Pleural Loculation Research Articles

Evaluation of the Diagnostic Accuracy of a Computed Tomography-Based Scoring System in the Differentiation between Malignant and Benign Pleural Effusion

Abstract Background Pleural effusion in particular is considered a sign of an underlying pathology, so ti is necessary ot search for the cause and determine whether it is a benign cause or a malignant one as they differ in treatment and prognosis. Aim of the Work To assess the accuracy of contrast-enhanced CT chest to predict the nature of pleural effusion whether benign or malignant using the CT-based scoring system developed by Porcel et al.'(1) Patients and Methods This study was a retrospective study that involved reviewing the contrast-enhanced CT chest done at the radiodiagnosis department in Ain Shams University Hospitals of 30 adult patients (age >18 years old) withunilateral or bilateral pleural effusion, and scoring ti according to hte Porcel et al (" CT scoring system while being blinded to the final diagnosis. The total score was then compared to the biopsy or cytology of the patient to determine its accuracy. Results Analyzing the data showed that the highly significant item of the scoring system denoting malignancy was pleural lesion followed by lung masses, liver metastasis, abdominal masses, and absence of pericardial effusion. The cutoff value in our study was found to be total score >7 denoting malignancy with a sensitivity of 94.12%, a specificity of 100%, a PPV (positive predictive value) of 100, a NPV (negative predictive value) of 92.2 and AUC (area under curve) = 0.986. On the other hand, the cutoff value of the study done by Porcel et al ( (27 denotes malignancy) gave a sensitivity of 94.1%, a specificity of 92.3%,a PPV of 94.12, a NPV of 92.31, and an accuracy of 93.33% in our study while in their study gave a sensitivity of 88%, aspecificity of 94%, and AUC = 0.919. Conclusion This is a simple chest CT scan scoring system, which includes the evaluation of pleural nodularity or thickening, liver metastases, abdominal masses, lung nodules or masses, pleural loculations, pericardial effusions, and cardiomegaly. It can be used as a reliable tool that helps determine the differential diagnosis ofpleural effusion yet does not replace cytology/biopsy. Further studies assessing this C T scan score are recommended.

A PET-CT score for discriminating malignant from benign pleural effusions

Background and objectivesThe results of previous PET-CT studies are contradictory for discriminating malignant from benign pleural effusions. We purpose to develop a PET-CT score for differentiating between benign and malignant effusions. Patients and methodsWe conducted a prospective study of consecutive patients with pleural effusions undergoing PET-CT from October 2013 to October 2019 (referral cohort). PET-CT scan features evaluated using the SUV were: linear thickening; nodular thickening; nodules; masses; circumferential thickening; mediastinal and fissural pleural involvement; intrathoracic lymph nodes; pleural loculation; inflammatory consolidation; pleural calcification; cardiomegaly; pericardial effusion; bilateral effusion; lung mass; liver metastasis and other extra-pleural malignancy. The results were validated in an independent prospective cohort from November 2019 to June 2021. ResultsOne hundred and ninety-nine patients were enrolled in the referral cohort (91 with malignant effusions and 108 benign). The most useful parameters for the development of a PET-CT score were: nodular pleural thickening, pleural nodules with SUV>7.5, lung mass or extra pleural malignancy (10 points each), mammary lymph node with SUV>4.5 (5 points) and cardiomegaly (−1 point). With a cut-off value of >9 points in the referral cohort, the score established the diagnosis of malignant pleural effusion with sensitivity 87.9%, specificity 90.7%, positive predictive value 88.9%, negative predictive value 89.9%, positive likelihood ratio 7.81 and negative likelihood ratio 0.106. These results were validated in an independent prospective cohort of 75 patients. ConclusionsPET-CT score was shown to provide relevant information for the identification of malignant pleural effusion.

