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OBJECTIVE: Neoadjuvant chemotherapy (NAC) is essential for surgical downstaging of early-stage breast cancer, but taxane administration is associated with neuropathy. We investigated whether eribulin induces less neuropathy than paclitaxel. METHODS: In this multicentre, randomised study (UMIN000012817), patients diagnosed with invasive breast cancer between December 2013 and April 2016 were randomly assigned to group E (eribulin followed by fluorouracil, epirubicin, and cyclophosphamide; FEC) or group P (paclitaxel followed by FEC). The primary endpoint was incidence of grade 1 or higher peripheral neuropathy according to the Common Terminology Criteria for Adverse Events (CTCAE). Secondary endpoints were pathological complete response (pCR), clinical response, breast-conserving surgery, adverse events, disease-free survival (DFS), and patient neurotoxicity questionnaire (PNQ) analysis. RESULTS: One hundred and eighteen cases were analyzed for safety and 115 were evaluated for efficacy. Peripheral sensory neuropathy was significantly lower in group E after week 6, while peripheral motor neuropathy in group E was significantly lower at weeks 9, 12, and 15. pCR in groups E and P was 20.7% and 29.8% (P = .289), respectively, and clinical response was 55.2% and 77.2% (P = .017), respectively. Three-year DFS was 89.7% in group E and 86.0% in group P (P = .561). Neutropenia was more frequent and more severe in group E. PNQ was evaluated for 4 years, and item 1 (sensory) was consistently lower in group E. CONCLUSION: Neuropathy was significantly less frequent and less severe in patients who received eribulin compared with paclitaxel. Thus, eribulin could be a good alternative to paclitaxel in patients suffering severe neuropathy.

DOI： 10.1016/j.clbc.2022.08.007

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INTRODUCTION: β-ray strontium-89 (Sr-89) intra-irradiation therapy has been approved and clinically used to reduce bone metastasis pain not alleviated by bone-modifying agents, external radiation, and analgesic agents. We examined the efficacy of zoledronic acid (ZOL) and Sr-89 combination therapy compared with ZOL alone in breast cancer patients with bone metastases. MATERIALS AND METHODS: A randomized controlled trial was conducted on breast cancer patients with bone metastasis to compare the efficacy between ZOL monotherapy and ZOL plus Sr-89 combination therapy. The primary endpoints were changes in urinary NTX levels at 13 weeks and brief pain inventory scores. The secondary endpoints were analgesic drug usages, response rates, changes in bone metabolism markers, quality of life, and adverse event rates. RESULTS: Thirty of the planned 60 cases were randomly assigned to ZOL alone or ZOL + Sr-89. There were no significant differences in the changes in urinary NTX levels between the 2 groups (P = 0.365). There was no consistent difference in the pain score changes between the 2 groups. Sr-89 addition to ZOL slightly reduced the white blood cell and platelet counts. However, all adverse events were Grade 1. Safety and analgesic drug dose reduction were more evident in ZOL + Sr-89. CONCLUSION: This trial showed the lack of benefits from Sr-89 addition to ZOL for breast cancer patients with painful bone metastases. However, safety and analgesic drug dose reduction were more evident in ZOL + Sr-89, indicating its potential for pain control. Sr-89 therapy is safe, thus more effective radiopharmaceuticals are anticipated.

DOI： 10.1007/s00774-022-01366-y

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ctro.2022.09.005

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Because a relationship has been reported between masticatory behavior, obesity, and postprandial blood glucose, it is recommended to chew well and take a longer time to eat. The purpose of this study was to examine the possibility of changing masticatory behavior using a small ear-hung wearable chewing counter, which can monitor masticatory behavior without disturbing daily meals. In total, 235 healthy volunteers participated in a 4-wk randomized controlled trial and were divided into 3 groups. All participants were instructed about the importance of mastication at the first visit. During the intervention, group B used the chewing counter without an algorithm during each meal (notification of the number of chews after meal), and group C used the chewing counter with a masticatory behavior change algorithm (setting a target value and displaying the number of chews in real time). Group A was set as the control group. The number of chews and the meal time when consuming 1 rice ball (100 g) were measured before and after the intervention using the chewing counter, and the rate of change in these values was evaluated. Participants also provided a subjective evaluation of their changes in masticatory behavior. The number of chews and the meal time of 1 rice ball increased significantly in groups B and C compared with before the intervention, and the rate of change was significantly higher in group C than in group A and group B. In addition, the subjective evaluation of the change in the number of chews was highest in group C. Self-monitoring of masticatory behavior by providing a target value and the degree of achievement for the number of chews using a wearable chewing counter with a behavioral change algorithm could promote effective change in masticatory behavior and lead to an increased number of chews. (Trial ID: UMIN000034476)

DOI： 10.1177/00220345221118013

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BACKGROUND: The nationwide registry of the Japanese Gastric Cancer Association collected data of surgically resected cases of gastric cancer between 2001 and 2013. These retrospective analyses aimed to delineate tumor characteristics, surgical history, and survival distribution. METHODS: Data from 254,706 patients with primary gastric cancer were included. The 5-year survival rates were calculated for various subsets of prognostic factors. RESULTS: The number of patients over 70 years old increased from 2001 to 2013. The frequency with which laparoscopic gastrectomy was opted for increased dramatically (from 3.5 to 40.8%) in 13 years. We focused on the patients registered between 2010 and 2013, for whom data collection was based on the 3rd edition of the Japanese classification and guidelines. Five-year overall survival (OS) rate among 92,305 patients with resected tumors was 70.6%. The 5-year OS rates of patients with pathological stage IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV disease were 89.6%, 83.2%, 77.6%, 68.1%, 59.3%, 45.6%, 29.9%, and 14.0%, respectively. CONCLUSION: Our detailed analysis highlights the historical changes in outcomes of surgically treated gastric malignancies in Japan, and provides robust dataset for future analysis.

DOI： 10.1007/s10120-022-01317-6

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AIMS: Neuronal and glial inclusions comprising transactive response DNA-binding protein of 43 kDa (TDP-43) have been identified in the brains of patients with corticobasal degeneration (CBD), and a possible correlation between the presence of these inclusions and clinical phenotypes has been speculated. However, the significance of TDP-43 pathology in the pathomechanism of CBD has remained unclear. Here, we investigated the topographical relationship between TDP-43 inclusions and neuronal loss in CBD. METHODS: We estimated semi-quantitatively neuronal loss and TDP-43 pathology in the form of neuronal cytoplasmic inclusions (NCIs), astrocytic inclusions (AIs), oligodendroglial cytoplasmic inclusions (GCIs), and dystrophic neurites in 22 CNS regions in 10 patients with CBD. Then, the degree of correlation between the severity of neuronal loss and the quantity of each type of TDP-43 inclusion was assessed. We also investigated tau pathology in a similar manner. RESULTS: TDP-43 pathology was evident in nine patients. The putamen and globus pallidus were the regions most frequently affected (80%). NCIs were the most prominent form, and their quantity was significantly correlated with the severity of neuronal loss in more than half of the regions examined. The quantities of TDP-43 NCIs and tau NCIs were correlated in only a few regions. The number of regions where the quantities of TDP-43 AIs and GCIs were correlated with the severity of neuronal loss was apparently small in comparison with that of NCIs. CONCLUSIONS: TDP-43 alterations in neurons, not closely associated with tau pathology, may be involved in the pathomechanism underlying neuronal loss in CBD. There was a significant topographical correlation between neuronal cytoplasmic aggregation of TDP-43 and neuronal loss in CBD, suggesting that TDP-43 protein aberration might be associated with neuronal degeneration in CBD. There was no close correlation between the burden of TDP-43 and that of tau in neurons.

DOI： 10.1111/nan.12786

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BACKGROUND: It has been widely recognized that mastication behaviors are related to the health of the whole body and to lifestyle-related diseases. However, many studies were based on subjective questionnaires or were limited to small-scale research in the laboratory due to the lack of a device for measuring mastication behaviors during the daily meal objectively. Recently, a small wearable masticatory counter device, called bitescan (Sharp Co), for measuring masticatory behavior was developed. This wearable device is designed to assess objective masticatory behavior by being worn on the ear in daily life. OBJECTIVE: This study aimed to investigate the relation between mastication behaviors in the laboratory and in daily meals and to clarify the difference in mastication behaviors between those with metabolic syndrome (MetS) and those without (non-MetS) measured using a wearable device. METHODS: A total of 99 healthy volunteers (50 men and 49 women, mean age 36.4 [SD 11.7] years) participated in this study. The mastication behaviors (ie, number of chews and bites, number of chews per bite, and chewing rate) were measured using a wearable ear-hung device. Mastication behaviors while eating a rice ball (100 g) in the laboratory and during usual meals for an entire day were monitored, and the daily energy intake was calculated. Participants' abdominal circumference, fasting glucose concentration, blood pressure, and serum lipids were also measured. Mastication behaviors in the laboratory and during meals for 1 entire day were compared. The participants were divided into 2 groups using the Japanese criteria for MetS (positive/negative for MetS or each MetS component), and mastication behaviors were compared. RESULTS: Mastication behaviors in the laboratory and during daily meals were significantly correlated (number of chews r=0.36; P<.001; number of bites r=0.49; P<.001; number of chews per bite r=0.33; P=.001; and chewing rate r=0.51; P<.001). Although a positive correlation was observed between the number of chews during the 1-day meals and energy intake (r=0.26, P=.009), the number of chews per calorie ingested was negatively correlated with energy intake (r=-0.32, P=.002). Of the 99 participants, 8 fit the criteria for MetS and 14 for pre-MetS. The number of chews and bites for a rice ball in the pre-MetS(+) group was significantly lower than the pre-MetS(-) group (P=.02 and P=.04, respectively). Additionally, scores for the positive abdominal circumference and hypertension subgroups were also less than the counterpart groups (P=.004 and P=.01 for chews, P=.006 and P=.02 for bites, respectively). The number of chews and bites for an entire day in the hypertension subgroup were significantly lower than in the other groups (P=.02 and P=.006). Furthermore, the positive abdominal circumference and hypertension subgroups showed lower numbers of chews per calorie ingested for 1-day meals (P=.03 and P=.02, respectively). CONCLUSIONS: These results suggest a relationship between masticatory behaviors in the laboratory and those during daily meals and that masticatory behaviors are associated with MetS and MetS components. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry R000034453; https://tinyurl.com/mwzrhrua.

DOI： 10.2196/30789

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Numerous studies have evaluated the relationship between eating behavior and obesity, however few studies have objectively assessed eating behavior. Additionally, the association of masticatory behaviors with masticatory performance remains unclear. This study aimed to verify the relationship between masticatory performance and behavior measured by a wearable masticatory counter, and BMI. 365 healthy adults participated. Mastication behaviors, i.e. number of chews and bites, chewing rate, and chewing time, were measured using wearable masticatory counter while consuming one rice ball (100 g). Masticatory performance was evaluated using testing gummy jelly. Lifestyle habits including exercise, walking, and breakfast, were surveyed by questionnaire. The correlation coefficients between masticatory behaviors and performance and BMI were analyzed. Furthermore, multiple regression analysis was performed. The number of chews showed positive correlation with chewing rate, number of bites and chewing time, but no correlation with masticatory performance. BMI had weak but significant negative correlation with number of chews, bites, chewing time, and masticatory performance, but had no correlation with chewing rate. Multiple regression analysis revealed that BMI was associated with sex, age, number of chews, bites, masticatory performance, and walking speed. In conclusion, masticatory behavior and performance were not interrelated, but both were independently associated with BMI weakly.

DOI： 10.1038/s41598-022-08084-5

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BACKGROUND: Ultrathin bioresorbable polymer sirolimus-eluting stents (BP-SESs) may easily lead to acute recoil. This study investigated acute recoil after BP-SES implantation on the basis of intravascular ultrasound (IVUS). METHODS: We enrolled 40 consecutive stents. Absolute acute recoil by quantitative coronary angiography was defined as the difference between the mean diameter of the last inflated balloon (X) and mean lumen diameter of the BP-SES immediately after balloon deflation (Y). Percent (%) acute recoil was defined as (X-Y)×100/X. IVUS was performed within the culprit lesion. Plaque eccentricity, % plaque burden and calcification grade score were assessed using IVUS. Calcification grade was scored on the basis of quadrants. On the basis of the median acute recoil value of 5.0%, the stents were divided into two groups: low (LAR, n = 20) and high % acute recoil (HAR, n = 20). RESULTS: Mean % acute recoil was 5.8 ± 5.3%. Plaque eccentricity, % plaque burden and stent/artery ratio were significantly higher in the HAR group than in the LAR group. Significant differences in % acute recoil were not observed regarding the types of stent diameter. In multivariate logistic regression and multiple linear regression analysis, plaque eccentricity and % plaque burden in the culprit plaque were significant positive predictors for the occurrence of % acute recoil. No significant differences, including clinical outcomes, were found between both groups at follow-up. CONCLUSION: Acute recoil of BP-SESs may be influenced by an eccentric plaque with a large burden, which did not affect long-term outcomes. However, the present study might suggest the proper strategy (e.g. a more exhaustive plaque preparation) before BP-SES implantation in a case with these IVUS characteristics.

