doi:10.1510/mmcts.2004.000133
Extrapleural pneumonectomy for malignant pleural mesothelioma Luis M. Argote-Greenea, Michael Y. Changb, David J. Sugarbakerc,* a
Division of Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 and Department of Surgery, Harvard Medical School, 25 Shattuck Street, Boston, MA, USA b
Division of Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 and Instructor in Surgery, Department of Surgery, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA c
Division of Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 and The Richard E. Wilson Professor of Surgical Oncology, Department of Surgery, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 and Phillip E. Lowe Senior Surgeon, Department of Surgical Services, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA Extrapleural pneumonectomy was introduced in the 1940s for the treatment of extensive infections of the lung and pleural space. Over the past 20 years, the extrapleural pneumonectomy technique has been modified and applied to the treatment of locally advanced malignant pleural mesothelioma, achieving substantial reductions in mortality. The current mortality rate of 3.4% at the Brigham and Women’s Hospital has permitted us to expand our use of this operation to treat locally advanced lung cancer and thymoma. The extrapleural pneumonectomy technique consists of five basic steps: (1) Incision and exposure of the parietal pleura: (2) Dissection of the tumor and parietal pleura from the chest wall, diaphragm, and mediastinum: (3) Division and control of the pulmonary vessels and bronchus followed by lymph node dissection: (4) En bloc resection of the lung, pleura, pericardium, and diaphragm; (5) Reconstruction of the diaphragm and pericardium. Extrapleural pneumonectomy is a complex and challenging operation. Accompanied by a 60% minor and major complication rate, it requires a unique management approach to achieve 3.4% mortality. Primary contributing factors to the reduction in mortality include a reduced operative time of 3 h, refinements in operative technique, and improved selection of patients. The technique discussed below is the culmination of 20 years’ experience with malignant pleural mesothelioma at the Brigham and Women’s Hospital/Dana Farber Cancer Institute, Boston, MA USA.
Keywords: Malignant pleural mesothelioma; Extrapleural pneumonectomy; Technique
* Corresponding author: Tel.: q1-617-732 5527; fax: q1-617-566-6434. E-mail: [email protected] 䉷 2005 European Association for Cardio-thoracic Surgery
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L.M. Argote-Greene et al. / Multimedia Manual of Cardiothoracic Surgery / doi:10.1510/mmcts.2004.000133
Introduction
Patient selection
The surgical technique of extrapleural pneumonectomy (EPP) was first described in the late 1940s by Sarot who used this resection for the treatment of tuberculous empyema w1x. In the 1980s and 1990s, as infectious diseases of the thorax decreased and thoracic malignancies increased, this operation was more commonly performed for malignant pleural mesothelioma (MPM) w2x. Most authors reported high perioperative morbidity and mortality w3–7x. In 1999, we reported a series of 183 patients from Brigham and Women’s Hospital who showed significant improvement over previous reports w8x. Our current 3.4% mortality rate was recently reported in a series of 496 patients who underwent EPP, along with a subset of 328 consecutive patients who were examined for detailed morbidity w9x (Table 1).
Patient selection criteria for EPP include a Karnofsky performance score greater than 70, normal renal and liver function tests, adequate cardiac and pulmonary functional assessment; and extent of disease limited to the ipsilateral hemithorax. There is no strict age cutoff. Rather, we rely on the overall functional status w10x (Table 2).
Table 1. Reported mortality with extrapleural pneumonectomy Author
Number Epithelial Operative 2-year 5-year
Worn w11x 62 Butchart et al. w3x 29 DeLaria et al. w4x 11 DaValle et al. w5x 33 Ruffie et al. w6x 23 Allen et al. w7xa 40 Rusch et al. w12xb 50 Sugarbaker et al. w8xc 183 Sugarbaker et al w9x 496
– 11 9 20 – 26 – 103 –
– 31 0 9 13 7.5 6 3.8 3.4
37 10 27 24 17 22.5 – 37 –
10 3 – 6 – 10 – 14 –
Extrapleural pneumonectomy followed by chemotherapy (cyclophosophamide, adriamycin wdoxorubicinx, and prednisone wcisplatinx wCAPx. b Median survival 9.9 months. c Extrapleural pneumonectomy followed by adjuvant radiation therapy (40.5 Gy"14.4 Gy boost dose to areas of residual disease, localized lymph nodes, and localized positive resection margins) and chemotherapy (doxorubicin wnine patientsx, CAP w80 patientsx, and carboplatin/paclitaxel w94 patientsx). The 2- and 5-year survival rates for 176 patients who survived surgery were 38% and 15%, respectively. a
Preoperative assessment Parameters and studies critical to the preoperative assessment include age and performance status; blood chemistries wserum, CBC (complete blood count), arterial blood gases, liver function testsx; pulmonary function tests and quantitative ventilationperfusion scan; cardiac function studies (echocardiography, electrocardiogram); radiological studies (chest CT, chest MRI); pleural biopsy; and if warranted, cervical mediastinoscopy. Radiologic studies are always needed preoperatively to determine the presence of intra- or extrathoracic disease. Pleural biopsy is required for histologic confirmation of mesothelioma. Ruling out contralateral hemithorax involvement, transdiaphragmatic extension, or invasion of mediastinal structures is required before surgery for the patient to be considered suitable for resection. Chest wall invasion, the most frequent cause that precludes resection, is ruled out intraoperatively wsee belowx w2, 8, 9x.
Essential steps of extrapleural pneumonectomy After induction of general anesthesia and doublelumen endotracheal intubation, the patient is placed in the right (or left) lateral decubitus position. The surgical technique consists of five basic steps:
Table 2. Patient selection criteria Karnofsky performance score Renal function Liver function Pulmonary function Cardiac function
Extent of disease
70 Creatinine -1.5 AST -80 IU/l, total bilirubin -1.9 mg/dl, PT -15 s Postoperative FEV1 0.8 L as per PFTs and quantitative ventilation-perfusion scans Grossly normal cardiac function as per ECG and echocardiography (EF preferably 45%, absence of pulmonary hypertension) Limited to ipsilateral hemithorax with no transdiaphragmatic, transpericardial, or extensive chest wall involvement
AST, Aspartate aminotransferase; PT, prothrombin time; FEV1, forced expiratory volume in 1 s; PFTs, pulmonary function tests; ECG, electrocardiography; EF, ejection fraction w9x.
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Schematic 3. Extrapleural dissection of the posterior mediastinal pleura and separation of the esophagus from the specimen.
Schematic 1. Right posterolateral thoracotomy incision.
Schematic 4. Diaphragmatic resection.
Schematic 2. After adequate initial dissection, two chest retractors are positioned anteriorly and posteriorly in the thoracotomy.