A PET-CT score for discriminating malignant from benign pleural effusions

Background and objectivesThe results of previous PET-CT studies are contradictory for discriminating malignant from benign pleural effusions. We purpose to develop a PET-CT score for differentiating between benign and malignant effusions. Patients and methodsWe conducted a prospective study of consecutive patients with pleural effusions undergoing PET-CT from October 2013 to October 2019 (referral cohort). PET-CT scan features evaluated using the SUV were: linear thickening; nodular thickening; nodules; masses; circumferential thickening; mediastinal and fissural pleural involvement; intrathoracic lymph nodes; pleural loculation; inflammatory consolidation; pleural calcification; cardiomegaly; pericardial effusion; bilateral effusion; lung mass; liver metastasis and other extra-pleural malignancy. The results were validated in an independent prospective cohort from November 2019 to June 2021. ResultsOne hundred and ninety-nine patients were enrolled in the referral cohort (91 with malignant effusions and 108 benign). The most useful parameters for the development of a PET-CT score were: nodular pleural thickening, pleural nodules with SUV>7.5, lung mass or extra pleural malignancy (10 points each), mammary lymph node with SUV>4.5 (5 points) and cardiomegaly (−1 point). With a cut-off value of >9 points in the referral cohort, the score established the diagnosis of malignant pleural effusion with sensitivity 87.9%, specificity 90.7%, positive predictive value 88.9%, negative predictive value 89.9%, positive likelihood ratio 7.81 and negative likelihood ratio 0.106. These results were validated in an independent prospective cohort of 75 patients. ConclusionsPET-CT score was shown to provide relevant information for the identification of malignant pleural effusion.

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

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. 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. 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. 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.

Risk factors of repetitive thoracentesis of malignant pleural effusion in naive non-small cell lung carcinoma

Almost 40% of Non Small Cell Lung (NSCLC) patients develop Malignant Pleural Effusion (MPE). Nowadays, clinicians prefer to perform a repetitive thoracentesis rather than a definitive procedure, which causes pleural loculations and inflammation. This study aimed to identify risk factors of repeated thoracentesis MPE in NSCLC. This was an observational analytic study with a retrospective cohort design held at Prof.Dr. I.G.N.G Ngoerah General Hospital from January 2018 to June 2022. There were 95 subjects who participated in this study. The median time of repetitive thoracentesis MPE in NSCLC is 3 days (95% CI 1,9-4). The difference in location tumor in the peripheral was 3 days (2.25-3.74) while in the central was 7 days (4.24-9.75), p=0.21. The difference in histology type, Adenocarcinoma was 3 days (1.86-4.13) while squamous cell carcinoma was 4 days (2.53-5.46), p=0.69. Pleural fluid cytology positive was 6 days (2.78-9.22) while negative was 3 days (1.83-4.16), p=0.51. The EGFR mutation positive was 4 days (2.48-5.52) while negative 3 days (1.68-4.31), p=0.78. LDH levels ≥821 IU/L was 3 days (1.49-4.50) while <821 IU/L was 4 days (2.32-5.67), p=0.81. The size of pleural effusion massive was 3 days (1.88-4.11) while non-massive was 4 days (0.93-7.06), p=0.49.

Update on Novel Targeted Therapy for Pleural Organization and Fibrosis.

Pleural injury and subsequent loculation is characterized by acute injury, sustained inflammation and, when severe, pathologic tissue reorganization. While fibrin deposition is a normal part of the injury response, disordered fibrin turnover can promote pleural loculation and, when unresolved, fibrosis of the affected area. Within this review, we present a brief discussion of the current IPFT therapies, including scuPA, for the treatment of pathologic fibrin deposition and empyema. We also discuss endogenously expressed PAI-1 and how it may affect the efficacy of IPFT therapies. We further delineate the role of pleural mesothelial cells in the progression of pleural injury and subsequent pleural remodeling resulting from matrix deposition. We also describe how pleural mesothelial cells promote pleural fibrosis as myofibroblasts via mesomesenchymal transition. Finally, we discuss novel therapeutic targets which focus on blocking and/or reversing the myofibroblast differentiation of pleural mesothelial cells for the treatment of pleural fibrosis.

Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial

ObjectivesWe describe techniques and results of image-guided delivery of mesothelin-targeted chimeric antigen receptor (CAR) T cells in patients with pleural malignancies in a phase I/II trial (ClinicalTrials.gov: NCT02414269). Materials and methodsPatients without a pleural catheter or who lack effusion for insertion of a catheter (31 of 41) were administered intrapleural CAR T cells by interventional radiologists under image guidance by computed tomography or ultrasound. CAR T cells were administered through a needle in an accessible pleural loculation (intracavitary) or following an induced loculated artificial pneumothorax. In patients where intracavitary infusion was not feasible, CAR T cells were injected via percutaneous approach either surrounding and/or in the pleural nodule/thickening (intratumoral). Pre- and post-procedural clinical, laboratory, and imaging findings were assessed. ResultsCAR T cells were administered intrapleurally in 31 patients (33 procedures, 2 patients were administered a second dose) with successful delivery of planned dose (10–186 mL); 14/33 (42%) intracavitary and 19/33 (58%) intratumoral. All procedures were completed within 2 h of T-cell thawing. There were no procedure-related adverse events greater than grade 1 (1 in 3 patients had prior ipsilateral pleural fusion procedures). The most common imaging finding was ground glass opacities with interlobular septal thickening and/or consolidation, observed in 12/33 (36%) procedures. There was no difference in the incidence of fever, CRP, IL-6, and peak vector copy number in the peripheral blood between infusion methods. ConclusionImage-guided intrapleural delivery of CAR T cells using intracavitary or intratumoral routes is feasible, repeatable and safe across anatomically variable pleural cancers.

Loculations and Associated Risk Factors of Childhood Pleural Tuberculosis.

Background: Pleural loculation in childhood pleural tuberculosis (TB) remains a problem in practice, it is usually associated with failure drainage. Therefore, to improve the management of childhood pleural TB, a retrospective study was conducted to identify the risk factors associated with loculated effusion in childhood pleural TB.Methods: Between January 2006 and December 2019, consecutive children (≤15 years old) with tuberculous pleural effusion (definite and possible) were included for further analysis. The demographic, clinical, laboratory, and radiographic features were collected from the medical records. Univariate and multivariate logistic regressions were used to explore the factors associated with the presence of pleural loculation in children with pleural TB.Results: A total of 154 children with pleural TB (definite, 123 cases; possible, 31 cases) were included in our study and then were classified as loculated effusion (n = 27) and non-loculated effusion (n = 127) groups by chest X-ray or ultrasonography. Multivariate analysis revealed that male gender (age-adjusted OR = 3.903, 95% CI: 1.201, 12.683), empyema (age-adjusted OR = 4.499, 95% CI: 1.597, 12.673), peripheral monocytes ≤0.46 × 109/L (age-adjusted OR = 4.122, 95% CI: 1.518, 11.193) were associated with the presence of loculated effusion in children with pleural TB.Conclusion: In conclusion, several characteristics, such as male gender, empyema, and peripheral monocyte count have been identified as risk factors for pleural loculation in children with pleural TB. Our findings may be helpful to improve the management of pleural loculation in childhood pleural TB.

Derivation and validation of a 18F-FDG PET/CT scoring model to predict malignant pleural effusion.

To develop an 18F-fluorodeoxyglucose PET/computed tomography (CT) scoring model based on metabolic and radiologic findings of the pleura and fluid to identify malignant pleural effusion. The PET and CT findings from patients with pleural effusion in the derivation dataset were used to develop a scoring model. Then, the diagnostic accuracy of the predictive score was verified by the validation dataset. Eight parameters independently predicting malignancy were retained in the scoring model, including pleural nodules or masses (4 points), focal pleural thickening (2 points), absence of pleural loculation (2 points), thickness of mediastinal pleura involvement ≥0.5 cm (2 points), maximum standardized uptake value (SUVmax) of mediastinal pleura involvement ≥2.3 (2 points), thickness of nonmediastinal pleura involvement ≥0.5 cm (1 point), SUVmax of nonmediastinal pleura involvement ≥3.0 (1 point) and fluid SUVmax ≥1.6 (1 point). The operating characteristics of the PET/CT score were 0.958 area under the curve (AUC), 88.6% sensitivity, 91.2% specificity, 10.09 positive likelihood ratio and 0.13 negative likelihood ratio, with 6 points as the threshold. These values in the validation dataset were 0.947, 91.7%, 88.4%, 7.91 and 0.094, respectively. No difference was found in AUCs between the derivation and validation datasets (z = 0.517, P = 0.697). The negative predictive value was 99.4% in the score from 0 to 2, and the positive predictive value was 98.3% for patients with score between 9 and 15. The PET/CT scoring model is a valuable strategy to help physicians to distinguish malignant-benign pleural effusion and stratify patients who will benefit from invasive procedures.

