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Abstract: In order to understand the properties of ion tracks and the microstructural evolution under accumulation of ion tracks in UO2, 100MeV Zr10+ and 210MeV Xe14+ ions irradiation examinations have been done at a tandem accelerator facility of JAEA-Tokai, and it has been observed the microstructure by means of a transmission electron microscope (TEM) and a scanning electron microscope (SEM) in CRIEPI. Comparison of the diameter of ion tracks between UO2 and CeO2 under irradiation with 100MeV Zr10+ and 210MeV Xe14+ ions at room temperature clarify that the sensitivity on high density electronic excitation of UO2 is much less than that of CeO2. By the cross-sectional observation of UO2 under irradiation with 210MeV Xe14+ ions at 300°C, elliptical changes of fabricated pores that exist till ∼6μm depth and the formation of dislocations have been observed in the ion fluence over 5×1014 ions/cm2. The drastic changes of surface morphology and inner structure in UO2 indicate that the overlapping of ion tracks will cause the point defects, enhance the diffusion of point defects and dislocations, and form the sub-grains at relatively low temperature. [ABSTRACT FROM AUTHOR]

In Abashiri, Hokkaido, northern Japan, composted sewage sludge (CSS) containing a large amount of zinc (Zn) and copper (Cu) is used as fertilizer in agriculture. The local environmental risks of Cu and Zn from such organic fertilizers were studied. The study area, especially the brackish lakes located near the farmlands, is important for inland fisheries. The risks posed by heavy metals to the brackish-water bivalve, Corbicula japonica, was therefore investigated as an example. First, the long-term effect of CSS application in agricultural fields was monitored. Second, using pot cultivation, factors influencing Cu and Zn availability in the presence of organic fertilizers were evaluated under different scenarios of SOM content. In addition, the mobility and availability of Cu and Zn in organic fertilizers were evaluated in a field experiment. In the pot cultivation, both organic and chemical fertilizers increased the availability of Cu and Zn with a decrease in pH, possibly caused by nitrification. However, this decrease in pH was inhibited by higher SOM content, i.e. SOM mitigated the heavy metal risk from organic fertilizer. In the field experiment, potato (Solanum tuberosum L.) was cultivated using CSS and pig manure (PM). As observed in the pot cultivation, the applied chemical and organic fertilizers increased the soil-soluble and 0.1 N HCl-extractable Zn with increased nitrate. Considering the habitat and the LC 50 values of C. japonica that were lower than the concentration of Cu and Zn in the soil solution phase, there is no significant risk from heavy metals in the organic fertilizers. However, the K d values for Zn were significantly lower for CSS or the PM-applied plot in the field experiment soil, indicating a higher Zn desorption rate from organically fertilized soil particles. The potential risk of heavy metals from agricultural lands under changing climate conditions must therefore be monitored carefully., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yasuo Mitsui Nakamaru reports financial support was provided by Tokyo University of Agriculture. Yasuo Mitsui Nakamaru reports a relationship with Tokyo University of Agriculture that includes: employment and funding grants. Yasuo Mitusi Nakamaru has patent pending to Yasuo Mitusi Nakamaru. Co-author Retsushi Matsuda previously studied at Tokyo University of Agriculture as a postgraduate student under the supervision of co-author Takeshi Sonoda., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: We investigated factors associated with the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody titer after the second dose of the BNT162b2 messenger RNA coronavirus disease 2019 (COVID-19) vaccine in Japanese patients undergoing hemodialysis., Methods: Overall, 75 patients (41 men, 34 women; mean age 71.4 ± 12.2 years) with a hemodialysis duration of 5.7 ± 6.1 [interquartile range, 1.0-8.5] years were enrolled in this single-center, prospective, cross-sectional study. We used multiple linear regression analysis to determine the relationships of the anti-SARS-CoV-2 spike antibody titer with patient demographic and clinical parameters. We also compared the anti-SARS-CoV-2 spike antibody titer between hemodialysis patients and 22 healthcare workers (10 men, 12 women; mean age 48.5 ± 14.4 years)., Results: Autoimmune disease presence (standard coefficient [β] =  - 0.290, p = 0.018), lymphocyte counts (β = 0.261, p = 0.015), hemoglobin levels (β = 0.290, p = 0.009), and blood urea nitrogen concentrations (β = 0.254, p = 0.033) were significantly and independently correlated with the log-anti-SARS-CoV-2 spike antibody titer. The anti-SARS-CoV-2 spike antibody titer was significantly lower in hemodialysis patients than in healthcare workers (3589 ± 3921 [813-4468] vs. 12,634 ± 18,804 [3472-10,257] AU/mL; p < 0.002)., Conclusions: Autoimmune disease presence, lymphocyte counts, hemoglobin levels, and blood urea nitrogen concentrations were associated with the anti-SARS-CoV-2 spike antibody titer after the second dose of the BNT162b2 messenger RNA COVID-19 vaccine in Japanese patients undergoing hemodialysis., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported., Methods: We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients., Results: Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer., Conclusion: Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: Soft tissue sarcomas in the elbow are extremely rare, and they have primarily been described in case series. Definitive concerning the prevalence and prognostic factors of elbow soft tissue sarcomas remain unknown. We examined the outcome of patients with elbow soft tissue sarcomas and identified the relevant prognostic factors., Methods: In total, 219 patients with elbow soft tissue sarcomas were identified using data from the bone and soft tissue tumor registry in Japan. Differences in demographics, disease characteristics, treatment and survival were compared among the patients. Survival analyses including local recurrence-free survival, distant metastasis-free survival, and overall survival were performed using the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model., Results: Two hundred nineteen patients with elbow soft tissue sarcomas were identified, including 119 males (54.3%) and 100 females (45.7%). In total, 189 patients (86.3%) underwent surgery including re-excision. Of the surgically treated patients, 180 (95.2%) underwent limb salvage surgery, and nine patients (4.8%) underwent amputation. The 5-year overall survival, local recurrence-free survival, and distant metastasis-free survival rates for the entire patient cohort were 76.3, 70.1, and 69.3%, respectively. After adjusting for clinically relevant factors, overall survival was significantly worse among patients with tumors: >10 cm (hazard ratio = 4.34; 95% confidence interval = 1.03-18.2) and metastatic disease (hazard ratio = 6.94; 95% confidence interval = 1.55-31.0)., Conclusions: Tumor size was identified as an independent risk factor for poor prognosis., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Purpose: To investigate the effects of lactoferrin (LF) on infectious diseases in Japanese summer., Methods: An intake of placebo, 200 mg, or 600 mg of LF were administered to healthy adults in Kyushu University of Health and Welfare for 12 weeks in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The primary endpoints were the prevalence and duration of infectious diseases and changes in immune parameters., Results: Three hundred and ten subjects were randomized (placebo, n = 104; 200 mg, n = 103; 600 mg, n = 103). Twenty subjects were lost to the follow-up, leaving 290 for a full analysis set (n = 99; n = 95; n = 96). The duration (day) of total infectious diseases was shorter in the 200 mg group (2.0, p = 0.045) and 600 mg group (2.0, p = 0.010) than in the placebo group (3.0). The duration of summer colds was shorter in the 600 mg group (2.0, p = 0.036) than in the placebo group (3.0). No significant differences were observed in the prevalence of infectious diseases or changes in immune parameters. In exploratory investigations, changes in the neutrophil phagocytic capacity, cortisol concentrations, and T score of "Vigor/Activity" in the Profile of Mood States 2 were greater in the 600 mg group than in the placebo group, when analysis was done on the lower half groups at the baseline. Adverse events were similar in each group and none had a causal relationship with the intake of the test foods., Conclusions: In summer, the intake of LF attenuates infectious diseases, including summer colds., Competing Interests: Declaration of Competing Interest HO, HW, MT, KY, and FA are employees of Morinaga Milk Industry. CS, HY, TS, and MK declare no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Cardiovascular disease is a major cause of death among travelers, but the clinical characteristics and clinical outcomes of patients who develop acute coronary syndrome (ACS) while traveling have not been assessed. We evaluated 2548 patients with ACS who underwent primary percutaneous coronary intervention (PCI) between 1999 and 2015 and compared the incidences of all-cause and cardiac death during follow-up between travelers and locals. We assessed 192 (7.5%) patients who developed ACS while traveling. These patients were younger and had a higher prevalence of ST-elevation myocardial infarction than local patients. During a median follow-up period of 5.3 years, 632 (24.8%) all-cause deaths were identified, including 310 cardiac deaths (12.2%). Kaplan-Meier analysis revealed that the cumulative incidence of all-cause death was significantly lower among the travelers than locals (P = 0.001, log-rank test). Multivariate Cox hazard analysis revealed that travel was significantly associated with a lower rate of all cause death (hazard ratio, 0.53; 95% confidence interval, 0.33-0.80; P = 0.002). Cardiac mortality did not significantly differ between travelers and locals (P = 0.29). Patients with ACS treated with primary PCI while traveling had more favorable long-term clinical outcomes than local patients. Appropriate initial treatments and secondary preventions might improve the prognosis of travelers.

