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To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer. We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (5-ARI; n = 119) or not using 5-ARIs (no 5-ARI; n = 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan–Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A p value 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p

To determine whether multi-parametric magnetic resonance imaging (mpMRI) can reliably predict proximity of prostate cancer to the prostatic urethra in a contemporary series of men undergoing radical prostatectomy (RP) at two academic centers. Clinical characteristics of consecutive men undergoing pre-operative mpMRI prior to RP and whole-mount axial serial step-sectioned pathology examination at two academic centers between Jun 2016 and Oct 2018 were analyzed retrospectively. Every tumor was characterized by its pathologic minimum distance to the prostatic urethral lumen (pMDUL). Only the cancer closest to the urethra represented the prostatic urethral index lesion. The radiologic minimum distance of the index lesion to the prostatic urethral lumen was measured and noted as ≤ 5 mm versus > 5 mm. The sensitivity, specificity, positive and negative predicting values (PPV and NPV) and area under the receivers operating characteristics curve (AUC) were calculated for performance of mpMRI for predicting pMDUL ≤ 5 mm. Of the 163 surgical specimens examined, 112 (69%) exhibited a pMDUL ≤ 5 mm. These men had significantly higher grade group (GG) and advanced pathological and clinical stage. The rates of high PI-RADS score and presence of gross extracapsular extension were also significantly greater for the group with pMDUL ≤ 5 mm. The AUC, sensitivity, specificity, PPV, and NPV were 0.641, 51.8, 76.5, 82.9, and 42.4%, respectively, for mpMRI to predict pMDUL

A 6-year-old girl was admitted with a mass lesion in the cerebellar vermis. She underwent subtotal tumor resection, and on immunohistopathology the tumor consisted of two different parts: typical medulloblastoma (MB) characteristics and atypical teratoid/rhabdoid tumor (AT/RT) features, despite positive integrase interactor 1 expression. The patient was diagnosed with MB with epithelioid features. Chemoradiation therapy was started because of tumor recurrence at the primary site and dissemination to the spinal cord, as determined on magnetic resonance imaging 2 weeks after surgery. The patient died due to tumor progression 13 months after initial diagnosis, although transient partial remission was achieved.

Aims Idiopathic pulmonary fibrosis continues to be a devastating clinical disorder for which there are few therapeutic options, and the pathogenesis of this disease remains largely unknown. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in cholesterol biosynthesis, and they have been reported to exert pleiotropic effects on the cellular signaling involved in tissue inflammation and in organ fibrosis/remodeling. We examined the preventive effects of statins on fibrogenic mediator expression and production in normal human lung fibroblasts (NHLF). Main methods NHLF were pretreated with 100 nM pitavastatin or medium alone (control), and were then stimulated with transforming growth factor-β1 (TGF-β1). mRNA expression and protein secretion of several mediators from cells were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay or multiplex assay. Key findings TGF-β1-induced expression or production of mediators, such as collagen-1, vascular endothelial growth factor and chemokine C–X–C motif ligand 8, in NHLF pretreated with pitavastatin was significantly suppressed with inhibition of Smad-3 phosphorylation, as compared to untreated controls. In addition, the inhibitory effects of pitavastatin were negated by addition of mevalonate. Significance Pitavastatin appeared to inhibit TGF-β1-induced fibrogenic mediator production from lung fibroblasts via the mevalonic cascade. Although further evaluation of the signaling pathways for these phenomena is necessary, our results suggest the potential benefits of pitavastatin.

Summary Statins are 3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors of cholesterol biosynthesis, and have been reported to exert pleiotropic effects on cellular signalling and cellular functions involved in inflammation. Recent reports have demonstrated that previous statin therapy reduced the risk of pneumonia or increased survival in patients with community-acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Interleukin (IL)-6 and IL-8 mRNA expression and protein secretion in LPS-stimulated cells were inhibited significantly by the lipophilic statin pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects of statin were negated by adding mevalonate, the anti-inflammatory effects of statins appear to be exerted via the mevalonic cascade. In addition, the activation levels of Ras homologue gene family A (RhoA) in BEAS-2B cells cultured with pitavastatin were significantly lower than those without the statin. These results suggest that statins have anti-inflammatory effects by reducing cytokine production through inhibition of the mevalonic cascade followed by RhoA activation in the lung.

