Mesothelioma: Current Perspectives

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Journal of M e d i c i n e

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Mesothelioma: Current Perspectives

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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

mesothe-lioma 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 epidemi-ological 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 ex-tensively 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 meso-thelioma.'-" 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 ( D r . Johnson).

Submitted Scrlember 29. 1980.

Reprint requests to: Lloyd P. Johnson, M D . Seattle Surpical Group, rnc, P.S., 801 Broadway. Suite 901, Seattle. W A 98122.

Sound area and New Orleans,, both with sub-stantial shipyard activity, had the highest inci-dence 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 Hutch-inson Cancer Research Center, Seattle).

Because of this somewhat unusual epidemiol-ogy ' the apparent increasing incidence of the dis-ease and the generally poor results of therapy, we wish to review our recent experience with meso-thelioma and propose some new directions for its diagnosis and management.

Clinical Presentation

The cases of 30 patients admitted to the Swed-ish Hospital Medical Center in Seattle between

1975 and 1979 were reviewed. In all of the pa-tients mesothelioma had been diagnosed by tissue analysis. There were 25 with diffuse malignant pleural disease, 4 with peritoneal tumor and 1

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with a benign localized pleural mesothelioma (Table 1 ) .

Peritoneal Mesothelioma

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 exami-nation 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 in-volvement of the colon and uterus as Well as omental nodules. She was treated by resection of the tumor, followed by radiation and chemo-therapy. She is still alive six years after the time of diagnosis, and there is no evidence of recurring disease.

Benign Pleural Mesothelioma

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 evi-dence of recurrent tumor.

Malignant Pleural Mesothelioma

Twenty of 25 patients with diffuse pleural mesothelioma were men. The average age at diag-nosis 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 be-nign pleural mesothelioma from 2 to 8 cm over five years.

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MESOTHELIOMA present in 20 of 25 patients. The common

find-ings on chest roentgenograms, as represented in Figure 2, included pleural effusion, pleural nod-ules—demonstrated best by pneumothorax—and pleural plaques, which were calcified and prob-ably benign.

Diagnostic procedures are listed in Table 2. In 19 patients a diagnosis was made by thoracotomy. Cytologic studies of pleural fluid and needle bi-opsies of the pleura have not been productive. Recently, thoracoscopy, using the mediastino-scope, 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 pleu-reciomy is shown in Figure 3.

Results

Results of treatment of diffuse pleural meso-thelioma are shown in Figure 4. The average length of survival after diagnosis was 15 months: One patient, who had been treated by total pleu-rectomy, survived for five years without evidence of recurrent tumor but subsequently died of a primary adenocarcinoma of the lung. Chemo-therapy in 15 patients consisted of various com-binations of doxorubicin, vincristine, cyclophos-phamide, actinomycin-D, rubidazone and dacar-bazine; 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 sub-stantial 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 ex-posure 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, oro-pharyngeal, 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.' Mesothelioma,

TABLE 2.—Method o/ Diagnosis in 25 Patients With

Dittuse Pleural Disease

No. of

Method 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.

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however, has no appcarant relationship to cigar-ette 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 medi-astinum.

Peritoneal mesothelioma has a worse prognosis than diffuse pleural disease, with an average sur-vival rate of three months to a year following diagnosis."-" As occurred in this series, how-ever, 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

tech-niques 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 pre-viously in the diagnosis of mesothelioma; how-ever, 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

with-out 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 re-ceiving no radiation. Chemotherapy, using doxo-rubicin 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—surgi-cal procedures, radiation and chemotherapy—

PLEURAL

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 dif-fuse pleural mesothelioma, re-moved by total pleurectomy, showing irregular, fibronodular appearance of pleura.

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may benefit patients with pleural mesothelioma. Intensive combined therapy using all three mo-dalities is under way as an intercooperative group study, involving plcurcctomy (recom-mended) and radiotherapy to 4,700 rads with or without doxorubicin therapy. (Written com-munication, June 1980; L. Wasser, L. Baker and M. Samson: Radiotherapy With and Without Chemotherapy for Malignant Pleural Mesotheli-oma Localized to One Hemithorax [Intergroup Mesothelioma Study] Eastern and Southwest Oncology Groups.) We recommend this protocol. Only with a prospective randomized clinical trial will the effects of the combined-modality treat-ment be measurable.

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