Pleural Lesions Research Articles

Diagnostic Performance of PET or PET/CT with Different Radiotracers in Patients with Suspicious Lung Cancer or Pleural Tumours according to Published Meta-Analyses

Purpose Several meta-analyses have reported data about the diagnostic performance of positron emission tomography or positron emission tomography/computed tomography (PET or PET/CT) with different radiotracers in patients with suspicious lung cancer (LC) or pleural tumours (PT). This review article aims at providing an overview on the recent evidence-based data in this setting. Methods A comprehensive literature search of meta-analyses published in PubMed/MEDLINE and Cochrane Library database from January 2010 through March 2020 about the diagnostic performance of PET or PET/CT with different radiotracers in patients with suspicious LC or PT was performed. This combination of keywords was used: (A) “PET” OR “positron emission tomography” AND (B) “lung” OR “pulmonary” OR “pleur∗” AND (C) meta-analysis. Only meta-analyses on PET or PET/CT in patients with suspicious LC or PT were selected. Results We have summarized the diagnostic performance of PET or PET/CT with fluorine-18 fluorodeoxyglucose (18F-FDG) and other radiotracers taking into account 17 meta-analyses. Evidence-based data demonstrated a good diagnostic performance of 18F-FDG PET or PET/CT for the characterization of solitary pulmonary nodules (SPNs) or pleural lesions with overall higher sensitivity than specificity. Evidence-based data do not support the routine use of dual time point (DTP) 18F-FDG PET/CT or fluorine-18 fluorothymidine (18F-FLT) PET/CT in the differential diagnosis of SPNs. Even if 18F-FDG PET/CT has high sensitivity and specificity as a selective screening modality for LC, its role in this setting remains unknown. Conclusions Evidence-based data about the diagnostic performance of PET/CT with different radiotracers for suspicious LC or PT are increasing, with good diagnostic performance of 18F-FDG PET/CT. More prospective multicenter studies and cost-effectiveness analyses are warranted.

Wait-and-See Treatment Strategy Could be Considered for Lung Adenocarcinoma with Special Pleural Dissemination Lesions, and Low Genomic Instability Correlates with Better Survival.

This study aimed to evaluate the feasibility of a wait-and-see strategy for non-small cell lung cancer (NSCLC) patients with special pleural dissemination lesions (r-pM1a and s-pM1a). Furthermore, the study characterized genomic alternations about disease progression. For this study, 131 NSCLC patients with a diagnosis of pM1a were retrospectively selected. Survival differences were evaluated among patients treated with three different initial postoperative treatments: chemotherapy, targeted therapy, and wait-and-see strategy. Whole-exome sequencing (WES) was performed on primary and metastatic tumors of 10 patients with dramatic progression and 13 patients with gradual progression. The wait-and-see group showed better progression-free survival (PFS) than the chemotherapy group (p < 0.001) but PFS similar to that of targeted group (p = 0.984). This pattern persisted in epidermal growth factor receptor (EGFR)-positive patients. For patients with EGFR-negative/unknown status, PFS was longer in the wait-and-see group than in the two treatment groups. Furthermore, better overall survival (OS) was observed for the patients who received chemotherapy or targeted therapy after the wait-and-see strategy than for those who received chemotherapy or targeted therapy immediately. Lymph node status was an independent prognostic factor for PFS and OS. Finally, WES analysis showed that a high genomic instability index (GIS) and chromosome 18q loss were more common in metastatic tumors, and low GIS was significantly associated with better PFS (p = 0.016). The wait-and-see strategy could be considered for special pM1a patients without lymph nodes metastasis, and patients with a low GIS may be suitable for this strategy.

Thoracic Involvement in IgG4-Related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that has been recognized to involve virtually any organ in the body and typically manifests mass-like lesions (tumefactive). Although initial reports of this disease (autoimmune pancreatitis [AIP]) were described in the Japanese population, it has since been reported worldwide. It is most commonly seen in adults of middle age or older, more often men than women. The pathogenesis of IgG4-RD is largely unknown, but genetic factors, microorganisms, and autoimmunity are thought to play important roles. Serum IgG4 concentration is elevated in the majority of patients with IgG4-RD but is a nonspecific finding. Characteristic histopathologic features include dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis. Lung involvement in IgG4-RD was first reported in 2004 in two patients with AIP and coexisting interstitial lung disease. Since then, a wide spectrum of intrathoracic involvement has been reported and includes not only parenchymal lung diseases but also pleural, airway, vascular, and mediastinal lesions. Thoracic involvement in IgG4-RD is often found incidentally during the workup of extrathoracic lesions but can sometimes be the presenting abnormality. The diagnosis of IgG4-RD requires correlation of clinical, laboratory, imaging, and histopathologic features. Glucocorticoids are the first-line therapy but other options including B cell depletion are being investigated. IgG4-RD is generally associated with an indolent clinical course and most patients improve with glucocorticoid therapy.

