Refer to: Taylor RA, Johnson LP: : Current J>cr-, jpcclivej. West J Med 13<:37WS3. May 1981 7". «.' /^ - <"-- t i : i r?> THEWESTEEN Journal of Medicine X'<2A-ftS6E-STQS PAP" A : Current Perspectives F^ ^, LLOYD P. JOHNSON, MD, Seattle^. A~ X\~ G^^J^j? ROY A. TAYLOR, MD, and Thirty patients with the diagnosis of mesothelioma were admitted to the Swedish Hospital Medical Center, Seattle, from 1975 to 1979. Of these, 26 had pleural and 4 had peritoneal mesothelioma. In 20 of the patients with pleural mesothelioma, the diagnosis had been made by open thoractomy and in only one by needle biopsy of the pleura. The average survival of the patients with pleural tumors from time of diagnosis was 15 months, and two are alive at th'ree and eight months, respectively, one of whom had an apparent solitary benign mesothelioma. The average survival of those with peritoneal mesothelioma was ten months, although one has survived six years. There were 17 patients with a known history of exposure to asbestos, 14 while working in shipyards. Because of the relatively high incidence of this previously rare tumor in the Puget Sound, Washington, area, and the generally dismal results of therapy, better methods of diagnosis including thoracoscopy and a more systematic approach to treatment are recommended. IN RECENT YEARS, mesothelioma, a tumor of serosal surfaces, has become a subject of growing interest among the medical profession and the lay public. The attention is due both to its increasing frequency of diagnosis and its strong epidemiological link to asbestos exposure. 1-7 Asbestos, a mineral fiber, is valued for its thermal properties and has found wide application in this century as an insulating material. Until recently, including the busy years of World War II. it was used extensively in ship building as pipe insulation. Growing evidence indicates that the populations in those areas with ship building activities have a significantly increased risk of developing mesothelioma.'-" In a tumor registry study by Hinds" of eight areas of the United States, the Puget From the Department of Surpcrv. the Swedish Hospital Medical Center. Seattle (Dr Taylor), and the Department of Surtrery. University or Washington School of Medicine. Seattle (Dr. Johnson). Submitted Scrlember 29. 1980. Reprint requests to: Lloyd P. Johnson, MD. Seattle Surpical Group, rnc, P.S., 801 Broadway. Suite 901, Seattle. WA 98122. Sound area and New Orleans,, both with substantial shipyard activity, had the highest incidence of mesothelioma. During the past 4!/i years, one registry reported 85 cases of malignant pleural mesothelioma in western Washington (written communication, June 1980, Fred Hutchinson Cancer Research Center, Seattle). Because of this somewhat unusual epidemiology ' the apparent increasing incidence of the disease and the generally poor results of therapy, we wish to review our recent experience with mesothelioma and propose some new directions for its diagnosis and management. Clinical Presentation The cases of 30 patients admitted to the Swedish Hospital Medical Center in Seattle between 1975 and 1979 were reviewed. In all of the patients mesothelioma had been diagnosed by tissue analysis. There were 25 with diffuse malignant pleural disease, 4 with peritoneal tumor and 1 THE WESTERN JOURNAL OF MEDICINE 379 TI04740777
N/ with a benign localized pleural mesothelioma (Table 1). Peritoneal Three of the four patients with peritoneal mesothelioma were men. The average ace at diagnosis was 59 years. Two patients had a known history of exposure to asbestos, one of these had worked in shipyards 25 years earlier. The most common symptoms were abdominal pain, loss of weight, abdominal distension and fever. Three of the patients had ascites and in one of these a gallium scan and abdominal ultrasound examination showed abnormalities. Paracentesis was carried out in two but was diagnostic in neither. Laparotomy was required for diagnosis in all four patients. The tumor was described as being diffuse with matting of the bowel in three patients. One patient had metastasis to the liver, lung and scalene nodes. Two of the patients died two weeks after diagnosis and a third died after nine months. Of interest, the fourth patient was a woman who had a predominant pelvic tumor with involvement of the colon and uterus as Well as omental nodules. She was treated by resection of the tumor, followed by radiation and chemotherapy. She is still alive six years after the time of diagnosis, and there is no evidence of recurring disease. Benign Pleural In the one patient with benign localized pleural mesothelioma, an asymptomatic mass of the left side was detected on an x-ray study of the chest- Over five years the lesion increased in size from 2 to 8 cm (see Figure 1). She had no history of asbestos exposure. During thoracotomy a solitary benign mesothelioma was found and was removed without difficulty. The