Step one: incision The extrapleural space is approached through an extended posterolateral thoracotomy incision in the sixth intercostal space with resection of the sixth rib to improve exposure (Schematic 1).
Packing the dissected areas diminishes blood loss. Avoiding vascular structures is of paramount importance. Surgical landmarks in the right hemithorax are the superior vena cava, subclavian vessels, azygos vein, internal mammary vessels, esophagus, and inferior vena cava (IVC) (Schematics 2 and 3).
Step two: extrapleural dissection
Important aspects to operating in the left hemithorax include maintaining a preaortic plane and avoiding avulsion of the intercostal arteries in the retroaortic plane.
The extrapleural dissection is accomplished with a combination of sharp, blunt, and cautery dissection. The dissection proceeds in the caudal-to-cephalad direction, followed by a lateral-to-medial dissection.
The diaphragm is divided and dissected from the underlying peritoneum using blunt dissection, with care taken to keep the peritoneum intact (Schematic 4). 3
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Schematic 5. Pericardial dissection.
Schematic 8. The Gore-Tex patch is trimmed to size.
Step three: division of the pulmonary vessels and bronchus With right-sided resection, control of the pulmonary vessels is obtained within the pericardium. A specific technique for safe dissection and division of the pulmonary hilar vessels is discussed below (Schematic 6).
Schematic 6. Dissection and division of the pulmonary vessels.
With left-sided resection, the shorter left pulmonary artery is dissected and controlled extrapericardially to avoid impingement of the main pulmonary artery. The pulmonary artery and veins are divided using a vascular stapler (technique described below). The intrapericardial dissection occurs after dissection of the pulmonary artery and then the pulmonary veins are divided within the pericardium, also using a vascular stapler. These maneuvers allow the specimen to be elevated permitting a complete subcarinal lymph node dissection. The carina and main stem bronchus are exposed and divided using a heavy-gauge bronchial stapler (Schematic 7). Step four: removal of specimen en bloc When the specimen is removed it should include en bloc resection of the lung with visceral and parietal pleurae, pericardium, and diaphragm. The complete nodal dissection is also obtained.
Schematic 7. Division of main stem bronchus.
It is helpful to enter the pericardium and follow the IVC toward the hiatus. Opening the pericardium widely will facilitate adequate exposure of the hilar vessels (Schematic 5). 4
Step five: reconstruction The bronchial stump is covered with a vascularized pericardial fat pad. Two Gore-Tex (MMCTSLink 40) patches are used to create a ‘‘dynamic patch’’ for dia-
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Video 1. Incision. Once abdominal involvement is ruled out, a posterolateral thoracotomy incision is started 2 cm lateral to the costovertebral junction, along the bed of the sixth rib and ending at the costochondral junction. The scars of previous incisions are excised as well, to prevent local recurrence (Schematic 1). Schematic 9. Circumferential anchoring sutures with buttons are placed in the chest wall to secure the diaphragmatic patch.
phragmatic reconstruction (Schematics 8 and 9), and one patch to reconstruct the pericardium (MMCTSLink 41). Impermeable material is used for diaphragmatic reconstruction to avoid peritoneal fluid from entering the chest cavity and causing mediastinal shift (Schematic 10). The pericardial patch must be fenestrated to avoid constrictive cardiac physiology (Schematic 11).
Schematic 10. The medial aspect of the patch is sutured to the mediastinal and pericardial structures.
Hemostasis is achieved and the chest is closed in usual fashion. A red rubber catheter placed through the anterior edge of the incision is used to centrally position the mediastinum. Air and fluid are withdrawn from the chest cavity via this catheter. The catheter is left in place for 48 h and may be used to rebalance the chest, assess for bleeding, or manage complications.
Surgical technique Right extrapleural pneumonectomy
Schematic 11. Pericardial reconstruction.
The patient undergoes standard intraoperative monitoring (arterial line, continuous oximetry, central venous access). A thoracic epidural catheter is placed preoperatively for intraoperative and postoperative pain management. After anesthesia induction and placement of a left-sided double-lumen endotracheal tube, the patient is positioned in left lateral decubitus position. A nasogastric tube is placed to facilitate localization of esophagus, ensure adequate stomach decompression, and minimize risk of aspiration. If transdiaphragmatic involvement is suggested by preoperative imaging, an abdominal exploration through a limited subcostal incision is warranted. Alternatively, a laparoscopic exploration can be performed – see Videos 1–22. 5
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Video 2. After periosteal stripping, the 6th rib is resected to provide adequate exposure of the hemithorax.
Video 3. Extrapleural dissection. Extrapleural dissection is initiated and advanced superiorly toward the apex of the thorax. Dissection is performed bluntly for the most part but can also be combined with sharp and cautery dissection.
Video 4. Posterior dissection is carried out after adequate anterior exposure has been obtained to provide good exposure of the mediastinal structures in the posterior portion of the visceral compartment.
Video 5. Anteriorly, the internal mammary artery and vein must be protected from injury because they are easily avulsed. The apex of the hemithorax is exposed carefully to avoid injury to the subclavian artery and vein. Dissection proceeds to the apex of the lung. Care is taken to avoid traction injury to the superior vena cava and azygos vein (Schematic 2).
Left extrapleural pneumonectomy Left extrapleural pneumonectomy (EPP) is similar to the technique for right EPP, but some important dif6
Video 6. Dissection of the medial parietal pleura is continued in the extrapleural plane until the right main stem and upper lobe bronchi are visualized. Posteriorly, the absence of aortic (left) or esophageal invasion (right) is confirmed by palpation and visualization of these structures. The esophagus is separated from the specimen using blunt and sharp scissor dissection (Schematic 3).
Video 7. The pericardium is opened anteriorly, and the pericardial space palpated to rule out invasion. If there are no signs of unresectable disease, we turn to the diaphragmatic dissection.
Video 8. Dissection of the diaphragm. The diaphragm is incised at its anterior margin and extended in a circumferential fashion laterally and posteriorly. The diaphragmatic muscle fibers may be divided with cautery or avulsed from their insertion (Schematic 4).
ferences exist. Lung isolation is achieved with a left endobronchial blocker or a right double-lumen endotracheal tube. Extrapleural dissection is performed similarly to the right side. The undersurface of the aortic arch is dissected with care to avoid left recurrent laryngeal nerve injury. We maintain a preaortic plane to avoid avulsion of intercostal vessels in the retroaortic plane. On the left side, we prefer to dissect and divide the pulmonary artery extrapleurally and extrapericardially using the stapling technique previously described. Pulmonary veins are divided intrapericardially. Complete radical lymph node dissection is performed similarly to the right side but with the addition of the aortopulmonary lymph nodes.
