Surgical Management of Malignant Mesothelioma Giacomo A. DeLaria, M.D., Robert Jensik, M.D., L. Penfield Faber, M.D., and C. Frederick Kittle, M.D. ABSTRACT The surgical management of 18 patients diagnosed as having malignant mesothelioma is reviewed. Of these patients, 7 received limited treatment-pleurectomy or biopsy. The mean survival was 10 months, and no patient was disease-free at time of death. The other 11 patients were treated by radical extrapleural pneumonectomy. There were 2 long-term, disease-free survivors at 2 and 4 years. Mean survival for the entire group was 15 months, but most patients received good palliation following tumor removal. Surgical procedures for removal of malignant mesothelioma can be accomplished safely and without major morbidity. When possible, radical extrapleural pneumonectomy affords the best palliation and the only opportunity for cure.
The indications for operative therapy in patients diagnosed as having pleural mesothelioma are uncertain. Most reports are pessimistic and recommend thoracotomy only for isolated lesions or patients for whom a diagnosis cannot be made by less invasive means. Nevertheless, there are occasional instances of long-term survivors following aggressive extirpative operation [4]. The present retrospective review was undertaken in an effort to define a systematic approach to the management of this problem. This series includes all patients with the diagnosis of pleural mesothelioma operated on by one thoracic surgical service over 19 years. Each patient’s chart was examined and selected slides of each were reviewed to confirm the recorded pathological diagnosis. Pathological classification was according to that outlined by Klemperer and Rabin in 1931 [5]. Diffuse or malignant mesoFrom the Department of Cardiovascular-Thoracic Surgery, Rush Cancer Center, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL. Presented at the Fourteenth Annual Meeting of The Society of Thoracic Surgeons, Jan 23-25, 1978, Orlando, FL. Address reprint requests to Dr. DeLaria, RushPresbyterian-St. Luke’s Medical Center, 1753 W Congress Pkwy, Chicago, IL 60612.
theliomas were classified as epithelial, spindle, or mixed cell type.
Material There were 18 patients in the series, divided into 2 groups according to management. All patients, 13 men and 5 women, had diffuse or malignant mesothelioma. The median age was 57 years (32 to 70 years). Careful questioning revealed a definite history of asbestos exposure in only 2 patients. Group 1 Group 1 was comprised of 7 patients who were managed by less radical operations or simple diagnostic procedures (Table 1). Two patients were women and 5 were men. The median age was 64 years. Five patients experienced recurrent effusions and had complete pleurectomy and pulmonary decortication. Two of these patients received, in addition, a course of cobalt radiation therapy to the operated side. One patient had pericardial tamponade and underwent partial pericardiectomy and pneumolysis, which was followed by chemotherapy (5-fluorouracil, methotrexate, and cyclophosphamide); and 1 patient underwent pleural biopsy alone followed by chemotherapy. In this group the average survival was 10 months after operation; 1 patient was lost to follow-up. There was 1 operative mortality subsequent to an acute myocardial infarction 1 week following pleurectomy and decortication. Of 2 patients who survived 20 months, 1 received cobalt irradiation (5,000 rads) and 1 received chemotherapy. All surviving patients were relieved of symptomatic shortness of breath and chest wall pain by pleurectomy. No patient’s postoperative period was complicated by the growth of tumor through the operative wound. Group 2 Group 2 was comprised of 11 patients diagnosed as having malignant mesothelioma, and
375 0003-4975/78/0026-O411$01.25 @ 1978 by Giacomo A. DeLaria
376 The Annals of Thoracic Surgery Vol 26 No 4 October 1978
Table I . Group I : Malignant Mesothelioma Managed by Pleurectomy or Biopsy Patient No., Age (yr), and Sex
Diagnosis
Side
Therapy
Result
1. 64, F
Spindle
L
Minimal pain relief
2. 69, M
Mixed
R
3. 62, F
Epithelial
L
4. 57, M 5. 49, M
Epithelial Spindle
R R
6. 70, M
Epith elia1
L
7. 65, M
Spindle
R
Pleurectomy ; intercostal neurectomy Decortication and pleurectomy, 5,000 rads Pleurectomy ; pericardial window; 5 FU, methotrexate; cyclophosphamide Pleurectomy Pleurectomy ; decortication; nitrogen mustard; cyclophosphamide; BCNU Lung biopsy; cyclophosphamide; 5 FU; methotrexate Pleurectomy ; subsegmentectomy; chest wall resection
Initial relief; progressive d yspnea No recurrence of pericardial tamponade Lost to follow-up No improvement
Excellent palliation Acute postoperative my ocard ia1 infarction
Survival (mo) 6 20 11
2
20
0
5 FU = 5-fluorouracil; BCNU = carmustine.
they were subjected to radical extrapleural pneumonectomy. This group, comprised of 8 men and 3 women, constitute the body of this report. The median age was 53 years. The first operation was done in 1958, and 6 were performed during the past year. The remaining procedures were done between 1958 and 1976 (Table 2). Five tumors were on the left and 6 were on the right; none were bilateral. All patients were seen with chest discomfort, and all were found to have unilateral pleural effusions on chest roentgenogram. Of the 11 patients, 3 were initially treated by thoracotomy and pleurectomy. In 1 of these (Patient 13), a diagnosis of mesothelioma was made at the time of thoracotomy, and she was referred for further therapy. In the 2 remaining patients, thoracotomy and pleurectomy were performed for diagnosis and relief of a recurrent pleural effusion. In both instances, no specific diagnosis was made because the pleural tissue was not diagnostic of malignancy. However, subsequent early return of symptoms and effusion
necessitated a second thoracotomy, at which time the diagnosis of mesothelioma was made and pneumonectomy was completed. Eight patients underwent extrapleural pneumonectomy as initial therapy. Prior to this radical approach, all patients had complete evaluations in an effort to demonstrate metastatic disease or to prove that the pleural disease was not the result of another occult primary tumor. For each patient a complete history was compiled, a complete physical examination and standard laboratory tests were done, and multiple chest roentgenograms were made. Patients with specific organ-system complaints or evidence of blood in the stool or urine were subjected to complete gastrointestinal studies by roentgenogram or intravenous pyelography. All patients had bone and liver scans to rule out metastatic disease. Bronchoscopy was done in the 8 most recent patients, and in none was the study diagnostic. Similarly, thoracentesis was never diagnostic of malignancy, but revealed only sanguineous effusion or nonspecific
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DeLaria et al: Malignant Mesothelioma
Table 2 . Group 2: Malignant Mesothelioma Managed b y EPP Patient No., Age (yr), and Sex
Diagnosis
Side
Therapy
Result
8. 52, M 9. 53, F
Mixed Epithelial
R L
EPP EPP; 2,000 rads
14 36
10. 37, M
Epithelial
R
EPP
11. 59, F
Epithelial
L
12. 51, M
Epithelial
R
EPP; cyclophosphamide EPP
Early improvement Long symptom-free interval Weight loss; little improvement Disease-free
24
13. 32, F
Epithelial
L
Weight gain; disease-free No real improvement
14. 54, M 15. 52, M 16. 58, M
Epithelial Mixed Epithelial
R R L
17. 57, M 18. 53, M
Epithelial Epithelial
L R
Pleurectomy; EPP; daunomycin; vincristine; cyclophosphamide; 5 FU Pleurectomy; EPP Pleurectomy; EPP EPP; cyclophosphamide EPP EPP
Survival (mo)
5
48
6
Died Metastatic disease Metastatic disease
3 9 9
Died Disease-free
4 4
EPP = extrapleural pneumonectomy; 5 FU = 5-fluorouracil.
