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At the Nuclear Fuel Cycle Engineering Laboratories of the Japan Atomic Energy Agency (JAEA), small pieces of indium foil incorporated into personal dosemeters have been used for personnel screening in criticality accidents. Irradiation tests of the badges were performed using the SILENE reactor to verify the calibration of the indium activation that had been made in the 1980s and to recalibrate them for simulated criticalities that would be the most likely to occur in the solution process line. In addition, Monte Carlo calculations of the indium activation using the badge model were also made to complement the spectral dependence. The results lead to a screening level of 15 kcpm being determined that corresponds to a total dose of 0.25 Gy, which is also applicable in posterior–anterior exposure. The recalibration based on the latest study will provide a sounder basis for the screening procedure in the event of a criticality accident. [ABSTRACT FROM PUBLISHER]

Background Little is known about long-term outcome of tacrolimus therapy for ulcerative colitis. Aim To evaluate long-term efficacy and safety of tacrolimus in Japanese patients with refractory ulcerative colitis. Methods Twenty-seven patients with UC refractory to conventional therapy were administered tacrolimus with trough whole-blood levels of 10–15 ng/mL to induce remission and 5–10 ng/mL to maintain remission. Median treatment duration was 11 months (1–39 months) and median follow-up duration was 17 months (2–65 months). Evaluation of the clinical response was based on a modified Truelove–Witts severity index (MTWSI). Results Tacrolimus produced a clinical response in 21 patients (77.8%), and remission was achieved in 19 of these 21 (70.4%) within 30 days. Overall cumulative colectomy-free survival was estimated as 62.3% at 65 months. In 18 of 19 patients treated with corticosteroids at the initiation of tacrolimus therapy, corticosteroids were discontinued or tapered. Adverse events were tremor (25.9%), renal function impairment (18.5%), infectious disease (14.8%), hot flashes (11.1%), hyperkalaemia (7.4%), headache (7.4%), epigastralgia (7.4%) and nausea (3.7%). No mortality occurred. Conclusion Long-term administration of tacrolimus appears to be an effective and well-tolerated treatment for Japanese patients with refractory ulcerative colitis. [ABSTRACT FROM AUTHOR]

Throughout Japan a total of 543 cases of vitamin K deficiency occurring in infants over 2 weeks of age were reported from January 1981 to June 1985. Of these cases, 427 showed no obvious reasons for vitamin K deficiency; this sort of case is known as "idiopathic vitamin K deficiency in infancy". Another 57 cases had bleeding episodes due to vitamin K deficiency associated with obvious hepatobiliary lesions, chronic diarrhoea, long-term antibiotic therapy, etc; this sort is called "secondary vitamin K deficiency in infancy". The third group, consisting of 59 cases, was made up of the so-called "near miss" type, in which a haemorrhagic tendency, without any obvious clinical haemorrhage, was discovered by Normotest, at the time of mass screening in most cases. In the idiopathic group, 269 cases (63.0%) developed bleeding episodes between the 1st and 2nd months of age, and 387 cases (90.0%) were entirely breast-fed. Intracranial haemorrhage was observed in 353 cases (82.7%) of this group. Moreover, slight elevation of serum transaminase and direct type bilirubin levels were observed in the idiopathic group. Liver dysfunction of unknown origin may play some role in the onset of vitamin K deficiency in infancy. [ABSTRACT FROM AUTHOR]

Background and Aim: While several predictive models for the development of hepatocellular carcinoma (HCC) have been proposed, including those for patients with chronic hepatitis C virus (HCV) infection who have achieved sustained virologic response (SVR), the best model may differ between regions. We compared the ability of six reported models to stratify the risk of post-SVR HCC in Japan, where rigorous surveillance and early detection of HCC is common., Methods: A total of 6048 patients with no history of HCC who achieved SVR by oral direct-acting antiviral drugs were enrolled in this nationwide study. Patients continued HCC surveillance every 6 months after SVR. The incidence of post-SVR HCC was compared between risk groups using the aMAP score, FIB-4 index, Tahata model, GAF4 criteria, GES score, and ADRES score., Results: During the observation period with a median duration of 4.0 years after SVR, post-SVR HCC developed in 332 patients (5.5%). All six models performed significantly at stratifying the incidence of HCC. However, Harrell's C-index was below 0.8 for all models (range, 0.660-0.748), indicating insufficient stratification ability., Conclusion: Although all six proposed models demonstrated a good ability to predict the development of post-SVR HCC, their ability to stratify the risk of post-SVRHCC was unsatisfactory. Further studies are necessary to identify the best model for assessing the risk of post-SVR HCC in regions where early detection of HCC is common., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Abnormalities in homologous recombination contribute to the aggressive nature of castration-resistant prostate cancer. Retinoblastoma transcriptional corepressor 1 (RB1) and breast cancer 2 (BRCA2) exist close to each other in the same chromosome, and the significance of their concurrent loss has become a hot topic in the field of cancer research., Case Presentation: A 61-year-old man presented with a chief complaint of a mass on his head and was diagnosed as multiple bone metastases from prostate cancer. He was treated with standard medication, but he died 2 years 6 months after being diagnosed with prostate cancer. Simultaneous biallelic loss of RB1 and BRCA2 as well as a truncating mutation of tumor protein p53 (TP53) were revealed by genomic analysis., Conclusion: To our knowledge, this is the first report of castration-resistant prostate cancer (CRPC) with BRCA2 and RB1 co-loss and TP53 mutation. To establish a treatment strategy for highly malignant cases with such multiple genetic features is important., (© 2022. The Author(s).)

Abstract: According to the implementing arrangement between the Japan Atomic Energy Agency (JAEA) and the Korea Atomic Energy Research Institute (KAERI) in the field of radiation protection and environmental radiation monitoring, a joint survey program was performed to assess ground deposition of radioactive cesium in areas surrounding the Fukushima Daiichi Nuclear Power Plants. The purpose of this joint survey was to evaluate the field applications of the developed survey systems and methodologies. Understanding the performance of each system within a cesium-deposited contaminated zone is important for ensuring an appropriate response following a nuclear accident. The results of the measured ambient dose rates determined using each survey method were compared. Two kinds of survey system were used in the mobile gamma-ray spectrometry, which were MARK-M1 (Monitoring of Ambient Radiation of KAERI-the 1st Multipurpose system) based on two LaBr3(Ce) detectors of KAERI and KURAMA-II (Kyoto University Radiation Mapping - II) system with one CsI(Tl) detector of JAEA. First, mobile gamma-ray spectrometry using a backpack survey platform was conducted to assess the distribution of dose rates around specific survey sites, which were expected to be slightly contaminated by radioactive cesium in Minamisoma and Tomioka. A carborne survey using two gamma-ray spectrometers loaded inside a vehicle was successfully conducted to compare the measured dose rates in routes from site to site and verify evaluation methods, including attenuation correction., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Health Physics Society.)