DOI： 10.1097/MCA.0000000000001067

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Background: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. Methods: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. Results: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB. Conclusion: Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

DOI： 10.1177/17588359221119538

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AIMS: Although shortening of the corrected QT interval (QTc) is a key finding in the diagnosis of short QT syndrome (SQTS), there may be overlap of the QTc between SQTS patients and normal subjects in childhood and adolescence. We aimed to investigate electrocardiographic findings for differentiation of SQTS patients. METHODS AND RESULTS: The SQTS group comprised 34 SQTS patients <20 years old, including 9 from our institutions and 25 from previous reports. The control group comprised 61 apparently healthy subjects with an QTc of <360 ms who were selected from 13 314 participants in a school-based screening programme. We compared electrocardiographic findings, including QT and Jpoint-Tpeak intervals (QT and J-Tpeak, respectively), those corrected by using the Bazett's and Fridericia's formulae (cB and cF, respectively) and early repolarization (ER) between the groups. QT, QTc by using Bazett's formula (QTcB), QTc by using Fridericia's formula (QTcF), J-Tpeak, J-Tpeak cB, and J-Tpeak cF were significantly shorter in the SQTS group than in the control group. On receiver operating characteristic curve analysis, the area under the curve (AUC) was largest for QTcB (0.888) among QT, QTcB, and QTcF, with a cut-off value of 316 ms (sensitivity: 79.4% and specificity: 96.7%). The AUC was largest for J-Tpeak cB (0.848) among J-Tpeak, J-Tpeak cB, and J-Tpeak cF, with a cut-off value of 181 ms (sensitivity: 80.8% and specificity: 91.8%). Early repolarization was found more frequently in the SQTS group than in the control group (67% vs. 23%, P = 0.001). CONCLUSION: A QTcB <316 ms, J-Tpeak cB < 181 ms, and the presence of ER may indicate SQTS patients in childhood and adolescence.

DOI： 10.1093/europace/euab097

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DOI： 10.1186/s40478-021-01217-3

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DOI： 10.2196/preprints.30789

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DOI： 10.1186/s40478-021-01202-w

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BACKGROUND: The National Clinical Database (NCD) nationwide registry program of gastric cancer started in 2018. The purpose of this study was to report the treatment results of the NCD registry in the form of treatment results of the real world in Japan. METHODS: Patients' characteristics, tumor features, treatments, and outcomes were collected using a web-based data entry system. We analyzed the initial NCD database for data on surgically treated gastric cancer patients in 2011. RESULTS: A total of 30,257 patients with malignant gastric tumors were enrolled by the NCD registry program from 501 hospitals in all 47 prefectures. Of these, the status of data entry was not approved in 8.8% of the registered data, and follow-up information was missing in 1.2% of the approved cases. Excluding 1777 cases, which were not resected for primary gastric cancer, 25,306 resected cases included 44.4% of stomach surgeries recorded in the NCD. The 5 year survival rate of the resected cases was 71.3% and the operative mortality rate was 0.41%. The stage-specific 5 year survival rates were as follows: 89.6% for stage IA, 83.8% for stage IB, 77.3% for stage IIA, 69.1% for stage IIB, 58.7% for stage IIIA, 44.1% for stage IIIB, 30.1% for stage IIIC, and 13.4% for stage IV. CONCLUSIONS: The NCD gastric cancer registry program demonstrated validity for database construction. The gastric cancer registry is expected to become a nationwide registry with the dissemination of data entry system and method in the NCD.

DOI： 10.1007/s10120-021-01178-5

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PURPOSE: To evaluate the accuracy of various claims-based definitions of diabetes-related complications (coronary artery disease [CAD], heart failure, cerebrovascular disease and dialysis). METHODS: We evaluated data on 1379 inpatients who received care at the Niigata University Medical & Dental Hospital in September 2018. Manual electronic medical chart reviews were conducted for all patients with regard to diabetes-related complications and were used as the gold standard. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each claims-based definition associated with diabetes-related complications based on Diagnosis Procedure Combination (DPC), International Classification of Diseases, Tenth Revision (ICD-10) codes, procedure codes and medication codes were calculated. RESULTS: DPC-based definitions had higher sensitivity, specificity, and PPV than ICD-10 code definitions for CAD and cerebrovascular disease, with sensitivity of 0.963-1.000 and 0.905-0.952, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. Sensitivity, specificity, and PPV were high using procedure codes for CAD and dialysis, with sensitivity of 0.963 and 1.000, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. DPC and/or ICD-10 codes + medication were better for heart failure than the ICD-10 code definition, with sensitivity of 0.933, specificity of 1.000, and PPV of 1.000. The PPVs were lower than 60% for all diabetes-related complications using ICD-10 codes only. CONCLUSION: The DPC-based definitions for CAD and cerebrovascular disease, procedure codes for CAD and dialysis, and DPC or ICD-10 codes with medication codes for heart failure could accurately identify these diabetes-related complications from claims databases.

DOI： 10.1002/pds.5213

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BACKGROUND/AIM: We evaluated the impact of the relative dose intensity (RDI) of neoadjuvant chemotherapy (NAC) on the survival of patients with breast cancer (BC). PATIENTS AND METHODS: This randomized phase II trial included 188 patients with human epidermal growth factor receptor 2 (HER2)-negative BC treated with anthracycline followed by paclitaxel as NAC. We grouped patients using a relative dose intensity (RDI) threshold of 85% and evaluated clinicopathological features and clinical outcomes. RESULTS: The 5-year overall survival rate was 91.2% and 76.3%, when RDI ≥85% and <85%, respectively (p=0.015). Age, tumor, and node status, and the RDI were significantly different on univariate analysis, but not on multivariate analysis. An exploratory subgroup analysis revealed that a low RDI was associated with low overall survival of patients with obesity, T1/2 disease, and lymph node metastases. CONCLUSION: Maintaining the RDI of NAC is crucial for achieving the survival benefit in selected patients with HER2-negative BC.

DOI： 10.21873/anticanres.14863

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Amyloid β-proteins (Aβs) Aβ1-42 and Aβ1-43 are converted via two product lines of γ-secretase to Aβ1-38 and Aβ1-40. This parallel stepwise processing model of γ-secretase predicts that Aβ1-42 and Aβ1-43, and Aβ1-38 and Aβ1-40 are proportional to each other, respectively. To obtain further insight into the mechanisms of parenchymal Aβ deposition, these four Aβ species were quantified in insoluble fractions of human brains (Brodmann areas 9 to 11) at various Braak senile plaque (SP) stages, using specific enzyme-linked immunosorbent assays. With advancing SP stages, the amounts of deposited Aβ1-43 in the brain increased proportionally to those of Aβ1-42. Similarly, the amounts of deposited Aβ1-38 correlated with those of Aβ1-40. Surprisingly, the ratios of deposited Aβ1-38/Aβ1-42 and Aβ1-40/Aβ1-43 were proportional and discriminated the Braak SP stages accurately. This result indicates that the generation of Aβ1-38 and Aβ1-40 decreased and the generation of Aβ1-42 and Aβ1-43 increased with advancing SP stages. Thus, Aβs deposition might depend on γ-secretase activity, as it does in the cerebrospinal fluid. Here, the extracted γ-secretase from Alzheimer disease brains generates an amount of Aβ1-42 and Aβ1-43 compared with cognitively normal brains. This refractory γ-secretase localized in detergent-solubilized fractions from brain cortices. But activity modulated γ-secretase, which decreases Aβ1-42 and Aβ1-43 in the cerebrospinal fluid, localized in detergent-insoluble fractions. These drastic alterations reflect Aβ situation in Alzheimer disease brains.

DOI： 10.1016/j.ajpath.2020.02.009

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BACKGROUND: No guidelines are available for defining the extent of lymph node (LN) dissection in patients with remnant gastric carcinoma (RGC). Hence, this retrospective study aimed to determine the optimal extent of LN dissection in patients with RGC. METHODS: We retrospectively evaluated the therapeutic outcomes of node dissection for RGC from a nationwide registry. When the metastatic rate or 5-year survival rate exceeded 10%, dissection was recommended. We calculated the dissection index by multiplying the incidence of metastasis at that nodal station by the 5-year survival rate of patients with metastasis at the station. A dissection index of > 1.0 was considered significant. RESULTS: We included 1133 patients with RGC (T2-T4 tumor) who had undergone distal gastrectomy as the primary surgery for the evaluation of the survival benefit of nodal dissection. Any regional node station was considered significant. When the primary surgery was for malignant disease, the index was high for Nos. 3 (10.2), 7 (9.5), 1 (7.1), and 9 (8.0) nodes. For nodes at the splenic hilum, the index value was 4.4, which was higher than that for the perigastric nodes (Nos. 4sa and 4sb). The index for No. 10 nodes was the highest (10.5) when tumors involved a greater curvature. CONCLUSIONS: The therapeutic strategy for RGC remains the same, regardless of the histology of the primary disease during the initial surgery. Total gastrectomy and dissection of the perigastric LNs (Nos. 1-4), suprapancreatic LNs (Nos. 7-9 and 11), and LNs at the splenic hilum (No. 10) are justified.

DOI： 10.1007/s10120-020-01081-5

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BackgroundAlthough the incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. An international study reported higher survival in Korea and Japan than other countries, including the US. We examined the determinant factors of the high survival in Japan, compared with the US.MethodsWe analysed data on 78,648 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007 and compared them with 16,722 cases from the Surveillance, Epidemiology, and End Results Program (SEER), a US population-based cancer registry data from 2004-2010. We estimated five-year relative survival and applied a multivariate excess hazard model to compare the two countries, considering the effect of number of lymph nodes (LNs) examined.ResultsFive-year relative survival in Japan was 81.0%, compared with 45.0% in the US. After controlling for confounding factors, we still observed significantly higher survival in Japan. Among N2 patients, a higher number of LNs examined showed better survival in both countries. Among N3 patients, the relationship between number of LNs examined and differences in survival between the two countries disappeared.ConclusionAlthough the wide differences in GC survival between Japan and US can be largely explained by differences in the stage at diagnosis, the number of LNs examined may also help to explain the gaps between two countries, which is related to stage migration.

DOI： 10.2188/jea.JE20190351

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BACKGROUND: The proportion of elderly patients undergoing surgery for gastric cancer is increasing. However, limited number of therapeutic outcomes in the elderly has been reported. Here we examined the surgical results based on a nationwide survey of elderly patients who underwent surgery for Stage I gastric cancer. METHODS: Data from 68,353 Stage I patients who underwent gastrectomy between 2001 and 2007 were retrospectively collected. The accumulated data were reviewed and analyzed by the Japanese Gastric Cancer Association registration committee. We first classified the patients as those aged ≤ 74 years and ≥ 75 years. We further classified those patients aged ≥ 75 years into groups by 5-year increments to examine their short- and long-term postoperative outcomes. RESULTS: Patients aged ≥ 75 years accounted for 46.5%. The 30-day mortality rate was < 0.7% for any age group, but for those aged ≥ 75 years, the 60-day and 90-day mortality rates were 0.9-2.3% and 1.2-5.1%, respectively. An examination of long-term survival indicated that, as the class of age increased, the 5-year overall survival (OS) was 47.0-93.1% and disease-specific survival (DSS) was 91.4-98.2%, respectively. Although high DSS rates of ≥ 90% were found for all age groups, OS only accounted for ≤ 82% of patients aged ≥ 75 years. CONCLUSION: Among elderly patients with Stage I gastric cancer, deaths due to other diseases were frequently observed in the long term. Thus, for elderly patients, it may be appropriate to reconsider the treatment strategy with respect to the balance between the invasiveness of the treatment and the prognosis.

DOI： 10.1007/s10120-019-01000-3

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BACKGROUND: Parechovirus-A3 (PeV-A3) and the enteroviruses (EVs) are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants; however, differences in the clinical presentations of two infections are not well described. OBJECTIVES: To describe the clinical presentations of PeV-A3- and EVs-related diseases and develop a novel scoring system to differentiate two diseases. STUDY DESIGN: This prospective study used real-time PCR and genetic sequencing to evaluate viral etiologies of febrile neonates and infants <4 months with suspected sepsis or meningoencephalitis in Niigata area, Japan, in 2014-2016. The clinical manifestations of PeV-A3- and EVs-infected patients were compared, and a novel scoring system was developed after identifying the most distinguishable clinical findings, followed by the external cohort validation. RESULTS: In 210 patients evaluated, we identified 56 PeV-A3-infected (27%) and 43 EVs-infected (20%) patients. The following clinical manifestations were significant in PeV-A3-infected patients, as compared with EVs-infected patients; a higher body temperature (38.9°C vs. 38.5°C, P < .01) and heart rate (181/min vs. 168/min, P = .01), cold extremities (72% vs. 34%, P < .01) and skin mottling (65% vs. 23%, P < .01), lower white blood cell count (5,200/μL vs. 8,900/μL, P < .01) and incidence of cerebrospinal fluid (CSF) pleocytosis (2% vs. 63%, P < .01). Using some of these significant findings, the scoring system successfully distinguished the diseases (accuracy: 86% and 83% for the derivative and external validation cohorts, respectively). CONCLUSIONS: We found significant clinical manifestations in PeV-A3-infected patients compared to EVs-infected patients. The scoring system may be helpful to distinguish two infections, especially at onset of outbreak.