The Contribution of the Urokinase Plasminogen Activator and the Urokinase Receptor to Pleural and Parenchymal Lung Injury and Repair: A Narrative Review.

Pleural and parenchymal lung injury have long been characterized by acute inflammation and pathologic tissue reorganization, when severe. Although transitional matrix deposition is a normal part of the injury response, unresolved fibrin deposition can lead to pleural loculation and scarification of affected areas. Within this review, we present a brief discussion of the fibrinolytic pathway, its components, and their contribution to injury progression. We review how local derangements of fibrinolysis, resulting from increased coagulation and reduced plasminogen activator activity, promote extravascular fibrin deposition. Further, we describe how pleural mesothelial cells contribute to lung scarring via the acquisition of a profibrotic phenotype. We also discuss soluble uPAR, a recently identified biomarker of pleural injury, and its diagnostic value in the grading of pleural effusions. Finally, we provide an in-depth discussion on the clinical importance of single-chain urokinase plasminogen activator (uPA) for the treatment of loculated pleural collections.

Insufficient Fibrinolysis in COVID-19: A Systematic Review of Thrombolysis Based on Meta-Analysis and Meta-Regression

Background: How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists. To investigate whether abnormal fibrinolysis is a culprit or protector or both, we associated elevated plasma D-dimer with clinical variables to identify a panoramic view of the derangements of fibrinolysis that contribute to the pathogenesis of COVID-19 based on studies available in the literature.Methods: We performed this systematic review based on both meta-analysis and meta-regression to compute the correlation of D-dimer at admission with clinical features of COVID-19 patients in retrospective studies or case series. We searched the databases until Aug 18, 2020, with no limitations by language. The first hits were screened, data extracted, and analyzed in duplicate. We did the random-effects meta-analyses and meta-regressions (both univariate and multivariate). D-dimer associated clinical variables and potential mechanisms were schematically reasoned and graphed.Findings: Our search identified 42 observational, or retrospective, or case series from six countries (n=14,862 patients) with all races and ages from 1 to 98-year-old. The weighted mean difference of D-dimer was 0.97 ug/mL (95% CI 0.65, 1.29) between relatively mild (or healthy control) and severely affected groups with significant publication bias. Univariate meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels, including 3 demographics, 5 comorbidities, 22 laboratory tests, 18 organ injury biomarkers, 8 severe complications, and 2 outcomes (discharge and death). Of these, 11 readouts were negatively associated with the level of plasma D-dimer. Further, age and gender were confounding factors for the identified D-dimer associated variables. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN, bilirubin, ALT, AST, systolic blood pressure, and CK. We thus propose that insufficient hyperfibrinolysis (fibrinolysis is accelerated but unable to prevent adverse clinical impact for clinical deterioration COVID-19) as a peculiar mechanism.Interpretation: The findings of this meta-analysis- and meta-regression-based systematic review supports elevated D-dimer as an independent predictor for mortality and severe complications. D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and locally (i.e., in the lung) hyperactive derangements of fibrinolysis. D-dimer and associated clinical biomarkers and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.Funding: NIH grants: HL87017 (HLJ), HL095435 (MAM), HL134828 (MAM), HL130402 (AK&SI), AI112381(SLL), AI150473 (SLL), HL154103 (SI &AK), and HL14285301 (SI)Declaration of Interests: None of the authors have any conflict of interest to declare. Unrelated to the subject of this review, Dr. Idell serves as a Founder and Chief Scientific Officer of Lung Therapeutics Inc., (LTI) and a member of the Board of Directors of LTI, which has conducted Phase 1 trial and and is now conducting a Phase 2 clinical trial of urokinase plasminogen activator for patients with infectious pleural loculation and failed drainage. He has an equity position (first tier COI) in the company, as does the University of Texas Horizon Fund and The University of Texas Health Science Center at Tyler (UTHSCT). He has a conflict of interest plan acknowledging and managing these declared conflicts of interest through The University of Texas Health Science Center at Tyler (UTHSCT) and UT System. Dr. Komissariv has received funding from LTI and has a COI management plan at UTHSCT accordingly.