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Video 9. The diaphragmatic muscle fibers are dissected from the peritoneum by placing Babcock clamps on the diaphragm to provide cephalad retraction. Blunt caudad dissection of the peritoneum is performed using a sponge stick. Care is taken not to enter the peritoneum. If an opening is created, the peritoneum is closed before diaphragmatic reconstruction (Schematic 4). To complete the diaphragmatic incision, the diaphragmatic attachments are divided just lateral to the inferior vena cava and the esophagus. A 2-cm rim of the crus is preserved with the esophagus. This tissue is used as a point of attachment for the diaphragmatic patch during the reconstruction phase of the operation.
Video 12. The pericardium is opened widely to facilitate adequate exposure of the hilum. For this dissection it is helpful to follow the IVC toward the hiatus (Schematic 5).
Video 13. Dissection and division of the pulmonary vessels. A soft-flanged catheter (endoleader) is passed around the superior pulmonary vein to guide the endovascular stapler (MMCTSLink 44 and MMCTSLink 45) safely around the vessel w18x (Schematic 6).
Video 10. Pericardial dissection. After the diaphragm is resected, the specimen is retracted posteriorly and the pericardium is opened to the level of the hilar vessels. Completion of the pericardial incision is performed anteromedially to the phrenic nerve and hilar vessels, as described by Garcia and coworkers (1998) w17x (Schematic 5). Video 14. The pulmonary artery and inferior pulmonary vein are each isolated and stapled intrapericardially in the same fashion (Schematic 6).
Results
Video 11. The main pulmonary artery is then dissected, isolating it from the superior vena cava and superior pulmonary vein.
Initially, we did not reconstruct the pericardium for left-sided resections, but Byrne et al. w14x in 2002 reported constrictive cardiac physiology in seven patients. When these patients were treated with epicardiectomy, there was complete resolution of symptoms. The pathology report revealed only chronic inflammation and fibrotic tissue. Now we routinely reconstruct the left pericardial defect to avoid constrictive cardiac physiology in all of our cases.
We recently published the largest single-institution compilation of extrapleural pneumonectomies in the literature w9x. This latest review incorporates 20 years’ experience (1980–2000) with MPM at Brigham and Women’s Hospital/Dana Farber Cancer Institute (Boston, MA, USA) and exemplifies the constant adaptation required to develop a new surgical procedure. The success of this evolutionary process depends on the incorporation of novel surgical techniques that lead to improved survival, reduced operative time, and a steady reduction in postoperative mortality w8, 9, 15x. In 1976, Butchart and associates reported a prohibitive operative mortality of 31% for EPP w3x. Several other series have been reported with mortalities rang7
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Video 15. Division of the bronchus and removal of the specimen. The surgical specimen is retracted anteriorly, and the esophagus is retracted medially as the posterior pericardium is divided and dissection is continued laterally to the esophagus. This completes the pericardial dissection. The right main bronchus is dissected down to the carina. It is then encircled with a heavy-gauge wire bronchial stapler (TA-30MMCTSLink 44) (Schematic 7). Before firing the stapler, the anesthesia team handbags the patient to rule out encroachment of the trachea or contralateral main stem bronchus. Once the stapler is adequately positioned, it is fired, and en bloc resection of the specimen is completed. Small unresected gross areas of disease are marked with clips for subsequent radiotherapy targeting. A complete radical nodal dissection is performed for tumor staging (paratracheal, subcarinal, paraesophageal, and inferior pulmonary nodes).
Video 18. Diaphragmatic and pericardial reconstruction. Reconstruction is done using 2-mm thickness ePTFE biomaterial (Gore-Tex DUALMESH䊛 – MMCTSLink 40). We create an oversize patch, sewing together two 20 cm=30 cm DUALMESH䊛 patches. The creation of a dynamic floppy and loose diaphragmatic reconstruction decreases the incidence of patch dehiscence and herniation of abdominal contents into the chest. The diaphragmatic patch is contoured to the shape of the hemithorax (Schematic 8).
Video 19. Nine heavy silk sutures are placed circumferentially around the patch. Both ends of the silk sutures are exteriorized through the intercostal space and tied to a 14-mm polypropylene button (MMCTSLink 47).
Video 16. A pericardial fat pad, intercostal muscle pedicle or pericardial pedicle, is raised and rotated to cover the bronchial stump and separate it from the pulmonary artery stump. It is sutured circumferentially around the bronchial stump with absorbable 3-0 polyglactin (Vicryl – MMCTSLink 38) The bronchial stump is tested for leaks with increase of the airway pressure to 30 mmHg (Schematic 7).
Video 17. The thorax is inspected for hemostasis. Special attention is paid to the divided edges of diaphragm, hilum and phrenic vessels. Liberal use of the argon beam coagulator (MMCTSLink 46) on the chest wall has proved useful for hemostasis.
ing between 8% w7x and 15% w12x. Our institution presently reports the lowest published mortality 8
Video 20. The patch is secured anteriorly, laterally and posteriorly to the chest wall using the silk sutures (Schematic 8). The patch is sewn medially to the diaphragmatic edge of the divided pericardium and the crus fibers using interrupted 2-0 Ethibond sutures (MMCTSLink 24) (Schematic 10).
associated with EPP of 3.4% w9x. A total of 496 patients undergoing EPP were reviewed for mortality rates, with a subset of 328 consecutive patients who were analyzed for morbidity between 1980 and 2000. The median age was 58 years (range 28–77 years). Data analysis yielded a 10-day median length of stay (range 4–101). The detailed examination of the morbidity data using this prospective database revealed the following essential aspects of care in the perioperative period. ● Prophylaxis for atrial fibrillation.
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Video 21. Pericardium is reconstructed using ePTFE (GORE PRECLUDE䊛 – MMCTSLink 41) 15 cm=20 cm piece of 0.1-mm thick pericardial membrane. The patch is fenestrated to prevent fluid accumulation around the heart that could lead to constrictive cardiac physiology and secured with interrupted 2-0 Ethibond sutures to the anterior and posterior pericardial cut edges (Schematic 11). Graph 2. Patients survival based on revised staging system, all patients. (Reproduced from Ref. w8x with permission from Elsevier.)
● Perioperative diagnosis and aggressive management of deep vein thrombosis. ● Immediate reoperation and open cardiac massage for relief of cardiac herniation and tamponade due to cardiac patch dysfunction. Video 22. The thoracotomy edges are reapproximated in the usual fashion for airtight closure. A 12 F red rubber catheter is placed in the pneumonectomy space to permit central mediastinal positioning. Before extubation, air is withdrawn from the chest cavity via this catheter using a 50-cc syringe connected to the red rubber catheter through a 3-way stopcock. Right EPP: female patient – 750 ml. Male patient – 1000 ml Left EPP: female patient – 500 ml. Male patient – 750 ml The catheter is left in place for 48 h and may be used to rebalance the chest, assess for bleeding, or manage complications. The patient is extubated in the OR after bronchoscopic examination for inspection of the bronchial stump, clearing of airway secretions and/ or blood.
