Extra-pleural pneumonectomy
Review Article

Extra-pleural pneumonectomy

Leonardo Duranti1, Alessandro Pardolesi1, Luca Bertolaccini2, Luca Tavecchio1, Paolo Scanagatta1, Luigi Rolli1, Ugo Pastorino1

1Thoracic Surgery Unit, National Cancer Institute, Milan, Italy;2Thoracic Surgery, Maggiore Teaching Hospital, Bologna, Italy

Contributions: (I) Conception and design: L Duranti; (II) Administrative support: U Pastorino; (III) Provision of study materials or patients: L Duranti; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: L Bertolaccini, L Duranti, A Pardolesi; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Leonardo Duranti. Division of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milan 20133, Italy. Email: leonardo.duranti@istitutotumori.mi.it.

Abstract: The extra-pleural pneumonectomy (EPP) is a standardised surgical procedure born for pleural tuberculosis and later used in pleural cancer treatment, especially in malignant pleural mesothelioma (MPM). This systematic review aimed to focus on the actual overall EPP role in surgical oncology. The literature search was performed from January 1985 to January 2018 In PubMed, Embase, and Cochrane according to PRISMA protocol. The search was restricted to publications in English with the research words “extrapleural pneumonectomy”, “malignant pleural mesothelioma”, “pleural malignancies”. The results were then filtered focusing only on papers with series of patients treated with EPP, for mesothelioma and non-mesothelioma malignancies. The search was restricted to publications in English. We found a 5-year overall survival (OS) ranging from 0 to 78%. The peri-operative mortality and morbidity ranged from 0 to 11.8% and 0 to 82.6%, respectively. The most represented and described post-operative complications reported were ARDS, pericardial tamponade, cardiac herniation, pulmonary embolism, respiratory infections, respiratory failure, atrial arrhythmia, myocardial infarction. In referral centres and selected patients, EPP is a cytoreductive or radical surgical treatment in extended pleural malignancies. Prospective studies are needed to standardise the timing of the procedure in a multimodality treatment program, according to the oncological and functional indications, to keep an acceptable complications rate and post-operative quality of life status.

Keywords: Extra-pleural pneumonectomy (EPP); malignant pleural mesothelioma (MPM); pleural malignancies

Submitted Nov 21, 2018. Accepted for publication Jan 24, 2019.

doi: 10.21037/jtd.2019.02.61


The extra-pleural pneumonectomy (EPP) is a standardised procedure of en bloc resection of the parietal and visceral pleura with the ipsilateral lung, pericardium, and hemidiaphragm (1).

In 1949, Sarot described the EPP technique for tuberculous infection resistant to collapse therapy or thoracoplasty (2) and in 1976, for the first time, Butchart et al. employed EPP malignant pleural mesothelioma (MPM) patients (3).

For many years, the EPP represented the gold standard surgical choice in MPM patients, but its clinical role has been revised after publication of the mesothelioma and radical surgery (MARS I) trial (4).

For other pleural malignancies, such as thymomas, low-grade sarcomas (5-7) this surgical procedure is accepted in many referral centres in selected cases, while it is more questionable its use in non-small cell lung cancer (NSCLC) with pleural carcinosis (8).

Nowadays, this type of surgery is always a part of a multimodality treatment program, consisting of neoadjuvant chemotherapy, hyperthermic intraoperative chemotherapy (HIOC), adjuvant chemo/radiotherapy (9-11).


The search strategy and the selection

We performed our literature search using In PubMed, OVID, Embase, and Cochrane, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews according to PRISMA protocol, from January 1985 to January 2018 (12). The words for the research were “extra-pleural pneumonectomy”, “malignant pleural mesothelioma”, “pleural malignancies”. We found 89,475 references. Data were extracted using a standard collection form. Two independent reviewers extracted information from each study including author names, year of publication, number of patients, intervention, control, outcomes, and adverse effect. Two independent reviewers and disagreements assessed discussion and consensus settled the risk of bias. By reading the titles and the abstracts, we eliminated duplicated articles, cases reports, comments, letters to the editor and publications about infective and benign pathologies (search result: 1,986 papers). In the end, the references with surgical interest for EPP operation were 68.


From 68 articles, we had a total of 3,220 patients who underwent EPP for MPM (3,117 patients) or other pleural malignancies (103 patients) obtained from our selected studies All the information about type of study, number of patients, 5 years overall survival (OS), morbidity, mortality and adjuvant/neoadjuvant treatments are summarized in Table 1. Since the retrospective study may contain selection bias, we show the results from prospective studies in Table 2.

