Eur J Cardiothorac Surg 2008;34:204-207. doi:10.1016/j.ejcts.2008.03.003
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
Outcome after extrapleural pneumonectomy for malignant pleural mesothelioma
Clemens Aigner,
Mir Ali Reza Hoda,
Gyoergy Lang,
Shahrokh Taghavi,
Gabriel Marta,
Walter Klepetko*
Department of Cardio-Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria
Received 17 September 2007;
received in revised form 6 February 2008;
accepted 4 March 2008.
* Corresponding author. Tel.: +43 1 40400 5644; fax: +43 1 40400 5642. (Email: walter.klepetko{at}meduniwien.ac.at).
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Abstract
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Background Malignant pleural mesothelioma is a mainly asbestos-related neoplasm that occurs with increasing frequency and is associated with a poor prognosis. Extrapleural pneumonectomy which was initially performed as a stand-alone treatment in patients with resectable disease is now currently almost uniformly applied as part of a multi-modal approach. Its value and advantage over other therapeutic strategies remain points of discussion. We therefore analysed our experience with extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. Methods We retrospectively reviewed our institutional experience with all consecutive patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma from 1994 to 2005. Patients were analysed with regard to hospital mortality and morbidity and long-term outcome. Results Forty-nine patients (10 female/39 male, mean age 58
+
12 years) underwent extrapleural pneumonectomy during the observation period. Median ICU stay was 1 day, median postoperative length of hospital stay was 13 days. After a mean follow-up of 2573 days, median survival was 376 days (mean 672
+
121 days, range 9–3384). One-year survival was 53%, 3-year survival 27% and 5-year survival 19%. Conclusion Extrapleural pneumonectomy as part of a multi-modality treatment regimen is a good treatment option for selected patients with malignant pleural mesothelioma. The long-term results of this limited series compare favourably to non-surgical treatment regimens. Larger randomised prospective multi-centre trials are warranted to establish clear guidelines.
Key Words: Malignant pleural mesothelioma • Extrapleural pneumonectomy • Pleuropneumonectomy • Multi-modal treatment • MPM • EPP
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1. Introduction
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Malignant pleural mesothelioma is a mainly asbestos-related neoplasm. It occurs with increasing frequency and predominantly affects male patients (
75%) above 50 years. A latency period of 20–40 years is observed between the asbestos exposure and the development of the disease. Poor median survival rates of 4–12 months have been reported. Sarcomatoid histology, poor performance status, extensive disease and N2 lymph node involvement [1,2] are associated with worse prognosis. Extrapleural pneumonectomy, as the only option to radically resect non-localised malignant pleural mesothelioma, was initially performed as a stand-alone treatment in patients with resectable disease, however is currently almost uniformly applied as part of a multi-modality approach. Its value and advantage over other therapeutic strategies remain points of discussion. We therefore analysed our experience with extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma
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2. Patients and methods
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We retrospectively reviewed our institutional experience with all consecutive patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma from 1994 to 2005. Patients were analysed with regard to hospital mortality and morbidity and long-term outcome.
All patients underwent routine preoperative staging including CT, PET-scan and in cases with suspect mediastinal lymph nodes, mediastinoscopy to exclude distant metastases. Functional assessment included blood gas analysis, spirometry and echocardiography. Cytological or histological samples were obtained by puncture, VATS or open biopsy. Reduced lung function with a predicted postoperative FEV1 <1 l was considered a contraindication. In case of a reduced FEV1 a V/Q scan was performed to assess regional distribution of lung function. Preoperative blood gas values showing a PCO2 >45 mmHg or a PO2 <65 mmHg posed a contraindication to resection as well as significantly reduced left or right ventricular ejection fraction.
The surgical technique was standardised with a posterolateral approach. Lung, pleura, pericardium and diaphragm were resected en-bloc. A systematic mediastinal lymph node dissection was routinely performed as part of the procedure. The diaphragm was reconstructed using a Gore-Tex® Dual Mesh patch. The pericardium was reconstructed using either a Vicryl mesh or a Gore-Tex® Dual Mesh patch. The bronchial stump was not routinely covered.
Postoperative follow-up included regular CT scans in 3–6 months intervals and, if clinically indicated, histological or cytological samples were taken.
Statistical analysis was performed using the SPSS 15.0 software package applying the appropriate statistical methods. Actuarial survival rates were calculated using Kaplan–Meier curves.
2.1 Study limitations
The study is limited by its retrospective design. This study analyses the outcome of all patients in whom extrapleural pneumonectomy was performed as part of the treatment strategy. No direct comparison to other treatment modalities is made. Due to the long observation period, treatment protocols have evolved. The administered chemotherapeutics and radiotherapy protocols in our study are not standardised and were at the discretion of the referring department. Therefore a heterogeneous patient collective is analysed in this study.