patient is doing well six months following resection, and there is no evidence of recurrent tumor. Malignant Pleural Twenty of 25 patients with diffuse pleural mesothelioma were men. The average age at diagnosis was 61 years. Fifteen patients had a known exposure to asbestos, 13 of them in shipyards. The average interval from time of exposure to diagnosis was 32 years. The clinical presentation of these cases is given in Table 1. The most common symptoms were chest pain and dyspnea. Pleural effusion was TABLE 1. Clinical Symptoms ol 25 Patients With Dilluse Pleural Disease',Vo. o/ Patients Symploms Dyspnea II Chest pain 9 Weakness 7 Fever 7 Findings on roentgenograms Pleural effusion 20 Pleural nodularity 11 In one olhcr patient with pleural mesothelioma, the condition was diagnosed as a solitary benign tumor. Figure 1. X-ray studies ol the chest showing growth of a benign pleural mesothelioma from 2 to 8 cm over five years. 380 MAY 1981 134 T104740778
present in 20 of 25 patients. The common findings on chest roentgenograms, as represented in Figure 2, included pleural effusion, pleural nodules demonstrated best by pneumothorax and pleural plaques, which were calcified and probably benign. Diagnostic procedures are listed in Table 2. In 19 patients a diagnosis was made by thoracotomy. Cytologic studies of pleural fluid and needle biopsies of the pleura have not been productive. Recently, thoracoscopy, using the mediastinoscope, produced good visualization of large areas of the parietal, visceral and diaphragmatic pleura in two patients and allowed adequate biopsy studies of the pleural nodules. At thoracoiomy or thoracoscopy the pleura appears as a thickened, nodular rind, constricting and compressing the lung. A typical specimen removed by total pleureciomy is shown in Figure 3. Results Results of treatment of diffuse pleural mesothelioma are shown in Figure 4. The average length of survival after diagnosis was 15 months: One patient, who had been treated by total pleurectomy, survived for five years without evidence of recurrent tumor but subsequently died of a primary adenocarcinoma of the lung. Chemotherapy in 15 patients consisted of various combinations of doxorubicin, vincristine, cyclophosphamide, actinomycin-d, rubidazone and dacarbazine; however, these drugs did not appear to significantly alter the progression of the disease. Radiotherapy also appeared to be of little benefit in seven patients. Discussion The present series of patients bears out the strong relationship of pleural mesothelioma to asbestos exposure and probably reflects the substantial shipyard activity in the Pugct Sound area. The long latency 32 years between last known exposure and diagnosis is in agreement with other series and is of concern because significant exposure to abestos by certain occupational groups still continues. 7 Since Wagner and co-workers first reported the relntionship between asbestos exposure and mesothelioma in I960, numerous reports have appeared describinc the high incidence, not only of mesothelioma, but also of bronchogenic, oropharyngeal, laryngeal, gastrointestinal and renal tumors among those who have been exposed to asbestos. 1 -''-" Lung cancer death rates may be increased to 60 times those of controls by asbestos exposure and cigarette /smoking.', TABLE 2. Method o/ Diagnosis in 25 Patients With Dittuse Pleural Disease Method No. of Patients Thoractomy 19 Needle biopsy of pleura (5 attempted)... 1 Cytology (II attempted) I Thoracoscopy 1 Unknown 2 * Figure 2. X-ray studies of the j chest showing typical findings in diffuse pleural mesothelioma: pleural effusion, pleural nodules and pleural plaques. THE WESTERN JOURNAL OF MEDICINE 381 TI04740779
V' however, has no appcarant relationship to cigarette smoking.* Solitary benign tumors have not been shown to be related to asbestos exposure and are almost always cured by local resection.' 0-12 Their major significance is in the occasional production of local symptoms and the difficulty of differentiating them from malignant lesions of the lung or mediastinum. Peritoneal mesothelioma has a worse prognosis than diffuse pleural disease, with an average survival rate of three months to a year following diagnosis."-" As occurred in this series, however, there may be an occasional patient with a predominant mass that resembles mesothelioma histologically, who may be cured by resection of the tumor combined with chemotherapy and radiation. Although others have reported good results in diagnosing diffuse pleural disease by obtaining blind needle biopsies of the pleura or doing cytologic studies of pleural fluid, 0 -' 5-10 these techniques were not productive in the present series. Thoracotomy was used to make the diagnosis in most patients in this group, although, recently, thoracoscopy was used successfully with minimal morbidity in two patients. The latter is certainly not a new procedure and has been reported previously in the diagnosis of mesothelioma; however, this is the first known report using a rigid mediastinoscope. 