(Chest. 1999;116:446S-449S.)
© 1999
American College of Chest Physicians
Surgical Treatment of Mesothelioma: Pleurectomy*
John R. Roberts, MD, FCCP
*
From Division of General Thoracic Surgery, Department of Cardiac and Thoracic Surgery, Vanderbilt Hospital, Nashville, TN.
Correspondence to: John R. Roberts, MD, FCCP, 2986 The Vanderbilt Clinic, Nashville, TN 37232; e-mail: bob.roberts{at}mcmail.vanderbilt.edu
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Abstract
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Malignant diffuse mesothelioma is the most common type of
mesothelioma, with a median survival ranging from 8.5 to 18 months
after diagnosis. Good performance status, absence of chest pain,
age < 50 years, and epithelial histology are all associated with
improved survival. Several investigators have described staging systems
for this tumor and have emphasized the importance of thoracoscopy in
the diagnosis and staging of the disease. Pleurectomy is the most
common surgery employed to manage patients with diffuse mesothelioma,
and this procedure is associated with minimal postoperative morbidity
and mortality. Because mesothelioma usually recurs locally after
surgery, efforts at optimizing local control have included both
intraoperative phototherapy and chemotherapy. However, neither of these
techniques has demonstrated any significant benefit to date and thus
should not be considered as standards of care. No studies have compared
pleurectomy to extrapleural pneumonectomy (EPP) in randomized trials.
However, nonrandomized series suggest a significant improvement in
disease-free survival for those undergoing EPP versus pleurectomy.
Other data suggest that EPP may improve local control but may
predispose the patient to distant metastases. A randomized comparison
of these techniques may be beneficial in identifying the most effective
procedure for patients with malignant diffuse mesothelioma.
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Introduction
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Mesothelioma
occurs as three types, each with distinctly different outcomes and
treatments. Benign localized mesothelioma usually develops as a
well-defined mass, quite often projecting on a stalk, on either the
visceral or parietal pleura. These tumors are of variable size and
generally only cause symptoms if very large. They are associated with
hypoglycemia, arthralgias, and clubbing. Benign localized mesotheliomas
are usually resected because of concern about the appropriate
diagnosis, and resection is generally curative.
Malignant localized mesotheliomas may develop on either pleura and are
associated with chest pain, fever, dyspnea, and cough. In contrast to
benign localized mesotheliomas, clubbing is unusual. Malignant
localized mesotheliomas are exceedingly rare, but the recommended
therapy has been resection, with generally good results. Without
complete resection, the median survival is only 7 months.
Malignant diffuse mesothelioma is the most common of the three types of
mesothelioma and will be the focus of the remainder of this paper.
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Malignant Diffuse Mesothelioma
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The diffuse malignant variant of mesothelioma may develop on any
visceral or parietal surface. It is characterized by sheets of
spreading, nodular tissues that infiltrate between lobes, along
fissures, and along diaphragmatic and pericardial surfaces. The tumor
more commonly presents in the lower lobes and tends to be more
extensive inferiorly. The tumor may grow into the peritoneal cavity,
pericardial spaces, or through wounds.
The diagnosis can be suspected because of the characteristic
radiographic findings, but the differential diagnosis also includes
other causes of malignant pleural effusions. Initial misdiagnosis is
common. Pathologic differentiation between the other causes of
malignant pleural effusions can not usually be done by thoracentesis
but requires pleural tissue, obtained either by pleural biopsy or
thoracoscopy. Bronchoscopy is important to exclude endobronchial
disease. The literature on the natural history of malignant
mesothelioma is summarized in Table 1
.
Antman et al1
reviewed the pathologic
diagnoses at the Dana-Farber Cancer Institute between 1965 and 1985 and
found a median survival of 18 months. These authors also found that
good performance status, absence of chest pain, age < 50 years, and
epithelial histology all portended a better survival. Boutin et
al2
analyzed a large French series and found a
median survival of 8.5 months with 1-year and 2-year survivals of 50%
and 25%, respectively. This analysis emphasized the importance of
thoracoscopy in staging and diagnosis. Ruffie et
al3
summarized data from two large centers in
Ontario and Quebec from 1965 to 1984. Their findings were similar to
other analyses; and they reported a median survival of 9 months, and
they found that median survival was better in patients with earlier
disease, no weight loss, and epithelial histology. Finally, Spirtas et
al4
reviewed Surveillance, Epidemiology, and
End Results (SEER) data on 1,475 patients and also found a median
survival of 9 months. These investigators found that age at diagnosis,
gender, stage of disease, type of treatment, and geographic area of
residence were important predictors of patient survival.
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Staging of Mesothelioma
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Butchart et al5
described the first
staging system for diffuse malignant mesothelioma (Table 2)
.