● Immediate reoperation for diaphragmatic patch dehiscence, hemorrhage, or both. ● Thoracoscopic or open drainage treatment and staged removal of the patch for early signs of infection due to bronchopleural fistula. ● Intraoperative catheter placement for monitoring and treatment of excessive perioperative mediastinal shift. The complications of EPP require a unique approach to management, and mortality can be minimized by early detection and aggressive treatment w9x. The disciplined approach to the perioperative care outlined above has lowered our mortality in this complex procedure to 3.4% (Table 1). Long-term survival The latest report of long-term survival from our group yielded a median survival of 19 months in 176 patients after the 30-day survival landmark was reached; with 2- and 5-year survivals of 38% and 15%, respectively w8x (Graph 1). In this group of patients, the Brigham and Women’s Hospital revised staging system was confirmed to have prognostic significance w8x (Graph 2) (Table 3).
Graph 1. Patient survival. (Reproduced from Ref. w8x with permission from the American Association for Thoracic Surgery.)
● Early ambulation, aspiration precautions, endoscopic assessment of vocal cords, and avoidance of fluid overload.
Moreover, a subset of 31 patients with epithelial cell type, negative resection margins, and negative extrapleural nodal status had a 51-month median survival, with 2- and 5-year survival of 68% and 46%, respectively w8x (Graph 3). 9
L.M. Argote-Greene et al. / Multimedia Manual of Cardiothoracic Surgery / doi:10.1510/mmcts.2004.000133 Table 3. The revised* staging system for malignant pleural mesothelioma Stage
Description
I
Disease confined to the interior parietal pleura, or chest wall disease limited to previous biopsy sites All of stage I with positive intrathoracic lymph nodes (N1, N2) Local extension of disease into the chest wall or mediastinum; heart, diaphragm, peritoneum; or with extrapleural lymph node involvement Distant metastatic disease
II III IV
Note: Patients with Butchart stage II and III w9x disease are combined into stage III. Stage I represents patients with resectable disease and negative nodes. Stage II indicates resectable disease but positive nodes. *Revised from Sugarbaker DJ, Strauss GM, Lynch TJ, Richards W, Mentzer SJ, Lee TH, Corson JM, Antman KH. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 1993;11:1172–8. (Reproduced from Ref. w13x with permission of WB Saunders Company.)
w3x
w4x
w5x
w6x Graph 3. Kaplan-Meier survival curves of patients with epithelial type tumor, Brigham stage I, ns31; stage II, ns51, and stage III, ns21 (ns103, Ps0.0044). (Reproduced from Ref. w8x with permission from the American Association for Thoracic Surgery.)
Recently approved chemotherapeutic agents, including gemcitabine and pemetrexed (MMCTSLink 42 and MMCTSLink 43), show promising results with mesothelioma w16x. New strategies and techniques are being actively investigated in multiple referral centers, including the Brigham and Women’s Hospital Thoracic Surgery Division and Dana Farber Thoracic Oncology Program. At our institution, intraoperative intracavitary lavage with hyperthermic chemotherapy is also being investigated for its ability to improve local control and extend survival in this aggressive disease.
References w1x Sarot I. Extrapleural pneumonectomy and pleurectomy in pulmonary tuberculosis. Thorax 1949;4:173–223. w2x Chang M, Sugarbaker D. Technique of extrapleural pneumonectomy for diffuse mesothelioma. In: Shields T, LoCicero JI, Ponn R, Rusch V, 10
w7x
w8x
w9x
editors. General Thoracic Surgery. Vol. 1. Philadelphia: Lippincott Williams and Wilkins, 2004:922–929. Butchart E, Ashcroft T, Barnsley W, Holden M. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura; experience with 29 patients. Thorax 1976;31: 15–24. DeLaria G, Jensik R, Faber L, Kittle C. Surgical management of malignant mesothelioma. Ann Thorac Surg 1978;26:375–382. DaValle M, Faber L, Kittle C, Jensik R. Extrapleural pneumonectomy for diffuse, malignant mesothelioma. Ann Thorac Surg 1986;42:612–618. Ruffie P, Feld R, Minkin S, Cormier Y, BoutanLaroze A, Ginsberg R, Ayoub J, Shepherd FA, Evans WK, Figueredo A. Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients. J Clin Oncol 1989;7:1157–1168. Allen K, Faber L, Warren W. Malignant pleural mesothelioma: extrapleural pneumonectomy and pleurectomy. Chest Surg Clin N Am 1994;4:113– 126. Sugarbaker D, Flores R, Jaklitsch M, Richards W, Strauss G, Corson J, DeCamp M, Swanson SJ, Bueno R, Lukanich JM, Baldini E, Mentzer S. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 1999;117:54–63. Sugarbaker DJ, Jaklitsch MT, Bueno R, Richards W, Lukanich J, Mentzer SJ, Colson Y, Linden P, Chang M, Capalbo L, Oldread E, NeragiMiandoab S, Swanson SJ, Zellos LS. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg 2004;128:138–146.
L.M. Argote-Greene et al. / Multimedia Manual of Cardiothoracic Surgery / doi:10.1510/mmcts.2004.000133 w10x Sugarbaker DJ, Chang M. Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma: techniques and complications. Thorac Surg Clin 2004;4:523–530. w11x Worn H. wChances and results of surgery of malignant mesothelioma of the pleura (author’s transl)x. Thoraxchir Vask Chir 1974;22:391–393. w12x Rusch VW, Piantadosi S, Holmes EC. The role of extrapleural pneumonectomy in malignant pleural mesothelioma. A Lung Cancer Study Group trial. J Thorac Cardiovasc Surg 1991;102:1–9. w13x Sugarbaker DJ, Strauss GM, Lynch TJ, Richards W, Mentzer SJ, Lee TH, Corson JM, Antman KH. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 1993;11:1172– 1178. w14x Byrne JKA, Colson Y, Bueno R, Richard W, Sugarbaker D. Cardiac decortication (epicardiectomy) for occult constrictive cardiac physiology after left extrapleural pneumonectomy. Chest 2002;122:2256. w15x Sugarbaker DJ, Garcia JP, Richards WG, Harpole
DH Jr, Healy-Baldini E, DeCamp MM Jr, Mentzer SJ, Liptay MJ, Strauss GM, Swanson SJ. Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma: results in 120 consecutive patients. Ann Surg 1996;224:288–294. w16x Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21:2636–2644. w17x Garcia J, Richards W, Sugarbaker D. Surgical treatment of malignant mesothelioma. In: Kaiser L, Kron I, Spray T, editors. Mastery of cardiothoracic surgery. Philadelphia: LippincottRaven, 1998. w18x Sugarbaker DJ, Norberto JJ, Swanson SJ. Extrapleural pneumonectomy in the setting of multimodality therapy for diffuse malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg 1997;9:373–382.
