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The surgical management of pleural mesothelioma (PM) can be divided into diagnostic, staging, palliation, and cytoreductive surgery. In the cytoreductive surgical setting, the combination of different treatment modalities has led to better outcomes than surgery alone. The scarcity of high-quality studies has led to heterogeneity in management of PM across the mesothelioma treatment centers. Here, we review the literature regarding the most important open questions and ongoing clinical trials., (© 2022 Wiley Periodicals LLC.)

Background: Postoperative empyema after pleurectomy decortication (PDC) for malignant pleural mesothelioma (MPM) is a serious complication that necessitates prolonged hospitalization. This study determined the incidence, risk factors, and prognosis in patients when postoperative empyema develops after PDC., Methods: The background, type of PDC, neoadjuvant treatment, date of empyema, pleural fluid cultures, treatment after empyema, and prognosis from a series of consecutive 355 patients treated over 9 years at a single high-volume center were investigated. Fisher exact test, Kaplan-Meier estimators, and log-rank test were used to identify significant risk factors for postoperative empyema and compare the overall survival., Results: During the 9-year period, 355 patients (263 men) underwent PDC for MPM at a median age of 69 years. Neoadjuvant therapy was given to 87, and 282 received intraoperative heated chemotherapy. During the study, empyema developed in 24 patients (6.8%). The length of stay of patients with postoperative empyema was significantly longer. Median survival was 11.7 months for patients with postoperative empyema and 21.3 months for patients without empyema (hazard ratio, 1.78; P = .009). Postoperative empyema was associated with male sex, prolonged air leak, and use of prosthetic mesh., Conclusions: Postoperative empyema after PDC is associated with prolonged length of stay and higher mortality. The rates of this serious postoperative complication might decrease by developing better strategies to avoid prolonged air leak after PDC., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: We report a series of 355 consecutive patients treated over 9 years in a single institution with intended PDC., Background: Surgery for MPM has shifted from extra-pleural pneumonectomy to PDC with the goal of MCR., Methods: Clinical and outcome data were reviewed. Kaplan-Meier estimators and log rank test were used to compare the overall survival, and logistic regression models were used., Results: MCR was achieved in 304. There were 223 males, median age was 69 and histology was epithelioid in 184. The 30 and 90-day mortality were 3.0% and 4.6%.Most complications were low grade. Prolonged air leak in 141, deep venous thrombosis in 64, Atrial fibrillation in 42, chylothorax in 24, Empyema in 23, pneumonia in 21, Hemothorax in 12 and pulmonary embolus in 8. Median/5-year survival were 20.7 months/17.9% in the intent-to-treat cohort and 23.2months/21.2% in the MCR group. The survivals were best for patients with Tlstage and epithelioid histology (69.8months/54.1%). In a multivariable analysis, factors that were found to be associated with longer patient overall survival included epithelioid histology, T stage, quantitative clinical stage/tumor volume staging, adjuvant chemotherapy, intraoperative heated chemo, female sex, and length of stay shorter than 14 days., Conclusions: PDC is feasible with low mortality and is associated with manageable complication rates. 5-year survival of patients undergoing PDC with MCR in multi-modality setting is approaching 25% depending on quantitative and clinical stage, sex and histological subtype and is better than PDC without- MCR., Competing Interests: The research did not receive any specific grant from funding agencies in the public, commercial or nonprofit sectors. The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The purpose of this study was to determine the incidence of venous thromboembolism and utility of a routine surveillance program in patients undergoing surgery for mesothelioma., Methods: Patients undergoing pleurectomy from May 2016 to August 2018 were included. A standardized surveillance program to look for venous thromboembolism in this group included noninvasive studies every 7 days postoperatively or earlier if symptomatic. All patients received external pneumatic compression sleeves in addition to prophylactic heparin. If deep vein thrombosis or pulmonary embolus was discovered, heparin drip was initiated until conversion to therapeutic anticoagulation., Results: A total of 100 patients underwent pleurectomy for mesothelioma. Seven patients were found to have preoperative deep vein thrombosis, and as such only 93 patients were included for analysis. The median age of patients at surgery was 71 years (30-85 years). During the study, 30 patients (32%) developed evidence of thrombosis; 20 patients (22%) developed only deep vein thrombosis without embolism, 3 patients (3%) developed only pulmonary embolism, and 7 patients (7%) developed both deep vein thrombosis