Malignant Pleural Disease Research Articles

Use of chest CT scan scoring system for diagnostic and therapeutic decision making in pleural effusion.

Aim To investigate the usage of chest computed tomography (CT) scan score for improvement in diagnostic and treatment efficacy of repetitive pleural effusion. Methods CT scan scoring system was used as a part of diagnostic procedures in patients with repetitive pleural effusion. Patients with at least two pleurocentesis were included in the study. Chest and abdominal ultrasound, chest x-ray, bronchoscopy, biochemical, microbiological and cytological analysis of pleural fluid specimen were performed for all patients. Results In a two-year period (during 2017-2018) 79 patients were analysed, 27 (34.17%) female and 52 (65.82%) male patients. Malignant pleural diseases were confirmed in 32 cases (40.5%), nonmalignant pleural effusions in 38 (48.1 %) cases, and nine (11.4%) patients rested without exact cause of pleural effusion after two pleurocenteses. Binary regression model showed odds ratio of 1.314; CI 95% 1.119-1.543) (p=0.00088). Confirmed malignancies with pleural effusion were in high correlation with the number of points in CT scan score. Conclusion CT scan scoring system was helpful for diagnostic and treatment decision making in patients with repetitive pleural effusion.

Abstract CT036: A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: Safety and efficacy

Abstract Background: Malignant pleural disease (MPD) from primary malignant pleural mesothelioma (MPM) or secondary metastatic disease (lung and breast cancers) affects more than 150,000 patients a year in the US alone. We developed chimeric antigen receptors (CARs) to target mesothelin (MSLN), a cell-surface antigen that we have shown is highly expressed in MPD, is associated with aggressiveness and poor survival, and has low expression in normal tissues. Methods: Using a second-generation CD28-costimulated MSLN CAR with the Icaspase-9 safety gene (IcasM28z), we initiated a phase I clinical trial (NCT02414269) to determine the safety and maximum tolerated dose of intrapleurally administered CAR T cells. Patients with biopsy-proven MPD expressing MSLN were eligible for the study. A single dose of IcasM28z CAR T cells was administered intrapleurally (with or without cyclophosphamide preconditioning) by either pleural catheter or an interventional radiology procedure. On-target, off-tumor toxicity, serial serum soluble MSLN-related peptide (SMRP) levels and C-reactive protein levels were assessed, and CT and PET scans were performed, in addition to routine clinical and laboratory tests. Results: Twenty-one patients with MPD (19 MPM, 1 lung cancer, 1 breast cancer) were treated (40% received ≥3 lines of prior therapy). Eighteen of the 21 patients received cyclophosphamide preconditioning (3E5 - 1E7 CAR T cells/kg); the first cohort did not receive cyclophosphamide. Twelve patients were administered CAR T cells using an interventional radiology procedure. One patient had febrile neutropenia (grade 3) related to cyclophosphamide. No CAR T-cell-related toxicities higher than grade 2 were observed. The last cohorts of patients were admitted 2 weeks after infusion with a temperature of 101°F and fatigue. Intense monitoring for on-target, off-tumor toxicity by clinical (chest or abdominal pain), radiological (CT/PET or echocardiogram for pericardial effusion, ascites), laboratory (troponin elevation), and other (electrocardiogram) evaluation found no evidence of toxicity. One patient successfully underwent curative-intent surgical resection 6 weeks after CAR T-cell infusion. CAR T cells were detected in the peripheral blood of 13 patients (day 1 to 38 weeks), as evidenced by vector copy number. T-cell persistence was associated with decreased serum SMRP levels (>50% compared to pretreatment) and evidence of tumor regression on imaging studies. Once lack of toxicity had been established (6-17 weeks after CAR T-cell infusion), 14 patients received anti-PD1 checkpoint blockade agents (1-21 cycles), off protocol, with no toxicity. The best response among the 19 MPM patients (13 patients received anti-PD1 agent; PD-L1 <10% in all except 1) was - 2 patients had complete metabolic response on PET scan (60 and 32 weeks ongoing); 5 with partial response and 4 with stable disease. Conclusion: In this phase I clinical trial, intrapleurally administered MSLN-targeted CAR T cells had no evidence of on-target, off-tumor or therapy related toxicity, and there was evidence of CAR T-cell antitumor activity. MSLN-targeted CAR T-cell therapy combined with anti-PD1 agents shows encouraging clinical outcomes, thus a combination therapy trial is planned to recruit patients in the second quarter of 2019. Citation Format: Prasad S. Adusumilli, Marjorie G. Zauderer, Valerie W. Rusch, Roisin E. O'Cearbhaill, Amy Zhu, Daniel A. Ngai, Erin McGee, Navin K. Chintala, John C. Messinger, Alain Vincent, Elizabeth F. Halton, Claudia Diamonte, John Pineda, Shanu Modi, Stephen B. Solomon, David R. Jones, Renier J. Brentjens, Isabelle Rivière, Michel Sadelain. A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: Safety and efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT036.