Aims: Living alone is reported as an independent risk factor for cardiovascular disease. However, little is known about the association between clinical outcomes and living alone in patients with acute coronary syndrome (ACS). The aim of this study was to determine whether living alone is an independent prognostic risk factor for long-term mortality stratified by age in patients with ACS who were treated with primary percutaneous coronary intervention (PCI)., Methods and Results: We conducted an observational cohort study of ACS patients who underwent PCI between January 1999 and May 2015 at Juntendo University Shizuoka Hospital, Japan. The primary endpoint was all-cause death. Among 2547 ACS patients, 381 (15.0%) patients were living alone at the onset of ACS. The cumulative incidence of all-cause death was comparable between living alone and living together (34.8% vs. 34.4%, log-rank P = 0.63). However, among younger population (aged <65 years), the incidence of all-cause death was significantly higher in the living alone group (log-rank P = 0.01). Multivariate Cox hazard analysis revealed a significant association between living alone and all-cause death, even after adjusting for other risk factors (hazard ratio 2.30, 95% confidence interval 1.38-3.84, P = 0.001)., Conclusion: Although living alone was not significantly associated with long-term clinical outcomes in patients with ACS, it was a predictive risk factor among younger ACS patients. Careful attention should be paid to patients' lifestyle, especially younger patients with ACS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: In terms of the balance between benefits and risks of long-term treatment with bisphosphonate, uncertainties remain regarding the optimal treatment duration. We investigated effects of continuous long-term treatment for 10 years with bisphosphonate in postmenopausal osteoporosis patients., Materials and Methods: Fifty five patients in the outpatient clinic of our hospital have been continuously treated with alendronate or risedronate for 10 years. All data were retrospectively collected. The age, height, weight, total muscle volume, total fat volume, and BMD at the lumbar spine, total hip and distal 1/3 radius, alkaline phosphatase (ALP), urinary type I collagen cross-linked N-telopeptide (uNTX) and tartrate-resistant acid phosphatase-5b (TRAP5b), calcium (Ca) and phosphate (P) levels were measured pre- and after the start of 10-year continuous treatment., Results: BMD at the lumbar spine increased continuously over the 10-year period, while BMD at the total hip slightly but significantly decreased, and that at the 1/3 radius did not show any significant change over the 10 years. Serum Ca value was significantly decreased after the start of treatment, and became stable within the reference range from the second year. Bone resorption markers such as uNTX and TRAP5b significantly decreased from the second year after the start of treatment and no significant changes were observed thereafter. There were no serious medical adverse events including atypical femoral fractures and osteonecrosis of the jaw., Conclusion: We believe that the continuous use of alendronate and risedronate for 10 years could be an option for the treatment of postmenopausal osteoporosis patients.