and pulmonary embolus. Of the 27 patients who developed deep vein thrombosis, 9 (33%) were asymptomatic at the time of diagnosis, and none of these developed a pulmonary embolus or other bleeding complications. There were 2 (2%) events of major postoperative bleeding related to therapeutic anticoagulation., Conclusions: The incidence of venous thromboembolism is high (32%) among patients undergoing surveillance after pleurectomy for mesothelioma. Up to 33% of patients with deep vein thrombosis are asymptomatic at the time of diagnosis, and the incidence of complications related to anticoagulation is low. Routine surveillance may be useful to diagnose and treat deep vein thrombosis before it progresses to symptomatic or fatal pulmonary embolus., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: The primary objective of this single-institution phase I clinical trial was to establish the maximum tolerated dose of gemcitabine added to cisplatin and delivered as heated intraoperative chemotherapy after resection of malignant pleural mesothelioma., Methods: The extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) treatment arms were based on investigators' assessment of patient fitness and potential for macroscopic complete resection. Previously established intracavitary dosing of cisplatin (range 175-225 mg/m 2 ) with systemic cytoprotection was used in combination with escalating doses of gemcitabine, following a 3-plus-3 design from 100 mg/m 2 in 100-mg increments., Results: From 2007 to 2011, 141 patients were enrolled and 104 completed treatment. The median age of those completing treatment was 65 years (range 43-85 years), and 22 (21%) were female. In the EPP arm (n = 59), 31 patients (53%) had the epithelioid histologic type and the median radiographic tumor volume was 236 cm 3 (range 16-4285 cm 3 ). In the P/D arm (n = 41), 29 patients (71%) had the epithelioid histologic type and the median tumor volume was 79 cm 3 (range 6-1107 cm 3 ). The operative mortality rate was 2%, and 35 and 22 serious adverse events were encountered among 27 patients (46%) and 16 patients (39%) in the EPP and P/D arms, respectively. Dose-limiting toxicity (grade 3 leukopenia) was observed in two patients who were receiving 1100 mg/m 2 of gemcitabine, thus establishing the maximum tolerated dose at 1000 mg/m 2 , in combination with 175 mg/m 2 of cisplatin. The median overall and recurrence-free survival times in treated patients were 20.3 and 10.7 months, respectively., Conclusions: Combination cisplatin and gemcitabine heated intraoperative chemotherapy can be administered safely and feasibly in the context of complete surgical resection of malignant pleural mesothelioma by EPP or P/D., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objective: Surgery-based multimodality therapy is associated with long-term survival in a significant number of pleural mesothelioma patients. We explored factors associated with 3-year survival in patients with malignant pleural mesothelioma, who underwent extrapleural pneumonectomy, to help refine patient selection criteria for surgery and other therapies., Methods: With Institutional Review Board approval, we reviewed records in the International Mesothelioma Program Patient Data Registry to identify all patients, who underwent extrapleural pneumonectomy for malignant pleural mesothelioma between 1 January 1988 and 31 May 2007. Vital status as of 31 May 2010 was confirmed. Fisher's exact test was used to compare dichotomous variables for patients who survived at least 3 years with those who did not. Kaplan-Meier analysis was used to estimate the cumulative survival probability for all 3-year survivors., Results: Among 636 patients who underwent extrapleural pneumonectomy, 117 (18%) survived at least 3 years following surgery, including 26 remaining alive and four lost to follow-up. Of the 3-year survivors, 39 (33%) were female, 61 (52%) had left-sided disease, and the median age was 56 years (range 27-77). Relatively more 3-year survivors were younger than, or at the median age (p=0.0005), or female (p=0.0007), had epithelial tumor histology (p<0.0001) and/or had normal white blood cell count (p=0.0001), hemoglobin (p<0.0001), or platelet count (p<0.0001) preoperatively. The median survival of the 117 patients who survived 3-years was 59 months. Among these patients, a significant association between age and survival was found only for women., Conclusions: A significant proportion of patients undergoing extrapleural pneumonectomy for pleural mesothelioma experienced extended survival. Although favorable prognostic features were more common, the cohort of 3-year survivors included a substantial number of patients with late-stage disease. The longest survival (median greater than 7 years) was experienced by women under the median age of 56 years. These data support the role of macroscopic cytoreduction through extrapleural pneumonectomy in the context of multimodality therapy to extend survival for malignant pleural mesothelioma. Further efforts to treat micrometastatic disease and improve patient selection are warranted., (Copyright © 2011. Published by Elsevier B.V.)