ASO Author Reflections: Lung Adenocarcinoma with Accidental Invisible Pleural Dissemination Lesions: Wait-and-See Strategy for Tumors with Indolent Biologic Characteristics.

ASO Author Reflections: Lung Adenocarcinoma with Accidental Invisible Pleural Dissemination Lesions: Wait-and-See Strategy for Tumors with Indolent Biologic Characteristics.

Malignant mesothelioma cells secrete natriuretic peptides: Data and diagnostic clinical implications.

Mesothelial cells and cardiomyocytes have shared embryonic mesodermal origin. Cardiomyocytes release BNP under stretch. We searched whether malignant mesothelioma cells also secrete BNP and if so, this has a meaningful impact. Part I: Prospectively, patients with pleural lesions on CT having malignant mesothelioma effusions (MME, n = 13) were compared to patients with malignant effusions with pleural lesions (MEa, n = 14). Age-matched patients with ME without pleural lesions (MEb, n = 16) and non-malignant effusions (NME, n = 25) were analysed. Part II: Retrospectively, samples from patients with mesothelioma (n = 14), lung cancer (n = 8) or heart failure (n = 9) were used. BNP was measured in pleural fluid and blood/plasma. Part III: BNP was assessed in the culture supernatants of benign (MeT-5A) and malignant mesothelioma cell lines (M14K-epithelioid, MSTO-biphasic and ZL34-sarcomatoid) (n = 10 per cell line in three different biological replicates). In vitro, BNP concentration was significantly higher in the supernatant of all malignant cell lines than benign ones (P < 0.01), denoting BNP's production from the former. The pleural fluid to blood BNP ratio in MME was extremely high in Part I and Part II subjects (28.3 ± 12.1 and 25.9 ± 8.6, respectively) versus 1.1 ± 0.3 and 0.4 ± 0.1 in Part I ME and NME, respectively (P < 0.0001), and 0.8 ± 0.1 and 0.4 ± 0.1 in Part II ME and NME, respectively (P < 0.0001). BNP ratio ≥2.11 in Part I had 92% sensitivity and 94.5% specificity for MME (P < 0.0001). BNP is secreted from malignant mesothelial cells. In clinical practice, the pleural fluid to blood BNP ratio can help in the diagnosis of malignant mesothelioma.

Clinicopathological significance of microRNA-21 in extracellular vesicles of pleural lavage fluid of lung adenocarcinoma and its functions inducing the mesothelial to mesenchymal transition.

BackgroundPre‐resection pleural lavage cytology is useful to predict tumor recurrence and the prognosis of lung cancer patients. Recently, extracellular vesicles (EVs) isolated from effusion specimens have come under the spotlight, and several studies showed that microRNA in EVs is associated with prognosis. MicroRNA‐21 (miR‐21) is a representative onco‐microRNA, and miR‐21 in EVs (EV‐miR‐21) promotes cancer dissemination by inducing mesothelial to mesenchymal transition (MMT) in the peritoneal cavity. In this study, we isolated EVs from pleural lavage fluid and focused on EV‐miR‐21 as a diagnostic factor with a relationship to pleural dissemination.MethodsThe Cancer Genome Atlas dataset comprising of 448 cases of lung adenocarcinoma, tissue microarray of 144 cases of lung adenocarcinoma, and pleural lavage fluid of 41 cases was used to examine miR‐21 expression levels. The function of EV‐miR‐21 was investigated in vitro.ResultsThe miR‐21 expression level in primary sites was associated with a poor prognosis and correlated with pleural invasion of adenocarcinoma. EV‐miR‐21 levels in pleural lavage fluid were associated with positive cytology and pleural invasion in the primary sites, even in cytology‐negative cases. In vitro studies demonstrated that EV‐miR‐21 induces the MMT. Mesothelial cells in the MMT showed functions similar to cancer‐associated fibroblasts, which are an important stromal component in primary sites and disseminated pleural lesions.ConclusionsEV‐miR‐21 in pleural lavage fluid is important as a diagnostic and prognostic factor. Moreover, EV‐miR‐21 induces the MMT, which can form premetastatic niches of dissemination in the pleural cavity.