cytological information. Pleural biopsy was consistent with malignancy in 2 patients and mesothelioma in another. Patients who did not have a preoperative diagnosis of mesothelioma underwent biopsy at the time of thoracotomy. On return of a frozen section with a diagnosis of malignancy from a patient with other characteristics of this disease, such as thick, rubbery pleura and contracted lung, a diagnosis of mesothelioma was made and extrapleural pneumonectomy was undertaken. Prior to 1976, 5 patients in Group 2 were operated on. Two were women, and the median age was 52 years. There were no operative deaths, and the average survival was 22 months. One individual did not benefit from operation and died 5 months later. The procedure afforded good palliation to 2 patients. One of them (Patient 8) experienced weight gain and increased strength but died in l4 months with metastatic disease; and the other (Patient 9) enjoyed a 30-month, symptom-free interval before dying of recurrent mesothelioma 3 years after
Fig 1 . PreOperatiVe posteroanterior chest roentgenogram (915173)of Patient 1 1 who remains free of disease 4 years after extrapleural pneumonectomy. Characteristic pleural thickening with nodularity is seen.
378 The Annals of Thoracic Surgery Vol 26 No 4 October 1978
the initial procedure. At 2 and 4 years after operation, 2 patients have no evidence of recurrent disease and are alive. Both patients had epithelioid tumors and in neither did the diaphragm require resection. The initial chest roentgenogram of the 4-year survivor (Fig 1)is typical for a patient with pleural mesothelioma. During the years 1976 and 1977, 6 patients with the diagnosis of malignant mesothelioma, were operated on, and all underwent extrapleural pneumonectomy. Chest roentgenograms of 3 patients representative of this group are shown in Figure 2. The median age was 52 years and only 1 patient was a woman. There were 3 right and 3 left tumors. One patient, (Patient 13), died of continued spread of the tumor 6 months after the procedure and after repeated hospitalizations. In this instance, residual tumor was left attached to the diaphragm. Of the remaining 5 patients, l died 3 months and another 4 months after operation, and 2 have evidence of recurrent disease at 9 months. One has liver metastases, and the other has an inguinal node with metastatic tumor. Another patient remains disease-free at 4 months. In each patient, every attempt was made to remove all gross tumor. Operative technique was uniform.
Method We prefer to use a posterolateral thoracotomy with incision into the sixth interspace. A tumor biopsy specimen is then obtained. After malignancy is confirmed, care is taken to remain in the extrapleural space as dissection toward the hilum is completed. The pericardial cavity is entered anteriorly if tumor extension has occurred in this direction. The involved pericardium is excised en bloc with the lung and pleura. The hilar structures are divided either intrapericardially or extrapericardially using a stapling technique. Finally, the diaphragm, except for a peripheral rim, is excised and the tumor removed. If free access to the diaphragm in its lateral and posterior extension is unavailable through the first incision, a secFig 2 . Representative chest roentgenograms from this series show the variable appearance of mesothelioma. Multinodular pleural thickening, contracted hemithorax, and pleural effusion are typical of the tumor.
379
DeLaria et al: Malignant Mesothelioma
ond parallel incision in a lower intercostal space is made to improve visualization and ensure complete resection. The diaphragm is then reconstructed with Marlex mesh reinforced with woven Dacron cut from a prosthetic tube graft and sewn to the mesh to make it watertight. All patients survived the operation and were discharged from the hospital. Except for 1 patient whose diaphragm was reconstructed with unreinforced Marlex and in whom ascites developed after operation, there were no complications specific to the procedure. Survivors had initial relief of chest wall pain and shortness of breath.
Illustrative Case Report A 53-year-old white man (Patient 18) sustained an acute myocardial infarction 1 year before admission. He did well for 8 months, at which time he experienced the onset of constant right chest pain. Pain was neither pleuritic nor exertional and remained on the right side. Evaluation at a referring institution included a chest roentgenogram that demonstrated both pleural fluid and thickening. Biopsy of the pleura was consistent with mesothelioma. The patient denied any previous pulmonary problems, and except for occasional cough and chest pain, he was without symptoms or complaints. The patient’s history included smoking seventy-five packs a year and employment in an asbestos factory as a pipe wrapper for a period of 3 to 6 months in 1946. On physical examination, the patient was found to be a well-developed white man in no distress. The examination was entirely normal except for decreased breath sounds over the right hemithorax. There was no lymphadenopathy and the abdomen was without masses or hepatomegaly . However, the fingers did show early clubbing. After admission, the patient was evaluated to rule out metastatic disease. All standard hematological and biochemical tests were normal. Chest roentgenogram confirmed a right pleural effusion with pleural thickening. Fulllung tomograms showed no pulmonary masses on either side. Liver and bone scan were normal, but a gallium scan demonstrated increased uptake over the right hemithorax. Computerized axial tomography of the chest dem-
Fig 3 . Computerized axial tomogram of the chest, demonstrating marked pleural thickening. Other sections confirmed the absence of pulmonary disease.
onstrated an encircling mass in the lower half of the right side of the chest and no parenchymal lesion (Fig 3). On August 31, 1977, the patient underwent right extrapleural pneumonectomy, with resection and replacement of the diaphragm. After operation the patient had no complications and was discharged. He remains active and without evidence of recurrent disease.