ASPERGILLUS FUMIGATUS EMPYEMA IN AN IMMUNOCOMPROMISED PATIENT WITH RHEUMATOID ARTHRITIS

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Fungal empyema is a rare entity (less than 1 percent of all cases) with Candida spp. being the most common etiological agents and only a few cases due to Aspergillus spp (1). CASE PRESENTATION: A 74-year-old male with history of rheumatoid arthritis on maintenance prednisone and methotrexate presented with progressive exertional shortness of breath and productive cough for 3 months. Chest X-ray showed a large left pleural collection with air-fluid level and thick wall. Computed tomography (CT) of the chest showed a large pleural loculation with an air fluid level surrounded by thickened wall, consolidation of the left lower lobe, and scattered tree-in-bud opacities bilaterally. A small right pleural effusion with multiple benign appearing pulmonary nodules was also noted. Video-assisted thoracoscopic surgery (VATS) with decortication was done. Pleural biopsy showed a dense mat of branching, septated fungal hyphae involving necrotic pleura. Pleural fluid cultures grew Aspergillus fumigatus. IV liposomal amphotericin was started, caused hypotension, was changed to IV voriconazole which led to acute liver injury and was eventually treated with micafungin. Repeat cultures from thoracostomy drainage grew Streptococcus viridans and Neisseria flava. They were suspected to have seeded from a bronchopleural fistula and IV piperacillin-tazobactam was given for coverage. The hospital course was complicated by left sided pneumothorax post-VATS requiring reinsertion of chest tube, atrial fibrillation with rapid ventricular rate, dysphagia and right sided pleural effusion requiring diagnostic thoracentesis (exudative fluid with negative culture). Patient requested discontinuation of medical therapy and transition to comfort measures due to his extended hospital stay. He was eventually transferred to hospice. DISCUSSION: Among the Aspergillus empyema cases, A. fumigatus is isolated most often, though other spp., such as A. flavus and A. terreus, have also been implicated (2). Fifty percent of such cases are polymicrobial. Risk factors include immunocompromised state and conditions predisposing to bronchopleural fistula (tuberculosis, sarcoidosis, cavitary pneumonia, thoracic surgery, pneumonectomy and lung transplantation). Diagnosis is made from pleural fluid culture or pleural biopsy stains showing characteristic hyphae. Pleural fluid is generally turbid with high protein, low glucose, increased neutrophils and galactomannan. Treatment is combined surgical (drainage of the pleural cavity, necrotic tissue resection and closure of bronchopleural fistula) and prolonged systemic antifungal therapy with triazoles (first line) or echinocandins (salvage therapy for treatment failure or tolerability concerns) (3). CONCLUSIONS: Aspergillus empyema is a rare but highly morbid entity that should be considered in immunocompromised hosts and requires surgical and prolonged medical management. Reference #1: Ko SC, Chen KY, Hsueh PR, Luh KT, Yang PC. Fungal empyema thoracis: an emerging clinical entity. Chest. 2000;117(6):1672. Reference #2: Albelda SM, Gefter WB, Epstein DM, Miller WT. Bronchopleural fistula complicating invasive pulmonary aspergillosis. Am Rev Respir Dis. 1982 Jul;126(1):163-5 Reference #3: Bonatti H, Lass-Floerl C, Angerer K, Singh N, Lechner M, Stelzmueller I, Singh R, Schmid T, Geltner C. Successful Management of Post pneumonectomy Aspergillus pleural empyema by combined surgical and antifungal treatment with voriconazole and caspofungin. Mycoses. 2010 Sept; 53(5) 448-54 DISCLOSURES: No relevant relationships by Amit Rout, source=Web Response No relevant relationships by Adrian Sarzynski, source=Web Response No relevant relationships by Sahib Singh, source=Web Response

SPONTANEOUS BACTERIAL EMPYEMA: HOW IS IT ACTUALLY DEFINED?

