Tomohiro Uto

Higher Sensitivity and Specificity for Diffusion-weighted Imaging of Malignant Lung Lesions without Apparent Diffusion Coefficient Quantification

PURPOSE To compare the performance of apparent diffusion coefficient (ADC) with that of signal intensity of the lesion-to-spinal cord ratio (LSR) in differentiating lung cancer from benign lesions on high-b value diffusion-weighted (DW) magnetic resonance (MR) images. MATERIALS AND METHODS This study received institutional review board approval; written informed consent was provided by all patients. Twenty-eight patients (six women, 22 men; mean age, 64.2 years) with pulmonary nodules seen at chest computed tomography were prospectively reviewed. Two DW images with different motion-probing gradient strengths (b(h) = 1000 sec/mm(2) and b(l) = 0 sec/mm(2)) were analyzed semiquantitatively by measuring the signal intensities of the lesions and the spinal cord. ADC was calculated by using linear regression analysis of the natural logarithm of mean signal intensity versus the gradient factor. For reference, LSR was also measured on the same image with a diffusion gradient of b(h) = 1000 sec/mm(2). RESULTS The LSR of cancer nodules was significantly higher than that of benign lesions, while there were no significant differences between them in relation to ADC. In the receiver operating characteristic curve analysis, LSR had a higher area under the curve than did ADC (0.911 vs 0.600). By using a cutoff value of 1.135, LSR had a positive predictive value of 86.7% a negative predictive value of 90%, and an accuracy of 85.7% for the detection of lung cancer with LSR. CONCLUSION LSR measurement on high-b value DW imaging may be useful for differentiating between benign and malignant lung nodules.

Possible therapeutic effect of direct haemoperfusion with a polymyxin B immobilized fibre column (PMX-DHP) on pulmonary oxygenation in acute exacerbations of interstitial pneumonia.

Background and objective:  Acute exacerbations of interstitial pneumonias (IP) can occasionally occur, and have an extremely poor prognosis. Recently, direct haemoperfusion with a polymyxin B immobilized fibre column (PMX‐DHP) was shown to have a beneficial effect in acute exacerbations of IPF. However, little is known about the efficacy of PMX‐DHP in acute exacerbations of other IP. This study investigated the effectiveness and safety of PMX‐DHP in acute exacerbations of IP.

Clinical Significance of Interleukin 33 (IL-33) in Patients with Eosinophilic Pneumonia

BACKGROUND Interleukin 33 (IL-33) works as a functional mediator in allergic disease by enhancing the activity of eosinophils and inducing expression of T helper 2 (Th2)-associated cytokines. However, the role of IL-33 in pulmonary eosinophilia has not been elucidated. We investigated the levels of IL-33 in eosinophilic pneumonia (EP) together with associated cytokines, and discussed the clinical significance of IL-33 in EP. METHODS Sera and bronchoalveolar lavage fluid (BALF) were obtained from 16 patients with EP, including acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP). Twelve patients with acute respiratory distress syndrome (ARDS) were also included for comparison. The concentration of IL-33 and Th2 cytokines (IL-4, IL-5, IL-13) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS The concentration of serum IL-33 was significantly higher in patients with AEP than in CEP. In CEP, only patients with atopic factors showed mild increase of serum IL-33. The concentration of BALF IL-33 was also significantly elevated in AEP, however, it remained quite low in CEP. Among Th2 cytokines, IL-5 was significantly increased in both serum and BALF in AEP, and the level of IL-5 was positively correlated with that of IL-33. ARDS showed no increase of serum and BALF IL-33. CONCLUSIONS The remarkable increase of BALF IL-33 in AEP indicated the local production of IL-33 in lungs. IL-33 is considered to be a local key molecule for triggering pulmonary eosinophilia, together with IL-5. BALF IL-33 appears to be a useful marker for discriminating AEP from CEP and ARDS.

A novel vaccine strategy to induce mycobacterial antigen-specific Th1 responses by utilizing the C-terminal domain of heat shock protein 70.

Heat shock protein 70 (HSP70) is a member of a highly conserved superfamily of intracellular chaperones called stress proteins that can activate innate and adaptive immune responses. We evaluated the effect of a fusion DNA vaccine that encoded mycobacterial HSP70 and MPT51, a major secreted protein of Mycobacterium tuberculosis. Spleen cells from mice immunized with fusion DNA of full-length HSP70 and MPT51 produced a higher amount of interferon-γ (IFN-γ) in response to the CD4+, but not the CD8+ T-cell epitope peptide on MPT51 than those from mice immunized with MPT51 DNA. Furthermore, because HSP70 comprises the N-terminal ATPase domain and the C-terminal peptide-binding domain, we attempted to identify the domain responsible for its enhancing effect. The fusion DNA vaccine that encoded the C-terminal domain of HSP70 and MPT51 induced a higher MPT51-specific IFN-γ production by CD4+ T cells than the vaccine that encoded MPT51 alone, whereas that with the N-terminal domain did not. Similar results were obtained by immunization with the fusion proteins. These results suggest that the DNA vaccine that encodes a chimeric antigen molecule fused with mycobacterial HSP70, especially with its C-terminal domain, can induce a stronger antigen-specific T-helper cell type 1 response than antigen DNA alone.