Malignant SFT with nodal metastasis, a case report

Solitary fibrous tumours (SFT) are generally rare neoplasms. These tumours were first described in the pleura and later appeared to involve almost every organ. They affect all ages with no sex predilection. Most of the pleural lesions are discovered incidentally. The majority of these tumours are benign with 13–25% considered malignant. Microscopically the tumours are cellular and consist of fibroblastic spindle cells in a pattern-less pattern with a variable amount of hemangiopericytoma like vascular spaces and stromal hyalinisation. The lesions are positive for CD34, BCL2, CD99 and STAT6. Malignant SFTs are differentiated from benign SFTs by hypercellularity, pleomorphism, necrosis and mitosis of more than 4/10 HPFs. In this case report, we present a patient who presented to their GP with back pain and during workup was found to have a right lower lobe lung mass. A lobectomy was performed and the tumour was found to be a malignant pleural based SFT with metastasis to a single peri-hilar lymph node. Seventeen months later, the patient presented with a secondary metastatic nodule with features similar to the primary lung tumour. At this stage, the patient was considered unamenable to further surgery or curative radiotherapy.

An evaluation of the economic effects of bovine respiratory disease on animal performance, carcass traits, and economic outcomes in feedlot cattle defined using four BRD diagnosis methods.

Bovine respiratory disease (BRD) causes significant economic losses to the feedlot industry due to decreased production and increased costs associated with treatment. This study aimed to assess the impacts of BRD on performance, carcass traits, and economic outcomes defined using four BRD diagnosis methods: number of BRD treatments an animal received, pleural lesions at slaughter, lung lesions at slaughter, and clinical BRD status defined using both treatment records and lung and pleural lesions. Crossbred steers (n = 898), with an initial body weight of 432 kg (± SD 51), were followed from feedlot entry to slaughter. Veterinary treatment records were collected and lungs scored at slaughter for lesions indicative of BRD. There was an 18% morbidity rate and a 2.1% BRD mortality rate, with an average net loss of AUD$1,647.53 per BRD mortality. Animals treated ≥3 times for BRD had 39.6 kg lighter carcasses at slaughter and returned an average of AUD$384.97 less compared to animals never treated for BRD (P < 0.001). Animals with severe lung lesions at slaughter grew 0.3 kg/d less, had 14.3 kg lighter carcasses at slaughter, and returned AUD$91.50 less than animals with no lung lesions (P < 0.001). Animals with subclinical and clinical BRD had 16.0 kg and 24.1 kg lighter carcasses, respectively, and returned AUD$67.10 and AUD$213.90 less at slaughter, respectively, compared to healthy animals that were never treated with no lesions (P < 0.001). The severity of BRD based on the number of treatments an animal received and the severity of lung and pleural lesions reduced animal performance, carcass weight and quality, and economic returns. Subclinical BRD reduced animal performance and economic returns compared to healthy animals; however, subclinical animals still had greater performance than animals with clinical BRD. This information can be used to plan for strategic investments aimed at reducing the impacts of BRD in feedlot cattle such as improved detection methods for subclinical animals with lesions at slaughter and BRD treatment protocols.

Pleural translocation and lesions by pulmonary exposed multi-walled carbon nanotubes.

Carbon nanotubes (CNTs) are recently developed tubular nanomaterials, with diameters ranging from a few nanometers to tens of nanometers, and the length reaching up to several micrometers. They can be either single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs). Due to their nano-scaled structure, CNTs have a unique set of mechanical, electrical, and chemical properties that make them useful in information technologies, optoelectronics, energy technologies, material sciences, medical technologies, and other fields. However, with the wide application and increasing production of CNTs, their potential risks have led to concerns regarding their impact on environment and health. The shape of some types of CNTs is similar to asbestos fibers, which suggests that these CNTs may cause characteristic pleural diseases similar to those found in asbestos-exposed humans, such as pleural plaques and malignant mesothelioma. Experimental data indicate that CNTs can induce lung and pleural lesions, inflammation, pleural fibrosis, lung tumors, and malignant mesothelioma upon inhalation in the experimental animals. In this review, we focus on the potential of MWCNTs to induce diseases similar to those by asbestos, molecular and cellular mechanisms associated with these diseases, and we discuss a method for evaluating the pleural toxicity of MWCNTs.