Comment Many reviews that attempt to define the clinical characteristics and natural history of pleural mesothelioma have been published. Ehrenhaft and associates [3], in 1960, discussed a series of 16 patients with pleural mesothelioma; 8 of the tumors were benign and 8 were malignant. Survival of patients with malignant tumors averaged 12 months. Similarly, in 1963, Semb [9] reported on an additional 10 patients with malignant mesothelioma. Although this was a postmortem study, a 42-year-old man who had been treated by pleuropneumonectomy survived 4 years. Pathological characteristics of mesothelioma were interpreted in a clinical diagnostic sense by Manfredi and co-workers [7]. The association of pleural fluid with a contracted homolateral hemithorax was considered to be highly suspicious for pleural mesothelioma. We found this noteworthy association in several of our patients, particularly those in whom the tumor had reached massive proportions, compressing the lung and drawing the mediastinurn toward it. The report by Porter and Cheek [81 dealt
380 The Annals of Thoracic Surgery Vol 26 No 4 October 1978
with 12 patients, and the data were collected over 17 years. Eleven of their patients had malignant disease. Average survival from the time of diagnosis was 6 months for the complete operative series. One patient treated with radiation therapy lived for 8 years. In 1975, Shearin and Jackson [lo] reported on 19 patients with malignant mesothelioma. The data on this series were collected over a 14-year period. Mean survival in this group was 10 months. No patient received extrapleural pneumonectomy, but the longest survivor (43 months) was a man who underwent decortication and partial pulmonary resection. A pessimistic view was presented by Taryle and associates [ll]. Patients in their series received either no treatment or radiation therapy and chemotherapy, alone or in combination. Average survival was 11 months, and no patient was disease-free at the time of observation. Thoracotomy was recommended only for diagnosis. The importance of early, certain diagnosis to avoid unnecessary operation was stressed. Kovarik [6] contributed data on an additional 9 patients. Of these, 1individual had recurrence of tumor 7 years following complete resection of a histologically benign fibrous mesothelioma. This aggressive behavior in a benign tumor has been documented in earlier reports by Clagett [2] and Utley [12] and their co-workers. The mean survival in the group with malignant disease was only 9 months. The largest recent review (66 patients) originated from the Memorial-Sloan Kettering Cancer Center and was reported by Wanebo and colleagues [13]. The diagnoses of malignancy were divided into two categories according to tissue type, epithelial or fibrosarcomatous mesothelioma, and were discussed separately. In the first group were 39 patients. Survival in the operatively treated patients averaged 28 months, and 4 were disease-free at 21,32,53, and 69 months, respectively. Radiation alone rendered no patient tumor-free, and average survival was only 13 months. The remaining patients all died of the disease in less than a year. The 27 patients in the second group had fibrosarcomatous tumors, and 16 underwent resection. The average survival was reduced to 17 months, but 3 patients were
disease-free at the time of analysis. From these data it was recommended that operative removal of the pleura, when possible, in combination with external irradiation and chemotherapy provided the best expectation of success in patients with this disease. This concept of aggressive surgical therapy of the tumor was brought into focus in 1976 in a review of 29 patients treated with pleuropneumonectomy for malignant mesothelioma by Butchart and co-workers [l]. The series demonstrated a high hospital mortality of 31% and a complication rate of 43%, and only 3 patients survived longer than 2 years. However, careful analysis of the data suggested that better postoperative management and improved patient selection could well have improved the results. In particular, the authors concluded that if patients chosen for pleuropneumonectomy were less than 60 years old, had no major systemic disease, and had tumors of the epithelial type, the risk of the operation was justified. Our own series of 11patients undergoing extrapleural pneumonectomy may support that view. Utilizing well-known techniques of intraoperative and postoperative care, we have had no intraoperative mortalities, and all patients have survived hospitalization. The safe technical possibility of the procedure has been established; its ultimate effect on the natural history of this disease remains to be determined. Nevertheless, careful review of the literature reveals isolated instances of long-term, disease-free survivors, all of whom have had resective operation for mesothelioma. On this basis, it is possible to presume that a safely performed operation that removes the entire tumor has strong expectations of improving the survival of and perhaps curing the individual with malignant pleural mesothelioma. Our 2 longterm, disease-free survivors at 2 and 4 years support this view. However, the rapid death or recurrence of disease in 5 of our most recent patients suggests otherwise and underscores the dismal prognosis of malignant mesothelioma. Palliation can be achieved in the patient with malignant mesothelioma by extrapleural pneumonectomy. A tumor that fails to respond to radiation therapy or chemotherapy continues to enlarge in the thoracic cavity. The massive bulk of the tumor compresses the in-
381 DeLaria et al: Malignant Mesothelioma
volved lung a n d pushes the mediastinum to the contralateral side, compromising function of the opposite lung. The compressed lung is ventilated poorly a n d left-to-right shunts appear, further decreasing arterial oxygen saturation. Slow, b u t progressive, chest discomfort and pain require increasing amounts of narcotics. Thus a n operative procedure that can alleviate these symptoms a n d physiological abnormalities w i t h minimal operative risk is of benefit to the patient, even though chances of cure are small. For these reasons, we make the following recommendations for the management of this group of patients.
1. Malignant pleural mesothelioma should not be considered a n inoperable disease. 2. Patients suspected of having malignant mesothelioma should undergo complete evaluation by nuclear scan, roentgenography, a n d other currently available diagnostic techniques to eliminate the possibility of metastatic disease. 3. Patients without extrapulmonary disease w h o are judged clinically able to tolerate radical surgery should have thoracotomy for tiss u e diagnosis a n d extrapleural pneumonectomy. If possible, all tumor-bearing tissue m u s t be resected, including the diaphragm a n d pericardium, a n d reconstruction is accomplished a s described. 4. The importance of tissue type to survival of the patient after successful extrapleural pneumonectomy is n o t known, a n d for this reason it should not be used at this time in patient selection for this type of operation. However, the results both in o u r patients a n d in series reported by others suggest that the pure epithelial tumor is the more favorable lesion.