17 Although the survival rate of the patients in our series is similar to that of others, these studies represent a somewhat heterogenous approach to therapy by a number of physicians."-'"-" 1 Wanebo and colleagues," 1 using plcurectomy with or without radiation and chemotherapy, reported 5-year survival of 5 of 33 patients with diffuse pleural mesothelioma. DcLaria and co-workers'" reported 11 patients having radical plcuropncumoncctomy, witli two surviving after two and four years, respectively. Schlienger and colleagues'-" reported a median survival of 13 months in patients treated with megavoltage radiotherapy to one hemithorax compared with 9.8 months survival in those receiving no radiation. Chemotherapy, using doxorubicin in combination with various other drugs, has been reported to induce a response rate of 20 percent to 40 percent in some patients."! - " Thus, there is evidence that all three modalities surgical procedures, radiation and chemotherapy 100 PLEURAL 9 12 15 no. of months Alt p«ti»ms 25 24 60 Figure 4. Survival curve ot all 25 patients with diffuse pleural mesothelioma, ranging from 2 to 60 months from time of diagnosis. Figure 3. Gross specimen of diffuse pleural mesothelioma, removed by total pleurectomy, showing irregular, fibronodular appearance of pleura. 382 MAY 1981 134 TI04740780
\7 may benefit patients with pleural mesothelioma. Intensive combined therapy using all three modalities is under way as an intercooperative group study, involving plcurcctomy (recommended) and radiotherapy to 4,700 rads with or without doxorubicin therapy. (Written communication, June 1980; L. Wasser, L. Baker and M. Samson: Radiotherapy With and Without Chemotherapy for Malignant Pleural Localized to One Hemithorax [Intergroup Study] Eastern and Southwest Oncology Groups.) We recommend this protocol. Only with a prospective randomized clinical trial will the effects of the combined-modality treatment be measurable. REFERENCES 1. McDonald JC. MacDonald AD: Epidemiology of mesothelioma from estimated incidence. Prevcnl Med 6:426-446, 1977 2. Wagner JC. Slcggs CA, Marchand P: Diffuse pleural mesothelioma and asbestos exposure in the Northwestern Cape Province. Br J lndustr Med 17:260-270. 1960 3. Theriault GP, Crand-Bois L: and asbestos in the Province of Quebec, 1969-1972. Arch Environ Health 33:15-19. Jan-Feb 1978 4. Ncwhousc ML. Berry G: Predictions of mortality from mesothelial tumors in asbestos factory workers. Br J lndustr Med 33: 147-131, Aug 1976 5. Borrow M. Conston A. Livornese L, et al: following-exposure to asbestos: A review of 72 cases. Chest 64: 641-646, Nov 1973 6. Edge JR. Choudhury SL: Malignant mesothelioma of the pleura in Barrow-in-Furness. Thorax 33:26-3D, Feb 1978 7. Chovil A. Stewart C: Latency period for mesothelioma. Lancet 2:S53. Oct 20. 1979 8. Hinds MW: in the United States Incidence in the 1970s. J Occupat Med 20-469-471, Jul 197S 9. Selikoff )J. Hammond EC: Asbestos and smoking (Editorial). JAMA 242:458. Aug 3. 1979 10. Scharifker D, Kaneko M: Localized fibrous "mesothelioma'* of pleura (submesothelial fibroma) A ciinicopathologic study of 18 cases. Cancer 43:627-635. Feb 1979 11. Shabanah FH. Saycgh SF: Solitary (localized) pleural mesothelioma Report of two cases and review of the literature. Chest 60-558-563. Dec 1971 12. Utley JR. Parker JC. Hahn RS. et al: Recurrent benign fibrous mesothelioma of the pleura. J Thorac Cardiovasc Surg 65:830-834. May 1973 13. Kannerstcin M. Churg J: Peritoneal mesothelioma. Human Pathol 8:83-94. Jan 1977 14. Jones DEC, Silver D: Peritoneal mesothelioma. Surgery 86:356-560. Oct 1979 13. FU12cr ER. Pool JL. Melamed MR: Pleural mesotheliomas Clinical experiences with thirty-seven patients. Am J Roentgenol 99:863-880. Apr 1967 16. Oels HC, Harrison EG, Carr DT. et al: Diffuse malignant mesothelioma of the pleura: A review of 37 cases. Chest 6:564-570, Dec 1971 17. Boushy SF, North LB, Helgason AA: Thoracoscopy: Technique and results in eighteen patients with pleural effusion. Chest 74:386-389. Oct 1978 18. Wanebo HJ. Martini N. Melamed MR. et al: Pleural mesothelioma. Cancer 38:2481-2488, Dec 1976 19 DcLaria GA, Jcnsik R. Fabcr LP, et al: Surgical management of malignant mesothelioma. Ann Thorac Surg 26:375-382, Oct 1978 20. Schliengcr M. Eschwege F. Blache R. et al: Mesolheliomes pleuraux malins. Bull Cancer (Paris) 56:265-308, 1969 21. Sprcmulli E, Wampicr G, Regelson W, el al: Chemotherapy of malignant mesothelioma. Cancer 40:2038-2045. Nov 1977 22. Yap B, Benjamin RS. Burgess MA. et al: The value of -adrtamycin in the treatment of diffuse malignant pleural mesothelioma. Cancer 42:1692-1696. Oct 1978 23. Chahinian AP. Suzuki Y. Mandel EM. et al: Diffuse pulmonary malignant mesothelioma Response to doxorubicin and 5-azacytidlne. Cancer 42:1687-1691, Oct 1978