Diagnostic method for malignant pleural effusion distinguishing malignant mesothelioma from lung cancer using pleural carcinoembryonic antigen and hyaluronic acid levels.

ABSTRACT: Malignant mesothelioma (MM) is difficult to diagnose because of the lack of parenchymal opacities, often revealing minimal or absent pleural thickening. Furthermore, pleural effusion has diverse differential diagnoses, including malignancies, infections, as well as collagen vascular and other benign diseases. In general practice, lung cancer (LC) is the most common malignancy causing pleural effusion; therefore, a simple method using pleural diagnostic markers to differentiate between LC and mesothelioma is crucial.We retrospectively reviewed the data of 530 adult patients diagnosed with pleural effusion between January 2010 and December 2020 in an outpatient or inpatient setting. Patients with pathologically diagnosed MM or LC with cytologically positive (class IV or V) pleural effusion were analyzed, and the characteristics of these 2 diseases were compared.During the study period, 27 patients diagnosed with MM and 100 patients diagnosed with LC were enrolled. Receiver operating characteristic curve analysis demonstrated that pleural carcinoembryonic antigen (CEA) and hyaluronic acid (HA) could discriminate MM from LC with an area under the curve of 0.925 (95% confidence interval [CI]: 0.879-0.972, P < .001) and 0.815 (95% CI: 0.686-0.943, P < .001), respectively. To diagnose MM, the accuracy of pleural HA >30,000 ng/mL revealed a sensitivity of 75.0%, specificity of 72.6%, and odds ratio of 7.94 (95% CI: 2.5-25.2, P = .001); pleural CEA <6.0 ng/mL revealed a sensitivity of 95.2%, specificity of 84.9%, smaller negative likelihood ratio of 0.06, and odds ratio of 112.5% (95% CI: 14.4-878.1, P < .001). Multiple logistic regression analysis revealed that these 2 parameters could discriminate MM from LC, with a hazard ratio of 23.6 (95% CI: 2.437-228.1, P = .006) and 252.3 (95% Cl: 16.4-3888.1, P < .001), respectively, and their combination had a high specificity of 98.3%.Pleural CEA (≥6.0 ng/mL) can rule out MM with a high degree of certainty, and the positive results for combination of pleural CEA <6.0 ng/mL and HA >30,000 ng/mL can confirm MM with high specificity, prior to cytological or pathological examinations.

Novel predictive factors for patient discomfort and severe cough during bronchoscopy: A prospective questionnaire analysis.

During bronchoscopy, discomfort is mainly caused by an unavoidable cough; however, there are no reports of any predictive factors for strong cough during bronchoscopy identified before the procedure. To clarify the factors underlying the discomfort status and predictive factors for strong cough during bronchoscopy, we prospectively evaluated patients who underwent bronchoscopy at Kyorin University Hospital between March 2018 and July 2019. Before and after bronchoscopy, the enrolled patients answered a questionnaire regarding the procedure. At the same time, bronchoscopists evaluated cough severity using a four-grade cough scale. We evaluated patient characteristics and predictive factors associated with bronchoscopy from the perspective of discomfort and strong cough. A total of 172 patients were ultimately enrolled in this study. On multivariate logistic regression analysis, comparison of the subjective data between the discomfort and comfort groups revealed that factors that were more common in the former group were younger age (OR = 0.96, p = 0.002), less experienced bronchoscopist (OR = 2.08, p = 0.047), and elevation of cough score per 1 point (OR = 1.69, p < 0.001). Furthermore, the predictive factors for strong cough prior to performing bronchoscopy were female sex (OR = 2.57, p = 0.009), EBUS-TBNA (OR = 2.95, p = 0.004), and prolonged examination time of more than 36 min (OR = 2.32, p = 0.022). Regarding patients' discomfort, younger age, less experienced bronchoscopist, and the elevation of cough score per 1 point were important factors for discomfort in bronchoscopy. On the other hand, female sex, EBUS-TBNA, and prolonged examination time were crucial factors for strong cough.

