Mesothelioma pleural symptom

Pleural fluid characteristics of 26 patients diagnosed with malignant mesothelioma over an 18-year period were reviewed and compared with those of patients with effusions due to other malignancies. Survival from time of initial thoracentesis was directly correlated with pleural pH and decreased pleural fluid/serum glucose ratios but was not related to protein or LDH concentration. Decreased pleural fluid pH was statistically related to a decreased pleural fluid/serum glucose ratio. Patients with low pH (<7.30) pleural effusions had statistically decreased mean survival and decreased mean pleural fluid/serum glucose ratios compared with patients with normal pH ([greater than or equal to] 7.30). Patients with malignant mesothelioma pleural effusions had statistically decreased mean pleural fluid pH compared with patients with other malignant pleural effusions. Decreased levels of pleural fluid pH and pleural fluid/serum glucose ratios have negative prognostic significance and probably correlate with the degree of tumor bulk affecting the pleural surface.

LDH = lactic dehydrogenase; PF/S = pleural fluid/serum ratio

Malignant pleural mesothelioma, once considered a rare disease, should reach a peak incidence over the next 20 years due to its long latency period and the institution of dust control measures in the late 1960s and early 1970s.[1,2]

Up to 95 percent of affected patients will have a pleural effusion during their clinical course.[3] These effusions usually are an early manifestation of the disease and tend to resolve as the disease progresses and tumor bulk increases. Although there are isolated reports of pleural fluid findings in patients with malignant mesothelioma and a single small series,[4] a large series has not been reported. It also is notable that the relationship between pleural fluid characteristics and prognosis has not been investigated despite the marked variation in survival. A recent study by Sahn and Good[5] involving malignant pleural effusions showed a significantly decreased survival in patients with a low pleural fluid pH (<7.30). However, patients with malignant pleural mesothelioma were not included in the study population. To better delineate the characteristics of pleural effusions associated with malignant mesothelioma and to correlate these with clinical course and prognosis, we reviewed the medical records of all patients diagnosed with malignant mesothelioma from 1972 to 1990 with associated pleural effusions at two medical centers and at a private community hospital.

Methods

The medical records from all patients with malignant mesothelioma diagnosed at the Medical University of South Carolina, the University of Colorado affiliated hospitals and from a private community hospital in Charleston from January 1972 to June 1990 were reviewed. All patients with pleural fluid analyses were included for study. Results of pleural fluid pH, protein, glucose, LDH, with comparisons to serum values and pleural fluid erythrocyte and leukocyte counts were recorded.

The relationships between pleural fluid pH, glucose, protein, LDH, erythrocyte and leukocyte counts, and PF/S ratios of glucose, protein and LDH and survival were assessed by linear regression analysis. The relationship between pleural fluid pH and other pleural fluid parameters also were analyzed by linear regression. Mean differences in survival and pleural fluid characteristics between low pH (<7.30) and normal pH ([is greater than or equal to] 7.30) effusions were assessed by the Student t test for unpaired values. Statistical differences in mean pleural fluid values between patients with malignant mesothelioma and those with effusions due to other malignancies (previously reported by Sahn add Good[5]) were assessed by the Student t test for unpaired values.

Results

Twenty-six patients with malignant mesothelioma and a pleural effusion were studied. The diagnosis of malignant mesothelioma was established by pleural fluid cytologic studies in two patients, closed pleural biopsy in 14 patients (diagnoses confirmed by autopsy in three patients), thoracotomy in nine patients (diagnosis confirmed by autopsy in one patient) and thoracoscopy in one patient. At thoracotomy, a thick pleural rind and multiple (lung) nodules of various sizes were the most common findings (six of nine patients). When light microscopic analysis was equivocal, electron microscopy (multiple cytoplasmic tonofilaments and elongated microvilli on the cell surface) was used to confirm the diagnosis. Radiographic, clinical or laboratory evidence for a primary nonpleural malignancy was not found in any patient. At the time of this writing, two patients remain alive, 9 and 11 months after initial thoracentesis.

