Pleural Tissue Research Articles

Performance of Xpert\xae MTB/RIF in diagnosing tuberculous pleuritis using thoracoscopic pleural biopsy

BackgroundEtiological diagnosis of tuberculous pleuritis is challenging, owing to a paucity of Mycobacterium tuberculosis (MTB) in the affected region. Moreover, currently available methods, such as the detection of acid-fast bacilli and microbiological culture, are not always conducive to timely diagnosis and treatment. In this study, we evaluated the performance of Xpert® MTB/RIF assay (hereinafter referred to as “Xpert”) in detecting MTB in difficult-to-diagnose patients using suspensions of pleural biopsy tissue specimens obtained under direct thoracoscopic guidance.MethodsOne hundred and sixty patients with an unexplained pleural effusion were included from the Shenyang Tenth People’s Hospital and Shenyang Chest Hospital, China, between 2017 and 2018. The included patients underwent thoracoscopy under local anesthesia, with an intercostal incision of approximately 1.0 cm for biopsy. The biopsy specimens were used for pathological and etiological examinations. The Xpert test was evaluated for its sensitivity and specificity, as well as positive and negative predictive values (PPV and NPV, respectively), against data obtained using standards: the BACTEC™ MGIT™ 960 liquid culture system and a composite reference standard (CRS).ResultsThe sensitivity and specificity of Xpert were 68.8 and 64.6%, respectively, against the MGIT 960 culture data. The PPV and NPV of Xpert were 56.4 and 75.6%, respectively. The sensitivity of Xpert was 69.0% against the CRS data, which was significantly higher than that of MGIT 960 culture (56.6%). The PPV and NPV of Xpert against the CRS data were 100.0 and 57.3%, respectively.ConclusionsXpert is a good rule-in test but has limited value as a rule-out test for the diagnosis of tuberculosis pleuritis.

Transmembrane protein 88 inhibits transforming growth factor-β1-induced-extracellular matrix accumulation and epithelial-mesenchymal transition program in human pleural mesothelial cells through modulating TGF-β1/Smad pathway

Pleural fibrosis is an irreversible pathological process occurred in the development of several lung diseases. TMEM88 is a member of transmembrane (TMEM) family and has been found to be involved in the regulation of fibrogenesis. However, the role of TMEM88 in pleural fibrosis remains unknown. In this study, we aimed to explore the role of TMEM88 in pleural fibrosis in vitro using transforming growth factor-β1 (TGF-β1)-induced human pleural mesothelial cell line MeT-5A cells. Our results showed that the expression levels of TMEM88 were downregulated in pleural fibrosis tissues and TGF-β1-treated Met-5A cells. Overexpression of TMEM88 inhibited the proliferation of Met-5A cells under TGF-β1 stimulation. In addition, TMEM88 overexpression prevented TGF-β1-induced extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) in Met-5A cells with decreased expression levels of Col I and fibronectin, increased levels of cytokeratin-8 and E-cadherin, as well as decreased levels of vimentin and α-SMA. Furthermore, overexpression of TMEM88 inhibited the expression of TGF-β receptor I (TβRI) and TβRII and suppressed the phosphorylation of Smad2 and Smad3 in Met-5A cells. In conclusion, these results indicated that TMEM88 exhibited an anti-fibrotic activity in pleural fibrosis via inhibiting the activation of TGF-β1/Smad signaling pathway.

Imprint Cytology of Thoracoscopic Pleural Biopsy Tissue for Early Etiological Diagnosis of Pleural Effusion: A Pilot Study From India.

Thoracoscopic pleural biopsy provides the highest diagnostic yield in both malignant and tubercular pleural effusions. However histopathologic report takes 3 to 5 days to provide the diagnosis, resulting in a delay of further management plans like pleurodesis or chest tube removal. Imprint cytology of biopsy tissue can provide early information about the etiological diagnosis. Thus, we conducted this pilot study in 66 patients of exudative pleural effusions undergoing medical thoracoscopy. One or 2 biopsy pieces obtained during medical thoracoscopy from pleural nodules were used to prepare imprint cytology slides in the thoracoscopy suite. In comparison to thoracoscopic pleural biopsy, the diagnostic yield of imprint cytology of pleural tissue was 92% (49 of 53 cases) in cases of malignant pleural effusion and 75% (9 of 12 cases) in cases of tuberculosis pleural effusions. Imprint cytology provided a definite idea about the type of diagnosis, about 2.5 days before the histopathology results. By providing early etiological diagnosis, it may also decrease the duration of hospital stay and health care expenditure. A large prospective trial has been planned in our center to confirm this hypothesis.

Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells.

Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin-3a. A combination of CPT-11 and nutlin-3a inhibited the growth of MM cells more effectively than either drug alone. Knocking down CES2 in MM cells reduced the effect of the drug combination, and its forced expression in MESO4 cells enhanced the growth inhibitory activity of CPT-11 in the absence of nutlin-3a. Enhancement of the growth inhibitory activity of CPT-11 by nutlin-3a suggests a possible new combinatorial MM chemotherapy regimen.

The effect of Cyclic-di-GMP on biofilm formation by Pseudomonas aeruginosa in a novel empyema model.

BackgroundPseudomonas aeruginosa (P. aeruginosa) is a common pathogenic bacterium which causes pleural empyema, and infection of P. aeruginosa is often associated with biofilm. The aim of this study was to establish a model of rabbit empyema infected by P. aeruginosa to determine whether it causes the formation of biofilm in the pleural cavity. Furthermore, we investigated the effect of cyclic diguanosine monophosphate (c-di-GMP) on biofilm formation in this P. aeruginosa empyema model.MethodsTwenty rabbits were used and randomly divided into five groups: PAO1, PAO1ΔwspF, and PAO1/plac-yhjH infection groups, and Luria-Bertani (LB) broth and turpentine control groups. A drainage catheter was implanted into the pleural cavity through thoracentesis. The three infection groups were respectively infected with PAO1, PAO1ΔwspF, and PAO1/plac-yhjH strains, which caused empyema. The two control groups were injected with LB or turpentine. After 4 days of infection, we sacrificed the rabbits. We evaluated the pathology of pleura through hematoxylin-eosin staining. Colony count and crystal violet assay were used to analyze the biofilm formation on the surface of catheters. Scanning electron was used to observe the biofilm on the surface of the pleura. Peptide nucleic acids-fluorescence in situ hybridization (PNA-FISH) was used to observe the biofilm in the fibrinous deposition.ResultsBy the PNA-FISH assay, biofilms were observed in the fibrinous deposition of the three infection groups. The red fluorescence area of the PAO1ΔwspF infection group was larger than that of the PAO1 and PAO1/plac-yhjH infection groups. Through electron microscopy, we observed that PAO1 strains were embedded in an electron-dense extracellular matrix on the surface of pleural tissue, and appeared to be biofilm-like structures. For the crystal violet assay, the optical density values of different groups were significantly different: PAO1ΔwspF > PAO1 > PAO1/plac-yhjH > control groups (P<0.05).ConclusionsTo the best knowledge of the authors, this is the first study to report P. aeruginosa forming biofilm in a novel animal model of pleural empyema. In addition, c-di-GMP signaling molecules played an important role in biofilm formation in the pleural cavity.

Comparison of Hydroxyethyl starch 130/0.4 (6%) with commonly used agents in an experimental Pleurodesis model

BackgroundHydroxyethyl Starch (HES) 130/0.4 (6%) is a commonly used intravascular volume expander with anti-inflammatory and antioxidant properties. In this study, we aimed to compare the histopathologic activity of HES 130/0.4 (6%) with various widely-used agents in pleurodesis.MethodsForty male Wistar-Albino rats were divided into five groups: controls, povidone-iodine recipients (PI group), sterile talcum recipients (Talcum group), autologous blood recipients (AB group) and HES 130/0.4 (6%) recipients (HES group). Thirty days after application of agents, pleural and lung tissues were resected. Evaluation was performed via macroscopic scoring (adhesion) and specimens were stained with H&E for microscopic examination (inflammation and fibrosis).ResultsHES recipients had significantly higher adhesion compared to controls (lower grade 0, higher grade 1 frequency vs. controls), they were found to have significantly lower frequency of grade 2 adhesion (vs. PI, Talc and AB) and grade 3 adhesion (vs. AB), indicating that the adhesion-generating properties of HES were only superior to the control group. HES recipients had significantly higher inflammatory grades compared to controls (lower grade 0, higher grade 1 frequency), while they had lower grades compared to the PI, Talc and AB groups. Although the PI, Talc and AB groups were statistically similar in most comparisons, we observed a trend towards higher success with the use of Talc and especially AB.ConclusionOur results do not support a role for HES in pleurodesis. We believe that the autologous blood method remains as an effective and successful procedure without side effects.