A novel diagnostic method for distinguishing parapneumonic effusion and empyema from other diseases by using the pleural lactate dehydrogenase to adenosine deaminase ratio and carcinoembryonic antigen levels.

Pleural effusions are a common medical problem not only for pulmonologists but also for general physicians, often needing thoracentesis for a definite diagnosis. However, thoracentesis cannot always reveal malignant cells or microbiological evidence.In this context, we prospectively enrolled a total of 289 patients with pleural effusions due to diverse etiologies: parapneumonic effusion (PPE) (63), empyema (22), tuberculous pleural effusion (TBPE) (54), malignant pleural effusion (MPE) (140), or chronic renal failure (CRF)/congestive heart failure (CHF) (10). The MPE group consisted of lung cancer (adenocarcinoma, n = 90; squamous cell carcinoma, n = 5; small cell carcinoma, n = 4), malignant lymphoma (n = 17), malignant mesothelioma (n = 11), malignant melanoma (n = 3), and metastasis from other organs (n = 10).This study demonstrated that the pleural lactate dehydrogenase (LDH)to adenosine deaminase (ADA) ratios differed significantly between patients with CHF/CRF, MPE, TBPE, empyema, and PPE. We discovered a simple method to differentiate pleural diseases based on the pleural LDH to ADA ratio and carcinoembryonic antigen (CEA). A pleural LDH to ADA ratio greater than 15.5 and a pleural CEA level of less than 5 ng/mL is indicative of PPE or empyema rather than TBPE, MPE, or transudative pleural effusion (CRF, CHF).This method has a sensitivity of 62.0%, a specificity of 91.0%, and an area under the receiver operating characteristic curve of 0.765 (95% confidence interval [CI]: 0678-0.852, P < .001), odds ratio of 16.6 (95% CI: 7.28-37.8, P < .001), a positive likelihood ratio (LR) of 6.8, and a negative LR of 0.02.

Correlation between clinical features, high-resolution computed tomography findings, and a visual scoring system in patients with pneumonia due to Mycoplasma pneumoniae.

BACKGROUND: Mycoplasma pneumoniae (MP) is the primary cause of community-acquired pneumonia. We aimed to evaluate the correlation between clinical features, with special reference to hypoxemia and the total affected area obtained using high-resolution computed tomography (HRCT). METHODS: Medical records of MP pneumonia patients > 15 years of age at Kyorin University Hospital between January 2006 and November 2013 were reviewed retrospectively and compared to patients with Streptococcus pneumoniae pneumonia, diagnosed between January 2013 and September 2014. RESULTS: We identified 65 and 32 patients with MP- and S. pneumoniae pneumonia, respectively. HRCT data were available for 42 and 32 patients with MP- and S. pneumoniae pneumonia, respectively. Data were available for all hypoxemic patients. Hypoxemia was significantly higher in patients with S. pneumoniae (14/32, p = 0.008) than those with MP (5/39). Total visual score on HRCT correlated significantly with hypoxemia in both groups, but showed significantly higher scores with MP- than with S pneumoniae pneumonia in hypoxemic patients. MP pneumonia showed significant positive correlation between the total visual score and serum inflammatory markers (C-reaction protein [r = 0.43, p = 0.025] and lactate dehydrogenase [r = 0.466, p = 0.016]). In both groups, individual scores in the middle and lower lung fields were significantly higher than in the upper field, suggesting zonal predominance. CONCLUSIONS: This study provides the first evidence that the total affected area on lung HRCT was more with MP compared to S. pneumoniae pneumonia in hypoxemic patients and positively correlated with hypoxemia and serum inflammatory markers.

A Novel Diagnostic Scoring System to Differentiate between Legionella pneumophila Pneumonia and Streptococcus pneumoniae Pneumonia.

