Malignant pleural effusion due to angiosarcoma: A rare entity.

ABSTRACT: Angiosarcoma is a rare and aggressive vascular malignancy that typically originates in the skin or soft tissue of the body. It is known to have a propensity for metastasis to the lung parenchyma in the form of pulmonary nodules and cavitary lesions; however, a less commonly described entity is in the form of a malignant pleural effusion. Management of a malignant pleural effusion due to angiosarcoma presents a unique challenge. This article describes the challenges faced during one patient's diagnostic and treatment course, and the anticipated future complications of his aggressive disease.

Mesothelioma in situ with regressive malignant pleural effusion and an unexpected evolution: A case report.

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that originates from hyperplasia and metaplasia of the mesothelial cells that cover the pleural cavity. Previous exposure to asbestos is the main risk factor. Since MPM is often diagnosed at an advanced stage with rapid evolution and resistance to treatment, it is associated with an unfavorable outcome. Mesothelioma in situ (MIS) has been postulated as a preinvasive phase of MPM; however, its diagnostic criteria have been defined only recently. Diagnosis of MIS may represent an opportunity for early therapies with better results, but the optimal approach has not been defined thus far. Here, we report on a case of a 74-year-old man with right-sided pleural effusion and a previous history of occupational exposure to asbestos for 9 years who was diagnosed with MIS after a latency of 36 years. During follow-up, spontaneous disease regression was observed 5 months after the initial diagnosis; however, it recurred in the form of invasive epithelioid MPM. There is a paucity of literature on MIS and its evolution; however, our case provides relevant knowledge of this unusual behavior, which is important to define follow-up and therapeutic strategies for future cases.

Effect of malignant-associated pleural effusion on endothelial viability, motility and angiogenesis in lung cancer.

Malignant pleural effusion (MPE) and paramalignant pleural effusion (PPE) remain debilitating complications in lung cancer patients with poor prognosis and limited treatment options. The role of vascular endothelial cells has not been explored in the pleural environment of lung cancer. By integrating MPE and PPE as malignant-associated pleural fluid (MAPF), the current study aimed to evaluate the effect of MAPF on cell proliferation, migration and angiogenesis of HUVEC. First, increased capillaries were identified in the subpleural layer of lung adenocarcinoma. Compatible with pathological observations, the ubiquitous elevation of HUVEC survival was identified in MAPF culture regardless of the underlying cancer type, the driver gene mutation, prior treatments and evidence of malignant cells in pleural fluid. Moreover, MAPF enhanced HUVEC motility with the formation of lamellipodia and filopodia and focal adhesion complex. Tube formation assay revealed angiogenic behavior with the observation of sheet-like structures. HUVEC cultured with MAPF resulted in a significant increase in MAPK phosphorylation. Accompanied with VEGFR2 upregulation in MAPF culture, there was increased expressions of p-STAT3, HIF-1α and Nf-kB. VEGF/VEGFR2 blockade regressed endothelial migration and angiogenesis but not cell proliferation. Our data indicate the angiogenic activities of MAPF on vascular endothelial cells that revealed increased pleural capillaries in lung cancer. Targeting the VEGF/VEGFR2 pathway might modulate the angiogenic propensity of MAPF in future clinical investigations.

Novel pleural-bladder pump in malignant pleural effusions: from animal model to man.

Malignant pleural effusion is common and causes disabling symptoms such as breathlessness. Treatments are palliative and centred around improving symptoms and quality of life but an optimal management strategy is yet to be universally agreed. A novel pump system, allowing fluid to be moved from the pleural space to the urinary bladder, may have a role for the management of recurrent malignant pleural effusion. We hereby describe the first animal study using this device and the results of the first application in patients.

Driver mutations of young lung adenocarcinoma patients with malignant pleural effusion.