Table 1
Table 1 Published evidence
Full table
Table 2
Table 2 Published evidence from prospective studies
Full table

The cardio-respiratory pre-operative evaluation is necessary for all EPP patients’ selection: pulmonary function test, diffusion capacity, pulmonary scan, complete cardiological study with a stress test for inducible myocardial ischemia, echocardiogram with Doppler, pulmonary artery measurement (51).

There are general guidelines about the predictive post-pneumonectomy FEV1 tested at least 0.8 L, but in EPP there is not a cut-off value shared from all the authors; someone considered predictive post-operative FEV1 cut-off 1.2 L because of the diaphragm removal, and for more extended surgical incision, with possibility of muscles damage (52), although there are other functional evaluations for pneumonectomy according to ACCP guidelines (53).

This not standardised pre-operative evaluation makes more complicated the interpretation of the results from so many different centres, and this is true for mortality, morbidity and QoL.

The anaesthesiologic preparation for EPP includes placement of an arterial line, a central line, and an epidural catheter for perioperative regional pain control and sometimes a Swan-Ganz catheter, double-lumen endotracheal tube, a nasogastric tube (54).

The EPP is a surgical procedure performed and studied mainly in MPM patients. This tumour can be surgically treated with EPP or with pleurectomy/decortication (P/D), so it represents a comparative analysis model between two different types of surgery: lung-sparing procedure vs. more radical and aggressive surgery (43). All the most essential information about EPP, arise from MPM patients series, who have been studied with the aim to match the results of EPP vs. P/D or more recently any surgery but chemo/radiotherapy (4,55-57).

For many years, the EPP radical surgery in mesothelioma patients has been performed by many authors until multicentre randomised controlled MARS trial (4) showed no more benefit derived to MPM patients, from this vs. chemotherapy alone.

However, in both cases, the MPM staging is critical, and the PET-computed tomography is necessary for distant metastases detection but, for nodal involvement evaluation, sometimes, the endobronchial ultrasonography and or cervical mediastinoscopy can be necessary (21,58). Chest MRI is useful to evaluate for chest wall, transdiaphragmatic, or transmediastinal invasion of a tumour (59).

In other non-mesothelioma pleural malignancies, because of the smaller number of patients and heterogeneity of biological behaviours, this comparative analysis has never been performed and could never get the same statistical significance than in MPM.

The overall five years survival ranged from 0 to 78% (6) in thymoma patients and 56% (43) in MPM patients.

An extended posterolateral or lateral thoracotomy is required. The extra-pleural plane is dissected from endothoracic fascia all over the pleural space. Posteriorly the limits are the azygous vein on the right and the aorta on the left; superiorly the subclavian vessels and anteriorly the mammalian vessel and the thymic fat. The hemi-diaphragm represents the inferior limit with his pericardial and chest wall attachments. Heart (when there is an intrapericardial extension), aorta, superior and inferior vena cava, oesophagus represent the essential structures we should care to not damage, during the dissection.

The phrenic nerves and vessels can be clipped especially if the hemidiaphragm is resected. After pericardial anterior and posterior incision, the vascular, pulmonary hilum is prepared, and the vessels are sutured and divided. The mainstem bronchus is divided and closed with a heavy wire stapler, and it can be buttressed with thymic tissue or omentum mobilised on a vascularized flap. It is preferable to avoid intercostal muscle pedicle, particularly if the rib is removed. The diaphragm can be reconstructed with different mesh/patch (52). The diaphragm resection and reconstruction are a critical point in EEL. Autologous latissimus dorsi reverse or alloplastic materials can be used for diaphragmatic repair flap (60,61). The division of chest from abdomen prevents the herniation of the stomach and other abdominal organs.

Post-operative complications

The post-EPP behaves differently to post-pneumonectomy, and this must be considered in a mediastinal shift and for fluid/air balance (62).

The early identification of the most life-threatening post-operative complications such as ARDS, pericardial tamponade, cardiac herniation, pulmonary embolism, respiratory infections, respiratory failure, atrial arrhythmia, myocardial infarction described by Sugarbaker in 2004 on 328 cases (1), is necessary for keeping a low accidents rate.


The peri-operative mortality and morbidity, in mesothelioma patients, ranged from 0–11.8% (16), and from 0–82.6% (45), respectively. Already in his old article, in 1999 Sugarbaker (20), showed in MPM patients a perioperative mortality rate of 3.8% with five years OS of 15%. In MPM, Sugarbaker and Rusch (51,63) showed as a significant factor of OS staging, histology (epithelial better prognosis), integrated treatment and sex; while N2 status was a worse prognostic factor in de Perrot analysis (43) and Flores series (56,58). In 1999, it was already accepted that locally advanced T and N status, and non-epithelial histology was prognostic factors of poor prognosis (21).

There are also two studies evaluating quality of life (QoL) after EPP in MPM patients (64,65), and Cao et al. showed an improvement in QoL at three months.