Prospective Study of the Utility of Computed Tomography Triage of Pleural Biopsy Strategies in Patients With Pleural Diseases.

This study aimed to prospectively evaluate the efficacy and reliability of a diagnostic workup, triaging pleural biopsy method according to baseline computerized tomography (CT) findings in the diagnosis of pleural diseases. Patients with pleural pathology were divided into 3 arms according to findings on CT scan images. Arm A: patients with pleural thickening/lesion in addition to pleural effusion. These patients underwent CT scan-guided Abrams' needle pleural biopsy. Arm B: patients with pleural effusion alone or suspected benign asbestos pleurisy. This group underwent medical thoracoscopy (MT). Arm C: patients with only pleural thickening. This group underwent ultrasonography-guided cutting needle pleural biopsy. MT was planned in patients who did not have a specific diagnosis in the CT scan-guided Abrams' needle pleural biopsy group. When patients with a histopathologic diagnosis of fibrinous pleuritis after MT were assessed in terms of the risk factors for malignant pleural diseases, we offered a further invasive procedure. A total of 164 patients were enrolled in the study. Diagnostic sensitivity after the initial procedure was 90.2% in Arm A, 93.3% in Arm B, 95.2% in Arm C, and 92.4% in the entire workup. The negative predictive value of the entire workup was 90.4% for malignant pleural mesothelioma, 97.1% for metastatic malignant pleural diseases, and 100% for tuberculous pleurisy. Five cases who had a diagnosis of fibrinous pleuritis after MT were detected to have risk factors, 4 of which (80%) indicated malignant disease. Complication rates were low and acceptable. Use of CT scans to triage an appropriate pleural biopsy method is associated with high diagnostic success. We recommend that the proposed diagnostic workup in this study may be used as a diagnostic algorithm for pleural diseases that require a histopathologic analysis. Determination of risk factors predicting malignant disease in patients where fibrinous pleuritis is reported after MT would be useful for clinical practice.

Diffusion-Weighted Imaging Can Differentiate between Malignant and Benign Pleural Diseases.

It is not clear whether magnetic resonance imaging (MRI) is useful for the assessment of pleural diseases. The aim of this study is to determine whether diffusion-weighted magnetic resonance imaging (DWI) can differentiate malignant pleural mesothelioma (MPM) from pleural dissemination of lung cancer, empyema or pleural effusion. The DWI was calibrated with the b value of 0 and 800 s/mm2. There were 11 MPMs (8 epithelioid and 3 biphasic), 10 pleural disseminations of lung cancer, 10 empyemas, and 12 pleural effusions. The apparent diffusion coefficient (ADC) of the pleural diseases was 1.22 ± 0.25 × 10−3 mm2/s in the MPMs, 1.31 ± 0.49 × 10−3 mm2/s in the pleural disseminations, 2.01 ± 0.45 × 10−3 mm2/s in the empyemas and 3.76 ± 0.62 × 10−3 mm2/s in the pleural effusions. The ADC of the MPMs and the pleural disseminations were significantly lower than the ADC of the empyemas and the pleural effusions. Concerning the diffusion pattern of DWI, all 11 MPMs showed strong continuous diffusion, 9 of 10 pleural disseminations showed strong scattered diffusion and 1 pleural dissemination showed strong continuous diffusion, all 10 empyemas showed weak continuous diffusion, and all 12 pleural effusions showed no decreased diffusion. DWI can evaluate pleural diseases morphologically and qualitatively, and thus differentiate between malignant and benign pleural diseases.