References 1. Butchart EG, Ashcroft, A, Barnsley WC, et al: Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Thorax 31:15, 1976 2. Clagett OT, McDonald JD, Schmidt HW: Localized fibrous mesotheliomas of the pleura. J Thorac Surg 24:213, 1952 3. Ehrenhaft JL, Sensenig DM, Lawrence MS:
Mesotheliomas of the pleura. J Thorac Cardiovasc Surg 40:393, 1960 4. Elmes PC, Simpson MJC: The clinical aspects of mesothelioma. Q J Med 45:427, 1976 5. Klemperer P, Rabin CB: Primary neoplasm of the pleura. Arch Pathol 11:385, 1931 6. Kovarik JL: Primary pleural mesothelioma. Cancer 38:1816, 1976 7. Manfredi R, Rosenbaum D, Childress RH: Diffuse malignant mesothelioma of the pleura. Am Rev Respir Dis 92:269, 1965 8. Porter JM, Cheek JM: Pleural mesothelioma. J Thorac Cardiovasc Surg 55:882, 1968 9. Semb G: Diffuse malignant pleural mesothelioma. Acta Chir Scand 126:78, 1963 10. Shearin JC, Jackson D: Malignant pleural mesothelioma. J Thorac Cardiovasc Surg 71:621, 1976 11. Taryle DA, Lakshminarayan S, Sahn SA: Pleural mesotheliomas. Medicine 55:153, 1976 12. Utley JR, Parker JC, Hahn RS, et al: Recurrent benign fibrous mesothelioma of the pleura. J Thorac Cardiovasc Surg 65:830, 1973 13. Wanebo HJ, Martini N, Melamed MR, et al: Pleural mesothelioma. Cancer 38:2481, 1976
Discussion DR. EDWARD J. BEATTIE, JR (New York, NY): We certainly agree that mesothelioma is a most serious disease requiring further study and aggressive management. I think it is important to stress that there are two types of this disease: localized and diffuse. The patients with the localized type can be surgically cured. Those with the diffuse type are the problem. In our surgical attack, we have not resected the diaphragm as the authors have done, but from the patients I have seen I think it would be very difficult to remove all gross disease. Frequently, the disease goes through the costal pleura. Time will show whether these patients are cured. In 1976, we reported on 33 patients with mesothelioma. Only 2 of these patients lived 5 years. We gave up resecting lung tissue because we believed that this procedure resulted in shortness of breath as time went by. More recently we have treated patients with mesothelioma with decortication, tumor excision, and pleurectomy to control the effusion and followed up with internal-external radiotherapy and prolonged chemotherapy. We believe this treatment prolongs useful life. I will quickly summarize two interesting case histories. One man with diffuse mesothelioma was first explored in August, 1966. He was treated with pleurectomy, internal radiotherapy, subsequent external radiotherapy, and chemotherapy. The right chest finally opacified, but he lived 61/4 years. The second history indicates that the localized form of the disease may be aggressive, too. The patient, a man, had a paraspinal mesothelioma resected
382 The Annals of Thoracic Surgery Vol 26 No 4 October 1978
in 1961. Ten years later metastasis in the fifth thoracic vertebra was removed with bilateral thoracotomy. A fibular graft was used. Sixteen years after the original operation and 6 years after the spine operation, the patient is still alive. He has had two additional operations for local recurrent fibrosarcomatous mesothelioma. I agree with the authors that an aggressive approach is indicated, but I suspect that even with a radical operation we need better adjuvants. (Staten Island, NY): I wish to congratulate the authors and summarize my experience with pleural mesothelioma. In the past 10 years I have operated on 7 patients with pleural mesothelioma. The procedure consisted of resection of the tumor, including the underlying lung parenchyma. I performed 4 lobectomies, 2 pneumonectomies, and 1 local excision of a very large mesothelioma attached to the parietal pleura. Generally, the extent of the resection was tailored to the size of the tumor. Only 1 patient with a lobectomy survived 11/2 years. On the contrary, 1patient with a pneumonectomy is alive 7 years after the operation and, at the present time, has recurrence of the tumor in the peritoneal cavity. The other patient who underwent pneumonectomy has lived for 3 years after the procedure without evidence of recurrence, and the patient who had simple excision of the mesothelioma is well 2 years later. The factor common to these patients is that they all had large tumors, weighing more than 3 kg each. It may be that tumors that reach this size are less aggressive than smaller lesions. I emphasize two points: that the behavior of pleural mesothelioma is difficult to predict by the histological patterns and that lesions that are quite large have, in my experience, a better prognosis than smaller ones. I ask the authors of the paper to comment on this latter point.
DR. ANTONIO A. GARZON
surement of hyaluronic acid in the pleural fluid or in the tissue. I wonder if the authors have any information or experience with this. If such a biochemical method is accurate, it would allow block dissection without the necessity of entering the tumor for the purpose of biopsy. Please expand a little more on what you do with the diaphragm. If you remove it completely, how do you repair the defect? DR. AGUSTIN ARBULU (Detroit, MI): Recently we had a patient who was seen with malignant mesothelioma. After failing to make a diagnosis, we undertook pleurectomy and decortication. The results were not successful. The patient is still alive, but she now has edema of the breast, which we considered for a while to be an inflammatory carcinoma of the breast. I wonder if the authors would consider using their approach for this type of patient.
I thank all of the discussants. Regarding Dr. Beattie’s questions, in patients on whom we have operated, there has been no growth of the tumor through the chest wall. Instead, the tumor surface has imprints of the ribs. Those imprints were produced by the pressure of tumor growth against the chest wall. We believe that in the patients in whom we performed extrapleuralpneumonectomy, lung salvage was not possible. The mesothelioma covers the lung, compressing and contracting it. For this reason and with the expectation of better long-term control we think it preferable to remove the entire lung. Dr. Garzon, we are pleased that you also have had a positive experience with malignant mesothelioma. I think the fact that you have 3 patients who have lived a relatively long time is very encouraging. Dr. Johnston, I think you speak to what is a commonly held opinion about mesothelioma, and I agree that the experience of most surgeons with it has been dismal. Fortunately, despite biopsies and thoracotomy incisions, none of our patients has shown tumor growth through the wound and none DR. FRANK R. JOHNSTON (Winston-Salem, NC): Over the years, we have had experience with 19 patients has complained of incisional chest wall pain. We have not measured the hyaluronic acid and with diffuse pleural mesothelioma. The experience has been bad uniformly. In fact, I believe that most of have no experience with that procedure. We do excise the diaphragm when it is necessary. these patients would have been better off if they had not seen a surgeon at all. The tumor seems to have a Butchart and colleagues thought this an important predilection for biopsy wounds, needle biopsy aspect of the operation, and we agree. As the lung tracts, and the chest wall, and results in increased and tumor are mobilized, the diaphragm is removed, pain and discomfort. One patient who had a left leaving a rim for attachment of a Marlex mesh reinlower lobectomy and partial pleurectomy survived 4 forced with Dacron. The Dacron reinforcement is years. Some years ago we wondered about the possi- important because ascites may develop from bility of an en bloc dissection of pleura, lung, and pneumonectomy fluid going across the Marlex mesh. Regarding Dr. Arbulu’s question, if his patient did part of chest wall but became discouraged after readnot have inflammatory carcinoma of the breast, we ing the reports of those who had tried it. The experience of Dr. DeLaria, as reported today, would recommend extrapleural pneumonectomy. We suggests that in some instances radical operation have had 3 patients in whom biopsy was negative and pleurectomy was not diagnostic. At a submay be worthwhile. The Japanese and Europeans have been interested sequent procedure, the diagnosis was mesothelioma, in the biochemical diagnosis of this lesion by mea- and completion pneumonectomy was performed. DR. DB LARIA:
The indications for operative therapy in patients diagnosed as having pleural mesothelioma are uncertain. Most reports are pessimistic and recommend thoracotomy only for isolated lesions or patients for whom a diagnosis cannot be made by less invasive means. Nevertheless, there are occasional instances of long-term survivors following aggressive extirpative operation [4]. The present retrospective review was undertaken in an effort to define a systematic approach to the management of this problem. This series includes all patients with the diagnosis of pleural mesothelioma operated on by one thoracic surgical service over 19 years. Each patient’s chart was examined and selected slides of each were reviewed to confirm the recorded pathological diagnosis. Pathological classification was according to that outlined by Klemperer and Rabin in 1931 [5]. Diffuse or malignant mesoFrom the Department of Cardiovascular-Thoracic Surgery, Rush Cancer Center, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL. Presented at the Fourteenth Annual Meeting of The Society of Thoracic Surgeons, Jan 23-25, 1978, Orlando, FL. Address reprint requests to Dr. DeLaria, RushPresbyterian-St. Luke’s Medical Center, 1753 W Congress Pkwy, Chicago, IL 60612.