Interstitial Lung Fibrosis Imaging Reporting and Data System: What Radiologist Wants to Know?

The aim of this work is to review interstitial lung fibrosis Imaging Reporting and Data System (ILF-RADS) that was designed for reporting of interstitial lung fibrosis (ILF). Findings include pulmonary and extrapulmonary findings and is subsequently designed into 4 categories. Pulmonary findings included lung volume, reticulations, traction bronchiectasis, honeycomb, nodules, cysts, ground glass, consolidation, mosaic attenuation and emphysema, and distribution of pulmonary lesions; axial (central, peripheral and diffuse), and zonal distribution (upper, middle, and lower zones). Complications in the form of acute infection, acute exacerbation, and malignancy were also assessed. Extrapulmonary findings included mediastinal, pleural, tracheal, and bone or soft tissue lesions. The lexicon of usual interstitial pneumonia (UIP) was classified into 4 categories designated as belonging in 1 of 4 categories. Lexicon of ILF-RADS-1 (typical UIP), ILF-RADS-2 (possible UIP), ILF-RADS-3 (indeterminate for UIP), and ILF-RADS-4 (inconsistent with UIP).

Molecular diagnostics for verification of pleural tuberculosis in Morocco

Pleural tuberculosis (pTB) is a very common form of extrapulmonary tuberculosis (TB). pTB diagnostics represents a major burning challenge worldwide due to the limitations of available conventional diagnostic tools. These latter include microscopic examination of the pleural fluid for acid-fast bacilli, mycobacterial culture of pleural fluid in solid or liquid media, sputum or pleural tissue, and histopathological examination of pleural tissue; these tests have recognized limitations for clinical use. Hence, to overcome these limitations, attention has been devoted to new nucleic acid amplification (NAA) diagnostic tests such as the polymerase chain reaction (PCR) and real-time PCR (RT-PCR), owing to their accuracy, rapidity, high sensitivity and specificity. Within this context, this prospective study was conducted to evaluate the performance of molecular diagnosis methods for differentiation between tuberculosis and non-tuberculosis pleural effusions. Fifty patients with pleural effusion were enrolled in this prospective study in Rabat, Morocco. The efficacy of conventional polymerase chain reaction (PCR) in the diagnostics of tuberculous pleurisy by targeting IS6110 and mycobacterial internal transcribed spacer (MYITS) was evaluated compared to histopathologic examination and culture data. Our results showed that IS6110 PCR could “rule in” pTB, the sensitivity and specificity being 41.6% and 85.7%, respectively. Therefore, the findings confirmed that molecular tests exert a relatively high specificity in EPTB but lower sensitivity, thus a positive test is considered as a pTB case whereas negative one cannot exclude the disease. Although the study was limited by a small sample size, it adds to the body of evidence of usefulness of molecular testing as adjuncts to histopathologic examination for accurate diagnosis of pTB, to treat timely and to avoid the emergence and spread of drug resistant pTB. However, further efforts should be made to increase the sensitivity of NAA methods and to identify the best molecular targets to be useful in clinical practice.

