The Annals of Thoracic Surgery

About the journal

Publisher: Elsevier
Published: 1965 to the present, Netherlands
Language: English
ISSN: 0003-4975 (print), 1552-6259 (electronic)
Its record in the NLM Catalog

2020s

Characteristics of Long-term Survivors With Malignant Pleural Mesothelioma. I. Opitz, O. Lauk, R. Werner, et al. 2025;120(1):108-116. PubMed · Publisher

Abstract

Background: Pleural mesothelioma (PM) is a cancer with a usually dismal prognosis. However, long-term survivors do exist. Herein, we analyzed long-term survivors (>5 years after surgery) from high-volume centers around the world.

Methods: This is a multicenter retrospective descriptive analysis of long-term survivors (overall survival ≥5 years from surgery) treated within a multimodality therapy approach, including macroscopic complete resection. Overall survival was calculated with Kaplan-Meier analysis, and patients were matched by center and surgery year and compared with a control group of short-term survivors (<2 years) in a conditional logistic regression analysis.

Results: There were 276 long-term survivors (166 men [63%]), with a median age of 59 years (range 21-83 years) at the time of diagnosis. The histology was epithelioid for 246 patients and nonepithelioid for 30 patients. The disease was on the right side in 58% of the patients. As of this analysis, 148 patients had died, 104 were alive, and 10 were lost to follow-up. Pathologic tumor stages were: pT1 (n = 50), pT2 (n = 63), pT3 (n = 90), or pT4 (n = 16) and pN0 (n = 150), pN1 (n = 20), and pN2 (n = 39). The matched control data set included 333 patients, 95 cases and 238 controls. Comparing short- with long-term survivors, we found moderate evidence that a low white blood cell count before surgery was more often observed in long-term survivors.

Conclusions: The data show that long-term survival in PM is possible in a subgroup of surgically treated patients. Histologic subtype and white blood cell count seem to be prognosticators for longer survival.

Copyright © 2025. Published by Elsevier Inc.
Extrapleural Pneumonectomy Versus Pleurectomy/Decortication for Malignant Pleural Mesothelioma. N. Zhou, D.C. Rice, A.S. Tsao, et al. 2022;113(1):200-208. PubMed · Publisher

Abstract

Background: Whether extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D) is the optimal resection for malignant pleural mesothelioma remains controversial. We therefore compared perioperative outcomes and long-term survival of patients who underwent EPP versus P/D.

Methods: Patients with the diagnosis of malignant pleural mesothelioma who underwent either EPP or P/D from 2000 to 2019 were identified from our departmental database. Propensity score matching was performed to minimize potential confounders for EPP or P/D. Survival analysis was performed by the Kaplan-Meier method and Cox multivariable analysis.

Results: Of 282 patients, 187 (66%) underwent EPP and 95 (34%) P/D. Even with propensity score matching, perioperative mortality was significantly higher for EPP than for P/D (11% vs 0%; P = .031); when adjusted for perioperative mortality, median overall survival between EPP and P/D was 15 versus 22 months, respectively (P = .276). Cox multivariable analysis for the matched cohort identified epithelioid histology (hazard ratio [HR], 0.56; P = .029), macroscopic complete resection (HR, 0.41; P = .004), adjuvant radiation therapy (HR, 0.57; P = .019), and more recent operative years (HR, 0.93; P = .011)-but not P/D-to be associated with better survival. Asbestos exposure (HR, 2.35; P = .003) and pathologic nodal disease (HR, 1.61; P = .048) were associated with worse survival.

Conclusions: In a multimodality treatment setting, P/D and EPP had comparable long-term oncologic outcomes, although P/D had much lower perioperative mortality. The goal of surgical cytoreduction should be macroscopic complete resection achieved by the safest operation a patient can tolerate.

Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Inhibition of Cyclin Dependent Kinase 4/6 Overcomes Primary Resistance to Programmed Cell Death 1 Blockade in Malignant Mesothelioma. H.J. Jang, C.Y. Truong, E.M. Lo, et al. 2022;114(5):1842-1852. PubMed · Publisher · Free full text

Abstract

Background: Despite the profound number of malignant pleural mesothelioma (MPM) patients now treated with programmed cell death 1 (PD-1) blockade, insight into the underpinnings of rational therapeutic strategies to treat resistance to checkpoint immunotherapy remains unrealized. Our objective was to develop a novel therapeutic approach to overcome primary resistance to PD-1 blockade in MPM.

Methods: We generated a transcriptome signature of resistance to PD-1 blockade in MPM patients treated with nivolumab (4 responders and 4 nonresponders). We used The Cancer Genome Atlas MPM cohort (n = 73) to determine what genomic alterations were associated with the resistance signature. We tested whether regulation of identified molecules could overcome resistance to PD-1 blockade in an immunocompetent mouse malignant mesothelioma model.

Results: Immunogenomic analysis by applying our anti-PD-1 resistance signature to The Cancer Genome Atlas cohort revealed that deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) was highly associated with primary resistance to PD-1 blockade. Under the hypothesis that resistance to PD-1 blockade can be overcome by cyclin dependent kinase 4/6 (CDK4/6) inhibition, we tested whether CDK4/6 inhibitors could overcome resistance to PD-1 blockade in subcutaneous tumors derived from Cdkn2a-/- AB1 malignant mesothelioma cells, which were resistant to PD-1 blockade. The combination of daily oral administration of CDK4/6 inhibitors (abemaciclib or palbociclib) and intraperitoneal anti-PD-1 treatment markedly suppressed tumor growth compared with anti-PD-1 or CDK4/6 inhibitor alone.

Conclusions: We identified a therapeutic target, CDK4/6, to overcome primary resistance to PD-1 blockade through comprehensive immunogenomic approaches. These data provide a rationale for undertaking clinical trials of CDK4/6 inhibitors in more than 40% of patients with MPM who demonstrate loss of CDKN2A.

Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Japanese Current Status of Curative-Intent Surgery for Malignant Pleural Mesothelioma. M. Hashimoto, H. Yamamoto, S. Endo, et al. 2022;113(4):1348-1353. PubMed · Publisher

Abstract

Background: Few reports about surgical outcomes in malignant pleural mesothelioma (MPM) have been based on reliable nationwide databases. Here, we analyzed the incidence, surgical outcome, and operative risk factors using Japanese nationwide database.

Methods: Characteristics and perioperative data from 622 patients who underwent curative-intent surgery for MPM between January 2014 and December 2017 were recorded from National Clinical Database of Japan. We analyzed the incidence, surgical outcomes, and risk factors for surgical complications after 2 surgical procedures (extrapleural pneumonectomy [EPP] and pleurectomy/decortication [P/D]).

Results: During 4 years, EPP was performed in 279 patients and P/D in 343. EPP was more frequently performed in institutions less experienced in MPM, while P/D was more frequently performed in institutions well experienced in MPM (P < .001), especially in high-volume centers with more than 10 cases during this period. P/D was more frequently performed, especially in high-volume centers. The morbidity rates were 45.2% in EPP and 35.9% in P/D. Heart failure and pneumonia were most frequent in EPP, while prolonged air leakage was most frequent in P/D. Thirty-day and in-hospital mortality rates were 1.1% and 3.2% (EPP) and 1.2% and 3.2% (P/D), respectively. Regression analyses revealed that higher age (>65 years) was associated with operative complications in EPP (odds ratio, 3.56 [95% confidence interval, 1.26-8.56]), whereas no risk factor was observed in P/D.

Conclusions: In Japanese nationwide annual database, P/D was more frequently performed, especially in high-volume centers. Morbidity was higher in EPP than P/D; however, the mortality rates were quite low in Japan regardless surgical procedures.

Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Diagnostic Laparoscopy Improves Staging of Malignant Pleural Mesothelioma With Routine Positron Emission Tomography Imaging. R.T. Ripley, N. Palivela, S.S. Groth, et al. 2021;112(5):1568-1574. PubMed · Publisher

Abstract

Background: With a multimodal treatment strategy, cytoreductive surgery extends survival in malignant pleural mesothelioma. Improving the accuracy of staging can refine patient selection. Our objective was to determine whether diagnostic laparoscopy (DL) improves staging for patients with malignant pleural mesothelioma with the routine use of positron emission tomography (PET).

Methods: We performed a retrospective review of our prospectively maintained database from February 2014 to May 2019. Inclusion criteria were patients who had disease in the chest that was deemed potentially resectable by radiographic criteria and who underwent DL as part of the staging evaluation before surgery.

Results: Of 187 patients (71% men, 80% epithelial) who underwent DL during staging, 76% proceeded to surgery; 22% were unresectable at exploratory thoracotomy and 78% underwent resection (pleurectomy and decortication, 68%; extrapleural pneumonectomy, 32%). Also, 89% had a PET computed tomography (CT), and 11% had a preoperative CT without PET. DL revealed peritoneal disease in 17%. Among patients with pathologically proven disease at DL, 77% had negative PET-CT imaging. Based on the pathologic findings at DL the sensitivity, specificity, positive predictive value, and negative predictive value of PET-CT were 23%, 78%, 17%, and 83%, respectively. The accuracy of PET-CT was 68%.

Conclusions: PET-CT has low sensitivity and diagnostic accuracy to identify peritoneal disease in malignant pleural mesothelioma. DL as part of the preoperative staging defines an important subset of patients with bicavitary disease. We recommend DL as a component of staging before surgery.

Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Prognostic Role of PD-L1 in Malignant Pleural Mesothelioma: Unraveling the Complexity of the Tumor Microenvironment in Mesothelioma. M. de Perrot. 2021;112(5):1583-1584. Comment PubMed · Publisher
Prognostic Role of Programmed Cell Death 1 Ligand 1 in Resectable Pleural Mesothelioma. H.S. Lee, M. Hamaji, N. Palivela, et al. 2021;112(5):1575-1583. Meta-analysis PubMed · Publisher

Abstract

Background: The prognostic role of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) is incompletely understood. Our objectives were to evaluate the evidence for tumor PD-L1 as a prognostic biomarker in MPM through meta-analysis and to determine whether tumor PD-L1 expression is associated with survival in MPM patients undergoing macroscopic complete resection.

Methods: Meta-analysis was performed to determine the association of PD-L1 with overall survival in MPM (n = 1655) from 14 studies containing overall survival and tumor PD-L1 expression. Univariable and multivariable analyses tested the relationship of tumor PD-L1 with overall survival and recurrence-free survival in an institutional cohort of MPM patients treated by macroscopic complete resection (n = 75). To validate the association of PD-L1 with overall survival, we utilized two independent MPM cohorts (n = 284).

Results: Meta-analysis demonstrated that high tumor PD-L1 expression was associated with poor overall survival. Among 75 patients undergoing macroscopic complete resection, 49 tumors (65%) expressed PD-L1 (1% or more), and high PD-L1 (50% or greater) was more commonly expressed on nonepithelial (29%) compared with epithelial tumors (14%). High tumor PD-L1 expression was independently associated with poor overall survival (P < .001, hazard ratio 5.67) and recurrence-free survival (P = .003, hazard ratio 3.28). The association of PD-L1 overexpression with unfavorable survival was more significant in epithelial MPMs than nonepithelial MPMs. These findings were validated in RNA sequencing analyses in two independent cohorts. Exploratory transcriptome analysis revealed that MPM tumors with PD-L1 overexpression displayed coexpression of other immune regulatory molecules, programmed cell death 1 ligand 2 and T-cell immunoglobulin mucin receptor 3.

Conclusions: Tumor PD-L1 expression is a prognostic biomarker in patients undergoing surgical resection for MPM and may be useful in perioperative decision making.

Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Clinical Outcomes With Recurrence After Pleurectomy/Decortication for Malignant Pleural Mesothelioma. A. Nakamura, T. Takuwa, M. Hashimoto, et al. 2020;109(5):1537-1543. PubMed · Publisher

Abstract

Background: Most patients with malignant pleural mesothelioma experience recurrence after treatment. However no clinical studies have evaluated postrecurrence survival after pleurectomy/decortication for malignant pleural mesothelioma. This study aimed to clarify postrecurrence survival, treatment, prognostic factors, and recurrence pattern after pleurectomy/decortication.

Methods: We conducted a retrospective cohort study of 90 patients who underwent neoadjuvant chemotherapy followed by pleurectomy/decortication at our hospital between September 2012 and December 2017. Survival and recurrence were calculated using the Kaplan-Meier method with the log-rank test. Clinical factors related to postrecurrence survival were assessed using multivariate analysis with the Cox proportional hazards model.

Results: Of 90 patients, 57 (63.3%) developed recurrence. The 1- and 3-year recurrence-free survival rates were 69.7% and 34.0%, respectively (median recurrence-free survival time, 19.0 months). With regard to initial recurrence, 39 patients (68.4%) developed local recurrence, 6 (10.5%) developed distant recurrence, and 12 (21.1%) developed both local and distant recurrences. The 1-year postrecurrence survival rate was 59.5% (median post-recurrence survival time, 14.4 months). Forty-three patients (75.4%) underwent a postrecurrence treatment. Multivariate analysis revealed that postrecurrence treatment (hazard ratio, 0.2; 95% confidence interval, 0.07-0.55; P = .002), performance status 0 to 1 (hazard ratio, 0.24; 95% confidence interval, 0.08-0.76; P = .01), and disease-free interval more than 12 months (hazard ratio, 0.4; 95% confidence interval, 0.16-0.99; P = .04) were the independent, favorable, and significant prognostic factors of postrecurrence survival.

Conclusions: Postrecurrence survival after pleurectomy/decortication is acceptable, and postrecurrence treatment, performance status, and disease-free interval are important prognostic factors of postrecurrence survival.

Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Impact of Hospital Volume on Outcomes of Elective Pneumonectomy in the United States. J. Hadaya, V. Dobaria, E. Aguayo, et al. 2020;110(6):1874-1881. PubMed · Publisher

Abstract

Background: Despite advances in surgical technique and perioperative management, pneumonectomy remains associated with significant morbidity and mortality. The purpose of this study was to examine the impact of annual institutional volume of anatomic lung resections on outcomes after elective pneumonectomy.

