Eur J Cardio-thorac

Surg (1991) 5: 466-473

Diagnostic and therapeutic strategy in malignant pleural mesothelioma * D. Branscheid, S. Krysa, E. Bauer, H. Biilzebruck, and J. Schirren Department

of Thoracic Surgery, Clinic for Thoracic Medicine, Rohrbach

Hospital,

Heidelberg,

FRG

Abstract. We retrospectively analysed 301 patients with diffuse malignant pleural mesothelioma (235 male, 66 female; median age 59 years). Prognosis depended significantly on patient age, evidence of pain, loss of weight, tumour cell type, stage, local and distant metastasis, involvement of peritoneum and surgical treatment. The overall median survival rate was 238 days, after extended pleuropneumonectomy 284 days, and after decortication 315 days - significantly better than the prognosis in patients without surgical treatment or exploratory thoracotomy. Pleuropnenmonectomy should only be considered in young patients with an epithelial cell-type tumour (possibly with adjuvant chemotherapy). Decortication seems nowadays to be the treatment of choice. [Eur J Cardio-thorac Surg (1991) 5:466-4731 Key words: Pleural mesothelioma

- Surgical treatment - Prognosis

Diffuse malignant pleuromesothelioma was first described as distinct from the localised type by Klemperer and Rabin 1171in 1931. They defined the classification into the epithelial, the sarcomatous and the mixed biphasic type, which is still in use today. While at the beginning of this century, pleural mesothelioma was found very rarely, it has appeared increasingly in the last two decades. The increased incidence can be ascribed to the more widespread use and processing of asbestos after the Second World War, taking into account a latency period of more than 20 years [5, 25, 351. The causal relationship between this disease and occupational exposure to asbestos has been clearly shown [26, 331. The prognosis is unfavourable with or without treatment. The median survival reported in literature varies from 7 to 16 months after first manifestation [ll, 211. The aims of the study were (1) to review the effectiveness of diagnostic procedures, (2) to review the evidence and applicability of the stage classification, (3) to define modality of treatment suitable to each stage, and (4) to correlate each therapeutic modality to prognosis and patient benefit. Read at the 4th Annual Meeting of the European Association Cardio-thoracic Surgery, Naples, September 17- 19, 1990

for

* Dedicated with graditude to our teacher and pioneer in our speciality, Professor Ingolf Vogt-Moykopf, on the occasion of his 60th birthday

Patients and methods Between 1978 and 1989, the cases of 301 patients with diffuse pleural malignant mesothelioma were analysed retrospectively. The cut-off date for evaluation was March 31, 1990. The starting point for calculation of survival probabilities was either the date of resection or, in non-resected patients, the day on which an alternative treatment was started. The calculation of the survival probabilities was done by the Kaplan-Meier method. Significance of differences between the survival of the various groups of patients was checked by the log-ranktest. To compare the incidence rates, tables divided in four were drawn up and analysed using the x2 test and Fisher’s exact test.

Results This report includes 150 men and 44 women. Their median age was 59 years (range 22 - 87 years). The age distribution did not show any significant peak for the onset of disease. In 44% of the patients a work-related exposure was described in retrospect; 28% of the patients were smokers. The most frequent symptoms were chest pain (61%) dyspnoea/cough (67%), loss of weight (35%) and high temperature (11%). Diagnostic procedures

Six percent of the patients presented initially as a result of a routine chest X-ray examination. Computed tomogra-

467 Table 1. Diagnostic

procedures:

Procedure

Diagnostic thoracotomy Thoracoscopy Biopsy Puncture Bronchoscopy

invasiveness n

37 178 124 219 239

and sensitivity

%

(n=301)

Sensitivity W)

12 59 41 73 79

86 81 60 37 0.5

phy (CT) was part of the preoperative staging procedure in 187 patients, for the assessment of tumour spread, lymph node involvement and formation of distant metastases. The findings of both chest X-ray and CT confirmed the presence of a pleural effusion in 85% of the patients and thickened pleura in 76%. Nodular growth was found in 44%. Evidence of pulmonary fibrosis from asbestosis was seen in 3% only, but pleural plaques were more frequently seen in 8%. Puncture of the pleural cavity, punch needle biopsy of the pleura, thoracoscopy or even exploratory thoractomy was carried out in order to establish the diagnosis. The rate of 58% positive or suspected positive puncture cytologies mostly resulted from repeated punctures. The more invasive the methods, the more decisive were the results (Table 1). It should be noted that pleural mesothelioma has a strong tendency to disseminate into puncture channels and thoracotomy wounds: a risk which increases with the extent and number of incisions or punctures [30]. A specific review of this problem in 215 patients reported implantation metastasis in 26 (12%). Consequently, we carry out punctures and thoracoscopies in the part of the chest wall where later thoracotomy is to be performed. It is difficult to distinguish between pleural mesothelioma and carcinomatous pleurisy of adenocarcinoma [14-16, 26, 321. Pleural mesothelioma was definitely identified in 83% of patients from a resected surgical specimen obtained from autopsy or repeatedly obtained typical histological findings. In 17% a presumptive diagnosis was made on the basis of history or clinical or cytological findings. The epithelial type of tumour was seen in 50%, tumours with mixed histology in 25%, and the sarcomatous type in 12%. In 13% of the patients no exact histological classification was possible. The lung was analysed in 112 patients by hydrolysing a specimen cube of 1 cm3 through millipore filtration. The quantity of needle-shaped particles was increased in 69 patients (62%), indicating work-related exposure to asbestos, occupational disease being consequently acknowledged officially [26]. We composed our own staging system for pleural mesothelioma according to the UICC classification for bronchial carcinoma (1987) (Table 2). This classification system includes preoperative staging and intraoperative exploration as well as the histopathological findings. By these means 252 patients could be definitely classified to one stage (Table 3), while this was impossible in 49 patients, as the relevant data were missing.