What's the Score? Do Pleural Effusion Clinical Scoring Systems Help in Management of Disease?

Pleural effusion is a common condition, affecting over 3,000 people per million population every year. More than 50 causes of pleural effusions are known, including pleural infection and malignant pleural disease. These conditions place a large burden on healthcare systems with one-fourth of patients with pleural infection having a length of hospital stay of more than 1 month. Malignant pleural effusion represents advanced malignant disease with a correspondingly high mortality. Prognostic models using clinical information in combination with blood or pleural fluid biomarkers predicting survival and other outcome measures are therefore a priority in improving clinical care, and potentially outcomes. Identifying patients with poor prognosis may help avoid discomfort and unnecessary interventions at the end of their lives, while, on the other hand, individuals with scores predicting a particularly good prognosis might be selected for more aggressive early treatment. Such scores must be based on data representing routine practice in a general hospital and variables chosen based on their clinical availability at clinical decision points (i.e., before treatment is instituted), making the findings widely applicable.

La thoracoscopie médicale en pratique pneumologique : expérience du CHU de Liège

The incidence of pleural disease continues to increase worldwide. Medical thoracoscopy remains the standard method for exploration of the pleural cavity. We report the retrospective evaluation, the efficacy and the observed complications in 1024 medical thoracoscopies undertaken in the University Hospital of Liège between 2000 and 2017. In total, 100 pneumothoraces and 400 benign and 501 malignant pleural diseases were identified. The main indication for thoracoscopy remains the diagnosis of an exudative, lymphocytic pleural effusion of unknown aetiology after thoracocentesis. The diagnostic sensibility of thoracoscopy was 99.2% in distinguishing benign from malignant pleural disease. Talc pleurodesis was performed in 69.5% of the total population and in 66.1% of pleural effusions or thickening. Failure of pleurodesis was observed in 11% of the patients with recurrent pneumothorax and in 7.8% of neoplastic pleural effusion. We report a mortality of 0.6% in the 30 days post procedure, long duration of drainage in 8.3% and serious complications in 4.7%. In 22/1024 (2.1%) thoracoscopic evaluation was not feasible because of dense pleural fibrosis. Medical thoracoscopy is a safe, well-tolerated procedure with high accuracy in the diagnostic and therapeutic management of pleural disease.

Does Spectral CT Provide Added Diagnostic Value for Defining Malignant Pleural Disease?

Does Spectral CT Provide Added Diagnostic Value for Defining Malignant Pleural Disease?

Nodules and masses are associated with malignant pleural effusion in dogs and cats but many other intrathoracic CT features are poor predictors of the effusion type.

Thoracic CT may be used in the workup of patients with pleural effusion. In humans, certain pleural features on CT aid in diagnosing an underlying cause for pleural effusion, whereas this is not well studied in veterinary medicine. This retrospective cross-sectional analytical study assessed pleural and other intrathoracic abnormalities on CT in dogs and cats with pleural effusion and explored potential discriminatory features between effusion types. Eighty-nine dogs and 32 cats with pleural cytology and/or histopathology were categorized into malignant pleural disease (15 dogs and 11 cats), pyothorax (34 dogs and 7 cats), chylothorax (20 dogs and 11 cats), transudative (11 dogs and 2 cats), and hemorrhagic effusion (9 dogs and 1 cat). Multivariable logistic regression analysis comparing malignancy to other effusions found that older patient age (dogs: odds ratio 1.28, P=0.015; cats: odds ratio 1.53, P=0.005), nodular diaphragmatic pleural thickening (dogs: odds ratio 7.64, P=0.021; cats: odds ratio 13.67, P=0.031), costal pleural masses (dogs: odds ratio 21.50, P=0.018; cats: odds ratio 32.74, P=0.019), and pulmonary masses (dogs: odds ratio 44.67, P=0.002; cats: odds ratio 18.26, P=0.077) were associated with malignancy. In dogs, any costal pleural abnormality (odds ratio 47.55, P=0.002) and pulmonary masses (odds ratio 10.05, P=0.004) were associated with malignancy/pyothorax, whereas any costal pleural abnormality (odds ratio 0.14, P=0.006) and sternal lymphadenopathy (odds ratio 0.22, P=0.040) were inversely associated with transudates. There were, however, many overlapping abnormalities between effusion types, so further diagnostic testing remains important for diagnosis.