Pulmonary Metastasis from Urothelial Carcinoma Showing Progressive Multiple Cystic Lesions

Multiple thin-walled cystic lesions in the lung can reflect a variety of diseases (Table E1 in the online supplement), such as lymphangioleiomyomatosis, pulmonary Langerhans’ cell histiocytosis, Birt-Hogg-Dubé syndrome, lymphoid interstitial pneumonia, alveolar septal amyloidosis, and cystic pneumocystis pneumonia (1–4). Bronchioloalveolar carcinoma (5, 6), pulmonary metastasis of sarcomas (7, 8), and meningioma (9) are also reported, but they are extremely rare. We herein describe a patient with pulmonary metastasis from urothelial carcinoma of the urinary bladder presenting as multiple thin-walled cystic lesions on computed tomography (CT), which is an uncommon manifestation. A 76-year-old man with a smoking history of 50 pack-years was admitted to our hospital for the sudden onset of dyspnea. Six months earlier, he had undergone transurethral resection of a bladder tumor with the diagnosis of high-grade urothelial carcinoma. Radical cystectomy and bilateral distal ureterectomy with creation of a ureter–skin conduit were performed. A chest X-ray on admission showed bilateral pneumothoraces, which required placement of chest tubes bilaterally. Chest CT performed after reexpansion revealed multiple thin-, smooth-walled cysts measuring up to 1.5 cm in diameter (Figure 1B). No other types of pulmonary lesions, such as nodules or cavitary lesions with thick or irregular walls, were found; however, some of the pulmonary arteries were dilated. These findings had not been detected on chest CT scans taken 4 months earlier (Figure 1A). Pleurodesis was performed on the left side, which prevented air leakage. Because of the recurrence of right pneumothorax, the patient underwent thoracoscopy with right upper and lower lobe wedge resections and pleurodesis. The macroscopic features of the cystic lesion were consistent with a pulmonary bulla. The walls of the cysts lacked a lining epithelium and comprised a dense proliferation of tumor cells (Figure E1a). The histological findings closely resembled those of the previously resected bladder tumor, and a diagnosis of metastatic urothelial carcinoma was made. Around the cysts, tumor cells extended along the alveolar walls, and some alveoli were distended (Figure E1b). Some terminal bronchioles were invaded and narrowed by tumor growth (Figure E1c). Tumor emboli in the pulmonary arteries and capillaries were also noted (Figures E1c and E1d). The patient’s general condition worsened with the progression of bladder carcinoma. Serial CT scans demonstrated progression and marked enlargement of the cystic lesions (Figure 1C). He deteriorated and died 2 months after the diagnosis of his pulmonary complications. The lung is one of themost common sites of distant metastasis from bladder cancer (10, 11). Usual patterns of pulmonary involvement include multiple nodules, a solitary mass, or interstitial micronodules (2, 10, 11), but it rarely manifests as cavitary pulmonary lesions with thick, irregular walls (12–15). The present case is unusual in that the cystic metastasis had thin, smooth-walled bulla-like features. Metastatic soft tissue sarcomas (7, 8) or primary bronchioloalveolar carcinoma (5, 6) may show the same pattern, but this has not previously been reported in metastatic urothelial carcinoma.

Low WSS and High OSI Measured by 3D Cine PC MRI Reflect High Pulmonary Artery Pressures in Suspected Secondary Pulmonary Arterial Hypertension.

Purpose: Institutional Review Board (IRB)-approved prospective study was conducted to test whether objective and quantitative hemodynamic markers wall shear stress (WSS) and oscillatory shear index (OSI) measured by three-dimensional (3D) cine phase-contrast (PC) can reflect pulmonary arterial hypertension (PAH). Patients and Methods: Seventeen consecutive patients of suspected secondary PAH were examined for pulmonary artery pressures (PAPs) with right heart catheterization (RHC) and three-dimensional (3D) cine PC MR. Based on the RHC data, patients were subdivided into two groups of 12 non-PAH (median age of 74.5 years) and 5 PAH (median age of 77 years) patients. Based on 3D cine PC magnetic resonance (MR), hemodynamic parameters including spatially averaged systolic WSS (sWSS), diastolic WSS (dWSS), mean WSS (mWSS), OSI and blood vessel section area (BVSA) at the pulmonary arterial trunk were calculated. Streamline images in the pulmonary arteries were also assessed. All the parameters were compared between non-PAH and PAH groups. Results: sWSS (N/m2) and mWSS (N/m2) of PAH group was lower than that of non-PAH group (0.594 ± 0.067 vs. 0.961 ± 0.590, P = 0.001), (0.365 ± 0.035 vs. 0.489 ± 0.132, P = 0.027). OSI of PAH group was higher than that of non-PAH (0.214 ± 0.026 vs. 0.130 ± 0.046, P = 0.001). sWSS, mWSS, and dWSS were inversely correlated and OSI was positively correlated to mean PAP or systolic PAP with r values of –0.638 (P = 0.005), –0.643 (P = 0.005), –0.485 (P = 0.049), and 0.625 (P = 0.007); or –0.622 (P = 0.008), –0.629 (P = 0.007), –0.484 (P = 0.049), and 0.594 (P = 0.012), respectively. sWSS was also inversely correlated to BVSA with r value of –0.488 (P = 0.049), and OSI was correlated to BVSA with r value of 0.574 (P = 0.016). Vortex or helical flows were observed more frequently in PAH patients. Conclusions: The low sWSS and mWSS as well as high OSI measured with 3D cine PC MR could be potential hemodynamic markers for the increased PAP in suspected secondary PAH patients.

