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Intrapleural Urokinase Directly Under Medical Thoracoscopy for the Diagnosis of Malignant Pleural Mesothelioma With Severe Multiloculated Pleural Effusions

Terashita, Satoshi MD; Kawachi, Hiroaki MD; Horikawa, Sadao MD; Noguchi, Susumu MD; Ikeue, Tatsuyoshi MD; Sugita, Takakazu MD

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Journal of Bronchology & Interventional Pulmonology: April 2019 - Volume 26 - Issue 2 - p e26-e27
doi: 10.1097/LBR.0000000000000576
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To the Editor:

Pleural fluid loculations or trapped lungs frequently occur in patients with malignant pleural effusions. In these patients, augmented procoagulant and depressed fibrinolytic activity contribute to fibrin deposition within the pleural space.1 These conditions obstruct the field of view under medical thoracoscopy, and thereby make it difficult to conduct a pleural biopsy. In this paper, we report a case of the successful diagnosis of malignant pleural mesothelioma with severe multiloculated pleural effusion by using intrapleural urokinase directly under medical thoracoscopy. This technique has not been documented in the literature.

A 50-year-old man with no significant past medical history presented to the outpatient department with a 2-week history of dyspnea. The patient’s chest radiograph showed a right-sided pleural effusion which was confirmed on computed tomographic scan. Pleural nodularity or enhancement was not detected. Diagnostic thoracentesis was nondiagnostic. Medical thoracoscopy was accordingly conducted.

The loculations were appreciated before the procedure on ultrasound. In fact, a thoracoscope inserted through the trocar into the thoracic cavity revealed remarkable intrapleural fibrin deposition and we were unable to adequately view the pleural space (Fig. 1A). We attempted to break and remove the fibrin nets by moving the distal end of the thoracoscope back and forth by using biopsy forceps. Despite these actions, the field of view under endoscopy remained insufficient and poor. Therefore, we attempted to instill urokinase into the multiloculated pleural space.

FIGURE 1
FIGURE 1:
Medical thoracoscopic findings. A, Intrapleural fibrin deposition is remarkable. Multiloculated pleural effusions are visible. B, Approximately 10 minutes after administering urokinase, it is possible to identify the parietal pleura because urokinase fibrinolysis has progressed and the intrapleural fibrous septa has vanished.

A dose of 60,000 IU urokinase reconstituted in 100 mL of 0.9% saline was instilled through the biopsy port of the semirigid thoracoscope. Approximately 5 minutes after administering urokinase, intrapleural fibrinolysis was observed, along with the consequent reduction of fibrin nets. Approximately 10 minutes after administering urokinase, intrapleural fibrinolysis had continued to proceed and the intrapleural fibrous septa had vanished in the vicinity of the thoracoscope. As a result, the field of view under endoscopy became clear and we were able to identify the parietal pleura, which showed diffuse thickening (Fig. 1B).

Although its findings were observed within a limited space, that was sufficient to conduct biopsies of the parietal pleural thickening. After the biopsy, we completed the medical thoracoscopy without any complications. The examination time was 78 minutes. Hematoxylin and eosin staining of the biopsy specimen revealed atypical oval cells with round nuclei and moderate amounts of eosinophilic cytoplasm. Immunohistochemical staining revealed positive reactions to calretinin, WT1, and D2-40, and revealed negative reactions to CEA and TTF-1. We consequently diagnosed epithelioid pleural mesothelioma. The next day, the chest radiograph showed well-expanded right lung.

Medical thoracoscopy is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surface and allows for both diagnostic and therapeutic procedures.2 Its utility, however, is limited when fibrous adhesions are substantial.2 In fact, based on British Thoracic Society guidelines, lungs adherent to the chest wall throughout the hemithorax is an absolute contraindication to this procedure.3 Many reports, however, have focused on the efficacy of using fibrinolytic agents to break down pleural loculations, primarily in the setting of pleural infection. Furthermore, several small series have also reported the use of intrapleural fibrinolysis for the management of loculated malignant effusions.1,4,5 The application of intrapleural urokinase directly through a medical thoracoscope for loculated pleural effusions, however, has not been reported. In our patient, intrapleural urokinase instillation through the biopsy port of a semirigid thoracoscope at a dose of 60,000IU (diluted in 100 mL of normal saline) induced fibrinolysis and dissolution of multiloculated pleural effusions in the vicinity of the thoracosope within only 10 minutes. It improved the field of view under medical thoracoscopy to the extent that we were able to perform parietal pleural biopsies and obtain the successful diagnosis of malignant pleural mesothelioma.

We conclude that intrapleural instillation of urokinase may expand the diagnostic capability of medical thoracoscopy.

Satoshi Terashita, MD

Hiroaki Kawachi, MD

Sadao Horikawa, MD

Susumu Noguchi, MD

Tatsuyoshi Ikeue, MD

Takakazu Sugita, MD
Department of Respiratory Medicine Japanese Red Cross Wakayama Medical Center, Wakayama, Japan

REFERENCES

1. Hsu LH, Soong TC, Feng AC, et al. Intrapleural urokinase for the treatment of loculated malignant pleural effusions and trapped lungs in medically inoperable cancer patients. J Thorac Oncol. 2006;1:460–467.
2. Murthy V, Bessich JL. Medical thoracoscopy and its evolving role in the diagnosis and treatment of pleural disease. J Thorac Dis. 2017;9(suppl 10):S1011–S1021.
3. Rahman NM, Ali NJ, Brown G, et al. British Thoracic Society Pleural Disease Guideline Group. Local anaesthetic thoracoscopy: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65(suppl 2):ii54–ii60.
4. Thommi G, Nair CK, Aronow WS, et al. Efficacy and safety of intrapleural instillation of alteplase in the management of complicated pleural effusion or empyema. Am J Ther. 2007;14:341–345.
5. Davies CW, Traill ZC, Gleeson FV, et al. Intrapleural streptokinase in the management of malignant multiloculated pleural effusions. Chest. 1999;115:729–733.
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