Pleural fluid findings and survival from time of initial thoracentesis are shown in Table 1. In all patients, survival from time of initial thoracentesis was 6.42 [+ or -] 0.99 months (mean [+ or -] SE). All effusions were exudates by protein and LDH criteria. Seventeen patients had pleural fluid pH measured; nine patients had low pH (<7.30) pleural effusions and eight patients had normal pH ([is greater than or equal to] 7.30) pleural effusions. All patients with low pH effusions had negative pleural fluid smears and cultures and there was no evidence of rheumatoid disease, systemic lupus erythematosus, tuberculosis or esophageal rupture (all causes of pleural fluid acidosis, pH<7.30). There was a significant direct correlation between survival and pleural fluid pH (r = 0.76; p<0.001) and PF/S glucose ratio (r = 0.46; p<0.04); the lower the pH and PF/S glucose ratio, the shorter the survival. There was no significant correlation between pleural fluid protein, LDH, and PF/S protein and LDH ratios and survival. Pleural fluid pH was directly correlated with PF/S glucose ratio (r = 0. 72; p = 0.002). There was no significant correlation between pleural fluid erythrocyte or leukocyte count, LDH, protein or PF/S ratios of LDH or protein with pleural fluid pH or survival (all p = NS).

The overall survival among patients in whom pleural pH was measured was 7.6 [+ or -] 1.2 months. Patients with a low pH pleural effusion (pH<7.30) had a significantly shorter survival (4.7 [+ or -] 1.0 months) than those with pleural fluid pH([is greater than or equal to]) 7.30 (10.9 4- 1.8 months) (p = 0.008; those with low pH effusions had significantly decreased mean PF/S glucose ratio (0.36 [+ or -] 0.11) compared with patients with a pleural fluid pH[is greater than or equal to]-7.30 (0.80 [+ or -] 0.06) (p<0.003). No statistically significant relationship was observed between pleural fluid pH and protein and LDH concentration, PF/S protein and LDH ratios or with pleural fluid leukocyte or erythrocyte count.

Mean pleural fluid pH, glucose, LDH protein and erythrocyte and leukocyte counts from patients with malignant mesothehoma and effusions due to other malignancies were compared. The only parameter that differed between effusions from patients with malignant mesothelioma and those with other malignancies was pleural fluid pH. The pleural fluid pH in mesothelioma pleural fluid (7.22 [+ or -].06) was significantly lower than the pleural fluid pH from other malignancies (7.33 [+ or -].01) (p<0.004

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Discussion

As the incidence of malignant mesothelioma is expected to increase into the first decade of the 21st century,[6,7] more clinicians will be involved with management decisions in affected patients. The long-term prognosis for these patients is dismal, with a median survival of 8 to 15 months.[2,3,8,9]

Certain clinical and pathologic features have been associated with better short-term prognosis. These include epithelial subtype, female sex, age less than 60 years, dyspnea as the only symptom and left-sided unilaterality.[2,6,10,11]

Partial pleural fluid findings from a small number of patients with malignant mesothelioma have been reported.[4,9,12] However, studies delineating complete pleural fluid analyses are lacking, and the association between pleural fluid parameters with survival has not been investigated.

All patients had exudative pleural effusions; this is in agreement with prior studies.[4,12] A pleural fluid pH<7.00 usually is associated with only three diagnoses: esophageal rupture (pH characteristicalyl 6.00), empyema (pH range: 7.29 to 6.00), and rheumatoid pleurisy (pH 7.00).[13] Patients with tuberculous pleurisy, lupus pleuritis, carcinoma and lymphoma who have pleural fluid pH<7.30 (approximately 20 to 30 percent) usually have pleural fluid pH values in a narrow range between 7.05 and 7.29. However, four of our patients had a pleural fluid pH<7.00 and none had evidence of infection or rheumatologic disorders.