Management of Intrapleural Sepsis with Once Daily Use of Tissue Plasminogen Activator and Deoxyribonuclease.

BACKGROUND: Pleural infection remains a significant cause of morbidity, mortality, prolonged hospital stay, and increased healthcare costs, despite advances in therapy. Twice daily intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) initiated at the time of diagnosis has been shown to significantly improve radiological outcomes and decrease the need for surgery. OBJECTIVES: To analyze our experience with once daily tPA/DNase for intrapleural sepsis. METHODS: Data derived from consecutive patients with empyema and complicated parapneumonic effusion who received once daily intrapleural tPA/DNase between January 2012 and August 2014 were reviewed. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity, length of hospital stay, need for surgery, and adverse events. RESULTS: 55 consecutive patients (33 male; mean age ± SD, 54.6 ± 16.1 years) were treated with once daily intrapleural tPA/DNase for 3 days. The majority of the patients (n = 51; 92.7%) were successfully managed without the need for surgical intervention. The mean change in pleural opacity measured on chest radiograph at day 7 was -28.8 ±17.6%. The median amount of fluid drained was 2,195 ml. No serious adverse events requiring discontinuation of intrapleural medications were observed. The most common complication was pain requiring escalating doses of analgesics (n = 8; 15%). Compliance with the protocol was excellent. CONCLUSION: Early administration of once daily intrapleural tPA/DNase for 3 days is safe, effective, and represents a viable option for the management of empyema and complicated parapneumonic effusion.

Management of chronic empyema with unexpandable lung in poor surgical risk patients using an empyema tube.

OBJECTIVES: High preoperative risk precludes decortication and other surgical interventions in some patients with chronic empyema. We manage such patients by converting the chest tube into an "empyema tube," cutting the tube near the skin and securing the end with a sterile clip to allow for open pleural drainage. The patient is followed serially, and the tube gradually withdrawn based on radiological resolution and amount of drainage. METHODS: Between 2010 and 2014, patients with chronic empyema and unexpandable lung, deemed high-risk surgical candidates, had staged chest tube removal, and were included for the study. The volume of fluid drained, culture results, duration of drainage, functional status, and comorbidities were recorded. MEASUREMENTS AND RESULTS: Eight patients qualified. All had resolution of infection. The tube was removed after an average of 73.6 ± 49.73 (95% confidence interval [CI]) days. The mean duration of antibiotic treatment was 5.37 ± 1.04 (95% CI) weeks. None required surgery or experienced complications from an empyema tube. CONCLUSION: A strategy of empyema tube drainage with staged removal is an option in appropriately selected patients with chronic empyema, unexpandable lung, and poor surgical candidacy.

Treatment of alveolar-pleural fistula with endobronchial application of synthetic hydrogel.

BACKGROUND: Alveolar-pleural fistula with persistent air leak is a common problem causing significant morbidity, prolonged hospital stay, and increased health-care costs. When conventional therapy fails, an alternative to prolonged chest-tube drainage or surgery is needed. New bronchoscopic techniques have been developed to close the air leak by reducing the flow of air through the leak. The objective of this study was to analyze our experience with bronchoscopic application of a synthetic hydrogel for the treatment of such fistulas. METHODS: We conducted a retrospective study of patients with alveolar-pleural fistula with persistent air leaks treated with synthetic hydrogel application via flexible bronchoscopy. Patient characteristics, underlying disease, and outcome of endoscopic treatment were analyzed. RESULTS: Between January 2009 and December 2013, 22 patients (14 men, eight women; mean age ± SD, 62 ± 10 years) were treated with one to three applications of a synthetic hydrogel per patient. The primary etiology of persistent air leak was necrotizing pneumonia (n = 8), post-thoracic surgery (n = 6), bullous emphysema (n = 5), idiopathic interstitial pneumonia (n = 2), and sarcoidosis (n = 1). Nineteen patients (86%) had complete resolution of the air leak, leading to successful removal of chest tube a mean ( ± SD) of 4.3 ± 0.9 days after last bronchoscopic application. The procedure was very well tolerated, with two patients coughing up the hydrogel and one having hypoxemia requiring bronchoscopic suctioning. CONCLUSIONS: Bronchoscopic administration of a synthetic hydrogel is an effective, nonsurgical, minimally invasive intervention for patients with persistent pulmonary air leaks secondary to alveolar-pleural fistula.

