Incidence Of Malignant Pleural Mesothelioma Research Articles

Malignant pleural mesothelioma incidence and survival in the Republic of Ireland 1994–2009

ObjectiveMalignant pleural mesothelioma (MPM) is a rare malignancy associated with exposure to asbestos. The protracted latent period of MPM means that its incidence has continued to rise across Europe after the introduction of restrictions on asbestos use. In order to obtain a clearer indication of trends in the Republic of Ireland (ROI), incidence and survival were assessed based on all MPM cases reported since the establishment of the National Cancer Registry of Ireland (NCR). MethodsNCR recorded 337 MPM diagnoses in the ROI during 1994–2009. Survival was assessed for all cases diagnosed with adequate follow-up (n=330). Crude and European age-standardized incidence rates were calculated for all cases and for 4-year periods. A Cox model of observed (all-cause) survival was used to generate hazard ratios for the effect of: gender; age at diagnosis; diagnosis cohort; region of residence; histological type; and tumour stage. Single P-values for the variables indicated were calculated using either a stratified log-rank test or stratified trend test. ResultsOver the study period the age-standardized MPM incidence in the ROI rose from 4.98cases per million (cpm) to 7.24cpm. The 1-year survival rate for all MPM cases was 29.6% (CI 24.7–34.6%). Excess mortality risk was associated with age at diagnosis (75–89 yrs vs. 55–64 yrs, HR 1.88, 95% CI 1.35–2.63, P<0.001) and tumour stage (III vs. I HR 1.57, 95% CI 1.00–2.48, P<0.05; IV vs. I HR 1.55, 95% CI 1.08–2.21, P<0.05). Age showed a significant survival trend (P<0.001) but tumour stage did not (P=0.150). There was significant heterogeneity between the survival of patients resident in different regions (P=0.027). ConclusionMPM incidence and mortality continued to rise in the ROI after the restrictions on asbestos use and the predictors of survival detected in this study are broadly consistent with those identified for other countries.

272 Estimating health effects of asbestos exposure in the construction industry

ObjectivesThe use of asbestos in the construction industry stopped in mid 1970s in Sweden, but is still in use in some countries. The exposure may vary depending on time, country...

106P PROTEOMIC ANALYSIS SHOWED HEAT SHOCK 70 KDA PROTEIN AND 78 KDA GLUCOSE-REGULATED PROTEIN WERE UP-REGULATED IN HUMAN MALIGNANT PLEURAL MESOTHELIOMA CELLS

Malignant pleural mesothelioma (MPM) is a malignant neoplasm arising from mesothelial cells existing in pleura. It is difficult to identify a crucial symptom in patients with MPM, and there is no standard curative therapy for this malignancy. The incidence of MPM is increasing worldwide, and many patients can not survive more than one year after diagnosis. MPM is an asbestos-related disease, and it is believed that the incidence is closely related to the amount and time of exposure to asbestos. Since the latency period after exposure to asbestos is very long, the incidence may increase over the next two decades. Therefore, it is important to understand the biology of MPM, and to find a molecular target for its therapy. Three of human malignant pleural mesothelioma (MPM) cell lines (NCIH28, NCI-H2052, NCI-H2452) and a human pleural mesothelial cell line (MeT-5A) were analyzed by proteomics with the use of twodimensional gel electrophoresis (2-DE) and liquid chromatographytandem mass spectrometry (LC-MS/MS). From the results of 2-DE between MeT-5A and three MPM cell lines, 9 protein spots showed increased expression levels in MPM cells compared to MeT-5A. These spots were analyzed by LC-MS/MS analysis, and identified by a peptide sequence tag. Identified increased spots included 78 kDa glucose regulated protein (GRP78), heat shock 70 kDa protein (HSP70), protein disulfide isomerase A3, annexin A3, peroxiredoxin-2 and 14 kDa phosphohistidine phosphatase. Western blotting using specific antibodies against GRP78 and HSP70 confirmed the elevated expression level of GRP78 and HSP70 in MPM cell lines compared to MeT-5A cells. These results suggest that GRP78 and HSP70 expression is likely to be associated with the tumorigenesis of MPM, and they may be expectable as biomarkers or therapeutic targets for MPM. Disclosure: All authors have declared no conflicts of interest.

