Asbestos: Mineralogical features and fiber analysis in biological materials.

Asbestos is a mineral with unique physical and chemical properties that make it highly resistant to heat, fire, and corrosion. Nevertheless, exposure to asbestos fibers has been linked to serious health problems, including lung cancer, mesothelioma, and asbestosis. Despite the ban on asbestos usage, asbestos-related diseases are still a major cause of morbidity and mortality worldwide. Analyzing the mineralogical features and fiber analysis of asbestos in biological materials is critical for scenarios where an asbestos exposure history cannot be obtained, a clinical diagnosis cannot be made, or legal aspects necessitate further investigation. This review outlines the mineralogical features and fiber analysis techniques of asbestos in biological materials.

Behçet's Disease-related Budd-Chiari Syndrome Successfully Managed with anti-TNF Antibody: A Case Report and Review of the Literature.

Behçet's disease (BD) is multisystemic vasculitis with heterogeneous clinical manifestations. We describe the case of a 26-year-old man who presented with Budd-Chiari syndrome (BCS) related to BD. The patient received infliximab (IFX) due to the severity of vascular involvement. Subsequently, after IFX therapy, hospital-acquired pneumonia, trapped lung, and fungal infection of the lung and central nervous system developed as complications. The patient benefited from a second course of IFX and clinical remission was achieved following early identification and treatment of complications. Data on the presentation and prognosis of BCS related to BD are extremely limited. Our case report supports the growing evidence that anti-TNF antibody is a promising treatment for BD-related BCS. LEARNING POINTS: Behçet's disease-related Budd-Chiari syndrome is a rare form of vascular involvement that severely affects mortality.Behçet's disease-related Budd-Chiari syndrome is frequently confused with idiopathic thrombosis and may be underdiagnosed.Infliximab could be a therapeutic option for refractory Behçet's disease with major vascular involvement, but the increased risk of opportunistic infections should be kept in mind.

Evaluation of Exudative Pleural Effusions: A Multicenter, Prospective, Observational Study.

PURPOSE: The aim of this study is to determine the diagnostic performances of pleural procedures in undiagnosed exudative pleural effusions and to evaluate factors suggestive of benign or malignant pleural effusions in tertiary care centers. METHODS: This was a multicenter prospective observational study conducted between January 1 and December 31, 2018. A total of 777 patients with undiagnosed exudative pleural effusion after the initial work-up were evaluated. The results of diagnostic procedures and the patients' diagnoses were prospectively recorded. Sensitivity, specificity, and accuracy estimates with 95% confidence intervals were used to examine the performance of pleural procedures to detect malignancy. RESULTS: The mean age ± SD of the 777 patients was 62.0 ± 16.0 years, and 68.3% of them were male. The most common cause was malignancy (38.3%). Lung cancer was the leading cause of malignant pleural effusions (20.2%). The diagnostic sensitivity and accuracy of cytology were 59.5% and 84.3%, respectively. The diagnostic sensitivity of image-guided pleural biopsy was 86.4%. The addition of image-guided pleural biopsy to cytology increased diagnostic sensitivity to more than 90%. Thoracoscopic biopsy provided the highest diagnostic sensitivity (94.3%). The highest diagnostic sensitivity of cytology was determined in metastatic pleural effusion from breast cancer (86.7%). CONCLUSION: The diagnostic performance increases considerably when cytology is combined with image-guided pleural biopsy in malignant pleural effusions. However, to avoid unnecessary interventions and complications, the development of criteria to distinguish patients with benign pleural effusions is as important as the identification of patients with malignant pleural effusions.

Pazopanib-induced chylothorax in a patient with renal cell carcinoma.

