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Eén van de grootste problemen bij het maligne mesothelioom (longvlies- of buikvlieskanker) is het stellen van een correcte diagnose. Er zijn nog steeds geen merkers noch morfologisch kenmerken ontdekt die exclusief voorkomen bij deze tumoren. Suster en Moran beschrijven in een overzichtsartikel de ontwikkelingen in de technieken van de diagnosestelling. Speciale aandacht wordt gegeven aan de mogelijke bijdragen van moleculaire technieken. Bron: Suster S & Moran C (2005). Malignant mesothelioma: current status of histopathologic diagnosis and molecular profile. Expert Rev Mol Diagn., Sep.5(5):715-2.
Suster S & Moran C (2005). Malignant mesothelioma: current status of histopathologic diagnosis and molecular profile. Expert Rev Mol Diagn., Sep.5(5):715-2

Abstract

Malignant mesothelioma of the pleura is a relatively rare neoplasm that has been estimated to account for 20 deaths per million males per year in North America and Europe. A causative association has been well established with asbestos exposure. Paradoxically, the incidence of this tumor continues to rise despite public efforts to reduce, contain or eliminate exposure to asbestos fibers over the past few decades. Another paradoxical feature of the disease is that the majority of malignant mesotheliomas represent morphologically low-grade, well-differentiated neoplasms, yet they follow a relentlessly aggressive and virtually uniformly fatal outcome. For this reason, identification of clinical, morphologic, immunohistochemical or molecular genetic parameters is of extremely limited value for prognostication. Surprisingly, for a disease that currently has no known cure, one of the major problems still lies in establishing the correct diagnosis. Diagnosis acquires a particular relevance in light of the medicolegal ramifications of this disease, and diagnosis of malignant mesothelioma is still fraught with difficulties. Despite the advances in modern diagnostic techniques, no specific markers or morphologic features exist that are exclusive to these tumors. Herein, the current status of malignant mesothelioma diagnosis is reviewed, including the possible contributions of modern molecular techniques for their diagnosis.

Tan en Treasure beschrijven in dit overzichtsartikel de ontwikkelingen in de behandeling van het mesothelioom (longvlies-/buikvlieskanker). Zij concluderen dat er nog geen behandeling aanwijsbaar is die werkelijk een verschil maakt in de genezing van patiënten. Zolang dit zo blijft, heeft het daarom geen zin om patiënten in een vroeg stadium te screenen op deze ziekte. Bron: Tan, C. & Treasure, T. (2005). Mesothelioma: time to take stock. Journal of the Royal Society of Medicine, 98, october, 455-458.

Van Meerbeeck en collega’s onderzochten de werking van het medicijn raltitrexed gecombineerd met cisplatine in vergelijking tot cisplatine alleen. De onderzoeksgroep bestond uit 250 patiënten met mesothelioom die aselect aan twee groepen waren toegewezen. Van de patiënten die de combinatie toegediend kregen, nam bij 24% de tumorgroei af in vergelijking tot 14% van de groep die alleen cisplatine toegediend kreeg. 46% Van de patiënten in de combinatiegroep leefde langer dan een jaar na diagnose nog in vergelijking tot 40% van de groep die alleen cisplatine kreeg. Bron: Meerbeeck, J.P. van, et al. (2005). Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. Journal Clinical Oncology oct 1, 23(28), 6881-9.
Meerbeeck JP van, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, Legrand C, Bottomley A, Debruyne C, Giaccone G

Abstract

Purpose: We conducted a phase III trial to determine whether first-line treatment with raltitrexed, a thymidine synthase inhibitor, and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma (MPM).

Patients and methods: Eligible patients with histologically proven advanced MPM, not pretreated with chemotherapy, WHO performance status (PS) 0 to 2, and adequate hematological, renal, and hepatic function were randomly assigned to receive cisplatin 80 mg/m2 IV on day 1, alone (arm A) or combined with raltitrexed 3 mg/m2 (arm B). In patients with measurable disease, response was monitored using the Response Evaluation Criteria in Solid Tumors criteria. Health related quality of life (HRQOL) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 and Lung Module (QLQ-LC13).

Results: Two hundred fifty patients were randomized: 80% male. median age, 58 years. and WHO PS, 0, 1, 2 in 25, 62, and 13% of cases, respectively. There were no toxic deaths. The main grade 3 or 4 toxicities observed were neutropenia and emesis, reported twice as often in the combination arm. Among 213 patients with measurable disease, response rate was 13.6% (arm A) versus 23.6% (arm B. P = .056). No difference in HRQOL was observed on any of the scales. Median overall and 1-year survival in arms A and B were 8.8 (95% CI, 7.8 to 10.8) v 11.4 months (95% CI, 10.1 to 15), respectively, and 40% v 46%, respectively (P = .048).