107P IMPACT OF PREINTERVENTIONAL PLASMA FIBRINOGEN AS A PROGNOSTIC MARKER IN MALIGNANT PLEURAL MESOTHELIOMA

Malignant pleural mesothelioma (MPM) is a malignant neoplasm arising from mesothelial cells existing in pleura. It is difficult to identify a crucial symptom in patients with MPM, and there is no standard curative therapy for this malignancy. The incidence of MPM is increasing worldwide, and many patients can not survive more than one year after diagnosis. MPM is an asbestos-related disease, and it is believed that the incidence is closely related to the amount and time of exposure to asbestos. Since the latency period after exposure to asbestos is very long, the incidence may increase over the next two decades. Therefore, it is important to understand the biology of MPM, and to find a molecular target for its therapy. Three of human malignant pleural mesothelioma (MPM) cell lines (NCIH28, NCI-H2052, NCI-H2452) and a human pleural mesothelial cell line (MeT-5A) were analyzed by proteomics with the use of twodimensional gel electrophoresis (2-DE) and liquid chromatographytandem mass spectrometry (LC-MS/MS). From the results of 2-DE between MeT-5A and three MPM cell lines, 9 protein spots showed increased expression levels in MPM cells compared to MeT-5A. These spots were analyzed by LC-MS/MS analysis, and identified by a peptide sequence tag. Identified increased spots included 78 kDa glucose regulated protein (GRP78), heat shock 70 kDa protein (HSP70), protein disulfide isomerase A3, annexin A3, peroxiredoxin-2 and 14 kDa phosphohistidine phosphatase. Western blotting using specific antibodies against GRP78 and HSP70 confirmed the elevated expression level of GRP78 and HSP70 in MPM cell lines compared to MeT-5A cells. These results suggest that GRP78 and HSP70 expression is likely to be associated with the tumorigenesis of MPM, and they may be expectable as biomarkers or therapeutic targets for MPM. Disclosure: All authors have declared no conflicts of interest.

Mesothelioma- and asbestos-related pleural disease: a review

•. Asbestos exposure is known to cause both parenchymal and pleural disease. •. Pleural disease includes malignant pleural mesothelioma (MPM) as well as benign disease, such as pleural plaques, benign pleural effusion and diffuse pleural thickening. •. The incidence of MPM is yet to peak in view of its prolonged latency period. •. Diagnosis of asbestos-related disease has crucial implications in terms of monetary compensation. •. Imaging plays an important role in differentiating between malignant and benign disease as well as in the follow-up of these patients.

Editorial Comment: Lung-sparing total pleurectomy: the surgical option of choice in malignant pleural mesothelioma?

The incidence of malignant pleural mesothelioma (MPM) in Western Europe is increasing significantly [1]. Increased patient awareness of potential therapy and results from North American centres have stimulated specialist European surgical centres to expand their programs. There has been a shift in specialist surgical opinion away from extrapleural pneumonectomy (EPP) towards lung-sparing surgery in MPM. This may be attributed to an increasing age at presentation with consequent increasing comorbidity, particularly COPD. There is also an increasing appreciation that lung-sparing surgery can prolong survival from MPM. This finding is confirmed by Bolukbas et al .[ 2] in this issue, who report 28% 5-year survival in 42 patients with IMIG Stage III MPM. In their series, survival was even greater (median survival 38 months) in those who underwent a complete resection. Unfortunately, macroscopic complete resection was not achieved in 16 of the 42 patients and one wonders whether EPP may have been preferable in these cases. These authors highlight other important prognostic factors, particularly tumour infiltration of previous diagnostic biopsy sites. While also noted by the Boston group [3], this finding may in itself be a surrogate marker for increased tumour volume, thus leading to incomplete R2 resection, or for unfavourable tumour biology. The clinical implication of this is that core biopsy of suspicious biopsy sites should be performed prior to radical surgery. Positive results could then prompt induction chemotherapy to exclude those who may progress inexorably despite therapy. The time interval between diagnosis and major surgery is not clear in the Wiesbaden experience, but this should be kept as short as possible. Apart from involvement of previous incisions and completeness of excision, Bolukbas did not identify nodal status or cell type as significant prognostic factors. These findings do not correlate with the largest series of survival data for mesothelioma surgery reported by the IASLC staging group [4] and probably reflect the small sample. It is imperative that radical surgery should only be considered in patients whose prognosis would be better than with non-surgical treatment. Comparable data are limited but a Nordic study has reported survival from chemotherapy alone in early-stage disease of 22 months [5]. In the IASLC database, postoperative survival was inferior to this in Stages III and IV disease and in non-epithelioid cell types. The inference is that surgery with life prolongation as its aim should be limited to those patients with epithelioid MPM without nodal metastases, particularly in the upper mediastinum. This area is proposed to represent a later stage of MPM based on a ‘gravitational hypothesis’ in which the disease is suggested to progress from the base to the apex of the hemithorax. The poorer prognosis of paratracheal nodal disease suggested from several series [3, 6] promotes the use of mediastinoscopy in patient selection for radical surgery. As alluded to above, there is increasing enthusiasm for lungsparing radical surgery over EPP. The reduced risk of pneumonectomy avoidance may be as high as 40% [7] together with the potential for preserved respiratory function. The recent under