Methods: We evaluated all patients who underwent elective pneumonectomy from 2005 to 2014 in the National Inpatient Sample. Patients less than 18 years of age, or with trauma-related diagnoses, mesothelioma, or a nonelective admission were excluded. Hospitals were divided into volume quartiles based on annual institutional anatomic lung resection caseload. We studied the effect of institutional volume on inhospital mortality, complications, and failure to rescue, as well as costs and length of stay.

Results: During the study period, an estimated 22,739 patients underwent pneumonectomy, with a reduction in national mortality from 7.9% to 5.5% (P trend = .045). Compared with the highest volume centers, operations performed at the lowest volume hospitals were associated with 1.74 increased odds of mortality (95% confidence interval, 1.14 to 2.66). Despite similar odds of postoperative complications, low volume hospital status was associated with increased failure to rescue rates (18.3% vs 12.7%, P = .024) and adjusted odds of mortality (1.70; 95% confidence interval, 1.09 to 2.64) after any complication.

Conclusions: High volume hospital status is strongly associated with reduced mortality and failure to rescue rates after pneumonectomy. Efforts to centralize care or disseminate best practices may lead to improved national outcomes for this high-risk procedure.

Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
New Information on Talc and Mesothelioma. J.B. Shrager. 2020;110(3):1099. Letter · Comment PubMed · Publisher
Posterior Intercostal Lymph Nodes Double Recurrence and Death Risk in Malignant Pleural Mesothelioma. J.S. Friedberg, C.B. Simone, M.J. Culligan, et al. 2020;110(1):241-250. PubMed · Publisher

Abstract

Background: Posterior intercostal lymph nodes, previously undescribed for cancer staging, are part of the lymphatic drainage of the pleural space. This study assessed the impact of posterior intercostal lymph nodes on survival in patients undergoing extended pleurectomy/decortication for malignant pleural mesothelioma.

Methods: As part of the thoracic lymphadenectomy, posterior intercostal lymph nodes were accessed by incising the endothoracic fascia at the level of the rib heads. These nodes were systematically harvested in 56 consecutive patients undergoing extended pleurectomy decortication in a clinical trial. The impact of these nodes on progression-free (PFS) and overall survival (OS) was analyzed by multiple statistical methods.

Results: Median PFS and OS were 11.6 and 25.5 months, respectively. In 6 of 56 patients (11%), posterior intercostal lymph nodes were the only positive nodes, and overall, 48.2% had posterior intercostal lymph node metastases. Patients with N2 disease had significantly poorer prognosis if the posterior intercostal lymph nodes were involved: PFS (7.3 vs 14.9 months, P = .002) and OS (14.4 vs 26.1 months, P = .028). In the multivariable models, after adjustment for nodal stage and other prognostic factors, intercostal nodes remained associated with a 2.5-fold elevated risk of progression (P < .001) and a 2.3-fold elevated risk of death (P < .001).

Conclusions: Metastases to posterior intercostal lymph nodes independently more than doubled the risk of progression and death and were the only site of nodal metastases in 11% of patients. These nodes warrant further investigation, including nonoperative techniques to identify and factor them into treatment decision making.

Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Talc Pleurodesis: A Medical, Medicolegal, and Socioeconomic Review. I. Baiu, E. Yevudza, J.B. Shrager. 2020;109(4):1294-1301. Systematic review PubMed · Publisher

Abstract

Background: Talcum has been used in pleurodesis for more than 8 decades. Despite a wealth of research, controversy remains over the optimal sclerosant for pneumothorax and pleural effusions. Talc's historical primacy has been challenged because of its potential for pulmonary toxicity, possible carcinogenicity, and recent concerns surrounding availability and legal liability, thus making this an ideal time for a review.

Methods: This systematic review of the talc literature, focused on publications after the year 2000, evaluated mechanism of action, efficacy, side effect profile, and alternative sclerosants; included is an overview of current socioeconomic and legal controversies.

Results: The data support talc as the most effective agent for pleurodesis. There is evidence to suggest that mean particle size has a direct relationship with the side effect profile and that significant hypoxemic events after talc administration are exceedingly rare when using available graded talc preparations. Concerns regarding the development of malignant diseases after topical talc application remain incompletely resolved but appear related to cosmetic powder preparations that were contaminated with asbestos. Purified talc in the pleural space has not been implicated. Recent difficulties accessing commercial talc preparations have been solved. Although safe and effective talc alternatives do exist, these agents are not as well studied.

Conclusions: Talc pleurodesis with modern, purified, graded talc preparations is safe and highly effective. Talc is an inexpensive and accessible option that remains appropriate for pleurodesis despite existing controversies.

Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

2010s

A Clinical Trial of TumorGlow to Identify Residual Disease During Pleurectomy and Decortication. J.D. Predina, A.D. Newton, C. Corbett, et al. 2019;107(1):224-232. PubMed · Publisher · Free full text

Abstract

Background: Macroscopic complete resection can improve survival in a select group of patients with malignant pleural mesothelioma. During resection, differentiating residual tumor from inflammation or scar can be challenging. This trial evaluated near-infrared (NIR) intraoperative imaging using TumorGlow (a novel NIR imaging approach utilizing high-dose indocyanine green and delayed imaging) technology to improve detection of macroscopic residual disease.

Methods: Twenty subjects were enrolled in an open-label clinical trial of NIR intraoperative imaging with TumorGlow (Indocyanine Green for Solid Tumors [NCT02280954]). Twenty-four hours before pleural biopsy or pleurectomy and decortication (P/D), patients received intravenous indocyanine green. All specimens identified during standard-of-care surgical resection and with NIR imaging underwent histopathologic profiling and correlative microscopic fluorescent tomographic evaluation. For subjects undergoing P/D (n = 13), the hemithorax was evaluated with NIR imaging during P/D to assess for residual disease. When possible, additional fluorescent lesions were resected.

Results: Of 203 resected specimens submitted for evaluation, indocyanine green accumulated within 113 of 113 of resected mesothelioma specimens, with a mean signal-to-background fluorescence ratio of 3.1 (SD, 2.2 to 4.8). The mean signal-to-background fluorescence ratio of benign tissues was 2.2 (SD, 1.4 to 2.4), which was significantly lower than in malignant specimens (p = 0.001). NIR imaging identified occult macroscopic residual disease in 10 of 13 subjects. A median of 5.6 resectable residual deposits per patient (range, 0 to 11 deposits per patient), with a mean size of 0.3 cm (range, 0.1 to 1.5 cm), were identified.

Conclusions: TumorGlow for malignant pleural mesothelioma is safe and feasible. Excellent sensitivity allows for to reliable detection of macroscopic residual disease during cytoreductive surgical procedures.

Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Disparities in Compliance With National Guidelines for the Treatment of Malignant Pleural Mesothelioma. F. Espinoza-Mercado, J.D. Borgella, D. Berz, et al. 2019;108(3):889-896. PubMed · Publisher

Abstract

Background: Current guidelines support cancer-directed surgery, chemotherapy, or active surveillance for clinical stages 1 to 3 of epithelial malignant pleural mesothelioma (MPM). Definitive chemotherapy is recommended for sarcomatoid/biphasic histologies. Our objective is to assess compliance with recommendations, measuring their impact on overall survival.

Methods: The National Cancer Database participant user file (2004 to 2014) was queried for patients diagnosed with MPM clinical stages 1 to 3. Multivariable logistic regression model identified factors independently associated with guideline compliance. Kaplan-Meier analysis and Cox proportional hazards were used for overall survival comparison with histologic subgroup analysis.

Results: A total of 3419 patients with clinical stages 1 to 3 met criteria for analysis and comprised epithelial (68.5%), sarcomatoid (17.2%), and biphasic subtypes (14.3%). Cancer-directed surgery was significantly underutilized in epithelial MPM, with 29.3% having no treatment. On multivariable analysis, insurance status and facility type were the strongest predictors of guideline compliance. High-volume hospitals were the most compliant with guidelines (odds ratio 3.58, 95% confidence interval (CI), 2.34 to 5.49, P < .001). Median survival estimates for no treatment, chemotherapy alone, surgery plus chemotherapy, and trimodal therapy were 10.2, 15.4, 21.1, and 21.7 months, respectively (log rank P < .001). In epithelial MPM, a significant increase in overall survival was observed in surgery plus chemotherapy (hazard ratio 0.62, 95% CI, 0.53 to 0.73, P < .001) and trimodality (hazard ratio 0.61, 95% CI, 0.49 to 0.76, P < .001; reference: no treatment).

Conclusions: There is a suboptimal compliance with national guidelines for the treatment of MPM, particularly in low-volume nonacademic settings. Adherence to recommended surgery-based multimodal therapy is associated with an overall survival improvement.

Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Is There a Role for Cancer-Directed Surgery in Early-Stage Sarcomatoid or Biphasic Mesothelioma?. S. Kim, D.A. Bull, L. Garland, et al. 2019;107(1):194-201. PubMed · Publisher

Abstract

Background: Benefits of surgical resection for early-stage nonepithelioid malignant pleural mesothelioma (MPM) have not been clearly elucidated. This study investigated whether cancer-directed surgery affects overall survival compared with nonsurgical therapies for T1-T2 N0 M0 sarcomatoid or biphasic MPM patients.

Methods: Adult patients with clinical stage I or II MPM were identified in the National Cancer Database from 2004 to 2103. Patients who underwent cancer-directed surgery were matched by propensity score with patients who had received chemotherapy/radiotherapy or no treatments. Overall survival was compared using a Cox proportional hazard regression model.

Results: From National Cancer Database queries, 878 patients with clinical stage I or II MPM with sarcomatoid (n = 524) or biphasic (n = 354) histology were identified. Overall median survival was 5.5 months for patients with sarcomatoid mesothelioma. The cancer-directed surgery improved overall survival compared with no operation (median survival, 7.56 months vs 4.21 months, respectively; p < 0.01). In the biphasic group, median overall survival was 12.2 months. Again, the cancer-directed surgery improved survival compared with no operation (15.8 months vs 9.3 months, p < 0.01). For both histologies, the cancer-directed surgery improved overall survival compared with those who underwent chemotherapy or radiotherapy, or both, without resection (p < 0.05). Perioperative mortality was 6.0% at 30 days and 21.4% at 90 days.

Conclusions: The cancer-directed surgery is associated with improved survival in early-stage MPM patients with nonepithelioid histology compared with those who did not undergo resection or chose medical therapy. Given the high perioperative mortality, a careful patient selection and multidisciplinary evaluation is recommended.

Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Metachronous Lung Cancer After Pleurectomy/Decortication. Y. Kai, Y. Tsutani, M. Ito, et al. 2019;107(1):e1-e3. PubMed · Publisher

Abstract

Pleurectomy/decortication is a surgical procedure for malignant pleural mesothelioma (MPM) and has been proposed as an alternative to extrapleural pneumonectomy. We report a second primary lung cancer developing after pleurectomy/decortication for MPM. A 59-year-old man was diagnosed with MPM on the right side and underwent pleurectomy/decortication. Follow-up computed tomography detected a nodule in the right upper lobe that was diagnosed as adenocarcinoma by wedge resection. Lung cancer and MPM are associated with asbestos exposure. However, predicting lung cancer after treatment for MPM is difficult. Careful follow-up of the spared lung is necessary for detecting second primary lung cancer or MPM recurrence.

Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Mesothelioma With a Large Prevascular Lymph Node: N1 Involvement or Something Different?. L. Berzenji, P.E. Van Schil, A. Snoeckx, et al. 2018;105(5):e189-e191. Case report PubMed · Publisher

Abstract

A 64-year-old man presented with a large amount of right-sided pleural fluid on imaging, together with calcified pleural plaques and an enlarged nodular structure in the prevascular mediastinum, presumably an enlarged lymph node. Pleural biopsies were obtained during video-assisted thoracoscopic surgery to exclude malignancy. Histopathology showed an epithelial malignant pleural mesothelioma. Induction chemotherapy with cisplatin and pemetrexed was administered followed by an extended pleurectomy and decortication with systematic nodal dissection. Histopathology confirmed the diagnosis of a ypT3N0M0 (stage IB) mesothelioma, and an unexpected thymoma type B2 (stage II) was discovered in the prevascular nodule. Simultaneous occurrence of a mesothelioma and thymoma is extremely rare.

Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
National Trends in the Epidemiology of Malignant Pleural Mesothelioma: A National Cancer Data Base Study. S.A. Saddoughi, Z.M. Abdelsattar, S.H. Blackmon. 2018;105(2):432-437. PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma (MPM) remains an aggressive malignancy that is difficult to cure. However, the treatment paradigm of MPM has evolved, and the national practice patterns are unknown. This study examined the national trends in the epidemiology, national treatment patterns, and survival of patients with this disease.

Methods: We identified all patients (n = 19,134) with MPM from the National Cancer Data Base from 2004 to 2013. We analyzed patient, tumor characteristics, and treatment patterns using descriptive statistics and used Kaplan-Meier and Cox proportional hazards models to estimate survival stratified by the type of therapy administered.

Results: Four histologic subtypes were represented in the National Cancer Data Base, these included sarcomatoid (n = 2,355 [12.3%]), epithelioid (n = 6,858 [35.8%]), biphasic (n = 13,617 [11%]), and not otherwise specified (n = 8,560 [44.7%]). Across all subtypes, the prevalence of mesothelioma was highest among white men. Sarcomatoid had the worst survival (adjusted hazard ratio, 2.2; p < 0.001). Most patients did not receive any specific modality of treatment (40.2%). Chemotherapy alone was the most common treatment used (31.8%). Trimodality treatment with chemotherapy, surgical resection, and radiation therapy was associated with the best survival (adjusted hazard ratio, 0.43; p < 0.001), followed by combination chemotherapy and resection (adjusted hazard ratio, 0.49; p < 0.001).