Pazopanib is an oral multi-kinase inhibitor approved for the treatment of advanced renal cell carcinoma (RCC). It is an anti-angiogenic agent, which blocks the activation signaling pathways of tyrosine kinases and prevents the activities of primarily vascular endothelial growth factor receptors (VEGFR)-2 and VEGFR-3, which are important in lymphangiogenesis. Herein, we report a patient with advanced RCC who developed asymptomatic left-sided chylothorax under pazopanib therapy. Chylothorax developed in the 16th month and gradually increased until it was diagnosed by thoracentesis in the 22nd month. The development of chylothorax was attributed to pazopanib therapy after ruling out all possible traumatic and nontraumatic etiologies. The 'Adverse Drug Reaction Probability Scale' revealed a total score of 6, which fell into 'probable' category. Chylothorax regressed significantly 5 weeks after the discontinuation of pazopanib therapy.

Ultrasound Assessment of Sarcopenia in Patients With Sarcoidosis.

OBJECTIVES: Sarcoidosis can cause sarcopenia like other chronic diseases. Ultrasonography is a simple method, which has been used frequently in recent years. We aimed to evaluate the sarcoidosis patients with ultrasonography for sarcopenia and to compare the results of ultrasonography with the accepted standard method, bioelectrical impedance analysis (BIA). METHODS: BIA and handgrip test were applied to all patients diagnosed with sarcoidosis. The patients were classified according to the presence of probable sarcopenia with their handgrip results and the presence of sarcopenia with the appendicular skeletal muscle mass index calculated with using BIA. Ultrasonography was applied to each patient and the thickness of seven different muscle groups of the patients were evaluated. The ability of muscle thickness values measured by ultrasonography to predict sarcopenia was compared with the reference standard test BIA. RESULTS: Forty patients (women/men = 31/9) were included in our study. The mean age was 53.2 ± 12.5 years. A statistically significant positive correlation was observed between handgrip strength and gastrocnemius medialis (GM), rectus femoris (RF) cross-sectional area, rectus abdominis (RA), external oblique (EO), transversus abdominus (TA), and diaphragm thicknesses. Therefore, there was a significant correlation between fat free mass index with RA, EO, and TA muscles. According to the ROC analysis, statistically significant muscle groups predicting sarcopenia were found as GM, RF cross-sectional area, EO, and IO. Again, according to the ROC analysis, it was seen that the thicknesses of GM, RA, EO, IO, and TA muscles corrected for BMI predicted probable sarcopenia with quite high sensitivity and specificity. CONCLUSIONS: Muscle thicknesses measured by ultrasonography are helpful for the diagnosis of sarcopenia that may develop in chronic diseases such as sarcoidosis. Further studies with higher number of patients are needed to validate the results of the present pilot study.

Is there any contribution of bronchial washing to biopsy in the diagnosis of patients with endobronchial pathology in the era of personalized medicine?

INTRODUCTION: Bronchoscopic biopsies and bronchial washings (BW) are commonly used together for the diagnosis of centrally located tumors. This study aimed to investigate the clinical relevance of routinely collecting BWs in patients who simultaneously had biopsies for visible endobronchial lesions in the current molecular analysis-driven personalized medicine era. MATERIALS AND METHODS: We retrospectively reviewed the patients who underwent fiberoptic bronchoscopy (FOB) between October 2011 and December 2016. Patients who had both BW and biopsy specimens (EBB: endobronchial forceps biopsy and/or EBNA: endobronchial needle aspiration biopsy) for visible endobronchial lesions were included in this study. Demographic and clinical data, macroscopic findings during FOB, pathology results, and final diagnoses were collected from the hospital database. RESULT: The study included 269 patients (220 males/49 females) with a mean age of 61.6 ± 10.6 years. While the overall diagnostic yield of FOB was 71.4%, the diagnostic yields of bronchoscopic procedures were 68.2% for EBB, 83.3% for EBNA, and 19.7% for BW. Only three patients (1.1%) with undiagnostic biopsies had positive BW cytology revealing merely malignant epithelial cells. CONCLUSIONS: BW provided a negligible diagnostic contribution in 1.1% (n= 3) of the patients. These three patients had undergone further diagnostic procedures for making a proper therapeutic management plan. In the era of personalized therapy, it is logical to obtain more biopsy in the time spent for BWs.