DOI： 10.1016/j.jcv.2019.104256

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OBJECTIVE: The pallidonigroluysian (PNL) system, the primary component of corticosubcortical circuits, is generally spared in amyotrophic lateral sclerosis (ALS). We evaluated the clinicopathological features of an unusual form of ALS with PNL degeneration (PNLD) and assessed whether ALS with PNLD represents a distinct ALS subtype. METHODS: From a cohort of 97 autopsied cases of sporadic ALS with phosphorylated 43kDa TAR DNA-binding protein (TDP-43) inclusions, we selected those with PNLD and analyzed their clinicopathological features. RESULTS: Eleven cases (11%) that showed PNLD were divided into 2 subtypes depending on the lesion distribution: (1) extensive type (n = 6), showing widespread TDP-43 pathology and multisystem degeneration, both involving the PNL system; and (2) limited type (n = 5), showing selective PNL and motor system involvement, thus being unclassifiable in terms of Brettschneider's staging or Nishihira's typing of ALS. The limited type showed a younger age at onset and predominant PNLD that accounted for the early development of extrapyramidal signs. The limited type exhibited the heaviest pathology in the subthalamus and external globus pallidus, suggesting that TDP-43 inclusions propagated via indirect or hyperdirect pathways, unlike ALS without PNLD, where the direct pathway is considered to convey TDP-43 aggregates from the cerebral cortex to the substantia nigra. INTERPRETATION: The PNL system can be involved in the disease process of ALS, either nonselectively as part of multisystem degeneration, or selectively. ALS with selective involvement of the PNL and motor systems exhibits unique clinicopathological features and TDP-43 propagation routes, thus representing a distinct subtype of ALS. ANN NEUROL 2020;87:302-312.

DOI： 10.1002/ana.25652

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BACKGROUND: In China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) differ in terms of multiple primary cancer (MPC) and male-to-female sex ratio (MFSR). METHODS: We studied site-specific variation in familial cancer by comparing family history (FH), MPC, age at onset (AO), and MFSR among 8768 patients with ESCC/GCA. RESULTS: ESCC/GCA patients with a positive FH are associated with a significantly higher rate of MPC and a younger AO than those without (sex-specifically: MPC 1.6% vs. 0.7%, P<0.01 and 3.2% vs. 0.8%, P<0.01; AO 53.1 ± 8.1 vs. 54.5 ± 8.2, P=0.000 and 52.9 ± 7.4 vs. 54.0 ± 8.0, P=0.005). Among patients with a positive FH, MPC decreases significantly from upper-, middle-, and lower-third ESCC to GCA (sex-specifically: 53.6%, 1.8%, 1.6%, 0.8%, P=0.000; and 71.4%, 1.5%, 2.2%, 1.6%, P=0.000). From MPC, upper-, middle-, and lower-third ESCC to GCA, AO increased sex-specifically: 51.9 ± 7.2, 52.8 ± 7.9, 52.1 ± 8.3, 54.3 ± 8.4, 55.6 ± 7.6 (P=0.000) and 49.3 ± 6.5, 51.8 ± 9.8, 52.6 ± 7.8, 54.4 ± 8.0, 55.7 ± 7.2 (P=0.000), and FH decreased: 43.8%, 35.1%, 28.2%, 29.5%, 24.4% (P=0.000) and 55.2%, 26.7%, 25.0%, 24.3%, 22.3% (P=0.000). The preponderance of males, smoking, alcohol consumption, and patients ≥50 years old increased from 2.2:1, 1.7:1, 1.0:1, 2.0:1 in ESCC to 6.1:1, 2.8:1, 2.5:1, 4.0:1 in GCA, yet more MPCs were associated with non-preponderant than preponderant counterparts; particularly in GCA, the difference was statistically significant. CONCLUSION: The proportion of familial cancer may decrease from upper-, middle-, and lower-third ESCC to GCA. This entails molecular investigation, and appreciating this may help us devise a better screening strategy or individualize cancer treatment.

DOI： 10.3389/fonc.2020.579379

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Aim: Olaparib monotherapy improves progression-free survival in patients with metastatic breast cancer and BRCA1/2 mutations. We evaluated the cost-effectiveness of BRCA1/2 mutation profiling to target olaparib use. Methods: A Markov cohort model was generated to compare the 5-year cost-effectiveness of BRCA1/2 mutation profiling to target olaparib use. Results: The incremental cost-effectiveness ratio of BRCA1/2 mutation profiling plus olaparib monotherapy was JPY14,677,259/quality-adjusted life year (QALY) (US$131,047/QALY), compared with standard chemotherapy alone. Conclusion:BRCA1/2 mutation profiling to target olaparib use is not a cost-effective strategy for metastatic breast cancer. The strategy provides minimal incremental benefit at a high incremental cost per QALY. Hence, further cost reductions in the cost of both BRCA1/2 mutation profiling and olaparib are required.

DOI： 10.2217/pme-2018-0141

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BACKGROUND/AIM: Risk factors for chemotherapy-induced nausea and vomiting (CINV) with anthracycline-containing regimen for breast cancer patients remain unknown. The risk factors for CINV with FEC100 were investigated. PATIENTS AND METHODS: Data on CINV events and patient backgrounds of 180 patients were collected from the first cycle of FEC100 treatment. In this regimen, patients were administered various antiemetics (ADs). The combinations of ADs were classified into four categories, while body mass index (BMI) was stratified into three categories. Risk factors were selected based on patient characteristics and combination of ADs. Risks for CINV were analyzed by univariate and multivariate analyses. RESULTS: In the univariate analysis of nausea, BMI was a significant factor, while BMI and combination of ADs were significant in vomiting. In the multivariate analysis concerning nausea, BMI was a significant factor. In the analysis concerning vomiting, the combination of ADs and BMI were significant. CONCLUSION: BMI was the most important risk factor for nausea and vomiting, while the combination of ADs was for vomiting.

DOI： 10.21873/anticanres.13596

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Background: Current practice guidelines recommend the use of ultrasound (US) as an initial surveillance tool for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. Patients with liver cirrhosis, however, frequently have coarse liver parenchyma, masking the presence of tiny nodules during B-mode US. Contrast-enhanced US (CEUS) with Sonazoid has a long-lasting, stable Kupffer phase, which makes it possible to scan the entire liver to depict small lesions. In addition, defect reperfusion imaging (reinjection imaging) enables to determine whether the detected nodule is HCC or not. This prospective, multicenter, randomized, controlled trial was conducted to demonstrate the usefulness of Kupffer phase surveillance in the detection of small HCC compared to B-mode US. Methods: A total of 23 institutions joined this study. In total, 656 patients with hepatitis B- or C-related liver cirrhosis were randomized either to the B-mode US surveillance group (n = 313) or the Kupffer phase CEUS with Sonazoid surveillance group (n = 309). The primary endpoint was the maximum size of HCC at the time of the first detection. Secondary endpoints included time to HCC detection, number of tumors, and Barcelona Clinic Liver Cancer stage at the first detection, and sensitivity, specificity, and accuracy of each method in the diagnosis, and the cumulative detection rate of HCC. Results: The mean HCC size at the first detection was significantly smaller in the CEUS (13.0 ± 4.1 mm; n = 28) than in the B-mode US group (16.7 ± 4.1 mm; n = 26) (p = 0.011). Of the 38 patients with HCV cirrhosis diagnosed with HCC by US alone, mean tumor size at the first detection was significantly smaller in the 20 patients diagnosed by CEUS alone than in the 18 diagnosed by B-mode US alone (12.7 ± 3.1 vs. 17.6 ± 7.0 mm, p = 0.012). In contrast, among the 16 patients with HBV cirrhosis diagnosed by US alone, mean tumor size at the first detection was similar in the 8 patients diagnosed by CEUS alone and the 8 diagnosed by B-mode US (13.6 ± 6.0 vs. 14.5 ± 2.7 mm, p = 0.715). Conclusion: Kupffer phase CEUS surveillance with Sonazoid is extremely useful for the early detection and confirmation of HCC using a reinjection technique. Kupffer phase CEUS with Sonazoid contrast combined with the reinjection technique is, therefore, recommended as first-line screening tool for HCC in patients with liver cirrhosis, especially those with very coarse liver parenchyma.

DOI： 10.1159/000501082

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Background: Surgical stress and inflammation can cause hyperbilirubinemia, which sometimes occurs after esophagectomy for esophageal cancer (EC). The aim of this study was to elucidate the clinical significance of postoperative hyperbilirubinemia in the management of EC patients. Materials and methods: We retrospectively reviewed records of 81 EC patients who underwent esophagectomy from 2009 to 2014. We compared the clinicopathological and perioperative factors, including the presence of hyperbilirubinemia (total bilirubin ≥1.5 mg/dL), between patients with postoperative infectious complications (PIC group) and those without (Non-PIC group). Results: PIC developed in 52 patients (64.2%). There were significant differences in incidence of postoperative hyperbilirubinemia between the PIC group and the non-PIC group (34.6% vs. 3.4%, P = 0.002), as well as the approach of esophagectomy (P = 0.045), the surgical duration (469 vs. 389 min, P < 0.001), the amount of blood loss (420 vs. 300 mL, P = 0.018), the frequency of intraoperative blood transfusions (32.7% vs. 6.9%, P = 0.012) and the peak postoperative C-reactive protein level (17.3 vs. 8.6 mg/dL, P = 0.007). Multivariate analysis revealed hyperbilirubinemia was independently associated with the occurrence of PICs (odds ratio: 38.6, P = 0.010). The median time to the diagnosis of hyperbilirubinemia was significantly shorter than that of PICs (3.0 vs. 4.5 days, P = 0.025). Conclusions: Postoperative hyperbilirubinemia was associated with the occurrence of PICs and frequently occurred before any PICs become apparent. More attention should be paid to the serum bilirubin level in the management after esophagectomy for EC.

DOI： 10.1016/j.amsu.2019.02.004

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DOI： 10.1016/j.jelectrocard.2018.12.008

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PURPOSE: Clinical evidence demonstrating the effectiveness of systemic therapy for advanced salivary duct carcinoma (SDC) is lacking because of the disease's rarity. We assessed the efficacy and toxicity of trastuzumab plus docetaxel in patients with locally advanced and/or recurrent or metastatic human epidermal growth factor receptor 2-positive SDC. PATIENTS AND METHODS: This was a single-center, single-arm, open-label, phase II study in Japan. The patients received trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Docetaxel 70 mg/m2 was administrated every 3 weeks. The primary end point was the overall response rate; the secondary end points included the clinical benefit rate, progression-free survival, overall survival, and toxicity. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry (Identification No. UMIN000009437). RESULTS: Fifty-seven eligible patients with SDC were enrolled. The overall response rate was 70.2% (95% CI, 56.6% to 81.6%), and the clinical benefit rate was 84.2% (95% CI, 72.1% to 92.5%). Median progression-free and overall survival times were 8.9 months (95% CI, 7.8 to 9.9 months) and 39.7 months (95% CI, not reached), respectively. The most frequent adverse event was anemia (52 patients [91%]), followed by a decreased WBC count (51 patients [89%]) and neutropenia (50 patients [88%]). The most frequently observed grade 4 adverse event was a decreased neutrophil count (34 patients [60%]). Grade 3 febrile neutropenia was reported in eight patients (14%). No grade 2 or greater adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred. CONCLUSION: Our data show encouraging efficacy of trastuzumab plus docetaxel therapy in patients with human epidermal growth factor receptor 2-positive SDC, with a manageable toxicity profile.

DOI： 10.1200/JCO.18.00545

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DOI： 10.1097/MD.0000000000013907

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© 2019 Tohoku University Medical Press. Acetaldehyde is a potential carcinogen for esophageal cancer, and some oral microorganisms produce acetaldehyde from ethanol or glucose. In this prospective study, we examined the influence of professional oral care on acetaldehyde levels in mouth air of esophageal cancer patients. Acetaldehyde concentrations in mouth air and breath were measured by a portable gas chromatograph, and acetaldehyde production from oral microbiota was also evaluated. Samples were taken from 21 esophageal cancer patients (median age 68 years) and 20 age-matched healthy volunteers (control group) before and after oral care. Postoperative samples were also taken from 17 patients who had undergone surgery. All samples (mouth air, breath, and saliva) were collected 2 to 3 hours after lunch. Oral microbial samples were prepared from saliva. Genotype analysis of alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes revealed no significant differences in the genotypes between the two groups. In the control group, acetaldehyde levels in mouth air showed no significant changes after oral care, while the amount of microbial acetaldehyde production from ethanol was significantly decreased. By contrast, among the patients, acetaldehyde levels in mouth air were significantly decreased after oral care and after operation, while the amount of microbial acetaldehyde production from ethanol showed no significant changes. Moreover, microbial acetaldehyde production from glucose was significantly decreased after operation. Overall, oral health was poorer in the patient group. In conclusion, professional oral care for esophageal cancer patients is effective for reducing acetaldehyde levels in mouth air due to the reduction of microbial count.