Conclusion: A combination of raltitrexed and cisplatin improves overall survival compared with cisplatin alone. This study confirms that a combination of cisplatin and an antifolate is superior to cisplatin alone in patients with MPM, without harmful effect on HRQOL.

In het Amerikaanse CARET onderzoek werden 4060 beroepsmatig aan asbest blootgestelde mannen en 14.254 zware rokers gedurende 10 tot 18 jaar gevolgd. De onderzoekers vonden een relatief hoog risico op dikke darmkanker bij de subgroep zware rokers die aan asbest was blootgesteld geweest en bij wie op röntgenfoto’s van het longvlies niet-kwaadaardige abestgerelateerde afwijkingen waren te zien. Bron: Aliyu OA. et al. (2005). Evidence for Excess Colorectal Cancer Incidence among Asbestos-exposed Men in the Beta-Carotene and Retinol Efficacy Trial. Am J Epidemiol. Nov 1.162(9):868-78.

Aliyu OA, Cullen MR, Barnett MJ, Balmes JR, Cartmel B, Redlich CA, Brodkin CA, Barnhart S, Rosenstock L, Israel L, Goodman GE, Thornquist MD, Omenn GS.

Abstract

The relation between asbestos exposure and colorectal cancer remains controversial. The authors of this 1984-2004 US study examined the association among 3,897 occupationally exposed participants in the Beta-Carotene and Retinol Efficacy Trial (CARET) for chemoprevention of lung cancer, followed prospectively for 10-18 years. When a Cox stratified proportional hazards model was used, risks of colorectal cancer were elevated among male heavy smokers exposed to asbestos. Their relative risk was 1.36 (95% confidence interval: 0.96, 1.93) when compared with that for CARET heavy smokers not exposed to asbestos, after adjusting for age, smoking history, and intervention arm. The presence of asbestos-induced pleural plaques at baseline was associated with a relative risk of 1.54 (95% confidence interval: 0.99, 2.40). colorectal cancer risk also increased with worsening pulmonary asbestosis (p = 0.03 for trend). A dose-response trend based on years of asbestos exposure was less evident. Nonetheless, these data suggest that colorectal cancer risk is elevated among men occupationally exposed to asbestos, especially those with evidence of nonmalignant asbestos-associated radiographic changes.

“Soluble mesothelin-related protein”(SMRP) is een proteïne die in het bloedplasma voorkomt. In dit onderzoek werden 48 mesothelioompatiënten vergeleken met een controlegroep van 228 mensen, gezond of met een andere ziekte deels wel, deels niet aan asbest blootgesteld. De resultaten ondersteunen de hypothese dat SMRP behulpzaam kan zijn bij de diagnose van maligne mesothelioom, bij de beoordeling van de ziekte-progressie en bij de vroeg-screening van deze ziekte. Bron: Robinson BW, et al. (2005). Soluble mesothelin-related protein:a blood test for mesothelioma. Lung Cancer. 2005 Jul.49 Suppl 1:S109-11.

Robinson BW, Creaney J, Lake R, Nowak A, Musk AW, de Klerk N, Winzell P,

Abstract

Identification of tumor marker for mesothelioma (MM) might prove useful in

diagnosis as well as for monitoring tumor in response to therapy and for

screening at-risk individuals. We tested the hypothesis that soluble

mesothelin-related protein (SMRP), a mesothelin family member, in the serum

would be such a marker. Our data show that determination of SMRP in serum is a

marker of MM with a sensitivity of sensitivity 83% and specificity 95% in the

first 48 MM patients tested. Changes in serum SMRP levels parallel clinical

course/tumor size and SMRP is elevated in 75% of patients at diagnosis. SMRP

should also be useful for monitoring disease progression, and importantly, may

prove useful for screening asbestos-exposed individuals for early MM.

Bhattacharya en collega’s beschrijven in dit overzichtsartikel het totaal aan biologische reacties in het lichaam nadat iemand aan asbest is blootgesteld. Onderscheid wordt gemaakt naar indicatoren van (1) blootstelling (reacties op vezels), (2) effect (ziekte) en (3)kwetsbaarheid (verschillen tussen individuen en/of populaties). Bron: Bhattacharya K, Dopp E, Kakkar P, Jaffery FN, Schiffmann D, Jaurand MC, Rahman I, Rahman Q. (2005). Biomarkers in risk assessment of asbestos exposure. Mutation Research, Aug 17, article in press.
Bhattacharya K, Dopp E, Kakkar P, Jaffery FN, Schiffmann D, Jaurand MC, Rahman I, Rahman Q. (2005). Biomarkers in risk assessment of asbestos exposure. Mutation Research, Aug 17, article in press. 9: Mutat Res. 2005 Aug 17. [Epub ahead of print]

Abstract

Developments in the field of molecular epidemiology and toxicology have given

valuable tools for early detection of impending disease or toxic condition.