Performance of pulmonary embolism severity index in predicting long-term mortality after acute pulmonary embolism.

OBJECTIVE: In this study, we aimed to evaluate the accuracy of the original and simplified pulmonary embolism (PE) severity index (PESI) to predict all-cause mortality after 30 days of acute PE diagnosis up to five years within consecutive sub-periods. METHODS: Adult patients diagnosed with acute PE between January 1, 2003, and June 30, 2013, were retrospectively included. Data on baseline characteristics and mortality during a five-year follow-up were collected. RESULTS: The study included 414 patients (Male/Female=192/222). The median age at diagnosis was 61.5 (minimum-maximum, 18-93) years. Mortality rates were 13.3% at 30 days, 21.8% at 90 days, 32.6% at one year, and 51.0% at five years. Both stratification into risk classes according to the original PESI and low vs. high-risk classification of original and simplified PESI were significantly correlated with the 30-day, 31-90-day, 91-day-one-year, and one-five-year mortality. Significant PESI predictors for mortality were history of cancer [hazard ratio (HR): 3.31, 95% confidence interval (CI): 1.64-6.68; p=0.001] and heart failure (HR: 2.35, 95% CI: 1.04-5.32, p=0.041) at 31-90-day, history of cancer (HR: 5.45, 95% CI: 2.86-10.40, p<0.001) at 91-day-one-year, advancing age (HR: 1.04, 95% CI: 1.02-1.06, p<0.001) and history of cancer (HR: 5.53, 95% CI: 3.41-8.98, p<0.001) at one-five-year after acute PE diagnosis. CONCLUSION: All-cause long-term mortality in high-risk patients with acute PE according to original or simplified PESI significantly increased up to five years of follow-up. This survival disadvantage was mainly related to cancer and comorbidities rather than acute clinical manifestations. Future prospective studies are needed to demonstrate the effect of various comorbidities on long-term mortality in these patients.

Can surgical adhesives may cause false positivity in follow-up positron emission tomography after lung cancer resection?

INTRODUCTION: Postoperative complications following thoracic procedures are a major cause of morbidity and mortality. Alveolar air leaks and/or bronchopleural fistulas are associated with increased risk of infection, prolonged chest tube, and hospital stay duration and therefore generate economical concern for health care providers. A variety of surgical sealants or adhesives have been introduced to overcome this complication. Since intraoperative BioGlue® application can also cause an inflammatory reaction and mimic tumor recurrence on FDG PET-CT, in the present study we aimed to investigate its potential role in false-positive PET-CT results in patients operated for NSCLC. MATERIALS AND METHODS: Data of six patients who underwent resection for primary NSCLC at our institution (Department of Thoracic Surgery, Hacettepe University Medical Faculty) between January 2015 and December 2018 and had false positivity, due to BioGlue® application, at the bronchial stump in follow-up FDG PET-CT were retrospectively analyzed from a prospectively collected database. RESULT: One of the 6 patients was female and 5 were male. The mean age was 68 years (range, 56-79 years). The average time interval between operation and postoperative FDG-PET imaging was 4.3 months (range, 4-6 months). Follow-up FDG-PET imaging SUVmax values ranged between 3.0 and 9.0 (median: 5.33). All patients have been evaluated by FDG-PET scan following the detection of soft tissue densities at the surgical site suspicious for recurrence at their follow-up chest CT scans. Four patients underwent a bronchoscopic examination, bronchial stumps were examined and multiple biopsies were taken from suspicious nodules or tissues and sent for pathologic examination. Histopathological results revealed inflammation which is compatible with foreign body granuloma, without any suspicion for malignancy, in all cases. Two patients were solely followed-up and subsequent FDG-PET imaging after 3 months revealed complete resolution of FDG uptake. CONCLUSIONS: To avoid unnecessary biopsies or surgical procedures, the possibility of false-positive results due to surgical adhesive product use should be taken into account while interpreting follow-up FDG-PET imaging results and the operative reports should be written in detail, describing which surgical materials used and their exact application sites.