theliomas were classified as epithelial, spindle, or mixed cell type.
Material There were 18 patients in the series, divided into 2 groups according to management. All patients, 13 men and 5 women, had diffuse or malignant mesothelioma. The median age was 57 years (32 to 70 years). Careful questioning revealed a definite history of asbestos exposure in only 2 patients. Group 1 Group 1 was comprised of 7 patients who were managed by less radical operations or simple diagnostic procedures (Table 1). Two patients were women and 5 were men. The median age was 64 years. Five patients experienced recurrent effusions and had complete pleurectomy and pulmonary decortication. Two of these patients received, in addition, a course of cobalt radiation therapy to the operated side. One patient had pericardial tamponade and underwent partial pericardiectomy and pneumolysis, which was followed by chemotherapy (5-fluorouracil, methotrexate, and cyclophosphamide); and 1 patient underwent pleural biopsy alone followed by chemotherapy. In this group the average survival was 10 months after operation; 1 patient was lost to follow-up. There was 1 operative mortality subsequent to an acute myocardial infarction 1 week following pleurectomy and decortication. Of 2 patients who survived 20 months, 1 received cobalt irradiation (5,000 rads) and 1 received chemotherapy. All surviving patients were relieved of symptomatic shortness of breath and chest wall pain by pleurectomy. No patient’s postoperative period was complicated by the growth of tumor through the operative wound. Group 2 Group 2 was comprised of 11 patients diagnosed as having malignant mesothelioma, and
375 0003-4975/78/0026-O411$01.25 @ 1978 by Giacomo A. DeLaria
376 The Annals of Thoracic Surgery Vol 26 No 4 October 1978
Table I . Group I : Malignant Mesothelioma Managed by Pleurectomy or Biopsy Patient No., Age (yr), and Sex
Diagnosis
Side
Therapy
Result
1. 64, F
Spindle
L
Minimal pain relief
2. 69, M
Mixed
R
3. 62, F
Epithelial
L
4. 57, M 5. 49, M
Epithelial Spindle
R R
6. 70, M
Epith elia1
L
7. 65, M
Spindle
R
Pleurectomy ; intercostal neurectomy Decortication and pleurectomy, 5,000 rads Pleurectomy ; pericardial window; 5 FU, methotrexate; cyclophosphamide Pleurectomy Pleurectomy ; decortication; nitrogen mustard; cyclophosphamide; BCNU Lung biopsy; cyclophosphamide; 5 FU; methotrexate Pleurectomy ; subsegmentectomy; chest wall resection
Initial relief; progressive d yspnea No recurrence of pericardial tamponade Lost to follow-up No improvement
Excellent palliation Acute postoperative my ocard ia1 infarction
Survival (mo) 6 20 11
2
20
0
5 FU = 5-fluorouracil; BCNU = carmustine.
they were subjected to radical extrapleural pneumonectomy. This group, comprised of 8 men and 3 women, constitute the body of this report. The median age was 53 years. The first operation was done in 1958, and 6 were performed during the past year. The remaining procedures were done between 1958 and 1976 (Table 2). Five tumors were on the left and 6 were on the right; none were bilateral. All patients were seen with chest discomfort, and all were found to have unilateral pleural effusions on chest roentgenogram. Of the 11 patients, 3 were initially treated by thoracotomy and pleurectomy. In 1 of these (Patient 13), a diagnosis of mesothelioma was made at the time of thoracotomy, and she was referred for further therapy. In the 2 remaining patients, thoracotomy and pleurectomy were performed for diagnosis and relief of a recurrent pleural effusion. In both instances, no specific diagnosis was made because the pleural tissue was not diagnostic of malignancy. However, subsequent early return of symptoms and effusion
necessitated a second thoracotomy, at which time the diagnosis of mesothelioma was made and pneumonectomy was completed. Eight patients underwent extrapleural pneumonectomy as initial therapy. Prior to this radical approach, all patients had complete evaluations in an effort to demonstrate metastatic disease or to prove that the pleural disease was not the result of another occult primary tumor. For each patient a complete history was compiled, a complete physical examination and standard laboratory tests were done, and multiple chest roentgenograms were made. Patients with specific organ-system complaints or evidence of blood in the stool or urine were subjected to complete gastrointestinal studies by roentgenogram or intravenous pyelography. All patients had bone and liver scans to rule out metastatic disease. Bronchoscopy was done in the 8 most recent patients, and in none was the study diagnostic. Similarly, thoracentesis was never diagnostic of malignancy, but revealed only sanguineous effusion or nonspecific
377
DeLaria et al: Malignant Mesothelioma
Table 2 . Group 2: Malignant Mesothelioma Managed b y EPP Patient No., Age (yr), and Sex
Diagnosis
Side
Therapy
Result
8. 52, M 9. 53, F
Mixed Epithelial
R L
EPP EPP; 2,000 rads
14 36
10. 37, M
Epithelial
R
EPP
11. 59, F
Epithelial
L
12. 51, M
Epithelial
R
EPP; cyclophosphamide EPP
Early improvement Long symptom-free interval Weight loss; little improvement Disease-free
24
13. 32, F
Epithelial
L
Weight gain; disease-free No real improvement
14. 54, M 15. 52, M 16. 58, M
Epithelial Mixed Epithelial
R R L
17. 57, M 18. 53, M
Epithelial Epithelial
L R
Pleurectomy; EPP; daunomycin; vincristine; cyclophosphamide; 5 FU Pleurectomy; EPP Pleurectomy; EPP EPP; cyclophosphamide EPP EPP
Survival (mo)
5
48
6
Died Metastatic disease Metastatic disease
3 9 9
Died Disease-free
4 4
EPP = extrapleural pneumonectomy; 5 FU = 5-fluorouracil.