Young lung cancer patients have several distinct characteristics. However, there are limited epidemiological data of genetic abnormalities in this population. We conducted a prospective cohort study to delineate the various oncogenic driver mutations of lung adenocarcinoma in young Asian patients. We consecutively collected malignant pleural effusions (MPEs) from lung adenocarcinoma patients. RNA was extracted from MPEs for mutation analysis by reverse transcription-polymerase chain reaction and direct sequencing. Selected gene mutations for testing included EGFR, HER2, BRAF, KRAS, PIK3CA, JAK2, MEK1, NRAS, and AKT2 mutations, as well as EML4-ALK, ROS1, and RET fusions. We collected MPEs from 142 patients aged ≤50 years and 730 patients aged >50 years. Patients aged ≤50 years (91%) had a higher incidence of driver gene mutations than those aged >50 years (84%; P = .036), especially EML4-ALK (P < .001) and ROS1 (P < .001). Among patients aged ≤50 years, EGFR mutation was the major oncogenic driver mutation. The mutation rates of other genes were 18% EML4-ALK, 6% ROS1, 5% HER2, 1% RET, 1% BRAF, and 1% KRAS. We did not detect PIK3CA, JAK2, MEK1, NRAS, or AKT2 mutations. No difference in gender or smoking history was noted among those with different driver mutations. Patients who had a good performance status or received appropriate targeted therapy had longer overall survival. In conclusion, lung adenocarcinoma in Asian patients aged ≤50 years had a higher gene mutation rate than in those aged >50 years, especially EML4-ALK and ROS1 fusion. Mutation analysis may be helpful in determining targeted therapy for the majority of these patients.

Survivin is a negative prognostic factor in malignant pleural effusion.

BACKGROUND: Survivin is a well-known member of the inhibitor of apoptosis family, and has been related to increased tumour aggressivity, both in tissue and in pleural fluid. OBJECTIVES: In patients with malignant pleural effusion, we sought to investigate the changes in pleural fluid survivin concentrations induced by talc instillation into the pleural space. Those changes were also examined in relation to pleurodesis outcome and patient survival. METHODS: We investigated 84 patients with malignant pleural effusion who underwent talc pleurodesis. Of them, 32 had breast cancer, 25 lung cancer and 27 had mesothelioma. Serial samples of pleural fluid were obtained before thoracoscopy (baseline) and 24 hours thereafter. RESULTS: Survivin levels were successfully quantified in all pleural fluid samples, and they were significantly higher in samples obtained after thoracoscopic talc poudrage compared with baseline (P < .001). Patients with higher pleural fluid survivin levels at baseline had a significantly poorer pleurodesis outcome (P = .004). A 30 pg/mL cut-off for baseline survivin in pleural fluid predicted failure of pleurodesis with a 54% sensitivity and 79% specificity (P = .009). Moreover, median postpleurodesis survival of patients with baseline survivin levels ≥30 pg/mL was 4 months (range: 0.1-38), compared with 13 months (range: 0.1-259) in patients below that cut-off (P < .001). CONCLUSION: Elevated pleural fluid survivin concentrations are useful to predict failure of pleurodesis and are associated with shorter survival in patients with malignant pleural effusion.

Unexpandable lung from pleural disease.

Unexpandable lung is a common complication of malignant pleural effusions and inflammatory pleural diseases, such as pleural infection (e.g. empyema and complicated parapneumonic effusion) and noninfectious fibrinous pleuritis. Unexpandable lung due to pleural disease may be because of an active pleural process, and is referred to as malignant or inflammatory lung entrapment. An unexpandable lung may also be encountered in the setting of remote pleural inflammation resulting in a mature fibrous membrane overlying the visceral pleura preventing full expansion of the lung. This condition is termed trapped lung and may be understood as a form of defective healing of the pleural space. Trapped lung typically presents as a chronic, stable pleural effusion without evidence of active pleural disease. An unexpandable lung most often manifests itself as an inability of fully expanding the lung with pleural space drainage. Patients will either develop chest pain preventing complete drainage of the pleural space or develop a post-procedure pneumothorax. Pleural manometry and radiological imaging are useful in the assessment of an unexpandable lung. Pleural manometry can demonstrate abnormal lung expansion during drainage and imaging will demonstrate abnormal visceral pleural thickening found in trapped lung or malignant and inflammatory lung entrapment.

Treatment outcome comparisons between exons 19 and 21 EGFR mutations for non-small-cell lung cancer patients with malignant pleural effusion after first-line and second-line tyrosine kinase inhibitors.

Recent studies demonstrated a significantly increased frequency of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC) patients with malignant pleural effusions (MPEs). The purpose of this study is to investigate the effect of first-line and second-line EGFR-tyrosine kinase inhibitors (TKIs) in the treatment of NSCLC with MPEs harboring exon 19 deletion and L858R mutation. From 2010 to 2015, 203 NSCLC patients with MPEs harboring EGFR mutation treated with EGFR-TKIs were reviewed. The efficacy were evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. The objective response rate (ORR) and disease control rate (DCR) for patients treated with first-line and second-line EGFR-TKIs were 21.9%, 91.4% and 14.7%, 85.3%, respectively. The overall median PFS and OS of enrolled NSCLC patients with MPE were 9.3 months (95% CI, 8.4-10.2 months), 20.9 months (95% CI, 18.9-22.9 months) after first-line TKIs, and 7.6 months (95% CI, 6.6-8.6 months), 15.3 months (95% CI, 13.6-15.9 months) after second-line TKIs. The exon 19 deletion arm had a longer median PFS (9.4 vs 7.1 months, p=0.003) and OS (16.8 vs 13.8 months, p=0.003) compared with the L858R mutation arm after second-line TKIs. In a conclusion, EGFR genotype was an independent predictor of PFS and OS. No significant side effects differences between the two mutation groups was observed for first or second-line EGFR-TKIs. This study demonstrated that EGFR mutations are significant predictors for advanced NSCLC patients with MPE receiving second-line EGFR-TKIs treatment.