Conclusions: This is the first publication to date to analyze the mesothelioma National Cancer Data Base. Although survival remains poor, multimodality therapy with surgical resection is associated with the best survival for MPM. Further research is needed to improve survival and overall patient outcomes.

Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Pericardial Pleomorphic Mesothelioma and Heart Failure: A Unique Case. G. Laguna, M. Blanco, G. Martínez, et al. 2018;106(6):e321-e322. Case report PubMed · Publisher
Pseudomesotheliomatous Type of Sarcomatoid Squamous Cell Lung Cancer Presenting With Hemothorax. N.K. Sangani, S.M. Naliath. 2018;106(4):e201-e203. Case report PubMed · Publisher

Abstract

A 44-year-old man presented with spontaneous massive hemothorax. Computed tomographic scan revealed thickened and nodular pleura with no evidence of lung tumor. The patient underwent right open total pleurectomy. Histopathologic and immunohistochemical studies of the pleura confirmed poorly differentiated sarcomatoid squamous cell carcinoma of the lung with metastasis to the pleura. The carcinoma was psuedomesothelimatous type because of its presentation as diffuse pleural thickening. This presentation of sarcomatoid cancer as pseudomesotheliomatous type with massive hemothorax is rare and can be considered as a differential diagnosis in diffuse pleural thickening or hemothorax, especially in the absence of a clinically identifiable primary lung tumor.

Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Radiofrequency Ablation Effectively Treated Focal Recurrence of Mesothelioma. A. Nakamura, T. Takuwa, M. Hashimoto, et al. 2018;105(6):e265-e267. Case report PubMed · Publisher

Abstract

A 55-year-old man with malignant pleural mesothelioma underwent multimodality treatment comprising induction chemotherapy followed by extrapleural pneumonectomy and radiation therapy. After 2.5 years, focal recurrence occurred, with computed tomography revealing a tumor in the left cardiophrenic angle. Surgery was considered a problem for the patient because of the previous extrapleural pneumonectomy and difficult tumor location. Radiofrequency ablation was therefore performed; the course was uneventful, and there was no recurrence. Radiofrequency ablation should be considered an option to treat recurrence of malignant pleural mesothelioma.

Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Recurrence of Pericardial Mesothelioma Affecting the Myocardium After Pericardial Resection. M. Rodríguez, H.R. Mallidi, A. da Silva, et al. 2018;106(5):e243-e245. Case report PubMed · Publisher

Abstract

Primary pericardial mesothelioma represents less than 1% of all malignant mesotheliomas. These tumors are very rare, difficult to diagnose, and have a poor response to established treatments. Common clinical presentations include constrictive symptoms, cardiac tamponade, and cardiac failure. Surgical resection can be curative in early stages and for localized tumors, and pericardiectomy and chemotherapy are often used as palliative approaches. We present the case of a 54-year-old woman who has so far survived 4 years after a primary resection of a pericardial mesothelioma and was referred with myocardial and aortopulmonary window recurrences for further treatment.

Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Utility of Site-Specific Biopsy for Diagnosis of Desmoplastic Malignant Mesothelioma. T. Sakai, K. Tane, Y. Usui, et al. 2018;106(3):e125-e128. Case report PubMed · Publisher

Abstract

Desmoplastic malignant mesothelioma (DMM) is a relatively rare histologic subtype of malignant pleural mesothelioma (MPM). Among MPMs, the diagnosis of DMM is particularly difficult because the tumor is largely composed of dense hyalinized fibrous stroma and few malignant cells. We present two cases of DMM, one in a 47-year-old man and the other in a 64-year-old man. From detailed pathologic findings in these two cases, we conclude that cases of DMM that cannot otherwise be diagnosed with the use of conventional pleural biopsy, may be diagnosed successfully with the use of wedge lung resection.

Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Amount of Epithelioid Differentiation Is a Predictor of Survival in Malignant Pleural Mesothelioma. W.T. Vigneswaran, D.Y. Kircheva, V. Ananthanarayanan, et al. 2017;103(3):962-966. PubMed · Publisher

Abstract

Background: Macroscopic complete surgical resection with adjuvant chemotherapy can provide a survival advantage in patients with malignant pleural mesothelioma (MPM). Patients with nonepithelioid histology are largely excluded from such radical operations even though they might benefit. The degree of epithelioid differentiation varies in biphasic histology. We report the outcomes of pleurectomy and decortication and the effect of epithelioid differentiation on overall survival of patients with MPM.

Methods: This report is based on the outcomes of 144 patients who underwent pleurectomy and decortication at a single institution between 2008 and 2015. The variables assessed were age, gender, histology, and pathologic T and N stage. No patients with pure sarcomatoid histology were included. Two independent pathologists estimated the percentage of epithelioid histology. A Cox regression model was used to identify significant predictors of survival. The Kaplan-Meier method was used to summarize overall and subgroup survival.

Results: Included were 116 men and 28 women with a median age of 69 years (range, 43 to 88 years). The 2-year survival from pleurectomy and decortication was 20%. Median survival overall was 13.34 months and was 20.1 months for the 100% epithelioid subgroup (n = 77), 11.8 months for the 51% to 99% epithelioid subgroup (n = 39), and 6.62 months for the less than 50% epithelioid subgroup (n = 28). The amount of epithelioid differentiation was a significant predictor of survival (p < 0.001). Differences in survival based on the T, but N stage, were not statistically significant.

Conclusions: The percentage of epithelioid differentiation is an independent predictor of survival in MPM and should be taken into careful consideration when recommending surgical treatment for patients with biphasic MPM.

Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Diode-Pumped Laser for Lung-Sparing Surgical Treatment of Malignant Pleural Mesothelioma. S. Bölükbas, C. Biancosino, B. Redwan, et al. 2017;103(6):e529-e530. Case report PubMed · Publisher

Abstract

Surgical resection represents one of the essential cornerstones in multimodal treatment of malignant pleural mesothelioma. In cases of tumor infiltration of the lung, lung-scarifying procedures such as lobectomies or pneumonectomies might be necessary to achieve macroscopic complete resection. However, this increases the morbidity of the patients because it leads to possible delay of the planned chemotherapy or radiotherapy. Innovative surgical techniques are therefore required to enable salvage of the lung parenchyma and optimization of surgical treatment. Here we report our first experience with a diode-pumped neodymium-doped yttrium aluminium garnet laser for parenchyma-sparing lung resection during surgery for malignant pleural mesothelioma.

Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Extended Pleurectomy-Decortication-Based Treatment for Advanced Stage Epithelial Mesothelioma Yielding a Median Survival of Nearly Three Years. J.S. Friedberg, C.B. Simone, M.J. Culligan, et al. 2017;103(3):912-919. PubMed · Publisher · Free full text

Abstract

Background: The purpose of this study was to assess survival for patients with malignant pleural mesothelioma (MPM), epithelial subtype, utilizing extended pleurectomy-decortication combined with intraoperative photodynamic therapy (PDT) and adjuvant pemetrexed-based chemotherapy.

Methods: From 2005 to 2013, 90 patients underwent lung-sparing surgery and PDT for MPM. All patients had a preoperative diagnosis of epithelial subtype, of which 17 proved to be of mixed histology. The remaining 73 patients with pure epithelial subtype were analyzed. All patients received lung-sparing surgery and PDT; 92% also received chemotherapy. The median follow-up was 5.3 years for living patients.

Results: Macroscopic complete resection was achieved in all 73 patients. Thirty-day mortality was 3% and 90-day mortality was 4%. For all 73 patients (89% American Joint Commission on Cancer stage III/IV, 69% N2 disease, median tumor volume 550 mL), the median overall and disease-free survivals were 3 years and 1.2 years, respectively. For the 19 patients without lymph node metastases (74% stage III/IV, median tumor volume 325 mL), the median overall and disease-free survivals were 7.3 years and 2.3 years, respectively.

Conclusions: This is a mature dataset for MPM that demonstrates the ability to safely execute a complex treatment plan that included a surgical technique that consistently permitted achieving a macroscopic complete resection while preserving the lung. The role for lung-sparing surgery is unclear but this series demonstrates that it is an option, even for advanced cases. The overall survival of 7.3 years for the node negative subset of patients, still of advanced stage, is encouraging. Of particular interest is the overall survival being approximately triple the disease-free survival, perhaps PDT related. The impact of PDT is unclear, but it is hoped that it will be established by an ongoing randomized trial.

Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
New Keywords in the Treatment of Malignant Pleural Mesothelioma. P. Bertoglio, M. Lucchi, A. Mussi. 2017;104(4):1434. Letter · Comment PubMed · Publisher
Polytetrafluoroethylene or Acellular Dermal Matrix for Diaphragmatic Reconstruction?. J.K. Bassuner, D.C. Rice, M.B. Antonoff, et al. 2017;103(6):1710-1714. PubMed · Publisher

Abstract

Background: We aimed to evaluate the impact of collagen matrix in the reconstruction of the diaphragm.

Methods: We queried the electronic medical record for patients who had resection of the diaphragm and simultaneous pulmonary resection between 1999 and 2016. All reconstructions were performed with either polytetrafluoroethylene or acellular dermal matrix. We evaluated the rate of empyema and herniation in each group.

Results: A total of 208 patients met inclusion criteria. Polytetrafluoroethylene was used in 168 cases (80.8%) and dermal matrix in 40 cases (19.2%). Dermal matrix was used in 8 extrapleural pneumonectomies (5.4%), in 26 pleurectomy decortications (55.3%), and in 6 other types of resections (40%). Follow-ups were for a median of 15.0 months in the polytetrafluoroethylene group and 11.6 months in the dermal matrix group. Patients in the dermal matrix group had a chest tube for a median of 2.5 days longer than patients with polytetrafluoroethylene (p = 0.006). Empyema occurred in 11 polytetrafluoroethylene reconstructions (6.5%) and 3 dermal matrix reconstructions (7.5%) (p = 0.735). Seven patients (63.6%) with polytetrafluoroethylene infection required removal of the graft, whereas none in the dermal matrix group needed removal (p = 0.351). There were nine herniations in the polytetrafluoroethylene group and four in the dermal matrix group (p = 0.281), all were acute and due to anchorage failure.

Conclusions: Although infection rates were similar between polytetrafluoroethylene and acellular dermal matrix, re-operation for removal was not necessary in the latter. The use of a thick acellular dermal matrix may be a reasonable option when diaphragmatic reconstruction is potentially associated with a higher risk of infection.

Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Soluble Mesothelin-Related Peptides to Monitor Recurrence After Resection of Pleural Mesothelioma. B.M. Burt, H.S. Lee, V. Lenge De Rosen, et al. 2017;104(5):1679-1687. PubMed · Publisher

Abstract

Background: Most patients undergoing surgical resection of malignant pleural mesothelioma (MPM) will experience recurrence, and radiographic diagnosis of recurrence can be difficult in the postoperative chest. Our objective was to determine the utility of the serum biomarker soluble mesothelin-related peptide (SMRP; or mesothelin) in monitoring of the postoperative MPM patient.

Methods: We retrospectively evaluated a prospectively maintained single institution clinical database. SMRP levels were evaluated preoperatively and postoperatively in patients undergoing surgical resection of MPM.

Results: One hundred two patients underwent pleurectomy/decortication (58%), extrapleural pneumonectomy (20%), chest wall resection (2%), or exploratory thoracotomy (20%) for MPM of 81% epithelial histology. Sixty percent received heated intraoperative chemotherapy and 57% received perioperative systemic chemotherapy. Patients with epithelial histology had substantially greater mean (± SD) preoperative SMRP levels (4.5 ± 7.3 nmol/L) than did patients with biphasic (1.9 ± 2.5 nmol/L) or sarcomatoid (1.2 ± 1.0 nmol/L) histology. Radiologic 3-dimensional tumor volume and tumor mesothelin gene (MSLN) expression correlated with preoperative SMRP. In patients with epithelial histology undergoing complete resection (n = 66), preoperative SMRP (3.4 ± 4.9 nmol/L) dramatically decreased immediately after operation (0.8 ± 0.5 nmol/L), and preoperative SMRP was independently associated with poor disease-free survival. Percentage of change in serial postoperative SMRP values at the best statistical cutoff at 48% revealed high predictive capability of disease recurrence with 90% sensitivity and 93% specificity (area under the curve = 0.96, p < 0.001).

Conclusions: SMRP is a promising serum biomarker for the detection of recurrence after resection of epithelial MPM that may have value in clinical practice and should be studied in a prospective cohort.

Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
A Multicenter Study of Volumetric Computed Tomography for Staging Malignant Pleural Mesothelioma. V.W. Rusch, R. Gill, A. Mitchell, et al. 2016;102(4):1059-66. PubMed · Publisher · Free full text

Abstract

Background: Standard imaging modalities are inaccurate in staging malignant pleural mesothelioma (MPM). Single-institution studies suggest that volumetric computed tomography (CT) is more accurate but labor intensive. We established a multicenter network to test interobserver variability, accuracy (relative to pathologic stage), and the prognostic significance of semiautomated volumetric CT.

Methods: Six institutions electronically submitted to an established multicenter database clinical and pathologic data for patients with MPM who had operations. Institutional radiologists reviewed preoperative CT scans for quality and then submitted by electronic network (AG Mednet, www.agmednet.com) to the biostatistical center. Two reference radiologists blinded to clinical data performed semiautomated tumor volume calculations using Vitrea Enterprise 6.0 software (Vital Images, Minnetonka, MN) and then submitted readings to the biostatistical center. Study end points included feasibility of the network, interobserver variability for volumetric CT, correlation of tumor volume to pTN stages, and overall survival (OS).

Results: Of 164 patients, the CT scans for 129 were analyzable and read by reference radiologists. Most tumors were less than 500 cm(3). A small bias was observed between readers because one provided consistently larger measurements than the other (mean difference, 47.9; p = .0027), but for 80%, the absolute difference was 200 cm(3) or less. Spearman correlation between readers was 0.822. Volume correlated with pTN stages and OS, best defined by three groups with average volumes of 91.2, 245.3, and 511.3 cm(3) associated with median OS of 37, 18, and 8 months, respectively.