Incidence and Survival of Malignant Pleural Mesothelioma in Norway: A Population-Based Study of 1686 Cases

Asbestos-related malignant pleural mesothelioma is one of the most lethal tumor types. The advent of antimetabolite treatment as pemetrexed, introduced in the early 2000s, may have increased survival on a population basis. In this study, we have analyzed population-based incidence and survival data over the last 40 years. Complete national data on 1686 patients from the Cancer Registry of Norway sampled from 1970 to 2009 are presented, with incidence rates in 5-year periods. Relative survival for 1 year and 3 years and median survival in 5-year intervals were calculated. The incidence of malignant pleural mesothelioma has been significantly and steadily increasing from 1970 until 2009, with 50 patients diagnosed in the period 1970-1974 and 377 diagnosed in 2005-2009. The incidence was highest among men in all time periods. A slight decline was observed in the last period. The 1-year survival rate increased from 20.7% to 44.0% during the period 1970-2009, whereas the 3-year survival rate remained below 10%. Median survival increased from 4.0 months in the first period to 9.3 months in the last period. The incidence of malignant pleural mesothelioma follows the curve of asbestos exposure with a 20- to 40-year lag. There has been a significant increase in survival, most likely because of earlier diagnosis and improvements in cytostatic treatment.

1531P - Nuclear Factor-Kappa B as a Molecular Target in Malignant Pleural Mesothelioma

ABSTRACT Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer associated with exposure to asbestos. Currently rates of MPM are rising and estimates indicate that the incidence of MPM will peak within the next 10-15 years for the western world. Untreated, MPM has a median survival time of 6 months, and most patients die within 24 months of diagnosis. Nuclear Factor kappa B (NFkB) is a pro-inflammatory transcription factor often described as the master regulator of pro-inflammatory responses within the cellular setting. We and others have shown that NFκB is linked to cisplatin resistance (abstract 2307). Several lines of evidence also link NFkB to the pathogenesis of MPM. Using IHC we examined the expression of NFkB in a cohort of MPM patients (n = 200) and correlated expression with various clinicopathological variables. Cytoplasmic or membranous immunostaining was seen in the majority of tumour samples (96.5%), but nuclear localisation of NFkB was seen in only 11% cases. There was no significant correlation between the level of expression of NFkB and standard clinicopathological prognostic factors. Kaplan-Meier Survival analysis showed that nuclear NFkB expression correlated with reduced survival with (p = 0.05). NFkB was expressed in all MPM cell lines tested to a varying extent (n = 20), with no associations to histology. Although small-molecule inhibitors of NFkB have been proposed as single-agent therapies for cancers with aberrant NFkB activity, most classic NFkB inhibitors are poorly selective and result in off-target effects. Dehydroxymethyl-epoxyquinomicin (DHMEQ) is a novel NFkB inhibitor of low molecular weight designed from the structure of the antibiotic epoxyquinomicin C. When bound DHMEQ irreversibly inhibits NFkB and prevents its translocation to the nucleus. A series of MPM cell lines including a panel of isogenic parent/cisplatin resistant cell lines were treated with various concentrations of DHMEQ. The effects of DHMEQ on cellular viability were examined using various methodologies (including multi-parametric High Content Screening) and the results will be presented at the meeting. Disclosure All authors have declared no conflicts of interest.