Туберкулез у больных ВИЧ-инфекцией в терапевтическом стационаре в регионе с высокой пораженностью ВИЧ

Objective. To analyze the role and character of tuberculosis (TB) among all respiratory diseases in HIV-infected patients treated in a therapeutic hospital Patients and methods. This longitudinal retrospective study included all consecutive HIV-positive patients with respiratory diseases (n = 185) treated in the Therapeutic Department of the City Hospital No 2 in Novokuznetsk in 2017–2018. Results. TB was diagnosed in 50 HIV-infected patients (27.0%) admitted to hospital. Median CD4 count was 124 cells/μL. Only 14.3% of patients were adherent to antiretroviral therapy. Sputum smear microscopy in TB dispensary was positive twice as often as in the therapeutic hospital (54.4% vs 23.4%). Abdominal lymphadenopathy was detected in 52.8% of patients examined, regardless of the pulmonary lesion pattern (p &gt; 0.05); 25.0% of patients were diagnosed with endobronchial TB. The main radiological syndromes of TB in the HIV-infected population included dissemination (52.0%), infiltration (26.0%), and intrathoracic lymphadenopathy (10.0%). Pleural lesions were identified in 28% of participants with TB and HIV coinfection. Conclusion. TB was the only cause of focal dissemination (100.0%, p &lt; 0.001), while pleural lesions and intrathoracic lymphadenopathy were significantly more common in TB patients than in individuals with non-tuberculosis diseases (11.6% and 0.8%, respectively, p &lt; 0.05). Hospital mortality rate among TB patients in a therapeutic hospital was 8.0%. Key words: HIV infection, immunosuppression, tuberculosis

Photodynamic Diagnosis for Pleural Disseminated Lesions of Lung Cancer Using a Combination of 5-Aminolevulinic Acid and Autofluorescence Observation System.

We developed a diagnostic method for pleural disseminated lesions of lung cancer using a combination of 5-aminolevulinic acid (5ALA) and autofluorescence observation system. We utilized a phenomenon in which externally ingested 5ALA is metabolized to protoporphyrin IX, a precursor of heme, which remains inside malignant cells and emits red fluorescence of approximately 630 nm. The diagnosis was made employing an observation system based on autofluorescence emitted from normal tissues that we have investigated. Between January 2017 and April 2019, we examined 82 lung cancer patients with suspected pleural invasion. We orally administered 5ALA (20 mg/m2) to the patients 4 hours before surgery, and malignant pleural lesions were thoracoscopically visualized using the autofluorescence observation system. (1) Pleural disseminated lesions were observed in six patients. Of these lesions, two were not detected by usual white light inspection, and the use of this method enabled the diagnosis of disseminated lesions. (2) Regarding the diagnosis of lung cancer pleural invasion to estimate the risk of pleural dissemination, if limited to adenocarcinoma, the sensitivity was 93.9%; specificity, 74.3%; positive predictive value, 60.8%; and negative predictive value, 96.2%. This method may facilitate the detection of minute disseminated lesions that are difficult to detect by usual inspection. In addition, the degree of pleural invasion may be diagnosed to evaluate the need for limited resection such as segmentectomy.

Bevacizumab as First-line Treatment for HER2-negative Advanced Breast Cancer: Paclitaxel plus Bevacizumab Versus Other Chemotherapy.

The efficacy of paclitaxel and bevacizumab (PB) compared with other chemotherapies in patients with human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer is unclear. We retrospectively investigated 301 patients with HER2- ABC who received first-line chemotherapy from January 2011 to December 2016. We included 114 patients who received PB and 187 patients who received other chemotherapies. After propensity score matching, the PB group showed a significantly superior overall response rate (77.8% vs. 38.9%, p<0.0001) and median time to treatment failure (7.3 vs. 5.9 months, p=0.035). In subgroup analyses, PB improved the median overall survival of patients with pleural lesions or pulmonary lymphangiopathy (not reached vs. 18.9 months, p=0.037), and of patients with three or more metastatic sites without liver metastases, (48.0 vs. 27.3 months, p=0.015). Compared with conventional chemotherapy, PB improved the overall response rate and time to treatment failure in patients with HER2- advanced breast cancer and improved overall survival in some patient subgroups.