P2.01-67 The Prognostic Analysis of Lung Cancer Patients with Occult Malignant Pleural Disease at Thoracotomy

This study aims to determine the clinicopathological prognostic factors for occult malignant pleural disease (MPD) first detected at thoracotomy in patients with non-small cell lung cancer (NSCLC) and assess the outcome of surgical intervention. A total of 120 patients with MPD at thoracotomy from January 2006 to October 2016 were evaluated. Survival curves were estimated by the Kaplan–Meier method, and Cox regression analysis was performed to validate the selected risk factors. Clinical and pathologic parameters were balanced by propensity score matching when assessing surgical intervention. With a median follow-up of 34 months, the 5-year overall survival of 120 patients was 28.0%. Multivariate analyses showed male (p=0.044), advanced T stages (p<0.001), advanced N stages (p=0.02), pleural invasion in image (p=0.005), pleural effusion (p=0.027), surgical intervention (p=0.008) and EGFR status (p=0.003) were independent predictors of survival. The 5-year survival rate and median survival time (MST) for 21 patients with lobectomy were 71.6% and undefined, compared with 25.6% and 40.0 months in 46 patients with sublobectomy. When 53 patients only subjected to open-close surgery, their 5-year survival rate and MST were 23.4% and 30.2 months. After propensity score matching, both 21 patients were included in lobectomy group and sublobectomy /open-close group. The overall survival of lobectomy group was better than the control group (p=0.046). The prognosis of MPD patients first detected at thoracotomy was affected by gender, stage, pleural invasion, pleural effusion, surgical intervention and EGFR status. Lobectomy maybe confers better survival compared with sublobectomy and exploratory thoracotomy.

P2.06-28 Assessment of Chest Wall Motion Using Structured Light Plethysmography (SLP) in Mesothelioma and Benign Pleural Disease

Diagnosis of mesothelioma can be a prolonged and distressing process for patients. Non-invasive assessment of ribcage and abdominal movements is possible with structured light plethysmography (SLP) which is quick and easy to perform; we sought to assess whether changes in respiratory movements could be used to differentiate benign pleural disease from mesothelioma. Patients attending the preoperative assessment clinic prior to diagnostic pleural biopsy were recruited prospectively. SLP was performed prior to surgery and the recordings processed by a blinded technician. Binary logistic regression was used performed based upon histology results and the model was assessed with area under the curve (AUC) analysis. Survival analysis (Kaplan Meier plot and Log Rank test) was performed to assess whether survival was different depending on SLP results. Seventy-five patients were recruited, meeting the required sample size (40 benign, 35 malignant). Factors entered into the model were the contribution of the affected hemithorax to ribcage tidal volumes, synchrony between abdominal and ribcage movements and variability of inspiratory to expiratory flow. The model was not significant (X2 4.234, p=0.237, Nagelkerke R2 0.073) and correctly classified 57.3% of cases. AUC was 0.581 (p=0.230, 95% confidence interval 0.450 to 0.712), this is not sufficient to be a clinically useful test. The contribution of the affected hemithorax to ribcage motion showed a trend for association with survival in patients who had biopsy proven mesothelioma (mean survival 334 days for <45% contribution, 95% confidence interval 218-450, vs 993 days for >45% contribution, 95% confidence interval 633-1353, p=0.065). Performing SLP prior to biopsy does not aid in the differentiation of benign versus malignant pleural disease. Further research into the usefulness of assessing chest wall motion in prognostication and staging of mesothelioma is required.