Analyses of the Fourier Transform Infrared Spectra of Pleural Mesothelioma Tissues

Eleven cases of pleural mesothelioma and two cases of pleural normal tissue were detected using Fourier transform infrared spectroscopy. The differences between pleural mesothelioma and normal pleural tissues identified by comparison of their respective Fourier transform infrared spectra were as follows: (1) a higher relative intensity of the protein amide I band at 1641 cm–1 for pleural mesothelioma compared to normal pleural tissues, a pointed peak of amide II band at l550 cm–1 for pleural mesothelioma, and a higher relative intensity compared to normal pleural tissues, all relating to increased protein content in pleural mesothelioma; (2) a symmetric stretch of the vibration band of phosphodiester bonds in the nucleic acid molecules of pleural mesothelioma towards the long 1240 cm–1 wave, and a higher relative intensity compared to normal pleural tissues, indicating increased nucleic acid content of the pleural mesothelioma; (3) a lower relative intensity of the absorption peak near 2854–2922 cm–1 in the pleural mesothelioma compared to normal pleural tissue, indicating reduced lipid content of the pleural mesothelioma; (4) a lower relative intensity of the absorption peak near 1047 cm–1 associated with soluble sugar content of the pleural mesothelioma compared to normal pleural tissues. Our results show that Fourier transforms infrared spectra exists differences between pleural mesothelioma and normal pleural tissues. It is expected to become a new method for rapid identification of pleural mesothelioma.

Normal mesothelial cell lines newly derived from human pleural biopsy explants.

Mesothelial cells are arranged as a monolayer on covering membranes that invest surfaces of body cavities like the pleura and peritoneum. Primary human mesothelial cell (HMC) cultures are needed for studying mesothelial cell homeostasis and developing disease models, such as wound healing or cancers. Remarkably, there is a paucity of useable HMC lines that are currently available that faithfully recapitulate normal in vivo phenotypic characteristics. Here, we present a strategy to recover HMC from human pleural tissue and to immortalize them for extended in vitro culturing. Human pleural membrane was harvested by minimally invasive surgical techniques. HMC were isolated using a two-step process combining explant cellular outgrowth from biopsy tissue and flow cytometry based on cell surface expression of cadherin-1 and CD71. Cell cultures were generated after lentiviral transfection with human telomerase. The new HMC cultures retain the same phenotypic traits and physiologic features as their in vivo counterparts, yet they can be adapted for short-term or long-term culture in large-scale in vitro experimentation. In particular, we generated a new HMC line harboring a germline mutation in breast cancer type-1-associated protein-1 (BAP1), a causal tumor suppressor gene, that could be instrumental to malignant mesothelioma research. Patient-specific, normal HMC may serve as novel discovery tools allowing more powerful research models of both normal physiology and disease processes. Our surgically driven approach leads to a limitless resource of novel mesothelial cell cultures.

Abstract A53: Demonstration of the carcinogenicity of a flexible tangled multiwalled carbon nanotube in the rat lung

Abstract Carbon nanotubes (CNTs) are composed of one or more one-atom thick graphene cylinders. CNTs have remarkable mechanical, thermal, chemical, and electrical properties, and their tubular structure makes them very lightweight. However, these properties also make CNTs easily airborne and highly biopersistent, and respired CNTs have the potential to induce inflammatory lesions in tissues. Similar to asbestos, several MWCNTs were shown to induce peritoneal malignant mesotheliomas after intraperitoneal administration in rats and mice. MWCNT-N was the first CNT shown to induce lesions in lung and pleural tissue after administration via the airway: in this study, MWCNT-N was administered to rats using intratracheal, intrapulmonary spraying (TIPS). Shortly thereafter, MWCNT-7 was shown to induce bronchioloalveolar tumors in rats after inhalation exposure. These two MWCNTs have walls of more than 40 layers and form rod-shaped aggregates, and consequently have the potential to act similarly to asbestos and induce neoplastic lesions in the lung and/or pleural tissue. To investigate the effects of wall thickness on the carcinogenicity of MWCNTs, we conducted a 2-year study comparing 2 different types of MWCNTs, rigid rod-shaped MWCNT-A (213 layers, 150 nm in diameter, forming rigid rod shape aggregates) and flexible MWCNT-B (15-18 layers, 15 nm in diameter, forming tangled shaped aggregates). Crocidolite asbestos was used as the reference material. The rats were administered MWCNTs and asbestos using TIPS once a week over an 8-week period (total low and high doses of 0.5 and 1.0 mg/rat), followed by 2-year observation without further treatment (Suzui et al., 2016; Xu et al., 2014; Abdelgied and Elgazzar, 2019). In the MWCNT-B group, the combined incidence of bronchioloalveolar tumors was increased in the group administered 1.0 mg MWCNT-B compared to the vehicle control group. Malignant pleural mesothelioma was not induced in any of the groups. MWCNT-A and crocidolite asbestos also induced bronchioloalveolar tumors; however, the incidence was not statistically significant compared to the controls. The results indicate that the carcinogenic potential of inhaled flexible, tangled MWCNT-B is as high or higher than that of rigid, rod-shaped MWCNT-A. This is the first study to show that a thin, flexible MWCNT induces lung tumors after administration via the airway. Further studies are warranted to investigate the association of shape and rigidity with the carcinogenicity of respirable CNTs. Citation Format: Hiroyuki Tsuda, William T. Alexander, Takamasa Numano, Mohamed Ahmed Mahmoud Abdelgied, Ahmed Maher Mahmoud Ibrahim Elgazzar, Hiroshi Takase, Jiegou Xu, Aya Naiki, Satoru Takahashi, Akihiko Hirose, Makoto Ohnishi, Jun Kanno, David B. Alexander. Demonstration of the carcinogenicity of a flexible tangled multiwalled carbon nanotube in the rat lung [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A53.