Comparing the diagnostic accuracy of semi-rigid and rigid pleuroscopy in diagnosis of exudative lymphocyte dominant pleural effusion with.

Background and Objectives:Pleuroscopy is an appropriate technique for visualization and biopsy of the pleural lesions, performed by two different techniques. In this study, we aimed to investigate the diagnostic accuracy of semi-rigid and rigid pleuroscopy in patients with lymphocyte dominant exudative pleural effusion.Materials and Methods:In this study, patients with lymphocyte dominant pleural effusion with negative results for tuberculosis who referred to Imam Khomeini Hospital, Ahvaz, Iran; from 2018 to 2019 were selected by census method and randomized to undergo semi-rigid or rigid pleuroscopy (30 in each group). Patients' demographic, such as age and gender, were recorded and the pathologic results reported by the two pleuroscopy methods were compared and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were reported for each method. All statistical analyses were performed using SPSS v. 21.Results:Thirty patients were included in each group. The frequency of tuberculosis, malignancy, and other causes of pleural effusion had no difference between the two methods (P > 0.05). Semirigid pleuroscopy had a sensitivity of 81.5%, specificity of 66.6%, PPV of 75.6%, and NPV of 74%, while the relevant values in rigid pleuroscopy were 87.2%, 68.4%, 87.2%, and 68.4%, respectively.Conclusion:These results, consistent with previous studies, indicated that both semi-rigid and semi-flexible pleuroscopy methods are accurate for diagnosis of lymphocyte dominant pleural effusion when performed by skilled specialists and other considerations, such as availability and costs, can be used for selection of each method.

Diagnostic utilization of thoracoscopy for the pleural metastases of breast cancer

Introduction: Breast cancer is the most commonly diagnosed malignancy and the leading cause of cancer related deaths in women. Objective: This study aimed to investigate the efficacy of thoracoscopy in the diagnosis of pleural metastasis of breast carcinomas. Material and Methods: A retrospective study was conducted to include 68 patients with freshly diagnosed breast cancer who had undergone thoracoscopy to drain pleural effusions and to perform pleural biopsies. Whole group of patients were evaluated in terms of age, type of primary breast cancer, macroscopic appearance of pleura during thoracoscopy in addition to presence of malignancy detected in pleura and/or pleural effusion. Results: All of the patients were female and mean age was 53.42 ± 11.20 years. Metastatic disease was diagnosed in the pleura of 42 (61.8%) and in the pleural effusion of 40 (58.8%) patients. The most common type of breast cancer was invasive ductal carcinoma while invasive lobular cancer was the most vulnerable to metastatize to pleura. Age of the patients was not a coefficient in pleural metastasis whereas nodular pleural lesions were significantly related with the development of metastatic disease in both pleura and pleural effusion. Conclusion: Thoracoscopy is a safe and reliable diagnostic tool for the pleural metastases of breast cancer.

Diagnostic utility of medical thoracoscopy in undiagnosed exudative pleural effusions

Background: Medical thoracoscopy is a minimally invasive technique to inspect the pleural space and to perform biopsy of pleural lesions under direct vision. In this study, the diagnostic utility of thoracoscopy for undiagnosed exudative lymphocytic pleural effusions from a tertiary care respiratory center will be discussed. Materials and Methods: In a retrospective analysis of thoracoscopic procedures, we performed between September 2017 and August 2019, the yield of thoracoscopic pleural biopsy for achieving a diagnosis in undiagnosed exudative lymphocytic pleural effusions was evaluated. Undiagnosed exudative pleural effusions were defined as pleural effusions where an etiologic diagnosis could not be ascertained by initial pleural fluid biochemical and microbiological analysis, including protein, sugar, lactate dehydrogenase, Gram and acid-fast bacilli stains and Mycobacterium tuberculosis culture, pleural fluid adenosine deaminase levels, and at least two pleural fluid cytologies negative for malignant cells or other definite causes. We analyzed the clinical, radiological, cytological, and histopathological data of the patients and also the complications of thoracoscopy. Results: We performed thoracoscopy in 68 cases of undiagnosed exudative pleural effusions using the rigid thoracoscope. The overall diagnostic yield of thoracoscopic pleural biopsy was 95.6% in patients with undiagnosed exudative pleural effusions. Malignant pleural effusion was diagnosed in 67.6% of patients, while tuberculosis was diagnosed with pleural biopsy in 25% of patients. Three cases of subcutaneous emphysema, 2 cases of postprocedure fever were observed, and one patient had prolonged air leak. Conclusion: Medical thoracoscopy has a good diagnostic yield in patients with undiagnosed exudative lymphocytic pleural effusions and is a safe procedure as well.