These investigators reported the first large series of
pleuropneumonectomy for mesothelioma and described a hospital mortality
of 31%. Boutin et al emphasized thoracoscopy in the diagnosis and
staging of mesothelioma.2
Sugarbaker and
colleagues6
subsequently proposed a staging
system based on nodal status that combined the stages II and III
defined by Butchart et al into a new stage III and separated stage I
into stages I and II (Table 3)
.6
They identified a 5-year survival of 45% in epithelial histology
patients treated with extrapleural pneumonectomy and postoperative
chemoradiotherapy. Finally, the International Mesothelioma Interest
Group proposed a TNM staging system that also incorporated both tumor
and nodal descriptors.
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Surgical Technique of Pleurectomy
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Pleurectomy in the treatment of malignant mesothelioma includes
the complete decortication of the lung (resection of visceral pleura)
and the parietal pleura. Patients are placed in a full lateral position
after placement of a double-lumen endotracheal tube. A posterolateral
thoracotomy incision is made, completely dividing the latissimus
muscle, and the chest is entered through either the fourth or fifth
interspace. Occasionally, the serratus muscle can be spared, but
usually must also be divided to have adequate access. An additional
eighth or ninth interspace thoracotomy within the same skin incision
may be necessary for adequate exposure of the inferior thorax.
Pleurectomy involves the complete resection of both visceral and
parietal pleura and can include both pericardial and diaphragmatic
resection, as well as resection of additional lung nodules. The
parietal pleura is first dissected off the chest wall and then the
mediastinum. The pleura is then opened and the visceral pleura removed.
Although the procedure can allow extensive debulking, it is not
generally possible to attain complete macroscopic debulking of tumor
with this procedure.
Postoperative management requires good pain management with epidural
catheters, intravenous patient-controlled analgesia, intercostal rib
blocks, or a combination of these maneuvers. Aggressive chest
physiotherapy with early ambulation, incentive spirometry, and other
methods of sputum mobilization are used to prevent atelectasis and
pneumonia. Chest tubes are placed to evacuate both fluid and air.
Sclerosing maneuvers (ie, talc, doxycyline) are often necessary to seal
persistent air leaks.
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Results of Pleurectomy
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Table 4
summarizes the large studies describing results after pleurectomy that
have been reported in the literature. Martini et
al7
reported a series from Memorial
Sloan-Kettering Cancer Center and found an operative mortality of 10%
and perioperative morbidity of 29%. Achatzy et
al8
described 245 patients treated in Germany,
118 of whom underwent either partial or complete pleurectomy. In this
series, the median survival was 9.2 months, with a 5-year survival of
4.1%. The 30-day mortality was 8.5%. These authors noted that the
long-term survival of patients treated nonoperatively (11.4%)
was better than the surgically treated group (2.2%).
Brancatisano et al9
summarized results of 50
patients surgically treated at the Concord and Royal Prince Alfred
Hospital, 45 of whom underwent pleurectomy. One patient died from the
surgery, for a perioperative mortality of 2.2%; surgery-related
morbidity was 16%. The authors described a median survival of 16
months and a 2-year survival of 21%. They also noted that pleurectomy
was very effective in controlling pleural fluid accumulation.
Finally, Soysal et al10
reported a 19-year
series of 100 patients undergoing pleurectomy at Inonu Universitesi
Hospital in Malatya, Turkey. The results of this series suggested that
the procedure was safe (postoperative mortality, 1%; morbidity, 22%)
and resulted in good palliation of symptoms. Postoperative recurrence
of the tumor in the incision was prevented by prophylactic
radiotherapy.
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Pleurectomy and Intrapleural Therapy
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Because mesothelioma usually causes death by local recurrence,
even after resection, efforts at optimizing local control have included
both intraoperative phototherapy and chemotherapy (Table 5)
.
Pass and colleagues11
have studied
intraoperative phototherapy in 78 patients after resection (39 after
pleurectomy, 39 after extrapleural pneumonectomy). In this series, the
overall postoperative mortality and morbidity was 2% and 36%,
respectively. Of 39 patients who underwent extrapleural pneumonectomy,
7 developed bronchopleural fistulae. Pass et
al11
described a slight improvement in
long-term survival in patients who underwent pleurectomy (14.5 months)
compared with those who underwent extrapleural pneumonectomy (9.4
months). The recurrence rate was equivalent in the two procedures, but
one third of recurrences were distant in those patients who underwent
extrapleural pneumonectomy, while only 10% of recurrences were distant
in patients undergoing pleurectomy.
Rusch et al12
described a trial involving
pleurectomy for the treatment of malignant mesothelioma with
intrapleural chemotherapy using cisplatin and mitomycin. The
postoperative mortality was 3.6%, and significant perioperative
morbidity was also reported, especially grade 4 renal toxicity. The
median survival was 17 months, but locoregional relapse occurred in 16
of 20 patients, despite the aggressive regimen designed to optimize
local control.
Takita et al13
14
described results in 31
patients undergoing combined resection and intraoperative phototherapy.
Twenty-three patients underwent pleurectomy followed by intraoperative
phototherapy, while 6 underwent extrapleural pneumonectomy. Fifty
percent of patients suffered some significant postoperative morbidity
(including a 10% bronchopleural fistulae rate), and one of 22 patients
died (mortality rate, 4.5%). The median survival for all patients
after treatment was 12 months; patients with earlier stage (I and II)
disease had a median survival of 21 months.