Background: Several pathologic staging systems for malignant pleural mesothelioma (MPM) have been published, but none of them provide optimal survival stratification or stage distribution among patients treated with surgery. Interpretation of prior studies that correlate pathologic factors with outcome has been confounded by the inclusion of patients undergoing differing surgical procedures and with varied tumor histology., Methods: We examined pathologic characteristics, previously included in published studies, and explored correlations with outcome among patients with epithelioid MPM who underwent extrapleural pneumonectomy (EPP) at Brigham and Women's Hospital (BWH). Comparisons of survival among patients with and without each tumor or lymph node feature guided adjustments to the American Joint Commission on Cancer (AJCC)/International Union Against Cancer (UICC) classification criteria. Proportional hazards modeling of TN combinations guided adjustments to stage groupings., Results: Three hundred fifty-four patients were resectable by EPP and had complete pathologic data. Overall median survival was 18 months from surgery. By AJCC/UICC criteria, 233 (66%) patients were stage III, whereas by BWH criteria, 194 (55%) patients were stage III. T classification criteria were adjusted based on prevalence and relation to survival. N status correlated significantly with survival. Regrouping of TN combinations based on relative hazard and Kaplan-Meier survival analysis resulted in improved stage distribution (stage I-IV: 8%, 43%, 33%, 16%, respectively) and survival stratification (51, 26, 15, 8 months, respectively)., Conclusions: Proposed adjustments to TNM staging criteria improved outcome stratification of patients with epithelial tumor histology who received surgical therapy by EPP and complete pathologic assessment. Determining relevance to other treatment or staging modalities will require verification in additional cohorts.

Objective: We sought to prospectively determine the feasibility and safety of hyperthermic intraoperative intracavitary cisplatin perfusion immediately after extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma., Methods: Patients with malignant pleural mesothelioma who were surgical candidates underwent extrapleural pneumonectomy followed by hyperthermic intraoperative intracavitary cisplatin perfusion, consisting of a 1-hour lavage of the chest and abdomen with cisplatin (42 degrees C) at 225 mg/m(2). Pharmacologic cytoprotection consisted of intravenous sodium thiosulfate with or without amifostine. Morbidity and mortality were recorded prospectively., Results: Ninety-six (79%) of 121 enrolled patients underwent extrapleural pneumonectomy, of whom 92 (76%) received hyperthermic intraoperative intracavitary cisplatin perfusion after extrapleural pneumonectomy. Fifty-three (58%) patients had epithelial tumors, and 39 (42%) had nonepithelial histology. Hospital mortality was 4.3%. Morbidity (grade 3 or 4, 49%) included atrial fibrillation in 22 (23.9%) patients, venous thrombosis in 12 (13%) patients, and laryngeal nerve dysfunction in 10 (11%) patients. Nine patients had renal toxicity, which was attributable to cisplatin in 8 of them. Among the 27 patients who also received amifostine (910 mg/m(2)), 1 patient had grade 3 renal toxicity attributable to cisplatin. Recurrence of malignant pleural mesothelioma was documented in 47 (51%) patients, with ipsilateral recurrence in 17.4% of patients. The median survival of the 121 enrolled patients was 12.8 months., Conclusions: Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy can be performed with acceptable morbidity and mortality. The use of amifostine in addition to sodium thiosulfate might reduce cisplatin-associated renal toxicity. Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy might enhance local control in the chest.