Malignant Pleural Effusion with Filariasis.

The occurrence of microfilaria in pleural fluid is rare. Filarial lung involvement occurs in the form of Tropical Pulmonary Eosinophilia with pulmonary infiltrates and peripheral eosinophilia. We report a 74-year-old male patient, non smoker who was admitted to our hospital with breathlessness and chest discomfort of two weeks duration. He had, eosinophilia and deranged renal function. X-ray chest revealed massive left sided pleural effusion. Pleural fluid analysis revealed atypical cells and pleural fluid cytology showed microfilaria (Wuchereria bancrofti), which were also found on peripheral smear.

Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity.

BACKGROUND: Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especially when cancer is diagnosed at a late stage. Moreover patients' responses vary and the outcome is unpredictable. Therefore, the identification of patients who will benefit most of chemotherapy treatment is important for accurate prognostication and better outcome. In this study, using malignant pleural effusions (MPE) from non-small cell lung cancer (NSCLC) patients, we established a collection of patient-derived Adenocarcinoma cultures which were characterized for their sensitivity to chemotherapeutic drugs used in the clinical practice. METHODS: Tumor cells present in MPEs of patients with NSCLC were isolated by density gradient centrifugation, placed in culture and genotyped by next generation sequencing. In a subset of cases patient derived xenografts (PDX) were obtained upon tumor cell inoculation in rag2/IL2 knock-out mice. Isolated primary cultures were characterized and tested for drug sensitivity by in vitro proliferation assays. Additivity, antagonism or synergy for combinatorial treatments were determined by analysis with the Calcusyn software. RESULTS: We have optimized isolation procedures and culture conditions to expand in vitro primary cultures from Malignant Pleural Effusions (MPEs) of patients affected by lung adenocarcinomas, the most frequent form of non small cell lung cancer. Using this approach we have been able to establish 16 primary cultures from MPEs. Cells were banked at low passages and were characterized for their mutational pattern by next generation sequencing for most common driver mutations in lung cancer. Moreover, amplified cultures were shown to engraft with high efficiency when injected in immunocompromised mice. Cancer cell sensitivity to drugs used in standard chemotherapy regimens was assessed either individually or in combination. Differential chemosensitivity and different mutation profiles were observed which suggests that this isolation method could provide a platform for predicting the efficacy of chemotherapy in the clinical setting. Most importantly for six patients it was possible to establish a correlation between drug response in vitro and response to therapy in the clinic. CONCLUSIONS: Results obtained using primary cultured cells from MPEs underscore the heterogeneity of NSCLC in advanced stage as indicated by drug response and mutation profile. Comparison of data obtained from in vitro assays with patients' responses to therapy leads to the conclusion that this strategy may provide a potentially useful approach for evaluating individual chemosensitivity profile and tailor the therapy accordingly. Furthermore, combining MPE-derived primary cultures with their genomic testing allows to identify patients eligible to trials with novel targeted agents.

Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial.

