Combination Tissue Plasminogen Activator and DNase for Loculated Malignant Pleural Effusions: A Single-center Retrospective Review.

BACKGROUND: Indwelling pleural catheters (IPCs) are frequently used for the management of malignant pleural effusions (MPEs), but drainage can be impaired by pleural loculations. We aimed to evaluate the safety and effectiveness of intrapleural tissue plasminogen activator (tPA) versus combination tPA-deoxyribonuclease (DNase) in the treatment of loculated MPE. METHODS: We performed a retrospective review of patients with confirmed or presumed MPEs requiring IPC insertion. We compared the efficacy of intrapleural tPA, tPA-DNase, and procedural intervention on pleural fluid drainage. Secondary endpoints included the need for future pleural procedures (eg, thoracentesis, IPC reinsertion, chest tube insertion, or surgical intervention), IPC removal due to spontaneous pleurodesis, and IPC-related complications. RESULTS: Among 437 patients with MPEs, loculations developed in 81 (19%) patients. Twenty-four (30%) received intrapleural tPA, 46 (57%) received intrapleural tPA-DNase, 4 (5%) underwent a procedural intervention, and 7 (9%) received ongoing medical management. tPA improved pleural drainage in 83% of patients, and tPA-DNase improved pleural drainage in 80% of patients. tPA alone may be associated with increased rates of spontaneous pleurodesis compared with tPA-DNase. There was no difference in complications when comparing tPA, combination tPA-DNase, procedural intervention, and no therapy. CONCLUSION: Both intrapleural tPA and combination tPA-DNase appear to be safe and effective in improving pleural fluid drainage in selected patients with loculated MPE, although further studies are needed.

Pre-transplant malignancy is associated with increased risk of de novo malignancy post-lung transplantation.

BACKGROUND: At least 20% of lung transplant recipients will be diagnosed with a malignancy within 5 years of transplant. Transplant candidates with a history of pre-transplant malignancy must meet remission criteria before listing to minimize the risk of recurrence, however these patients may have an intrinsic predisposition to developing subsequent cancers which can be amplified by immunosuppression. We assessed whether pre-transplant malignancy was associated with an increased risk of developing malignancy of any type after lung transplant. METHODS: We conducted a single centre retrospective cohort study of patients undergoing lung transplant between January 2006 and December 2017. We used a proportional hazards regression model to test whether preTM was associated with the risk of developing one or more postTM after lung transplant, adjusted for known cancer risk factors. RESULTS: 497 adult patients underwent lung transplantation during the study period and 26 (5.2%) had pre-transplant malignancies. Out of 29 pre-transplant cancer diagnoses, prostate cancer was the most common (17.2%), followed by breast cancer and basal cell carcinoma (13.8% each). 108 (22%) patients developed post-transplant malignancy with a total of 328 cancer diagnoses. The most common post-transplant malignancy was non-melanoma skin cancer (86.3%), followed by solid organ cancers (7.6%). Pre-transplant malignancy was associated with an adjusted HR of 3.24 (95% CI 1.71 to 6.14, p < 0.001) for the development of post-transplant malignancy. Recurrence of the pre-transplant malignancy only occurred in 3 patients post-transplant. CONCLUSIONS: History of pre-transplant malignancy was associated with a more than three times likelihood of development of a post-transplant malignancy compared to recipients without a previous history of cancer, the majority being unrelated to the initial malignancy. These findings highlight the importance of frequent cancer surveillance in lung transplant recipients, especially in those with a history of pre-transplant malignancy.

Quantification of lung water in heart failure using cardiovascular magnetic resonance imaging.

BACKGROUND: Pulmonary edema is a cardinal feature of heart failure but no quantitative tests are available in clinical practice. The goals of this study were to develop a simple cardiovascular magnetic resonance (CMR) approach for lung water quantification, to correlate CMR derived lung water with intra-cardiac pressures and to determine its prognostic significance. METHODS: Lung water density (LWD, %) was measured using a widely available single-shot fast spin-echo acquisition in two study cohorts. Validation Cohort: LWD was compared to left ventricular end-diastolic pressure or pulmonary capillary wedge pressure in 19 patients with heart failure undergoing cardiac catheterization. Prospective Cohort: LWD was measured in 256 subjects, including 121 with heart failure, 82 at-risk for heart failure and 53 healthy controls. Clinical outcomes were evaluated up to 1 year. RESULTS: Within the validation cohort, CMR LWD correlated to invasively measured left-sided filling pressures (R = 0.8, p < 0.05). In the prospective cohort, mean LWD was 16.6 ± 2.1% in controls, 17.9 ± 3.0% in patients at-risk and 19.3 ± 5.4% in patients with heart failure, p < 0.001. In patients with or at-risk for heart failure, LWD >  20.8% (mean + 2 standard deviations of healthy controls) was an independent predictor of death, hospitalization or emergency department visit within 1 year, hazard ratio 2.4 (1.1-5.1, p = 0.03). CONCLUSIONS: In patients with heart failure, increased CMR-derived lung water is associated with increased intra-cardiac filling pressures, and predicts 1 year outcomes. LWD could be incorporated in standard CMR scans.