A gene-expression-based test can outperform bap1 and p16 analyses in the differential diagnosis of pleural mesothelial proliferations.

The demonstration of tissue invasion by histology is an essential criterion for the differential diagnosis of benign and malignant mesothelial proliferations. When tissue invasion cannot be identified, the use of ancillary tests is sometimes necessary. Among investigated markers, the loss of BRCA1 associated protein 1 (BAP1) protein expression and the homozygous deletion of p16 have shown 100% specificity in separating benign and malignant mesothelial lesions. However, beyond the excellent specificity of these two markers, their low sensitivity limits their clinical utility. In this context, a previous study developed and tested a novel tool for use in the differential diagnosis of malignant pleural mesothelioma (MPM) using the NanoString System and a classification algorithm. In the current study, the performance of gene classifiers were compared using BAP1 and p16 testing. p16 FISH and BAP1 immunohistochemistry were performed on the same series of 34 epithelioid MPM and 20 benign pleural lesions, which were previously analyzed by the system. The diagnostic performance of p16, BAP1 and our classification models were compared using ROC analysis. It was observed that BAP1 loss and p16 deletion were highly specific for MPM, since they were not detected in benign lesions. However, their AUC values were not completely satisfying (BAP1: 0.8235; p16: 0.7647) particularly due to their low sensitivities. As expected, combining BAP1 and p16 tests increased the diagnostic sensitivity, thus improving the AUC (0.8824). In the same series of cases, our MPM tool outperformed BAP1 and p16 tests using the 22 and 40-gene classification models (AUC 22-gene model: 0.9996; AUC 40-gene model: 0.9990). In conclusion, the present gene-expression-based classification exhibited great potential and further validation is required to support these findings in a prospective fashion, in order to provide a solid alternative for pleural proliferation diagnosis.

Intraspinal Paragonimiasis in Children: MRI Findings and Suggestions for Pathogenesis.

Intraspinal paragonimiasis is a rare entity for which imaging findings have seldom been described. The present study investigated the MR imaging features of spinal paragonimiasis, thus providing diagnostic imaging evidence and exploring the possible pathogenesis of intraspinal paragonimiasis. The clinical and imaging findings of spinal paragonimiasis in 6 children were analyzed retrospectively. Spinal MR imaging was performed in all patients, 5 of whom also underwent enhanced MR imaging. The diagnosis was confirmed by enzyme-linked immunosorbent assay in all cases and postoperative pathology in 4 cases. All cases manifested as fusiform-shaped or beanlike masses in the extradural space in the thoracic spine. The extradural masses were connected with pleural lesions through the intervertebral foramen. The plain MR imaging scan showed mixed signals with predominant isointensity on T1WI and hyperintensity on T2WI, among which 5 (5/6) masses presented as patchy hemorrhage with hyperintensity on T1WI. On enhanced scans, all masses (5/5) showed heterogeneous marked enhancement, with thickening and enhancement in the adjacent spinal meninges (5/5). Various degrees of spinal cord compression and edema were found in 5 cases (5/6). MR imaging is sensitive for detecting and characterizing spinal paragonimiasis. The MR imaging features of intraspinal granulomas included localization to the extradural space and thoracic segment, connections between intraspinal lesions and pleural lesions through the intervertebral foramen, and hemorrhagic foci within the mass. These findings support an intraspinal mode of paragonimiasis pathogenesis: The Paragonimus larvae migrate from the chest into the extradural space through the intervertebral foramen.