Objective We investigated a novel diagnostic scoring system to differentiate Legionella pneumophila pneumonia from Streptococcus pneumoniae pneumonia. Methods We retrospectively reviewed the clinical data of 62 patients with L. pneumophila pneumonia (L-group) and 70 patients with S. pneumoniae pneumonia (S-group). Results The serum sodium (Na) levels tended to be lower according to the severity [age, dehydration, respiratory failure, orientation disturbance, low blood pressure (A-DROP)] score in the L-group. On a multivariate analysis, we found that four factors were independent predictive markers for inclusion in the L-group: relative bradycardia [hazard ratio (HR) 5.177, 95% confidence interval (CI): 1.072-24.993, p=0.041], lactate dehydrogenase (LDH) levels ≥292 IU/L (HR 6.804, 95% CI: 1.629-28.416, p=0.009), C-reactive protein (CRP) levels ≥21 mg/dL (HR 28.073, 95% CI: 5.654-139.462, p<0.001), and Na levels ≤137 meq/L (HR 5.828, 95% CI: 1.411-24.065, p=0.015). Furthermore, a total score [ranging from 0 to 4, the sum of the points for each factor (0 or 1)] ≥3 points indicated a higher probability of inclusion in the L-group than in the S-group. The diagnostic accuracy of a total score of 3 had a sensitivity of 36.3%, specificity of 100%, and area under the curve of 0.682 (95% CI: 0.558-0.806, p=0.004), and that of a total score of 4 had a sensitivity 27.4%, specificity of 98.2%, and area under the curve (AUC) of 0.627 (95% CI: 0.501-0.754, p=0.045). The diagnostic accuracy had low sensitivity but high specificity. Conclusions We found four markers that might be useful for differentiating L-group from S-group and created a novel diagnostic scoring system.

Rapid diffuse pleural thickening due to metastatic meningioma.

A 64-year-old man was referred to our hospital because of persistent dyspnoea for the past 1 month. He had recurrent brain anaplastic meningioma after two operations and irradiation. He suffered from right pleural effusion in the previous few months and was diagnosed with malignant mesothelioma via pleural biopsy 1 month prior to coming to our hospital. At his first visit to our hospital, thoracic computed tomography demonstrated rapidly developed large inhomogeneously enhancing pleural thickening up to 3 cm, which surrounded the right hemithorax, together with left-sided pleural effusion. After re-evaluation of the pathological specimens retrieved from the local hospital, he was finally diagnosed with pleural metastasis secondary to anaplastic meningioma (WHO classification, grade 3). Generally, brain meningiomas are believed to be benign and seldom metastasize to other organs. However, the present case clearly demonstrated the unique clinical presentation of anaplastic meningioma, also known as malignant meningioma, which mimicked the pathological and radiological findings of a malignant mesothelioma.

Clinical significance of respiratory virus detection in patients with acute exacerbation of interstitial lung diseases.

BACKGROUND: The impact of viral infections on acute exacerbations in idiopathic pulmonary fibrosis (IPF) and/or non-IPF interstitial lung disease (ILDs) has been scarcely described. OBJECTIVES: To elucidate the frequency of virus infections in patients with IPF or non-IPF ILDs including idiopathic interstitial pneumonia (IIP) or connective tissue disease (CTD)-associated pneumonia, and its influence on their short-term mortality. METHODS: We prospectively enrolled adult patients with acute exacerbation of IPF and non-IPF ILDs who were admitted to the hospital during the last 3 years, and examined the respiratory samples obtained from nasopharyngeal, sputum, and bronchoalveolar lavage fluid. RESULTS: A total of 78 patients were identified, consisting of 27 patients with acute exacerbation of IPF and 51 patients with non-IPF ILDs (IIP: n = 27, CTD-associated IP: n = 24). Of all patients, 15 (19.2%) had viruses detected in their respiratory samples including the human herpesvirus 7 (HHV7; n = 4) and cytomegalovirus (CMV) plus HHV7 (n = 3). The proportion of virus infections in the IPF and non-IPF ILDs groups was comparable. The Kaplan-Meier survival curves over 60 days revealed a lower survival probability in the virus positive group (n = 15, 60%) than in the virus negative group (n = 60, 83.3%, p < 0.05). However, the virus infection itself could not predict the 60-day survival probability using simple logistic regression analysis. CONCLUSIONS: Viral infections, mostly CMV or HHV7, were identified in both patients with acute exacerbation of IPF and non-IPF ILDs, but the clinical significance on short-term mortality or isolation itself from respiratory samples remains to be determined.

