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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

PURPOSE: To assess the feasibility, safety and outcomes of an expedited One-Stop prostate cancer (PCa) diagnostic pathway. PATIENTS AND METHODS: We identified 370 consecutive patients who underwent multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound fusion prostate biopsy (MRI/TRUS-PBx) from our institutional review board-approved database. Patients were divided according to diagnostic pathway: One-Stop (n=74), with mpMRI and same-day PBx, or Standard (n=296), with mpMRI followed by a second visit for PBx. mpMRIs were performed and interpreted according to Prostate Imaging-Reporting and Data System (PI-RADS v2). Grade Group ≥2 PCa defined clinically significant PCa (csPCa). Statistical significance was considered when p

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 0.05 was considered statistically significant.Baseline characteristics and the prostate biopsy rate were similar between the two groups. Median (range) follow-up was 5.7 (2.0-17.2) years. Five-year and 10-year TFS was 92% and 59% for the 5-ARI group versus 80% and 51% for the no 5-ARI group (p = 0.005), respectively. Five-year and 10-year PPFS was 77% and 41% for the 5-ARI group versus 70% and 32% for the no 5-ARI group (p = 0.04), respectively. Independent predictors for treatment and PP were not taking 5-ARIs (p = 0.005; p = 0.02), entry PSA 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p 0.001; p 0.001), respectively. The main limitation is the retrospective study design.5-ARIs reduces reclassification and cross-over to treatment in men on active surveillance for prostate cancer. Further, taking 5-ARIs was an independent predictor for prostate cancer progression and definitive treatment.

We report outcomes of hemigland high intensity focused ultrasound ablation as primary treatment for localized prostate cancer in the United States.A total of 100 consecutive men underwent hemigland high intensity focused ultrasound (December 2015 to December 2019). Primary end point was treatment failure, defined as Grade Group 2 or greater on followup prostate biopsy, radical treatment, systemic therapy, metastases or prostate cancer specific mortality. IIEF (International Index of Erectile Function), I-PSS (International Prostate Symptom Score) and 90-day complications were reported.At study entry patients had very low (8%), low (20%), intermediate favorable (50%), intermediate unfavorable (17%) and high (5%) risk prostate cancer. Median followup was 20 months. The 2-year survival free from treatment failure, Grade Group 2 or greater recurrence, repeat focal high intensity focused ultrasound and radical treatment was 73%, 76%, 90% and 91%, respectively. Bilateral prostate cancer at diagnosis was the sole predictor for Grade Group 2 or greater recurrence (p=0.03). Of men who underwent posttreatment biopsy (58), 10 had in-field and 8 out-of-field Grade Group 2 or greater positive biopsy. Continence (zero pad) was maintained in 100% of patients. Median IIEF-5 and I-PSS scores before vs after hemigland high intensity focused ultrasound were 22 vs 21 (p=0.99) and 9 vs 6 (p=0.005), respectively. Minor and major complications occurred in 13% and 0% of patients. No patient had rectal fistula or died.Short-term results of focal high intensity focused ultrasound indicate safety, excellent potency and continence preservation, and adequate short-term prostate cancer control. Radical treatment was avoided in 91% of men at 2 years. Men with bilateral prostate cancer at diagnosis have increased risk for Grade Group 2 or greater recurrence. To our knowledge, this is the initial and largest United States series of focal high intensity focused ultrasound as primary treatment for prostate cancer.

PURPOSE: We evaluated 5-year oncologic and functional outcomes of hemigland cryoablation of localized prostate cancer. MATERIALS AND METHODS: We reviewed the records of 160 consecutive men who underwent hemigland cryoablation of localized prostate cancer. Recurrent and/or residual clinically significant prostate cancer was defined as Grade Group 2 or greater on followup biopsy. A prostate specific antigen nadir plus 2 ng/ml according to the Phoenix criteria was used to define biochemical failure. Radical treatment was defined as any whole gland therapy. Treatment failure was defined as any radical and/or whole gland treatment, systemic therapy initiation, metastasis or prostate cancer specific mortality. The study primary end point was treatment failure-free survival. The secondary end points were survival free of biochemical failure, clinically significant prostate cancer and radical treatment. Followup biopsy and functional outcomes were also evaluated. Statistical analysis included the Kaplan-Meier method, and univariate and multivariable Cox and logistic regression with significance considered at p