First-in-Human Imaging of Multiple Myeloma Using Copper-64-Labeled Daratumumab: Preliminary Results

Introduction: 18Fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and non-malignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with copper-64 via the chelator DOTA (64Cu-DOTA-Dara), led to improved sensitivity and specificity over that of FDG (Caserta et al, Blood 2018). Herein, we report the results of a Phase 1 trial (NCT#03311828) designed to 1) assess the safety and feasibility of 64Cu-DOTA-Dara PET/CT and 2) to evaluate and characterize the ability of 64Cu-DOTA-Dara to accurately detect or exclude MM lesions compared with FDG PET/CT. Methods: Patients with biopsy-proven MM and/or a plasmacytoma received an FDG PET/CT scan within 60 days of enrollment. On Day 0, patients were infused with unlabeled ("cold") Dara at one of four dose levels (0 mg, 10 mg, 45 mg, 95 mg) to optimize biodistribution of radioconjugated 64Cu-DOTA-Dara, especially in the liver and the spleen. Within 6 hours of unlabeled Dara administration, patients received 64Cu-DOTA-Dara at a dose of 13.63-16.68 mCi (~5 mg). Whole-body PET scans were obtained at 24 hours and at 48 hours (the latter scan encompassing known tumors). 64Cu-DOTA-Dara standardized uptake values (SUV) were evaluated in MM lesions and normal organs, which were then compared with values from standard FDG PET/CT. Biopsies were performed on accessible discordant lesions. Results: A total of 10 Dara-naïve patients were imaged. Patients were treated with 0 (n=3), 10 (n=3), 45 (n=3), or 95 mg (n=1) of unlabeled Dara. Four patients had newly diagnosed disease, one had biochemical relapse, one had a recurrent plasmacytoma by MRI, and four had possible recurrence by standard PET/CT. No significant adverse events were observed from either cold or 64Cu-DOTA-Dara. With the exception of the one patient with a recurrent plasmacytoma, radiolabeled antibody was eliminated from systemic circulation in subjects analyzed at the first three dose levels within 30 min post injection. In the patient with a recurrent plasmacytoma, the radiolabeled antibody was elevated in the blood for over two days. One newly diagnosed patient had extensive disease by FDG PET and had a biopsy-proven target lesion in the sternum, which had an SUVmax of 14.7 on 64Cu-DOTA-Dara PET/CT vs. 3.3 onFDG PET/CT. A second biopsy from the same patient was taken from a discordant iliac crest lesion (positive for 64Cu-DOTA-Dara but negative for FDG PET/CT) that showed 20-30% MM cell infiltration. In another patient, an iliac crest lesion was 64Cu-DOTA-Dara positive and FDG-negative; biopsy revealed 6% plasmacytosis in the bone. A third patient had an FDG PET/CT positive pleural lesion with an SUVmax of 8.98 and negative on 64Cu-DOTA-Dara (Figure 1A). The lesion did not show recurrence upon biopsy. Furthermore, 64Cu-DOTA-Dara PET/CT yielded superior imaging of bone lesions in the calvarium (Figure 1B). Escalating doses of unlabeled Dara decreased liver and spleen uptake by 64Cu-DOTA-Dara. Conclusions: In this ongoing study, 64Cu-DOTA-Dara PET/CT imaging is to date safe and provides whole body imaging of MM. Further dose escalation of cold Dara (145 mg, 195 mg) is planned to optimize background interference. This modality has the potential to improve sensitivity and specificity over FDG PET/CT scanning in early-stage MM as well as in recurrent disease. Disclosures Krishnan: Celgene, Janssen, Sanofi, BMS: Consultancy; Sutro BioPharma, zPredicta: Consultancy; Amgen, Takeda: Speakers Bureau; Celgene, Z Predicta: Other: Stock Ownership; Takeda: Research Funding. Palmer:Gilead Sciences: Consultancy. Rosenzweig:Celgene, Takeda: Speakers Bureau. Wu:ImaginAb, Inc.: Consultancy, Other: Board Member.

Thoracoscopic pleural brushing - an innovative method of pleural sampling in diagnostic medical thoracoscopy.