Objective: This study was undertaken to determine maximum tolerated dose and toxicity of intraoperative intracavitary hyperthermic cisplatin perfusion with amifostine after extrapleural pneumonectomy for malignant pleural mesothelioma., Methods: Patients with mesothelioma were prospectively enrolled. Those with resectable disease received amifostine and 1-hour hyperthermic cisplatin perfusion of ipsilateral hemithorax and abdomen. Morbidity, recurrence, and survival were recorded., Results: Forty-two patients were enrolled; 29 underwent resection (operative mortality 7%, 2/29). Median age was 57 years. Eighteen were in pathologic stage I or II; 11 were in stage III. Median hospitalization was 15 days. Common complications were atrial fibrillation (66%, 19 patients), deep venous thrombosis (31%, 9 patients), and grade 3+ renal toxicity (31%, 9 patients). Feasibility was determined. Renal toxicity was unrelated to cisplatin dose, with no maximum tolerated dose determined. Overall median survival was 17 months (resected 20 months, unresected 10 months). Median survivals were 26 months for patients receiving higher cisplatin doses and 16 months for those receiving lower doses (P = .35). Survival was significantly longer with negative extrapleural nodes (31 vs 14 months, P = .0115) and early stage (all resected 35 months for stage I-II vs 14 months for stage III, P = .0022, epithelial 39 months for stage I-II vs 15 months for stage III, P = .0072)., Conclusion: Early stage and negative extrapleural lymph nodes were associated with prolonged survival. Single-dose amifostine did not protect adequately against cisplatin-induced renal toxicity. Additional cytoprotective strategies are needed to allow determination of cisplatin maximum tolerated dose.

Purpose: To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM)., Patients and Methods: Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42 degrees C and then intravenous sodium thiosulfate (16 g/m2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression., Results: Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2. Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time., Conclusion: Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.

MPM is an uncommon disease with limited treatment options. Early diagnosis, a standardized staging system, early referral to centers experienced in MPM, and efforts to develop collaborative multicenter trials are essential to improving treatment for patients with MPM. Efforts to manage this malignancy, which is projected to peak in the twenty-first century, constitute an important international health concern, particularly because the use of asbestos, despite successful regulatory efforts in many parts of the world, continues unabated in others.

Background: Survival after tri-modality therapy with extrapleural pneumonectomy (EPP) and postoperative chemoradiotherapy is longer for patients with epithelial MPM versus mixed or sarcomatoid subtypes, leading some to decline aggressive therapy for patients with nonepithelial histology. However, pathologic diagnosis of malignant pleural mesothelioma (MPM) and subclassification into one of the three histologic subtypes (epithelial, mixed, sarcomatoid) can be challenging. Pleural biopsy has been proposed as the diagnostic gold standard. We investigated the accuracy of open pleural biopsy for diagnosis and subtype identification in MPM., Methods: Patients with suspected MPM routinely undergo open pleural biopsy to establish diagnosis. Those diagnosed definitively by pleural biopsy or cytology are offered pleurectomy or EPP dependent on stage and cardiorespiratory status. We reviewed medical records for all patients undergoing EPP at our institution, comparing tissue and subtype diagnosis at initial diagnostic biopsy versus definitive resection., Results: Between 1988 and 2000, 305 of 332 consecutive patients undergoing EPP had MPM. One patient diagnosed with MPM at pleural biopsy was misclassified. Subtype analysis at pleural biopsy proved correct in 80% (226/282). Most patients (174/192) with epithelial subtype at final diagnosis were diagnosed correctly at pleural biopsy. However, 44% (45/103) with pathologic diagnosis of nonepithelial subtype at resection were initially misdiagnosed with the epithelial subtype. The sensitivity of pleural biopsy for epithelial MPM was 97% with a specificity of 56%., Conclusions: Open pleural biopsy is accurate and should be considered the gold standard diagnostic method for MPM. It is less sensitive for determining histologic subclass, particularly with nonepithelial subtypes.

Prompt medical evaluation and aggressive treatment can lead to prolonged survival or successful palliation of symptoms for patients with malignant pleural mesothelioma, but the window for implementing treatment is short. Clinical recognition of the cancer is confounded by numerous factors, including long latency between exposure to asbestos and expression of the disease, nonspecific nature of the presenting symptoms, rarity of the disease, a lack of experience in clinical diagnosis, and rapidly deteriorating clinical course after diagnosis. Heightened clinical suspicion and proper patient selection through accurate staging and pathologic identification are paramount to defining and delivering therapy for this rare, lethal cancer.