Background: Proton pump inhibitors (PPIs) are known to increase the risk of mortality and cardiovascular events in the general population. However, in patients with maintenance hemodialysis, PPI effects are under investigated., Methods: We analyzed the risk of PPIs for cardiovascular events using the Kagoshima Dialysis (KIDS) registry, a prospective, multicenter, observational study in patients with maintenance hemodialysis in Japan., Results: In all, 531 patients were enrolled from June 2015 to December 2018. One-year follow-up data were available for 376 patients (Use of PPIs at baseline (PPI group): 217 patients and without PPIs (No PPI group): 159 patients). The incidence of a composite outcome (all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke) was higher in patients in the PPI group than the No PPI group (15.2% vs. 4.4%; hazard ratio (HR): 3.65, 95% confidence interval (CI): 1.61-8.23, P = 0.002). In the multivariate analysis, even after adjustment for covariates, the use of PPIs was an independent risk factor for a composite outcome (HR: 2.38, 95% CI: 1.02-5.54, P = 0.045). We performed propensity score matching analysis as a sensitivity analysis, showing a consistent result. The incidence of bleeding showed no difference between the two groups (15.7% vs. 11.3%; HR: 1.46, 95% CI: 0.83-2.59, P = 0.19)., Conclusions: These results indicate that the use of PPIs in patients with maintenance hemodialysis might increase mortality and cardiovascular events without decreasing the risk of bleeding. Therefore, it should always be analyzed if a patient truly needs PPIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: In the past two decades several antineoplastic agents have been approved for the treatment of advanced non-small-cell lung cancer (NSCLC), and the management of these patients has drastically changed. However, there is limited information regarding the impact of these advances on patient survival in clinical practice., Materials and Methods: We analyzed the survival of patients with stage IV NSCLC who received any treatment in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR) between January 1, 1995 and March 1, 2017. A total of 1,547 consecutive patients were included in this case series. In this analysis, five diagnostic periods were evaluated: 1995-1999 (period A), 2000-2004 (period B), 2005-2009 (period C), 2010-2014 (period D), and 2015-2017 (period E). We compared overall survival (OS) between the periods before and after propensity score matching (PSM) and in patients with EGFR mutation, with ALK fusion gene, or without driver mutation., Results: In the past two decades the OS of patients with stage IV NSCLC improved. The median OSs for periods A, B, C, D, and E were 9.0, 11.0, 13.7, 17.9 months, and not reached, respectively. After PSM with known baseline characteristics, the trend of improvement in OS was similar. However, the OS of patients with EGFR mutation or ALK fusion gene did not improve between periods, despite the availability of several tyrosine kinase inhibitors in Japan. The OS of patients without a driver mutation was slightly longer in the period E., Conclusion: The introduction of new classes of drugs has significantly improved the survival of patients with stage IV NSCLC. However, the approval of similar types of drugs may not be associated with further improvement in survival., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to identify any potential correlation between postoperative mortality and bowel resection in patients with obturator hernias., Methods: In total, 21 patients who underwent emergency surgery for a primary incarcerated obturator hernia during a 9-year period were retrospectively assessed regarding the correlation between postoperative mortality within 30 days from surgery and bowel resection., Results: The 21 hernias occurred in 20 women and 1 man. The mean age at presentation was 83.3 years. Eight hernias required bowel resection, and operations using mesh were performed for eight hernias. Complications occurred in association with nine hernias, and three patients died. Postoperative mortality was correlated with complications (p = 0.016) and bowel resection (p = 0.010). Patients undergoing bowel resection had a significantly longer operation time (p = 0.009) and a higher rate of postoperative complications (p = 0.018). The systolic blood pressure, pH, and base excess were significantly lower in patients who did than did not undergo bowel resection (p = 0.017, 0.009, and 0.015, respectively)., Conclusion: As the aging population continues to expand, the number of patients with obturator hernias is speculated to increase. Elderly people with comorbidities require immediate operative procedures because their general condition tends to be exacerbated by bowel obstruction. Postoperative management may be carefully performed in patients with bowel resection because the postoperative mortality rates may be higher in these patients.

Aim: The Friedewald equation is the standard method for estimating low-density lipoprotein cholesterol (LDL-C) levels [LDL-C(F)] and fixes the ratio of triglyceride (TG) to very LDL-C at 5. However, this has been reported to underestimate LDL-C, particularly in patients with LDL-C ＜70 mg/dL. A novel method for LDL-C estimation [LDL-C(M)] using an adjustable factor instead of a fixed value of 5 has recently been proposed. The purpose of this study was to validate LDL-C(M) in Japanese patients with cardiovascular disease (CVD) treated with statins., Methods: In 385 consecutive CVD patients treated with statins, LDL-C(M) and LDL-C(F) levels were compared with directly measured LDL-C [LDL-C(D)]., Results: Mean LDL-C(D), LDL-C(F), and LDL-C(M) were 81.7±25.5, 76.4±24.6, and 79.9±24.5 mg/dL, respectively. In all patients, both LDL-C(F) and LDL-C(M) were significantly correlated with LDL-C(D) [LDL-C(F) vs. LDL-C(D): R=0.974, p＜0.001; LDL-C(M) vs. LDL-C(D): R=0.987, p＜0.001]. In patients with LDL-C(D) ＜70 mg/dL, LDL-C(M) showed a better correlation with LDLC(D) compared with LDL-C(F) [LDL-C(M) vs. LDL-C(D): R=0.935, p＜0.001; LDL-C(F) vs. LDLC(D): R=0.868, p＜0.001]. In contrast, the correlation of LDL-C(D) with LDL-C(M) or LDL-C(F) was similar in patients with LDL-C(D) ≥70 mg/dL., Conclusions: In Japanese patients with CVD treated with statins, LDL-C level estimated by this novel method might be more accurate than those estimated using the Friedewald equation for LDL-C levels ＜70 mg/dL.

Background & Aims: Endoscopic sphincterotomy (ES) is performed routinely before self-expandable metallic stents (SEMS) are placed in malignant distal biliary strictures to prevent postprocedural pancreatitis. However, it is not clear whether ES actually prevents pancreatitis or affects other adverse events (AEs). We conducted a noninferiority trial to examine the necessity of ES before SEMS placement., Methods: Two hundred patients with distal biliary strictures caused by unresectable pancreatic cancer were assigned randomly to groups that received ES or did not receive ES (non-ES) before SEMS placement, at 25 hospitals in Hokkaido, Japan, from August 2010 through November 2012. The primary outcome was early AEs (≤30 d) specifically related to the presence or absence of ES (pancreatitis, bleeding, or perforation). Secondary outcomes measured included the effect of ES omission on time to SEMS dysfunction and patient survival times., Results: The proportions of patients with early AEs were 9.2% in the non-ES group and 10.4% in the ES group (a difference of 1.2%, noninferior). The median times to SEMS dysfunction was longer than 594 days in the non-ES group and 541 days in the ES group (P = .88). The median overall survival times were 202 in the ES group vs 255 days in the non-ES group; P = .20)., Conclusions: ES before SEMS does not affect the incidence of AEs, SEMS patency, or patient survival times. Our data provide no evidence for a benefit of ES to patients undergoing SEMS placement for a biliary stricture caused by pancreatic cancer. UMIN clinical trials registry number: 000004044., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the effectiveness of phenol for the relief of cancer pain by endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN)., Methods: Twenty-two patients referred to our hospital with cancer pain from August 2009 to July 2011 for EUS-CPN were enrolled in this study. Phenol was used for 6 patients with alcohol intolerance and ethanol was used for 16 patients without alcohol intolerance. The primary endpoint was the positive response rate (pain score decreased to ≤ 3) on postoperative day 7. Secondary endpoints included the time to onset of pain relief, duration of pain relief, and complication rates., Results: There was no significant difference in the positive response rate on day 7. The rates were 83% and 69% in the phenol and ethanol groups, respectively. Regarding the time to onset of pain relief, in the phenol group, the median pre-treatment pain score was 5, whereas the post-treatment scores decreased to 1.5, 1.5, and 1.5 at 2, 8, and 24 h, respectively (P < 0.05). In the ethanol group, the median pre-treatment pain score was 5.5, whereas the post-treatment scores significantly decreased to 2.5, 2.5, and 2.5 at 2, 8, and 24 h, respectively (P < 0.01). There was no significant difference in the duration of pain relief between the phenol and ethanol groups. No significant difference was found in the rate of complications between the 2 groups; however, burning pain and inebriation occurred only in the ethanol group., Conclusion: Phenol had similar pain-relieving effects to ethanol in EUS-CPN. Comparing the incidences of inebriation and burning pain, phenol may be superior to ethanol in EUS-CPN procedures.