What is the significance of non-specific pleuritis? A trick question.

Non-specific pleuritis (NSP) is defined as fibrinous or inflammatory pleuritis which cannot be attributed to a specific benign or malignant etiology. It can be diagnosed in biopsies in up to 30% of cases of exudative pleuritis after thoracoscopy, with a mean of 19.2%. In 66 out of 469 (14.2%) patients in combined series, a malignant pleural disease (mostly mesothelioma) was found during a follow-up of at least 21months. Most likely, a follow-up time of 12months is sufficient, although the current routine is a follow-up of 2years. Because of a benign course in 85% of patients with NSP, a repeated invasive procedure after thoracoscopy is only indicated in a limited group of patients. The most important indications for a repeated pleural biopsy are persistent chest pain, recurrent pleural effusion, radiologic findings suggestive for malignant pleural disease.

Video-assisted thoracoscopic surgery in the management of malignant pleural disease

Surgical treatment of malignant pleural diseases is usually indicated in advanced disease with a limited prognosis. associated with significant morbidity. Minimally invasive approaches must be offered as first line treatment since they reduce chest wall trauma, preserve respiratory muscle function and therefore expedite recovery. Most of the evidence for therapeutic video-assisted thoracoscopic surgery (VATS) pleural surgery is for primary malignant pleural mesothelioma (MPM) whilst in the treatment of metastatic non-small cell lung cancer (NSCLC) therapeutic VATS is concerned mainly in the prevention of pleural effusion or the treatment of malignant empyema. An increasing amount of management decisions using VATS in malignant pleural disease is evidence-based. There have been and continue to be well constructed clinical trials of the various potential therapeutic applications of VATS in this context. VATS allow for therapeutic manipulation of the pleural environment including dissection techniques aimed at symptom control by direct tumour debulking. We will consider the role of VATS in the management of malignant pleural disease in the context of a lung that will expand; when the lung is entrapped and when the lung is entrapped by a malignant empyema. In the first scenario the therapeutic choice is between simple VATS administration of chemical pleurodesis or the more controversial subtotal parietal pleurectomy. When the lung is entrapped but the cavity still cleans the choice is between the insertion of an indwelling pleural catheter (IPC) or the highly disputed VATS visceral pleurectomy to re-expand the lung. When a malignant effusion becomes infected the entrapped lung may form a malignant pleural empyema and the debate is between just debridement or the more technically challenging decortication. We will attempt to evaluate all of these procedures and formulate a management algorithm.

Biological mechanisms of non-linear dose-response for respirable mineral fibers

Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3. Lysosomal destabilization, efflux of cytosolic potassium ions and influx of calcium ions, signals from damaged mitochondria, both translational and post-translational controls, and prion-like polymerization have increasingly clear roles in regulating NLRP3 activation.As the molecular biology of inflammation-mediated responses to REMP exposure becomes clearer, a practical question looms: What do these mechanisms imply for the shape of the dose-response function relating exposure concentrations and durations for EMPs to risk of pathological responses? Dose-response thresholds or threshold-like nonlinearities can arise from (a) Cooperativity in assembly of supramolecular signaling complexes; (b) Positive feedback loops and bistability in regulatory networks; (c) Overwhelming of defensive barriers maintaining homeostasis; and (d) Damage thresholds, as in lysosome destabilization-induced activation of NLRP3. Each of these mechanisms holds for NLRP3 activation in response to stimuli such as REMP exposures. It is therefore timely to consider the implications of these advances in biological understanding for human health risk assessment with dose-response thresholds.

Cone-Beam CT Virtual Navigation-Guided Percutaneous Needle Biopsy of Suspicious Pleural Metastasis: A Pilot Study.