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Extrapleural pneumonectomy for malignant pleural mesothelioma Luis M. Argote-Greenea, Michael Y. Changb, David J. Sugarbakerc,* a
Division of Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 and Department of Surgery, Harvard Medical School, 25 Shattuck Street, Boston, MA, USA b
Division of Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 and Instructor in Surgery, Department of Surgery, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA c
Division of Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 and The Richard E. Wilson Professor of Surgical Oncology, Department of Surgery, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 and Phillip E. Lowe Senior Surgeon, Department of Surgical Services, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA Extrapleural pneumonectomy was introduced in the 1940s for the treatment of extensive infections of the lung and pleural space. Over the past 20 years, the extrapleural pneumonectomy technique has been modified and applied to the treatment of locally advanced malignant pleural mesothelioma, achieving substantial reductions in mortality. The current mortality rate of 3.4% at the Brigham and Women’s Hospital has permitted us to expand our use of this operation to treat locally advanced lung cancer and thymoma. The extrapleural pneumonectomy technique consists of five basic steps: (1) Incision and exposure of the parietal pleura: (2) Dissection of the tumor and parietal pleura from the chest wall, diaphragm, and mediastinum: (3) Division and control of the pulmonary vessels and bronchus followed by lymph node dissection: (4) En bloc resection of the lung, pleura, pericardium, and diaphragm; (5) Reconstruction of the diaphragm and pericardium. Extrapleural pneumonectomy is a complex and challenging operation. Accompanied by a 60% minor and major complication rate, it requires a unique management approach to achieve 3.4% mortality. Primary contributing factors to the reduction in mortality include a reduced operative time of 3 h, refinements in operative technique, and improved selection of patients. The technique discussed below is the culmination of 20 years’ experience with malignant pleural mesothelioma at the Brigham and Women’s Hospital/Dana Farber Cancer Institute, Boston, MA USA.
Keywords: Malignant pleural mesothelioma; Extrapleural pneumonectomy; Technique
* Corresponding author: Tel.: q1-617-732 5527; fax: q1-617-566-6434. E-mail: [email protected] 䉷 2005 European Association for Cardio-thoracic Surgery
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L.M. Argote-Greene et al. / Multimedia Manual of Cardiothoracic Surgery / doi:10.1510/mmcts.2004.000133
Introduction
Patient selection
The surgical technique of extrapleural pneumonectomy (EPP) was first described in the late 1940s by Sarot who used this resection for the treatment of tuberculous empyema w1x. In the 1980s and 1990s, as infectious diseases of the thorax decreased and thoracic malignancies increased, this operation was more commonly performed for malignant pleural mesothelioma (MPM) w2x. Most authors reported high perioperative morbidity and mortality w3–7x. In 1999, we reported a series of 183 patients from Brigham and Women’s Hospital who showed significant improvement over previous reports w8x. Our current 3.4% mortality rate was recently reported in a series of 496 patients who underwent EPP, along with a subset of 328 consecutive patients who were examined for detailed morbidity w9x (Table 1).
Patient selection criteria for EPP include a Karnofsky performance score greater than 70, normal renal and liver function tests, adequate cardiac and pulmonary functional assessment; and extent of disease limited to the ipsilateral hemithorax. There is no strict age cutoff. Rather, we rely on the overall functional status w10x (Table 2).
Table 1. Reported mortality with extrapleural pneumonectomy Author
Number Epithelial Operative 2-year 5-year
Worn w11x 62 Butchart et al. w3x 29 DeLaria et al. w4x 11 DaValle et al. w5x 33 Ruffie et al. w6x 23 Allen et al. w7xa 40 Rusch et al. w12xb 50 Sugarbaker et al. w8xc 183 Sugarbaker et al w9x 496
– 11 9 20 – 26 – 103 –
– 31 0 9 13 7.5 6 3.8 3.4
37 10 27 24 17 22.5 – 37 –
10 3 – 6 – 10 – 14 –
Extrapleural pneumonectomy followed by chemotherapy (cyclophosophamide, adriamycin wdoxorubicinx, and prednisone wcisplatinx wCAPx. b Median survival 9.9 months. c Extrapleural pneumonectomy followed by adjuvant radiation therapy (40.5 Gy"14.4 Gy boost dose to areas of residual disease, localized lymph nodes, and localized positive resection margins) and chemotherapy (doxorubicin wnine patientsx, CAP w80 patientsx, and carboplatin/paclitaxel w94 patientsx). The 2- and 5-year survival rates for 176 patients who survived surgery were 38% and 15%, respectively. a
Preoperative assessment Parameters and studies critical to the preoperative assessment include age and performance status; blood chemistries wserum, CBC (complete blood count), arterial blood gases, liver function testsx; pulmonary function tests and quantitative ventilationperfusion scan; cardiac function studies (echocardiography, electrocardiogram); radiological studies (chest CT, chest MRI); pleural biopsy; and if warranted, cervical mediastinoscopy. Radiologic studies are always needed preoperatively to determine the presence of intra- or extrathoracic disease. Pleural biopsy is required for histologic confirmation of mesothelioma. Ruling out contralateral hemithorax involvement, transdiaphragmatic extension, or invasion of mediastinal structures is required before surgery for the patient to be considered suitable for resection. Chest wall invasion, the most frequent cause that precludes resection, is ruled out intraoperatively wsee belowx w2, 8, 9x.
Essential steps of extrapleural pneumonectomy After induction of general anesthesia and doublelumen endotracheal intubation, the patient is placed in the right (or left) lateral decubitus position. The surgical technique consists of five basic steps:
Table 2. Patient selection criteria Karnofsky performance score Renal function Liver function Pulmonary function Cardiac function
Extent of disease
70 Creatinine -1.5 AST -80 IU/l, total bilirubin -1.9 mg/dl, PT -15 s Postoperative FEV1 0.8 L as per PFTs and quantitative ventilation-perfusion scans Grossly normal cardiac function as per ECG and echocardiography (EF preferably 45%, absence of pulmonary hypertension) Limited to ipsilateral hemithorax with no transdiaphragmatic, transpericardial, or extensive chest wall involvement
AST, Aspartate aminotransferase; PT, prothrombin time; FEV1, forced expiratory volume in 1 s; PFTs, pulmonary function tests; ECG, electrocardiography; EF, ejection fraction w9x.
2
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Schematic 3. Extrapleural dissection of the posterior mediastinal pleura and separation of the esophagus from the specimen.
Schematic 1. Right posterolateral thoracotomy incision.
Schematic 4. Diaphragmatic resection.