Diagnostic Value of Vascular Endothelial Growth Factor, Transforming Growth Factor-ß, Interleukin-8, and the Ratio of Lactate Dehydrogenase to Adenosine Deaminase in Pleural Effusion.

PURPOSE: We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGF-ß), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid. METHODS: Prospective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted. RESULTS: We enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were significantly higher in empyema patients than in CRF/CHF or PPE patients. In all patients, the pleural fluid VEGF and IL-8 values were significantly positively correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-ß was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA ratio in patients with MPE or empyema/PPE was significantly higher than in patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p < 0.001). CONCLUSIONS: VEGF and IL-8 production in the pleural cavity appear to accelerate the progression of PPE to empyema, by enhancing vascular permeability associated with inflammation. Sequential sampling would be needed to confirm this. The pleural LDH/ADA ratio may be a useful diagnostic tool for discriminating between various pleural effusion etiologies.

Clinical characterization of 52 patients with immunoglobulin G4-related disease in a single tertiary center in Japan: Special reference to lung disease in thoracic high-resolution computed tomography.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a rare multi-organ disorder. Physicians rarely encounter patients with IgG4-RD and its range of symptoms. METHODS: To elucidate the clinical characterization of IgG4-RD, along with the clinical significance of lung involvement, we retrospectively reviewed the medical records of patients who satisfied the comprehensive diagnostic criteria for IgG4-RD. RESULTS: We identified 52 patients with IgG4-RD. Of these, 32 patients underwent tissue biopsies, resulting in categorization as definite (n = 23) or possible (n = 9) IgG4-RD cases. Among the 23 definite IgG4-RD cases, those with positive lung involvement (n = 8) had significantly higher values of serum LDH (median 220 IU/L, interquartile range (IQR) 175-378 vs. median 184, IQR 136-249, p = 0.039), IgG (median 2769 mg/dL, IQR 2028-7807 vs. median 2048, IQR 1168-4376, p = 0.009), and soluble interleukin-2 receptors (median 1620 U/mL, IQR 871-2250 vs. median 733, IQR 271-1600, p = 0.003) than those with negative lung involvement (n = 15). Similarly, a significant number of patients with positive lung involvement were positive for rheumatoid factor (71.4% vs. 23.1%, p = 0.041) or hypocomplementemia (50% vs. 0%, p = 0.036). Sixteen patients also showed lung involvement (definite n = 8, possible n = 8); thoracic computed tomography (CT) of these patients revealed mediastinal lymphadenopathies (n = 14, 87.5%), ground glass opacity (n = 11, 68.8%), consolidation (n = 8, 50%), thickening of the bronchovascular bundles (n = 7, 43.8%), small nodules (n = 5, 31.3%), bronchiectasis (n = 4, 25%), and reticular shadows (n = 4, 25%), and pulmonary function tests, using a standard technique involving a single breath, revealed decreased diffusion capacity for carbon monoxide. CONCLUSIONS: IgG4-RD is associated with diverse thoracic CT findings and a decreased diffusion capacity, and careful multidisciplinary assessment is needed to enable differentiation of IgG4-RD from lymphoproliferative disorders.

The Correlation between Chest X-ray Scores and the Clinical Findings in Children and Adults with Mycoplasma pneumoniae Pneumonia.