Teriparatide is an anabolic therapy for osteoporosis approved in the United States since 2002 and European Union since 2003; however, approval in Japan lagged significantly. This report describes analyses based on International Conference on Harmonisation (ICH) E-5 guidelines that support bridging between Japanese studies and the large Fracture Prevention Trial (FPT). We analyzed data from single teriparatide doses in healthy Japanese and Caucasian postmenopausal women (J-PK) and from studies of 6 months [Phase 2, dose ranging (J-Ph2)] and 12 months [Phase 3, efficacy and safety (J-Ph3)] of randomized, placebo-controlled, once-daily treatment in Japanese subjects with osteoporosis. In J-PK, apparent teriparatide area-under-the-curve (AUC) and peak concentration (C max) were up to 40% higher in Japanese versus Caucasian women; however, body weight-adjusted values were comparable between populations; these findings were supported by population pharmacokinetic analyses. Between the FPT and Japanese studies, baseline demographic characteristics were similar but bone mineral density (BMD) at lumbar spine (L1–L4) and body weight were lower for Japanese subjects. With teriparatide 20 μg/day, significant increases in BMD were observed compared to placebo at 12 months in both the FPT and J-Ph3 study, and percent change and actual change in BMD were comparable between studies. Dose response at 6 months was also comparable across populations. No novel safety signals were identified in Japanese subjects. These analyses show that teriparatide clinical data met ICH E-5 criteria for bridging. Findings from foreign trials such as the FPT can thus be extrapolated to Japanese subjects treated with teriparatide 20 μg/day.

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.

A 78-year-old man with an 18-year history of rheumatoid arthritis (RA) was treated with tumor necrosis factor (TNF)-α inhibitor adalimumab. Chest computed tomography showed a previously detected consolidation. The patient's arthritic symptoms substantially decreased with the initiation of adalimumab, with a simultaneous improvement of the lung lesion. However, additional interstitial pneumonia was found a month after starting adalimumab. This course suggested that adalimumab might be effective against RA-associated lung disease, but may also have caused drug-induced interstitial pneumonia. This is the first report indicating that TNF-α inhibitor shows simultaneously conflicting actions in a patient with RA-related lung disease.

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.

A 71-year-old man was admitted due to persistent pyrexia of over 2 weeks duration, dry cough, and chest computed tomographic (CT) findings of interstitial pneumonia. On admission, his body temperature was 38.0 degrees C, and there was mild livedo reticularis observed on the trunk and skin of the extremities. Fine crackles were detected in the lower lung fields. Laboratory examinations showed high levels of an inflammatory reaction and a positive rheumatoid factor, but the findings were negative for any other autoantibodies, including the antineutrophil cytoplasmic antibody. His bronchoalveolar lavage fluid revealed an increase in CD4+ lymphocytes. A biopsy specimen of the abdominal skin showed necrotizing vasculitis of the muscular arteries. Lung biopsy specimens showed necrotizing and granulomatous vasculitis of the pulmonary arteries in the usual interstitial pneumonia pattern, with numerous lymphoid follicles. Therefore, a diagnosis of polyarteritis nodosa was clinically and pathologically established. This case of interstitial pneumonia associated with polyarteritis nodosa was difficult to discriminate from microscopic polyarteritis.

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.

We present a case of desquamative interstitial pneumonia (DIP) with elevated serum levels of angiotensin-converting enzyme and lysozyme, which are often found in sarcoidosis. After steroid therapy, improvements in the lung opacity and the serum lysozyme level were observed. Retrospective evaluation of four additional DIP cases showed that four of the five cases studied had an elevated serum lysozyme level. In an immunohistochemical analysis of the lung specimens, increased expression of lysozyme were found in the neutrophils and the alveolar macrophages. Elevated levels of serum lysozyme can occur in diseases such as DIP in which the neutrophil and macrophage activity may affect a patient's pathological condition.

A 47-year-old man was admitted for further examination of uveitis. He had noticed scrotal swelling before his admission. A computed tomographic scan of the chest showed hilar and mediastinal lymphadenopathy, multiple micronodules and thickening of the interlobular septum, and these findings were consistent with sarcoidosis. Bronchoalveolar lavage fluid showed lymphocytosis. Gallium-67 scintigraphy revealed an abnormal accumulation in the hilar and mediastinal lymph nodes and in the bilateral scrotum. The resected and biopsied specimens of the epididymis and testis demonstrated numerous noncaseating epithelioid cell granulomas but no evidence of neoplasm. Therefore, systemic sarcoidosis was diagnosed. A review of the Japanese literature found most cases to be associated with a history of painless scrotal swelling with chest roentgenogram findings of stage I or II, while also indicating it was important to perform biopsy or surgically resect any epididymal and testicular lesion.