Morphological changes in small pulmonary vessels are associated with severe acute exacerbation in chronic obstructive pulmonary disease

Background Pulmonary vascular remodeling is essential for understanding the pathogenesis of chronic obstructive pulmonary disease (COPD). The total cross-sectional area (CSA) of small pulmonary vessels has been reported to correlate with the pulmonary artery pressure, and this technique has enabled the assessment of pulmonary vascular involvements. We investigated the contribution of morphological alterations in the pulmonary vessels to severe acute exacerbation of COPD (AE-COPD). Methods This study enrolled 81 patients with COPD and 28 non-COPD subjects as control and assessed the percentage of CSA (%CSA) less than 5 mm2 (%CSA<5) and %CSA in the range of 5–10 mm2 (%CSA5–10) on high-resolution computed tomography images. Results Compared with the non-COPD subjects, the COPD patients had lower %CSA<5. %CSA<5 was positively correlated with airflow limitation and negatively correlated with the extent of emphysema. COPD patients with lower %CSA<5 showed significantly increased incidences of severe AE-COPD (Gray’s test; P=0.011). Furthermore, lower %CSA<5 was significantly associated with severe AE-COPD (hazard ratio, 2.668; 95% confidence interval, 1.225–5.636; P=0.010). Conclusion %CSA<5 was associated with an increased risk of severe AE-COPD. The distal pruning of the small pulmonary vessels is a part of the risk associated with AE-COPD, and %CSA<5 might be a surrogate marker for predicting AE-COPD.

Cumulative incidence of tuberculosis in lung cancer patients in Japan: A 6-year observational study.

BACKGROUND Tuberculosis (TB) remains a health-related problem worldwide, and certain malignancies are known to be associated with an increased risk of TB. Lung cancer is the leading cause of cancer-related death, and the number of patients with lung cancer has been reportedly increasing. As the prognosis of lung cancer remains poor, aggressive comprehensive therapies have been used. The immunosuppression caused by cancer itself and treatment-associated immune modulation may increase the risk of TB. The present study was conducted to investigate the cumulative incidence of TB in lung cancer patients. METHODS This observational study included 904 consecutive patients diagnosed with histologically confirmed lung cancer from March 2007 to March 2013 and followed until March 2015 (mean 25.2 months). The cumulative incidence of TB was estimated using the Kaplan-Meier method. RESULTS Nine lung cancer patients (1.00%) developed TB during the observation period. In all cases, TB occurred within 2 years of the diagnosis of lung cancer. The cumulative incidence of TB at 6 months, 1 year, and 2 years was 0.65%, 1.15%, and 1.38%, respectively. CONCLUSIONS The cumulative incidence of TB in lung cancer patients was 1.38% in Japan.

Organizing pneumonia associated with myeloperoxidase anti‐neutrophil cytoplasmic antibody

Organizing pneumonia (OP) is a clinicopathological entity that occurs idiopathically or in association with several conditions, but there are few reports about myeloperoxidase anti‐neutrophil cytoplasmic antibody (MPO‐ANCA)‐associated OP. We describe a patient with OP whose clinical conditions improved spontaneously. Moreover, serum MPO‐ANCA titers paralleled the clinical activity of the disease, which disappeared in association with disease quiescence. Based on these findings, a subset of patients may have OP related to MPO‐ANCA. ANCA testing should be considered in the work‐up of patients with suspected OP.

Diffuse alveolar hemorrhage caused by exposure to organic dust.

Diffuse alveolar hemorrhage, a life-threatening disease, can complicate various conditions. We herein describe, for the first time, a patient with diffuse alveolar hemorrhage caused by exposure to organic dust. A 49-year-old woman who worked as a cantaloupe farmer in a greenhouse was referred to our hospital for sudden onset of dyspnea 3 h after exposure to organic dust. A chest X-ray and computed tomography scan performed on admission showed diffuse ground-glass opacities in both lung fields. Suspecting hypersensitivity pneumonitis, fiberoptic bronchoscopy was performed. Mucopurulent sputum was present in the trachea and both bronchi, and bronchoalveolar lavage revealed a progressively bloody return, typical of diffuse alveolar hemorrhage. Based on the history and bronchoscopy findings, she was diagnosed with diffuse alveolar hemorrhage following exposure to organic dust and was treated with antibiotics and corticosteroids. Diffuse alveolar hemorrhage should be considered in the differential diagnosis of diffuse ground-glass opacities observed on radiographs in farmers following exposure to organic dust.