Objective: Extrapleural pneumonectomy for therapy of mesothelioma has been associated with significant perioperative mortality and morbidity. Postoperative complications of this procedure require a unique management approach. We developed treatment algorithms for most of the common complications of extrapleural pneumonectomy resulting in reduced mortality and hospital stay. Complications after extrapleural pneumonectomy were further analyzed to elucidate means of prevention, early detection, and treatment., Methods: A total of 496 patients undergoing extrapleural pneumonectomy were reviewed for mortality rates, with a subset of 328 consecutive patients between 1980 and 2000 who were examined for detailed morbidity data by using a prospective clinical database., Results: Median age was 58 years (range, 28-77 years), with a 10-day (range, 4-101 days) median length of stay. One hundred ninety-eight (60.4%) of 328 patients experienced minor and major complications, and 11 of 328 patients died, for an overall mortality rate of 3.4%. Complications included the following: atrial fibrillation (145 [44.2%]), prolonged intubation (26 [7.9%]), vocal cord paralysis (22 [6.7%]), deep vein thrombosis (21 [6.4%]), technical complications (patch dehiscence, hemorrhage, or both; 20 [6.1%]), tamponade (12 [3.6%]), acute respiratory distress syndrome (12 [3.6%]), cardiac arrest (10 [3%]), constrictive physiology (9 [2.7%]), aspiration (9 [2.7%]), renal failure (9 [2.7%]), empyema (8 [2.4%]), tracheostomy (6 [1.8%]), myocardial infarction (5 [1.5%]), pulmonary embolus (5 [1.5%]), and bronchopleural fistula (2 [0.6%]). Clinical data demonstrated the following: (1) prophylaxis for atrial fibrillation is recommended; (2) early ambulation, aspiration precautions, endoscopic assessment of the vocal cords, and avoidance of fluid overload are crucial; (3) perioperative diagnosis and aggressive management of deep vein thrombosis are important; (4) immediate reoperation and open cardiac massage are essential for relief of cardiac herniation and tamponade from cardiac patch dysfunction; (5) diaphragmatic patch dehiscence, hemorrhage, or both require immediate reoperation; (6) early signs of infection might indicate bronchopleural fistula or empyema and should be treated with thoracoscopic or open drainage and staged removal of patch material; and (7) excessive perioperative mediastinal shift is treated with a catheter placed intraoperatively., Conclusion: Complications after extrapleural pneumonectomy require a unique approach to management, and mortality can be minimized by early detection and aggressive treatment.

Background: We have recently demonstrated that simple ratios of the expression levels of selected genes in tumor samples can be used to distinguish among types of thoracic malignancies. We examined whether this technique could predict treatment-related outcome for patients with mesothelioma., Methods: We used gene expression profiling data previously collected from 17 mesothelioma patients with different overall survival times to define two outcome-related groups of patients and to train an expression ratio-based outcome predictor model. A Student's t test was used to identify genes among the two outcome groups that had statistically significant, inversely correlated expression levels; those genes were used to form prognostic expression ratios. We used a combination of several highly accurate expression ratios and cross-validation techniques to assess the internal consistency of this predictor model, quantitative reverse transcription-polymerase chain reaction of tumor RNA to confirm the microarray data, and Kaplan-Meier survival analysis to validate the model among an independent set of 29 mesothelioma tumors. All statistical tests were two-sided., Results: We developed an expression ratio-based test capable of identifying 100% (17/17) of the samples used to train the model. This test remained highly accurate (88%, 15/17) after cross-validation. A four-gene expression ratio test statistically significantly (P =.0035) predicted treatment-related patient outcome in mesothelioma independent of the histologic subtype of the tumor., Conclusions: Gene expression ratio-based analysis accurately predicts treatment-related outcome in mesothelioma samples. This technique could impact the clinical treatment of mesothelioma by allowing the preoperative identification of patients with widely divergent prognoses.