cytological information. Pleural biopsy was consistent with malignancy in 2 patients and mesothelioma in another. Patients who did not have a preoperative diagnosis of mesothelioma underwent biopsy at the time of thoracotomy. On return of a frozen section with a diagnosis of malignancy from a patient with other characteristics of this disease, such as thick, rubbery pleura and contracted lung, a diagnosis of mesothelioma was made and extrapleural pneumonectomy was undertaken. Prior to 1976, 5 patients in Group 2 were operated on. Two were women, and the median age was 52 years. There were no operative deaths, and the average survival was 22 months. One individual did not benefit from operation and died 5 months later. The procedure afforded good palliation to 2 patients. One of them (Patient 8) experienced weight gain and increased strength but died in l4 months with metastatic disease; and the other (Patient 9) enjoyed a 30-month, symptom-free interval before dying of recurrent mesothelioma 3 years after
Fig 1 . PreOperatiVe posteroanterior chest roentgenogram (915173)of Patient 1 1 who remains free of disease 4 years after extrapleural pneumonectomy. Characteristic pleural thickening with nodularity is seen.
378 The Annals of Thoracic Surgery Vol 26 No 4 October 1978
the initial procedure. At 2 and 4 years after operation, 2 patients have no evidence of recurrent disease and are alive. Both patients had epithelioid tumors and in neither did the diaphragm require resection. The initial chest roentgenogram of the 4-year survivor (Fig 1)is typical for a patient with pleural mesothelioma. During the years 1976 and 1977, 6 patients with the diagnosis of malignant mesothelioma, were operated on, and all underwent extrapleural pneumonectomy. Chest roentgenograms of 3 patients representative of this group are shown in Figure 2. The median age was 52 years and only 1 patient was a woman. There were 3 right and 3 left tumors. One patient, (Patient 13), died of continued spread of the tumor 6 months after the procedure and after repeated hospitalizations. In this instance, residual tumor was left attached to the diaphragm. Of the remaining 5 patients, l died 3 months and another 4 months after operation, and 2 have evidence of recurrent disease at 9 months. One has liver metastases, and the other has an inguinal node with metastatic tumor. Another patient remains disease-free at 4 months. In each patient, every attempt was made to remove all gross tumor. Operative technique was uniform.
Method We prefer to use a posterolateral thoracotomy with incision into the sixth interspace. A tumor biopsy specimen is then obtained. After malignancy is confirmed, care is taken to remain in the extrapleural space as dissection toward the hilum is completed. The pericardial cavity is entered anteriorly if tumor extension has occurred in this direction. The involved pericardium is excised en bloc with the lung and pleura. The hilar structures are divided either intrapericardially or extrapericardially using a stapling technique. Finally, the diaphragm, except for a peripheral rim, is excised and the tumor removed. If free access to the diaphragm in its lateral and posterior extension is unavailable through the first incision, a secFig 2 . Representative chest roentgenograms from this series show the variable appearance of mesothelioma. Multinodular pleural thickening, contracted hemithorax, and pleural effusion are typical of the tumor.
379
DeLaria et al: Malignant Mesothelioma
ond parallel incision in a lower intercostal space is made to improve visualization and ensure complete resection. The diaphragm is then reconstructed with Marlex mesh reinforced with woven Dacron cut from a prosthetic tube graft and sewn to the mesh to make it watertight. All patients survived the operation and were discharged from the hospital. Except for 1 patient whose diaphragm was reconstructed with unreinforced Marlex and in whom ascites developed after operation, there were no complications specific to the procedure. Survivors had initial relief of chest wall pain and shortness of breath.
Illustrative Case Report A 53-year-old white man (Patient 18) sustained an acute myocardial infarction 1 year before admission. He did well for 8 months, at which time he experienced the onset of constant right chest pain. Pain was neither pleuritic nor exertional and remained on the right side. Evaluation at a referring institution included a chest roentgenogram that demonstrated both pleural fluid and thickening. Biopsy of the pleura was consistent with mesothelioma. The patient denied any previous pulmonary problems, and except for occasional cough and chest pain, he was without symptoms or complaints. The patient’s history included smoking seventy-five packs a year and employment in an asbestos factory as a pipe wrapper for a period of 3 to 6 months in 1946. On physical examination, the patient was found to be a well-developed white man in no distress. The examination was entirely normal except for decreased breath sounds over the right hemithorax. There was no lymphadenopathy and the abdomen was without masses or hepatomegaly . However, the fingers did show early clubbing. After admission, the patient was evaluated to rule out metastatic disease. All standard hematological and biochemical tests were normal. Chest roentgenogram confirmed a right pleural effusion with pleural thickening. Fulllung tomograms showed no pulmonary masses on either side. Liver and bone scan were normal, but a gallium scan demonstrated increased uptake over the right hemithorax. Computerized axial tomography of the chest dem-
Fig 3 . Computerized axial tomogram of the chest, demonstrating marked pleural thickening. Other sections confirmed the absence of pulmonary disease.
onstrated an encircling mass in the lower half of the right side of the chest and no parenchymal lesion (Fig 3). On August 31, 1977, the patient underwent right extrapleural pneumonectomy, with resection and replacement of the diaphragm. After operation the patient had no complications and was discharged. He remains active and without evidence of recurrent disease.