Incidence, risk factors and clinical characteristics of extra-pulmonary tuberculosis patients: a ten-year study in the North of Iran.

To determine the incidence of extra-pulmonary tuberculosis (EPTB) and examine the risk factors and the clinical features of the disease over a ten-year period. Retrospective study of records of patients who were followed and registered in the TB registry programme in the health district of Gorgan, Iran from January 1, 2008, through December 31, 2017. Among 2280TB records, 609 (26.71%) were EPTB. They were mostly female patients (53.7%) and residents in rural areas (56.5%) with a mean age of 40.55years [±16]. The average age of female patients (37.55years [±16.99]) was lower than of male patients (44.07years [±20.59]). The median of the incidence rate was 7.5 per 100000 inhabitants for EPTB; biopsy and pathology were the best methods for the detection of EPTB. The most frequent forms of EPTB were lymphatic TB (193/609=31.7%) and pleural TB (158/609=25.9%). In most cases (245/609=40.2%), one to three months elapsed between occurrence of symptoms and final confirmation of EPTB. The outcome of EPTB was weaker than of pulmonary TB (PTB). Our most important finding was the increasing incidence of EPTB, which shows the importance of attention to this disease. Lymph node and pleural tissue were the most commonly infected tissues. Skeletal TB presents a challenge in the diagnosis and treatment of EPTB.

Role of pleural biopsy in patients of undiagnosed exudative pleural effusion

Introduction: Sometimes etiological diagnosis of pleural fluid is not possible by cytology, biochemical and microbiological examinations and labeled as undiagnosed exudative pleural effusion. Our aim of this study to make an etiological diagnosis in such undiagnosed exudative cases with pleural biopsy. Material and method: In this study patients with undiagnosed exudative pleural effusion, where the diagnosis was not made by laboratory investigations were included. Pleural tissue was obtained by Abram’s Needle and sent for histopathology and culture to find mycobacterium tuberculosis. Result: Out of 45 patients 34 (75.5%) were males and 11 (24.5%) were females. The side of pleural effusion was right-sided in 30 (66.6%) and left-sided in 15 (33.4%). The mean value of polymorphs and lymphocytes count was 7.24% and 92.76% respectively. Pleural fluid was hemorrhagic in 10 (22.22%) patients, straw-colored in 30 (71.11%) patients, and clear in 5 (11.11%) patients. The mean level of glucose was 65.66 mg/dl, the lowest being nil and highest being 110 mg/dl. The mean level of protein was 5.54 gm/dl (range 3.7-7.21 gm/dl). The mean value of the pH of pleural fluid was 65.44. Histopathology showed granulomatous inflammation compatible with tuberculosis in 24 (53.3%) cases, metastatic malignancy in 7 (15.5%) cases, chronic inflammation in 10 (22.3%) cases. In 4 (8.9%) cases pleural tissue was inadequate to give any opinion. Among 7 cases of malignancy, 5 (71.42%) cases showed adenocarcinomas and 2 (28.58%) cases showed squamous cell carcinoma. Conclusion: This study suggests that tuberculosis and malignancy are the two common etiologies for exudative pleural effusion. The role of pleural biopsy is pivotal as it helps in making the diagnosis in the majority of cases where other laboratory investigations fail to provide a diagnosis.