Conclusions: For the first time, a multicenter network was established and initial correlations of tumor volume with pTN stages and OS are shown. A larger multicenter international study is planned to confirm the results and refine correlations.

Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Resected Lung Cancer Patients Who Would and Would Not Have Met Screening Criteria. F. Farjah, D.E. Wood, M.E. Zadworny, et al. 2016;101(1):274-9. PubMed · Publisher · Free full text

Abstract

Background: Current eligibility criteria for lung cancer screening may underestimate the risk of malignancy for some individuals. We compared the predicted risk of lung cancer among patients who would have met screening criteria to those who would not have despite being at moderate-risk.

Methods: A retrospective cohort study of resected lung cancer patients was performed. The screen eligible group was based on criteria provided by the United States Preventive Services Task Force; age 55 to 80 and a 30 or greater pack-year smoking history. The screen ineligible group was based on criteria provided by the National Comprehensive Cancer Network for a moderate-risk individual not recommended screening; age greater than 50 years, greater than 20 pack-year smoking history, and no history of asbestos exposure or chronic obstructive pulmonary disease. A recently validated risk-prediction model was used to compare the risk of lung cancer across eligibility groups based on measured and imputed patient-level variables.

Results: Screen ineligible patients (n = 88) had a lower estimated probability of lung cancer than screen eligible patients (n = 419); 1.3% versus 3.1%, p value less than 0.001. However, 20% of screen ineligible patients had a predicted probability of lung cancer greater than or equal to the prevalence of lung cancer (3.7%) among National Lung Screening Trial participants; 17% of screen ineligible patients had a predicted probability of lung cancer greater than or equal to the American Association for Thoracic Surgery threshold (5%) defining high-risk individuals.

Conclusions: Current eligibility criteria for lung cancer screening underestimate the risk of lung cancer for some individuals who might benefit from lung cancer screening.

Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
50th Anniversary Perspective on Volume 1: Urschel HC, Paulson DL. Mesotheliomas of the Pleura. Ann Thorac Surg 1965;1:559-73. V.W. Rusch. 2015;100(4):1148-50. Editorial · Historical article PubMed · Publisher
Disseminated Pleural Siliconoma Mimicking Malignant Pleural Mesothelioma. T. Tanaka, H. Tao, T. Hayashi, et al. 2015;100(6):2339-40. Case report PubMed · Publisher

Abstract

A 48-year-old woman with a 3-month history of back pain was admitted for further examination of multiple left pleural nodules. She had undergone bilateral breast augmentation with silicone implants 10 years previously. Nine years after the operation, both ruptured implants were removed, and autologous fat was injected. Computed tomography revealed multiple pleural nodules suggestive of malignant pleural mesothelioma. Thoracoscopic exploration revealed multiple pleural nodules with massive pleural adhesions. The nodules were filled with viscous liquid and were histologically determined to be siliconomas. Disseminated pleural siliconoma should be recognized as a late adverse event of silicone breast implantation.

Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Effects of extended pleurectomy and decortication on quality of life and pulmonary function in patients with malignant pleural mesothelioma. D. Burkholder, D. Hadi, R. Kunnavakkam, et al. 2015;99(5):1775-80. PubMed · Publisher

Abstract

Background: Maximal cytoreductive surgeries--extrapleural pneumonectomy and extended pleurectomy and decortication (EPD)--are effective surgical treatments in selected patients with malignant pleural mesothelioma. Extended pleurectomy and decortication results in equivalent survival yet better health-related quality of life (HRQoL).

Methods: Patients with malignant pleural mesothelioma were studied for the effects of EPD on HRQoL and pulmonary function. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionaire-C30 was used to evaluate HRQoL before operation, and at 4 to 5 and 7 to 8 months postoperatively. Pulmonary function tests were measured immediately before and 5 to 7 months after the operation. Patients were compared according to World Health Organization baseline performance status (PS).

Results: Of the 36 patients enrolled, 17 were PS 0 and 19 were PS 1 or PS 2 at baseline. Patients in groups PS 1 and PS 2 had significantly worse global health, functional, and symptoms scores. After EPD, PS 0 patients had no change in global health or function and symptoms scores except for emotional function, whereas PS 1 or PS 2 patients showed improvements at 4 to 5 months with further improvements at 7 to 8 months. The PS 0 patients demonstrated a significant decrease in forced vital capacity (p = 0.001), forced expiratory volume in 1 second (p = 0.002), total lung capacity (p = 0.0006) and diffusing capacity of the lung for carbon monoxide (p = 0.003) after EPD, whereas no change was observed in PS 1 and PS 2 patients.

Conclusions: Extended pleurectomy and decortication did not improve overall HRQoL and had a negative impact in pulmonary function in minimally symptomatic patients. In symptomatic patients, a significant improvement in HRQoL was observed after EPD, which continued at late follow-up, although the pulmonary function was not affected. As changes in HRQoL are multidimensional, the preservation of the pulmonary function may have contributed to the net benefit observed in PS 1 and PS 2 patients.

Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Extended Pleurectomy and Decortication for Malignant Pleural Mesothelioma Is an Effective and Safe Cytoreductive Surgery in the Elderly. T. Williams, H. Duraid, S. Watson, et al. 2015;100(5):1868-74. PubMed · Publisher

Abstract

Background: A survival advantage has been observed among patients with malignant pleural mesothelioma undergoing maximal cytoreductive surgery and adjuvant therapy. Elderly patients are considered higher risk for these radical operations and are commonly not offered surgical treatment. We reviewed our experience with extended pleurectomy and decortication among patients 70 years or older and compared them with a cohort of younger patients undergoing extended pleurectomy and decortication for malignant pleural mesothelioma.

Methods: We performed a retrospective review of 117 consecutive patients undergoing extended pleurectomy and decortication at a university hospital from January 2008 to December 2013. Patients 70 years and older were compared with younger patients for postoperative outcome and survival. Survival was estimated using the Kaplan-Meier method.

Results: Fifty-four patients were 70 years or older; 63 were younger than 70 years. Older patients had more hypertension (71.2% versus 45.2%; p = 0.004) and coronary artery disease (22.6% versus 6.5%; p = 0.006). Major complications occurred in 3 patients (5.5%) in the older group and in 7 patients (11.1%) of the younger group (not significant). There were 2 deaths in each group after surgery (3.7% older versus 3.2% younger; not significant). Median survival was 15.6 months in the older patients and 14.0 months in the younger patients (not significant). Kaplan-Meier survival curves based on age groups were not significantly different with 1- and 2-year survivals of 64% versus 55% and 29% versus 32%, respectively.

Conclusions: Our study demonstrates that whereas age may be associated with more comorbid conditions in patients with malignant pleural mesothelioma undergoing extended pleurectomy and decortication, this does not necessarily translate into increased operative morbidity or mortality or shorter long-term survival.

Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Extrapleural Pneumonectomy and Pleurectomy Decortication: Can We Really Compare Their Survival?. P. Bertoglio, S. Korasidis. 2015;100(4):1508-9. Letter · Comment PubMed · Publisher
Intrapleural Photodynamic Therapy for Mesothelioma: What Place and Which Future?. C. Munck, S.R. Mordon, A. Scherpereel, et al. 2015;99(6):2237-45. Review PubMed · Publisher

Abstract

In the surgical multimodal management of malignant pleural mesothelioma, it seems crucial to proceed with an efficient local adjuvant treatment to kill residual tumor cells. Intrapleural photodynamic therapy has recently emerged as a potential candidate in this goal. In this review, we analyzed and classified 16 articles in which patients with malignant pleural mesothelioma received intrapleural photodynamic therapy after maximal surgical resection. The toxicity, effect on survival, and development of the technique were assessed. After two decades of clinical studies, intrapleural photodynamic therapy after surgical resection became a safe treatment that significantly improved the survival of patients.

Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Invited commentary. V.W. Rusch. 2015;99(5):1780. Comment PubMed · Publisher
Invited commentary. L. Lang-Lazdunski. 2015;99(2):481. Comment PubMed · Publisher
Invited Commentary. B.M. Burt. 2015;100(5):1874. Comment PubMed · Publisher
Meta-Analysis of Different Procedures: The Importance of Recognizing the Spectrum of Pleurectomy/Decortication Techniques. C. Cao, D.H. Tian, H. Wolfenden, et al. 2015;100(3):1133. Letter · Comment PubMed · Publisher
Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma. E. Taioli, A.S. Wolf, R.M. Flores. 2015;99(2):472-80. Meta-analysis PubMed · Publisher

Abstract

Background: This comprehensive meta-analysis was conducted to answer the question as to which procedure, pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP) is more beneficial to malignant pleural mesothelioma patients' outcome.

Methods: Original research studies that evaluated long-term outcomes of P/D versus EPP were identified, from January 1990 to January 2014. The combined percent perioperative and 2-year mortality, and median survival were calculated according to both a fixed and a random effect model. The Q statistics and I(2) statistic were used to test for heterogeneity between the studies.

Results: There were 24 distinct data sets, for a total of 1,512 patients treated with P/D, and 1,391 treated with EPP. There was a significantly higher proportion of short-term deaths in the EPP group versus the P/D group (percent mortality meta estimate; 4.5% vs 1.7%; p < 0.05). There was no statistically significant difference in 2-year mortality between the 2 groups, but there was significant heterogeneity.

Conclusions: The reanalysis of the large number of studies comparing P/D to EPP suggests that P/D is associated with a 2 ½-fold lower short-term mortality (perioperatively and within 30 days) than EPP. Pleurectomy decortication should therefore be preferred when technically feasible.

Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Persistent lung expansion after pleural talc poudrage in non-surgically resected malignant pleural mesothelioma. O. Rena, R. Boldorini, E. Papalia, et al. 2015;99(4):1177-83. PubMed · Publisher

Abstract

Background: To investigate the prognostic effect of persistent lung expansion after pleural talcage and other variables in non-surgically resected malignant pleural mesothelioma (MPM) patients.

Methods: All consecutive patients submitted to video-assisted thoracoscopic (VAT) pleurodesis by talc poudrage for MPM between 2006 and 2011 were studied. The following parameters were prospectively recorded: age; sex; smoking history; asbestos exposure; C-reactive protein (CRP) levels; platelet (PLT) count; Eastern Cooperative Oncology Group performance status (ECOG PS); histologic subtype; clinical stage (cStage); chemotherapy; pleural fluid volume; and persistence of lung expansion at 3 months follow-up. Survival was assessed in June 2013.

Results: A total of 172 patients were considered; 146 of 172 patients demonstrated a complete lung expansion at discharge, whereas only 85 of 172 patients had persistent expanded lung on the affected side at the 3-month follow-up chest x-ray. Median survival was 11.5 months (95% confidence interval [CI], 10% to 14%) and 2-year disease-specific survival was 13% (95% CI, 7% to 24%) for the entire cohort. Multivariate analysis showed that non-epithelioid histology (hazard ratio [HR], 2.81; 95% CI, 1.82% to 5.09%), pleural fluid recurrence (HR 2.54; 95% CI, 1.73% to 4.40%), cStage greater than II (HR 2.36; 95% CI, 1.50% to 4.32%), ECOG PS greater than 1 (HR 2.19; 95% CI, 1.26% to 4.23%), CRP greater than 5 mg/L (HR 2.01; 95% CI, 1.18% to 4.12%), and PLT count greater than 400,000 (HR 1.76; 95% CI 1.14% to 3.92%) were independent predictors of poor prognosis.

Conclusions: Persistent lung expansion after pleural talc poudrage and absence of fluid recurrence is demonstrated to be a stronger factor in predicting survival rather than clinical stage and other clinical variables in not surgically resected MPM patients.

Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis. G. Leuzzi, F. Rea, L. Spaggiari, et al. 2015;100(3):890-7. PubMed · Publisher

Abstract

Background: Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few patients undergoing extrapleural pneumonectomy experience long-term survival (LTS). This study aims to explore predictors of LTS after extrapleural pneumonectomy and to define a prognostic score.

Methods: From January 2000 to December 2010, we retrospectively reviewed clinicopathologic and oncological factors in a multicenter cohort of 468 malignant pleural mesothelioma patients undergoing extrapleural pneumonectomy. LTS was defined as survival longer than 3 years. Associations were evaluated using χ(2), Student's t, and Mann-Whitney U tests. Logistic regression, Cox regression hazard model, and bootstrap analysis were applied to identify outcome predictors. Survival curves were calculated by the Kaplan-Meier method. Receiver operating characteristic analyses were used to estimate optimal cutoff and area under the curve for accuracy of the model.

Results: Overall, 107 patients (22.9%) survived at least 3 years. Median overall, cancer-specific, and disease-free survival times were 60 (95% confidence interval [CI], 51 to 69), 63 (95% CI, 54 to 72), and 49 months (95% CI, 39 to 58), respectively. At multivariate analysis, age (odds ratio, 0.51; 95% CI, 0.31 to 0.82), epithelioid histology (odds ratio, 7.07; 95% CI, 1.56 to 31.93), no history of asbestos exposure (odds ratio, 3.13; 95% CI, 1.13 to 8.66), and the ratio between metastatic and resected lymph nodes less than 22% (odds ratio, 4.12; 95% CI, 1.68 to 10.12) were independent predictors of LTS. According to these factors, we created a scoring system for LTS that allowed us to correctly predict overall, cancer-specific, and disease-free survival in the total sample, obtaining two different groups with favorable or poor prognosis (area under the curve, 0.74; standard error, 0.04; p < 0.0001).

Conclusions: Our prognostic model facilitates the prediction of LTS after surgery for malignant pleural mesothelioma and can help to stratify the outcome and, eventually, tailor postoperative treatment.

Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Reply: To PMID 24726598. L. Spaggiari, G. Marulli, G.L. Pariscenti, et al. 2015;100(2):770-1. Letter · Comment PubMed · Publisher
Reply: To PMID 25534527. R.M. Flores, E. Taioli, A.S. Wolf. 2015;100(3):1133-4. Letter · Comment PubMed · Publisher
Reply: To PMID 25534527. E. Taioli, A.S. Wolf, R.M. Flores. 2015;100(4):1509. Letter · Comment PubMed · Publisher
Surgical Strategy for Malignant Pleural Mesothelioma: Where Are We Going and What Are We Missing?. F. Lococo, M. Paci, T. Ricchetti, et al. 2015;100(2):769-70. Letter · Comment PubMed · Publisher
Extrapleural pneumonectomy after induction chemotherapy: perioperative outcome in 251 mesothelioma patients from three high-volume institutions. O. Lauk, M.A. Hoda, M. de Perrot, et al. 2014;98(5):1748-54. Randomized trial PubMed · Publisher

Abstract

Background: Several publications have suggested that induction chemotherapy followed by extrapleural pneumonectomy (EPP) for patients with malignant pleural mesothelioma (MPM) patients is associated with exceedingly high morbidity and mortality, and the role of EPP is controversially debated. The present retrospective study analyzed the perioperative outcome in 251 consecutively treated patients at three high-volume mesothelioma centers.

Methods: 251 MPM patients completed EPP after platinum-based induction chemotherapy at three institutions for thoracic surgery over more than 10 years. The rates of 30-day and 90-day mortality and of major morbidities (pulmonary embolism, postoperative bleeding, acute respiratory distress syndrome, empyema, bronchopleural fistula (BPF), chylothorax, patch failure) were recorded. Perioperative outcome was correlated to risk factors such as smoking history (pack years), age at operation, body mass index, spirometry results, C-reactive protein, American Society of Anesthesiologists classification, chemotherapy regimen used, blood loss during operation, duration of operation, and characteristics of the tumor (laterality, histologic subtype, pT and pN stage) to find factors predicting 30-day and 90-day mortality or major morbidity.

Results: The overall 30-day mortality was 5%. Within 90 days after operation, 8% of the patients died. The rates of 30-day and 90-day mortality were significantly higher in patients with high preoperative C-reactive protein values (p=0.001 and p<0.0005). The spirometry values forced expiratory volume in 1 second and forced vital capacity exhaled (FVCex) were both associated with 30-day and 90-day mortality (p=0.001 and p<0.0005; and p=0.002 and p<0.0005). Major morbidity occurred in 30% of the patients, significantly more often after right-sided EPP (p=0.01) and after longer operations (p<0.0005). Empyema (p<0.0005) and acute respiratory distress syndrome (p=0.02) were associated with longer duration of operation.

Conclusions: EPP after induction chemotherapy is a demanding procedure but can be performed with acceptable morbidity and mortality if patients are well selected and treated at dedicated high-volume MPM centers.

Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Extrapleural pneumonectomy for malignant mesothelioma: an Italian multicenter retrospective study. L. Spaggiari, G. Marulli, P. Bovolato, et al. 2014;97(6):1859-65. PubMed · Publisher

Abstract

Background: This study assessed perioperative outcome and long-term survival in a large series of patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP) to identify prognostic factors allowing better patient selection.

Methods: We retrospectively collected data from nine referral centers for thoracic surgery in Italy. Perioperative outcome and survival data were available for 518 malignant pleural mesothelioma patients (84.4% with epithelial tumors, 68.0% with pathologic stage 3 disease) who underwent EPP with intention-to-treat (R0/R1) between 2000 and 2010. Induction chemotherapy was administered in 271 patients (52.3%) and adjuvant therapy in 373 patients (72.0%), including radiotherapy in 213 patients (41.1%), adjuvant chemotherapy in 43 patients (8.3%), and both in 117 patients (22.6%).

Results: In all, 136 patients (26.3%) had major complications after EPP, and 36 (6.9%) died within 90 days after surgery. The median overall survival was 18 months, with a 1-, 2-, and 3-year overall survival of 65%, 41%, and 27%, respectively. At multivariable analysis adjusted for age and disease stage, male sex (hazard ratio [HR] 1.47, 95% confidence interval [CI]: 1.12 to 1.92), nonepithelial histology (HR 1.96, 95% CI: 1.48 to 2.58), and trimodality treatment using induction chemotherapy (HR 0.61, 95% CI: 0.43 to 0.85) were significantly associated with survival. Development of a major complication also significantly worsened outcome (HR 1.85, 95% CI: 1.37 to 2.50).

Conclusions: The success of EPP in the context of a multimodality treatment depends on a series of patient characteristics. Female patients, patients with epithelial tumors, and patients who received induction chemotherapy will best benefit from EPP.

Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Invited commentary. B.C. Tong. 2014;98(5):1754. Comment PubMed · Publisher
Invited commentary. S.C. Murthy. 2014;98(3):1024-5. Comment PubMed · Publisher
Invited commentary. R.M. Flores. 2014;97(6):1865-6. Comment PubMed · Publisher
Nonspecific pleuritis: optimal duration of follow-up. Z.S. DePew, A. Verma, D. Wigle, et al. 2014;97(6):1867-71. PubMed · Publisher

Abstract

Background: Nonspecific pleuritis (NSP) is a frequent diagnosis after parietal pleural biopsy, but the clinical significance of this finding and need for further follow-up have not been firmly established. Previous reports suggest that 5% to 25% of patients with NSP are subsequently diagnosed with pleural malignancy.

Methods: Our pathology database was queried for patients with histologic evidence of NSP from January 01, 2001, to December 31, 2012 (n = 413). Patients with less than 1 year of follow-up after biopsy, diagnosis of empyema, tuberculous pleuritis, active systemic connective tissue disease or vasculitis, or active malignancy were excluded (n = 327). The remaining patients were included and their medical records were reviewed.

Results: Eighty-six patients were included. Mean follow up was 1,824 ± 1,032 days (range, 409 to 4,599 days). Three of the 86 patients with NSP (3.5%) were subsequently diagnosed with pleural malignancy. All 3 patients were found to have mesothelioma with a mean time from biopsies to diagnosis of 205 ± 126 days (range, 64 to 306 days). Twenty-two of 86 patients (25.5%) had a possible identifiable cause of pleural inflammation (benign disease). After exclusion of these 22 patients, the incidence of malignancy was 3 of 64 (4.7%).

Conclusions: The incidence of subsequent pleural malignancy (mesothelioma) among patients found to have NSP based on pleural biopsy was 3.5%. Occult mesothelioma in patients with NSP will most likely be diagnosed within 1 year of the initial pleural biopsy; therefore, these patients should be followed for a minimum of 1 year to allow for timely detection of occult pleural malignancy.

Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Thirty-day mortality underestimates the risk of early death after major resections for thoracic malignancies. R.R. McMillan, A. Berger, C.S. Sima, et al. 2014;98(5):1769-74; discussion 1774-5. PubMed · Publisher · Free full text

Abstract

Background: Operative mortality rates are of great interest to surgeons, patients, policy makers, and payers as a metric for quality assessment. Thirty-day mortality and discharge mortality have been presumed to capture procedure-related deaths. However, many patients die after the 30-day mark or are transferred to other facilities or to home and die there, leading to the underreporting of surgically related deaths. We hypothesized that a longer period of observation would address these concerns and provide a more accurate measure of operative mortality.

Methods: We retrospectively reviewed institutional databases of patients undergoing resection for lung cancer, esophageal cancer, and mesothelioma. Mortality rates at 30 and 90 days were calculated with 95% confidence intervals (CIs).

Results: From 1999 to 2012, 7,646 surgical resections were performed: 6,119 for lung cancer, 1,258 for esophageal cancer, and 269 for mesothelioma. Among the different cancers and across operations, the additional mortality from day 31 to 90 (1.4%; 95% CI, 1.2% to 1.8%; n=111) was similar to that by day 30 (1.2%; 95% CI, 1.0% to 1.5%; n=95), resulting in overall 90-day mortality (2.7%; 95% CI, 2.3% to 3.1%; n=206) that was more than double the 30-day mortality.

Conclusions: Among patients who have undergone operations for thoracic malignancies, mortality attributable to the operation occurs beyond the first 30 postsurgical days as well as after hospital discharge. Because cancer operations constitute a large portion of general thoracic surgery, we recommend national databases consider the inclusion of 90-day mortality in their data collection.

Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Women with malignant pleural mesothelioma have a threefold better survival rate than men. E. Taioli, A.S. Wolf, M. Camacho-Rivera, et al. 2014;98(3):1020-4. PubMed · Publisher

Abstract

Background: Many studies have reported that women with malignant pleural mesothelioma (MPM) experience longer survival compared with men, whereas others have not. To date, no large population-based studies have evaluated MPM outcome and its determinants in female patients.

Methods: All pathologically confirmed cases of MPM in the Surveillance, Epidemiology and End Results database from 1973 to 2009 were evaluated. Age, year of diagnosis, race, stage, cancer-directed surgery, radiation, and vital status were analyzed according to gender. Cox proportional hazard models were derived to assess the association between prognostic factors and survival.

Results: There were 14,228 cases of MPM, of which 3,196 (22%) were women. Despite similar baseline characteristics for both genders, 5-year survival was 13.4% in women and 4.5% in men (p < 0.0001). The effect of female gender on survival persisted when stratified by age (dichotomized at 50 years), stage, or race, but differed depending on treatment. Even when adjusted for age, stage, race, and treatment, female MPM patients experienced longer survival than men (hazard ratio = 0.78; 95% confidence interval 0.75 to 0.82).

Conclusions: This large data set confirms that although MPM is less common in women, they present with similar stage and are offered similar treatment options compared with men. Nevertheless, survival is far better in women compared with men, independent of confounders such as age, stage, and treatment. Differences in asbestos exposure, tumor biology, and the impact of circulating hormones on host response must be investigated to understand this survival advantage and improve prognosis for patients of both genders.

Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Invited commentary. J.S. Donington. 2013;95(4):1188. Comment PubMed · Publisher
Primary pericardial mesothelioma in a 19-year-old presenting as pericarditis. M.O. Kayatta, S.P. Dineen, G. Sica, et al. 2013;96(2):680-1. Case report PubMed · Publisher

Abstract

Primary pericardial mesothelioma is a rare clinical entity. The association between asbestos and pericardial mesothelioma has not been well established, partly due to the small number of reported patients. Treatment options are limited for this very aggressive cancer. Surgical resection in the form of pericardiectomy can be curative, but owing to the frequently late presentation, surgical intervention is usually palliative. Chemotherapy and radiotherapy have overall poor results. We present the case of a 19-year-old man who initially had symptoms of pericarditis. He died 1 year after initial presentation.

Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Snail expression is associated with a poor prognosis in malignant pleural mesotheliomas. M. Kobayashi, C.L. Huang, M. Sonobe, et al. 2013;95(4):1181-8. PubMed · Publisher

Abstract

Background: Malignant pleural mesotheliomas (MPMs) are aggressive tumors with a poor prognosis. We aimed to clarify the mechanisms of epithelial-to-mesenchymal transition (EMT) in MPMs by analyzing the expressions of EMT-associated transcription factors and E-cadherin in relation to tumor proliferation rates and patient survival.

Methods: One hundred nine patients with MPMs were investigated. Among these patients, there were 61 epithelioid tumors, 21 sarcomatoid tumors, 20 biphasic tumors, and 7 desmoplastic tumors. Immunohistochemical analyses were performed to evaluate the expressions of Snail, ZEB1, Twist, E-cadherin, and the Ki-67 proliferation index.

Results: The expressions of Snail and ZEB1 were significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p<0.0001 and p=0.0051, respectively). Furthermore, the E-cadherin expression was significantly lower in the Snail-high tumors than in the Snail-low tumors (p=0.0423). The E-cadherin expression was significantly lower in the nonepithelioid tumors than in the epithelioid tumors (p=0.0126). The Ki-67 proliferation index was significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p=0.025). Patient survival was significantly lower in patients with Snail-high MPMs than in those with Snail-low MPMs (p=0.0016), especially in patients with nonepithelioid tumors (p=0.0089). The multivariate analysis also demonstrated that nuclear Snail expression was a significant predictor of poor prognosis in patients with MPMs (p=0.0142).

Conclusions: The Snail expression is associated with EMT and a poor prognosis in MPMs. Snail could be a potential molecular target for the treatment of patients with MPMs.

Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Use of the posterior pericardium to cover the bronchial stump after right extrapleural pneumonectomy. M. de Perrot. 2013;96(2):706-8. PubMed · Publisher

Abstract

Limited tissue is available to cover the bronchial stump after right extrapleural pneumonectomy for malignant pleural mesothelioma. After completing the resection, the pericardial reflection can be freed from the superior vena cava, the right pulmonary artery and veins, and the posterior wall of the pericardial sac between the transverse and oblique pericardial sinuses. The length and mobility from the posterior pericardium can then provide excellent coverage for the right bronchial stump. This technique has the advantage of being easy to perform and requiring limited time and dissection.

Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Extrapleural pneumonectomy for primary pleural mullerian tumor in a young woman. A.S. Farivar, B.E. Louie, R.W. Aye, et al. 2012;93(1):e1-2. Case report PubMed · Publisher

Abstract

We present a case of a low-grade mullerian tumor of right pleural origin in a 23-year-old woman treated with an aggressive multimodal treatment paradigm. This tumor is heretofore undescribed in the medical literature. She received induction therapy of carboplatin and paclitaxel with minimal response, then had a maximally cytoreductive right extrapleural pneumonectomy. She subsequently underwent intensity-modulated radiotherapy to the right hemithorax. We propose a treatment paradigm for this previously undescribed primary pleural mullerian tumor.

Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Initial experience with the use of biological implants for soft tissue and chest wall reconstruction in thoracic surgery. A. Barua, J.A. Catton, L. Socci, et al. 2012;94(5):1701-5. PubMed · Publisher

Abstract

Background: Synthetic materials have traditionally been used for tissue reconstruction in thoracic surgery. New biomaterials have been tested in other areas of surgery with good results. The aim of our study is to evaluate our initial experience using prostheses in extended thoracic surgery.

Methods: A review was performed of all patients who underwent extended surgical procedures requiring soft tissue reconstruction with bioprosthetic materials after thoracic surgery from August 2009 to August 2011. A total of 44 consecutive patients were included. Operations involved radical pleurectomy and decortication for mesothelioma (n = 29), extended operations for thoracic malignancies (n = 8), surgery for trauma or perforated organs or complications (n = 6), and for benign infectious causes (n = 1).

Results: A total of 76 patches were used in 44 patients (median of 2; range 1 to 3 per patient). Median hospital stay was 13 (range 5 to 149) days. Three patients died during the postoperative period (6.8%); pulmonary embolism 5 days after intrapericardial pneumonectomy with chest wall reconstruction, fatal pneumonia 26 days after radical pleurectomy and decortication for mesothelioma, and bronchopleural fistula 11 days after pneumonectomy with diaphragm and atrium excision for lung cancer after initial chemoradiotherapy. No other surgical exploration or removal of patches has been required for infection.

Conclusions: Our initial experience of using bioprosthetic patches for soft tissue reconstruction in thoracic surgery has proven satisfactory with overall acceptable results. The infection rates are low even when a proportion of procedures were performed under contaminated environments. Biologic prosthesis should be part of the surgical options to reconstruct soft tissues in thoracic surgery.

Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Invited commentary. H.I. Pass. 2012;94(4):1092-3. Comment PubMed · Publisher
Laparoscopic repair of gastric herniation after extrapleural pneumonectomy for mesothelioma. M. Egan, B.E. Louie, A.S. Farivar, et al. 2012;93(5):e127-9. Case report PubMed · Publisher

Abstract

Acute herniation of intra-abdominal organs into the chest after extrapleural pneumonectomy is an uncommon but morbid and potentially mortal complication. We report a case of acute diaphragmatic hernia after extrapleural pneumonectomy for mesothelioma repaired laparoscopically. This approach is an alternative to repeated thoracotomy and is a viable option for treatment of this difficult problem with potentially less morbidity.

Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Laparoscopic thoracic duct clipping for persistent chylothorax after extrapleural pneumonectomy. N. Tsubokawa, Y. Hamai, J. Hihara, et al. 2012;93(5):e131-2. Case report PubMed · Publisher

Abstract

We describe a 68-year-old man who was treated by laparoscopic thoracic duct clipping for persistent chylothorax after an extrapleural pneumonectomy for malignant pleural mesothelioma. Initial conservative treatment did not resolve the postoperative chylothorax. A second surgery through the thoracic approach was considered invasive and difficult after extrapleural pneumonectomy. A laparoscopic approach proved effective and resolved the chylothorax. Thus, laparoscopic thoracic duct clipping is considered very useful for treating chylothorax.

Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Quality of life after radical pleurectomy decortication for malignant pleural mesothelioma. N.M. Mollberg, Y. Vigneswaran, H.L. Kindler, et al. 2012;94(4):1086-92. PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma is an aggressive malignancy in which radical surgical treatment appears to improve survival. It is unknown, however, if radical surgical treatment affects quality of life (QoL) adversely. Our objective was to assess patient-reported symptoms of health-related QoL after radical pleurectomy decortication (PD).

Methods: Patients with malignant pleural mesothelioma were prospectively enrolled between 2010 and 2011 to determine the effects of PD on baseline QoL. Health-related QoL was assessed using the European Organization for Research and Treatment of Cancer core Quality of Life Questionnaire-C30 tool (EORTC QLQ-C30) before operation and at 1, 5 to 6, and 8 to 9 months postoperatively. Patients were grouped based on World Health Organization baseline performance status (PS) and compared.

Results: Of the 28 patients enrolled, 16 (57.1%) and 12 (42.9%) were World Health Organization PS 0 and PS 1, respectively. At baseline, PS 1 patients had significantly worse global QoL functional and symptom scores at baseline. At 5 to 6 months' follow-up, PS 0 patients had no significant change in global QoL or functional domain scores. PS 1 patients had significant improvement in global QoL (p=0.038), symptoms of fatigue (p=0.05), and dyspnea (p=0.048). At 8 to 9 months' follow-up, PS 0 patients showed significant improvement in symptoms of fatigue (p=0.026) from baseline and PS 1 maintained the improvements in symptoms of fatigue (p=0.049) and dyspnea (p=0.048).

Conclusions: Radical PD does not negatively impact minimally symptomatic patients at intermediate follow-up. Patients who have symptoms at baseline can have significant improvement in their QoL after surgical treatment.

Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Radical pleurectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma. J.S. Friedberg, M.J. Culligan, R. Mick, et al. 2012;93(5):1658-65; discussion 1665-7. PubMed · Publisher · Free full text

Abstract

Background: Radical pleurectomy (RP) for mesothelioma is often considered either technically unfeasible or an operation limited to patients who would not tolerate a pneumonectomy. The purpose of this study was to review our experience using RP and intraoperative photodynamic therapy (PDT) for mesothelioma.

Methods: Thirty-eight patients (42-81 years) underwent RP-PDT. Thirty five of 38 (92%) patients also received systemic therapy. Standard statistical techniques were used for analysis.

Results: Thirty seven of 38 (97%) patients had stage III/IV cancer (according to the American Joint Committee on Cancer [AJCC manual 7th Edition, 2010]) and 7/38 (18%) patients had nonepithelial subtypes. Macroscopic complete resection was achieved in 37/38 (97%) patients. There was 1 postoperative mortality (stroke). At a median follow-up of 34.4 months, the median survival was 31.7 months for all 38 patients, 41.2 months for the 31/38 (82%) patients with epithelial subtypes, and 6.8 months for the 7/38 (18%) patients with nonepithelial subtypes. Median progression-free survival (PFS) was 9.6, 15.1, and 4.8 months, respectively. The median survival and PFS for the 20/31 (64%) patients with N2 epithelial disease were 31.7 and 15.1 months, respectively.

Conclusions: It was possible to achieve a macroscopic complete resection using lung-sparing surgery in 97% of these patients with stage III/IV disease. The survival we observed with this approach was unusually long for the patients with the epithelial subtype but, interestingly, the PFS was not. The reason for this prolonged survival despite recurrence is not clear but is potentially related to preservation of the lung or some PDT-induced effect, or both. We conclude that the results of this lung-sparing approach are safe, encouraging, and warrant further investigation.

Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Invited commentary. C.P. Clarke. 2011;91(6):1745-6. Comment PubMed · Publisher
Metastasis of pleural mesothelioma presenting as bleeding colonic polyp. S. Sibio, P. Sammartino, F. Accarpio, et al. 2011;92(5):1898-901. Case report PubMed · Publisher

Abstract

We report the case of a 72-year-old woman with metastatic malignant mesothelioma presenting as right colonic polyp. She was diagnosed with malignant pleural mesothelioma 2 years previously and underwent surgery, radiotherapy, and chemotherapy. After 2 years with a negative follow-up, she was admitted to the infectious disease department for malaria and severe anaemia. A computed tomographic scan and a colonoscopy showed a huge bleeding polypoid lesion in the right colon diagnosed as adenocarcinoma. She underwent a right hemicolectomy; a pathologic examination found neoplastic cell population positive to anti-cytokeratin7, anti-calretinin, anti-vimentin, and negative for anti-cytokeratin 20, MOC-31, and thyroid transcription factor 1, providing a diagnosis of metastatic mesothelioma.

Copyright Â© 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Paclitaxel-loaded expansile nanoparticles in a multimodal treatment model of malignant mesothelioma. M.D. Schulz, K.A. Zubris, J.E. Wade, et al. 2011;92(6):2007-13; discussion 2013-4. PubMed · Publisher

Abstract

Background: Malignant mesothelioma has a poor prognosis even when treated aggressively with multimodal therapy. Traditional murine tumor models can be used to evaluate drug efficacy and toxicity in malignant mesothelioma, but not to assess the effect of a multimodal approach that includes the surgical resection of tumor. We therefore developed a murine model of multimodal therapy in which we evaluated paclitaxel-loaded expansile nanoparticles (Pax-eNP) for delivering intracavitary chemotherapy in malignant mesothelioma.

Methods: Paclitaxel-loaded expansile nanoparticles (Pax-eNP) of 100 nm, designed to release drug at an endosomal pH below 5, were synthesized. Xenografts of human malignant mesothelioma were established intraperitoneally in nude mice, followed by cytoreductive surgery (CRS) via laparotomy, and with omentectomy and resection of abdominal fat pads done 14 days later. At fascial closure, 10 mg/kg paclitaxel was delivered as traditional paclitaxel/paclitaxel Cremophor-EL (Pax-CE) or Pax-eNP. Morbidity and survival were assessed over a period of 90 days.

Results: Cytoreductive surgery in mice was feasible and reproducible, and incurred less than 5% operative mortality. By itself, CRS did not significantly prolong survival; however, the addition of intraoperative Pax-CE or Pax-eNP significantly increased survival as compared with that of mice with untreated disease. In the case of Pax-eNP, the increase in survival was also statistically significant as compared with that following resection alone.

Conclusions: A murine model of CRS for malignant mesothelioma allows the in vivo assessment of multimodal therapy, including nanoparticle delivery. Combination therapy was superior to no treatment or CRS alone in prolonging survival. Treatment with Pax-eNP improved overall survival in the setting of CRS, suggesting that Pax-eNP merits further evaluation for intracavitary drug delivery following the surgical resection of malignant mesothelioma.

Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Photodynamic therapy and the evolution of a lung-sparing surgical treatment for mesothelioma. J.S. Friedberg, R. Mick, M. Culligan, et al. 2011;91(6):1738-45. PubMed · Publisher

Abstract

Background: Photodynamic therapy (PDT) is a light-based cancer treatment that acts to a depth of several millimeters into tissue. This study reviewed the results of patients who underwent a macroscopic complete resection, by two different surgical techniques, and intraoperative PDT as a treatment for malignant pleural mesothelioma.

Methods: From 2004 to 2008, 28 patients with malignant pleural mesothelioma underwent macroscopic complete resection, 14 by modified extrapleural pneumonectomy (MEPP) and 14 by radical pleurectomy (RP) and intraoperative PDT. The surgical technique evolved over this period such that 13 of the last 16 patients underwent lung-sparing procedures, even in the setting of large-bulk tumors.

Results: Demographics in the MEPP and RP cohorts were similar in age, sex, stage, nodal status, histology, and adjuvant treatments. Stage III/IV disease was present in 12 of 14 patients (86%), with 50% or more with +N2 disease. The median overall survival for the MEPP group was 8.4 months, but has not yet been reached for the RP group at a median follow-up of 2.1 years.

Conclusions: In addition to the inherent advantages of sparing the lung, RP plus PDT yielded a superior overall survival than MEPP plus PDT in this series. The overall survival for the RP plus PDT group was, for unclear reasons, superior to results reported in many surgical series, especially for a cohort with such advanced disease. Given these results, we believe RP plus PDT is a reasonable option for appropriate patients pursuing a surgical treatment for malignant pleural mesothelioma and that this procedure can serve as the backbone of surgically based multimodal treatments.

Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Thoracoscopic extrapleural pneumonectomy for mesothelioma. T.L. Demmy, I.E. Platis, C. Nwogu, et al. 2011;91(2):616-8. Case report PubMed · Publisher

Abstract

Mesothelioma is the most common primary pleural malignancy. Surgical therapy offers limited cure benefits at the cost of high morbidity. Although technically challenging and performed rarely, a less invasive approach to extrapleural pneumonectomy was developed with the intent to speed convalescence, hasten adjuvant therapies, improve quality of life, and reduce wound surface area for possible tumor contamination.

Copyright Â© 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
A rare cause of dysphagia: malignant pleural mesothelioma in the posterior mediastinum. M. Hayama, H. Maeda. 2010;90(4):1358-61. Case report PubMed · Publisher

Abstract

A 69-year-old man presented to the emergency room with dysphagia and vomiting. A computed tomographic scan revealed a posterior mediastinal mass surrounding the lower portion of the esophagus. Endoscopic examination demonstrated narrowing of the lower esophagus without malignant mucosal lesions. Thoracoscopic biopsies of the mediastinal mass failed to yield a pathologic diagnosis. The hyaluronic acid concentration in the left pleural effusion was remarkably high (755 mg/L), which is a finding strongly suggestive of malignant mesothelioma. Four months after the initial admission, a subcutaneous nodule was found in the left chest wall and a biopsy was taken. The histopathologic and immunohistochemical findings of the biopsy were consistent with the diagnosis of pleural malignant mesothelioma.

Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Characteristics of malignant pleural mesothelioma in women. A.S. Wolf, W.G. Richards, T.R. Tilleman, et al. 2010;90(3):949-56; discussion 956. PubMed · Publisher

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Invited commentary. D. Rice. 2010;89(1):210-1. Comment PubMed · Publisher
Second surgery for recurrence of malignant pleural mesothelioma after extrapleural pneumonectomy. L. Politi, G. Borzellino. 2010;89(1):207-10. PubMed · Publisher

Abstract

Background: Extrapleural pneumonectomy is a treatment option for malignant pleural mesothelioma (MPM), but disease recurrence is common. Among different therapeutic options for recurrence, we have found no reports for second surgical procedures.

Methods: We retrospectively evaluated the types and outcomes of surgical management of solid recurrences of MPM, in a series of 74 patients treated with extrapleural pneumonectomy over a 20-year period.