Objectives: Vasohibin-1 (VASH1) is an endogenous angiogenesis regulator expressed in activated vascular endothelial cells. We previously reported that high VASH1 expression is a predictor of progression in acinar adenocarcinoma of the prostate. In this study, we evaluated the characteristics of ductal adenocarcinoma of the prostate by comparing the level of VASH1 expression between ductal and acinar adenocarcinoma specimens., Design and Setting: A retrospective cohort study at two centres in Japan., Participants: Among the 1495 patients who underwent radical prostatectomy or transurethral resection for the past 15 years, a total of 14 patients diagnosed with ductal adenocarcinoma and 20 patients diagnosed with acinar adenocarcinoma with a Gleason score of 4+4 were included., Interventions: We immunohistochemically examined the CD34 expression as the microvessel density (MVD) and activated endothelial cells as the VASH1 density (vessels per mm 2 )., Primary and Secondary Outcome Measures: The primary outcome was the association of MVD and VASH1 density between ductal and acinar adenocarcinoma, and the secondary outcome was their oncological outcomes., Results: Nine patients (64.3%) with ductal adenocarcinoma were diagnosed at an advanced clinical stage, and five patients (35.7%) died from cancer during a median follow-up of 56.0 months. The VASH1 densities (mean±SD) in ductal and acinar adenocarcinoma were 45.1±18.5 vs 16.1±21.0 (p<0.001), respectively, while the MVD (mean±SD) in ductal and acinar adenocarcinoma were 65.3±21.9 vs 80.8±60.7 (p=0.666), respectively. The 5-year cancer-specific survival rates for high and low VASH1 expression were 70.0% and 100.0% (p=0.006), respectively. High VASH1 expression and a diagnosis of ductal adenocarcinoma were significant predictors of cancer-specific survival., Conclusions: Ductal adenocarcinoma was more aggressive and had higher VASH1 expression than acinar adenocarcinoma, although MVD was equivalent. These results indicate that VASH1 expression may serve as a novel biomarker for the aggressive nature of ductal adenocarcinoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC., Methods: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features., Results: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years., Conclusion: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Radiation air dose rates near the Fukushima Daiichi Nuclear Power Plant (FDNPP) have been steadily decreasing over the past eight years since the release of radioactive elements in March 2011. Currently, the radiation monitoring program is expected to transition to long-term monitoring after most of the remediation activities are completed. The main long-term monitoring objectives are to (1) confirm the continuing reduction of contaminant and hazard levels, (2) provide assurance for the public, (3) accumulate the basic datasets for scientific knowledge and future preparation, and (4) detect changes or anomalies in contaminant mobility (if they occur), or any unexpected processes or events. In this work, we have developed a methodology for optimizing the monitoring locations of radiation air dose-rate monitoring. Our approach consists of three steps in order to determine monitoring locations in a systematic manner: (1) prioritizing the critical locations, such as schools or regulatory requirement locations, (2) diversifying locations that cover the key environmental controls that are known to influence contaminant mobility and distributions, and (3) capturing the heterogeneity of radiation air-dose rates across the domain. For the second step, we use a Gaussian mixture model to identify the representative locations among multiple environmental variables, such as elevation and land-cover types. For the third step, we use a Gaussian process model to capture and estimate the heterogeneity of air-dose rates across the domain. Employing an integrated dose-rate map derived from Bayesian geostatistical methods as a reference map, we distribute the monitoring locations in such a way as to capture the heterogeneity of the reference map. Our results have shown that this approach allows us to select monitoring locations in a systematic manner such that the heterogeneity of air dose rates is captured by the minimal number of monitoring locations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Ductal carcinoma of the prostate is a histological subtype with a higher mortality than acinar adenocarcinoma. The number of cases is small and there are no treatment guidelines. We believe that this is the first report of ductal carcinoma of the prostate with an adenomatosis polyposis coli (APC) gene mutation in Japan., Case Presentation: An 85-year-old man presented with gross hematuria, and a papillary tumor in the prostatic urethra that was diagnosed as ductal carcinoma of the prostate following transurethral resection. Genetic analysis found an APC mutation with loss of heterozygosity. Immunostaining revealed focal nuclear translocation of β-catenin. APC mutations associated with loss of β-catenin degradation in the Wnt signaling pathway and result in over accumulation of β-catenin are thought to increase mortality. In this patient, β-catenin migrated into tumor cell nuclei., Conclusion: To the best of our knowledge, this is the first report of ductal carcinoma of the prostate with an APC mutation in Japan. The development of a therapeutic Wnt inhibitor is discussed.

Background and Aim: The presence of cirrhosis is an important factor for the management of patients with hepatitis C virus (HCV) infection and it determines the duration of treatment for HCV with the direct-acting antiviral (DAA) regimen of glecaprevir (GLE) and pibrentasvir (PIB), that is, 8 or 12 weeks, if patients do not have a history of DAA failure. However, in real-world settings, determination of cirrhosis depends on the discretion of the attending hepatologists, and it is unclear whether compensated cirrhosis was homogenously diagnosed or not. In this study, we investigated the real-world diagnosis of cirrhosis by characterizing DAA-naïve patients who underwent a 12-week GLE/PIB regimen in whom cirrhosis was diagnosed, comparing their characteristics with those of patients who underwent an 8-week regimen in whom cirrhosis was absent., Methods: In a large, multicenter cohort study, we compared background characteristics and treatment outcomes among DAA-naïve patients who underwent an 8-week versus a 12-week GLE/PIB regimen., Results: Among 977 patients enrolled, 296 (30.3%) were determined to have cirrhosis and underwent a 12-week regimen. Some patient characteristics largely overlapped between the two groups, including liver fibrosis indices. Sustained viral response rates were similar between groups after adjusting liver fibrosis index with propensity score matching., Conclusion: Although adequately diagnosed, the determination of cirrhosis varied widely among institutions or by hepatologists in real-world settings, and the severity of liver fibrosis overlapped significantly between patients in whom compensated cirrhosis was determined to be present and patients in whom cirrhosis was absent. Virologic efficacy was similar after adjusting for the degree of liver fibrosis., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The usefulness of brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, is not fully known for the management of treated hypertensive patients with a history of coronary artery disease (CAD) who have blood pressure less than 130/80 mmHg, a recommended blood pressure target in the updated major hypertension guidelines. We analyzed data for 447 treated hypertensive patients with CAD enrolled in FMD-J Study A for assessment of the predictive value of baPWV for future cardiovascular events. The primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 47.6 months, the primary outcome occurred in 64 patients. Blood pressure less than 130/80 mmHg was significantly associated with a lower risk of the composite outcome independent of other cardiovascular risk factors in treated hypertensive patients with CAD (hazard ratio, 0.59; 95% confidence interval (CI), 0.35-0.99; P = 0.04). In treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, baPWV above the cutoff value of 1731 cm/s, derived from receiver-operator characteristic curve analysis for the composite outcome was significantly associated with a higher risk of the composite outcome independent of conventional risk factors (hazard ratio, 2.83; 95% CI, 1.02-7.91; P = 0.04). baPWV was an independent predictor of cardiovascular events in treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, for whom measurement of baPWV is recommended for cardiovascular risk assessment.