Objective To compare the radiological and laboratory data of children and adults with Mycoplasma pneumoniae pneumonia (MPP) and to evaluate the correlation between the total affected lung area and the clinical findings. Methods We retrospectively examined the data from MPP patients who visited our hospital during the period from April 2006 to July 2014. All data were retrieved at the time of the diagnosis of MPP and were analyzed to investigate the correlation between the clinical findings and the total affected lung area using a chest X-ray scoring system. Results We identified 71 children and 54 adults with MPP. The incidence of consolidation, which was the most common chest X-ray finding in both groups, was similar (children: n = 62, 87.3%; adults: n = 45, 83.3%). In contrast, air bronchogram, bronchial thickening, and atelectasis were observed significantly more frequently among children than among adults. In both groups, a chest X-ray scoring system revealed a zonal predominance of the affected area (middle-to-lower lung fields). The body temperature and serum data such as the C-reactive protein level, white blood cell count, and lactate dehydrogenase level were significantly higher in the child group than in the adult group. The total score did not significantly correlate with the above-mentioned inflammatory markers or the presence of hypoxemia in either group. Conclusion This study showed the first evidence of a correlation between the extent of lung abnormalities on chest X-ray (calculated as a total score) and the clinical findings, including the presence of hypoxemia, in children and adults with MPP.

Giant bulla formation in the lung because of a check-valve mechanism.

The pathogenesis of bulla formation has not yet been demonstrated in pathologic examinations or through direct visualization during thoracotomy or thoracoscopic surgery. We present two cases of giant bulla formation after pneumothorax because of cryptogenic organizing pneumonia and lung abscess. The case findings suggested that the pathogenesis was attributable to a check-valve mechanism, secondary to bronchiolitis obliterans, or the presence of an obstructing air leakage due to a lung fistula. The lung fistula had been covered by inflammatory membranes consisting of blood and/or fibrous precipitates with detached visceral pleura.

Clinical significance of the "galaxy sign" in patients with pulmonary sarcoidosis in a Japanese single-center cohort.

BACKGROUND: The galaxy sign is an irregularly marginated pulmonary nodule formed by a confluence of multiple small nodules, and it is a diagnostic radiological finding for pulmonary sarcoidosis. However, the clinical significance of the galaxy sign for sarcoidosis has been poorly investigated. OBJECTIVE: This study aimed to investigate the clinical significance and detailed radiological features of the galaxy sign in patients with pulmonary sarcoidosis. METHODS: We retrospectively reviewed 87 patients with biopsy-proven sarcoidosis and 108 patients with pulmonary tuberculosis. Galaxy sign incidence was assessed on thoracic high-resolution computed tomography (HRCT) images from each group. Correlations of galaxy sign with clinical characteristics and disease outcomes were evaluated for patients with sarcoidosis. RESULTS: HRCT findings were available for 65 of 87 patients with pulmonary sarcoidosis and all 108 patients with pulmonary tuberculosis. Galaxy sign incidence was significantly higher in patients with pulmonary sarcoidosis (n=15, 23.1%) than in those with pulmonary tuberculosis (n=2, 1.9%, p<0.001). Among the 65 patients with pulmonary sarcoidosis, those with galaxy signs (n=15) were significantly younger (median: 32 years, interquartile range [IQR] 28-38 years) than those without (n=50) (median: 62 years, IQR 37.7-73 years). The CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) was also significantly lower in the former group (median: 2.6, IQR 2.0-3.9 vs. median 5.8, IQR 3.7-8.6, p<0.001). CONCLUSION: Galaxy signs are associated with younger age and low BALF CD4/CD8 ratio but not disease severity.

Tracheobronchial Amyloidosis in a Patient with Sjögren's Syndrome.

A 65-year-old woman was referred to our respiratory department because of incidentally detected endobronchial deposits. She had been diagnosed with Sjögren's syndrome 12 years earlier. Bronchoscopy showed protrusion of the reddened, shiny or edematous mucosa at the orifice of the lower lobe bronchus, suggesting a submucosal tumor. Based on the pathological findings of the transbronchial biopsied specimens, the patient was diagnosed with non-classified type tracheobronchial amyloidosis associated with Sjögren's syndrome, which was negative for both λ and κ chains, transthyretin and amyloid A. She has remained in good health without a relapse of the tumor.

Evidence of unilateral metastatic pulmonary calcification with a prolonged Fever and arthralgia caused by acute lymphoblastic leukemia in a chronic dialysis patient.