Background: There are substantial differences in inflammatory bowel disease (IBD) genetics depending on the populations examined. We aimed to identify Japanese population-specific or true culprit susceptibility genes through a meta-analysis of past genetic studies of Japanese IBD., Methods: For this study, we reviewed 2,703 articles. The review process consisted of three screening stages: we initially searched for relevant studies and then relevant single nucleotide polymorphisms (SNPs). Finally, we adjusted them for the meta-analysis. To maximize our chances of analysis, we introduced proxy SNPs during the first stage. To minimize publication bias, no significant SNPs and solitary SNPs without pairs were combined to be reconsidered during the third stage. Additionally, two SNPs were newly genotyped. Finally, we conducted a meta-analysis of 37 published studies in 50 SNPs located at 22 loci corresponding to the total number of 4,853 Crohn's disease (CD), 5,612 ulcerative colitis (UC) patients, and 14,239 healthy controls., Results: We confirmed that the NKX2-3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24)., Conclusions: Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions.

Diatom fossils from core sediments and living diatoms from water samples of Notoro Lagoon in northern Japan were examined to evaluate natural climate effects on lagoon environmental changes. In 1974, the artificial inlet was excavated. Immediately after, the anoxic bottom water in Notoro Lagoon began to disappear due to an increasing water exchange rate. However, chemical oxygen demand (COD) in the bottom water of Notoro Lagoon gradually increased, with fluctuations, during the last 30 years. In addition, the dominant diatom assemblages in Notoro Lagoon shifted to ice-related and spring bloom taxa after the excavation. The dominant taxa of each year in the sediment core were also strongly related to the timing of lagoon ice melting. This is because the COD in Notoro Lagoon was affected by the deposited volume of blooming diatoms, which was controlled by the duration of ice cover and the timing of ice discharge to the Okhotsk Sea likely due to an air pressure pattern change over the northern North Pacific like the Pacific Decadal Oscillation (PDO)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We hypothesized that environmental factors might affect the relationship between genetic predisposition and the risk of bone mineral density (BMD) loss. Cases were 114 Japanese women with a confirmed diagnosis of postmenopausal osteoporosis and controls were 171 general Japanese women. Genetic risk of SNPs in the estrogen receptors was analyzed by a case-control study. The interaction between gene and environmental factors for osteoporosis were assessed by a case-only design. Significant increases in osteoporosis risk were observed with minor alleles of rs2077647 located in the first exon and rs2234693 located in the first intron of estrogen receptor α (ESRα). Haplotype CC at these risk SNPs was strongly associated with osteoporosis risk (odds ratio [OR] =  3.15, 95% confidence interval [CI] = 1.83-5.41). There was a statistically significant interaction between haplotype CC and alcohol drinking; moderate alcohol consumption decreased genetic risk of osteoporosis (OR  =  0.22, 95%CI  =  0.05-0.83)., (Copyright © 2012 Orthopaedic Research Society.)

Background: In Japan, older adults are assessed by frailty checklist for care prevention. However, the effect of care prevention programs in community-dwelling frail older adults is still unclear., Objectives: The purpose of this study was to investigate whether the care prevention program would reduce care and disability and to measure its cost-effectiveness in frail older adults., Design: This is a prospective study using propensity score matching., Setting and Subjects: A total of 610 community-dwelling older adults were recruited in 2 cities of Japan., Intervention: Subjects in the exercise group (n = 305) attended physical exercise sessions once a week for 16 consecutive weeks. The exercise sessions were in a standardized format consisting of moderate-intensity aerobic exercise, progressive strength training, flexibility and balance exercises, and cool-down activities. The control group (n = 305) received only screening evaluation., Measurements: Primary outcome was long term care insurance requirement certification during the 1-year follow-up period. Secondary outcome measurements were changes of frailty checklist, and care and medical cost., Results: Twenty-five subjects (8.1%) in the exercise group and 55 (18%) in the control group were newly certified for long-term care insurance service requirement in 1 year after the intervention (RR = 2.16, 95% CI = 1.46-3.20). Consequently, the health care cost for the subjects in the exercise group was significantly lower than in the control group (P < .001). Moreover, subjects in the exercise group had significant improvements in total scores of the frailty checklist compared with the control group that worsened after 1 year (exercise group: from 7.41 ± 3.98 to 7.11 ± 4.00, control group: from 7.34 ± 4.27 to 8.02 ± 4.81, F = 12.84, P < .001)., Conclusion: These results suggested that physical exercise is effective in preventing the progression of frailty and further disability in older adults living in the community. We could save heath care costs by our care prevention program., (Copyright © 2012 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.)

Smartphones are very common devices in daily life that have a built-in tri-axial accelerometer. Similar to previously developed accelerometers, smartphones can be used to assess gait patterns. However, few gait analyses have been performed using smartphones, and their reliability and validity have not been evaluated yet. The purpose of this study was to evaluate the reliability and validity of a smartphone accelerometer. Thirty healthy young adults participated in this study. They walked 20 m at their preferred speeds, and their trunk accelerations were measured using a smartphone and a tri-axial accelerometer that was secured over the L3 spinous process. We developed a gait analysis application and installed it in the smartphone to measure the acceleration. After signal processing, we calculated the gait parameters of each measurement terminal: peak frequency (PF), root mean square (RMS), autocorrelation peak (AC), and coefficient of variance (CV) of the acceleration peak intervals. Remarkable consistency was observed in the test-retest reliability of all the gait parameter results obtained by the smartphone (p<0.001). All the gait parameter results obtained by the smartphone showed statistically significant and considerable correlations with the same parameter results obtained by the tri-axial accelerometer (PF r=0.99, RMS r=0.89, AC r=0.85, CV r=0.82; p<0.01). Our study indicates that the smartphone with gait analysis application used in this study has the capacity to quantify gait parameters with a degree of accuracy that is comparable to that of the tri-axial accelerometer.