Background: In clinical trials, a pangenotype direct-acting antiviral (DAA) regimen consisting of glecaprevir (GLE) and pibrentasvir (PIB) exhibited high virologic efficacy and tolerability in patients with hepatitis C virus (HCV) infection. This study sought to confirm these findings in real-world settings, focusing on patients with cirrhosis, history of DAA failure, or HCV genotype 3 who were treated with a 12-week regimen in a large multicenter study from Japan., Methods: In a nationwide multicenter prospective cohort study, we analyzed background characteristics, tolerability, and treatment outcome of patients who underwent a 12-week GLE/PIB regimen., Results: Of 1190 patients, 509 (42.8%) underwent the 12-week regimen, and the remaining patients underwent an 8-week regimen. The rate of sustained virologic response (SVR) of patients treated with the 12-week regimen was 99.0%, comparable with that of patients treated with the 8-week regimen. The adverse events were observed in 29.1% of patients. The main adverse event was pruritus, which was observed in 14.7%. Ten patients (2.0%) discontinued therapy during treatment period., Conclusion: The 12-week GLE/PIB regimen was well-tolerated with high virologic efficacy in patients with cirrhosis, experience of DAA, or HCV genotype 3; tolerability and SVR rate were comparable with those of DAA-naïve, non-cirrhotic, non-genotype 3 patients who underwent 8-week regimen., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment., Methods: In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed., Results: Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10 -5 ; genotype 2 vs. 3, p = 3.28 × 10 -5 ) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1-3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4-5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512-148.550), p value (p = 4.06 × 10 -5 )] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153-13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4-5 (41.6% [79/190]) than CKD stage 1-3 (26.1% [319/1220]) patients (p = 2.00 × 10 -5 ). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10 -18 ) patients., Conclusions: G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.

Five intercomparisons of in situ gamma spectrometry by 6-7 participating teams were conducted between December 2011 and August 2015 at sites in Fukushima Prefecture that were affected by the fallout from the accident at the Fukushima Dai-ichi Nuclear Power Plant in March 2011. The evaluated deposition densities agreed within 5% and 4% in terms of the coefficient of variation for radiocesium ( 134 Cs and 137 Cs) and 40 K, respectively, and the ratio of 134 Cs/ 137 Cs in deposition density agreed within 1% in terms of the coefficient of variation, by our best achievement through five intercomparisons. Two different methods for intercomparison were conducted: 1) simultaneous measurements in a narrow area within a 3 m radius; and 2) sequential measurements at an identical point. In a comparison between the two methods at a site where radiocesium was almost homogeneously distributed, no significant difference was observed between the results. The guidance for intercomparison method was proposed based on our experience, and are expected to be used effectively to ensure the reliability of in situ spectrometry., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The deposition densities of radiocesium and the air dose rates were repeatedly measured in a large number of undisturbed fields within the 80 km zone that surrounds the Fukushima Dai-ichi Nuclear Power Plant site between 2011 and 2016, and features of their temporal changes were clarified. The average air dose rate excluding background radiation in this zone decreased to about 20% of the initial value during the period from June 2011 to August 2016, which was essentially a result of the radioactive decay of 134 Cs with a half-life of 2.06 y. The air dose rate reduction was faster than that expected from the decay of radiocesium by a factor of about two, with most of this reduction being attributed to the penetration of radiocesium into the soil. The average deposition densities of 134 Cs and 137 Cs in fields that were not decontaminated were found to have decreased nearly according to their expected radioactive decay, which indicated that the movement of radiocesium in the horizontal direction was relatively small. The effect of decontamination was apparently observed in the measurements of air dose rates and deposition densities. Nominally, the average air dose rates in the measurement locations were reduced by about 20% by decontamination and other human activities, of which accurate quantitative analysis is and continue to be a challenge. In this paper, new original data obtained during 2013-2016 were added to the previously reported data collected up to 2012, and it is discussed throughout., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this study, we quantify the temporal changes of air dose rates in the regional scale around the Fukushima Dai-ichi Nuclear Power Plant in Japan, and predict the spatial distribution of air dose rates in the future. We first apply the Bayesian geostatistical method developed by Wainwright et al. (2017) to integrate multiscale datasets including ground-based walk and car surveys, and airborne surveys, all of which have different scales, resolutions, spatial coverage, and accuracy. This method is based on geostatistics to represent spatial heterogeneous structures, and also on Bayesian hierarchical models to integrate multiscale, multi-type datasets in a consistent manner. We apply this method to the datasets from three years: 2014 to 2016. The temporal changes among the three integrated maps enables us to characterize the spatiotemporal dynamics of radiation air dose rates. The data-driven ecological decay model is then coupled with the integrated map to predict future dose rates. Results show that the air dose rates are decreasing consistently across the region. While slower in the forested region, the decrease is particularly significant in the town area. The decontamination has contributed to significant reduction of air dose rates. By 2026, the air dose rates will continue to decrease, and the area above 3.8 μSv/h will be almost fully contained within the non-residential forested zone., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Germline mutations and copy number changes in DNA damage repair (DDR) genes such as BRCA2 are associated with aggressive forms of prostate cancer (PCa). Although the prevalence of BRCA2 variants in PCa is increasing in Japan, the genomic and biological implications in Japanese patients are unclear. An 81-year-old male presented with prostatic adenocarcinoma with neuroendocrine differentiation accompanied by metastatic lung nodule and brain metastases. Platinum-based doublet chemotherapy combined with etoposide resulted in partial and complete remissions of brain and lung metastases, respectively. Next-generation sequencing of biopsy and peripheral blood samples demonstrated a somatic BRCA2 mutation at c.7008-2A>C and a germline mutation at p.E2877*. The patient's son had been diagnosed with breast cancer 2.5 years ago and was found to have the same germline BRCA2 mutation. BRCA2 mutation increases the risks of aggressive PCa and other cancer types in Japanese males. These forms may be highly responsive to platinum-based chemotherapy., (© 2019 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