Background and objective: More than 100 000 Japanese die of pneumonia every year. The number of people residing in nursing homes is increasing with the ageing of the population. In 2005, the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) published important guidelines for the management of healthcare-associated pneumonia (HCAP). In Japan, however, the optimum strategy for management of HCAP is still unclear. The purpose of this study was to clarify the clinical features of patients with HCAP. Methods: Patients (n = 202) who were consecutively admitted with a diagnosis of acute pneumonia between October 2007 and September 2009 were retrospectively evaluated. Using the ATS/IDSA guidelines, patients were divided into three groups: a community-acquired pneumonia (CAP) group (n = 123), a nursing home-acquired pneumonia (NHAP) group (n = 46) and a HCAP other than NHAP (O-HCAP) group (n = 33). These groups were then compared with respect to laboratory data, microbiological findings and mortality. Results: Thirty-day mortality in the NHAP group (10.9%) tended to be higher than that in the CAP group (3.3%) or the O-HCAP group (0%). The pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae in the CAP group, methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae in the NHAP group, and S. pneumoniae and K. pneumoniae in the O-HCAP group. Conclusions: The NHAP group was clinically different from the O-HCAP group, based on bacteriological examination and mortality rates. In order to accurately diagnose, and formulate optimum treatment strategies for Japanese patients, the categories of HCAP, as specified in the ATS/IDSA guidelines, should not be applied directly either to patients with NHAP or those with O-HCAP.

The diagnosis of sarcoidosis, a multisystem granulomatous disease of unknown etiology, is established when clinicoradiological findings are supported by histological evidence of non-caseating epithelioid cell granulomas. For pathological diagnosis, an endobronchial biopsy of normal-appearing bronchial mucosa in combination with transbronchial lung biopsy (TBLB) has been reported to be useful for sarcoidosis patients in Europe or the U.S. This is the first report assessing the utility of endobronchial biopsy for diagnosis of Japanese patients with sarcoidosis. Eighteen consecutive patients with strongly suspected sarcoidosis were evaluated by endobronchial biopsy of normal-appearing bronchial mucosa, together with TBLB and bronchoalveolar lavage. The TBLB specimens demonstrated non-caseating epithelioid cell granulomas in the lungs of 11 patients (61.1%), but not any specific findings in those of other 7 patients. In contrast, endobronchial biopsy specimens confirmed a diagnosis of sarcoidosis in only one patient that required steroid therapy for deterioration of pulmonary sarcoidosis. All 18 patients of this study, including 5 patients with pathological findings obtained from extrapulmonary sites, met the pathological or clinical diagnostic criteria. In conclusion, endobronchial biopsy of normal-appearing bronchial mucosa in combination with TBLB does not improve the diagnostic capacity for detecting sarcoidosis in Japanese patients, despite earlier reports. Thus, this method is of limited usefulness as a conventional diagnostic modality for Japanese patients with suspicious sarcoidosis. The present study also suggests the racial difference in the endobronchial involvement in pulmonary sarcoidosis.

We encountered 2 immunocompromised children complicated by Raoultella ornithinolytica bacteremia. One had received methylprednisolone pulse therapy for IgA nephropathy, and the other had leukopenia because of chemotherapy for leukemia. Both children had no specific symptoms, and R. ornithinolytica bacteremia was identified by routine blood culture. Both patients were successfully treated with antibiotic treatment.

A 4-month old girl was diagnosed as having stage IV neuroblastoma of the right adrenal gland. Preoperative chemotherapy was given, followed by local surgical excision. Postoperatively, irradiation of the tumor bed and adjuvant chemotherapy was given for 11 months. Nine years after cessation of chemotherapy, the patient developed left hip-joint pain. Biopsy of the ischium showed chondroblastic osteosarcoma. Limb salvage surgery was performed after preoperative chemotherapy. Postoperatively, adjuvant chemotherapy was given for 14 months. Twenty-two months after treatment for the secondary osteosarcoma, the patient has been remained in disease-free condition without any evidence of relapse. A second osteosarcoma occurring outside the radiation field after treatment for neuroblastoma is quite rare. This unusual case emphasized the need for close monitoring for development of second malignant neoplasms in survivors of neuroblastoma even in the absence of a known predisposing factor, such as radiation therapy.