A 55-year-old man was transferred to our hospital with unilateral lung lesions, a persistent fever and vague chest pain with arthralgia lasting for three months. He had been treated for end-stage renal disease with hemodialysis for 15 years and had a medical history of recurrent subcutaneous calciphylaxis due to secondary hyperparathyroidism. Transbronchial biopsied specimens demonstrated metastatic pulmonary calcification, and a bone marrow biopsy showed Philadelphia chromosome-positive acute lymphoblastic leukemia. Although metastatic calcification often lacks specific symptoms, the lungs is a primary site for deposition. This is the first report of unilateral metastatic pulmonary calcification associated with secondary hyperparathyroidism.

Novel aspects on the pathogenesis of Mycoplasma pneumoniae pneumonia and therapeutic implications.

Mycoplasma pneumoniae (Mp) is a leading cause of community acquired pneumonia. Knowledge regarding Mp pneumonia obtained from animal models or human subjects has been discussed in many different reports. Accumulated expertise concerning this critical issue has been hard to apply clinically, and potential problems may remain undiscovered. Therefore, our multidisciplinary team extensively reviewed the literature regarding Mp pneumonia, and compared findings from animal models with those from human subjects. In human beings, the characteristic pathological features of Mp pneumonia have been reported as alveolar infiltration with neutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area. Herein, we demonstrated the novel aspects of Mp pneumonia that the severity of the Mp pneumonia seemed to depend on the host innate immunity to the Mp, which might be accelerated by antecedent Mp exposure (re-exposure or latent respiratory infection) through up-regulation of Toll-like receptor 2 expression on bronchial epithelial cells and alveolar macrophages. The macrolides therapy might be beneficial for the patients with macrolide-resistant Mp pneumonia via not bacteriological but immunomodulative effects. This exhaustive review focuses on pathogenesis and extends to some therapeutic implications such as clarithromycin, and discusses the various diverse aspects of Mp pneumonia. It is our hope that this might lead to new insights into this common respiratory disease.

Methicillin-resistant Staphylococcus aureus enterocolitis sequentially complicated with septic arthritis: a case report and review of the literature.

BACKGROUND: Although most reports describing patients infected with methicillin-resistant Staphylococcus aureus enterocolitis have been published in Japan, this concept remains a matter of debate and diagnostic criteria have not yet been defined. CASE PRESENTATION: The general status of a 74-year-old Japanese man referred to our hospital (day 1) with severe community-acquired pneumococcal pneumonia gradually improved with antibiotic therapy. Thereafter, up to 4 L/day of acute watery diarrhea that started on day 19 was refractory to metronidazole but responded immediately to oral vancomycin. Gram staining stool samples was positive for abundant fecal leukocytes from which dominant methicillin-resistant Staphylococcus aureus (10(4) CFU/mL) were isolated, suggesting methicillin-resistant Staphylococcus aureus enterocolitis. High fever with methicillin-resistant Staphylococcus aureus bacteremia was evident at day 30, and suppurative right hip arthritis developed around day 71. All methicillin-resistant Staphylococcus aureus strains isolated from stools, blood and aspirated synovial fluid separated in the same manner on pulsed-field gel electrophoresis, as well as two other strains isolated from sputum, belonged to the same clone as sequence type (ST) 764 (complex clonal 5), and carried SCCmec type II. CONCLUSION: The clinical, microbiological and molecular biological findings of this patient indicated methicillin-resistant Staphylococcus aureus enterocolitis that led to septic methicillin-resistant Staphylococcus aureus arthritis.

Evidence for cytomegalovirus-induced haemophagocytic syndrome in a young patient with AIDS.

A 29-year-old man with HIV infection was referred to our department because of a 1-month history of low-grade fever and fatigue. Bone marrow aspiration and biopsy showed findings consistent with haemophagocytic syndrome (HPS), and immunohistochemical assessment showed cytomegalovirus (CMV) infection. HIV-associated HPS can occur at any stages of HIV disease and requires diverse differential diagnosis. CMV-associated HPS (CMV-HPS) in patients with HIV infection is relatively rare, but the present case showed that the clinicians should consider the possibility of CMV-HPS as a clinical feature of CMV infection.