Schematic 2. After adequate initial dissection, two chest retractors are positioned anteriorly and posteriorly in the thoracotomy.
Step one: incision The extrapleural space is approached through an extended posterolateral thoracotomy incision in the sixth intercostal space with resection of the sixth rib to improve exposure (Schematic 1).
Packing the dissected areas diminishes blood loss. Avoiding vascular structures is of paramount importance. Surgical landmarks in the right hemithorax are the superior vena cava, subclavian vessels, azygos vein, internal mammary vessels, esophagus, and inferior vena cava (IVC) (Schematics 2 and 3).
Step two: extrapleural dissection
Important aspects to operating in the left hemithorax include maintaining a preaortic plane and avoiding avulsion of the intercostal arteries in the retroaortic plane.
The extrapleural dissection is accomplished with a combination of sharp, blunt, and cautery dissection. The dissection proceeds in the caudal-to-cephalad direction, followed by a lateral-to-medial dissection.
The diaphragm is divided and dissected from the underlying peritoneum using blunt dissection, with care taken to keep the peritoneum intact (Schematic 4). 3
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Schematic 5. Pericardial dissection.
Schematic 8. The Gore-Tex patch is trimmed to size.
Step three: division of the pulmonary vessels and bronchus With right-sided resection, control of the pulmonary vessels is obtained within the pericardium. A specific technique for safe dissection and division of the pulmonary hilar vessels is discussed below (Schematic 6).
Schematic 6. Dissection and division of the pulmonary vessels.
With left-sided resection, the shorter left pulmonary artery is dissected and controlled extrapericardially to avoid impingement of the main pulmonary artery. The pulmonary artery and veins are divided using a vascular stapler (technique described below). The intrapericardial dissection occurs after dissection of the pulmonary artery and then the pulmonary veins are divided within the pericardium, also using a vascular stapler. These maneuvers allow the specimen to be elevated permitting a complete subcarinal lymph node dissection. The carina and main stem bronchus are exposed and divided using a heavy-gauge bronchial stapler (Schematic 7). Step four: removal of specimen en bloc When the specimen is removed it should include en bloc resection of the lung with visceral and parietal pleurae, pericardium, and diaphragm. The complete nodal dissection is also obtained.
Schematic 7. Division of main stem bronchus.
It is helpful to enter the pericardium and follow the IVC toward the hiatus. Opening the pericardium widely will facilitate adequate exposure of the hilar vessels (Schematic 5). 4
Step five: reconstruction The bronchial stump is covered with a vascularized pericardial fat pad. Two Gore-Tex (MMCTSLink 40) patches are used to create a ‘‘dynamic patch’’ for dia-
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Video 1. Incision. Once abdominal involvement is ruled out, a posterolateral thoracotomy incision is started 2 cm lateral to the costovertebral junction, along the bed of the sixth rib and ending at the costochondral junction. The scars of previous incisions are excised as well, to prevent local recurrence (Schematic 1). Schematic 9. Circumferential anchoring sutures with buttons are placed in the chest wall to secure the diaphragmatic patch.
phragmatic reconstruction (Schematics 8 and 9), and one patch to reconstruct the pericardium (MMCTSLink 41). Impermeable material is used for diaphragmatic reconstruction to avoid peritoneal fluid from entering the chest cavity and causing mediastinal shift (Schematic 10). The pericardial patch must be fenestrated to avoid constrictive cardiac physiology (Schematic 11).
Schematic 10. The medial aspect of the patch is sutured to the mediastinal and pericardial structures.
Hemostasis is achieved and the chest is closed in usual fashion. A red rubber catheter placed through the anterior edge of the incision is used to centrally position the mediastinum. Air and fluid are withdrawn from the chest cavity via this catheter. The catheter is left in place for 48 h and may be used to rebalance the chest, assess for bleeding, or manage complications.
Surgical technique Right extrapleural pneumonectomy
Schematic 11. Pericardial reconstruction.
The patient undergoes standard intraoperative monitoring (arterial line, continuous oximetry, central venous access). A thoracic epidural catheter is placed preoperatively for intraoperative and postoperative pain management. After anesthesia induction and placement of a left-sided double-lumen endotracheal tube, the patient is positioned in left lateral decubitus position. A nasogastric tube is placed to facilitate localization of esophagus, ensure adequate stomach decompression, and minimize risk of aspiration. If transdiaphragmatic involvement is suggested by preoperative imaging, an abdominal exploration through a limited subcostal incision is warranted. Alternatively, a laparoscopic exploration can be performed – see Videos 1–22. 5
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Video 2. After periosteal stripping, the 6th rib is resected to provide adequate exposure of the hemithorax.
Video 3. Extrapleural dissection. Extrapleural dissection is initiated and advanced superiorly toward the apex of the thorax. Dissection is performed bluntly for the most part but can also be combined with sharp and cautery dissection.
Video 4. Posterior dissection is carried out after adequate anterior exposure has been obtained to provide good exposure of the mediastinal structures in the posterior portion of the visceral compartment.
Video 5. Anteriorly, the internal mammary artery and vein must be protected from injury because they are easily avulsed. The apex of the hemithorax is exposed carefully to avoid injury to the subclavian artery and vein. Dissection proceeds to the apex of the lung. Care is taken to avoid traction injury to the superior vena cava and azygos vein (Schematic 2).
Left extrapleural pneumonectomy Left extrapleural pneumonectomy (EPP) is similar to the technique for right EPP, but some important dif6
Video 6. Dissection of the medial parietal pleura is continued in the extrapleural plane until the right main stem and upper lobe bronchi are visualized. Posteriorly, the absence of aortic (left) or esophageal invasion (right) is confirmed by palpation and visualization of these structures. The esophagus is separated from the specimen using blunt and sharp scissor dissection (Schematic 3).
Video 7. The pericardium is opened anteriorly, and the pericardial space palpated to rule out invasion. If there are no signs of unresectable disease, we turn to the diaphragmatic dissection.
Video 8. Dissection of the diaphragm. The diaphragm is incised at its anterior margin and extended in a circumferential fashion laterally and posteriorly. The diaphragmatic muscle fibers may be divided with cautery or avulsed from their insertion (Schematic 4).
ferences exist. Lung isolation is achieved with a left endobronchial blocker or a right double-lumen endotracheal tube. Extrapleural dissection is performed similarly to the right side. The undersurface of the aortic arch is dissected with care to avoid left recurrent laryngeal nerve injury. We maintain a preaortic plane to avoid avulsion of intercostal vessels in the retroaortic plane. On the left side, we prefer to dissect and divide the pulmonary artery extrapleurally and extrapericardially using the stapling technique previously described. Pulmonary veins are divided intrapericardially. Complete radical lymph node dissection is performed similarly to the right side but with the addition of the aortopulmonary lymph nodes.