Malignant pleural mesothelioma (MPM) in elderly patients: A multicenter survey.

7082 Background: The incidence of malignant pleural mesothelioma (MPM) in elderly patients (pts) is increasing in Western countries. Elderly pts with MPM are under-represented in clinical trials, and there are no specific guidelines for their management. The aim of this study was to perform a retrospective survey on this patient population in four Oncology Departments with high MPM accrual and expertise. Methods: The clinical records of elderly pts (≥70 years old) with MPM referred to the participating centers from January 2005 to November 2011 were reviewed. For each patient, age and gender, histology, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and treatment modalities were collected. The study endpoint was overall survival (OS). Results: Out of a total of 610 cases, 210 elderly pts were identified (34% of the whole MPM population observed in the study period). Pts characteristics were: median age 75 yrs (range 70-92), M/F 132/78, epithelial/non-epithelial histology 140/70, ECOG-PS 0/1/2/unknown 130/67/9/4. CCI was 0 in 128 pts (61%), ≥4 in 59 pts (28%). Treatment was multimodality therapy including surgery in 16, chemotherapy in 153 (73%) and best supportive care only in 41 pts (19%). Chemotherapy was mainly pemetrexed-based. Median OS was 11.3 months. Non-epithelial histology, age ≥75 yrs and the presence of comorbidities (CCI ≥1, p=.003; CCI ≥4, p&lt;0.0001) were significantly correlated to a shorter OS. Conclusions: Pemetrexed-based chemotherapy is feasible in selected elderly pts with MPM. Comorbidity is a significant prognostic factor, and should be carefully considered in patient selection. Prospective dedicated trials in elderly pts with MPM selected according to comorbidity scales are warranted.

Prognostic Factors in Malignant Pleural Mesothelioma: A Retrospective Study

The incidence of malignant pleural mesothelioma (MPM) in Japan is predicted to increase over the next few decades. Prognostic factors remain unclear although several studies have reported this disease. In this study, we examined the prognostic factors of MPM from single institution practice data and tested the scoring systems of past reports. We retrospectively obtained clinical data from the medical records of patients who were diagnosed with MPM from 1991 to 2010. The European Organization for Research and Treatment of Cancer prognostic score (EPS) was calculated. We surveyed the records of 68 patients. Univariate analysis showed that significant prognostic factors were histological type, stage, performance status (PS), chemotherapy, and lactate dehydrogenase (LD). Multivariate analysis identified stage, PS and LD as independent prognostic factors. Low-risk group (EPS ≤1.27) survival was significantly better than that of the high-risk group (EPS >1.27) (17.0 months vs. 8.0 months; p=0.002). Stage, PS and LD were demonstrated to be independent prognostic factors. An EPS >1.27 was still considered a poor prognosis indicator in the practice data of MPM.

Asbestos-related Lung Disease

In this work, we describe both benign and malignant asbestos-related diseases and provide an updated review of recent advances in the field. It has long been appreciated that the inhalation of asbestos fibers causes several well-described respiratory diseases including pleural plaques, diffuse pleural thickening, asbestosis, lung cancer, and malignant pleural mesothelioma (MPM). However, despite this knowledge and stricter industrial controls, the incidence of these diseases continues to increase in many parts of the world. In fact, despite the introduction of strict limits early in the 20th century, the mortality rate due to MPM is still increasing in industrialized countries such as the United Kingdom and Australia. In this update we provide an overview of each disease entity while concentrating on the role that newer imaging techniques, including high-resolution computed tomography, magnetic resonance imaging, and positron emission tomography /computed tomography, play in the diagnosis of asbestos-related pleural and parenchymal diseases. As the incidence of MPM continues to increase in many parts of the world, this review also focuses on new approaches to the diagnosis and treatment of this devastating condition. A description of the potential use and limitations of biomarkers in the diagnosis and monitoring of the disease is included along with recent trial data examining novel vaccine-based biological therapies.