Malignant pleural mesothelioma (MPM) is a highly lethal pleural neoplasm that is often resistant to chemotherapeutic drugs, including cisplatin, and for which little is known regarding carcinogenic pathways. We used differential display to compare gene expression patterns in mesothelioma, normal pleura and normal lung, in order to better understand MPM pathobiology, and to search for genes that may facilitate drug resistance in this cancer. The human inhibitor of apoptosis protein-1 gene (IAP-1/MIHC/cIAP2) was discovered to be highly expressed in MPM. We confirmed overexpression of IAP-1 mRNA and protein in 39 additional human MPM tumor specimens and 3/5 (60%) MPM cell lines by multiple methods, including real time quantitative reverse transcription-PCR and western blot analysis. Using an antisense targeting approach, we found that attenuation of IAP-1 mRNA levels decreases baseline cell viability and increases the sensitivity of MPM cell lines to cisplatin by nearly 20-fold. Reduced IAP-1 gene expression also results in a concordant increase of the pro-apoptotic cleavage product of caspase 9 and a reduction in the number of viable tumor cells. Our observations strongly suggest that IAP-1 is at least partly responsible for promoting carcinogenesis and mediating resistance to cisplatin in many MPM tumors and that further study of this apoptotic pathway is warranted.

SV40 viral DNA sequences, particularly large T-antigen (T-ag) DNA, have been reported in malignant pleural mesothelioma (MPM) and suggested to play a role in the tumorigenesis of this cancer. These results remain somewhat controversial owing to variability among a number of laboratories in reported SV40 DNA and protein detection in MPM tissues. This could be explained in part if SV40 DNA is present in relatively low abundance in many MPM tissues determined to contain viral sequences and is therefore difficult to detect. To this end, we investigated the efficacy of real time quantitative PCR in detecting low copy number SV40 DNA sequences, then we quantified SV40 copy number in MPM tissues and cell lines at our institution. Quantitative PCR demonstrated consistent precision and accuracy in detecting SV40 DNA sequences over a large logarithmic range of viral copy number. In addition, SV40 sequences were found in 2/35 tissues and 3/7 cell lines in relatively low abundance. We conclude that SV40 is not a contributing factor in the pathobiology of the majority of MPM tumors from patients at our institution.

Malignant pleural mesothelioma (MPM) is a rare tumor that predominantly afflicts men over 50 years of age. Nearly 3000 MPMs are reported annually in the United States with the incidence expected to rise into the new millenium. Over the past 40 years, MPM has been unequivocally linked to asbestos exposure worldwide. Recently, however, a new theory on the carcinogenesis of this tumor has been proposed with the isolation of a simian virus (SV 40)-like gene sequence in mesothelioma tumor cells. The clinical presentation of MPM is variable, although most patients typically present with dyspnea, chest pain, or pleural effusion. Obtaining a diagnosis of MPM has been greatly assisted by video-assisted surgery and the use of immunohistochemistry and electron microscopic techniques, which help distinguish MPM from other tumor pathologies such as adenocarcinoma. Computed tomography and magnetic resonance imaging have been also useful for determining tumor burden and resectability. Traditionally, strategies for the treatment of MPM have included supportive care, surgery, radiotherapy, and chemotherapy. Survival with supportive care alone ranges between 4 and 12 months. Single-modality therapy using traditional approaches (surgery, radiotherapy, chemotherapy) alone has failed to improve patient survival significantly. Recently, results using a multimodality approach have been favorable. In particular, cytoreductive surgery (pleuropneumonectomy) followed by sequential chemotherapy and radiotherapy have demonstrated improved survival, especially for patients with epithelial histology, negative resection margins, and no metastases to extrapleural lymph nodes. Innovative therapies such as the use of photodynamic, targeted cytokines and gene therapy are currently being investigated for management of MPM.

Objectives: Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma., Methods: From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy., Results: Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P <.0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05)., Conclusions: (1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.

The incidence of malignant pleural mesothelioma is increasing. Untreated, patients with this disease experience a rapid and horrendous clinical decline. Surgery plays a role in the diagnosis, staging, and treatment of this malignancy. Surgery, chemotherapy, and radiotherapy alone have been unable to achieve major improvements in survival for most patients. More recent phase II trials suggest that surgery, at one time a purely palliative approach, may have a potentially curative role when used in combination with chemotherapy and radiotherapy.