Soy isoflavones and estrogen related genes may play a major role in the etiology of prostate cancer. This study examined whether the genetic polymorphisms of estrogen receptors (ESR-alpha and ESR-beta) and cytochrome P450 19A1 (CYP19A1) modified the protective effect of isoflavones against prostate cancer. One hundred and eighty cases and 177 controls were selected from three geographic areas of Japan. The odds ratio for more than or equal to 60 versus less than 60 mg/day of the intake of isoflavones was 0.63 (95% confidence interval=0.41-0.96). The TTTA long repeat was significantly associated with an increased risk (odds ratio=1.76, 95% confidence interval=1.15-5.70). The interaction between the polymorphisms and the intake of isoflavones on prostate cancer risk was analyzed by the multifactor dimensionality reduction method. The combination of the TTTA long repeats and the minor alleles of rs10046 in CYP19A1 and rs2077647 in ESR-alpha was a high risk for prostate cancer despite greater than or equal to 60 mg isoflavones/day. The combination of the TTTA short repeat and those homozygous for the major allele of rs10046 in CYP19A1 was low risk despite less than 60 mg isoflavones/day. In conclusion, the findings of this case-control study suggest that the protective effect of isoflavones may differ between the genotypes of estrogen related genes.

The traditional Japanese diet has been suggested by some researchers to be associated with a decreased risk of prostate cancer (PCa). In this paper, we assumed the following three characteristics of the traditional Japanese diet high in soybean products, high in fish, and low in red meat. Isoflavones, polyunsaturated long chain (n - 3) fatty acids, and saturated fatty acids were thought to be micronutrients in biological etiology relevant to soybean products, fish, and red meat, respectively. Analytical epidemiological studies on the risk of PCa were identified using the MEDLINE database from 1998 to 2007. Some published studies showed a negative association of soybean products and isoflavones to PCa risk, an inverse association for fish or polyunsaturated long chain (n - 3) fatty acids such as eicosapentaenic acid (EPA) and docosahexaenoic acid (DHA) with PCa risk, and a positive association of red meat or saturated fatty acids with PCa risk, respectively. In conclusion, although it is possible that the traditional Japanese diet may reduce the risk of PCa through a combination of characteristics such as being high in soybean products, high in fish, and low in red meat, further well-designed epidemiological studies such as nested case-control studies with nutritional analyses of blood samples are needed to confirm this association.

We examined associations between nutritional and other lifestyle factors and the prevalence of prostate cancer in a case-control study of Japanese men. Two hundred patients and 200 age-matched controls (+/-5 y) were selected from 3 geographic areas of Japan. BMI, physical activity, occupation, family history of prostate cancer, and medical history were not associated with prostate cancer risk. Isoflavones and their aglycones (genistein and daidzein) were significantly associated with decreased risk. The odds ratio for the highest category (> or = 89.9 mg/d) compared with the lowest category (<30.5 mg/d) of isoflavone intake was 0.42 (95% CI = 0.24-0.72) and the linear trend was significant (P < 0.01). PUFA, (n-6) fatty acids, and magnesium were significantly associated with decreased risk but not after adjustment for isoflavone intake. Isoflavone intake was correlated with the intake of PUFA (r = 0.68, P < 0.001), (n-6) fatty acids (r = 0.69, P < 0.001), and magnesium (r = 0.56, P < 0.001), because soy products contain high levels of these nutrients. On the other hand, isoflavone significantly decreased the risk of prostate cancer regardless of adjustment by PUFA, (n-6) fatty acids or magnesium. In conclusion, our findings indicate that isoflavones might be an effective dietary protective factor against prostate cancer in Japanese men.

Background/aims: Both the incidence of diabetes mellitus (DM) and mortality from Hepatocellular carcinoma (HCC) are increasing in Japan. As the association of overall cancer and HCC with impaired glucose tolerance (IGT) has been studied rarely in the world including Japan, this study assessed their associations using cohort data of Hokkaido, Japan., Methodology: After getting ethical consent, this study included 908 men and 1,081 women aged 30-77 years during 1977-78 and collected detailed information using the baseline survey. The subjects were followed until 2002 and deaths were recorded using ICD-9. Classifying them into three groups of diabetes status namely DM, IGT, and normal, the relative risk (RR) of mortality was estimated by diabetes status using multivariate Cox model., Results: This study revealed no association between overall cancer and diabetes status. However, the RR of mortality from HCC was about 11 times (HR= 10.8, 95%CI: 1.3-92.5) higher in IGT compared with normal group. DM group also showed higher risk of mortality than normal group., Conclusions: HCC mortality was significantly high among IGT group. However, as the results of the study were based on small data, further studies with large cohort are needed to address the association of IGT with overall cancer and HCC mortality in Japan.

In Japan, the number of kidney transplants for the patients with diabetic nephropathy is limited because of an extreme organ shortage and poor patient and graft survival rates. We analyzed the 5-year outcomes in kidney transplant recipients treated with tacrolimus with (group 1; n = 53) and without a diagnosis of diabetic nephropathy (group 2; n = 1432). We also investigated outcomes in patients who received simultaneous pancreas and kidney transplants since 2000 (group 3; n = 15). Patients in group 1 were older than those in group 2, with a shorter duration of pretransplant dialysis (P = .0001). Five-year patient survival rates in groups 1 and 2 were 89.7% and 97.9%, respectively (P = .13), and 5-year graft survival rates were 89.6% and 94.8%, respectively (P = .44). The incidence of acute rejection within 3 months of transplantation was 28.3% in group 1 and 29.2% in group 2 (P = .98). Tacrolimus-based induction therapy was used in 13 of the 15 group 3 cases. Both kidney and pancreas grafts are surviving to date in all but one of the group 3 patients; one patient had the pancreas removed due to venous thrombosis at 7 days. It was concluded that tacrolimus-based therapy resulted in excellent 5-year outcomes in patients who had kidney transplantation because of diabetic nephropathy, despite the higher risks associated with this condition. Tacrolimus was also beneficial in association with simultaneous pancreas and kidney transplantation. These data encourage us to perform kidney transplantation in patients with diabetic nephropathy.