Sauter and colleagues15
reported a small
series of 13 patients who underwent pleurectomy, followed by treatment
with intrapleural cisplatin and cytarabine as well as subsequent
systemic cisplatin and mitomycin. They reported minimal morbidity (6%)
and no treatment-related mortality. Median survival and time to
progression were significantly longer in patients who did not receive
intrapleural chemotherapy (21 vs 9 months, p = 0.04; 12 vs 6 months,
p = 0.01) compared with those who did.
The addition of intrapleural therapies, whether chemotherapy or
phototherapy, have not demonstrated any significant benefit to date.
Indeed, the overall perioperative morbidity and mortality appear to
have worsened with these therapies. In addition, the study by Sauter et
al15
suggests that intrapleural chemotherapy
may actually decrease long-term survival. Thus, neither of these
therapies should be considered standard.
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Selection of Surgical Procedure in Malignant Pleural
Mesothelioma
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No studies have randomized similarly staged patients to
pleurectomy or extrapleural pneumonectomy (EPP); thus the most
effective surgery for patients with malignant pleural mesothelioma has
not been defined. EPP is a very demanding procedure, and even the
busiest thoracic surgeons perform the procedure rarely unless they work
at a center known for the care of mesothelioma.
Several studies have compared nonrandomized series of patients with
mesothelioma who underwent either pleurectomy or extrapleural
pneumonectomy, depending on the surgeon’s choice. Rusch et al reported
a Lung Cancer Study Group trial in which 20 patients underwent EPP and
63 underwent pleurectomy.16
The postoperative
mortality rate for those undergoing EPP was 15%, while the mortality
rate for those having pleurectomy was not reported. Although there was
no difference in overall survival between the two procedures, there was
significant improvement in disease-free survival for those undergoing
EPP compared with pleurectomy (p = 0.03).
Some data suggest that performing EPP may improve local control but
perhaps predispose to distant spread. The analysis by Pass et
al11
identified a striking difference in the
proportion of distant relapse compared with local relapse for the two
procedures. Ninety percent of recurrences in those undergoing
pleurectomy occurred in the chest, while > 30% of recurrences in
those undergoing EPP occurred distantly.
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Conclusions
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Pleurectomy can be safely performed, and it effectively
controls the symptoms of pleural effusion that develop with malignant
pleural mesothelioma. The addition of postoperative phototherapy or
intrapleural chemotherapy does not improve long-term survival or result
in symptom palliation. Limited data suggest that EPP may give a greater
chance of long-term survival in patients with favorable histology and
earlier stage disease.
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Footnotes
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Abbreviations: EPP = extrapleural pneumonectomy;
SEER = surveillance, epidemiology, and end results
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References
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Antman, K, Shemin, R, Ryan, L, et al (1988) Malignant mesothelioma: prognostic variables in a registry of 180 patients, the Dana-Farber Cancer Institute and Brigham and Women’s Hospital experience over two decades, 1965–1985. J Clin Oncol 6,147-153[Abstract]
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Ruffie, P, Feld, R, Minkin, S, et al (1989) Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients. J Clin Oncol 7,1157-1168[Abstract]
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Spirtas, R, Connelly, RR, Tucker, MA (1988) Survival patterns for malignant mesothelioma: the SEER experience. Int J Cancer 41,525-530[ISI][Medline]
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Butchart, EG, Ashcroft, T, Barnsley, WC, et al (1976) Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax 31,15-24[Abstract]
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Sugarbaker, DJ, Strauss, GM, Lynch, TJ, et al (1993) Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 11,1172-1178[Abstract/Free Full Text]
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Martini, N, Bains, MS, Beattie, EJ, Jr (1975) Indications for pleurectomy in malignant effusions. Cancer 35,734-738[CrossRef][ISI][Medline]
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Achatzy, R, Beba, W, Ritschler, R, et al (1989) The diagnosis, therapy and prognosis of diffuse malignant mesothelioma. Eur J Cardiothorac Surg 3,445-448[Abstract]
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Brancatisano, RP, Joseph, MG, McCaughan, BC (1991) Pleurectomy for mesothelioma. Med J Aust 154,455-460[ISI][Medline]
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Soysal, O, Karaoglanoglu, N, Demiracan, S, et al (1997) Pleurectomy/decortication for palliation in malignant pleural mesothelioma: results of surgery. Eur J Cardiothorac Surg 11,210-213[Abstract]
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Pass, HI, Kranda, K, Temeck, BK, et al (1997) Surgically debulked malignant pleural mesothelioma: results and prognostic factors. Ann Surg Oncol 4,215-222[Abstract]
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Rusch, V, Saltz, L, Venkatraman, E, et al (1994) A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma. J Clin Oncol 12,1156-1163[Abstract/Free Full Text]
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Takita, H, Mang, TS, Loewen, GM, et al (1994) Operation and intracavitary photodynamic therapy for malignant pleural mesothelioma: a phase II study. Ann Thorac Surg 58,995-998[Abstract]
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Abstract
Introduction