Role of biochemistry, cytology, and biopsy in the etiological diagnosis of pleural effusion- a clinical study

Introduction:Pleural effusion is the most common pleural disorder. It refers to excessive or abnormal accumulation of fluid in the pleural space. It is a commonly occurring medical problem caused by various pathological conditions. To treat patients appropriately, it is important to establish an accurate etiological diagnosis. Material and Method: This is an observational study conducted at a tertiary health care center. The pleural effusion was assessed clinically, biochemically, bacteriologically, cytologically, and histopathologically. Result: Tuberculosis was the most common etiology, followed by malignancy. A pleural biopsy was done in 70 patients. Pleural tissue was obtained in 65 cases. On histopathology,Malignancy was diagnosed in 15, tuberculosis in 35, and non-specific inflammation in 13 cases. Out of 35 histological proven tuberculosis cases, 26 cases had adenosine de-aminase (ADA) more than 70 u/l. Conclusion:Every pleural effusion is not due to tuberculosis but can be due to other causes, malignancy should always be excluded. Pleural fluid cytology and biopsy can give a definite diagnosis in a significant number of cases of pleural effusion. Tuberculosis is still the most common cause of pleural effusion followed by malignancy.

Lung Pseudomesothelioma in Patient with Asbestos Exposure: A Case Report

Background: Pseudomesotheliomatous carcinoma is a rare case of lung cancer with marked pleural extension resembling malignant pleural mesothelioma on diagnostic imaging. One of tool to diagnose lung pseudomesothelioma is by performing thorocoscopy pleural biopsy. Diagnostic thoracoscopy also has a higher sensitivity than pleural fluid cytology and needle biopsy.Case: We report a rare case of pseudomesotheliomatous carcinoma of the lung in a 50-year-old man with asbestos exposure. The patient had complained of dyspnea and chest roentgenogram showed left pleural effusion. Computed tomography (CT) of the chest revealed diffuse irregular left pleural thickening and without a clear initial primary lesion found in both of lung parenchyma, which mimicked pleural mesothelioma. Pleural tissue sampling was performed to obtain definitive diagnosis by video-assisted thoracoscopic surgery. At the operation, the tumor was found to have spread along the pleural surface and primary lesion was not detected in the right lung parenchyma. Immunohistochemically, the tumor was positive for Thyroid Transcription Factor- 1 (TTF-1), but negative for calretinin, P63, and Neuron Specific Enolase (NSE). Final diagnosis was adenocarcinoma of the lung and patient had good clinical response to Gefitinib.Conclusion: Based on the results of clinical studies (images and clinical observations), although pseudomesotheliomatous in patient with asbestos exposure is difficult to distinguish from pleural mesothelioma, we have a case of pseudomesotheliomatous lung diagnosed by a thoracoscopic pleura biopsy. For such cases, thoracoscopic pleural biopsy should be performed at an early stage.

Metastatic behavior of mixed invasive ductal lobular carcinoma (mIDC/ILC).