ObjectiveTo evaluate the diagnostic performance of cone-beam computed tomography (CBCT) virtual navigation-guided percutaneous pleural biopsy for suspected malignant pleural disease.Materials and MethodsThis study enrolled 59 patients (31 males and 28 females; mean age, 63.4 years) with suspected malignant pleural disease diagnosed with CBCT from December 2010 to December 2016. Sixty-three CBCT-guided biopsies were performed using a coaxial system with 18- or 20-gauge cutting needles. Procedural details, diagnostic performance, radiation exposure, and complication rates were investigated.ResultsThe mean diameter perpendicular to the pleura of 51 focal and 12 diffuse pleural lesions was 1.53 ± 0.76 cm. The mean distance from the skin to the target was 3.40 ± 1.51 cm. Mean numbers of CT acquisitions and biopsies were 3.21 ± 0.57 and 3.05 ± 1.54. Total procedure time and coaxial introducer indwelling time were 11.87 ± 5.59 min and 8.78 ± 4.95 min, respectively. The mean dose area product was 12013.61 ± 7969.59 mGym2. There were 48 malignant, 10 benign, and 5 indeterminate lesions. Sensitivity, specificity, and diagnostic accuracy were 93.8% (45/48), 100% (10/10), and 94.8% (55/58), respectively. Positive and negative predictive values for malignancy were 100% (45/45) and 76.9% (10/13), respectively. Four patients (6.8%) with benign pathology during initial biopsy but still showing a high suspicion of malignancy underwent repeat biopsy and three of them were finally diagnosed with malignant pleural disease. There were three cases of minimal pneumothorax and no grave procedure-related complications.ConclusionCone-beam computed tomography-guided biopsy is an accurate and safe diagnostic technique for suspected malignant pleural lesion with reasonable radiation exposure and procedure time.

Effect of postoperative systemic therapy on pulmonary adenocarcinoma with unexpected pleural spread detected during thoracotomy or thoracoscopy.

BackgroundOccasionally, malignant pleural disease is only detected unexpectedly during surgery in patients with pulmonary adenocarcinoma. Previous studies mostly focused on the role of main tumor resection on patient's outcome, barely addressing the position of postoperative systemic therapy.MethodsThe medical records of 5321 non-small cell lung cancer patients who underwent thoracic surgery between January 1990 and December 2012 were reviewed. Pulmonary adenocarcinoma patients with unexpected pleural spread noted during surgery were included. The clinical and postoperative treatment variables were assessed for correlation with overall survival.ResultsIn 134 patients identified, main tumor resection was performed in 87 (64.9%) patients, while 89 (66.4%) and 57 (42.5%) patients received postoperative chemotherapy and epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR -TKI) therapy, respectively. Overall, the 5-year survival rate was 30.2% and median survival time was 29.3 months. Multivariate analysis showed main tumor resection and EGFR-TKI therapy were associated with better survival. Mutational status of EGFR was available in 57 patients and 43 (75.4%) had activating mutations. Resection of the main tumor conferred a better outcome in patients without EGFR mutation or with unknown EGFR mutation status and had not been treated with EGFR-TKI therapy (P = 0.003), but not in those with activating EGFR mutation and had been treated with EGFR-TKI (P = 0.857).ConclusionsIn pulmonary adenocarcinoma patients with unexpected pleural spread detected during surgery, main tumor resection and EGFR-TKI therapy correlated with better survival. Identifying EGFR mutation status before surgery can provide useful information for clinical decision during surgery.

P2.01-068 Lobectomy Improve the Survival of Non-Small Cell Lung Cancer Patients with Occult Malignant Pleural Disease First Detected at Thoracotomy

P2.01-068 Lobectomy Improve the Survival of Non-Small Cell Lung Cancer Patients with Occult Malignant Pleural Disease First Detected at Thoracotomy