Morbidity due to respiratory distress, which may be due to environmental and

occupational exposure, has drawn attention of researchers worldwide. Among the

occupational exposure to respiratory distress factors, fibers and particles have

been found to be main culprits in causing diseases like asbestosis, pleural

plaques, mesotheliomas and bronchogenic carcinomas. An early detection of the

magnitude of exposure or its’ effect using molecular end points is of growing

importance. The early inflammatory responses like release of the inflammatory

cells collected by non-invasive methods give an indication of the unwanted

exposure and susceptibility to further complications. Since free radicals like

O(2)(-), OH, OOH, NO, NOO, etc. are involved in the progression of

asbestos-related diseases and lead to cytogenetic changes, an evaluation of

antioxidant states reducing equivalents like GSH and ROS generation can be a

good biomarker. The cytogenetic end points like chromosomal aberration,

micronucleus formation and sister chromatid exchange give indication of genetic

damage, hence they are used as effective biomarkers. New techniques like

fluorimetric analysis of DNA unwinding, alkaline elution test, fluorescent in

situ hybridization and comet assay are powerful tools for early detection of

initiation of disease process and may help in planning strategies for minimizing

morbidity related to asbestos fiber exposure. The present review article covers

in detail possible biomarkers for risk assessment of morbidity due to

fibers/particles in exposed population.

Bêtacaroteen is een stof die in het lichaam wordt omgezet in vitamine A, een zgn. provitamine. Het komt voor in fruit en groenten. In dit overzichtsartikel wordt aan de hand van genetische technieken nagegaan hoe deze stof werkt in het lichaam. Bêtacaroteen lijkt namelijk zowel positieve als negatieve effecten voor de gezondheid te kunnen hebben. Enerzijds werkt het, bij normale inname, als antioxidant en beperkt daarmee o.a. het risico op kanker. Anderzijds is bij inname van extra doses, buiten de normale voeding, een verhoogd risico op longkanker waargenomen bij zware rokers en mensen die met asbest hebben gewerkt. Hoewel hiervoor verschillende verklaringen te geven zijn, concluderen Keijer en collega’s dat nog niet duidelijk is hoe bêtacaroteen deze effecten kan veroorzaken.

Bron: Keijer, J. et al. (2005). Beta-carotene and the application of transcriptomics in risk-benefit evaluation of natural dietary components. Biochim Biophys Acta. May 30.1740(2):139-46.

Abstract

Keijer J, Bunschoten A, Palou A, Franssen-van Hal NL.

RIKILT-Institute of Food Safety, Food Bioactives Group. Bornsesteeg 45, P.O. Box

230, 6700 AE, Wageningen, The Netherlands. jaap.keijer@wur.nl

Beta-carotene is a natural food component that is present in fruits and

vegetables and is also used as a food colorant and a supplement. Beta-carotene

is an anti-oxidant and a source of vitamin A. It is endowed with health

beneficial properties, but a number of studies showed that with high intakes it

may increase the risk for lung cancer in at risk individuals (heavy smokers,

asbestos workers and alcohol users). To establish the window of benefit, it is

necessary to identify early markers of effect and to obtain insight in the

mechanism of action of beta-carotene, in the absence and presence of

environmental risk factors. Genomics technologies are well suited to dissect the

mechanisms of action and identify the markers of effect. Human cell lines can be

used to analyse the effects of beta-carotene, but exposure studies with

beta-carotene show that cell lines display a widely variant behaviour, which

hampers translation to the in vivo situation in humans. Alternatively, animal

studies can be used. Especially the ferret seems to be a good model, but little

sequence information of this species is available. However, heterologous

hybridization on human cDNA seems possible and provides and a new tool for

molecular analysis of health effects of beta-carotene.

In de Nelson screeningsstudie is 70% van de longkankers, met behulp van een multi-slice CT scan, in een zeer vroeg en goed behandelbaar stadium ontdekt. Dit resultaat bespraken de onderzoekers in een bijeenkomst op 7 oktober j.l. Vaak is longkanker op het moment dat het ontdekt wordt al uitgezaaid naar andere delen van het lichaam en daardoor in 80% van de gevallen niet meer te opereren. De nieuwe CT techniek zou een belangrijke rol in de bestrijding van longkanker kunnen gaan spelen. Het Nelson-onderzoek is het enige grootschalige proefbevolkingsonderzoek op longkanker in Europa. Het wetenschappelijke bevolkingsonderzoek is gestart in september 2003 onder mannen en vrouwen tussen 50 en 75 jaar in een aantal regio’s. 16.000 Personen met een verhoogd risico op longkanker doen mee aan het onderzoek. De Gezondheidsraad schat dat iets meer dan 10% van de gevallen van longkanker gerelateerd is aan asbestblootstelling. Bron: Artsennet.nl, 10 oktober 2005.