SEOM guidelines for the treatment of malignant pleural mesothelioma

Mesothelioma is a rare malignant tumour. Asbestos is the principal aetiological agent of malignant pleural mesothelioma (MPM) (≈80% of cases). The incidence of MPM is still increasing and will peak within the next 10 years. There are three main histological types of MPM: epithelial (≈60%), sarcomatous and mixed. There is no standard approach for patients with MPM. Surgery (radical extra-pleural pneumonectomy or pleurectomy/decortication) may be part of the initial treatment for carefully selected patients, generally combined with neoadjuvant or adjuvant chemotherapy and/or adjuvant radiotherapy, and should only be performed by experienced thoracic surgeons as part of a multidisciplinary team. Radiotherapy could be used as prophylaxis to reduce the incidence of recurrence at sites of diagnoses or therapeutic instrument insertion, in a multimodal treatment to improve locoregional control and to palliate symptoms. Based on the better compliance of neoadjuvant chemotherapy, lower rate of surgical morbidity and the possibility to select the optimal patients to be submitted to surgery, a neoadjuvant strategy is a better option than adjuvant chemotherapy, although there is no standard optimal sequence and types of treatment for multimodal therapy. In patients with no resectable disease, chemotherapy is the best option with platinum and pemetrexed or raltitrexed. At this time there is no widely approved salvage therapy.

Targeted therapies in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose exposure to asbestos fibers is the main etiology. The incidence of MPM is anticipated to increase worldwide during the first half of this century. MPM is notoriously refractory to most treatments, and the only standard of care is cisplatin and antifolate first-line chemotherapy. The urgent need for additional therapeutic agents, in parallel with advances in the knowledge of the molecular events of oncogenesis, has resulted in the development of the so-called 'targeted agents' that specifically inhibit critical pathways in malignant cells and in their microenvironment. We carried out a comprehensive review of the literature from January 2000 to May 2010 on studies that assessed targeted agents for the systemic treatment of MPM. Although tyrosine kinase inhibitors directed against the epidermal growth factor and the platelet-derived growth factor receptors did not show significant clinical activity in phase II studies, some other targeted therapies seemed promising, notably histone deacetylase inhibitors and antiangiogenic agents. However, none of these has yet reached daily practice. That is the reason why efforts must continue in the area of clinical and translational research for MPM.

96PD RETROSPECTIVE REVIEW OF PROGNOSTIC FACTORS IN MALIGNANT PLEURAL MESOTHELIOMA (MPM)

Background: The incidence of malignant pleural mesothelioma (MPM) is anticipated to increase over the next 10 years in both Europe and developing nations. There are many conflicting inferences regarding the prognostic value of clinical variables. The aim of this study is to determinate clinical prognostic factors of patients diagnosed of MPM in our institution. Methods and Patients: Thirty one patients (pts) diagnosed of MPM in our institution between November 2002 and November 2009 were retrospectively reviewed. Baseline prognostic factors analyzed were age, performance status (PS), histology, stage, response rate to chemotherapy (CT) and interval from first diagnosis. Overall survival (OS) and progression free survival (PFS) were calculated by the Kaplan Meier method. Results: Baseline patients characteristics: median age 68 years (52 83 years), males 80.6%, PS 1: 77.4%, asbestos exposure 63.1%, chest pain 74.2%, dyspnea 74.2%, pleural effusion 93.5%, epithelial subtype 67%, stage III: 54.8% and median time from first symptom to diagnosis 2.5 months. All patients were considered initially unresectable and 77.4% of patients received chemotherapy (CT) in first line and 32.3% in second line. After a median follow up of 8.8 months, 27 pts relapsed and 22 had died. The median PFS was 6.7 months and OS was 16.4 months. We found significant increase in OS in patients with epithelial subtype (23.4 months vs 2.3 months in no-epithelial, p 75 years, (p = 0.28), stage III: 22.8m vs 16.4 months in stage IV (p = 0.65), patients with partial response (PR) to CT: 23.3 vs 16.4 months in pts with no response (p = 0.64) and shorter interval from first diagnosis: 22.8m vs 5.6m (p = 0.43). Conclusion: In our analysis, epithelial subtype and treatment with second line therapy are prognostic factor for OS in MPM. Second line CT treatment may have a role in MPM. Disclosure: All authors have declared no conflicts of interest. 97P A NEW 3D CONFORMATIONAL SOLUTION RADIOTHERAPY OF MALIGNANT PLEURAL MESOTHELIOMA