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Hepatic hydrothorax refers to a pleural effusion in a cirrhotic without another identifiable cause. When this pleural fluid becomes infected, it is called a spontaneous bacterial empyema (SBE). SBE needs to be distinguished from an effusion secondary to a primary lung infection because chest tube drainage is avoided in SBE. We present a case of a cirrhotic patient with an infected pleural space where the diagnosis is not clear based on existing diagnostic criteria for SBE. CASE PRESENTATION: A 64 year old male with alcoholic cirrhosis presented to the Emergency Department for shortness of breath. He had a history of refractory ascites requiring paracentesis every two weeks and a small, right-sided pleural effusion that had been present for two years. Upon presentation, he was tachycardic and hypoxic requiring three liters of oxygen. Initial workup was significant for a white blood cell (WBC) count of 14,000/uL, chest x-ray showed a moderate right-sided pleural effusion, thoracic ultrasound showed a loculated pleural space, and abdominal ultrasound revealed no ascites. A thoracentesis was performed with serosanguinous fluid appearance, WBC of 6,000/uL with 98% neutrophils, pH of 6.50, and a glucose of 172 mg/dL. A chest tube was placed soon after admission. After four days of drainage and intravenous antibiotics, the patient was weaned off supplemental oxygen and his leukocytosis resolved. The chest tube was removed, and he was discharged to complete six weeks of antibiotics. DISCUSSION: Chest tube drainage has been associated with increased incidence of protein loss, kidney injury, and infection in cirrhotic patients [1], and most guidelines recommend against tube drainage for SBE [1, 2, 3]. To our knowledge, there is no consensus definition of SBE (Table 1), and none incorporate the presence of loculations on chest imaging. This patient met some definitions of SBE while not meeting others (Table 1). Because of the low pleural fluid pH and complex appearing pleural space, we proceeded with chest tube drainage despite recommendations to avoid catheter placement in SBE because of concern for inadequate source control with antibiotics alone. The patient’s clinical improvement after chest tube drainage confirmed our suspicion that he likely had a parapneumonic effusion instead of SBE. Integrating pleural loculations and standardizing the definition for SBE may help stratify patients that require chest tube drainage from those that will improve with antibiotics alone. CONCLUSIONS: The diagnostic criteria for SBE is not clear. The lack of a consensus definition can lead to treatment uncertainty and inappropriate delays in chest drainage. Standardizing the diagnostic criteria will allow for more judicious use of chest tube drainage in cirrhotic patients that are at increased risk of catheter related complications. Reference #1: 1. Xiol X, Casais L. Spontaneous Bacterial Empyema in Cirrhotic Patients: Analysis of Eleven Cases. Hepatology. 1990 Mar; 11(3): 365-7 Reference #2: 2. Tu CY, Chen CH. Spontaneous Bacterial Empyema. Curr Opin Pulm Med. 2012 Jul; 18(4): 355-8 Reference #3: 3. Cardenas A, Kelleher B, Chopra S. Hepatic Hydrothorax. UptoDate. Retrieved January 25, 2019 from https://www.uptodate.com/contents/hepatic-hydrothorax DISCLOSURES: No relevant relationships by Kevin Ho, source=Web Response No relevant relationships by Jennifer McCallister, source=Web Response

Intrapleural Fibrinolytic Therapy for Empyema and Pleural Loculation: Knowns and Unknowns.

Intrapleural Fibrinolytic Therapy for Empyema and Pleural Loculation: Knowns and Unknowns.

Fibrin turnover and pleural organization: bench to bedside.

Recent studies have shed new light on the role of the fibrinolytic system in the pathogenesis of pleural organization, including the mechanisms by which the system regulates mesenchymal transition of mesothelial cells and how that process affects outcomes of pleural injury. The key contribution of plasminogen activator inhibitor-1 to the outcomes of pleural injury is now better understood as is its role in the regulation of intrapleural fibrinolytic therapy. In addition, the mechanisms by which fibrinolysins are processed after intrapleural administration have now been elucidated, informing new candidate diagnostics and therapeutics for pleural loculation and failed drainage. The emergence of new potential interventional targets offers the potential for the development of new and more effective therapeutic candidates.