We summarized temporal changes in air dose rates and radionuclide deposition densities over five years in the 80 km zone based on large-scale environmental monitoring data obtained continuously after the Fukushima Nuclear Power Plant (NPP) accident, including those already reported in the present and previous special issues. After the accident, multiple radionuclides deposited on the ground were detected over a wide area; radiocesium was found to be predominantly important from the viewpoint of long-term exposure. The relatively short physical half-life of 134 Cs (2.06 y) has led to considerable reductions in air dose rates. The reduction in air dose rates owing to the radioactive decay of radiocesium was more than 60% over five years. Furthermore, the air dose rates in environments associated with human lives decreased at a considerably faster rate than expected for radioactive decay. The average air dose rate originating from the radiocesium deposited in the 80 km zone was lower than that predicted from radioactive decay by a factor of 2-3 at five years after the accident. Vertical penetration of radiocesium into the ground contributed greatly to the reduction in air dose rate because of an increase in the shielding of gamma rays; the estimated average reduction in air dose rate was approximately 25% with penetration compared to that without penetration. The average air dose rate measured in undisturbed fields in the 80 km zone was estimated to be reduced owing to decontamination by approximately 20% compared to that without decontamination. The average deposition density of radiocesium in undisturbed fields has decreased owing to radioactive decay, indicating that the migration of radiocesium in the horizontal direction has generally been slow. Nevertheless, in human living environments, horizontal radiocesium movement is considered to contribute significantly to the reduction in air dose rate. The contribution of horizontal radiocesium movement to the decrease in air dose rate was estimated to vary by up to 30% on average. Massive amounts of environmental data were used in extended analyses, such as the development of a predictive model or integrated air dose rate maps according to different measurement results, which facilitated clearer characterization of the contamination conditions. Ecological half-lives were evaluated in several studies by using a bi-exponential model. Short-term ecological half-lives were shorter than one year in most cases, while long-term ecological half-lives were different across the studies. Even though the general tendency of decrease in air dose rates and deposition densities in the 80 km zone were elucidated as summarized above, their trend was found to vary significantly according to location. Therefore, site-specific analysis is an important task in the future., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In the eighth edition of the TNM classification of lung cancer, the M1b and M1c descriptors are newly defined by the number of extrathoracic metastases. To verify the prognostic value of these descriptors in Japan, we reclassified our cases and re-evaluated prognosis in M1b and M1c patients., Methods: All non-small cell lung cancer (NSCLC) patients with extrathoracic metastases who visited Saitama Medical Center from 2010 to 2016 were evaluated, divided according to the eighth edition of the TNM classification criteria into two groups (M1b, patients with single extrathoracic metastasis, and M1c, patients with multiple extrathoracic metastases), and followed up until December 31, 2017. Survival time analysis was performed using the Kaplan-Meier method, and between-group differences in overall survival time (OS) were evaluated by the log-rank test., Results: A total of 231 NSCLC patients were divided into 57 patients with M1b and 174 with M1c. Median OS was 15.2 months (95% confidence interval [CI]: 9.3-19.9) and 7.3 months (95% CI 5.7-10.7) for M1b and M1c, respectively, with no significant between-group difference (P = 0.239). However, after excluding patients with epidermal growth factor receptor (EGFR) mutation or echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK) fusion gene, median OS was 12.9 months (95% CI 7.2-19.9) for M1b and 5.4 months (95% CI 3.8-6.3) for M1c, respectively, showing a significant difference (P = 0.029)., Conclusions: The effect of therapy directed toward EGFR mutation or EML4-ALK fusion gene might obscure the significant prognostic difference between M1b and M1c.

As part of the investigation of the distribution of ambient dose equivalent rates around the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), car-borne surveys using Kyoto University RAdiation MApping (KURAMA) systems have been conducted over a wide area in eastern Japan since 2011. The enormous volume of measurement data collected until 2016, including those until 2012 which were reported in the previous paper, was analyzed, and dependencies of the decreasing trend of the dose rates in regions within 80 km of the FDNPP on land-use categories, evacuation order areas and magnitude of the dose rates were examined. The air dose rates within 80 km of the FDNPP tended to decrease considerably with respect to the physical decay of radiocaesium. The decrease of the dose rate in the "forest" was slower than its decrease in other regions, while that in "urban area" was the fastest. The decrease in the air dose rate from 2011 was the fastest outside the evacuation order area until 2015, and it was the slowest in the "difficult-to-return zone". However, the decreasing trend starting from 2013 showed that the decrease in the "zone in preparation for the lifting of the evacuation order" and in the "residence restriction area" was the fastest. It was found that the air dose rates decreased depending on the magnitude of the dose rates and elapsed time from the FDNPP accident, i.e. the decrease in air dose rates in areas with relatively low dose ranges (such as 0.2-0.5 μSv/h) was the largest during a period relatively early after the accident, and the decreasing rate in the dose rate ranges of 1.9-3.8 and 3.8-9.5 μSv/h were the fastest after 2013. The averaged ratios were analyzed to obtain the ecological half-lives of the fast and slow decay components, and those in whole area within 80 km of FDNPP were estimated to be 0.44 ± 0.05 y and 6.7 ± 1 y, respectively. The ecological half-lives with respect to the land use categories, evacuation order areas and magnitude of the dose rates were also evaluated. The decrease in the dose rates obtained by the car-borne survey was larger than that obtained on flat ground with few disturbances using the NaI(Tl) survey meter during approximately 1.5 y after the FDNPP accident. Thereafter, the difference of decreasing tendencies in the air dose rates between both the measurements was negligibly small, with the ratio of dose rates by the car-borne survey to those by the fixed-point measurement of 0.72-0.77., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan., (© 2019 John Wiley & Sons Ltd.)

Background and Aim: This study aimed to evaluate the efficacy and safety of elbasvir/grazoprevir in genotype 1b chronic hepatitis C Japanese patients with chronic kidney disease (CKD), including those undergoing hemodialysis., Methods: This post hoc analysis of a multicenter, retrospective study included patients who had received elbasvir/grazoprevir. CKD was defined by an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 . The sustained virologic response (SVR) rate and frequency of treatment-emergent adverse events were assessed in patients with CKD., Results: The study population comprised 155 men and 182 women. The median eGFR level at baseline was 69.6 mL/min/1.73 m 2 (range, 3.0-128.5 mL/min/1.73 m 2 ). Among the 337 patients, 109 (32.3%) had CKD: 72, 14, and 23 (including 20 hemodialysis) had CKD stages 3, 4, and 5, respectively. The SVR rates according to the baseline CKD stages were 98.1% (51/52) in stage 1, 98.3% (173/176) in stage 2, 93.9% (46/49) in stage 3a, 100% (23/23) in stage 3b, 100% (14/14) in stage 4, and 100% (23/23) in stage 5. All 20 patients undergoing hemodialysis achieved SVR. There was no significant decrease from baseline in the median eGFR level throughout the treatment period among the patients with CKD. The incidence of treatment-emergent adverse events was 6.4% (7/109) among the patients with CKD and 9.7% (22/228) among the patients without CKD (not significant, P = 0.323)., Conclusions: The present study demonstrated that elbasvir and grazoprevir are highly effective and safe for genotype 1b chronic hepatitis C Japanese patients with CKD, including those undergoing hemodialysis., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1., Methods: The rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics., Results: Overall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment., Conclusions: The EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.