1085 Background: Mixed invasive ductal lobular carcinoma (mIDC/ILC) is a poorly described subtype of invasive breast cancer, characterized by its composition of both ductal and lobular histopathology. It is unclear if individual or both components drive metastasis. Literature is sparse regarding sites of metastatic spread of this elusive subtype of invasive breast cancer. Methods: Cohorts of patients with mIDC/ILC, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) were identified from the UPMC Network Cancer Registry. Among these, 46 patients with mIDC/ILC, 1,131 patients with IDC, and 145 patients with ILC seen at UPMC Magee Women’s Hospital from 1990 – 2017 were found to have developed distant metastasis during the course of their disease. The metastatic pattern of spread was compared between the cohorts. Formalin-fixed, paraffin-embedded patient samples from the metastatic sites of a portion of the mIDC/ILC cases (n = 19) was acquired and evaluated by H&amp;E staining. Results: Patients with IDC were more likely than patients with ILC to have metastasis to the liver (p = 0.001) and lung (p &lt; 0.001), and less likely to have metastasis to the peritoneum (p &lt; 0.001). Patients with mIDC/ILC were more likely than patients with IDC to have peritoneal metastasis (p = 0.01), similar to patients with ILC. Compared to patients with ILC, patients with mIDC/ILC were more likely to have liver metastasis (p = 0.001), similar to patients with IDC. Evaluation of the metastatic lesions originating from mIDC/ILC displayed a spectrum of histopathology including mixed histology (n = 3), pure IDC (n = 3), pure ILC (n = 5), and indeterminate lesions with features of both IDC and ILC (n = 6). Two cases were uninterpretable due to significant crush artifact. Metastatic mIDC/ILC lesions with retained mIDC/ILC histology were found in vertebral, pleural, and skin tissues. Metastatic mIDC/ILC lesions with IDC histology were found in a cerebellar, liver, and chest wall lesion; whereas, those with ILC histology were found in bowel, omental fat, ovary, bone, and sacrum. Indeterminate histology metastatic lesions were found at liver, chest wall, cerebellar, and bone sites. Conclusions: mIDC/ILC metastasizes to a range of distant sites with a higher preference to the liver and peritoneum as compared to ILC and IDC, respectively. Metastatic lesions arising from mIDC/ILC tumors showed a spectrum of histologies, including mIDC/ILC, IDC, ILC and indeterminate lesions with features of both IDC and ILC. Ongoing genomics studies will provide further insight into development of metastases from mIDC/ILC tumors.

The diagnostic yield of closed needle pleural biopsy in exudative pleural effusion: a retrospective 10-year study.

BackgroundPleural effusion is a common presentation in clinical practice. About 40% of exudative pleural effusion is unable to be diagnosed through thoracentesis, and closed pleural biopsy (CPB) is needed. This study was designed to investigate the diagnostic yield of CPB in exudative pleural effusion.MethodsThis was a retrospective 10-year study of patients with unexplained exudative pleural effusion who underwent CPB in two centers. Malignant pleural effusion (MPE) was diagnosed when there was histopathological evidence of pleural tissue, pulmonary tissue, or pleural fluid. Tuberculous pleural effusion (TPE) was confirmed when granuloma or coagulative necrosis was observed in pleural tissue, Ziehl-Neelsen acid-fast staining was positive, or adenosine deaminase (ADA) in pleural effusion was higher than 35IU with clinical symptoms of TB orγ-interferon increased with symptoms of TB.ResultsA total of 644 patients were enrolled, of which 479 were specifically diagnosed (217 patients with TPE and 262 patients with MPE). The sensitivity of CPB in the diagnosis of MPE was 51.5%. Among the pathological types of MPE, lung adenocarcinoma accounted for 77.9% (204/262) of cases, making up the largest proportion. The sensitivity of CPB for diagnosing TPE was 68.7%.ConclusionsCPB has a relatively high sensitivity in the diagnosis of exudative pleural fluid, especially in relation to tuberculous lesions. CPB could provide an alternative technique in clinical practice, especially for basic hospital units without thoracoscopy.