IMPORTANCE: For treatment of malignant pleural effusion, nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided because they may reduce pleurodesis efficacy. Smaller chest tubes may be less painful than larger tubes, but efficacy in pleurodesis has not been proven. OBJECTIVE: To assess the effect of chest tube size and analgesia (NSAIDs vs opiates) on pain and clinical efficacy related to pleurodesis in patients with malignant pleural effusion. DESIGN, SETTING, AND PARTICIPANTS: A 2×2 factorial phase 3 randomized clinical trial among 320 patients requiring pleurodesis in 16 UK hospitals from 2007 to 2013. INTERVENTIONS: Patients undergoing thoracoscopy (n = 206; clinical decision if biopsy was required) received a 24F chest tube and were randomized to receive opiates (n = 103) vs NSAIDs (n = 103), and those not undergoing thoracoscopy (n = 114) were randomized to 1 of 4 groups (24F chest tube and opioids [n = 28]; 24F chest tube and NSAIDs [n = 29]; 12F chest tube and opioids [n = 29]; or 12F chest tube and NSAIDs [n = 28]). MAIN OUTCOMES AND MEASURES: Pain while chest tube was in place (0- to 100-mm visual analog scale [VAS] 4 times/d; superiority comparison) and pleurodesis efficacy at 3 months (failure defined as need for further pleural intervention; noninferiority comparison; margin, 15%). RESULTS: Pain scores in the opiate group (n = 150) vs the NSAID group (n = 144) were not significantly different (mean VAS score, 23.8 mm vs 22.1 mm; adjusted difference, -1.5 mm; 95% CI, -5.0 to 2.0 mm; P = .40), but the NSAID group required more rescue analgesia (26.3% vs 38.1%; rate ratio, 2.1; 95% CI, 1.3-3.4; P = .003). Pleurodesis failure occurred in 30 patients (20%) in the opiate group and 33 (23%) in the NSAID group, meeting criteria for noninferiority (difference, -3%; 1-sided 95% CI, -10% to ∞; P = .004 for noninferiority). Pain scores were lower among patients in the 12F chest tube group (n = 54) vs the 24F group (n = 56) (mean VAS score, 22.0 mm vs 26.8 mm; adjusted difference, -6.0 mm; 95% CI, -11.7 to -0.2 mm; P = .04) and 12F chest tubes vs 24F chest tubes were associated with higher pleurodesis failure (30% vs 24%), failing to meet noninferiority criteria (difference, -6%; 1-sided 95% CI, -20% to ∞; P = .14 for noninferiority). Complications during chest tube insertion occurred more commonly with 12F tubes (14% vs 24%; odds ratio, 1.91; P = .20). CONCLUSIONS AND RELEVANCE: Use of NSAIDs vs opiates resulted in no significant difference in pain scores but was associated with more rescue medication. NSAID use resulted in noninferior rates of pleurodesis efficacy at 3 months. Placement of 12F chest tubes vs 24F chest tubes was associated with a statistically significant but clinically modest reduction in pain but failed to meet noninferiority criteria for pleurodesis efficacy. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN33288337.

High plasma levels of the pro-inflammatory cytokine IL-22 and the anti-inflammatory cytokines IL-10 and IL-1ra in acute pancreatitis.

BACKGROUND/OBJECTIVES: Pancreatic acinar cells are major targets of IL-22. Our aim is to study early plasma levels of IL-22, of pro- and anti-inflammatory cytokines in acute pancreatitis, and their association with severity or necrosis infection. METHODS: Consecutive patients admitted to the Department of Hepato-Gastroenterology at Poitiers University of Medicine Hospital (France) with a diagnosis of AP were prospectively enrolled. Plasma concentrations of IL-22, IL-6, IL-8, IL-1 α, IL-1ß, TNF- α, IFN-γ, IL-17A, IL-10, IL-1ra and IL-4 were assessed by multiple immunoassay at the admission time. A thoracoabdominal contrast-enhanced CT scan was performed at day 2. RESULTS: Sixty-two patients were included; 13 patients (21%) had a severe acute pancreatitis, 5 patients (8%) developed necrosis infection and 29 patients (47%) had pleural effusion. Plasma levels of IL-22 were high in AP (135 ± 31 vs 4.2 ± 1.8 pg/ml for controls, p < 0.05), but did not correlate with the severity of the disease, whereas IL-6, IL-10 and IL-1ra where enhanced in patients with severe acute pancreatitis and with pleural effusion. Patients who further developed necrosis infection had higher levels of IL-1ra at admission (p = 0.0004). CONCLUSION: In acute pancreatitis, high plasma levels of IL-22 are observed, regardless the severity of the disease. In contrast, severe forms were associated with increased levels of IL-6, IL-10 and IL-1ra. The beneficial or deleterious role of IL-22 in AP remains to be further studied.

Outcomes of Pleural Space Infections in Patients With Indwelling Pleural Catheters for Active Malignancies.