Background: Standard treatments have not been established in metastatic papillary renal-cell carcinoma (PRCC). We aimed to investigate treatment outcomes in patients with mPRCC., Patients and Methods: This study included 51 patients who were diagnosed with PRCC at 14 institutions. Pathologic slides were reviewed by pathologists. The associations between clinical factors and overall survival (OS) were analyzed., Results: Final pathologic diagnoses could be determined in 50 patients. Thirty-five tumors were diagnosed as PRCC (type 2 PRCC, 91.4%), and 15 were diagnosed as other histologic types. Targeted therapies (TTs) were provided to 25 mPRCC patients. Patients treated with TT survived significantly longer than those treated before the era of TT (median OS, 22.5 vs. 6.3 months; P = .0035). Median OS of patients who experienced stable disease for ≥ 9 months using single TT was 43.1 months. Patients treated with a tyrosine kinase inhibitor (TKI) as first-line TT survived longer after TT initiation than those treated with an mTOR inhibitor (median, 22.4 vs. 11.7 months; P = .2684). Patients treated with TKIs in both first- and second-line settings had significantly better survival after TT initiation than those treated with a TKI in one therapy line and an mTOR inhibitor in the other (31.4 vs. 12.9 months, P = .0172). Patients treated with a TKI as second-line TT survived significantly longer after second-line TT initiation than did those treated with an mTOR inhibitor (16.2 vs. 7.4 months, P = .0016)., Conclusion: Prognoses of patients with mPRCC were improved by TT, and TKIs appeared to be the treatment of choice in both the first- and second-line settings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known., Methods and Results: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06-0.74; P =0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09-0.79; P =0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01-3.44; P =0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23-3.90; P =0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed., Conclusions: In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification., Clinical Trial Registration: URL: www.umin.ac.jp. Unique identifier: UMIN000012950., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Aims: Baseline brachial artery (BBA) diameter has been reported to be a potential confounding factor of flow-mediated vasodilation (FMD). The purpose of this study was to evaluate the relationships between BBA diameter and cardiovascular risk factors and compare the diagnostic accuracy of BBA diameter in subjects without cardiovascular risk factors and patients with cardiovascular disease (CVD) with that of FMD., Methods: We measured BBA diameter and FMD in 5695 male subjects. In addition, we retrospectively investigated the incidence of cardiovascular events using another population sample consisting of 440 male subjects, to compare the accuracy of BBA diameter with that of FMD in predicting cardiovascular events., Results: BBA diameter and FMD significantly correlated with age, body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose as well as Framingham risk score. The prevalence of cardiovascular risk factors and CVD increased with the increase in BBA diameter and FMD. Area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for BBA diameter to diagnose subjects without cardiovascular risk factors (0.59 vs. 0.62, p = 0.001) or patients with CVD (0.58 vs. 0.64, p < 0.001) was significantly lower than that for FMD. In the retrospective study, the AUC value of the ROC curve for BBA diameter to predict first major cardiovascular events was significantly lower than that of FMD (0.50 vs. 0.62, p = 0.03)., Conclusions: In men, BBA diameter was inferior to FMD for assessment of cardiovascular risk., (Copyright © 2017 Elsevier B.V. All rights reserved.)

During the Fukushima Dai-ichi Nuclear Power Plant (NPP) accident, radioactive cesium was released in the environment and deposited on the soils. Depth profiles of radioactive cesium in contaminated soils provide useful information not only for radiation protection and decontamination operations but also for geoscience and radioecology studies. Soil samples were collected using a scraper plate three times between December 2011 and December 2012 at 84 or 85 locations within a 100-km radius of the Fukushima Dai-ichi NPP. In most of the obtained radioactive cesium depth profiles, it was possible to fit the concentration to a function of mass depth as either an exponential or hyperbolic secant function. By using those functions, following three parameters were estimated: (i) relaxation mass depth β (g cm(-2)), (ii) effective relaxation mass depth βeff (g cm(-2)), which is defined for a hyperbolic secant function as the relaxation mass depth of an equivalent exponential function giving the same air kerma rate at 1 m above the ground as the inventory, and (iii) 1/10 depth L1/10 (cm), at which the soil contains 90% of the inventory. The average β value (wet weight) including ones by hyperbolic secant function in December 2012, was 1.29 times higher than that in December 2011. In fact, it was observed that depth profiles at some study sites deviated from the typical exponential distributions over time. These results indicate the gradual downward migration of radioactive cesium in the soils. The L1/10 values in December 2012 were summarized and presented on a map surrounding the Fukushima Dai-ichi NPP, and the average value of L1/10 was 3.01 cm (n = 82) at this time. It was found that radioactive cesium remained within 5 cm of the ground surface at most study sites (71 sites). The sech function can also be used to estimate the downward migration rate V (kg m(-2) y(-1)). The V values in December 2012 (n = 25) were in good agreement with those found by a realistic approach using a diffusion and migration model. Almost all values ranged between 1.7 and 9.6 kg m(-2) y(-1) in this study., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Spatial distributions and temporal changes of radioactive fallout released by the Fukushima Dai-ichi Nuclear Power Plant accident have been investigated by two campaigns with three measurement schedules. The inventories (activities per unit area) of the radionuclides deposited onto ground soil were measured using portable gamma-ray spectrometers at nearly 1000 locations (at most) per measurement campaign. Distribution maps of the inventories of (134)Cs, (137)Cs, and (110m)Ag as of March, September, and December 2012 were constructed. No apparent temporal change of the radionuclide inventories was observed from March to December 2012. Weathering effects (e.g., horizontal mobility) were not noticeable during this period. Spatial dependence in the ratios of (134)Cs/(137)Cs and (110m)Ag/(137)Cs were observed in the Tohoku and Kanto regions. The detailed maps of (134)Cs and (137)Cs as of September 2012 and December 2012 were constructed using the relationship between the air dose rate and the inventory., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Distribution maps of air dose rates around the Fukushima Dai-ichi Nuclear Power Plant were constructed using the results of measurement obtained from approximately 6500 locations (at most) per measurement period. The measurements were conducted 1 m above the ground using survey meters in flat and spatially open locations. Spatial distribution and temporal change of the air dose rate in the area were revealed by examining the resultant distribution maps. The observed reduction rate of the air dose rate over the 18 months between June 2011 and December 2012 was greater than that calculated from radioactive decay of radiocesium by 10% in relative percentage except decontaminated sites. This 10% difference in the reduction of the air dose rate can be explained by the mobility of radiocesium in the depth direction. In the region where the air dose rate was lower than 0.25 μSv h(-1) on June 2011, the reduction of the air dose rate was observed to be smaller than that of the other dose rate regions, and it was in fact smaller than the reduction rate caused by radioactive decay alone. In contrast, the reduction rate was larger in regions with higher air dose rates. In flat and spatially open locations, no significant difference in the reduction tendency of air dose rates was observed among different land use classifications (rice fields, farmland, forests, and building sites)., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A series of car-borne surveys using the Kyoto University RAdiation MApping (KURAMA) and KURAMA-II survey systems has been conducted over a wide area in eastern Japan since June 2011 to evaluate the distribution of air dose rates around the Fukushima Dai-ichi Nuclear Power Plant and to evaluate the time-dependent trend of decrease in air dose rates. An automated data processing system for the KURAMA-II system was established, which enabled rapid analysis of large amounts of data obtained using about 100 KURAMA-II units. The initial data used for evaluating the migration status of radioactive cesium were obtained in the first survey, followed by other car-borne surveys conducted over more extensive and wider measurement ranges. By comparing the measured air dose rates obtained in each survey (until December 2012), the decreasing trend of air dose rates measured through car-borne surveys was found to be more pronounced than those expected on the basis of the physical decay of radioactive cesium and of the air dose rates measured using NaI (Tl) survey meters in the areas surrounding the roadways. In addition, it was found that the extent of decrease in air dose rates depended on land use, wherein it decreased faster for land used as building sites than for forested areas., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: To investigate the efficacy and outcomes of endoscopic papillary large balloon dilation (EPLBD) for bile duct stones in a multicenter prospective study., Methods: Lithotomy by EPLBD was conducted in 124 patients with bile duct stones ≥ 13 mm in size or with three or more bile duct stones ≥ 10 mm. After endoscopic sphincterotomy, the papilla was dilated using balloons 12-20 mm in diameter fitting the bile duct diameter., Results: The success rate of first-time lithotomy was 86.3% (107/124) and the final lithotomy success rate was 100% (124/124). Lithotripsy was needed in 10 of the 124 (13.6%) patients. Adverse events due to the treatment procedure occurred in 6 (4.8%) patients, all of which were mild. Performing large balloon dilation after endoscopic sphincterotomy in patients with large stones or multiple stones in the bile duct is considered to ensure the safety of treatment and to reduce the need for lithotripsy., Conclusion: It is suggested that treatment by EPLBD for large bile duct stones may be safe and useful.