The ipsilateral chest is the most common site of treatment failure after EPP-based multimodality therapy (37,47,66).

Other pleural malignancies

We have only seven studies focused on non-mesothelioma pleural malignancies. About sarcoma pleural dissemination treated with EPP, the literature is limited to rare report (7); Sugarbaker reported a median survival of 3.7 months in 10 sarcoma patients (8). Wright (5) presented five patients who underwent EPP for stage IVa thymoma, with any postoperative deaths and one major complication (tamponade requiring removal of the pericardial patch); the overall 5-year survival was 53%.

In NSCLC stage IV with pleural effusion after induction chemotherapy (67), the EPP is one possibility, but we are so far from recognizing this as a standard treatment of non-distant- metastatic pleural carcinosis form NSCLC; it remains such a questionable indication, that is inevitably needed more prospective studies. Swanson et al. (14) presented 12 NSCLC patients with malignant pleural effusion and no N2/N3 nodal or distant metastases treated between 1994 and 1997. After neoadjuvant chemotherapy, the patients, who did not have any progression, underwent EPP, with 0% mortality and 58% of morbidity.

Sugarbaker et al. (8) between 1994 and 2007 reported 28 patients N0 stage IV NSCLC for pleural effusion treated with EPP, obtaining median survival for the nine patients with N0 disease of 52 months, 14 months for the 19 for N1 and/or N2 disease, suggesting a role of EPP in survival improvement. Yokoi et al. (15) at the Tochigi Cancer Centre in Japan treated with EPP 11 patients who for NSCLC with malignant pleural effusion, including three patients with the clinical N2 disease, showing an overall 5-year survival of 54.5%, and in pathological N0–N1 disease on final patients experienced a 5-year survival of 67%.

Multimodality integrated treatments

In MPM, the most used drugs as neoadjuvant treatment were carboplatin, cyclophosphamide, and gemcitabine, more recently replaced by pemetrexed and cisplatin (58). Sugarbaker and Wolf, in their 183 MPM patient’s series, reported already many chemotherapy cycles with doxorubicin and cyclophosphamide with or without cisplatin, and later carboplatin and paclitaxel (51). Three authors analysed in MPM HIOC (10,11,68) as hyperthermic intraoperative intracavitary chemotherapy perfusion following extrapleural pneumonectomy with acceptable morbidity and mortality. Schouwink et al. (22) showed, with meta-tetrahydroxyphenylchlorin (mTHPC) for intraoperative photodynamic therapy (IPDT), good results in local control of disease in 50% of the treated cases, although much toxicity rate is procedure-correlated. Aziz et al. presented a comparative analysis between two MPM groups: a series of 51 patients who underwent to EPP, adjuvant intrapleural normothermic carboplatin, and a series of 13 patients who underwent EPP alone. The results showed a better median OS in the group that received adjuvant intrapleural and systemic chemotherapy (35 versus 13 months) (26).


We decided to review the EPP for all the thoracic malignancies not only focusing on the MPM only since we want to have a complete revision of the literature. At the moment, in sarcoma and thymoma patients there are too much few data to standardise EPP as a recognised choice treatment. In MPM patients the indications are changed and in pleural carcinosis from NSCLC stage IV, “wet stage IV NSCLC”, the chemotherapy is the gold standard.

The references selected are published between 1991 and 2014, and the perioperative management has been changed drastically. Therefore, to discuss the perioperative mortality and morbidity, the study period should be narrowed.

Also, the EPP should be always a part of a multimodality treatment program and often is the only one possibility for thoracic locally extended cancer treatment, especially in young patients, with low-grade disease, non-responsive to systemic chemotherapy.

In very selected cases and with the aim to obtain R0 margins, in deeply extended diseases through the chest wall, this resection has been extended over the EPP to thoracopleuropneumonectomy (TPP) (69) so that, with an increased number of patients we should comparatively analyse EPP vs. TPP in non-mesothelioma low grade malignancies, such as it was done with P/D vs. EPP in MPM.

In the referral centre with expertise, EPP could represent a radical procedure for pleural malignancies, especially for rare diseases, in selected advanced stages, always sharing the indications in the multidisciplinary meeting.

The timing of surgery integrated approach, the identification of disease worth of this type of surgery, and the functional cardio-pulmonary cut-off and limits for correctly undergoing to EEP represent the most critical questions about this significant surgery we should try to standardise, although it could be useful just in a limited number of patients.




Conflicts of Interest: The authors have no conflicts of interest to declare.


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Cite this article as: Duranti L, Pardolesi A, Bertolaccini L, Tavecchio L, Scanagatta P, Rolli L, Pastorino U. Extra-pleural pneumonectomy. J Thorac Dis 2019;11(3):1022-1030. doi: 10.21037/jtd.2019.02.61

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