Etiology and prognostic evaluation of malignant pleural effusion

Background: Malignant pleural effusion is a common medical problem in patients with cancer. The survival of patients with malignant pleural effusion is generally poor. The objectives of our study were to reveal possible prognostic factors of malignant pleural effusion.Methods: Fifty-three consecutive patients, 34 male and 19 female patients of malignant pleural effusion diagnosed by pleural fluid positive for malignant cytology and/or pleural tissue positive for malignancy by thoracoscopy biopsy. Performance status by the Eastern Cooperative Oncology Group (ECOG) score and LENT score was calculated at the time of diagnosis. Median survival time was calculated using Kaplan-Meier analysis curve. Survival time was defined as the time from diagnosis to death or the last follow-up.Results: Most common cause of malignant pleural effusion was lung carcinoma 46 (86.79%). Adenocarcinoma was the most common 31 (58.5%) followed by NSCLC 10 (18.0%). Low, moderate and high-risk LENT score was found in 3 (5.7%), 35 (66%) and 15 (28.3%) respectively. The median survival time of pleural fluid sugar less than 20 were 3 months. The median survival time of LENT low, medium and high risk was 12 months, 5.2 months and 2.5 months respectively. The median survival time of patients with ECOG score of 1 and 4 was 6.5 months and 1 month respectively. Patients with bilateral pleural fluid had a mean survival time of 2 months.Conclusions: Adenocarcinoma lung is the most common etiology of malignant pleural effusion. The median overall survival time was 4 months. Higher ECOG score and LENT score are associated with shorter survival time.

Differential Diagnosis of Malignant Pleural Mesothelioma on Cytology: A Gene Expression Panel versus BRCA1-Associated Protein 1 and p16 Tests

Pleural effusions are among the first clinical manifestations of malignant pleural mesothelioma (MPM) and often constitute the only available material for diagnosis. Although an MPM diagnosis can be reliable on cytology, the reported sensitivity is low (30% to 75%). Particularly, it can be hard to discriminate epithelioid MPM, the most common histotype, from reactive mesothelial hyperplasia (MH). Currently, BRCA1-associated protein 1 (BAP1) and CDKN2A (p16), evaluated by immunohistochemistry and fluorescent in situ hybridization, respectively, are the most valuable markers to discriminate MPM and MH. Both markers have a high specificity, but their sensitivity is not always satisfying, even when used together. We have recently developed a 117-gene expression panel, based on Nanostring technology, able to differentiate epithelioid MPM from MH pleural tissues better than BAP1 and p16. Herein, we evaluated the efficacy of the same panel on an independent retrospective cohort of 23 MPM and 11 MH pleural effusions (cell blocks and smears). The overall sensitivity and specificity of the panel were equal to 0.9565 and 1, respectively. Moreover, the panel performance was compared with BAP1 and p16 on 25 cell blocks. Sensitivity levels of gene panel, BAP1 alone, p16 alone, and BAP1 plus p16 were 1, 0.5882, 0.4706, and 0.7647, respectively. Specificity was always 1. Although further validation is needed, this gene panel could really facilitate patients' management, allowing a definitive MPM diagnosis directly on pleural effusions.

Microbiological profile of tubercular and nontubercular empyemas and its impact on clinical outcomes: A retrospective analysis of 285 consecutively operated cases.

Background:Empyema thoracis is an entity seen across all age groups. This study aims at reporting a detailed microbiological profile of “pus and pleural tissue” in patients operated for empyema thoracis and also correlating it with perioperative clinical outcomes.Materials and Methods:Patients operated for empyema thoracis between 2012 and 2016 were included in the study. Patients were taken up for surgery after thorough preoperative evaluation. Perioperative outcomes were correlated with the results of microbiological analysis to evaluate their effect on clinical outcomes.Results:In the study, 285 patients were operated. There were 215 males (75.4%) and 70 females (24.6%). Tuberculosis (TB) was responsible for 58.2% of the cases (n = 166). Of 166, 32 patients were mycobacterial culture positive, suggesting 19.28% mycobacterial culture positivity rate. 21.8% of the total mycobacterial cultures were multidrug resistant. TB culture-positive patients had a significantly higher incidence of air leak (P = 0.03), inter-costal drain (ICD) duration (P = 0.03), and higher rates of recurrence (P = 0.03). Nontubercular empyema constituted 119 cases (41.8%). Forty-seven (39.5%) cases were culture positive. Gram-negative organisms were cultured in 30 (63.8%). Pseudomonas aeruginosa was the predominant isolate. Bacterial culture-positive patients had significantly higher conversions (P = 0.03), prolonged postoperative air leak (P = 0.04), and postoperative wound infections.Conclusions:This study highlights the emergence of Gram-negative organisms in bacterial empyema and emergence of multidrug resistance in tubercular empyema. Clinical outcome correlation revealed increased complications in culture-positive cases in both tubercular and nontubercular empyemas.