Inhibition of Glycogen Synthase Kinase 3β Blocks Mesomesenchymal Transition and Attenuates Streptococcus pneumonia–Mediated Pleural Injury in Mice

Pleural loculation affects about 30,000 patients annually in the United States and in severe cases can resolve with restrictive lung disease and pleural fibrosis. Pleural mesothelial cells contribute to pleural rind formation by undergoing mesothelial mesenchymal transition (MesoMT), whereby they acquire a profibrotic phenotype characterized by increased expression of α-smooth muscle actin and collagen 1. Components of the fibrinolytic pathway (urokinase plasminogen activator and plasmin) are elaborated in pleural injury and strongly induce MesoMT invitro. These same stimuli enhance glycogen synthase kinase (GSK)-3β activity through increased phosphorylation of Tyr-216 in pleural mesothelial cells and GSK-3β mobilization from the cytoplasm to the nucleus. GSK-3β down-regulation blocked induction of MesoMT. Likewise, GSK-3β inhibitor 9ING41 blocked induction of MesoMT and reversed established MesoMT. Similar results were demonstrated in a mouse model of Streptococcus pneumoniae-induced empyema. Intraperitoneal administration of 9ING41, after the induction of pleural injury, attenuated injury progression and improved lung function (lung volume and compliance; P<0.05 compared with untreated and vehicle controls). MesoMT marker α-smooth muscle actin was reduced in 9ING41-treated mice. Pleural thickening was also notably reduced in 9ING41-treated mice (P<0.05). Collectively, these studies identify GSK-3β as a newly identified target for amelioration of empyema-related pleural fibrosis and provide a strong rationale for further investigation of GSK-3β signaling in the control of MesoMT and pleural injury.

Lipoteichoic acid upregulates plasminogen activator inhibitor-1 expression in parapneumonic effusions.

Parapneumonic effusion (PPE) is commonly caused by Gram-positive bacteria (GPB) and often presents with pleural loculation, which is characterized by overproduction of plasminogen activator inhibitor (PAI)-1. Lipoteichoic acid (LTA), a surface adhesion molecule of GPB, binds to the pleural mesothelium and triggers inflammation. However, the effects of LTA on PAI-1 expression in PPE and underlying mechanisms remain unclear. Thirty consecutive patients with PPE were enrolled, including uncomplicated culture negative (CN, n = 11), Gram-negative bacteria (GNB, n = 7) and GPB (n = 12) groups stratified by pleural fluid characteristics and bacteriology, and the effusion PAI-1 levels were measured. In addition, human pleural mesothelial cells (PMC) were treated with LTA and the expression of PAI-1 and activation of signalling pathways were assayed. The median levels of PAI-1 were significantly higher in GPB (160.5 ng/mL) and GNB (117.0 ng/mL) groups than in the uncomplicated CN (58.0 ng/mL) group. In human PMC, LTA markedly upregulated PAI-1 mRNA and protein expression and enhanced elaboration of Toll-like receptor 2 (TLR2). Furthermore, LTA increased c-Jun N-terminal kinase (JNK) phosphorylation, induced activating transcription factor 2 (ATF2)/c-Jun nuclear translocation and activated PAI-1 promoter activity. Pretreatment with TLR2 siRNA significantly inhibited LTA-induced JNK phosphorylation and PAI-1 protein expression. Culture-positive PPE, especially that caused by GPB, has a significantly higher level of PAI-1 than uncomplicated CN PPE. LTA upregulates PAI-1 expression through activation of TLR2/JNK/activator protein 1 (AP-1) pathway in human PMC. Better understanding of the modulation of PAI-1 synthesis by LTA in PPE may provide potential therapies for infected pleural effusions.