Table 2. Proposed

TNM classification

for pleural mesothelioma

T,

No evidence of primary tumour.

T,

Tumour limited to the visceral pleural of one lobe or half of the parietal pleura.

T,

Tumour limited to the entire visceral and/or parietal pleura. (No extension to adjacent structures such as lung, diaphragm, pericardium, mediastinum, chest wall).

T,

Tumour has directly invaded trapleural structures/organs.

any of the ex-

N,

No evidence of lymph node involvement.

N,

Evidence of involvement nodes.

MCI

No evidence of distant metastases or extension to contralateral pleura or peritoneum.

M, M 1 (pleura) M, (peritoneum)

Distant metastases present. Extension to contralateral pleura. Extension to peritoneum.

Table 3. Distribution staging a

of tumours

of intrathoracic

lymph

in this study by retrospective

Stage

TNM classification

I II III IV

T,, N,, M, T,, N,, Mo T,, N,, Mo T,-a, N,, M,

n

%

5 34 168 45

2 11 56 15

a 49 tumours could not be classified

Table 4. Localisation of distant metastases

Lung (ipsilateral) (contralateral) Liver Bone AbdomJretroperit. lymph nodes Skin Brain Kidney Adrenal

n

%

12 3 7 6 5 3 1 1 1

4.0 1.0 2.3 2.0 1.7 1.0 0.3 0.3 0.3

Hilar and mediastinal lymph nodes were found to be involved in 24% of the patients. The peritoneum was affected in 4%, the contralateral pleura in 1.3%. Distant metastasis was seen in 11% of the patients at the time staging was carried out (for location see Table 4).

Conservative

treatment

No surgery was performed in 118 patients; they were in poor general condition or had an advanced-stage tumour, or did not consent to operative intervention. Chemotherapy was employed as primary therapy in 25 patients, but there was no difference in survival between

468

Fig. 1. Surgical specimen after right-sided pleuropneumonectomy with complete hemiresection of pericardium and diaphragm

these and the patients who received no treatment. Chemotherapy was applied as an adjuvant procedure in 49 patients. In this group median survival after extended pleuropneumonectomy was longer (98 days versus 76 days) than after decortication.

Surgical treatment In 76 patients extended pleuropneumonectomy with resection of the pericardium and diaphragm was performed. This intervention always implied a double thoracotomy on the same side, one using a posterolateral approach via the sixth or seventh rib, the other using a lateral approach between ribs 10 and 11, with simultaneous opening of the abdomen in this region, a thoracoabdominal approach. The latter method, continued abdominally or via the retroperitoneum, allows us to prepare and remove the diaphragm completely, including its origins in the lumbar segments. If this is not done, pleural tumour particles in the phrenicocostal sinus might be easily overlooked or left when preparing the adjacent structures (Fig. 1). All interventions of this kind were performed with radical intension. The substitute for the diaphragm was Marlex Mesh or nowadays Gore-Tex; the complete hemiresection of the pericardium was mostly covered with dura mater, or more recently with Gore-Tex membrane. In 82 patients palliative decortication was carried out. This kind of surgery was performed instead of radical pleuropneumonectomy in patients with poor cardiorespiratory reserves and in those in whom diffuse involvement of the chest wall of the mediastinum was found at operation.

Prognostic factors The median survival of all patients (n= 301) was 238 days. After 1 year 30% of the patients were still alive, after 3 years 8% and after 5 years 4%. No significant differences in survival were found in regard to patient sex. By contrast, survival was considerably influenced by age. Out of 19 patients under 40 years of age, 42% were alive after 1 year, 30% after 2 years and

g40 years hl = 19) 20%. lO%-

\

,40 years b-l- 282) L,

0%-l 0

12

24

36

46

60

72

months Fig. 2. Survival rate as a function of age

30% after 3 years. Of those patients over 40 years old, 29% survived 1 year, 11% 2 years and 7% 3 years (p ~0.05; Fig. 2). The analysis of the survival rate showed that this favourable prognosis for younger patients is not attributable to more of them having received surgical treatment or to a different distribution of the histological subtypes. The delay between the onset of symptoms and the establishment of diagnosis did not influence survival time, nor did it correlate with histological findings. Patients with chest wall pain had a worse prognosis than patients without pain (177 versus 305 days; p

Diagnostic and therapeutic strategy in malignant pleural mesothelioma.

We retrospectively analysed 301 patients with diffuse malignant pleural mesothelioma (235 male, 66 female; median age 59 years). Prognosis depended si...
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