Pulmonary manifestations of antiphospholipid syndrome: a retrospective analysis of 67 patients.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/ or venous thrombosis accompanied by persistently elevated levels of antiphospholipid antibodies (aPLs). The aim of this study is to evaluate the pulmonary manifestations of APS and compare the levels of aPLs in patients with and without pulmonary involvement. We retrospectively reviewed the files of patients with the diagnosis of APS between October 2010 and May 2017. Demographic data, clinical, radiological and laboratory findings were recorded. The study included 67 patients (56 female/11 male) with a mean age of 39 ± 13 years. Pulmonary manifestations such as parenchymal and/or vascular involvement were seen in 12 (17.9%) patients. The patients with and without pulmonary manifestations were not significantly different in terms of age (p = 0.46), comorbidities (p = 0.48) and APS duration (p = 0.66). Acute pulmonary thromboembolism (PE) was determined in 11 (16.4%), alveolar hemorrhage in 2 (3%) patients. Four patients with acute PE (36%) developed chronic thromboembolic pulmonary hypertension (CTEPH). One patient developed both CTEPH and diffuse alveolar hemorrhage after acute PE during follow up. Antiphosholipid antibody IgM was highly positive in patients with PE compared to patients without PE (p = 0.005). Other antibodies and lupus anticoagulant were not significantly different in patients with and without PE. None of the patients were deceased due to pulmonary manifestations of APS. PE was the most common pulmonary manifestation of APS. The development of CTEPH was high among APS patients. Patients with APS should be closely followed for the onset of PE and CTEPH.

The contribution of bronchoalveolar lavage in the diagnosis of welder's lung in a patient with pulmonary fibrosis.

Interstitial pulmonary fibrosis is rare clinical entity related to welding usually associated with long term and heavy exposure to welding fumes. A 56-year-old asymptomatic male patient was referred to our clinic due to abnormal chest X-ray findings that was requested for regular controls. He has been working as a welder both indoor and outdoor settings for the last 25 years. The radiological findings were compatible with usual interstitial pneumonia on computed tomography of thorax. Pulmonary function tests, exercise capacity and laboratory results were within normal limits. Collagen tissue markers were negative. In order to confirm the relation of welding with pulmonary fibrosis, bronchoalveolar lavage was performed and stained with Prussian blue. The demonstration of hemosiderin-laden macrophages (25%) confirmed this association and allowed differential diagnosis. Besides it helped the patient decide to leave his job.

Diagnostic value of BRCA1-associated protein-1, glucose transporter-1 and desmin expression in the discrimination between reactive mesothelial proliferation and malignant mesothelioma in tissues and effusions.

OBJECTIVE: The aim of this study was to investigate the utility of BRCA1-associated protein-1 (BAP1), glucose transporter (GLUT)-1 and desmin expression by immunohistochemistry in the discrimination between reactive and malignant mesothelial proliferations. METHODS: A total of 88 biopsies and 30 effusions from mesothelioma cases were studied. Control groups were composed of 35 tissues and 30 cell blocks. The 88 mesothelioma cases were from 43 males and 45 females (mean age 56 years). Tumours were mostly localised to pleura (66/88, 75%) and of epithelioid histology (75/88, 85%). Cytology samples were from 17 males and 13 females (mean age 58 years), and 16 pleural and 14 peritoneal effusions. Twenty cytology cases had corresponding tissue biopsies. RESULTS: BAP1 loss was detected in 61/88 (69%) tissues and in 20/30 (67%) cytology samples from mesothelioma with a specificity of 100% for both sampling methods. BAP1 loss was observed more frequently in pleural and biphasic tumours. GLUT-1 immunoreactivity was identified in 54/81 (67%) and 23/25 (92%) malignant tissues and effusions, and in 6/33 (18%) and 6/30 (20%) benign tissues and effusions, respectively. Desmin loss was observed in 74/80 (92%) malignant biopsy samples, 16/21 (76%) malignant effusions and 10/34 (29%) of benign tissues, but in none of the reactive effusions. Concordance rate of results between biopsy and cytology was as follows: BAP1 20/20 (100%); GLUT-1 13/18 (72%); and desmin 10/14 (71%). CONCLUSIONS: BAP1, GLUT-1 and desmin are useful markers in the discrimination between reactive and malignant mesothelial proliferations. BAP1 loss seems to be diagnostic for mesotheliomas both in biopsy and cytology samples.