DOI： 10.1620/tjem.249.75

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PURPOSE: Although chronic low back pain (CLBP) has profound effects on patients, society, and economy, its causes are difficult to identify. Psychogenic effects or social stress is known to affect CLBP; hence, investigation of its underlying causes requires a multifactorial approach. We determined the factors associated with CLBP by using an Internet-based survey. To prevent CLBP, we need to understand its cause and background. PATIENTS AND METHODS: A total of 1000 participants either with (+) or without (-) CLBP answered the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), which assesses five domains of CLBP: low back pain, lumbar function, walking ability, social life function and mental health. We also administered a new questionnaire for participants, that comprised five different domains: Body, Lifestyle, Emotion, Diet, and Social. To evaluate psychogenic effects on CLBP, we added two original factors, namely outshout and HIE, which have not yet been studied. HIE is a traditional concept (sense) of "feeling cold" or "chilly." All participants completed both questionnaires. RESULTS: Multivariate logistic regression analysis extracted four factors (sleep, room temperature, outshout, and HIE) that were associated with CLBP. The mental health domain was assessed using the JOABPEQ for each of these factors. The factors outshout and HIE differed between CLBP (+) and CLBP (-) patients. CLBP (-) participants also showed a difference in Sleep and HIE factors. CONCLUSION: Among psychogenic effects, Emotion was common to all the four extracted factors. There was no common physical divisor. Therefore, we hypothesized that acute low back pain might develop into CLBP in the presence of psychological stress or other emotional factors such as outshout or HIE. Hence, we need to consider both physical and psychogenic effects in the prevention and treatment of CLBP. Furthermore, appropriate evaluation and treatment of psychological stress may be effective in reducing CLBP.

DOI： 10.2147/JPR.S223190

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nature Publishing Group  

Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome. EGFR active mutations, i.e., those involving exon 19 deletion or an L858R point mutation, were seen in 43% of patients. Some differences in driver gene mutation prevalence were observed between the Japanese cohort described in the present study and the TCGA. Japanese cohort had significantly more genomic alterations in cell cycle pathway, i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or RB1, were associated with worse clinical outcome in patients with EGFR active mutations. Our data support the utility of comprehensive sequencing to detect concurrent genomic variations that may affect clinical outcomes in this disease.

DOI： 10.1038/s41598-017-18560-y

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Language：Japanese   Publisher：(一社)日本医療情報学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Background: Hemodialysis patients in Japan are aging, but the influence of lifestyle factors on EuroQoL 5-Dimension 5-Level (EQ-5D-5 L) scores in older hemodialysis patients is unclear. This study aimed to measure health-related quality of life using the EQ-5D-5 L for older hemodialysis patients and to identify the lifestyle factors affecting EQ-5D-5 L scores in Japan. Methods: Outpatients aged 65 years or older who had been receiving maintenance hemodialysis for more than 5 years were selected to determine their EQ-5D-5 L scores. Multiple linear regression analysis was applied to identify items affecting the EQ-5D-5 L scores. Results: The response rate was 59.7% (748/1251), after excluding 9 patients who did not fulfill the participation criteria, and we analyzed data from 739 patients (462 men, 277 women) aged 72.9 ± 6.5 years (mean ± standard deviation) with a mean duration of hemodialysis of 15.1 ± 8.8 years. The mean EQ-5D-5 L score was 0.738 ± 0.207. Higher Hospital Anxiety and Depression Scale scores (regression coefficient, −0.467
P &lt
0.001), reduced walking ability (−0.201
P &lt
0.001), duration of hemodialysis (−0.175
P &lt
0.001), age (−0.143
P &lt
0.001), and subjective symptoms (−0.128
P &lt
0.001) showed significant negative correlations with the EQ-5D-5 L score. Conclusions: Reduced walking ability, and Anxiety and Depression, were associated with lower EQ-5D-5 L score and appeared to be important factors in decreasing health for older hemodialysis patients. These results suggest that patients’ families and dialysis facility staff should be trained in early detection of depression and that patients should maintain their walking ability by exercise therapy.

DOI： 10.1016/j.archger.2018.06.006

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OBJECTIVES: While Japan has socioeconomic issues, such as income inequality, little is known about the association between socioeconomic factors and the risk of unintentional childhood injuries. The purpose of the study was to evaluate the influence of socioeconomic factors on the risk for unintentional injuries among preschool children in Japan. DESIGN: Cross-sectional study using data from a web-based questionnaire survey. SETTING: Japan (January 2015). PARTICIPANTS: 1000 households with preschool children under 6 years of age. OUTCOME MEASURES: Multivariate logistic regression was performed to analyse the influence of socioeconomic factors on the incidence of unintentional injuries. RESULTS: Overall, 976 households were eligible for the analysis, with 201 households reporting unintentional injuries. The incidence rates for unintentional injury were estimated to be constant across all strata constructed using combinations of socioeconomic factors. The multivariate logistic regression analysis showed no significant differences in socioeconomic factors between households that reported unintentional injuries and those that did not. CONCLUSION: The findings of our study demonstrated that unintentional injuries among preschool children occurred at approximately fixed rates, independent of socioeconomic factors. Accordingly, prevention strategies for unintentional injuries that concern socioeconomic disadvantages should be avoided in Japan.

DOI： 10.1136/bmjopen-2018-021621

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PURPOSE: To validate the safety and efficacy of percutaneous radiofrequency ablation (RFA) of breast carcinomas. METHODS: This retrospective study was conducted by the Breast Cancer Society for Minimally Invasive Therapy following approval from institutional review boards, and with the written informed consent of patients. A total of 386 patients with breast cancer treated with RFA at 10 institutions between July 2003 and June 2009 were identified and included in the analysis. Patients underwent a standard RFA procedure with ultrasound guidance and were followed up every 6 to 12 months. In this study, feasibility of RFA procedure and related safety and ipsilateral breast tumor recurrence (IBTR) were examined. Fisher exact or χ2 test evaluated associations between clinicopathological factors and IBTR, and local recurrence-free survival was estimated using the Kaplan-Meier method. RESULTS: RFA-related adverse events included local pain in 9 patients, skin burns in 15, and nipple retraction in 7. Patients were followed for a median of 50 months. IBTR was more frequently observed in patients with initial tumor sizes > 2 cm (3 of 30, 10%) than in those with initial tumors ≤ 2 cm (8 of 355, 2.3%; P = .015). IBTR-free rates 5 years after RFA were 97%, 94%, and 87% in patients with initial tumor sizes ≤ 1.0 cm, 1.1 to 2.0 cm, and > 2.0 cm, respectively. CONCLUSIONS: RFA in breast cancer is a safe and promising minimally invasive treatment for tumors ≤ 2 cm in diameter. Further studies are needed to optimize the technique and evaluate its future role as local therapy.

DOI： 10.1016/j.clbc.2017.09.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Ltd  

Background: Long-term changes of trabecular microstructure in human tooth extraction socket have not been investigated. Purpose: To examine the trabecular microstructure of human residual ridges at various intervals following tooth extraction, and to determine whether bone remodeling activity can attain points of relative stability and when such points are reached. Materials and Methods: Forty-four bone biopsy specimens were obtained from lower molar or premolar regions of residual ridges. Postextraction times ranged from 1.6 to 360 months. Samples were analyzed using micro-computed tomography and three-dimensional bone morphometry with histological analyses. Trabecular bone parameters were plotted against postextraction times, and a stepwise piecewise linear regression analysis was performed to determine at which points of time these parameters either increased or decreased. Results: Using piecewise linear regression, “inflection points” were found in most trabecular bone parameters between 7 and 12 months postextraction. Among the residual ridge samples, woven trabecular structure became mature, consisting of thick lamellar trabeculae with sufficient bone density, under dynamic bone remodeling until the 7th to 12th month post-tooth extraction. After this period, the mature network structure remained stable with low remodeling activity. Conclusion: Bone remodeling of trabecular structure in human residual ridge after tooth extraction had a stabilization period.

DOI： 10.1111/cid.12591

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer New York LLC  

Background: Lung squamous cell carcinoma (LSCC) is a major histological subtype of lung cancer. In this study, we investigated genomic alterations in LSCC and evaluated the clinical implications of mutation burden (MB) in LSCC. Methods: Genomic alterations were determined in Japanese patients with LSCC (N = 67) using next-generation sequencing of 415 known cancer genes. MB was defined as the number of non-synonymous mutations per 1 Mbp. Programmed death-ligand 1 (PD-L1) protein expression in cancer cells was evaluated by immunohistochemical analysis. Results: TP53 gene mutations were the most common alteration (n = 51/67, 76.1%), followed by gene alterations in cyclin-dependent kinase inhibitor 2B (CDKN2B
35.8%), CDKN2A (31.3%), phosphatase and tensin homolog (30.0%), and sex-determining region Y-box 2 (SOX2, 28.3%). Histological differentiation was significantly poorer in tumors with high MB (greater than or equal to the median MB) compared with that in tumors with low MB (less than the median MB
p = 0.0446). The high MB group had more tumors located in the upper or middle lobe than tumors located in the lower lobe (p = 0.0019). Moreover, cancers in the upper or middle lobes had significantly higher MB than cancers in the lower lobes (p = 0.0005), and tended to show higher PD-L1 protein expression (p = 0.0573). SOX2 and tyrosine kinase non-receptor 2 amplifications were associated with high MB (p = 0.0065 and p = 0.0010, respectively). Conclusions: The MB level differed according to the tumor location in LSCC, suggesting that the location of cancer development may influence the genomic background of the tumor.

DOI： 10.1245/s10434-018-6401-1

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BACKGROUND: Hepatic arterial infusion chemotherapy plus sorafenib in phase 2 trials has shown favourable tumour control and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. However, no randomised phase 3 trial has tested the combination of sorafenib with continuous arterial infusion chemotherapy. We aimed to compare continuous hepatic arterial infusion chemotherapy plus sorafenib with sorafenib alone in patients with advanced, unresectable hepatocellular carcinoma. METHODS: We did an open-label, randomised, phase 3 trial (SILIUS) at 31 sites in Japan. Eligible patients were aged 20 years or older, with advanced hepatocellular carcinoma not suitable for resection, local ablation, or transarterial chemoembolisation; Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Child-Pugh score 7 or lower; and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) via an interactive web response system with a computer-generated sequence to receive 400 mg sorafenib orally twice daily or 400 mg sorafenib orally twice daily plus hepatic arterial infusion chemotherapy (cisplatin 20 mg/m2 on days 1 and 8 and fluorouracil 330 mg/m2 continuously on days 1-5 and 8-12 of every 28-day cycle via an implanted catheter system). The primary endpoint was overall survival. The primary efficacy analysis comprised all randomised patients (the intention-to-treat population), and the safety analysis comprised all randomised patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01214343. FINDINGS: Between Nov 4, 2010, and June 10, 2014, 206 patients were randomly assigned (103 to the sorafenib group, 103 to the sorafenib plus hepatic arterial infusion chemotherapy group). One patient in the sorafenib plus hepatic arterial infusion chemotherapy group withdrew after randomisation. Median overall survival was similar in the sorafenib plus hepatic arterial infusion chemotherapy (n=102) and sorafenib monotherapy (n=103) groups (11·8 months [95% CI 9·1-14·5] vs 11·5 months [8·2-14·8]; hazard ratio 1·009 [95% CI 0·743-1·371]; p=0·955). Grade 3-4 adverse events that were more frequent in the sorafenib plus hepatic arterial infusion chemotherapy group than in the sorafenib monotherapy group included anaemia (15 [17%] of 88 vs six [6%] of 102), neutropenia (15 [17%] vs one [1%]), thrombocytopenia (30 [34%] vs 12 [12%]), and anorexia (12 [14%] vs six [6%]). INTERPRETATION: Addition of hepatic arterial infusion chemotherapy to sorafenib did not significantly improve overall survival in patients with advanced hepatocellular carcinoma. FUNDING: Japanese Ministry of Health, Labour and Welfare.

DOI： 10.1016/S2468-1253(18)30078-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Academic Press Inc.  