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3. Results
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Forty-nine patients (10 female/39 male, median age 59 years, range 28–81 years) underwent extrapleural pneumonectomy during the observation period. Twenty-four left-sided and 25 right-sided procedures were performed. Diagnosis was established by puncture in 14 patients. Video-assisted thoracic surgery confirmed the diagnosis in 22 patients and open biopsy was required in 11 patients. In two patients no histological confirmation could be obtained, however due to clear radiological and clinical symptoms surgery was performed and postoperative histology confirmed the diagnosis of mesothelioma. Postoperative histological examination of the resection specimens showed epithelial type mesothelioma in 30 cases, biphasic type in 15 and sarcomatous type in 4 cases. Postoperative pathological tumour staging is shown in Table 1
. Thirteen patients underwent induction chemotherapy. The administered chemotherapeutics are shown in Table 2
. Fourteen patients received adjuvant therapy (Table 2). Radical R0 resection was achieved in 39 patients, in 10 patients no microscopically radical resection margin was obtained. Median ICU stay was 1 day (range 0–19 days), median postoperative length of hospital stay was 13 days (range 2–97 days). Perioperative complications consisted of new onset of atrial fibrillation (n
= 10), transient recurrent laryngeal nerve palsy (n
= 3), haematothorax requiring revision (n
= 2), temporary paraplegia (n
= 2), wound healing problems (n
= 2), contralateral pneumonia (n
= 2), subclavian thrombosis (n
= 1), ARDS (n
= 1) and stroke (n
= 1).
After a mean follow-up of 2573 days median survival was 376 days (mean 672
+
121 days, range 9–3384). Ten patients were still alive at the time of the analysis. Thirty-day survival was 90% (causes of death were sepsis (n
= 2), pulmonary embolism (n
= 2) and cardiac arrest (n
= 1)), 1-year survival was 53%, 3-year survival 27% and 5-year survival 19%. The overall Kaplan–Meier survival curve is shown in Fig. 1
. When analysing survival with regard to the histological subtype a significantly better survival for patients with epithelial type compared to biphasic and sarcomatous type is observed (Fig. 2
, p
= 0.01). N2 positive patients had a significantly worse survival compared to N0 patients (Fig. 3
, p
= 0.01). No significant difference was observed between N1 and N0 as well as between N1 and N2 due to the low number of N1 patients. Survival rates according to stage are shown in Fig. 4
. A statistical significant difference was seen only between stage 2 and 4 (p
= 0.005). Between the other stages no significant differences were observed.
The most striking difference in survival rates was noted in patients who received induction chemotherapy. Those patients achieved a 5-year survival rate of 52% (Fig. 5
, p
< 0.001). There was no statistical significant difference between those patients receiving adjuvant therapy compared to surgery alone. When comparing patients with any form of multi-modality treatment to surgery alone, there was again a highly significant survival benefit (Fig. 6
, p
< 0.001). 67% of all patients and 75% of patients receiving induction therapy, who were alive at 5-year follow-up were free of tumour recurrence.
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4. Discussion
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The incidence of malignant pleural mesothelioma is rising throughout the world due to widespread exposure to asbestos throughout the past decades [3]. However, treatment is still not standardised and randomised trials are lacking. Initially surgical approaches were performed as stand-alone treatments without additional chemo- or radiotherapeutic measurements. However all single modality approaches failed to demonstrate a significant survival benefit. Two surgical concepts were developed and are, with modifications, still in use. Extrapleural pneumonectomy offers the chance to radically resect the entire tumour mass [4]. Yet the benefit of this extensive operation has been questioned due to the associated morbidity and mortality and lack of substantial improvements of survival rates in initial studies. Even though the rate of complications is high, they can usually be successfully managed. Perioperative morbidity has been described to be comparable to standard pneumonectomy [5]. The second approach is less aggressive and consists of a visceral and parietal pleurectomy/decortication (P/D) [6]. This approach can be applied either by videothoracoscopy or open thoracotomy with either a palliative or radical claim.
Correct staging is crucial in deciding on the best treatment strategy. Especially the selection of patients for extrapleural pneumonectomy is crucial given the potential complication of this procedure. Currently the most widely used clinical staging system is the International Mesothelioma Interest Group (IMIG) staging system [7]. Besides routine clinical staging integrated CT-PET scan has been reported to be beneficial in the selection of patients for extrapleural pneumonectomy [8]. The most commonly used surgical tool for staging is mediastinoscopy. Some groups even advocate an aggressive surgical staging with additional laparoscopy including a peritoneal lavage [9].
As supported by our data a significant survival benefit was reported if extrapleural pneumonectomy was performed as part of a multi-modality approach with induction chemotherapy and postoperative radiochemotherapy [10–12]. Another surgical approach is pleurectomy, which is offered to patients with advanced stages of disease as palliative tumour debulking. It also has been offered to patients with early stages of the disease to spare the lung, however if the patient's functional status allows extrapleural pneumonectomy this approach is preferred by many centres due to prolonged survival. A recent study describes no disadvantage in survival in patients with N2 disease who undergo pleurectomy compared to extrapleural pneumonectomy [13]. However N2 disease negatively impacts overall prognosis of patients with malignant pleural mesothelioma [2].
In general, single modality treatment has not been able to substantially increase survival and a multi-modality approach with chemotherapy and radiotherapy alongside surgery is the preferred treatment regimen in patients with respectable disease. This study supports the multi-modality approach in the treatment of malignant pleural mesothelioma. As induction chemotherapy a combination of cisplatin with new antifolate agents, like pemetrexed, seem to warrant favourable outcome [14,15] compared to previously established regimens.
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5. Conclusion
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Extrapleural pneumonectomy as part of a multi-modal treatment regimen is a good treatment option for selected patients with epithelial malignant pleural mesothelioma. The long-term results of this limited series compare favourably to non-surgical treatment regimens. Larger randomised prospective multi-centre trials are warranted to establish clear guidelines.
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Footnotes
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Presented at the 15th European Conference on General Thoracic Surgery, Leuven, Belgium, June 3–6, 2007.
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Abstract
1. Introduction