Results: Of 57 patients for whom follow-up data were available, 11 patients experienced recurrent disease in the form of a solid mass, 1.5 to 12 years after the initial treatment; 8 of these patients had sufficiently good clinical conditions to undergo a second surgery with curative intent. Chest wall resection was performed in 4 cases of parietal recurrence, radical retroperitoneal resection was done in 3 cases of retroperitoneal relapse, and segmental resection of the remaining lung was done in one case of pulmonary metastasis. In this latter case, although computed tomographic images showed a solid mass, at surgery the disease was found to have a serosal nature, precluding the possibility of a curative surgery. Median survival after the second surgery was 14.5 months (range, 6 to 29); no association between survival and site of recurrence, age or disease-free interval was found.

Conclusions: In this series, the second surgery did not offer the expected survival benefit of curative treatment strategies and should therefore be considered palliative. Second surgery may be a treatment option in a subset of patients who experience a solid recurrence of MPM that is symptomatic or near vital organs and who cannot undergo additional radiotherapy.

2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Therapeutic surgery for nonepithelioid malignant pleural mesothelioma: is it really worthwhile?. B. Balduyck, D. Trousse, A. Nakas, et al. 2010;89(3):907-11. PubMed · Publisher

Abstract

Background: Debate remains about the relative prognostic importance of the histologic subtype of malignant pleural mesothelioma.

Methods: From a prospective database, the details of 312 malignant pleural mesothelioma surgical patients were reviewed. A comparison was made of the survival from the three major cell types.

Results: One hundred ninety-five patients underwent radical surgery, and 117 underwent nonradical surgery. Final histologic subtype was epithelioid in 218 patients, biphasic in 66 patients, and sarcomatoid in 28 patients. The median survival was 15.3 months in the epithelioid group, 10.1 months in the biphasic group, and 5.0 months in the sarcomatoid group. On univariate analysis in the epithelioid group, age (p = 0.005), International Mesothelioma Interest Group stage (p = 0.001), radicality of the procedure (p = 0.001), leukocytosis (p = 0.016), and preoperative or postoperative chemotherapy (p = 0.012) were significant prognostic factors influencing postoperative survival. In the biphasic group, preoperative anemia was the only significant factor (p = 0.007). In sarcomatoid patients, International Mesothelioma Interest Group stage and radicality of the surgical procedure were significant prognostic variables (p = 0.012 and p = 0.015, respectively). Multivariate analysis in the epithelioid group identified International Mesothelioma Interest Group stage (p = 0.001), radicality of the procedure (p = 0.008), and preoperative or postoperative chemotherapy (p = 0.007) as significant prognostic factors, whereas in the sarcomatoid group, only the International Mesothelioma Interest Group stage (p = 0.012) was significant and the radicality of surgery had no effect.

Conclusions: The extremely poor prognosis of sarcomatoid malignant pleural mesothelioma is independent of the extent of surgery unlike other cell types. Patients with sarcomatoid histology should therefore be considered separately in trials evaluating radical procedures and adjuvant treatment. The treatment of biphasic pleural mesothelioma remains debatable.

2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

2000s

Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions. H.I. Pass, A. Wali, N. Tang, et al. 2008;85(1):265-72; discussion 272. PubMed · Publisher

Abstract

Background: Soluble mesothelin-related peptide (SMRP) is a potential marker for malignant pleural mesothelioma (MPM), which may be useful for screening high-risk asbestos-exposed individuals.

Methods: We evaluated SMRP in serum from MPM patients (n = 90), lung cancer patients (n = 170), age and tobacco-matched asbestos-exposed individuals (n = 66), and in MPM pleural effusions (n = 45), benign effusions (n = 30), and non-MPM effusions (n = 20) using the MesoMark enzyme-linked immunosorbent assay kit (Fujirebio Diagnostics, Malvern, PA). Receiver operating characteristic (ROC) curves were used to define true and false positive rates at various cutoffs.

Results: Mean serum SMRP levels were higher in MPM compared with lung cancer (5.67 +/- 0.82 nM [mean +/- standard error of the mean vs 1.99 +/- 0.43 nM, p < 0.001), and stage I MPM SMRP levels (n = 12; 2.09 +/- 0.41 nM) were significantly higher than those in asbestos-exposed individuals (0.99 +/- 0.09 nM, p = 0.02, respectively). Stage 2 to 4 SMRP serum levels were significantly higher than those for stage 1 MPM. The area under the ROC curve for serum SMRP was 0.81 for differentiating MPM and asbestos-exposed individuals; cutoff = 1.9 nM (sensitivity = 60%, specificity = 89%). The MPM pleural effusion SMRP was significantly higher than benign or other non-MPM pleural effusions (65.57 +/- 11.33 nM vs 27.46 +/- 11.25 nM [p = 0.003] and 18.99 +/- 7.48 nM [p = 0.044], respectively).

Conclusions: These data support SMRP as a promising marker for MPM in both serum and pleural effusion fluid, and justify prospective screening studies of SMRP in combination with other markers for screening of asbestos-exposed cohorts.
Flow cytometric analysis of a localized malignant mesothelioma. J.J. Gómez-Román, R. Mons-Lera, I.S. Olmedo, et al. 2002;73(4):1292-4. Case report PubMed · Publisher

Abstract

Malignant mesothelioma usually presents as a diffuse neoplasm. We report a localized malignant mesothelioma in the parietal pleura of a patient who was not exposed to asbestos. A complete clinical, pathologic, and immunohistochemical description is provided. Flow cytometric analysis showed an aneuploid DNA content in neoplastic cells. The patient is alive and well 8 months after complete surgical resection. Localized malignant mesothelioma must be included in the differential diagnosis in chest wall-based neoplasms.
Malignant mesothelioma with osseous differentiation. H.C. Suen, B. Sudholt, W.M. Anderson, et al. 2002;73(2):665. Case report PubMed · Publisher

Summary

This one-page 'Images in Cardiothoracic Surgery' report described a single patient with malignant mesothelioma showing osseous (bone-forming) differentiation, from the Departments of Cardiothoracic Surgery, Medicine, and Radiology at Memorial Hospital, Belleville, Illinois. The patient was an 80-year-old man with a history of prolonged asbestos exposure who presented with left-sided chest pain. A chest film showed a left pleural effusion with pleural calcification that had not been present on a film taken after coronary artery bypass surgery 2 years earlier. Computed tomography confirmed a large effusion surrounded by thickened, calcified pleura. Serum alkaline phosphatase was markedly elevated. A technetium bone scan showed marked uptake of isotope in the left pleura, with no evidence of distant bony metastasis. Attempts at left thoracentesis and thoracoscopy failed because neither the needle nor the trocar could penetrate the calcified pleura. Rib resection and open pleural biopsy revealed malignant mesothelioma with osseous differentiation. The patient died 4 months later. The authors stated that only 15 cases of malignant mesothelioma with osseous differentiation had been described in the literature, and that bone scan pictures of this condition had never been presented before.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Efficacy of repeated adenoviral suicide gene therapy in a localized murine tumor model. E.S. Lambright, S.D. Force, M.E. Lanuti, et al. 2000;70(6):1865-70; discussion 1870-1. PubMed · Publisher

Abstract

Background: Gene therapy using adenovirus to deliver herpes simplex virus thymidine kinase (Ad.HSVtk) followed by the administration of the prodrug ganciclovir has been an effective anticancer therapy in models of localized tumor (including malignant mesothelioma) and is currently being evaluated in clinical trials. To optimize this approach, we studied the effects of repeated injections of Ad.HSVtk in an animal model of localized tumor in both naive and immunized mice.

Methods: Immunocompetent animals with established abdominal tumor were treated with either one or three (given weekly) intraperitoneal injections of Ad.HSVtk (10(9) plaque-forming units) followed by daily ganciclovir and monitored for survival. Survival studies were also performed in mice previously immunized with adenovirus.

Results: Animals treated with multiple courses of Ad.HSVtk showed significantly improved survival versus singly injected animals and control animals with some long-term survivors in the multiple injected group. Preexisting neutralizing immunity did not diminish this survival advantage.

Conclusions: Multiple treatments using an adenoviral vector to deliver HSVtk significantly improves survival in a murine intraperitoneal tumor model. The presence of preexisting neutralizing antibodies does not blunt this effect. Repeat Ad.HSVtk is a feasible approach and may be a useful strategy in human cancer gene therapy.
Gene-modified PA1-STK cells home to tumor sites in patients with malignant pleural mesothelioma. L.H. Harrison, P.O. Schwarzenberger, P.S. Byrne, et al. 2000;70(2):407-11. PubMed · Publisher

Abstract

Background: Malignant mesothelioma is an uncommon but lethal cancer of increasing incidence, particularly among patients with a history of exposure to asbestos. Although numerous treatments have been employed, including chemotherapy, radiation therapy, surgical resection, and combinations of the above, no satisfactory treatment yet exists, and affected patients will die of this disease, usually within 12 months. Gene-based therapies constitute a new approach that offers hope of improved control of these tumors while being associated with less morbidity than conventional chemotherapeutic or surgical regimens. We demonstrated that PA1-STK cells home in vivo to mesothelioma deposits, a phenomenon that is required for optimal exertion of this therapeutic concept.

Methods: Gene-modified ovarian cancer cells expressing the thymidine-kinase gene (PA1-STK) were radiolabeled with 99Tc and infused into the pleural space of 4 patients with malignant pleural mesothelioma, then scanned to determine distribution of the cells.

Results: PA1-STK cells recognized and adhered preferentially to mesothelioma lining the chest wall.

Conclusions: Cell-based "suicide gene" therapy utilizing the "bystander effect" with the gene-modified ovarian cancer cell line PA1-STK is feasible in human pleural mesothelioma. We have shown that this trafficking and homing of the therapeutic cells to the intrapleural tumor sites, a requirement for success with this novel therapeutic concept, is also valid in humans.

1990s

Important prognostic factors in patients with malignant pleural mesothelioma, managed surgically. V.W. Rusch, E.S. Venkatraman. 1999;68(5):1799-804. PubMed · Publisher

Abstract

Background: The factors influencing outcome after resection of malignant pleural mesothelioma (MPM) are controversial. This analysis of a prospective surgical database identifies important prognostic factors.

Methods: Tumors were staged by the International Mesothelioma Interest Group staging system, and patients were followed until death. Prognostic factors were analyzed by log rank and Cox regression, and were considered significant if p was less than 0.05.

Results: From Oct 1983 to May 1998, 231 patients underwent thoracotomy, 115 had extrapleural pneumonectomy (EPP), and 59 pleurectomy/decortication (P/D). Among patients having EPP or P/D, 142 received adjuvant therapy. The median survival for stage I tumors was 29.9 months, for stage II 19 months, for stage III 10.4 months, and for stage IV 8 months. By multivariate analysis, stage, histology, gender, adjuvant therapy, but not the type of surgical resection, were significant.

Conclusions: The better survival previously reported for P/D compared with EPP is not seen in a large database with long follow-up. Stages I and II have better survival rates than generally assumed for MPM. Locally advanced T and N status, and nonepithelial histology, identify poor prognosis patients who should be considered for novel treatment regimens.
Surgery for invasive primary mediastinal tumors. E.A. Bacha, A.R. Chapelier, P. Macchiarini, et al. 1998;66(1):234-9. PubMed · Publisher

Abstract

Background: There have been few reports on results after extended radical resection for primary mediastinal tumors invading neighboring organs.

Methods: A retrospective analysis of 89 patients who underwent total or subtotal resection of a primary mediastinal tumor with resection of at least part of an adjacent structure between 1979 and 1995 was performed. Clinical data were collected from the medical records.

Results: There were 35 invasive thymomas, 12 thymic carcinomas, 17 germ cell tumors, 16 lymphomas, 3 neurogenic tumors, 3 thyroid carcinomas, 2 radiation-induced sarcomas, and 1 mediastinal mesothelioma. The tumor was located in the anterior mediastinum in 74% of patients. Residual masses after chemotherapy were excised in 14 patients with germ cell tumor and 8 with lymphoma. A median sternotomy was the most frequently used approach (79% of patients). Total resection was achieved in 79% and significantly improved survival (p < 0.01). Adjacent resected structures included 38 phrenic nerves, 21 superior venae cavae, 16 upper lobes, and 13 innominate veins, in 5 patients, a pneumonectomy was required. The complication rate was 17% and the mortality rate, 6%. With follow-up available for 86 patients, the overall 5-year survival rate was 69% for patients with thymoma, 42% for patients with thymic carcinoma, 48% for patients with germ cell tumor, and 83% for patients with lymphoma.