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Video 9. The diaphragmatic muscle fibers are dissected from the peritoneum by placing Babcock clamps on the diaphragm to provide cephalad retraction. Blunt caudad dissection of the peritoneum is performed using a sponge stick. Care is taken not to enter the peritoneum. If an opening is created, the peritoneum is closed before diaphragmatic reconstruction (Schematic 4). To complete the diaphragmatic incision, the diaphragmatic attachments are divided just lateral to the inferior vena cava and the esophagus. A 2-cm rim of the crus is preserved with the esophagus. This tissue is used as a point of attachment for the diaphragmatic patch during the reconstruction phase of the operation.
Video 12. The pericardium is opened widely to facilitate adequate exposure of the hilum. For this dissection it is helpful to follow the IVC toward the hiatus (Schematic 5).
Video 13. Dissection and division of the pulmonary vessels. A soft-flanged catheter (endoleader) is passed around the superior pulmonary vein to guide the endovascular stapler (MMCTSLink 44 and MMCTSLink 45) safely around the vessel w18x (Schematic 6).
Video 10. Pericardial dissection. After the diaphragm is resected, the specimen is retracted posteriorly and the pericardium is opened to the level of the hilar vessels. Completion of the pericardial incision is performed anteromedially to the phrenic nerve and hilar vessels, as described by Garcia and coworkers (1998) w17x (Schematic 5). Video 14. The pulmonary artery and inferior pulmonary vein are each isolated and stapled intrapericardially in the same fashion (Schematic 6).
Results
Video 11. The main pulmonary artery is then dissected, isolating it from the superior vena cava and superior pulmonary vein.
Initially, we did not reconstruct the pericardium for left-sided resections, but Byrne et al. w14x in 2002 reported constrictive cardiac physiology in seven patients. When these patients were treated with epicardiectomy, there was complete resolution of symptoms. The pathology report revealed only chronic inflammation and fibrotic tissue. Now we routinely reconstruct the left pericardial defect to avoid constrictive cardiac physiology in all of our cases.
We recently published the largest single-institution compilation of extrapleural pneumonectomies in the literature w9x. This latest review incorporates 20 years’ experience (1980–2000) with MPM at Brigham and Women’s Hospital/Dana Farber Cancer Institute (Boston, MA, USA) and exemplifies the constant adaptation required to develop a new surgical procedure. The success of this evolutionary process depends on the incorporation of novel surgical techniques that lead to improved survival, reduced operative time, and a steady reduction in postoperative mortality w8, 9, 15x. In 1976, Butchart and associates reported a prohibitive operative mortality of 31% for EPP w3x. Several other series have been reported with mortalities rang7
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Video 15. Division of the bronchus and removal of the specimen. The surgical specimen is retracted anteriorly, and the esophagus is retracted medially as the posterior pericardium is divided and dissection is continued laterally to the esophagus. This completes the pericardial dissection. The right main bronchus is dissected down to the carina. It is then encircled with a heavy-gauge wire bronchial stapler (TA-30MMCTSLink 44) (Schematic 7). Before firing the stapler, the anesthesia team handbags the patient to rule out encroachment of the trachea or contralateral main stem bronchus. Once the stapler is adequately positioned, it is fired, and en bloc resection of the specimen is completed. Small unresected gross areas of disease are marked with clips for subsequent radiotherapy targeting. A complete radical nodal dissection is performed for tumor staging (paratracheal, subcarinal, paraesophageal, and inferior pulmonary nodes).
Video 18. Diaphragmatic and pericardial reconstruction. Reconstruction is done using 2-mm thickness ePTFE biomaterial (Gore-Tex DUALMESH䊛 – MMCTSLink 40). We create an oversize patch, sewing together two 20 cm=30 cm DUALMESH䊛 patches. The creation of a dynamic floppy and loose diaphragmatic reconstruction decreases the incidence of patch dehiscence and herniation of abdominal contents into the chest. The diaphragmatic patch is contoured to the shape of the hemithorax (Schematic 8).
Video 19. Nine heavy silk sutures are placed circumferentially around the patch. Both ends of the silk sutures are exteriorized through the intercostal space and tied to a 14-mm polypropylene button (MMCTSLink 47).
Video 16. A pericardial fat pad, intercostal muscle pedicle or pericardial pedicle, is raised and rotated to cover the bronchial stump and separate it from the pulmonary artery stump. It is sutured circumferentially around the bronchial stump with absorbable 3-0 polyglactin (Vicryl – MMCTSLink 38) The bronchial stump is tested for leaks with increase of the airway pressure to 30 mmHg (Schematic 7).
Video 17. The thorax is inspected for hemostasis. Special attention is paid to the divided edges of diaphragm, hilum and phrenic vessels. Liberal use of the argon beam coagulator (MMCTSLink 46) on the chest wall has proved useful for hemostasis.
ing between 8% w7x and 15% w12x. Our institution presently reports the lowest published mortality 8
Video 20. The patch is secured anteriorly, laterally and posteriorly to the chest wall using the silk sutures (Schematic 8). The patch is sewn medially to the diaphragmatic edge of the divided pericardium and the crus fibers using interrupted 2-0 Ethibond sutures (MMCTSLink 24) (Schematic 10).
associated with EPP of 3.4% w9x. A total of 496 patients undergoing EPP were reviewed for mortality rates, with a subset of 328 consecutive patients who were analyzed for morbidity between 1980 and 2000. The median age was 58 years (range 28–77 years). Data analysis yielded a 10-day median length of stay (range 4–101). The detailed examination of the morbidity data using this prospective database revealed the following essential aspects of care in the perioperative period. ● Prophylaxis for atrial fibrillation.
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Video 21. Pericardium is reconstructed using ePTFE (GORE PRECLUDE䊛 – MMCTSLink 41) 15 cm=20 cm piece of 0.1-mm thick pericardial membrane. The patch is fenestrated to prevent fluid accumulation around the heart that could lead to constrictive cardiac physiology and secured with interrupted 2-0 Ethibond sutures to the anterior and posterior pericardial cut edges (Schematic 11). Graph 2. Patients survival based on revised staging system, all patients. (Reproduced from Ref. w8x with permission from Elsevier.)
● Perioperative diagnosis and aggressive management of deep vein thrombosis. ● Immediate reoperation and open cardiac massage for relief of cardiac herniation and tamponade due to cardiac patch dysfunction. Video 22. The thoracotomy edges are reapproximated in the usual fashion for airtight closure. A 12 F red rubber catheter is placed in the pneumonectomy space to permit central mediastinal positioning. Before extubation, air is withdrawn from the chest cavity via this catheter using a 50-cc syringe connected to the red rubber catheter through a 3-way stopcock. Right EPP: female patient – 750 ml. Male patient – 1000 ml Left EPP: female patient – 500 ml. Male patient – 750 ml The catheter is left in place for 48 h and may be used to rebalance the chest, assess for bleeding, or manage complications. The patient is extubated in the OR after bronchoscopic examination for inspection of the bronchial stump, clearing of airway secretions and/ or blood.