Tacrolimus was approved in Japan in April 1996 for the prevention of allograft rejection in patients receiving kidney transplants. There has been a concern that immunosuppressive therapy may be associated with cardiovascular and metabolic complications, including hyperlipidemia, hypertension, and posttransplant diabetes mellitus. A multicenter (59 institutions) study was conducted in Japan in patients who underwent renal transplantation and received tacrolimus immunosuppression. Patients were followed for >5 years, from April 1996 to December 2002. Of the 1569 patients enrolled, 1542 were evaluated. In this analysis, graft survival rate and medication usage patterns of antihyperlipidemics, antihypertensives, insulin, and oral hypoglycemics were observed for >5 years in patients receiving tacrolimus immunosuppression. The graft survival rates of patients requiring antihyperlipidemic therapy and experiencing acute rejection were significantly lower compared with all other patients (P < .05). The risk of graft rejection was significantly greater in patients with cardiovascular complications requiring antihyperlipidemics or antihypertensives. Graft survival was significantly lower in patients with acute rejection and antihyperlipidemic therapy than in other patients.

The safety and efficacy of tacrolimus (Tac)-based immunosuppressive treatments were studied in 115 pediatric renal transplant recipients (mean follow-up period, approximately 20 months). The acute rejection rate was 22.7% 6 months after transplantation and the steroid-resistant acute rejection rate was 6.4%. The 5-year patient and graft survival rates were 98.6% and 95.9%, respectively. Major adverse effects included infection, ie, cytomegalovirus (CMV) antigenemia (41.7%), renal dysfunction (29.6%), and impaired glucose tolerance (20.9%). The incidences of these adverse events were significantly decreased among patients who had undergone transplantation after March 2000 (n = 43), namely, 30.2%, 18.6%, and 11.6%, respectively.

In Japan, living donor kidney transplantation accounts for about 80% of all kidney transplants. This is in contrast to the United States and Europe, where transplantation of organs from cadaveric or brain-dead donors is more common. This study analyzed the results of 5 years of experience with tacrolimus in Japan, focusing on the efficacy of the drug in improving patient and graft survival in patients who underwent transplantation with ABO-incompatible kidney grafts. Of the 1542 evaluable patients, 1281 patients received grafts from living donors. Of these, 177 patients received kidneys from ABO-incompatible donors and 981 patients received kidneys from ABO-compatible donors. Graft survival rates in ABO-incompatible recipients ranged from 90.7% at 1 year to 80.5% at 5 years. Subsequent graft survival rates in ABO-compatible recipients were 98.1% and 92.9%, respectively (P < .001 between groups). Patient survival rates at 5 years were 93.2% in ABO-incompatible recipients and 98.1% in ABO-compatible recipients. The rejection rate for kidneys from ABO-compatible donors was 27.8%, while for ABO-incompatible donors the rejection rate was 45.2%. The excellent outcome from this study demonstrates that even suboptimal ABO-incompatible donors can be used successfully as a source of kidneys when using tacrolimus as the immunosuppressive regimen. This may go some way to addressing the shortage of kidney donors in Japan.

Purposes: Recently in Japan, major depression, a depressive state, and suicide are increasingly becoming social problems requiring preventive intervention. However, only few investigations have been performed of actual conditions of mental health. The present study was therefore planned and carried out to examine relations between stress and relevant factors in adolescents and to search for clues for preventive intervention., Methods: A total of 184 students in a junior college in Hokkaido were the subjects of this cross-sectional survey. In October 2003, age, sex, health-related factors, social supports, stressors, loci of control, coping styles, and depressive status were investigated. After excluding data from incomplete responses, we ultimately analyzed 153 students (mean age = 19.9, 141 females)., Results: Regardless of the CES-D categorization, after conducting univariate logistic regression analysis, we found that cognitive style and consciousness of stress were significantly associated with depressive symptomatology. The association remained significant even after multivariate logistic regression analysis., Conclusions: Cognitive style may influence depression in adolescents. We now need to consider preventive interventions applying the theory of cognitive-behavioral therapy.

Recently the incidence rate of multiple myeloma (MM) has increased in Japan. Epidemiologic efforts have suggested that certain occupational and chemical exposures are likely to increase the risk for MM. We therefore performed a case-control study of MM, examining occupational factors. Data for 57 cases and 57 controls were obtained from Sapporo Medical University Hospital and its affiliated hospitals in Hokkaido. Controls were matched to each case by gender, age (+/- 5 years) and hospital. Detailed information regarding several factors possibly related to MM was obtained by interviews in hospitals. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated with adjustment for cigarette smoking as confounding factor. The occupational category of agriculture and fishery showed a significant association with increased risk (OR = 5.89, 95% CI = 1.24-28.04). Occupational exposure to chemical products including organic solvents or petroleum showed a significant association with increased risk (OR = 8.05, 95% CI = 1.01-64.45). Medical histories of operation for appendicitis and blood transfusion were associated with decreased risk, but not significantly. Our results suggested that occupational exposure to chemicals might play a role in the risk of MM.

Aim: Our aims were to evaluate the prevalence of bacterial vaginosis (BV), Chlamydia trachomatis (C. trachomatis) infection and Mobiluncus spp. infection among pregnant women in Otaru, Hokkaido, Japan according to the month and year of the first prenatal visit, and to evaluate their risk factors., Methods: Six thousand and eighty-three pregnant women who were seen consecutively at our hospital between 1993 and 2000, were enrolled in the study. Vaginal and endocervical swabs were subjected to Gram stain and detection of C. trachomatis. Univariate and multivariate methods were used to investigate the association between each infection and potential risk factors including age, gravidity, parity, history of dilatation and curettage (D & C), and history of natural abortion., Results: The annual rate of BV increased from 13.6% in 1993 to 21.4% in 2000. The annual rate of C. trachomatis infection was relatively constant. The prevalence of bacterial vaginosis, C. trachomatis infection and Mobiluncus spp. infection over the 8-year period was 18.2%, 4.2%, and 4.1%, respectively. The prevalence of the three infections was significantly higher among teenagers and among women with a history of D & C. The prevalence of C. trachomatis and Mobiluncus spp. infections was significantly higher among women with no history of delivery. BV was not associated with parity on multivariate analysis. The monthly prevalence of BV was significantly higher in May than in December, and the monthly prevalence of C. trachomatis infection was high in August., Conclusion: The differences in the annual and monthly infection patterns between BV and C. trachomatis infection suggest that the etiologies of the two infections differ.