Comment Many reviews that attempt to define the clinical characteristics and natural history of pleural mesothelioma have been published. Ehrenhaft and associates [3], in 1960, discussed a series of 16 patients with pleural mesothelioma; 8 of the tumors were benign and 8 were malignant. Survival of patients with malignant tumors averaged 12 months. Similarly, in 1963, Semb [9] reported on an additional 10 patients with malignant mesothelioma. Although this was a postmortem study, a 42-year-old man who had been treated by pleuropneumonectomy survived 4 years. Pathological characteristics of mesothelioma were interpreted in a clinical diagnostic sense by Manfredi and co-workers [7]. The association of pleural fluid with a contracted homolateral hemithorax was considered to be highly suspicious for pleural mesothelioma. We found this noteworthy association in several of our patients, particularly those in whom the tumor had reached massive proportions, compressing the lung and drawing the mediastinurn toward it. The report by Porter and Cheek [81 dealt
380 The Annals of Thoracic Surgery Vol 26 No 4 October 1978
with 12 patients, and the data were collected over 17 years. Eleven of their patients had malignant disease. Average survival from the time of diagnosis was 6 months for the complete operative series. One patient treated with radiation therapy lived for 8 years. In 1975, Shearin and Jackson [lo] reported on 19 patients with malignant mesothelioma. The data on this series were collected over a 14-year period. Mean survival in this group was 10 months. No patient received extrapleural pneumonectomy, but the longest survivor (43 months) was a man who underwent decortication and partial pulmonary resection. A pessimistic view was presented by Taryle and associates [ll]. Patients in their series received either no treatment or radiation therapy and chemotherapy, alone or in combination. Average survival was 11 months, and no patient was disease-free at the time of observation. Thoracotomy was recommended only for diagnosis. The importance of early, certain diagnosis to avoid unnecessary operation was stressed. Kovarik [6] contributed data on an additional 9 patients. Of these, 1individual had recurrence of tumor 7 years following complete resection of a histologically benign fibrous mesothelioma. This aggressive behavior in a benign tumor has been documented in earlier reports by Clagett [2] and Utley [12] and their co-workers. The mean survival in the group with malignant disease was only 9 months. The largest recent review (66 patients) originated from the Memorial-Sloan Kettering Cancer Center and was reported by Wanebo and colleagues [13]. The diagnoses of malignancy were divided into two categories according to tissue type, epithelial or fibrosarcomatous mesothelioma, and were discussed separately. In the first group were 39 patients. Survival in the operatively treated patients averaged 28 months, and 4 were disease-free at 21,32,53, and 69 months, respectively. Radiation alone rendered no patient tumor-free, and average survival was only 13 months. The remaining patients all died of the disease in less than a year. The 27 patients in the second group had fibrosarcomatous tumors, and 16 underwent resection. The average survival was reduced to 17 months, but 3 patients were
disease-free at the time of analysis. From these data it was recommended that operative removal of the pleura, when possible, in combination with external irradiation and chemotherapy provided the best expectation of success in patients with this disease. This concept of aggressive surgical therapy of the tumor was brought into focus in 1976 in a review of 29 patients treated with pleuropneumonectomy for malignant mesothelioma by Butchart and co-workers [l]. The series demonstrated a high hospital mortality of 31% and a complication rate of 43%, and only 3 patients survived longer than 2 years. However, careful analysis of the data suggested that better postoperative management and improved patient selection could well have improved the results. In particular, the authors concluded that if patients chosen for pleuropneumonectomy were less than 60 years old, had no major systemic disease, and had tumors of the epithelial type, the risk of the operation was justified. Our own series of 11patients undergoing extrapleural pneumonectomy may support that view. Utilizing well-known techniques of intraoperative and postoperative care, we have had no intraoperative mortalities, and all patients have survived hospitalization. The safe technical possibility of the procedure has been established; its ultimate effect on the natural history of this disease remains to be determined. Nevertheless, careful review of the literature reveals isolated instances of long-term, disease-free survivors, all of whom have had resective operation for mesothelioma. On this basis, it is possible to presume that a safely performed operation that removes the entire tumor has strong expectations of improving the survival of and perhaps curing the individual with malignant pleural mesothelioma. Our 2 longterm, disease-free survivors at 2 and 4 years support this view. However, the rapid death or recurrence of disease in 5 of our most recent patients suggests otherwise and underscores the dismal prognosis of malignant mesothelioma. Palliation can be achieved in the patient with malignant mesothelioma by extrapleural pneumonectomy. A tumor that fails to respond to radiation therapy or chemotherapy continues to enlarge in the thoracic cavity. The massive bulk of the tumor compresses the in-
381 DeLaria et al: Malignant Mesothelioma
volved lung a n d pushes the mediastinum to the contralateral side, compromising function of the opposite lung. The compressed lung is ventilated poorly a n d left-to-right shunts appear, further decreasing arterial oxygen saturation. Slow, b u t progressive, chest discomfort and pain require increasing amounts of narcotics. Thus a n operative procedure that can alleviate these symptoms a n d physiological abnormalities w i t h minimal operative risk is of benefit to the patient, even though chances of cure are small. For these reasons, we make the following recommendations for the management of this group of patients.
1. Malignant pleural mesothelioma should not be considered a n inoperable disease. 2. Patients suspected of having malignant mesothelioma should undergo complete evaluation by nuclear scan, roentgenography, a n d other currently available diagnostic techniques to eliminate the possibility of metastatic disease. 3. Patients without extrapulmonary disease w h o are judged clinically able to tolerate radical surgery should have thoracotomy for tiss u e diagnosis a n d extrapleural pneumonectomy. If possible, all tumor-bearing tissue m u s t be resected, including the diaphragm a n d pericardium, a n d reconstruction is accomplished a s described. 4. The importance of tissue type to survival of the patient after successful extrapleural pneumonectomy is n o t known, a n d for this reason it should not be used at this time in patient selection for this type of operation. However, the results both in o u r patients a n d in series reported by others suggest that the pure epithelial tumor is the more favorable lesion.