Diagnosis of malignant pleural mesothelioma from pleural fluid by Fourier transform-infrared spectroscopy coupled with chemometrics.

This study was conducted to differentiate malignant pleural mesothelioma (MPM) from lung cancer (LC) and benign pleural effusion (BPE) from pleural fluids using the diagnostic power of Fourier transform-infrared spectroscopy with attenuated total reflectance mode coupled with chemometrics. Infrared spectra of MPM (n = 24), LC (n = 20), and BPE (n = 25) were collected, and hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to their spectra. HCA results indicated that MPM was differentiated from LC with 100% sensitivity and 100% specificity and from BPE, with 100% sensitivity and 88% specificity, which were also confirmed by PCA score plots. PCA loading plots indicated that these separations originated mainly from lipids, proteins, and nucleic acids-related spectral bands. There was significantly higher lipid, protein, nucleic acid, and glucose contents in the MPM and LC. However, the significant changes in triglyceride and cholesterol ester content, protein and nucleic acid structure, a lower membrane fluidity, and higher membrane order were only observed in the MPM. To check the classification success of some test samples/each group, soft independent modeling of class analogies was performed and 96.2% overall classification success was obtained. This approach can provide a rapid and inexpensive methodology for the efficient differentiation of MPM from other pleural effusions.

Triple test with tumor markers CYFRA 21.1, HE4, and ProGRP might contribute to diagnosis and subtyping of lung cancer.

BACKGROUND AND AIM: Early diagnosis and histological subtyping are important issues in the management of patients with lung cancer (LC). The aim of this study is to investigate the diagnostic value of a panel of serum tumor markers in newly diagnosed patients with LC. METHODS: Venous blood samples were collected from 99 patients with LC (42 adenocarcinoma, 35 squamous, and 22 small cell carcinoma) and 30 patients with benign lung disease. Progastrin releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCAg), cytokeratin 19-fragments (CYFRA 21.1), human epididymis protein 4 (HE4), Chromogranin A (CgA) and neuron specific enolase (NSE) levels were measured. The diagnostic value of the biomarkers was assessed with ROC curve analyses; the area under the curve (AUC) was calculated. RESULTS: Serum CYFRA 21.1, ProGRP, SCCAg, NSE levels were significantly higher in LC patients. While ProGRP levels were higher (p = 0.009) in SCLC; CYFRA 21.1 and SCCAg levels were higher in NSCLC (p = 0.019 and p = 0.001, respectively). The sensitivity and specificity of tumor markers were 72%, 83% for CYFRA 21.1; 70%, 57% for HE4; 18%, 93% for ProGRP; 43%, 77% for SCCAg; 54%, 53% for CgA; 73%, 50% for NSE. CYFRA 21.1 (p < 0.001, r = 0.394), HE4 (p = 0.014, r = 0.279) and CgA (p = 0.023, r = 0.259) levels were positively correlated with tumor stage in NSCLC. CgA levels were significantly higher in extensive stage SCLC (p = 0.004). CYFRA 21.1 had the highest diagnostic value for LC (AUC = 0.865). When it is combined with HE4, diagnostic value increased (AUC = 0.899). ProGRP had the highest diagnostic value (AUC = 0.875, p < 0.001) for discriminating SCLC from NSCLC. CONCLUSION: A panel of three tumor markers CYFRA 21.1, HE4 and ProGRP may play a role for discriminating LC from benign lung disease and subtyping as SCLC.

Diagnostic utility of conventional transbronchial needle aspiration in older patients.