Characteristics of Malignant Pleural Mesothelioma in Women

The incidence of malignant pleural mesothelioma (MPM) is higher in men than in women, likely due to increased occupational asbestos exposure among men. Women also appear to experience better long-term survival. This study evaluates the role of gender in relation to established prognostic factors in MPM. We reviewed 715 cases of MPM treated with extrapleural pneumonectomy at our institution between July 1987 and December 2008. Data for patients with epithelial and nonepithelial tumors were analyzed separately. Kaplan-Meier and Cox regression analyses were used to estimate survival for various cohorts to assess the relationship between gender and survival independent of age at surgery, stage, side, and preoperative laboratory studies. Of the 702 patients with complete data available, 114 out of 450 patients with epithelial tumors and 31 out of 252 patients with nonepithelial histology were women. Women with epithelial (and not nonepithelial) disease were found to differ significantly from men with respect to younger age, higher rate of thrombocytosis, and longer survival after surgery. The effect of gender on survival of patients with epithelial disease persisted when controlling for age, stage, thrombocytosis, leukocytosis, and anemia with a multivariable analysis. No significant differences in survival were seen among patients with nonepithelial disease with regard to gender, age, or anemia. In the absence of other negative prognostic factors, women with epithelial MPM demonstrated a survival advantage. These findings support an aggressive approach to treating MPM including extrapleural pneumonectomy in individuals with favorable prognostic predictors, particularly women with epithelial histology and no other risk factors.

Mésothéliome pleural malin chez un ouvrier d’une entreprise de réparation navale sénégalaise

Summary Objectives The incidence of malignant pleural mesothelioma is unknown in African countries south of the Sahara. This absence of epidemiological studies led us to research on the various risk factors of asbestos exposure in the work place in Senegal. Method We present this well-documented clinical case of a 53-year-old employee of a ship repair company suffering from malignant pleural mesothelioma. Results The employment history, clinical evidence, additional investigations and the care provided to this employee bring to light the diagnostic and therapeutic difficulties related to this disease within the context of a developing country. This observation also confirms the existence in work environments in Senegal of materials and products containing asbestos. The risk of asbestos exposure is linked to the following factors: (1) the importance of the “non-structured” sector referred to as the informal sector; (2) the poor management of occupational health and safety; (3) the non-tracking of materials and products containing asbestos; (4) the lack of knowledge of employees on asbestos exposure; (5) the minimal nature of individual protective equipment; (6) the absence of a legislative and regulatory framework relating to asbestos; (7) the absence of a national mechanism to monitor and declare asbestos-related pathologies. Conclusion This observation illustrates the need for public authorities and social partners in workplaces to heighten their awareness on the risks of asbestos and the urgency in taking the appropriate measures to control this affliction.

Epidemiology of mesothelioma in Egypt. A ten-year (1998-2007) multicentre study.

IntroductionMesothelioma is a cancer strongly linked to exposure to carcinogenic minerals, especially asbestos. The aim of the study was to detect the incidence of malignant pleural mesothelioma (MPM) in Egypt, to clarify the impact of occupational and environmental risk factors, and to characterise its demographic features.Material and methodsThey were 584 cases diagnosed as MPM detected in Cairo University Hospitals and National Cancer Institute from 1998 to 2007. Unfortunately, full epidemiological data were only available for 165 cases due to absence of a reliable registration system.ResultsA steady increase in the number of cases was detected, from 24 in 1998, peaking at 82 cases in 2005, followed by a gradual decline (though still high) with 68 cases in 2006 and 51 cases in 2007. Male/female ratio was 1.35/1 (p > 0.05). The occupational exposure to asbestos was 13.9%. Residential exposure plays a major role in two regions, Helwan and Shoubra (27.3% and 20.6% respectively), while in Upper and Lower Egypt the level was 12.7% and 17.5% respectively. Kaplan-Meier survival for sex, residence and the pathological types epithelioid, biphasic and sarcomatoid was insignificant. The median survival for different grades and treatment modalities was significant (P < 0.001).ConclusionsThere was a steady increase in the incidence of MPM from 1998 to 2005 followed by a decline during 2006-2007. Mesothelioma in Egypt is mainly concentrated in areas of high environmental pollution. The decline within the last 2 years may be attributed to recent strict industrial preventive measures. However, a better environmental control programme would benefit Egypt.

Evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005

The evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005 was analysed using data derived from the French network of cancer registries (FRANCIM) and the French National Mesothelioma Surveillance Program (PNSM). Mesothelioma proportions in pleural cancers were calculated by diagnosis year in the 1980-2000 period. Our results suggest that the incidences of pleural cancer and mesothelioma levelled off in French men since 2000 and continued to increase in French women. A decrease of the annual pleural cancer incidence average in men was noticed (-3.4% of annual rate of change) between 2000 and 2005. The proportion of pleural cancers that were mesothelioma was unchanged between 1980 and 2003 with an average of 86%. The age standardised incidence rate of pleural mesothelioma remained relatively stable between 1998 and 2005 with a slight falling trend. For women, the age standardised incidence rate of pleural cancers and mesothelioma increased during the period 1998-2005. Additionally, the proportion of pleural cancers that were mesothelioma increased during the same period of time. Finally, the increased trend observed in the incidence of pleural mesothelioma and cancers in women is credibly due to their under diagnosis in the 1980-1997 period. The comparison between the French incidence and the American and British ones shows that the decreasing trend in incidence of mesothelioma and pleural cancers in French men since 2000 is potentially associated with a lower amphibole consumption and by the implementation of safety regulations at work from 1977.

Surgery for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) remains a challenging disease from the surgical perspective. Its diffuse nature with involvement of the lung, pericardium, and diaphragm; the inability to reliably obtain negative margins; the significant morbidity and mortality associated with radical resection; and most importantly, the high recurrence rate after surgery, all contribute to the nihilistic attitude with which most clinicians view this disease. Despite major improvements in operative mortality over the last 2 decades, which is now between 2% and 8% at most centers, surgery alone is associated with high rates of local failure. For this reason, adjuvant and neoadjuvant modalities have been integrated into the surgical management of MPM. In most centers today, aggressive therapeutic approaches involve a trimodality regimen including extrapleural pneumonectomy (EPP), radiation therapy, and chemotherapy. The low incidence of MPM (2500-3000 cases per year in the United States) has contributed to the lack of reliable clinical data regarding optimal therapy for this disease. Most surgical series have been single-center retrospective studies that have spanned many years or prospective phase I and II trials that have involved small numbers of patients. To date, there has been no randomized study that has included surgery in the therapeutic regimen. Evidence for the efficacy of surgery has been largely based on comparison of highly selected patients who have undergone resection to unselected historical controls. Comparisons between retrospective studies in MPM are confounded by numerous factors including:

Biomarkers for Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose main etiology is exposure to asbestos fibers. The incidence of MPM is anticipated to increase worldwide during the first half of this century. For various reasons, MPM is difficult to diagnose and is notoriously refractory to most treatments. However, recently two active chemotherapy regimens have been demonstrated to significantly increase survival in patients with MPM, and several therapeutic agents and strategies are currently under evaluation.Researchers have actively sought MPM biomarkers for more than 20 years. Biomarkers would be helpful in managing three clinical aspects of MPM: early diagnosis, prognosis, and treatment outcome prediction. The aims of the present review are to summarize the published and recently presented data on MPM biomarkers and to identify the prospects for future translational research projects.Among the 'classical' diagnostic biomarkers measured in biological fluids, such as cytokeratins and cell surface antigens, none discriminate patients with MPM from those with other malignancies and nonmalignant diseases. Osteopontin, soluble mesothelin, and megakaryocyte potentiating factor (MPF) appear to be the most promising of the recent biomarkers, but are still subject to some limitations. Osteopontin lacks specificity for mesothelioma, while both soluble mesothelin and MPF lack sensitivity for detecting non-epithelial subtypes. Panels consisting of a small set of biomarkers do not improve the diagnostic yield, and results from molecular profiling are too preliminary to be brought into daily clinical practice. While a large number of biomarkers have been assessed in biological fluids and tumor tissue for their prognostic value, none have had a widespread impact on clinical practice. In contrast, data concerning predictive biomarkers are very limited, even though they are most interesting from the perspective of clinicians.Additional prospective studies, in large and independent samples of patients, with rigorous statistical methodology and standardized laboratory techniques are now warranted to validate and define the precise value of diagnostic and prognostic MPM biomarkers. Future research efforts should focus on biomarkers predictive of the efficacy and toxicity of standard chemotherapy. Translational research should be systematically incorporated into the design of clinical trials assessing new targeted agents in MPM.