Robinson en collega’s beschrijven de ontwikkelingen in de diagnostiek en behandeling van mesothelioom (longvlies-, buikvlieskanker) en het onderzoek naar de oorzaken. Zij bestudeerden artikelen geregistreerd in de medische databank Pubmed en webpagina’s naar aanleiding van een zoekopdracht in Google. Volgens de schrijvers is het inmiddels alom bekend in het westen dat asbest kanker kan veroorzaken en kennen steeds meer mensen het woord mesothelioom. Een aanwijzing hiervoor was een zoekopdracht naar deze term in Google die maar liefst 3 miljoen webpagina’s opleverde, meer dan voor meer bekende kankersoorten als bijvoorbeeld leukemie.

Bron: Robinson, B.W. et al. (2005). Malignant mesothelioma. The Lancet, vol 366, 30 juli, 397-408.

Robinson, B.W., Musk, A.W. & Lake, R.A. (2005). Lancet 2005.366:397 -408

Abstract

Malignant mesothelioma is an aggressive,treatment-resistant tumour,which is increasing in frequency throughout the world.Although the main risk factor is asbestos exposure,a virus,simian virus 40 (SV40),could have a role. Mesothelioma has an unusual molecular pathology with loss of tumour suppressor genes being the predominant pattern of lesions,especially the P 16 INK4A, and P 14ARF ,and NF 2 genes,rather than the more common p 53 and Rb tumour suppressor genes.Cytopathology of mesothelioma effusions or fine-needle aspirations are often sufficient to establish a diagnosis,but histopathology is also often required.Patients typically present with breathlessness and chest pain with pleural effusions.Median survival is now 12 months from diagnosis.Palliative chemotherapy is beneficial for mesothelioma patients with high performance status.The role of aggressive surgery remains controversial and growth factor receptor blockade is still unproven.Gene therapy and immunotherapy are used on an experimental basis only. Patterns identified from microarray studies could be useful for diagnosis as well as

prognostication.

Een cohort van 726 vuurtorenwachters dat in de periode vanaf 1917 tot 1967 werkzaam was geweest werd onderzocht op kankerincidentie in de periode 1960 tot 2002. Bij de subgroep die asbest via drinkwater had binnengekregen werd een relatief hoge incidentie van maag-darmkanker gevonden. Bron: Kjaerheim, K. et al. (2005).Cancer of the gastrointestinal tract and exposure to asbestos in drinking water among lighthouse keepers (Norway). Cancer causes and control. vol. 16 (2005), afl. 5, pag. 593-598 (6).

Kjaerheim, Kristina. Ulvestad, Bente. Martinsen, Jan Ivar. Andersen, Aage / In: Cancer causes and control. vol. 16 (2005), afl. 5, pag. 593-598 (6) / 2005

Abstract

Objective Previous studies of predominantly ecological design have indicated a possible elevation of gastrointestinal cancer risk in population groups exposed to drinking water contaminated with asbestos from natural sources or asbestos’ cement containing water pipes. In the present study the possible effect of ingested asbestos fibers on gastrointestinal cancer risk was investigated in an occupational group where a proportion of the employees was exposed to asbestos in their drinking water.

Method A cohort of 726 lighthouse keepers first employed between 1917 and 1967 were followed up for cancer incidence from 1960 to 2002. The standardized incidence ratio (SIR) was calculated as the number of new cancer cases divided by the expected number based on five-year age and sex specific incidence rates in the general rural population of Norway. A 95% confidence interval (CI) was calculated for all SIR values assuming a Poisson distribution of the cancer cases.

Results Risk of stomach cancer was elevated in the whole cohort (SIR: 1.6, CI: 1.0-2.3), in the subgroup with definite asbestos exposure (SIR: 2.5, CI: 0.9-5.5), and when the group was followed for 20&#8201.years and more after first possible exposure (SIR: 1.7, CI: 1.1-2.7). Less consistent results were found for colon cancer. SIR was 1.5 (CI: 0.9-2.2) overall, 0.8 (CI: 0.1-2.9) among the exposed, and 1.6 (CI: 1.0-2.5) twenty years and more after first possible exposure.

Conclusion The results support the hypothesis of an association between ingested asbestos and gastrointestinal cancer risk in general and stomach cancer risk specifically.