Objective: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The aim of this study is to evaluate the efficacy of radiofrequency ablation (RFA) in elderly patients with HCC and to investigate cause-specific excess deaths associated with increasing number of elderly patients., Materials and Methods: We enrolled 1401 naive patients with HCC who were treated initially by RFA from 1999 to 2011. Patients below 75 years of age were categorized as 'younger' and those at least 75 as 'elderly'. Differences in the demographic and laboratory data of these patients were assessed, along with Kaplan-Meier analysis of survival using the log-rank test. In addition, we assessed the causes of death, defined as liver related and liver unrelated, by competing risk analysis and risk factors for respective causes of death by a proportional subdistribution model., Results: Overall, 353 patients were categorized as elderly. Elderly patients were more likely to be women, infected with hepatitis C virus, and score better in the Child-Pugh classification. The mortality at 5 years was lower in the elderly than in the younger patients (47.3 vs. 37.1%; P<0.001). Competing risk analysis showed a significant difference in liver-unrelated death (P<0.001) between the two groups, whereas there were no significant differences in liver-related death (P=0.64). By the proportional subdistribution model, age was a significant risk factor only for liver-unrelated death., Conclusion: RFA provided satisfactory 5-year survival rates in elderly patients with HCC. The elderly tended to die from liver-unrelated causes.

Objective: To determine the relationships between flow-mediated vasodilation (FMD) and cardiovascular risk factors, and to evaluate confounding factors for measurement of FMD in a large general population in Japan., Methods: This was a cross-sectional study. A total of 5314 Japanese adults recruited from people who underwent health screening from 1 April 2010 to 31 August 2012 at 3 general hospitals in Japan. Patients' risk factors (age, Body Mass Index, blood pressure, cholesterol parameters, glucose level and HbA1c level) and prevalence of cardiovascular disease (coronary heart disease and cerebrovascular disease) were investigated., Results: Univariate regression analysis revealed that FMD correlated with age (r=-0.27, p<0.001), Body Mass Index (r=-0.14, p<0.001), systolic blood pressure (r=-0.18, p<0.001), diastolic blood pressure (r=-0.13, p<0.001), total cholesterol (r=-0.07, p<0.001), triglycerides (r=-0.10, p<0.001), high-density lipoprotein cholesterol (r=0.06, p<0.001), low-density lipoprotein cholesterol (r=-0.04, p=0.01), glucose level (r=-0.14, p<0.001), HbA1c (r=-0.14, p<0.001), and baseline brachial artery diameter (r=-0.43, p<0.001) as well as Framingham Risk score (r=-0.29, p<0.001). Multivariate analysis revealed that age (t value=-9.17, p<0.001), sex (t value=9.29, p<0.001), Body Mass Index (t value=4.27, p<0.001), systolic blood pressure (t value=-2.86, p=0.004), diabetes mellitus (t value=-4.19, p<0.001), smoking (t value=-2.56, p=0.01), and baseline brachial artery diameter (t value=-29.4, p<0.001) were independent predictors of FMD., Conclusions: FMD may be a marker of the grade of atherosclerosis and may be used as a surrogate marker of cardiovascular outcomes. Age, sex, Body Mass Index, systolic blood pressure, diabetes mellitus, smoking and, particularly, baseline brachial artery diameter are potential confounding factors in the measurement of FMD.

Purpose: Low 25-hydroxyvitamin D (25D), increased levels of fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were reported to be risk factors for mortality in chronic kidney disease (CKD). However, the independent associations of these factors with cardiovascular disease (CVD), the leading cause of death among CKD patients, remain unclear. Our purpose was to identify which of these factors predict incident CVD in CKD., Methods: In this prospective cohort study, we enrolled 738 predialysis outpatients in the two nephrology departments. We employed Cox proportional hazards analyses to elucidate predictors of the endpoint, defined as fatal or non-fatal cardiovascular event requiring hospitalization. Multiple imputation was performed for missing values., Results: Mean estimated glomerular filtration rate (eGFR) was 35 mL/min/1.73 m(2). During a median duration of 4.4 years, 86 patients developed the endpoint, of whom 62 patients achieved it before the initiation of dialysis. Multivariable analyses revealed that high serum intact FGF23 levels predicted the outcome preceding dialysis initiation (hazard ratio (HR) per lnFGF23 (SD), 1.64 (1.27-2.30)), while 25D, PTH, and bone-specific ALP did not. Adding FGF23 to the conventional model of age, sex, diabetes, prior CVD, pulse pressure, and eGFR, led to a net reclassification improvement of 6.87% (P=0.04). Not censoring the patients at the start of dialysis and continuing follow-up even after dialysis, FGF23 levels did not predict the outcome (HR, 1.16 (0.91-1.48)). Complete case analyses yielded similar results., Conclusions: Intact FGF23 levels in predialysis CKD predicted incident cardiovascular events requiring hospitalization before starting dialysis, but did not predict events during the entire follow-up period, including post dialysis initiation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The current standard treatment for patients infected with hepatitis C virus (HCV) of genotype 2 is the combination of peginterferon (PEG-IFN) plus ribavirin (RBV) for 24 weeks., Aims: We assessed the sustained virological response (SVR) rates in HCV genotype 2-infected Japanese patients in relation to the duration of treatment., Methods: Between 2006 and 2009, among 147 patients with HCV genotype 2-infection in Chiba Prefecture, 138 consecutive patients were finally enrolled. Twenty-one, 97 and 20 patients were treated with PEG-IFN-alfa 2b plus RBV for 16, 24 and 48 weeks, respectively. Epidemiological data and treatment outcomes were retrospectively evaluated. HCV RNA was measured with COBAS AMPLICOR HCV Monitor Test v. 2.0., Results: The overall SVR rate was 82.6% (114 of 138): treatment-naïve patients, 86.4% (89 of 103); patients with history of previous treatment, 71.4% (25 of 35). Patients treated for 16, 24 and 48 weeks obtained SVR rates of 66.6% (14 of 21), 86.5% (84 of 97) and 80.0 (16 of 20), respectively., Conclusions: The SVR rates of PEG-IFN-alfa 2b plus RBV in Japanese patients were similar to those in previous studies. Combination treatment for 24 weeks for some patients infected with HCV genotype 2 may be superior to that for 16 weeks. More precise patient selection will be needed to shorten the combination treatment.