BACKGROUND: In older patients, diagnosis and initial treatment should be considered as soon as possible because of high disease burden and complications. Conventional transbronchial needle aspiration (C-TBNA) is an important and safe method for the diagnosis of mediastinal lesions and staging lung cancer in the general population. We aimed to evaluate the diagnostic utility and complications of C-TBNA procedure in older patients aged ≥ 65 years. METHOD: We retrospectively evaluated C-TBNA results consecutively. Demographic data, clinical, radiological and flexible bronchoscopy (FB) findings, complications during C-TBNA and incidence of diagnostic C-TBNA with the presence of abundant lymphoid cells of polymorphous appearance both in patients aged ≥ 65 years and in younger patients were determined. RESULTS: C-TBNA was performed to a total of 317 patients, including 109 older and 208 younger patients attended to our clinic between 2012 and 2016. The mean ages of older and younger patients were 70.3 ± 4.6 and 52.5 ± 10 years, respectively (p < 0.001). Overall, 75.2% of older and 80.3% of younger patients had diagnostic C-TBNA. The diagnostic utility of C-TBNA did not differ significantly between older and younger patients (p = 0.297). During C-TBNA, one older patient had a complication of bronchospasm, and four younger patients had complications such as bleeding (n = 1) and bronchospasm (n = 3). There was no statistically significant difference between older and younger patients in terms of complications during C-TBNA procedure (p = 0.49). CONCLUSION: C-TBNA is a safe procedure with similar diagnostic yield in older patients.

Association of class II human leukocyte antigen (HLA) alleles with pulmonary sarcoidosis.

Background and objectives: Sarcoidosis is a systemic inflammatory disease of unknown etiology that involves any part of the body, mainly the lungs and thoracic lymph nodes. The clinical presentation is heterogeneous based on the degree and extent of organ involvement. The existence of variable clinical presentations and treatment responses suggest an important role of genetic predisposition. In genetic studies, sarcoidosis was found to be associated with several genes, but the strongest link was with HLA region. The aim of this study was to investigate the association of HLA class II alleles with the extent and course of disease in Turkish patients with sarcoidosis. Methods: The study included 103 patients with sarcoidosis and 100 unrelated healthy controls. HLA-DRB1 and HLA-DQB1 typing was performed by using Polymerase Chain Reaction-Sequence Specific Priming (PCR-SSP) method at low resolution level. Results: HLA-DRB1* and -DQB1* analysis revealed that while the frequency of HLA-DRB1*01 was significantly higher in the control group, HLA-DRB1*13 and -DQB1*06 alleles were more frequent in the sarcoidosis patients. When the patients were grouped based on clinical outcome as remitters and non-remitters, HLA-DRB1*10 allele was only detected in the remitters, whereas the frequency of HLA-DQB1*06 allele was significantly higher in non-remitters. Conclusions: This study supported the association of HLA alleles with sarcoidosis. In a considerably high number of patients with Turkish origin, the frequency of HLA-DRB1*13, -DRB1*10 and HLA-DQB1*06 alleles was significantly associated with increased risk and clinical outcome. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 143-149).

Acute massive pulmonary embolism associated with olanzapine.

Treatment with low-potency anti-psychotic agents is an important risk factor in the development of pulmonary embolism (PE). We report a case of 74years old female patient receiving olanzapine for psychotic depression admitted to the emergency service with the complaints of chest pain and shortness of breath. She had tachypnea, hypotension and tachycardia. Arterial blood gas analysis showed hypoxemia-hypocapnia and D-dimer level was high. Computed tomographic pulmonary angiography (CTPA) demonstrated pulmonary embolism in both main pulmonary arteries, through lobar and segmental branches. Tissue plasminogen activator (t-PA) was administered in intensive care unit. As the only possible risk factor for PE was olanzapine, olanzapine treatment was terminated with pyschiatry consultation. During the 12-month follow-up of the patient; malignancy was not observed. Diagnosis and prevention of PE are the important goals to reduce morbidity and mortality in subjects receiving olanzapine.