Background: Diagnostic imaging is important for predicting the pathological response to chemotherapy during neoadjuvant chemotherapy (NAC) and for considering the surgical management with appropriate resection after NAC. This study was performed to examine the accuracy of the present radiological imaging for predicting the pathological complete response (pCR). Methods: From 188 patients in our previous JONIE1 Study, a randomized controlled trial comparing chemotherapy with and without zoledronic acid for patients with human epidermal growth factor receptor 2-negative breast cancer, we evaluated 122 patients whose tumor size was examined by magnetic resonance imaging or ultrasound at three points: before NAC
after administering fluorouracil, epirubicin, and cyclophosphamide
and after NAC. The maximum tumor diameter was evaluated by magnetic resonance imaging or ultrasound. Tumor reduction ratios were calculated at the same three points. The association between the radiological clinical response and the pCR was examined. Results: Among the 122 patients evaluated, there were 98 and 24 patients with luminal (Lum) and triple-negative (TN) subtypes, respectively. There were no patients who showed tumor progression after treatment. The radiological size of the tumors was finally reduced by an average of 58.4%. Clinical complete response and pCR were achieved in 22 (18.0%) and 15 (12.3%) patients, respectively. In the overall population (n = 122), the accuracy, sensitivity, and specificity for predicting pCR were 86.1%, 88.8%, and 66.7%, respectively. The negative predictive value and false-negative rate were 45.5% and 11.2%, respectively. According to subtypes, the accuracies were 83.7% and 95.8% in Lum and TN, respectively. Negative predictive value and false-negative rate were markedly different between the Lum (29.4% and 13.5%) and TN subtypes (100% and 0%), respectively. Conclusions: This randomized clinical trial demonstrated that NAC was safe for operable breast cancer patients with appropriate radiological monitoring. Radiological evaluation after NAC may be a reliable method for predicting pathological response in the TN subtype, but not in the Lum subtype.

DOI： 10.1016/j.jss.2017.12.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 healthcare facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these healthcare facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a web-based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility-specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the “presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)”, the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility-specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4,962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2,237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1,171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480 and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively
those with type 2 diabetes were shown to be significantly older (median [interquartile range], 77.0 [68.0–83.0]) than those with type 1 diabetes (54.0 [41.0–67.0]) (P &lt
 0.001)
and the BMI was shown to be significantly higher for those with type 2 diabetes (22.0 [19.5–24.8] kg/m2) than for those with type 1 diabetes (21.3 [18.9–24.0] kg/m2) (P = 0.003). It was also found that the median estimated glomerular filtration rate (eGFR) was significantly lower among those with type 2 diabetes (50.6 mL [31.8–71.1]/min/1.73 m2) than among those with type 1 diabetes (73.3 [53.5–91.1] mL/min/1.73 m2) (P &lt
 0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3–8.1)% among all patients examined, 7.5 (6.9–8.6)% among those with type 1 diabetes, and 6.8 (6.1–7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes (P &lt
 0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [SUs]) (60.8%), SUs (159 insulin-naïve patients) (33.1%), and no insulin preparations or SUs (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment-related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia not only through education on hypoglycemia but through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia.

DOI： 10.1111/jdi.12790

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

Background: A combination of assays for the presence of serum anti-Helicobacter pylori IgG antibody (HPA) and serum pepsinogen (PG) concentrations can be used to screen for gastric cancer risk. In Japan, this “ABC method” is considered an effective means of stratifying gastric cancer risk. This study aimed to ascertain its cost-effectiveness for assessing gastric cancer risk. Methods: A Markov model was constructed to compare the cost-effectiveness of two strategies for gastric cancer-risk screening over a 30-year period: the ABC method, which uses a combination of assessing the presence of HPA and measuring serum PG concentrations and scheduling endoscopies accordingly, and annual endoscopic screening. Clinical and epidemiological data on variables in the model were obtained from published reports. Analyses were made from the perspective of the Japanese health care payer. Results: According to base-case analysis, the ABC method cost less than annual endoscopic screening (64,489 vs. 64,074 USD) and saved more lives (18.16 vs. 18.30 quality-adjusted life years). One-way analyses confirmed the robustness of the cost-effectiveness results. The probability that the ABC method is cost-effective in Japanese individuals aged 50 years was 0.997. Conclusions: A combination of HPA and serum PG assays, plus scheduling endoscopy accordingly, is a cost-effective method of screening for gastric cancer risk in Japan.

DOI： 10.1007/s10198-017-0901-y

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Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 health-care facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these health-care facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a Web-based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility-specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the "presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)", the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility-specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480, and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively; those with type 2 diabetes were shown to be significantly older [median (interquartile range), 77.0 (68.0-83.0)] than those with type 1 diabetes [54.0 (41.0-67.0)] (P < 0.001); and the BMI was shown to be significantly higher for those with type 2 diabetes [22.0 (19.5-24.8) kg/m2] than for those with type 1 diabetes [21.3 (18.9-24.0) kg/m2] (P = 0.003). It was also found that the median estimated glomerular filtration rate (eGFR) was significantly lower among those with type 2 diabetes [50.6 mL (31.8-71.1)/min/1.73 m2] than among those with type 1 diabetes [73.3 (53.5-91.1) mL/min/1.73 m2] (P < 0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3-8.1)% among all patients examined, 7.5 (6.9-8.6)% among those with type 1 diabetes, and 6.8 (6.1-7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes (P < 0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent, and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [SUs]) (60.8%), SUs (159 insulin-naïve patients) (33.1%), and no insulin preparations or SUs (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment-related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia, not only through education on hypoglycemia but also through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia.

DOI： 10.1007/s13340-018-0346-2

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BACKGROUND: Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. METHODS: A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. RESULTS: The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005-2.245 for CEA; HR 2.088, 95% CI 1.457-2.901 for CA15-3). CONCLUSIONS: These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

DOI： 10.1186/s12957-018-1325-6

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Purpose: The therapeutic effect of systemic treatment for breast cancer (BC) generally depends on its intrinsic subtypes. In addition, tumor infiltrating lymphocytes (TILs) are considered to be an independent factor for tumor shrinkage and disease prognosis. High TILs at baseline or after primary systemic chemotherapy are reported to be associated with better survival in triple-negative or human epithelial growth factor receptor 2 (HER2)-positive BCs. However, the prognostic value of TILs in estrogen receptor (ER)-positive and HER2-negative (ER+/HER2−) BC is still controversial. Methods: We assessed TIL score (low, intermediate, and high) before and after primary systemic chemotherapy in every subtype of BC, and compared the clinical outcomes. Biopsy specimens of 47 triple-negative, 58 HER2+ and 91 ER+/HER2− BCs were used to assess TILs before treatment. To assess TILs after treatment, we examined residual invasive carcinoma in surgically resected samples of 28 triple-negative, 30 HER2+ and 80 ER+/HER2− BCs. Results: A high TIL score in triple-negative BC before treatment resulted in a significantly higher proportion of pathological complete response (pCR). In contrast, ER+/HER2− BC exhibited fewer instances of pCR than other subtypes. Although not statistically significant, ER+/HER2− cases with a high TIL score also tended to achieve pCR (p = 0.088). Moreover, we revealed that low TIL BCs after chemotherapy, but not at baseline, had significantly better relapse-free survival in ER+/HER2− BC (p = 0.034). Conclusion: Pathological examination of TILs after treatment may be a surrogate marker for prognosis in ER+/HER2− BC.

DOI： 10.1007/s10549-017-4575-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Ltd  

Complete response (CR) after treatment for multiple myeloma is associated with superior progression-free survival (PFS). Multiple myeloma patients were prospectively recruited for induction treatment with bortezomib and dexamethasone (BD) followed by autologous hematopoietic cell transplantation (auto-HCT) between 2010 and 2012. If patients did not achieve CR after auto-HCT, BD consolidation therapy was added to target CR. After the BD induction phase (n = 46), greater than or equal to CR was achieved in 4 patients (8%). After auto-HCT (n = 34), greater than or equal to CR was achieved in 9 patients (20%) and very good partial response (VGPR) was achieved in 11 (24%). Of the 24 patients who received auto-HCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses. Finally, the maximum response with or without BD consolidation was greater than or equal to CR in 19 (41%), VGPR in 7 (15%), and PR in 6 (13%). Through BD consolidation, CR was achieved in 8 of 11 patients with post-HCT VGPR and in 2 of 12 patients with post-HCT PR. In total, 4 year PFS and overall survival were 43 and 80%, respectively. After adjusting for clinical factors, there was no difference in PFS between CR patients after auto-HCT and BD consolidation, while patients with less than or equal to VGPR after consolidation had a significantly lower PFS. Patients with post-HCT CR showed good PFS, and targeting CR through BD consolidation could improve the CR rate. It would be worthwhile to prospectively compare the efficacy of consolidation only for patients who failed to achieve CR to a universal consolidation strategy.

DOI： 10.1002/hon.2452

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Background: The aim of this retrospective study was to investigate the tumor characteristics, surgical details, and survival distribution of surgically resected cases of gastric cancer from the nationwide registry of the Japanese Gastric Cancer Association. Methods: Data from 118,367 patients with primary gastric carcinoma who underwent resection between 2001 and 2007 were included in the survival analyses. The 5-year survival rates were calculated for various subsets of prognostic factors. Results: The median age of the patients was 67 years. The proportions of patients with pathological stage (Japanese Gastric Cancer Association) IA, IB, II, IIIA, IIIB, and IV disease were 44.0%, 14.7%, 11.7%, 9.5%, 5.0%, and 12.4% respectively. The death rate within 30 days of operation was 0.5%. The 5-year overall survival rate in the 118,367 patients who were treated by resection was 71.1%. The 5-year overall survival rates of patients with pathological stage IA, IB, II, IIIA, IIIB, and IV disease were 91.5%, 83.6%, 70.6%, 53.6%, 34.8%, and 16.4% respectively. The 5-year disease-specific survival rates in the patients with pT1 (mucosa) disease after D1+ dissection of lymph node station no. 7 (D1 + α), D1+ dissection of lymph node station nos. 7, 8, and 9 (D1+ β), and D2 lymphadenectomy were 99.4%, 99.6%, and 99.1% respectively. The 5-year disease-specific survival rates in the patients with pT1 (submucosa) disease after D1 + α, D1 + β, and D2 lymphadenectomy were 97.3%, 98.1%, and 96.9% respectively. Conclusion: Detailed analyses of the data from more than 100,000 patients show the recent trends of the outcomes of gastric cancer treatment in Japan and provide baseline information for use by medical communities around world.

DOI： 10.1007/s10120-017-0716-7

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Purpose The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. Methods We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (\1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of \12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Findings Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of \3,870,077, resulting in an incremental cost-effectiveness ratio of \43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was &gt
\12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Implications Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival time and adverse event in advanced gastric cancer therapy, are needed.

DOI： 10.1016/j.clinthera.2017.10.017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background: A randomized phase 2 trial in women with HER2-negative breast cancer has shown that adding zoledronic acid (ZOL) to neoadjuvant chemotherapy (CT) has potential anticancer benefits in postmenopausal and triple-negative (TN) breast cancer patients. We report the data for the secondary end point of disease-free survival (DFS).
Methods: Patients were randomly assigned to receive CT or CT + ZOL (CT-Z). All patients received four cycles of FEC100 followed by 12 cycles of paclitaxel weekly. ZOL (4 mg) was administered 3-4 times weekly for 7 wk to the CT-Z group patients. The primary end point was pathologic complete response (pCR). The secondary end points were the clinical response rates, rate of breast-conserving surgery, safety, and DFS.
Results: Of the 188 patients enrolled, 95 were assigned to the CT group and 93 to the CT-Z group. DFS and overall survival were analyzed in 92 and 88 patients with the mean times of 5.15 y and 5.38 y, respectively. The 3-y DFS rate was 84.6% in the CT group and 90.8% in the CT-Z group (P = 0.188). The particular benefit from ZOL for the neoadjuvant CT seen as improvement of the pCR rate was indicated in the 3-y DFS period for TN cancer cases (CT versus CT-Z: 70.6% versus 94.1%) but not for postmenopausal cases.
Conclusions: ZOL did not improve DFS when combined with CT. However, the improvement of the pCR rate translated to survival outcomes in TN breast cancer. The short-term application of ZOL may not be sufficient to improve the outcome in postmenopausal patients. (C) 2017 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jss.2017.05.066

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In the original publication, the article category was published as "Review Article". The correct category should read as "Original Article".

DOI： 10.1007/s00595-017-1589-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IMPACT JOURNALS LLC  

Objectives: Anti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing.
Materials and methods: A total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway (PTEN and PIK3CA). Patients whose tumors had no alterations in these 12 genes, theoretically considered to respond to anti-EGFR therapy, were defined as "all wild-type", while remaining patients were defined as "mutant-type".
Results: Fifty-six patients (28%) and 145 patients (72%) had RCRC and LCRC, respectively. Regarding genetic alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) with RCRC were "all wild-type" compared with 41 of 145 patients (28%) with LCRC (P = 0.009). Among the 49 patients who received anti-EGFR therapy, RCRC showed significantly worse progression-free survival (PFS) than LCRC (P = 0.022), and "mutant-type" RCRC showed significantly worse PFS compared with "all wild-type" LCRC (P = 0.004).
Conclusions: RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy compared with LCRC. Furthermore, our data shows primary tumor sidedness is a surrogate for the non-random distribution of genetic alterations in CRC.