Treatment of isolated mediastinal and hilar recurrence of lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of chemotherapy with cisplatin.

PURPOSE: A common pattern of recurrence in lung cancer after receiving full dose external beam radiation therapy (EBRT) to targeted sites is isolated mediastinal and hilar recurrence (IMHR). Treatment options for these patients are limited to palliative radiation, chemotherapy, and/or best supportive care. We describe our experience with treating IMHR with bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of cisplatin (ITC). METHODS: Patients treated between Jan 2009-September 2014 with ITC for IMHR were included. Patient demographics, tumor histology, size, concurrent therapy, location, number of sites treated, treatment sessions, and encounters were abstracted. Responses were analyzed on follow-up scans 8-12 weeks after the last treatment session using RECIST 1.1 criteria. Locoregional recurrence, progression-free survival (PFS), and overall survival were measured. RESULTS: 50 sites were treated in 36 patients (19 males, 17 females) with mean age 61.9±8.5 years. Eight sites treated on subsequent encounters were excluded and one patient had an unevaluable response, leaving 35 patients and 41 sites for final analysis. 24/35 (69%) had complete or partial response (responders), whereas 11/35 (31%) had stable or progressive disease (non-responders). There were no significant differences in response based on histology, size, and concurrent therapy. Median survival for the group was 8 months (95% CI of 6-11 mo). Responders had significantly higher survival and PFS than non-responders. Two patients treated with concurrent EBRT, developed broncho-mediastinal fistula. CONCLUSION: EBUS guided intratumoral cisplatin for IMHR appears to be safe and effective, and may represent a new treatment paradigm for this patient population.

Restoration of Patency to Central Airways Occluded by Malignant Endobronchial Tumors Using Intratumoral Injection of Cisplatin.

RATIONALE: Malignant airway obstruction is commonly found in patients with lung cancer and is associated with significant morbidity and mortality. Relieving malignant obstruction may improve symptoms, quality of life, and life expectancy. OBJECTIVES: The objective of this study was to analyze our experience with bronchoscopic endobronchial intratumoral injection of cisplatin for malignant airway obstruction. METHODS: We conducted a retrospective analysis of patients with malignant airway obstruction treated with bronchoscopic intratumoral injection of cisplatin. Patient characteristics, histology, degree of airway obstruction, procedural methods, treatment cycles, performance status, and therapeutic outcomes were evaluated. Tumor response was analyzed based on bronchoscopic measurements performed on completion the of final treatment session. Adverse events and overall survival were abstracted. MEASUREMENTS AND MAIN RESULTS: Between January 2009 and September 2014, 22 patients (10 men, 12 women; mean age ± SD, 64.4 ± 9.5 yr) were treated with one to four injections of 40 mg of cisplatin mixed in 40 ml of 0.9% NaCl. Treatments were completed 1 week apart. The primary etiologies of airway obstruction included squamous cell carcinoma (n = 11), adenocarcinoma (n = 6), small cell carcinoma (n = 2), large cell undifferentiated carcinoma (n = 1), and metastatic endobronchial cancer (n = 2). Twenty-one of 22 patients were evaluable for response. The majority of patients (15/21, 71.4%) responded to therapy, defined as greater than 50% relative reduction in obstruction from baseline. Treatment response was obtained regardless of tumor histology, concurrent systemic therapy, number of treatment cycles administered, performance status, or use of additional ablative interventions. Responders had significantly improved overall survival as compared with nonresponders, although the difference was small. Severe treatment-related side effects or complications were not observed. CONCLUSIONS: Subject to the limitations of a single-center retrospective study and a subjective primary outcome measure, we have demonstrated the feasibility of improving the patency of central airways that are largely or completely occluded by endobronchial malignant tumor using intraluminal injection of cisplatin. Additional longer-term, larger-scale safety and comparative effectiveness studies of this palliative treatment modality are warranted.