Type 2 diabetes mellitus is a heterogeneous disorder, and the development of type 2 diabetes mellitus is associated with both insulin secretion defect and insulin resistance. The primary metabolic defect leading to type 2 diabetes mellitus has been thought to be varied among populations, especially in Japanese and Caucasians. Here, we have done the genome-wide scan for type 2 diabetes mellitus using 102 affected Japanese sib-pairs to identify the genetic factors predisposing to type 2 diabetes mellitus. Nonparametric linkage analysis showed one suggestive evidence for linkage to 11p13-p12 [D11S905: two-point maximum LOD score (MLS) of 2.89 and multipoint MLS of 2.32] and one nominally significant evidence for linkage to 6q15-q16 (D6S462: two-point MLS of 2.02). Interestingly, the 11p13-p12 region was reported to be a susceptibility locus for Japanese type 2 diabetes mellitus with suggestive evidence of linkage, and D11S905 was within 5 cM to D11S935 with the highest MLS in the previous linkage analysis reported. The only overlapped susceptibility region with suggestive evidence of linkage for Japanese type 2 diabetes mellitus was D11S935-D11S905 among the three reports including this study. These results taken together suggest that a susceptibility gene for type 2 diabetes mellitus in Japanese will reside in 11p13-p12.

Dietary factors are thought to be closely associated with the development of human cancers and hence numerous studies in this area have already been conducted in the United States and other Western countries. Comparatively few prospective studies have been published in Japan, especially for Hokkaido people. The present investigation was therefore performed to assess links between four leading cancers and some of the Japanese common dietary factors through a cohort study (1984-2002) in Hokkaido by analyzing 1,524 men and 1,634 women separately aged 40 and over. Adjusted Cox proportional hazard regression was used to calculate the relative risk (RR) for each dietary factor. For men, two dietary factors, miso soup (RR=0.2, 95% confidence interval (95%CI)=0.1-0.8) and pickled vegetables (RR=0.2, 95%CI=0.1-0.8) were associated with lower risk for stomach and colorectal cancer respectively. For women, three factors, namely salty confectionary (RR=3.5, 95%CI=1.1-10.9), black tea (RR=3.8, 95%CI=1.1-13.6), and carbonated drink/juice (RR=3.9, 95% CI=1.4-11.1) appeared related to an elevated risk of stomach cancer. However, further analysis simultaneously with all other adjusted factors indicated only carbonated drink/juice (RR=3.1, 95%CI=1.1-8.9) to present a significant risk factor for stomach cancer. One factor, namely wild edible plants (RR=3.3, 95%CI=1.1-9.8), increased the risk for colorectal cancer in women. None of the dietary components were significantly associated with lung or pancreatic cancers. This study also indicated a wide variation in the impact of dietary factors by sex and cancer site, in line with earlier work, pointing to a necessity for careful interpretation. Further epidemiological investigations by sex with more study subjects and confounding factors will be useful for determining the contribution of individual dietary factors to development of human cancers in Hokkaido, Japan.

Purpose: The purpose of this study was to determine health problems of citizens of the city of Obihiro with reference to the Healthy Japan 21 plan., Method: The subjects were a total of 2,000 men and women (6-74 years old) who were selected at random from the resident ledger of Obihiro. The questionnaire included the 6 fields (nutrient intake/dietary habits, physical activity/exercise, rest/mental health, tobacco, alcohol, dental health) of Healthy Japan 21. The path-analysis model was used by sex, in order to examine the relationship between lifestyle factors (dietary habits, restful sleep, stress, smoking habits, alcohol intake) and subjective health., Results: A total of 979 subjects (49.0%) responded. The items that showed a higher proportion than for all Japan were as follows: the proportions of persons who felt stress, required a drug or alcohol to sleep, drank heavily, and were female smokers. In questions about the harm caused to health by smoking, the following items showed lower awareness than deserved: bronchitis, gastric ulcer, problems with regard to pregnancy, and periodontitis. The following characteristics were found in the path-analysis: 1) If sleep rest is sufficient, subjective health is unaffected by stress in men and women; 2) Smoking affects dietary habits in men and women, especially in the latter; 3) Heavy smoking affects subjective health in men and women independent of whether dietary habits are good; 4) There is a positive relation between drinking and subjective health in women., Conclusion: This study showed that stress and smoking are problems for the health of citizens of the city of Obihiro, and suggested that the best measure to counter stress is sufficient sleep, while to counter smoking spread of knowledge about the harm to health caused by smoking is best.

The uranium solution in the precipitation tank in the JCO's uranium conversion facility was analyzed in order to evaluate the total number of fissions in the criticality accident. Two analytical groups at JAERI performed chemical analyses independently in order to check the validity of the results: the concentration of the fission products (95Zr, 99Mo, 103Ru, 131I, 140Ba, etc), uranium, boron and impurity elements in the solution. The analytical results obtained by the two groups were almost in agreement within the analytical error. The number of fissions per one gram of uranium in the accident was determined to be (1.5 +/- 0.1 ) x 10(14). Also, the total number of events was evaluated to be (2.5 +/- 0.1) x 10(18) fissions using the total amount of uranium (16.6 kg) fed into the precipitation tank at the accident.

The Role of Organ Transplant Network are the encouragement of the organ transplantation and fair organ sharing. Its principled are united, neutral open and nonprofit organization, so as to secure the fair and quick organ sharing based on the uniform allocation policy. Japan Kidney Transplant Network was established in 1995 nad reorganized into multi-organ sharing network, Japan Organ Transplant Network in 1997, when Japan Organ transplant Act was enacted. It consists of transplant coordinators, physicians, transplant surgeons, kidney banks, local administration, academic standings, other organization/associations and others. There are several committee, in which special subjects on organ transplantation and related matters are consulted, and review system in which each case is assessed and judged. And principal and essential items are decided by the board of members and then by the general assembly. The new computer system was introduced and registrants data are renewed every year, and recipient selection is done based on the latest registrants data. Standardized HLA examination tray was introduced and class II antigen was examined by means of DNA typing since 1997, which enabled more precise and accurate search. Hereafter, the education and encouragement of transplant coordinators to raise themselves and the more effective and extended distribution of donor cards are indispensable to promote organ donation/transplantation.

We analyzed the alteration of BRCA1 in DNA obtained from 83 individuals of 13 Japanese site-specific ovarian cancer families and 6 breast-ovarian cancer families. Six germline mutations were detected in 7 families, which consisted of 4 breast-ovarian cancer and 3 site-specific ovarian cancer families, by single-strand conformation polymorphism analysis, followed by direct sequence determination. The mutations included three frameshifts, two nonsense mutations, and one missense mutation causing loss of a zinc-binding motif. The frequency of loss of heterozygosity at the microsatellite markers on the BRCA1 gene was 57% (8 of 14 cases) in site-specific ovarian cancer families, and 100% (6 of 6 cases) in breast-ovarian cancer families. All tumors of the patients carrying a mutation of BRCA1 showed deletion of wild-type alleles, implicating BRCA1 as a tumor suppressor gene. These results suggest that germline mutations of the BRCA1 gene play an important role in the carcinogenesis of breast and/or ovarian cancer in a majority of breast-ovarian cancer families and in some site-specific ovarian cancer families.