DOI： 10.18632/oncotarget.20510

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Language：Japanese   Publisher：(一社)日本医療情報学会  

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PurposeLymphangioleiomyomatosis is a rare lung disease caused by proliferation of abnormal smooth muscle-like cells and typically occurs in premenopausal women. Sirolimus is now the first-line drug for the treatment of lymphangioleiomyomatosis. Sirolimus-induced stomatitis is the most frequent adverse event experienced during treatment. To identify risk factors, we investigated the association of stomatitis incidence with patient background data and treatment parameters, using data from the multicenter long-term sirolimus trial.
MethodsSubjects received sirolimus for 2years at doses adjusted to maintain a trough blood level of 5 to 15ng/mL. The incidence of stomatitis was correlated with baseline demographics, clinical characteristics, and changes in the longitudinal data. Risk factors at baseline were assessed by using univariate and multivariate analyses.
ResultsThe most frequent adverse event was stomatitis, with the cumulative rate reaching 88.9% by 9months, higher than that reported in postrenal transplant patients. The repetition, the duration, and the severity of stomatitis events were variable among patients. We found that patients with low hemoglobin (Hb) (&lt;14.5g/dL) showed significantly higher incidence than those with high Hb (14.5g/dL, P&lt;.01). The cumulative rate for stomatitis incidence was significantly associated with a decrease in the mean corpuscular volume, while the Hb level was constant; thus, red blood cell count in patients increased during the study.
ConclusionsBaseline Hb levels and a decrease in mean corpuscular volume during treatment were correlated with the incidence of stomatitis.

DOI： 10.1002/pds.4259

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Intertumoral heterogeneity represents a significant hurdle to identifying optimized targeted therapies in gastric cancer (GC). To realize precision medicine for GC patients, an actionable gene alteration-based molecular classification that directly associates GCs with targeted therapies is needed.& para;& para;Methods: A total of 207 Japanese patients with GC were included in this study. Formalin-fixed, paraffin-embedded (FFPE) tum or tissues were obtained from surgical or biopsy specimens and were subjected, to DMA extraction. We generated comprehensive genomic profiling data using a 435-gene panel including 69 actionable genes paired, with US Food and Drug Administration-approved targeted therapies, and the evaluation o f Epstein-Barr virus (EBV) infection and microsatellite instability (MSI) status.& para;& para;Results: Comprehensive genomic sequencing detected at least one alteration o f 435 cancer-related genes in 194 GCs (93.7%) and o f 69 actionable genes in 141 GCs (68.1%). We classified the 207 GCs into four The Cancer Genome Atlas (TCGA) subtypes using the genomic profiling data; EBV (N = 9), MSI (N = 17), chromosomal instability (N = 119), and genomicaliy stable subtype (N = 62). Actionable gene alterations were not specific and were widely observed throughout all TCGA subtypes. To discover a novel classification which more precisely selects candidates for targeted therapies, 207 GCs were classified using hypermutated. phenotype and the mutation profile of 69 actionable genes. We identified a hypermutated group (N = 32), while the others (N = 175) were sub-divided into six dusters including five with actionable gene alterations: ERBB2 (N = 25), CDKN2A, and CDKN2B (N = 10), KRAS (N = 10), BRCA2 (N = 9), and ATM duster (N = 12). The clinical utility of this classification was demonstrated by a case of unresectable GC. with a remarkable response to anti-HER2 therapy in the ERBB2 duster.& para;& para;Conclusions: This actionable gene-based classification creates a framework for further studies for realizing precision medicine in GC.

DOI： 10.1186/s13073-017-0484-3

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It has been well established that maximum standardized uptake value (SUVmax) for F-18-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p&lt;0.0001), but there was no significant association between pMAPK expression levels and SUVmax levels. Multivariable analysis showed that a high geminin level (odds ratio: 6.497, 95% confidence interval: 2.427-19.202, p = 0.0001) and large tumor size (6.438, 2.224-20.946, p = 0.0005) were significantly and independently associate d with SUVmax-high. Univariable but not multivariable analysis indicated that Ki67-high significantly correlated with SUVmax-high. Twenty of 23 (87.0%) breast cancers with tumor size &gt;2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers &lt;= 2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67-high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53.

DOI： 10.1371/journal.pone.0184508

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Background The use of absorbable sutures in wound closure has been shown to reduce the incidence of surgical site infection (SSI); however, there is no evidence that the intra-abdominal use of absorbable rather than silk sutures reduces the incidence of SSI after gastrointestinal surgery. We report the findings of a phase II trial, designed to evaluate the impact of the intra-abdominal use of absorbable sutures on the incidence of SSI.
Methods At 19 Japanese hospitals, 1147 patients undergoing elective gastrectomy, colorectal surgery, hepatectomy, or pancreaticoduodenectomy (PD) were randomly assigned to absorbable or silk intra-abdominal suture groups. The primary efficacy endpoint was the incidence of SSI. The secondary efficacy endpoints were the locations of SSI, time to resolution of SSI, length of hospital stay, and the incidence of bile leakage in hepatectomy and pancreatic fistula.
Results The incidence of SSI was 11.3%, 15.5%, 11.3%, and 36.9% after gastrectomy, colorectal surgery, hepatectomy, and PD, respectively. The incidence of SSI was higher in the absorbable suture group than in the silk suture group for all the surgical procedures, but the difference was not significant.
Conclusion The intra-abdominal use of absorbable sutures did not have enough of an effect on the reduction of SSI in this phase II trial to justify the planning of a large-scale phase III trial.

DOI： 10.1007/s00595-017-1480-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Objective: To determine the predictors of cognitive function in patients with drugresistant gelastic seizures (GS) related to hypothalamic hamartoma (HH) before and after stereotactic radiofrequency thermocoagulation surgery (SRT).
Methods: We studied 88 patients with HH who underwent SRT between October 1997 and December 2014. Patients received neuropsychological tests preoperatively and postoperatively. Based on the preoperative measures, patients were categorized as "high-functioning" (full-scale intelligence quotient [FSIQ] &gt;= 70; n = 48) and "low-functioning" group (FSIQ &lt;70; n = 40). Univariate and multivariate linear regression analyses determined the clinical, electroencephalography (EEG), and imaging factors associated with preoperative cognitive function as well as postoperative cognitive change.
Results: Eighty-seven patients (98.8%) were followed postoperatively for an average of 3.3 years, and 75 (85.2%) of them achieved GS remission at the last hospital visit. Neuropsychological performance was significantly improved after surgery in both groups. Multivariate linear regression analysis showed that a smaller HH size (p = 0.002) and a smaller number of antiepileptic drugs (p &lt; 0.001) were preoperatively associated with better neuropsychological performance. Multivariate linear regression analysis showed that better postoperative improvement in cognition was associated with a shorter duration of epilepsy (p = 0.03).
Significance: Cognitive impairment related to epileptic encephalopathy may improve following SRT in substantial proportions of HH patients. Reduced improvement in postoperative cognitive function in patients with longer duration of epilepsy warrants further studies to determine if earlier SRT provides a greater chance of postoperative cognitive improvement in patients with HH.

DOI： 10.1111/epi.13838

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：W B SAUNDERS CO-ELSEVIER INC  

HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2 positive because of HER2 MC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P &lt; .001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment. (C) 2017 The Authors. Published by Elsevier Inc.

DOI： 10.1016/j.humpath.2017.02.004

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DOI： 10.4236/health.2017.98084

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Adverse events related to endocrine therapies have a major impact not only on patients' quality of life but also on treatment discontinuation. Although vasomotor symptoms induced by aromatase inhibitors are frequently recognized, risk factors, especially for Japanese women, are not well reported. To identify risk factors for vasomotor symptoms of Japanese breast cancer patients treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs).
For this prospective cohort study (SAVS-JP, UMIN000002455), 391 postmenopausal Japanese estrogen receptor-positive breast cancer patients who were treated with adjuvant anastrozole were recruited from 28 centers. The PRO assessment was obtained from a self-reported questionnaire at baseline, 3, 6, 9 and 12 months between August 2009 and April 2012. Vasomotor symptoms, comprising hot flashes, night sweats, and cold sweats, were categorized into four grades (none, Grade 1: mild, Grade 2: moderate, Grade 3: severe). Pre-existing symptoms were only included if they had become worse than at baseline.
Hot flashes, night sweats, and cold sweats at baseline were reported by 20.5, 15.1, and 8.2 % of the patients, respectively, and new appearance or worsening of symptoms in comparison with baseline by 38.4, 29.3, and 28.7 %, respectively. About 80 % of newly occurring symptoms were Grade 1, and less than 5 % were Grade 3. Vasomotor symptoms were reported by 201 out of 362 patients (55.5 %) during the first year and the mean time to onset was 5.6 months. Patients with vasomotor symptoms were significantly younger (mean 62.8 years, range 38-86 vs 64.7 years, range 37-84; p = 0.02), had higher body mass index (BMI) (23.4 kg/m(2), range 15.8-39.9 vs 22.4 kg/m(2), range 15.8-34.9; p = 0.01), had vasomotor symptoms sooner after menopause (12.4 years, range 0-51 vs 15.1 years, range 1-37; p = 0.002), and had more menopausal disorders during menopause (63.3 vs 36.7 %; p = 0.002). Multivariate analysis showed that BMI [odds ratio (OR) 1.09 per unit of increase, 95 % confidence interval (CI) 1.02-1.16; p = 0.009] and experiencing menopausal disorders (OR 2.11, 95 % CI 1.35-3.30; p = 0.001) were significantly associated with vasomotor symptoms.
High BMI and experiencing menopausal disorders at menopause were found to be significantly associated with the occurrence of vasomotor symptoms. These findings are expected to prove useful for the management of postmenopausal Japanese women treated with aromatase inhibitors.

DOI： 10.1007/s12282-016-0735-y

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BackgroundThe study was conducted to examine esophageal and gastric cardia precursor progression.
MethodsAfter population-based baseline screening, 145 precursor and 335 chronic inflammation cases were endoscopically surveyed for sixyears.
ResultsSurveillance of interval and baseline diagnoses for 18 severe dysplasia (SD) cases later detected were: 13, 23, 39, and 44months since a diagnosis of chronic inflammation in four cases; 6, 6, 6, 11, 13, 16, 16, and 23months since mild dysplasia (mD) diagnoses in eight; and 6, 9, 10, 13, 18, and 48months since moderate dysplasia (MD) diagnoses in six. Rates for 11 carcinoma in situ (Cis) cases later detected were: 7 and 18months since basal cell hyperplasia (Bch) diagnoses in two; and 6, 6, 9, 13, 13, 18, 35, 44, and 50months since MD diagnoses in nine. In 10 cancer cases later detected, rates were: 6, 6, 7, 18, 19, 34, 36, and 48months since SD diagnoses in eight cases with submucosal carcinoma; 46months since MD diagnosis in a T2N0M0 carcinoma case; and 52months since Bch diagnosis in another T2N0M0 case.
ConclusionEsophageal and gastric cardia precursors are heterogeneous. Male gender, advanced age, family history of upper gastrointestinal cancer, and multifocal dysplasia are significant independent predictors for progression, and Bch/mD, MD, and SD constitute three distinctive entities regarding the risk of cancer.

DOI： 10.1111/1759-7714.12446

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Ovarian cancer is the most lethal malignancy among gynaecological cancers. Although many anticancer agents have been developed for the treatment of ovarian cancer, it continues to have an extremely poor prognosis. Heparin-binding epidermal growth factor-like grown factor (HB-EGF) has been reported to be a rational therapeutic target for ovarian cancer. Here, we evaluated the clinical significance of serum HB-EGF by examining the association between prognosis and serum HB-EGF levels in patients with primary ovarian cancer. We found that high serum HB-EGF concentrations were significantly associated with poor prognosis in a combined cohort of patients with all stages of ovarian cancer, as well as in a subset of patients with advanced disease. In addition, serum HB-EGF levels increased as the cancer advanced. These data suggest that serum HB-EGF may be a target for the design of novel therapies for ovarian cancer.

DOI： 10.21873/anticanres.11779

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

Introduction Comprehensive molecular profiling has become a pivotal component of precision medicine involving anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy for metastatic colorectal cancer. The objective of this study was to determine the cost-effectiveness of comprehensive molecular profiling before initiating anti-EGFR therapies for metastatic colorectal cancer. Methods A Markov model simulating the health outcomes and total costs was developed to estimate the life years and quality-adjusted life years (QALYs) gained by metastatic colorectal cancer patients treated with anti-EGFR drug. The cost-effectiveness of comprehensive screening versus RAS mutation screening was evaluated over a 5-year period using the incremental cost-effectiveness ratio (ICER). The ICER per additional QALY gained was calculated, and sensitivity analyses were performed to evaluate the robustness of the assumptions across a range of values. Analyses were made from the perspective of the Japanese healthcare payer. Results Comprehensive screening before monoclonal antibody therapy provided 0.063 additional QALYs (0.075 life years) at the cost of 268,274 Japanese Yen (JPY). The ICER was 4,260,187 JPY/QALY compared to RAS screening. The median progression-free survival obtained by sensitivity analyses for the subgroup not responding to anti-EGFR therapy showed that comprehensive screening and panitumumab prices had the strongest influence on cost-effectiveness. Conclusion The incremental cost per QALY gained indicated that comprehensive screening was more cost-effective compared to RAS screening. With a willingness-to-pay value of 6 million JPY/QALY, comprehensive screening can be considered for the genetic testing of patients before providing monoclonal antibody therapy.