Summary We herein describe the first case, to our knowledge, of surgical biopsy-proven usual interstitial pneumonia (UIP) as the pulmonary manifestation in primary biliary cirrhosis (PBC). A 56-year-old male was admitted to our hospital because of the identification of bilateral reticular infiltrate on a chest roentgenogram. He was histologically confirmed to have PBC without definite signs of Sjogren's syndrome at age 47. His chest CT scan showed bibasilar reticular opacities without a honeycomb appearance, while a bronchoalveolar lavage fluid analysis revealed no lymphocytosis. A surgical lung biopsy specimen revealed evidence of a UIP pattern. The patient's condition has remained stable for a follow-up period of two years without treatment. Our case indicates that the UIP pattern is an additional form of diffuse interstitial pneumonia/fibrosis that may develop in association with sporadic PBC.

The spread of human immunodeficiency virus (HIV) infection has exploded over the past two decades and such infections in young people are no longer uncommon. However, the major infection route of pediatric patients remains vertical transmission, and sexual, especially homosexual transmission, is highly unusual. We herein describe the case of a 17-year-old boy who developed hemophagocytic lymphohistiocytosis (HLH). Although HLH was remitted soon with dexamethasone therapy, an HIV infection caused by homosexual transmission was detected.

More than 100000 Japanese die of pneumonia every year. The number of people residing in nursing homes is increasing with the ageing of the population. In 2005, the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) published important guidelines for the management of healthcare-associated pneumonia (HCAP). In Japan, however, the optimum strategy for management of HCAP is still unclear. The purpose of this study was to clarify the clinical features of patients with HCAP.Patients (n = 202) who were consecutively admitted with a diagnosis of acute pneumonia between October 2007 and September 2009 were retrospectively evaluated. Using the ATS/IDSA guidelines, patients were divided into three groups: a community-acquired pneumonia (CAP) group (n = 123), a nursing home-acquired pneumonia (NHAP) group (n = 46) and a HCAP other than NHAP (O-HCAP) group (n = 33). These groups were then compared with respect to laboratory data, microbiological findings and mortality.Thirty-day mortality in the NHAP group (10.9%) tended to be higher than that in the CAP group (3.3%) or the O-HCAP group (0%). The pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae in the CAP group, methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae in the NHAP group, and S. pneumoniae and K. pneumoniae in the O-HCAP group.The NHAP group was clinically different from the O-HCAP group, based on bacteriological examination and mortality rates. In order to accurately diagnose, and formulate optimum treatment strategies for Japanese patients, the categories of HCAP, as specified in the ATS/IDSA guidelines, should not be applied directly either to patients with NHAP or those with O-HCAP.

Thrombospondin-1 (TSP-1), a multifunctional matricellular glycoprotein, can activate transforming growth factor-β, an important profibrotic cytokine involved in various fibrotic diseases. TSP-1 is expressed in the lung tissue of animal models of bleomycin-induced pulmonary fibrosis and in patients with some interstitial lung diseases. The present study investigated the serum and bronchoalveolar lavage fluid (BALF) levels of TSP-1 in the idiopathic interstitial pneumonias (IIPs) and the relationship between these levels and other clinical factors. The TSP-1 in the serum and BALF were measured in 45 patients with pathologically diagnosed IIPs [22 with usual interstitial pneumonia (UIP), 23 patients with non-specific interstitial pneumonia (NSIP)], as well as in 28 patients with pulmonary sarcoidosis and 15 healthy volunteers using a competitive enzyme immunoassay. The expression and localization of TSP-1 in the lungs were analyzed by immunohistochemical staining. The serum TSP-1 levels were significantly higher in patients with IIPs than in either those with sarcoidosis or the controls. These levels correlated well with those of an angiogenic cytokine vascular endothelial growth factor while correlating inversely with the %VC. Positive immunostaining of TSP-1 was predominantly observed in the regenerated alveolar epithelium and alveolar macrophages in the lung. Our findings suggest that the circulating TSP-1 levels are associated with the presence of interstitial pneumonia, but further studies are required before we can definitively conclude that TSP-1 plays a role in the pathogenesis of these diseases., Respiratory Medicine, 102(11), pp.1625-1630; 2008