A colorimetric test method using the microplate culture technique for the determination of susceptibility of Mycobacterium tuberculosis against antimycobacterial agents was developed and evaluated by the multicenter study. The test method utilizes an oxidation-reduction dye, 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC), as an indicator of mycobacterial growth. When compared to the presently available test method, some modifications were also included; lower inoculum density (10-fold dilution), inclusion of an inoculum diluted 1:100 as a growth control, and the preparation of inoculum preincubated in Middlebrook 7H9 broth and spectrophotometrically adjusted to McFarland #1 turbidity. The test method evaluated was highly precise and reliable to detect antimycobacterial resistances when the ATCC reference strains were tested. Also, the interpretations of the test result were highly comparable to those determined by the method of NCCLS M24-P, the % agreements ranging from 76.1% (ethambutol) to 91.3% (streptomycin). The test results were also comparable to those determined by Ogawa media; > 90% agreed with susceptible, intermediate, or resistant. The appearance of mycobacterial colonies on the test media was easily read, and the test results were more comparable to those of NCCLS M24-P. With these results, it can be concluded that the colorimetric microplate susceptibility test method described will be more suitable for clinical mycobacteriology laboratories.

Twenty-one patients with hepatocellular carcinoma (HCC) larger than 10 cm diameter were treated during the 18 year period from 1971 to 1988. The mean tumor size was 13 cm (range 10-18 cm). Nineteen patients (90.5%) had subjective symptoms. Eight patients (38.1%) had alpha-fetoprotein (AFP) levels over 10,000 ng/ml, and in 18 patients (85.7%) the levels were over 20 ng/ml. Nevertheless, only three (14.3%) were detected by AFP. Scintigraphy before 1981 and ultrasonography after 1982 appears to be most helpful for detection of HCC. Nineteen lesions (90.5%) were localized in the right hepatic lobe. Large HCC showed a low incidence of histologically verified concomitant cirrhosis (33%; 7 of 21) and a relatively well preserved hepatocellular function (indocyanine green test; 13.9 +/- 6.6%). Curative resection could be done for all 21 patients. There were three (14.3%) operative deaths. The 1-, 3-, and 5-year survival rates were 72.2, 32.9, and 8.2%, respectively. One patient who underwent a left hepatic lobectomy has survived for over 5 years, with recurrence. There were 14 recurrences (66.7%) in 21 patients: 11 were hepatic and three were in the lungs. In patients with large HCC, surgical resection should be done, provided the clinical status and hepatocellular reserves are adequate.

Three cases of spindle cell hemangioendothelioma were studied. Two had multiple nodules and the third had a single, recurrent lesion in the dermis or subcutis of the distal extremities. The tumor initiated at the age of 3 months in one patient and at the ages of 11 or 12 years in the remaining two. Local recurrence after surgical excision was observed in all cases. Microscopically the tumors were composed of two components; cavernous blood spaces and a proliferation of spindle cells. Among these spindle cells, there were occasional epithelioid endothelial cells with intracytoplasmic lumina. Phleboliths were observed in two cases. Most of the endothelial cells lining the cavernous spaces were positive for factor VIII-associated antigen in all cases; the intracytoplasmic lumina were also positive in two cases. The spindle cells were negative for that antigen in all cases. However, they were positive for desmin in one case. Electronmicroscopically, the spindle cells resembled primitive mesenchymal cells.

Four cases of mixed gonadal dysgenesis encountered in our institute are described here, and 65 cases of mixed gonadal dysgenesis in the Japanese literature, including our cases, are reviewed. Of the four cases reported here, three had a chromosomal structure of 46,XY and one of 45,XO/46,XYq-. A chromosomal structure of 45,XO/46,XY accounts for 35% of all cases of mixed gonadal dysgenesis reported in the Japanese literature, 46,XY for 31%, and other types for 24%. Two of our cases (50%) also had a gonadal tumor. The overall incidence of gonadal tumor occurring after onset of puberty and reported in the Japanese literature is 17%.

From September 1981 to December 1988, 163 patients underwent hepatic resection for hepatocellular carcinoma. The patients were divided into two groups: those operated on from September 1981 to March 1985 (n = 58) and those operated on from April 1985 to December 1988 (n = 105). There was an increase in the number of relatively small hepatocellular carcinomas in 1987-88. Differences in the incidence of accompanying liver cirrhosis (72 versus 62 per cent) were not statistically significant; however, values of the indocyanine green test (21.5 versus 17.0 per cent, P less than 0.01) aided in strict patient selection. In more recent years, initial hepatic hilar dissection for control of vascular structures was undertaken and an ultrasonic dissector was used in about three-quarters of these patients. Consequently, the mean estimated blood loss (2500 versus 1300 ml, P less than 0.001) and mean intraoperative blood replacement (2200 versus 560 ml, P less than 0.001) were significantly less than in the earlier period. Among the 58 patients treated in the early period, hospital morbidity and mortality rates were 52 and 29 per cent respectively. In contrast, the rates were 23.8 and 1.9 per cent respectively among the 105 patients operated on during the recent period (P less than 0.01). The decline in hospital mortality is attributed to the careful selection of patients, use of modern tools, and a diminished blood loss.

Clinical course and histological findings of 692 patients with bladder tumor were reviewed to reveal the statistics and clinical profile of carcinoma in situ and its related conditions in the urinary bladder. Primary papillary intraepithelial lesions were found in 83 cases (12.0%), whereas flat intraepithelial carcinoma was found in 16 cases (2.0%), 10 as primary and 6 as secondary tumors. In 35 cases (3.5%), the bladder lesion was flat and rather difficult to find by cystoscopy, and initially considered as chronic cystitis or flat carcinoma in situ. Post-operative histological diagnosis, however, revealed micro- or apparent invasion beyond the basement membrane. Thus they were tentatively classified as clinical carcinoma in situ. The result of the radical surgical treatments for the clinical carcinoma in situ was very poor with a rough 5-year survival of 19%. The management of primary or secondary flat intraepithelial carcinoma was carried out by radical surgery or bladder sparing operation followed by intravesical instillation of cytotoxic agents. The results of these procedures remain uncertain. Some confusion in terminology of carcinoma in situ is discussed and the term "flat carcinoma" was recommended to indicate carcinoma in situ and its related conditions.