DOI： 10.1016/j.jcpo.2017.03.008

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BackgroundThe international practice guidelines for patients with acute cholangitis and cholecystitis were released in 2007 (TG07) and revised in 2013 (TG13). This study investigated updated epidemiology and outcomes among patients with acute cholangitis on a larger scale for the first time.
MethodsThis is an international multi-center retrospective observational study in Japan and Taiwan. All consecutive patients older than 18years of age and given a clinical diagnosis of acute cholangitis by clinicians between 1 January 2011 and 31 December 2012 were enrolled. Those who met the diagnostic criteria of acute cholangitis by TG13 were statistically analyzed.
ResultsA total of 7,294 patients were enrolled and 6,433 patients met the TG13 diagnostic criteria. The severity distribution was Grade I (37.5%), Grade II (36.2%), and Grade III (26.2%). The 30-day all-cause mortality was 2.4%, 4.7%, and 8.4% in Grade I, II, III severity, respectively (P&lt;0.001). The incidence of liver abscess and endocarditis as complications of acute cholangitis was 2.0% and 0.26%, respectively.
ConclusionsThis is the first large scale study to investigate patients with acute cholangitis. This study provides the basis to define the best practices to manage patients with acute cholangitis in future studies.

DOI： 10.1002/jhbp.452

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BackgroundSince the publication of the Tokyo Guidelines (TG13) for the management of acute cholecystitis (AC), multidirectional studies have been published. However, epidemiological research about AC with big data was not projected. The aim of this study was to reveal the actual clinical conditions of AC.
MethodThe study was designed as an international multicenter retrospective study of AC in Japan and Taiwan from 2011 to 2013. The factors investigated comprised data related to demographic, history, physical examinations, laboratory and imaging findings. Based on these data, we investigated the various values of AC, and real situation with respect to severity and treatment.
ResultsA total of 5,459 patients with AC were reviewed. Thirty-day mortality rate was 1.1%. Based on the diagnostic criteria, 4,088 patients had a definite diagnosis and 291 had a suspected diagnosis. According to the severity grading, 939 patients were classified as Grade III, 2,308 as Grade II, and 2,130 as Grade I. Cholecystectomy was performed in total of 4,266 patients and 2,765 patients had laparoscopic cholecystectomy. The main etiologies were gallbladder stones in 4,623 cases.
ConclusionThis epidemiological study with large population will undoubtedly contribute to establish the best practice for managing AC worldwide.

DOI： 10.1002/jhbp.450

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BackgroundThe Tokyo Guidelines 2007 (TG07) first presented the diagnostic and severity grading criteria for acute cholangitis. Subsequently updated in 2013, the Tokyo Guidelines (TG13) have been widely adopted throughout the world as global standard guidelines. We set out to verify the efficacy of these TG13 criteria in an international multicenter study.
MethodsWe reviewed 6,063 patients who were clinically diagnosed with acute cholangitis in Japan and Taiwan over a 2-year period. The TG13 diagnostic and severity grading criteria were retrospectively applied, and 30-day mortality was investigated.
ResultsA diagnosis of acute cholangitis was made in 5,454 (90.0%) patients on the basis of the TG13 criteria, and in 4,815 (79.4%) patients on the basis of the TG07 criteria. The 30-day mortality rates of patients with Grade III, Grade II, and Grade I were 5.1%, 2.6%, and 1.2%, respectively, and increased significantly along with disease severity. The mortality rate in the 1,272 Grade II cases where urgent or early biliary drainage was performed was 2.0% (n = 25), which was significantly lower than that of 3.7% (n = 28) in the other 748 cases.
ConclusionBy using the TG13 diagnostic and severity grading criteria, more patients with possible acute cholangitis can be diagnosed, and patients whose prognosis can potentially be improved by early biliary drainage can be identified. The TG13 criteria are appropriate and useful for clinical practice.

DOI： 10.1002/jhbp.458

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BackgroundTokyo Guideline 2013 (TG13) proposed three drainage techniques for the treatment of acute cholecystitis. We evaluated the clinical efficacy and adverse events between percutaneous transhepatic intervention (PTGBI) including percutaneous transhepatic gallbladder drainage (PTGBD) and percutaneous transhepatic gallbladder aspiration (PTGBA) and endoscopic transpapillary gallbladder drainage (EGBD).
MethodsA cohort study was performed using propensity score matching to reduce treatment selection bias. This involved the analysis of collected data for 1,764 patients who underwent PTGBI and EGBD.
ResultsPropensity score matching extracted 330 pairs of patients. The difference in the clinical success rate within 3 days between PTGBI and EGBD were 62.5% and 69.8%, respectively (P = 0.085). The differences in the suboptimal clinical success rates within 7 days between PTGBI and EGBD were 87.6% and 89.2% (P = 0.579). The differences in the complication rate between PTGBI and EGBD were 4.8% and 8.2% (P = 0.083). The differences in the complication rate among PTGBD, PTGBA and EGBD were 5.6%, 1.6% and 8.2% (P = 0.11). Median required days of PTGBD (3.0 days) was significantly longer than those of PTGBA and EGBD (1.5 and 2.0 days, respectively) (P = 0.001).
ConclusionThe current study showed the PTGBI showed similar clinical efficacy compared with EGBD without significant discrepancy of complication rate for the treatment of acute cholecystitis.

DOI： 10.1002/jhbp.454

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BackgroundThe collaborative multicenter retrospective study of acute cholecystitis (AC) was performed in Japan and Taiwan. The aim for this study was evaluation of the clinical value of TG13 severity grading for AC.
MethodThe study was designed as an international multicenter retrospective study of AC from 2011 to 2013. Based on the data, we investigated the TG13 severity grading by analyzing the correlations between grade and prognosis, surgical procedures, histopathology, and organ dysfunction and prognosis.
ResultsAn investigation revealed that 30-day overall mortality rate was 1.1% for Grade I, 0.8% for Grade II, 5.4% for Grade III. The mortality rate for Grade III was significantly higher than lower grades (P&lt;0.001). The greater the number of organ dysfunction, the higher the mortality rate (P&lt;0.001). However, the mortality rate varied depending on the number of organ dysfunction (3.1-25%). With respect to the surgical procedures, laparoscopic cholecystectomy was performed for Grade I patients (P&lt;0.001), and the higher the grade, the more likely open surgery would be selected (P&lt;0.001).
ConclusionTG13 severity grading criteria for AC are providing great benefits in actual clinical settings. From this study, the position of each severity grade was obviously confirmed.

DOI： 10.1002/jhbp.457

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BackgroundAlthough early laparoscopic cholecystectomy is widely performed for acute cholecystitis, the optimal timing of a cholecystectomy in clinically ill patients remains controversial. This study aims to determine the best practice for the patients presenting with acute cholecystitis focused on disease severity and comorbidities.
MethodsAn international multicentric retrospective observational study was conducted over a 2-year period. Patients were divided into four groups: Group A: primary cholecystectomy; Group B: cholecystectomy after gallbladder drainage; Group C: gallbladder drainage alone; and Group D: medical treatment alone.
ResultsThe subjects of analyses were 5,329 patients. There were statistically significant differences in mortality rates between patients with Charlson comorbidity index (CCI) scores below and above 6 (P &lt; 0.001). The shortest operative time was observed in Group A patients who underwent surgery 0-3 days after admission (P &lt; 0.01). Multiple regression analysis revealed CCI and low body mass index &lt;20 as predictive factors of 30-day mortality in Grade I+II patients. Also, jaundice, neurological dysfunction, and respiratory dysfunction were predictive factors of 30-day mortality in Grade III patients. In Grade III patients without predictive factors, there were no difference in mortality between Group A and Group B (0% vs. 0%), whereas Group A patients had higher mortality rates than that of Group B patients (9.3% vs. 0.0%) in cases with at least one predictive factor.
ConclusionEven patients with Grade III severity, primary cholecystectomy can be performed safely if they have no predictive factors of mortality. Gallbladder drainage may have a therapeutic role in subgroups with higher CCI or higher disease severity.

DOI： 10.1002/jhbp.456

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: The oral hygiene of patients with a mental illness is an important concern in psychiatric care, and it is necessary to increase the level of self-care among these patients. In this study, we administered an oral care questionnaire to people with mental illness in Japan and compared their answers before (baseline) and at 1 week and 1, 3 and 6 months after they participated in an educational program.
Methods: The questionnaire was distributed to 390 patients. It included questions about age, education, income, between-meal snacks, number of teeth, frequency of tooth brushing, and other items. The educational program was developed for the purposes of improving self-care.
Results: Before the program, the proportion of male patients who had had a mental illness for &gt;= 10 years was significantly higher among those patients who did not brush their teeth before bed. In addition, such patients did not have primary care dentists, and a significantly higher proportion of male patients, compared with female patients, did not undergo routine dental checkups more than once per year. The educational program resulted in an improvement in the use of fluoride toothpaste from baseline to 6 months after the intervention (p = 0.001). The daily use of interdental brushes or floss was significantly different 6 months after the intervention.
Conclusions: Male and long-term inpatients need oral hygiene instructions. Our educational program showed the effects of using oral hygiene tools. Future studies should include a control group to measure the impact of the educational program.

DOI： 10.1186/s12903-017-0372-7

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：腎移植・血管外科研究会  

移植医療におけるドナー不足は大きな問題であり、高齢者ドナーや心停止後摘出臓器の利用が世界的にも増加している。移植後の腎機能に影響する因子を検討することは以前より行われてきた。当院における59例の心停止下献腎移植の移植腎機能にかかわるレシピエント因子、ドナー因子、graft因子をそれぞれ後方視的に解析した。その結果、UNOSの定義するExpanded criteria donor(ECD)とgraft hyalinosisの程度が移植後腎機能に大きく影響する因子であることが分かった。(著者抄録)

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Language：English   Publisher：(一社)日本胃癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier USA  

Background A shortage of donors poses a serious problem for organ transplantation around the world. In response, the concept of the expanded criteria donor (ECD) has been defined to include donors with traditionally less favorable characteristics. That definition has now been accepted and is being applied in kidney transplantation in the United States and Europe. However, the ECD has not yet been defined for deceased donor kidney transplantation in Japan. Patients and Methods We analyzed data on graft survival and relevant risk factors in patients who received deceased donor kidney transplants through the East Japan Branch of the Japan Organ Transplant network (n = 1051). Recipients were divided into two groups: the standard-function group (estimated glomerular filtration rate [eGFR] ≥20 mL/min/1.73 m2
n = 906) and the poor-function group (eGFR &lt
20 mL/min/1.73 m2
n = 145
Cox proportional hazards regression analysis
P &lt
.0001). Results The 10-year survival rate was significantly lower in the poor-function group than in the standard-function group (85.5% vs 22.5%
P &lt
.0001). The two groups differed significantly in recipient and donor risk for graft failure. Recipient risk factors were length of time on dialysis before renal transplantation and incidence of acute rejection after transplantation. Donor risk factors were donor category (heart death), age, history of hypertension, presence of cerebrovascular disease, mean urine output, and donor creatinine level immediately before donor nephrectomy, total ischemic time, and warm ischemic time. Conclusion Data from deceased donor transplantation should be analyzed in depth to determine which factors influence renal function after transplantation. In addition, ECD standards should be reconsidered for use in a Japanese context.

DOI： 10.1016/j.transproceed.2016.11.016

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables.
Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score.
Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74 +/- 0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54 +/- 0.03) and Japan Integrated Staging score (0.59 +/- 0.07).
Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

DOI： 10.2169/internalmedicine.56.7278

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DOI： 10.4236/health.2017.911110

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Copyright © 2016 by the American Thoracic Society. Rationale: Sirolimus has been shown in a randomized, controlled clinical trial to stabilize lung function in patients with lymphangioleiomyomatosis (LAM) treated for a 12-month time period; however the pretreatment decline in lung function after the drug was discontinued indicated that continued exposure is required to suppress disease progression. Objectives: To elucidate the durability and tolerability of long-term sirolimus treatment in Asian patients with LAM. Methods: We conducted a single-arm, open-label, investigatorinitiated safety and efficacy study of sirolimus in 63 women with LAM at 9 sites in Japan. Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5-15 ng/ml. Measurements and Main Results: Fifty-two subjects (82.5%) completed the trial with mean drug compliance of more than 80% overall during the study. The number of adverse events was greatest during the initial 6 months of therapy, but they continued to occur with declining frequency throughout the 2-year study period. Of the 1,549 adverse events, 27 were classified as serious, including reversible sirolimus pneumonitis in 3 patients. New hypercholesterolemia occurred in 30 patients (48%); microcytosis in 10 patients; loss of body weight in 33 patients; and increase in blood pressure that required treatment in 5 patients. FEV1, FVC, and quality-of-life parameters were stable in the overall study cohort during the study period, but baseline to 2-year improvements in lung function occurred in the subset of patients with a prior history of chylothorax. Conclusions: Although long-term sirolimus treatment of Asian patients with LAM was associated with a large number of adverse events, including three episodes of pneumonitis, most patients completed the 2-year course of medication with good drug compliance and stable quality of life and lung function.

