We correlated the preprocedure clinical diagnosis with the final histopathologic diagnosis. In patients with clinical suspicion of tuberculosis, only 58.5% (38/65) were finally diagnosed as tuberculosis (Table 4). Similarly in those with clinical suspicion of MPE, only 62.5% (85/136) had histopathologic evidence of malignancy. In patients with inconclusive clinical picture, a final histopathologic diagnosis of either tuberculosis or malignancy could be achieved in 47.3% (44/93) of the patients. A clinical diagnosis of tuberculosis had a positive predictive value (PPV) of 58.5% and a negative predictive value (NPV) of 83.9% for the final diagnosis of tuberculosis. Similarly, a clinical diagnosis of malignancy had a PPV and NPV of 62.5% and 89.1%, respectively, for confirmed MPE.
Pleural effusions were classified as having high ADA (>70 U/L), borderline ADA (41 to 70 U/L), and low ADA (≤40 U/L) (Table 5). A total of 61.2% and 70.5% of patients with borderline and high ADA, respectively, had tuberculosis, whereas only 14.4% of the patients with low ADA were diagnosed as tuberculosis. This difference was statistically significant (P=0.0001). In addition, malignancy and other nontubercular diagnoses were significantly more common in the subgroup with low ADA as compared with those with borderline and high ADA.
The clinical and radiologic findings, PF analysis, and thoracoscopic appearances of pleura in patients with a final histopathologic diagnosis of either tuberculosis or malignancy are shown in Table 6. Patients with malignancy had a higher age and were more likely to have a massive effusion, mediastinal shift, nodular pleural thickening on CT chest, large-sized/variable-sized pleural nodules visualized during thoracoscopy, and lower PF ADA levels. Patients with tuberculosis had higher PF ADA and protein levels and more often had small pleural nodules visualized during thoracoscopy.
Of the 248 patients who underwent thoracoscopic pleural biopsy, major complications occurred in 15 patients (Table 7). Three patients died following thoracoscopy. One patient with malignancy developed acute kidney injury on the second day of thoracoscopy and succumbed to the illness after 2 days. The second patient also had malignancy and developed reexpansion pulmonary edema and respiratory failure, which required noninvasive ventilation. Although the respiratory failure improved, his general condition deteriorated and the patient expired in the second week after thoracoscopy. The third patient had CKD, developed empyema following thoracoscopy followed by sepsis, and expired in the second week after thoracoscopy. All patients who died had poor baseline performance status. Death directly due to the procedure, however, was attributed only in the patient who developed empyema and sepsis. The most common major complication following thoracoscopy was empyema (n=10, 3.9%) followed by reexpansion pulmonary edema (n=4, 1.6%). Seven (8.3%) complications were encountered with CBPB. Most of the complications were with the trucut needle (5 instances of hemothorax), whereas 1 patient each developed subcutaneous hematoma and syncope, respectively, with the Abrams needle. There was no mortality with CBPB.
The results of this study suggest that MT is a useful and reasonably safe tool in the workup of undiagnosed EPE, and is superior to CBPB. However, if MT is unavailable, CBPB provides a good diagnostic yield, superior to clinical judgment. Undiagnosed EPE is a common problem encountered by pulmonary physicians. In countries where tuberculosis is endemic, differentiating tuberculosis from malignancy, the 2 most common causes of EPE, is of utmost importance as the treatment and prognosis vary. It is a common practice in resource-constrained settings to initiate empiric ATT in all undiagnosed EPE, and consider an alternate diagnosis only if the effusion fails to respond to therapy. However, treating MPE as tuberculosis would not only lead to an unnecessary delay in the initiation of appropriate therapy but also subject them to risk of adverse reactions of ATT.
In resource-constrained settings, CBPB continues to be performed. In fact, a combination of PF ADA, lymphocyte/neutrophil ratio of >0.75, and CBPB has been shown to have diagnostic accuracy similar to MT in diagnosis of TPE.2 In another study from tuberculosis endemic country in patients younger than 50 years, CBPB was found to have diagnostic accuracy approaching thoracoscopy.22 Thus, the debate on the role of CBPB as compared with MT as the initial diagnostic modality for undiagnosed EPE continues. Some pulmonary physicians favor CBPB as the initial investigation, with thoracoscopy only if the effusion still remains undiagnosed.7 In fact, if pleural biopsy is performed under image guidance, the diagnostic yield could be as high as 87%, albeit lower than MT.23,24
In our study, the success rate of a representative pleural biopsy was significantly higher with thoracoscopic biopsy. A recent randomized trial has also suggested the superiority of MT over CBPB with lower yield and higher risk of complications with the latter.25 Blind pleural biopsy was nonrepresentative in 15.5% patients who underwent CBPB, and similar rates of nonrepresentative samples with blind pleural biopsies have been reported in other studies also.3,15 Pleural biopsies could not be obtained in 6.8% of the patients undergoing MT in this study, and is marginally higher than the earlier reported rates.13,14 This is probably due to the delayed presentation of patients to our center, which led to the formation of multiple pleural adhesions.12 Moreover, chest ultrasound was not used routinely to confirm the site of entry before 2013. The success rate of MT significantly improved when a point-of-care ultrasound was used to guide the choice of a thoracoscope and determine the chest wall entry point. It has been demonstrated previously that ultrasound reliably identifies entry sites for trocar placement during MT, even in the presence of pleural adhesions.26,27
Finally, our study is not without limitations. It is a retrospective study from a single center. We do not have the recommended long-term follow-up of 1 year in those with nonspecific diagnosis on pleural biopsy. In addition, the results are applicable to CBPB and not image-guided CBPB.23 The strength of our study is the large sample size and the fact that we have compared the commonly used techniques for obtaining pleural biopsy.
In conclusion, MT is the procedure of choice in the diagnosis of undiagnosed EPE, given its better success rate and an acceptable safety profile, compared with CBPB. In centers where thoracoscopy is not feasible, we recommend CBPB (image guided, wherever feasible) over initiating empiric treatment (Fig. 1). Both RT and SRT are equally effective and the choice of the thoracoscope would depend on the availability, extent of pleural septations, and the need for additional procedures such as adhesiolysis.
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