To assess the position of Kuro-Koji molds in black Aspergillus, we performed sequence analysis of approximately 2500 nucleotides of partial gene fragments, such as histone 3, on a total of 57 Aspergillus strains, including Aspergillus kawachii NBRC 4308, 12 Kuro-Koji molds isolated from awamori breweries in Japan, Aspergillus niger ATCC 1015, and A. tubingensis ATCC10550. Sequence results showed that all black Aspergillus strains could be classified into 3 types, type N which includes A. niger ATCC 1015, type T which includes A. tubingensis ATCC 10550, and type L which includes A. kawachii NBRC 4308. Phylogenetic analysis showed these three types belong to different clusters. All 12 Kuro-Koji molds isolated from awamori breweries were classified as type L, thus we concluded type L represents the industrial Kuro-Koji molds. We found all type L strains lack the An15g07920 gene which is required for ochratoxin A biosynthesis in black Aspergillus. This sequence is present in the genome of A. niger CBS 513.88 and has homology to the polyketide synthase fragment of A. ochraceus which is involved in ochratoxin A biosynthesis. Based on the industrial importance and the safety of Kuro-Koji molds, we propose to classify the type L strains as Aspergillus luchuensis, as initially reported by Dr. Inui., (Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

In Japan, rising costs have impacted the framework of maintaining an efficient and effective healthcare system. Today, urgent implementation of programs to address this need have led to a rebuilding of the entire approach of medical evaluation and clinical care. Recent developments in clinical proteomics based on mass spectrometry (MS) for identifying, sequencing, and quantifying disease-relevant protein biomarkers is a promising means for optimal drug prescription using biomarker diagnosis. We illustrate in this report our experience with lung cancer cases with various drug therapies evaluated with proteomics studies.

Background: Recent evidence indicates that intravenous or oral therapy with tacrolimus (FK-506) is effective in treating patients with Crohn's disease. We evaluated the usefulness of tacrolimus therapy for Japanese patients with refractory Crohn's disease., Methods: Fourteen adult Japanese patients with Crohn's disease that was refractory to conventional therapies, including prednisolone (n = 5), azathioprine (n = 6), and infliximab (n = 5), were enrolled. Treatment with tacrolimus was started orally or intravenously and aimed for serum trough levels of 10-15 ng/ml. After the patients achieved clinical improvement, tacrolimus maintenance therapy was administered to maintain the trough level at 5-10 ng/ml., Results: All patients achieved remission or significant improvement 40 days after starting tacrolimus treatment. By 120 days after the start of therapy, 9 (64%) patients achieved remission, 2 patients (14%) achieved significant improvement, and only 3 patients (21%) relapsed. The relapsed patients were treated with infliximab therapy and achieved remission. Steroids were discontinued by the 5 patients who had taken steroids before the study began. Adverse effects of tacrolimus included a temporary increase in serum creatinine concentration (n = 1, 7%), hyperkalemia (n = 1, 7%), and tremor (n = 1, 7%)., Conclusions: Tacrolimus therapy is effective and well tolerated in patients with Crohn's disease that is refractory to conventional therapies.

Background/aims: The aim of this study was to investigate the effects of being overweight on autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) patients., Methodology/results: 44 AIH and 95 PBC patients were enrolled in this study. Body weight and body mass index (BMI) of AIH (57.6 +/- 10.4 kg and 23.8 +/- 2.9 kgm(-2), respectively) were higher than those of PBC (51.6 +/- 7.0 kg and 22.0 +/- 2.6 kgm(-2), respectively) (P < 0.001). The prevalence of overweight patients in AIH was also higher than those in PBC (P < 0.005). Being overweight and having 25 < or = BMI < 30 did not affect the progression of hepatic fibrosis in AIH and PBC. In comparison with the non-overweight with PBC, overweight patients with PBC tended not to be symptomatic, such as having itching or fatigue (P = 0.027)., Conclusions: Clinicians should be aware that not only non-alcoholic fatty liver disease but also PBC patients might be included among the overweight hepatic disease patients with unknown etiology.

Background and Aim: The pathogenesis of Crohn's disease is unclear, but many studies suggest that luminal bacteria play an important role in chronic intestinal inflammation in patients with this condition. Clarithromycin is a macrolide antibiotic with immunomodulatory activity. The aim of this study was to evaluate the effect of clarithromycin therapy in Japanese patients with Crohn's disease., Methods: Fourteen patients with active Crohn's disease (12 with ileocolonic, one with colonic, one with small bowel type) were treated with oral clarithromycin 200 mg twice daily for 4 weeks. Patients who showed a clinical response within 4 weeks continued the therapy for up to 24 weeks. Four patients also received azathioprine. Clinical activity was assessed with the Crohn's Disease Activity Index (CDAI) at entry and at 4, 12, and 24 weeks after starting clarithromycin., Results: The mean CDAI score at entry was 343.5. Within 4 weeks, eight (57.1%) of the 14 patients showed clinical improvement, and five (35.7%) of the eight patients achieved remission. All of those eight patients continued clarithromycin therapy after 4 weeks, and six (42.9%) were in clinical remission at 12 weeks. Of the 14 total patients, four (28.6%) continued clarithromycin for more than 24 weeks, and have remained in remission. Patients who received azathioprine concomitantly had a better response to clarithromycin therapy. No severe side-effects were observed during the study period., Conclusions: This open label study showed encouraging results of clarithromycin therapy in Japanese patients with active Crohn's disease.