Conclusions: Malignant mediastinal tumors can be safely resected even if they have invaded other mediastinal structures. Complete resection is important to achieve satisfactory long-term survival. A median sternotomy is an excellent approach, and a preoperative diagnosis by biopsy is desirable. Residual masses after chemotherapy for lymphoma or germ cell tumor should be resected. Extensive resection without a preoperative diagnosis is not indicated.
A dedicated prosthesis for open thoracostomy. L.T. Filomeno, J.M. de Campos, A.W. de Almeida, et al. 1997;63(5):1494-6. PubMed · Publisher

Abstract

Due to our dissatisfaction with the mutilation caused by the skin-lined open thoracostomy, we have developed a dedicated prosthesis that is expected to avoid or to substitute for the classic operation. The prosthesis is a corrugated silicone tube with an oval flange at one end (to fix it internally) and a mobile ring on the other (to fix it externally). It is inserted at the bottom of the empyematic cavity after 3 cm of a rib is removed. We have used it in 20 patients whose empyema was secondary to pneumonia (12) or complications of pneumonectomy (4), lobectomy (2), decortication (1), or pleuroscopy (1). Six of those patients have already been cured and their prosthesis removed after 54 to 305 days. In 1 with a persistent postpneumonectomy bronchopleural fistula the device was removed after 299 days and the patient was submitted to a limited thoracoplasty. Six other patients still have unresolved cavities and have been using the prosthesis for 63 to 302 days. Seven patients died of their underlying disease (bilateral pneumonia, 2; acquired immunodeficiency syndrome, 2; mesothelioma, 1; heart failure and pulmonary embolism, 1; unknown, 1) after using the prosthesis for 11 to 160 days. In those patients from whom the prosthesis already has been removed, the scar looks like those commonly seen after removal of an ordinary chest tube. Based on these early favorable results we feel most encouraged to persist in this research. Nevertheless, we are aware that a larger number of patients and a longer follow-up will be necessary before we may make definitive recommendations.
Gene transfer and thoracic surgery: more to come. L.R. Kaiser, S.M. Albelda. 1997;63(6):1527-8. Comment · Editorial PubMed · Publisher

Summary

This editorial commented on two experimental studies in the same issue of The Annals of Thoracic Surgery that applied gene transfer to problems in lung transplantation. Takeda and associates used HVJ-liposome-mediated transfer of an endothelin-1 gene to create an animal model of obliterative bronchiolitis. Boasquevisque and colleagues used an adenoviral vector to transfer a marker gene to lung isografts during cold preservation. The authors noted that both studies reported very low gene transfer efficiency, and they stated that gene delivery and efficiency remained the biggest obstacles to clinical use. They described the endothelin-1 model as a reproducible advance for studying obliterative bronchiolitis, but cautioned that it did not directly implicate endothelin-1 in human disease. For the transplant model, they discussed the possible effects of low temperature and of multiplicity of infection; gene expression had been poorer at 4°C than at 10°C. They suggested measuring messenger RNA, and they cited a pig study that found low (under 1%) expression and spread of vector to other organs. Drawing on their own work, they described moving adenovirus-mediated gene transfer for malignant mesothelioma from an animal model to a clinical trial, which took 3.5 years. In 15 patients, adenovirus given into the pleural space was feasible and safe and showed evidence of gene transfer. They concluded that progress from laboratory to patient was necessarily slow.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Malignant mesothelioma. D.B. Campbell. 1997;63(5):1503-5. PubMed · Publisher
Patterns of failure after trimodality therapy for malignant pleural mesothelioma. E.H. Baldini, A. Recht, G.M. Strauss, et al. 1997;63(2):334-8. PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma is uncommon, and presently, no standard treatment of this disease exists. The objective of our analysis was to study the patterns of failure for malignant pleural mesothelioma after trimodality treatment consisting of extrapleural pneumonectomy, chemotherapy, and radiation therapy.

Methods: Between 1987 and 1993, 49 patients with malignant pleural mesothelioma underwent extrapleural pneumonectomy. There were two perioperative deaths, and 1 patient died 5 weeks after extrapleural pneumonectomy. Thirty-five of the surviving patients received adjuvant chemotherapy (32/35 received cyclophosphamide, doxorubicin, and cisplatin) followed by hemithorax radiation therapy. Ten patients received chemotherapy but no radiation therapy, and 1 patient received no adjuvant therapy. Median follow-up time for the 23 living patients from the date of operation was 18 months.

Results: Of the 46 evaluable patients, 25 had recurrence (54%), with a median time to first failure of 19 months (range, 5 to 51 months). The sites of first recurrence were local in 35% of patients, abdominal in 26%, the contralateral thorax in 17%, and other distant sites in 8%. (Some patients had recurrence in multiple sites simultaneously.)

Conclusions: The most common site of failure after trimodality therapy was the ipsilateral hemithorax. Isolated distant failures were uncommon. Future strategies should investigate methods of enhancing local tumor control.
Extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. D.J. Sugarbaker, S.J. Mentzer, G. Strauss. 1992;54(5):941-6. PubMed · Publisher

Abstract

A technique for extrapleural pneumonectomy in diffuse, malignant, pleural mesothelioma is described. The technique used in a protocol at Brigham and Women's Hospital has resulted in improved operative mortality figures and length of hospital stay. The right-sided procedure is presented followed by differences in technique required by the left-sided approach.
Intraoperative photodynamic therapy for malignant mesothelioma. H.I. Pass, Z. Tochner, T. DeLaney, et al. 1990;50(4):687-8. Case report · Comment · Letter PubMed · Publisher

Summary

In this letter, responding to a published report of a giant benign mesothelioma, authors at the National Cancer Institute (Bethesda, Maryland) described intraoperative photodynamic therapy, an approach under investigation at their institution for diffuse pleural malignant mesothelioma. It combined preoperative delivery of a photosensitizer (dihematoporphyrin ether), surgical debulking of tumor to 5 mm thickness by pleurectomy or extrapleural pneumonectomy, and intraoperative delivery of 630-nm laser light. They reported one patient, a 58-year-old man with right-sided diffuse pleural mesothelioma, who underwent extrapleural pneumonectomy 2 days after receiving 2.0 mg/kg of the sensitizer. Light doses were 15 J/cm2 to the chest cavity and 11 J/cm2 to the heart. Operative time was 8 hours, including 37 minutes of laser time. The patient was extubated the next morning. Serum creatinine rose from 90 to 140 µmol/L and returned to normal with hydration within 48 hours. Creatine kinase rose from 44 to 11,030 U/L at 72 hours and was 369 U/L at discharge on the ninth postoperative day. The tumor was a mixed epithelial-fibrous mesothelioma. At follow-up 2 and 4 months after the procedure he needed no oxygen, his wounds had healed and he had returned to work. The authors reported that a phase I trial to determine the maximum tolerated dose was under way and stated that it was too early to comment on efficacy.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

1980s

Giant benign mesothelioma. D.M. Watts, G.P. Jones, G.A. Bowman, et al. 1989;48(4):590-1. Case report PubMed · Publisher

Abstract

Pleural mesothelioma is a rare neoplasm that is usually highly malignant, but benign mesotheliomas do occur; approximately 400 cases are described in the literature. We report the case of a young woman with a massive benign mesothelioma that filled the entire left hemithorax but was successfully resected with full reexpansion of the lung.
Chest wall stabilization using plate fixation. J.E. Sherman, A. Salzberg, N.M. Raskin, et al. 1988;46(4):467-9. Case report PubMed · Publisher

Abstract

Large defects of the chest wall require stabilization of the remaining thorax to prevent paradoxical movement. A technique of fixation using rib grafts and compression plates is presented.
Pleural mesothelioma. N. Martini, P.M. McCormack, M.S. Bains, et al. 1987;43(1):113-20. Review PubMed · Publisher

Abstract

Pleural mesotheliomas are uncommon tumors. Correct diagnosis of the benign variant is rarely made preoperatively, and resection is the treatment of choice and is curative. Malignant pleural mesotheliomas are locally aggressive and difficult to treat. They may be seen clinically as localized pleural tumors or as diffuse pleural disease with effusion and encasement of the lung and obliteration of the pleural space. The localized forms of malignant mesotheliomas are fibrosarcomatous. Their diagnosis and treatment do not differ from those for soft-part sarcomas seen elsewhere. Wide en-bloc excision is the treatment of choice and can be curative. The diffuse forms of malignant mesotheliomas are mainly epithelial. Treatment is generally unsatisfactory, and long-term survival is rare. Two surgical approaches are currently available: an extrapleural pneumonectomy and a pleurectomy with irradiation. The authors favor the latter approach because of its wider applicability, lower morbidity rate, and better survival advantage. Steps in selecting the best surgical mode of treatment are presented.
Extrapleural pneumonectomy for diffuse, malignant mesothelioma. M.J. DaValle, L.P. Faber, C.F. Kittle, et al. 1986;42(6):612-8. PubMed · Publisher

Abstract

Extrapleural pneumonectomy for malignant mesothelioma is a radical procedure that entails en bloc removal of the parietal pleura, lung, pericardium, and diaphragm. Minimal tumor remains after this procedure; palliation and occasional long-term survival may be achieved in properly selected patients. Extrapleural pneumonectomy for diffuse, malignant mesothelioma was done in 33 patients (27 male and 6 female) with 18 procedures on the left side and 15 on the right. There was a history of exposure to asbestos in 16 (48%) of the patients. Histological classification revealed that 20 tumors were epithelial, 10 were mixed, and 3 were sarcomatous. Good palliation, defined as survival for 24 months with a return to fairly normal activities, was obtained in 8 patients (24%) and survival for 36 months was achieved in 5 patients. Three patients died of the disease at 59 months, 60 months, and 82 months. There were 3 operative deaths (9.1%), and serious postoperative complications occurred in 8 patients (24%). Postoperative adjunctive therapy consisting of chemotherapy or irradiation or both was given to approximately one-half of the patients. These findings indicate that extrapleural pneumonectomy for malignant mesothelioma can be done with an acceptable morbidity and mortality. Palliation is achieved in 24% of patients, and there may be an occasional long-term survivor.
The modern use of thoracoplasty. R.A. Hopkins, R.M. Ungerleider, E.W. Staub, et al. 1985;40(2):181-7. PubMed · Publisher

Abstract

Thoracoplasty is a time-honored but, at present, rarely indicated procedure for reducing thoracic cavity volume. This study reviews a series of 30 patients treated with thoracoplasty over a 14-year period (1970 through 1983). Indications were to close a persistent pleural space in 28 patients and to tailor the thoracic cavity to accept diminished lung volume concomitant with a pulmonary resection in 2 patients. Persistent pleural space, often associated with a bronchopleural fistula (24 patients), occurred after operation in 19 patients: following pulmonary resection in 17 patients, resection of mesothelioma in 1 patient, and following decortication without resection in 1. In the remaining 9 patients with a persistent pleural space, problems developed from primary lung destruction due to tuberculosis (4 patients), postpneumonic empyema (1 patient), or as late infection of a residual pleural space many years after therapeutic pneumothorax and collapse therapy for tuberculosis (4 patients). The overall success rate of thoracoplasty in eliminating intrathoracic space problems was 73%. There were 3 deaths (10%) and 5 failures to heal, representing a 33% failure in the first half of the series (to 1976) and a 17% failure rate thereafter (1 death and 1 nonhealing patient). The primary underlying disease was tuberculosis in 23 patients, 8 of whom had concomitant aspergilloma and 1, atypical tuberculosis. The failures were analyzed and reviewed to clarify the principles for the successful use of thoracoplasty. It is concluded that thoracoplasty is a rarely required salvage-type procedure applicable to moderately debilitated patients in whom it is considered desirable to eliminate open drainage.(ABSTRACT TRUNCATED AT 250 WORDS)
Thoracic surgical problems in asbestos-related disorders. E.A. Gaensler, T.C. McLoud, C.B. Carrington. 1985;40(1):82-96. PubMed · Publisher

Abstract

Among 1,577 persons with asbestos exposure followed up from 3 to 30 years, 113 had thoracic surgical procedures for asbestos-related disorders. Twenty-six individuals suspected of having asbestosis with atypical features underwent open-lung biopsy; a different disease was revealed in 14. Most of the 29 patients with mesothelioma had a small thoracotomy for diagnosis only; chemotherapy in half of them proved entirely ineffective. Experience with 23 patients with bronchogenic carcinoma did not differ from that in persons not exposed to asbestos. Problems of causal relationship are discussed. Most of the 68 individuals with benign asbestos pleural effusion had no symptoms, but because of recurrence, 15 were operated on for decortication or for possible mesothelioma. Hyaline plaques often were mistaken for lung, rib, or diaphragmatic tumors, and sometimes mesothelioma was suspected. Operative intervention in the 24 patients with plaques could have been avoided by obtaining a more detailed occupational history and reviewing previous chest roentgenograms, which invariably showed identical or smaller plaques from 2 to 17 years earlier.
Diffuse, mixed malignant pleural mesothelioma. R.J. Lewis, G.E. Sisler, J.W. Mackenzie. 1981;31(1):53-60. Case report PubMed · Publisher

Abstract

Forty-six patients with diffuse, mixed malignant pleural mesothelioma were treated between January, 1970, and May, 1979. All had a history of exposure to asbestos. The diagnosis was established by thoracentesis in 3 patients, thoracoscopy in 28, thoracotomy in 5, and minithoracotomy in 9. Mediastinoscopy was performed in 31 patients and bronchoscopy in 32. Mediastinoscopy was positive in only 1 patient, and in no patient was bronchoscopy positive. Ten patients received no definitive therapy and survived an average of 9.1 months (1 lived for 16 months). Thirty-one patients received chemotherapy and survived an average of 9.6 months, the 2 longest survivors each lived for 24 months. Five patients appeared to have early disease and therefore underwent thoracotomy. In only 2 of these patients did resection of all gross disease appear possible. One patient with incomplete removal is still alive after 9 months. The other 4 are all dead, having survived an average of only 6.75 months. We believe that pleural mesothelioma should be considered an unresectable neoplasm because of its multicentric origin and its diffusely invasive nature, and that attempts at partial or complete resection are not indicated. Until prospective, controlled studies demonstrate otherwise, patients with diffuse, mixed malignant mesothelioma should have the most benign surgical procedure necessary to establish a diagnosis.

1970s

Thoracoscopy: a useful tool in the diagnosis of thoracic disease. J.I. Miller, C.R. Hatcher. 1978;26(1):68-72. Case report PubMed · Publisher

Abstract

During a 12-month period, 11 patients underwent diagnostic thoracoscopy for previously undiagnosed thoracic disease. In all patients, the diagnosis had been unobtainable by the usual diagnostic modalities of bronchoscopy, scalene node biopsy, mediastinoscopy, thoracentesis, or closed pleural biopsy. Thoracoscopy was diagnostic in 10 of the 11 patients. There was no morbidity or mortality. In all patients the indication for thoracoscopy was suspected malignancy. The majority of patients had recurrent pleural effusions in which routine cytological studies and tissue biopsies had been nondiagnostic. Pathological findings were mesothelioma in 3 patients, primary carcinoma of the lung in 4, congestive heart failure with pleural effusion in 1, metastatic carcinoma in 2, and inflammatory disease in 1 patient. Indications, techniques, and results are discussed. Thoracoscopy is a valuable tool in the diagnosis of thoracic disease; with it, unneccessary thoracotomy can often be avoided.

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