Pleural biopsy is the commonest mode of obtaining thoracoscopic pleural specimens from suspected pleural lesions. However, this may be associated with arisk of bleeding in certain cases. The decision to perform biopsy could be difficult, especially when the lesions are close to vascular structures and the visceral pleura. So, pleural brushing can be used to get safely thoracoscopic specimens in addition to biopsy samples. To determine the sensitivity and specificity of thoracoscopic pleural brushing in exudative pleural effusions. This prospective study was done in the Department of Pulmonary Medicine, Sri Manakula Vinayagar Medical College, Pondicherry, India on 80 patients with exudative pleural effusion in whom pleural fluid analysis and closed pleu-ral biopsy results were inconclusive. All these patients were subjected to medical thoracoscopy after getting informed consent. Pleural biopsy and pleural brushings were taken and sent for analysis. Thoracoscopic pleural biopsy was diagnostic in 76 of 80 patients (95%). Thoracoscopic pleural brushing was diagnostic in 74 patients (92.5%). Histopathology revealed malignancy (82.7%), granulomatous inflammation (11.5%) and nonspecific inflam-mation (5.7%). The sensitivity and specificity of pleural brushing were 96% and 75%, respectively. Interestingly, pleural brushing was the only diagnostic modality in one patient that was reported to be adenocarcinoma. Thoracoscopic pleural brushing is an easy, convenient and safe procedure as it can augment the diagnostic yield of thoracoscopy. It is of significant value, especially in sampling pleural lesions close to vessels and the visceral pleura compared to pleural biopsy.

Tuberculosis and HIV co-infection in inpatients of phthisio-pulmonological profile: frequency, form of lesion, diagnostic features (according to data of highly specialized institution)

Objective — to clarify the prevalence of tuberculosis infection in HIV-positive inpatients of the TB hospital for 2014—2018 and features of its diagnosis in the affection of the chest cavity organs.Materials and methods. The method of retrospective analysis was used to process medical records of the Institute’s clinic for the period 2014—2018. A database has been formed that includes all patients with HIV infection treated in the hospital, from which a group of patients with a final clinical diagnosis of co-infection tuberculosis and HIV was subsequently selected.Among them were 195 (68.9 %) men and 88 (31.1 %) women. The average age of men was (37.0 ± 0.5), women — (38.0 ± 1.2) years. Separate subgroups of patients were selected, taking into account the localization of the tuberculous process in the chest cavity. The general clinical data of patients, the presence of comorbidities, diagnostic methods, localization and prevalence of the tuberculous process were taken into account.Results and discussion. Among 496 hospitalized HIV-positive patients with various pathologies of the chest cavity, the diagnosis of tuberculosis, that is, the presence of HIV-TB co-infection, was established in 283 (57.1 %) cases. In 46 (16.3 %) cases the diagnosis of HIV infection was established for the first time during hospitalization. Comorbid pathology was present in 184 (65.0 %) patients.Specific lung damage prevailed, 123 (44 %) cases, most often infiltrative tuberculosis (48.8 %). In 33 % of cases, there was a widespread tuberculous lesion — pulmonary and extrapulmonary (pleura or lymph nodes were involved). Isolated pleural lesion was diagnosed in 13 % of cases. The main methods of laboratory diagnostics were classical bacteriological methods — simple direct light microscopy and MBT culture, the positive results of which were obtained in only half of all studies, as well as molecular-genotypic tests. Prevalence of multidrug-resistant MBT strains was found (66.7 %).In about half of the cases, (44.9 %), additional mini-invasive procedures or surgical interventions with therapeutic and diagnostic purposes were performed. Histological examination confirmed the diagnosis of tuberculosis in 92 % of cases, whereas in the absence of signs of tuberculosis, diagnoses of other opportunistic diseases were most often specified/established.Conclusions. In HIV-positive inpatients of a phthisiopulmonary profile, tuberculosis infection prevails in the structure of opportunistic morbidity, 57.1 %. The largest proportion of patients consist cases with pulmonary tuberculosis (44 %), is also a large group (33 %), formed by patients with the extended lesion of the organs of the chest cavity.Positive results of traditional bacteriological studies were obtained in approximately half of the cases, which required an expansion of the diagnostic algorithm with the implementation of mini-invasive diagnostic procedures with biopsy of the affected tissues and subsequent histological examination.Analysis of the results of laboratory diagnostics of tuberculosis in cases of TB/HIV co-infection showed that the use of not only different microbiological research methods is most effective, but an important component in the diagnostic search is the histological examination of biopsy material.