Video-thoracoscopic approach, without suture, of late thoracic esophageal perforations.

to evaluate the use of video-thoracoscopy, in the treatment of late perforations of the thoracic esophagus, without suture or organ resection. retrospective analysis of patients with late diagnosis (> 12 hours) of thoracic esophageal perforation treated by video-thoracoscopy, without suture or organ resection, over a 15-year period. sixteen patients were operated on, ten men and six women, aged between 48 and 66 years, with time between the diagnosis of the perforation and the surgery ranging from 16 to 26 hours. All patients underwent video-thoracoscopy, with pulmonary decortication, pleural loculations approach, opening of the mediastinal pleura near the perforation site and debridement of the devitalized tissues, followed by double drainage of the pleural cavity. No esophageal suture or resection was performed, and the patients evolved with complete closure of the lesions, without deaths. the video-thoracoscopic surgical approach was able to control pleural infection, pulmonary expansion and enable complete regeneration of the esophagus with late-diagnosed perforation.

Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models.

The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP.

Safety and outcome of medical thoracoscopy as diagnostic tool for pleural and pulmonary diseases

BackgroundThe accurate diagnosis of pleural effusion is challenging because even after thoracocentesis and/or closed pleural biopsy, 25–40% of pleural effusion remains undiagnosed. Thoracoscopy is now considered the approach of choice for diagnosis of certain kinds of pleural diseases such as pleural mass, malignant pleural effusion with negative pleural fluid cytology, and in the diagnosis of pleural tuberculosis. Aim of studyTo evaluate the diagnostic utility and safety of medical thoracoscopy in patients with undiagnosed exudative pleural effusion and pulmonary parenchyma lesions. MethodsThis study was conducted on 44 patients, 21 males and 23 females with age ranging between 32 and 74years (mean age 57.59±7.1years). There were 38 patients with undiagnosed exudative pleural effusion, 3 patients with multiloculated pleural effusion, 1 patient with undiagnosed pulmonary nodules and 2 patients with undiagnosed pulmonary parenchyma ground glass appearance and reticulation. There were 21 patients with co morbidities and 23 patients without co morbidities. ResultsForty four patients with undiagnosed pleural and pulmonary lesions underwent medical thoracoscopy, multiple pleural nodules were found in 24 out of 44 patients (54.54%). Pleural mass was found in 6 patients (13.63%) and pleural thickness was found in 8 patients (18.2%). Pleura loculation and adhesion was found in 3 patients (6.8%). Pulmonary nodules were found in 1 patient (2.3%). Normal thoracoscopy was found in 2 patients (4.54%) and lung biopsy was taken. As regards histopathology there were 16 patients (36.36%) diagnosed as epithelial mesothelioma, 3 patients (6.81%) diagnosed as metastatic squamous cell carcinoma, 1 patient (2.27%) diagnosed as non Hodgkin lymphoma, and 4 patients diagnosed as tuberculosis. In patients with pleural mass 3 patients (6.81%) diagnosed as sarcomatous mesothelioma and 3 patients (6.81%) diagnosed as non Hodgkin lymphoma. In 8 patients with pleural thickness, 6 patients (13.63%) diagnosed as non specific pleurisy and 2 patients (4.54%) diagnosed as tuberculosis. In 3 patients with pleural loculation they diagnosed as pleural fibrosis. One patient with pulmonary nodules (2.27%) diagnosed as small cell carcinoma. In 2 patients with normal thoracoscopy lung biopsy showed desquamative interstitial pneumonia in 1 patient (2.27%) and usual interstitial pneumonia in 1 patient (2.27%). The diagnostic yield of medical thoracoscopy was 86.4% (38 patients with definite histopathological diagnosis and 6 patients 13.6% diagnosed as non specific pleurisy). As regards thoracoscopic complications bleeding needed blood transfusion occurred in 1 patient (2.27%) with malignant mesothelioma, surgical emphysema occurred in 3 patients (1 with metastatic squamous cell carcinoma, 1 with tuberculous pleural effusion and 1 with loculated empyema), hypotension occurred in 1 patient underwent lung biopsy (desquamative interstitial pneumonia), the total thoracoscopic complications were 11.36% which was mild and statistically non significant. ConclusionMedical thoracoscopy is safe and effective for the diagnosis of benign and malignant pleural disease and pulmonary nodules.