Chemotherapy aims to cure cancer or inhibit the growth of cancer cells by administering the anticancer agent in blood vessels (BV) to the cancer body. So it is very important to inject the agent in BVs without fail because there is risk of extravasation which brings about the chemical necrosis of the tissue around. Thus, nurses involved in chemotherapy care should learn to take interventions for prevention from extravasation and immediate treatment for it, in case. In the interventions there are care practices with advanced thinking processes. Clarification of such thinking processes contributes to the visualization of nursing practice and the support for nurses to learn expert nursing practices. Also it is supposed to realize the nursing quality assurance for care receiver-patients.

The purpose of this study is to find out the differences in physical activity (PA), energy expenditure (EE) and energy intake (EI) under free-living conditions between Japanese prepubertal obese and nonobese boys. The subjects were 15 prepubertal obese boys (Age: 11.7+/-0.4 years old, Body fat: 35.2+/-1.6%) who do not have obese parents and siblings and 15 prepubertal nonobese boys (Age: 11.8+/-0.4 years old, Body fat: 18.5+/-0.8%). We assessed their daily PA by heart rate (HR) monitoring, pedometer step counts (PSC) and time for sedentary activities (SA). We also examined calculated EE from HR-VO(2) regression, EI and percentage of macronutrient EI. Results are as follows: Percentage of body fat had significant correlation with weight, BMI, time for SA, percentage EI of protein (positive, p<0.001), VO(2max), VO(2max) per body weight, VO(2max) per LBM, PSC, TEE per body weight, TEI per body weight (negative, p<0.001), percentage of EI of carbohydrate (negative, p<0.01). The values of the obese were significantly lower in total EE per body weight and in total EI per body weight. EI from dinner was significantly higher in the obese group. The values of the obese were significantly higher in percentage EI from protein and that from carbohydrate. The results of this study showed prepubertal obese boys who do not have obese parents and siblings have low PA and spend much time for sedentary activities. Obese boys consume higher percentage energy of protein and lower percentage of carbohydrate though differences in EE and EI were found only in total EE per body weight and total EI per body weight between obese boys and nonobese boys.

It has been reported that mutations in the FGFR3 gene cause autosomal dominant forms of dwarfism, achondroplasia (ACH) and hypochondroplasia (HCH). In the present study, we analyzed the FGFR3 gene in 26 Japanese patients with ACH and 14 with HCH. Genomic DNAs of the patients were isolated from whole blood. For the ACH patients, a 164-bp fragment of the FGFR3 gene that spans the entire transmembrane domain was amplified by polymerase chain reaction (PCR), and the PCR products were analyzed by direct sequencing of the PCR products and by digestion of the PCR products with restriction enzymes. For the HCH patients, a 206-bp fragment of the FGFR3 gene which encodes a part of the TK1 domain was amplified, and the PCR products were directly sequenced. The heterozygous G380R mutations were identified in all of the 26 ACH patients, whereas the heterozygous N540K mutations were identified in 8 out of 14 HCH patients. These results were consistent with previous reports from abroad.

To test Joossens's hypothesis that salt is a common cause of both cerebrovascular disease (CVD) and stomach cancer (SC), the standardized mortality ratios (SMRs) of SC and CVD were related to urinary Na and K and urinary Na/creatinine (Cr), K/Cr, and Na/K ratios. Fifty spot urine of females between 40 to 69 years was collected from each of 169 municipalities (88 urban and 81 rural) covering all prefectures in Japan using the filter paper sampling technique in 1985. While the SMR levels of CVD correlated significantly with Na, Na/Cr and Na/K, the SMR levels of SC showed no correlation with Na, K, Na/Cr, K/Cr or Na/K. It was therefore concluded that the geographical distribution of female SMR for SC could not be explained using only the urinary Na excretion as an index of Na intake, and that multiple risk factors and risk reducing factors should be taken into account to explain the distribution.

A simple method for measuring 24-hr urinary sodium excretion was applied to the evaluation of the individual effects of a health education program for sodium restriction in a rural community in Japan. Eighteen subjects (6 males and 12 females) between 35 and 72 years of age were advised to reduce their sodium intake. Twenty-four-hour urinary sodium, potassium excretion, and sodium/potassium ratio were measured using the simple method for seven consecutive days in three periods which were before the sodium restriction, 6 months after the sodium restriction, and 6 months after the end of the program. Mean sodium excretion of 18 subjects significantly decreased (p less than 0.05) after the end of the program. The reduced level was maintained until six months after the end of the program. Within individual cases, sodium excretion decreased significantly in subjects who had levels higher than 170 mmol at the initial stage. The reduced levels of sodium excretion were maintained until six months after the end of the program except for one subject. The subjects who had an initial level lower than 170 mmol of sodium, which is the upper limit of present recommendation for Japanese adults, did not change their levels.

The occurrence of hemorrhagic disease due to vitamin K (VK) deficiency beyond the neonatal period has come under investigation in Japan. In 1980 the 1st nationwide survey was conducted in Japan by Nakayama and others, and was followed by the 2nd nationwide survey in 1985 by Hanawa. The present survey was designed to further monitor the incidence of this disease in Japan during the 3-year period from July 1985 to June 1988. Questionnaires were sent to 1,315 hospitals having more than 200 beds, located throughout Japan. Responses were received from 775 hospitals, for an answer rate of 58.9%. The total number of reported cases was 175, including 129 idiopathic type, 28 secondary type and 18 near-miss type. In this survey it was revealed that the incidence rate of the idiopathic type of vitamin K deficiency in infancy (VKDI) has decreased remarkably, to about one-fourth that reported in the first survey. The declining incidence rate of VK deficiency in Japan is considered to be the result of ever more widespread prophylactic administration of VK during the neonatal period, as most occurrences of VK deficiency in infancy are preventable by prophylactic administration of VK from the neonatal period. However, in 16 cases of the idiopathic type of VK deficiency found in the present survey, VK had been administered at least once during or after the neonatal period. This shows the heterogeneity of this condition.

3 young Japanese sisters with congenital alpha 2-plasmin inhibitor (alpha 2-PI) deficiency are reported. They have mild umbilical bleeding and/or repeated prolonged bleeding after minor trauma, but rarely spontaneous bleedings. The most characteristic hemostatic findings were shortened whole blood clot lysis time and euglobulin lysis time. Activities of all hemostatic factors except alpha 2-PI were within normal range. Both functional and immunological absence of alpha 2-PI were found in the plasma, and this failure to detect alpha 2-PI was not corrected by the addition of the patient's plasma of the first described case of alpha 2-PI deficiency. Clinical and laboratory data revealed that these patients were probably homozygous for alpha 2-PI deficiency and born of heterozygous parents, but not of consanguineous ones. Bleeding episodes due to deficiency of alpha 2-PI in these patients were well controlled by an antifibrinolytic agent, tranexamic acid.