BACKGROUND: Pleural infections related to indwelling pleural catheters (IPCs) are an uncommon clinical problem. However, management decisions can be complex for patients with active malignancies due to their comorbidities and limited life expectancies. There are limited studies on the management of IPC-related infections, including whether to remove the IPC or use intrapleural fibrinolytics. METHODS: We conducted a retrospective cohort study of patients with active malignancies and IPC-related empyemas at our institution between January 1, 2005 and May 31, 2021. The primary outcome was to evaluate clinical outcomes in patients with malignant pleural effusions and IPC-related empyemas treated with intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) compared with those treated with tPA alone or no intrapleural fibrinolytic therapy. The secondary outcome evaluated was the incidence of bleeding complications. RESULTS: We identified 69 patients with a malignant pleural effusion and an IPC-related empyema. Twenty patients received tPA/DNase, 9 received tPA alone, and 40 were managed without fibrinolytics. Those treated with fibrinolytics were more likely to have their IPCs removed as part of the initial management strategy ( P =0.004). The rate of surgical intervention and mortality attributable to the empyema were not significantly different between treatment groups. There were no bleeding events in any group. CONCLUSION: In patients with IPC-related empyemas, we did not find significant differences in the rates of surgical intervention, empyema-related mortality, or bleeding complications in those treated with intrapleural tPA/DNase, tPA alone, or no fibrinolytics. More patients who received intrapleural fibrinolytics had their IPCs removed, which may have been due to selection bias.

Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Survival of lung adenocarcinoma patients with malignant pleural effusion.

In the era of targeted therapy, the association between lung adenocarcinoma patient survival and malignant pleural effusions (MPEs) remains unclear. This study investigated the clinical characteristics, survival and epidermal growth factor receptor (EGFR) gene (EGFR) mutation status of lung adenocarcinoma patients with MPE. From June 2005 to December 2010, consecutive pleural effusions were collected prospectively. Patient clinical characteristics, EGFR mutation status, and overall survival were analysed. We collected MPEs from 448 patients in stage IV lung adenocarcinoma at initial diagnosis. Median overall survival for patients with MPEs at initial diagnosis and following disease progression were 14.3 months and 21.4 months, respectively (p=0.001). There were 296 (66.1%) patients harbouring EGFR mutations, the mutation rates among patients with an MPE at initial diagnosis and one following disease progression were 68.2% and 56.6%, respectively (p=0.044); the L858R mutation rate was also higher among the former (32.6% versus 18.1%; p=0.009). Multivariate analysis revealed that patients who: developed MPEs following disease progression, harboured EGFR mutations, and received EGFR-tyrosine kinase inhibitor therapy, had longer overall survival. Patients in stage IV lung adenocarcinoma with MPEs at initial diagnosis have shorter overall survival and higher EGFR mutation rate, especially for L858R, than patients who develop MPEs following disease progression.

Comparison of modified Borg scale and visual analog scale dyspnea scores in predicting re-intervention after drainage of malignant pleural effusion.

BACKGROUND: Dyspnea is the most common symptom in patients with malignant pleural effusion (MPE). Treatment decisions are primarily based on the perception of dyspnea severity. AIMS: To study dyspnea perception following therapeutic thoracentesis using the visual analog scale (VAS) dyspnea score and modified Borg scale (MBS). To investigate whether patient reported outcome (PRO) measures can predict pleural re-interventions. PATIENTS AND METHODS: Consecutive patients presenting with symptomatic MPE and planned for therapeutic thoracentesis were asked to complete MBS and VAS dyspnea scores (both at rest and during exercise) daily for 14 consecutive days. Physicians, unaware of the results of these PRO measures, decided on the necessity of a re-intervention, according to routine care. PRO measures were analyzed and correlated with performed re-interventions and the volume of removed fluid. RESULTS: Forty-nine out of 64 consecutive patients returned the diaries. Twenty-eight patients (57 %) had a re-intervention within 30 days. Patients who required a re-intervention reported significantly higher MBS than patients who did not. The extent of increase in MBS during exercise was related to the need for re-intervention. Regarding the MBS during exercise, median time to maximal relief was 2 days. Re-intervention was required sooner when larger volumes were drained. CONCLUSION: Patient reported outcomes are useful tools to assess treatment effect of therapeutic thoracentesis. Median time to maximal relief is 2 days. MBS rather than VAS dyspnea score appears to be more prognostic for repeat pleural drainage within 30 days.

Malignant pleural effusion in the palliative care setting.

Malignant pleural effusion (MPE) is a distressing condition for the patient, causing many symptoms such as shortness of breath, dry cough, an uncomfortable feeling of heaviness in the chest, and pleuritic pain. MPE reduces quality of life and functional status. It indicates that the disease is now advanced and life expectancy is generally short, with a median prognosis of 3-12 months depending on the stage of the disease and the underlying malignancy. This paper discusses the palliative treatment options for MPE, which include thoracentesis, medical pleurodesis, and indwelling pleural catheter. It is important that decisions about treatment are made within the multidisciplinary team and alongside the patient and family. Treatment goals are concerned with the relief or elimination of dyspnoea, restoration of near-normal activity and function, and avoidance of inpatient care.

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.