Desquamative interstitial pneumonia (DIP) is a rare pattern of diffuse parenchymal lung disease known as one of the idiopathic interstitial pneumonias and is considered to be a smoking- or dust inhalation-related interstitial pneumonia in the majority of cases. This report presents the first case of DIP in which the pulmonary manifestation preceded the onset of rheumatoid arthritis. This case and our review of twenty-four DIP cases (nineteen cases previously-reported from Japan, plus five cases in our departments) indicate the possibility that the DIP pattern is an additional form of diffuse interstitial pneumonia that may develop in association with autoimmune diseases., Internal Medicine, vol.48(10), pp.827-830; 2009

Two cases of chronic pulmonary thromboembolism accidentally diagnosed in the clinical evaluation of COPD are reported. Case 1, a 69-year-old woman who had never smoked, was given a diagnosis of COPD since she had exertional dyspnea with obstructive pulmonary dysfunction and multiple low attenuation areas on her chest CT. Pulmonary ventilation and perfusion scintigram showed mismatched defects and as chronic pulmonary thromboembolism (CPTE) was finally diagnosed. Case 2, a 70-year-old former smoking man had also been previously given a diagnosis of COPD. He had exertional dyspnea, hypoxemia and multiple low attenuation areas in chest CT. Nonetheless his pulmonary function was normal. Pulmonary ventilation and perfusion scintigram showed mismatched defects and pulmonary angiography identified a floating thrombus in the pulmonary artery. Thus he CPTE was diagnosed. The diagnosis of CPTE in COPD is not easy. Physicians should recognize that CPTE can be associated with COPD and perform further examinations including pulmonary ventilation and perfusion scintigram when patients do not show typical results and/or adequately respond to conventional therapy for COPD.

A 72-year-old man, a Shiitake mushroom grower over fifty years, was admitted to our hospital because of bilateral chest interstitial shadow with chronic cough and breathlessness. Chest computed tomography showed traction bronchiectasis, subpleural micro-cystic changes and partial ground-glass opacities in both lungs, and mild mediastinal lymphadenopathy. A diagnosis of chronic hypersensitivity pneumonitis induced by Shiitake mushrooms was comprehensively confirmed by occupational history, radiological findings, and positive findings of an incidental environmental provocation test and lymphocyte stimulation test for Shiitake mushroom extracts. We reviewed the clinical features in five patients with chronic hypersensitivity pneumonitis induced by Shiitake mushrooms reported in Japan. There was a tendency toward increasing lymphocytes and high CD4/CD8 ratio in bronchoalveolar lavage fluids. Treatment with steroids seems to have a limited effect, while avoidance of the antigen is important.

We encountered a family in which two of four members, the husband and his wife, had summer-type hypersensitivity pneumonitis at the same time, about two months after they moved to the residence. A 45-year-old man had cough, fever and exertional dyspnea. Chest computed tomography showed diffuse centriloblar ground-glass attenuation in both lung fields. His 43-year-old wife had chest small nodular shadows and similar symptoms to his husband. Serum anti-Tricosporon cutaneum (T. asahi: serotype II and T. mucoides: serotype I) antibodies of both patients were at the positive level. They were given diagnosis as summer-type hypersensitivity pneumonitis by radiological, serological and histological examinations. The symptoms in both cases were improved immediately after administration of systemic corticosteroid. Summer-type hypersensitivity pneumonitis was assumed to be caused for about two months duration of expousure to antigen.

A 35-year-old man developed invasive pulmonary aspergillosis (IPA) with severe neutropenia after umbilical cord stem cell transplantation for chronic myelogenous leukemia. Filamentous fungus isolated from his sputum was identified as Aspergillus terreus. Despite systemic amphotericin B (AMPH) administration, IPA progressed. However, intravenous administration of micafungin (MCFG) and oral itraconazole improved clinical data and symptoms, although he later died of massive hemoptysis. Examination of the in vitro susceptibility of this A. terreus isolate to MCFG revealed a good minimum inhibitory concentration and good time-kill assay results compared to AMPH. Thus, MCFG might be useful for IPA caused by A. terreus.

The physiological importance of muscarinic M3 and M2 receptors for bladder function was investigated in vivo using mice lacking M3 or M2 receptors and littermate WT controls.Unanesthetized mice of each sex underwent continuous cystometry before and after administration of atropine (1 mg/kg).Male M3 knockout (KO) mice had longer voiding intervals, and larger micturition volumes and bladder capacity than M2 KO or WT males. There was no significant difference in any cystometric parameters between male M2 KO and WT mice. In females M3 KO and M2 KO mice had longer voiding intervals and larger micturition volumes than WT animals. Atropine had marked inhibitory effects on voiding efficacy in WT and M2 KO mice but it had no effect on any cystometric parameters in M3 KO mice.The current results confirm that M3 receptor is the principal muscarinic receptor subtype responsible for bladder contraction and the role of M2 receptors is of minor importance. Functional impairments found in M3 KO mice were milder than those elicited by acute blockade of muscarinic receptors by atropine in WT mice, suggesting that noncholinergic mechanisms can compensate for a chronic loss of M3 receptors.

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