● Immediate reoperation for diaphragmatic patch dehiscence, hemorrhage, or both. ● Thoracoscopic or open drainage treatment and staged removal of the patch for early signs of infection due to bronchopleural fistula. ● Intraoperative catheter placement for monitoring and treatment of excessive perioperative mediastinal shift. The complications of EPP require a unique approach to management, and mortality can be minimized by early detection and aggressive treatment w9x. The disciplined approach to the perioperative care outlined above has lowered our mortality in this complex procedure to 3.4% (Table 1). Long-term survival The latest report of long-term survival from our group yielded a median survival of 19 months in 176 patients after the 30-day survival landmark was reached; with 2- and 5-year survivals of 38% and 15%, respectively w8x (Graph 1). In this group of patients, the Brigham and Women’s Hospital revised staging system was confirmed to have prognostic significance w8x (Graph 2) (Table 3).
Graph 1. Patient survival. (Reproduced from Ref. w8x with permission from the American Association for Thoracic Surgery.)
● Early ambulation, aspiration precautions, endoscopic assessment of vocal cords, and avoidance of fluid overload.
Moreover, a subset of 31 patients with epithelial cell type, negative resection margins, and negative extrapleural nodal status had a 51-month median survival, with 2- and 5-year survival of 68% and 46%, respectively w8x (Graph 3). 9
L.M. Argote-Greene et al. / Multimedia Manual of Cardiothoracic Surgery / doi:10.1510/mmcts.2004.000133 Table 3. The revised* staging system for malignant pleural mesothelioma Stage
Description
I
Disease confined to the interior parietal pleura, or chest wall disease limited to previous biopsy sites All of stage I with positive intrathoracic lymph nodes (N1, N2) Local extension of disease into the chest wall or mediastinum; heart, diaphragm, peritoneum; or with extrapleural lymph node involvement Distant metastatic disease
II III IV
Note: Patients with Butchart stage II and III w9x disease are combined into stage III. Stage I represents patients with resectable disease and negative nodes. Stage II indicates resectable disease but positive nodes. *Revised from Sugarbaker DJ, Strauss GM, Lynch TJ, Richards W, Mentzer SJ, Lee TH, Corson JM, Antman KH. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 1993;11:1172–8. (Reproduced from Ref. w13x with permission of WB Saunders Company.)
w3x
w4x
w5x
w6x Graph 3. Kaplan-Meier survival curves of patients with epithelial type tumor, Brigham stage I, ns31; stage II, ns51, and stage III, ns21 (ns103, Ps0.0044). (Reproduced from Ref. w8x with permission from the American Association for Thoracic Surgery.)
Recently approved chemotherapeutic agents, including gemcitabine and pemetrexed (MMCTSLink 42 and MMCTSLink 43), show promising results with mesothelioma w16x. New strategies and techniques are being actively investigated in multiple referral centers, including the Brigham and Women’s Hospital Thoracic Surgery Division and Dana Farber Thoracic Oncology Program. At our institution, intraoperative intracavitary lavage with hyperthermic chemotherapy is also being investigated for its ability to improve local control and extend survival in this aggressive disease.
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w7x
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w9x
editors. General Thoracic Surgery. Vol. 1. Philadelphia: Lippincott Williams and Wilkins, 2004:922–929. Butchart E, Ashcroft T, Barnsley W, Holden M. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura; experience with 29 patients. Thorax 1976;31: 15–24. DeLaria G, Jensik R, Faber L, Kittle C. Surgical management of malignant mesothelioma. Ann Thorac Surg 1978;26:375–382. DaValle M, Faber L, Kittle C, Jensik R. Extrapleural pneumonectomy for diffuse, malignant mesothelioma. Ann Thorac Surg 1986;42:612–618. Ruffie P, Feld R, Minkin S, Cormier Y, BoutanLaroze A, Ginsberg R, Ayoub J, Shepherd FA, Evans WK, Figueredo A. Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients. J Clin Oncol 1989;7:1157–1168. Allen K, Faber L, Warren W. Malignant pleural mesothelioma: extrapleural pneumonectomy and pleurectomy. Chest Surg Clin N Am 1994;4:113– 126. Sugarbaker D, Flores R, Jaklitsch M, Richards W, Strauss G, Corson J, DeCamp M, Swanson SJ, Bueno R, Lukanich JM, Baldini E, Mentzer S. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 1999;117:54–63. Sugarbaker DJ, Jaklitsch MT, Bueno R, Richards W, Lukanich J, Mentzer SJ, Colson Y, Linden P, Chang M, Capalbo L, Oldread E, NeragiMiandoab S, Swanson SJ, Zellos LS. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg 2004;128:138–146.
L.M. Argote-Greene et al. / Multimedia Manual of Cardiothoracic Surgery / doi:10.1510/mmcts.2004.000133 w10x Sugarbaker DJ, Chang M. Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma: techniques and complications. Thorac Surg Clin 2004;4:523–530. w11x Worn H. wChances and results of surgery of malignant mesothelioma of the pleura (author’s transl)x. Thoraxchir Vask Chir 1974;22:391–393. w12x Rusch VW, Piantadosi S, Holmes EC. The role of extrapleural pneumonectomy in malignant pleural mesothelioma. A Lung Cancer Study Group trial. J Thorac Cardiovasc Surg 1991;102:1–9. w13x Sugarbaker DJ, Strauss GM, Lynch TJ, Richards W, Mentzer SJ, Lee TH, Corson JM, Antman KH. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 1993;11:1172– 1178. w14x Byrne JKA, Colson Y, Bueno R, Richard W, Sugarbaker D. Cardiac decortication (epicardiectomy) for occult constrictive cardiac physiology after left extrapleural pneumonectomy. Chest 2002;122:2256. w15x Sugarbaker DJ, Garcia JP, Richards WG, Harpole
DH Jr, Healy-Baldini E, DeCamp MM Jr, Mentzer SJ, Liptay MJ, Strauss GM, Swanson SJ. Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma: results in 120 consecutive patients. Ann Surg 1996;224:288–294. w16x Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21:2636–2644. w17x Garcia J, Richards W, Sugarbaker D. Surgical treatment of malignant mesothelioma. In: Kaiser L, Kron I, Spray T, editors. Mastery of cardiothoracic surgery. Philadelphia: LippincottRaven, 1998. w18x Sugarbaker DJ, Norberto JJ, Swanson SJ. Extrapleural pneumonectomy in the setting of multimodality therapy for diffuse malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg 1997;9:373–382.
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