References 1. Butchart EG, Ashcroft, A, Barnsley WC, et al: Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Thorax 31:15, 1976 2. Clagett OT, McDonald JD, Schmidt HW: Localized fibrous mesotheliomas of the pleura. J Thorac Surg 24:213, 1952 3. Ehrenhaft JL, Sensenig DM, Lawrence MS:
Mesotheliomas of the pleura. J Thorac Cardiovasc Surg 40:393, 1960 4. Elmes PC, Simpson MJC: The clinical aspects of mesothelioma. Q J Med 45:427, 1976 5. Klemperer P, Rabin CB: Primary neoplasm of the pleura. Arch Pathol 11:385, 1931 6. Kovarik JL: Primary pleural mesothelioma. Cancer 38:1816, 1976 7. Manfredi R, Rosenbaum D, Childress RH: Diffuse malignant mesothelioma of the pleura. Am Rev Respir Dis 92:269, 1965 8. Porter JM, Cheek JM: Pleural mesothelioma. J Thorac Cardiovasc Surg 55:882, 1968 9. Semb G: Diffuse malignant pleural mesothelioma. Acta Chir Scand 126:78, 1963 10. Shearin JC, Jackson D: Malignant pleural mesothelioma. J Thorac Cardiovasc Surg 71:621, 1976 11. Taryle DA, Lakshminarayan S, Sahn SA: Pleural mesotheliomas. Medicine 55:153, 1976 12. Utley JR, Parker JC, Hahn RS, et al: Recurrent benign fibrous mesothelioma of the pleura. J Thorac Cardiovasc Surg 65:830, 1973 13. Wanebo HJ, Martini N, Melamed MR, et al: Pleural mesothelioma. Cancer 38:2481, 1976
Discussion DR. EDWARD J. BEATTIE, JR (New York, NY): We certainly agree that mesothelioma is a most serious disease requiring further study and aggressive management. I think it is important to stress that there are two types of this disease: localized and diffuse. The patients with the localized type can be surgically cured. Those with the diffuse type are the problem. In our surgical attack, we have not resected the diaphragm as the authors have done, but from the patients I have seen I think it would be very difficult to remove all gross disease. Frequently, the disease goes through the costal pleura. Time will show whether these patients are cured. In 1976, we reported on 33 patients with mesothelioma. Only 2 of these patients lived 5 years. We gave up resecting lung tissue because we believed that this procedure resulted in shortness of breath as time went by. More recently we have treated patients with mesothelioma with decortication, tumor excision, and pleurectomy to control the effusion and followed up with internal-external radiotherapy and prolonged chemotherapy. We believe this treatment prolongs useful life. I will quickly summarize two interesting case histories. One man with diffuse mesothelioma was first explored in August, 1966. He was treated with pleurectomy, internal radiotherapy, subsequent external radiotherapy, and chemotherapy. The right chest finally opacified, but he lived 61/4 years. The second history indicates that the localized form of the disease may be aggressive, too. The patient, a man, had a paraspinal mesothelioma resected
382 The Annals of Thoracic Surgery Vol 26 No 4 October 1978
in 1961. Ten years later metastasis in the fifth thoracic vertebra was removed with bilateral thoracotomy. A fibular graft was used. Sixteen years after the original operation and 6 years after the spine operation, the patient is still alive. He has had two additional operations for local recurrent fibrosarcomatous mesothelioma. I agree with the authors that an aggressive approach is indicated, but I suspect that even with a radical operation we need better adjuvants. (Staten Island, NY): I wish to congratulate the authors and summarize my experience with pleural mesothelioma. In the past 10 years I have operated on 7 patients with pleural mesothelioma. The procedure consisted of resection of the tumor, including the underlying lung parenchyma. I performed 4 lobectomies, 2 pneumonectomies, and 1 local excision of a very large mesothelioma attached to the parietal pleura. Generally, the extent of the resection was tailored to the size of the tumor. Only 1 patient with a lobectomy survived 11/2 years. On the contrary, 1patient with a pneumonectomy is alive 7 years after the operation and, at the present time, has recurrence of the tumor in the peritoneal cavity. The other patient who underwent pneumonectomy has lived for 3 years after the procedure without evidence of recurrence, and the patient who had simple excision of the mesothelioma is well 2 years later. The factor common to these patients is that they all had large tumors, weighing more than 3 kg each. It may be that tumors that reach this size are less aggressive than smaller lesions. I emphasize two points: that the behavior of pleural mesothelioma is difficult to predict by the histological patterns and that lesions that are quite large have, in my experience, a better prognosis than smaller ones. I ask the authors of the paper to comment on this latter point.
DR. ANTONIO A. GARZON
surement of hyaluronic acid in the pleural fluid or in the tissue. I wonder if the authors have any information or experience with this. If such a biochemical method is accurate, it would allow block dissection without the necessity of entering the tumor for the purpose of biopsy. Please expand a little more on what you do with the diaphragm. If you remove it completely, how do you repair the defect? DR. AGUSTIN ARBULU (Detroit, MI): Recently we had a patient who was seen with malignant mesothelioma. After failing to make a diagnosis, we undertook pleurectomy and decortication. The results were not successful. The patient is still alive, but she now has edema of the breast, which we considered for a while to be an inflammatory carcinoma of the breast. I wonder if the authors would consider using their approach for this type of patient.
I thank all of the discussants. Regarding Dr. Beattie’s questions, in patients on whom we have operated, there has been no growth of the tumor through the chest wall. Instead, the tumor surface has imprints of the ribs. Those imprints were produced by the pressure of tumor growth against the chest wall. We believe that in the patients in whom we performed extrapleuralpneumonectomy, lung salvage was not possible. The mesothelioma covers the lung, compressing and contracting it. For this reason and with the expectation of better long-term control we think it preferable to remove the entire lung. Dr. Garzon, we are pleased that you also have had a positive experience with malignant mesothelioma. I think the fact that you have 3 patients who have lived a relatively long time is very encouraging. Dr. Johnston, I think you speak to what is a commonly held opinion about mesothelioma, and I agree that the experience of most surgeons with it has been dismal. Fortunately, despite biopsies and thoracotomy incisions, none of our patients has shown tumor growth through the wound and none DR. FRANK R. JOHNSTON (Winston-Salem, NC): Over the years, we have had experience with 19 patients has complained of incisional chest wall pain. We have not measured the hyaluronic acid and with diffuse pleural mesothelioma. The experience has been bad uniformly. In fact, I believe that most of have no experience with that procedure. We do excise the diaphragm when it is necessary. these patients would have been better off if they had not seen a surgeon at all. The tumor seems to have a Butchart and colleagues thought this an important predilection for biopsy wounds, needle biopsy aspect of the operation, and we agree. As the lung tracts, and the chest wall, and results in increased and tumor are mobilized, the diaphragm is removed, pain and discomfort. One patient who had a left leaving a rim for attachment of a Marlex mesh reinlower lobectomy and partial pleurectomy survived 4 forced with Dacron. The Dacron reinforcement is years. Some years ago we wondered about the possi- important because ascites may develop from bility of an en bloc dissection of pleura, lung, and pneumonectomy fluid going across the Marlex mesh. Regarding Dr. Arbulu’s question, if his patient did part of chest wall but became discouraged after readnot have inflammatory carcinoma of the breast, we ing the reports of those who had tried it. The experience of Dr. DeLaria, as reported today, would recommend extrapleural pneumonectomy. We suggests that in some instances radical operation have had 3 patients in whom biopsy was negative and pleurectomy was not diagnostic. At a submay be worthwhile. The Japanese and Europeans have been interested sequent procedure, the diagnosis was mesothelioma, in the biochemical diagnosis of this lesion by mea- and completion pneumonectomy was performed. DR. DB LARIA:
