cement production, railways, buildings, chemicals and many other industrial sectors. Latency of malignant mesothelioma generally shows a large variability and the relationship with the modality of asbestos exposure is still not fully clarified. We present an analysis of latency period among the case list collected by the Italian mesothelioma register (ReNaM) in the period of diagnosis 1993-2001 (2544 malignant mesothelioma (MM) cases with asbestos exposure history). Exposure is assessed retrospectively by interview. Statistical univariate analyses were performed to estimate median and variability measures of latency time by anatomical site, gender and diagnosis period. The role of diagnostic confidence level, the morphology of the tumour and the modalities of asbestos exposure were verified in a regression multivariate model. We found a median latency period of 44.6 years increasing in recent years with a linear trend. Anatomical site, gender and morphology were not relevant for MM latency time whereas a shorter latency period was documented among occupationally exposed subjects (43 years) with respect to environmentally and household exposed ones (48 years).