Non‐specific pleuritis in patients with active malignancy

Pleuroscopy is the test of choice for patients with suspected malignant pleural effusion and negative cytology. Biopsies negative for malignancy are frequently attributed to non-specific pleuritis, which poses a dilemma in patients with a known active malignancy, raising concern for a false-negative result. Our primary objective was to determine the outcomes of patients with active malignancy who had a non-malignant diagnosis on pleuroscopy. Retrospective review of all pleuroscopy cases from January 2005 to January 2015 at our institution was conducted. Biopsies were categorized by histopathology as malignant, eosinophilic or non-specific pleuritis. Malignant histopathology was considered a true positive. Eosinophilic or non-specific pleuritis was categorized as malignant, if malignancy was later identified during follow-up, or chemotherapy induced, possible radiation induced, other paramalignant, other benign or idiopathic. Of the 199 pleuroscopy cases reviewed, 172 (86%) had a history of active malignancy. On histopathology, 73 (42%) had malignancy, 9 (5%) had eosinophilic pleuritis and 90 (52%) had non-specific pleuritis. Three patients with non-specific pleuritis were diagnosed with malignancy at follow-up. Pleuritis in 24 patients was chemotherapy induced, 27 were possibly radiation induced, 11 were other paramalignant and 3 were other benign. Idiopathic pleuritis was diagnosed in 31 patients. Patients were monitored for a mean of 23 ± 11 months. The prevalence of malignant pleural disease was lower than expected for our patient population. Patients with no malignancy on histopathology were most likely to have non-specific pleuritis, a cause for which was identified in a majority of patients after clinical review.

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center.

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

Management of occult malignant pleural disease firstly detected at thoracotomy for non-small cell lung cancer patients.

The current study was to investigate the risk factors of occult malignant pleural disease (MPD) detected at thoracotomy and the outcomes of surgical intervention for these non-small cell lung cancer (NSCLC) patients with or without MPD. We reviewed 2,093 consecutive NSCLC patients who underwent thoracotomy from January 2006 to January 2015. We used univariate and multivariate statistics to analyze the associations between clinicopathological variables and occurrence of occult MPD. Survival probability was estimated by the Kaplan-Meier method. 5.26% (110/2,093) MPD was observed for these NSCLC patients with 28% of 5-year estimated survival rate. Age ≤50 (P=0.055), high CEA level (P=0.006), advanced N stage (P=0.005), adenocarcinoma (P=0.001) and pleural invasion (P=0.041) were detected to be independent risk factors for the occult MPD. Combination of these five factors, 0.756 of area under curve (AUC) was shown by the integrated prediction model test. Based on the optimal cut-off value (risk score =2.795), low-risk patients have better prognosis than the high-risk patients (median survival time 61.4 months vs. not reached, P<0.001; 5-year survival 71.8% vs. 51.1%, P<0.001). Significantly, 49.0 months/31.7% and 29.4 months/19.5% of the median survival time/5-year survival rate were found for the occult MPD 110 patients receiving primary lesion resection and open-close surgery, respectively (P=0.037). We summarized that a new prediction model including 5-risk factors of age, carcinoembryonic antigen (CEA), N stage, adenocarcinoma and pleural invasion was provided to diagnose MPD for the NSCLC patients and primary lesion resection greatly contributed for these MPD patients.

Intrapleural targeted therapies (anti-VEGF and anti-EGFR) in the model of malignant pleural effusion.

RationaleMalignant pleural effusion has few options of treatment and drugs administrated by different routes can lead to a less permissive microenvironment for the development of malignant pleural disease.ObjectivesTo analyze therapies administered intrapleurally in malignant pleural disease and to study EGFR and KRAS mutations in adenocarcinoma.MethodsMice received LLC cells and were treated intrapleurally with anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR or saline. Animal survival, weight and mobility, volume, biochemistry and immunology of fluid, gene expression, KRAS and EGFR mutation were evaluated.ResultsAll animals developed malignant effusion and presented progressive weight loss without difference between groups; however, groups treated with anti-EGFR were more active. No difference in mortality was observed. Temporal increase of volume and inflammatory markers was observed mainly in the untreated group. Gene expression in tumors was overexpressed in VEGF, EGFR and KRAS compared with normal tissue. Mutation in exon 2 of the KRAS gene was observed.ConclusionsIntrapleural Anti-VEGF and/or anti-EGFR reduced volume and inflammatory mediators in pleural fluid. Anti-EGFR and anti-VEGF+anti-EGFR decreased morbidity although without impact on survival. LLC tumors presented KRAS mutation, this could have influenced the action of these therapies.