DOI： 10.1513/AnnalsATS.201605-335OC

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: Prognoses vary substantially among patients with advanced gastric cancer following curative surgery. The aim of the current study was to develop and verify the validity of a novel nomogram that predicts the probability of 5-year relapse-free survival (RFS) in patients who underwent curative resection for stage II/III gastric cancer.
Materials and methods: A nomogram to predict 5-year RFS following surgical resection of gastric cancer was constructed based on the data of patients who underwent surgery for primary gastric carcinoma at three institutions in Japan in January 2001-December 2006. Multivariate analysis using a Cox proportional hazards regression model was performed, and the nomogram's predictive accuracy (discrimination) and the agreement between observed outcomes and predictions (calibration) were evaluated by internal validation.
Results: Multivariate analyses revealed that age at operation, depth of tumor, tumor location, lymph node classification, and presence of combined resection were significant prognostic factors for RFS. In the internal validation, discrimination of the developed nomogram for 5-year RFS was superior to that of the American Joint Committee on Cancer TNM classification (concordance indices of 0.80 versus 0.67; P &lt; 0.001). Moreover, calibration appeared to be accurate. Based on these results, we have created free software to more easily predict 5-year RFS.
Conclusion: We developed and validated a nomogram to predict 5-year RFS after curative surgery for stage II/III gastric cancer. This tool will be useful for the assessing a patient's individual recurrence risk when considering additional therapy in clinical practice. (C) 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ijsu.2016.09.080

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PIONEER BIOSCIENCE PUBL CO  

Background: Although lobectomy is the standard surgical procedure for non-small cell lung cancer (NSCLC), recent studies show favorable outcomes after limited resection in patients with small-sized peripheral tumors. We conducted a randomized controlled trial of such patients to estimate postoperative outcomes and pulmonary function following these surgical techniques.
Methods: Between 2005 and 2008, eligible patients with tumors of 2 cm or less were randomly assigned 1: 1 to undergo lobectomy or limited resection; 32 and 33 NSCLC patients in each group, respectively, were analyzed. The primary end points were 5-year overall survival (OS) and disease-free survival (DFS), while the secondary end points were postoperative pulmonary function including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1).
Results: The 5-year OS rates were 93.8% and 90.9% in the lobectomy and limited resection groups, respectively (P=0.921). The 5-year DFS rates were 93.8% and 90.9% in the lobectomy and limited resection groups, respectively (P=0.714). These rates did not differ significantly between the two resection groups. The median postoperative/preoperative FVC ratios were 84.1% and 90.0% in the lobectomy and limited resection groups, respectively, while the median postoperative/preoperative FEV1 ratios were 81.9% and 89.1%, respectively. Both ratios were significantly higher in the limited resection group (P=0.032 and P=0.005 for FVC and FEV1 ratios, respectively).
Conclusions: A similar outcome, with more preserved postoperative pulmonary function, was observed in patients who underwent limited resection compared to those who underwent lobectomy. Ongoing large-scale multi-institutional prospective randomized trials of lobar versus sublobar resection in patients with small peripheral NSCLCs will hopefully provide definitive information about intentional limited resection of small peripheral tumors.

DOI： 10.21037/jtd.2016.11.106

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Publishing type：Research paper (scientific journal)   Publisher：AMER THORACIC SOC  

Rationale: Sirolimus has been shown in a randomized, controlled clinical trial to stabilize lung function in patients with lymphangioleiomyomatosis (LAM) treated for a 12-month time period; however the pretreatment decline in lung function after the drug was discontinued indicated that continued exposure is required to suppress disease progression. Objectives: To elucidate the durability and tolerability of long-term sirolimus treatment in Asian patients with LAM. Methods: We conducted a single-arm, open-label, investigator-initiated safety and efficacy study of sirolimus in 63 women with LAM at 9 sites in Japan. Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5-15 ng/ml. Measurements and Main Results: Fifty-two subjects (82.5%) completed the trial with mean drug compliance of more than 80% overall during the study. The number of adverse events was greatest during the initial 6 months of therapy, but they continued to occur with declining frequency throughout the 2-year study period. Of the 1,549 adverse events, 27 were classified as serious, including reversible sirolimus pneumonitis in 3 patients. New hypercholesterolemia occurred in

DOI： 10.1513/AnnalsATS.201605-335OC

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DOI： 10.1055/s-0042-105869

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Association of Neurological Surgeons  

DOI： 10.3171/2015.5.JNS15785

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC NEUROLOGICAL SURGEONS  

DOI： 10.3171/2015.4.JNS1582

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Language：English   Publisher：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2016.34.15_suppl.e15103

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC NEUROLOGICAL SURGEONS  

OBJECTIVE The aim of this study was to elucidate the invasiveness, effectiveness, and feasibility of MRI-guided stereotactic radiofrequency thermocoagulation (SRT) for hypothalamic hamartoma (HH).
METHODS The authors examined the clinical records of 100 consecutive patients (66 male and 34 female) with intractable gelastic seizures (GS) caused by HH, who underwent SRT as a sole surgical treatment between 1997 and 2013. The median duration of follow-up was 3 years (range 1-17 years). Seventy cases involved pediatric patients. Ninety percent of patients also had other types of seizures (non-GS). The maximum diameter of the HHs ranged from 5 to 80 mm (median 15 mm), and 15 of the tumors were giant HHs with a diameter of 30 mm or more. Comorbidities included precocious puberty (33.0%), behavioral disorder (49.0%), and mental retardation (50.0%).
RESULTS A total of 140 SRT procedures were performed. There was no adaptive restriction for the giant or the subtype of HH, regardless of any prior history of surgical treatment or comorbidities. Patients in this case series exhibited delayed precocious puberty (9.0%), pituitary dysfunction (2.0%), and weight gain (7.0%), besides the transient hypothalamic symptoms after SRT. Freedom from GS was achieved in 86.0% of patients, freedom from other types of seizures in 78.9%, and freedom from all seizures in 71.0%. Repeat surgeries were not effective for non-GS. Seizure freedom led to disappearance of behavioral disorders and to intellectual improvement.
CONCLUSIONS The present SRT procedure is a minimally invasive and highly effective surgical procedure without adaptive limitations. SRT involves only a single surgical procedure appropriate for all forms of epileptogenic HH and should be considered in patients with an early history of GS.

DOI： 10.3171/2015.4.JNS1582

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ObjectiveNeuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the central nervous system characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of involvement of the anterior visual pathway (AVP) and neurodegeneration via glia-neuron interaction in NMOsd.
MethodsThirty Japanese patients with serologically verified NMOsd were assessed with a neuro-ophthalmological study. Using 27 tissue blocks from 13 other cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the AVP.
ResultsThe AVP involvement in NMOsd was characterized by the following, compared to multiple sclerosis: (1) longitudinally extensive optic neuritis (ON); (2) more severe visual impairment and worse prognosis for ON; (3) unique AQP4 dynamics, including loss of AQP4 immunoreactivity on astrocytes with complement activation in ON lesions, loss of AQP4 immunoreactivity on Muller cells with no deposition of complement in the retinas, and densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary anterograde/retrograde degeneration in the optic nerves and retinal nerve fiber layer (RNFL); and (4) more severe neurodegeneration, including axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology in ON lesions, mild loss of horizontal cells, and RNFL thinning and loss of ganglion cells with abundance of AQP4(+) astrocytes, indicating secondary retrograde degeneration after ON.
InterpretationSevere and widespread neuroaxonal damage and unique dynamics of astrocytes/Muller cells with alterations of AQP4 were prominent in the AVP and may be associated with poor visual function and prognosis in NMOsd. Ann Neurol 2016;79:605-624

DOI： 10.1002/ana.24608

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Indication for chemotherapy in estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancers is determined on the basis of Ki67 expression level. However, since Ki67-high cancers are not necessarily sensitive to chemotherapy, identification of such patients who do not need chemotherapy is an important issue.
We used immunohistochemical staining to examine the expression levels of ER, progesterone receptor (PgR), Ki67, and geminin, a marker of S to G2/M phases, in 80 ER-positive/HER2-negative breast cancers. The labeling indices of Ki67 and geminin were determined and cutoff values were set at 15 and 6 %, respectively.
Ki67 and geminin expression levels were significantly associated with nuclear grade. In the Ki67-low subset, 26 out of 28 (92.9 %) cancers were geminin low and in the Ki67-high subset, 31 out of 52 (59.6 %) were geminin high. Distant disease-free survival (DDFS) of the geminin-high subset was significantly poorer than that of the geminin-low subset (P = 0.009). In the Ki67-low subset, only one patient showed recurrence. Metastasis was detected in eight out of 31 (25.8 %) patients in the geminin-high group of the Ki67-high subset, but no recurrence was observed in the geminin-low group of the Ki67-high subset.
Geminin-high breast cancers are significantly associated with worse prognosis. Since poorer prognosis was recognized only in the geminin-high group in Ki67-high cancers, we speculate that geminin may be useful for identifying patients in the Ki67-high subset who can avoid unnecessary chemotherapy.

DOI： 10.1007/s12282-014-0556-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

Sitafloxacin (STFX) is a newly developed quinolone that has robust antimicrobial activity against periodontopathic bacteria. We previously reported that oral administration of STFX during supportive periodontal therapy was as effective as conventional mechanical debridement under local anesthesia microbiologically and clinically for 3 months. The aim of the present study was to examine the short-term and long-term microbiological and clinical effects of systemic STFX and azithromycin (AZM) on active periodontal pockets during supportive periodontal therapy. Fifty-one patients receiving supportive periodontal therapy were randomly allocated to the STFX group (200 mg/day of STFX for 5 days) or the AZM group (500 mg/day of AZM for 3 days). The microbiological and clinical parameters were examined until 12 months after the systemic administration of each drug. The concentration of each drug in periodontal pockets and the antimicrobial susceptibility of clinical isolates were also analyzed. The proportions of red complex bacteria, i.e., Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, which are the representative periodontopathic bacteria, were significantly reduced at 1 month and remained lower at 12 months than those at baseline in both the STFX and AZM groups. Clinical parameters were significantly improved over the 12-month period in both groups. An increase in the MIC of AZM against clinical isolates was observed in the AZM group. These results indicate that monotherapy with systemic STFX and AZM might be an alternative treatment during supportive periodontal therapy in patients for whom invasive mechanical treatment is inappropriate.

DOI： 10.1128/AAC.02575-15

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

Purpose The addition of bisphosphonates to adjuvant therapy improves survival in postmenopausal breast cancer (BC) patients. We report a meta-analysis of four randomised trials of neoadjuvant chemotherapy (CT) +/- zoledronic acid (ZA) in stage II/III BC to investigate the potential for enhancing the pathological response. Methods Individual patient data from four prospective randomised clinical trials reporting the effect of the addition of ZA on the pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (PCRb) and in the breast and lymph nodes (PCR). Trial-level and individual patient data meta-analyses were done. Predefined subgroup-analyses were performed for postmenopausal women and patients with triple-negative BC. Results PCRb and PCR data were available in 735 and 552 patients respectively. In the total study population ZA addition to neoadjuvant CT did not increase PCRb or PCR rates. However, in postmenopausal patients, the addition of ZA resulted in a significant, near doubling of the PCRb rate (10.8% for CT only versus 17.7% with CT+ZA
odds ratio [OR] 2.14, 95% confidence interval [CI] 1.01-4.55) and a non-significant benefit of the PCR rate (7.8% for CT only versus 14.6% with CT+ZA
OR 2.62, 95% CI 0.90-7.62). In patients with triple-negative BC a trend was observed favouring CT+ZA. Conclusion This meta-analysis shows no impact from the addition of ZA to neoadjuvant CT on PCR. However, as has been seen in the adjuvant setting, the addition of ZA to neoadjuvant CT may augment the effects of CT in postmenopausal patients with BC.

DOI： 10.1016/j.ejca.2015.10.011

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma.
A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model.
Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or a parts per thousand yen2; P = 0.005) and the LNR (0, 0-5, or &gt; 5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes.
The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.

DOI： 10.1245/s10434-015-4609-x

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Language：Japanese   Publisher：Japan Surgical Association  

DOI： 10.3919/jjsa.77.1289

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Purpose
Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT).
Methods
Asian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ) group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95) or the CTZ group (n = 93) from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)), followed by 12 cycles of paclitaxel at 80 mg/m(2) weekly. ZOL (4 mg) was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR) rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug.
Results
This randomized controlled trial indicated that the rates of pCR in CTZ group (14.8%) was doubled to CT group (7.7%), respectively (one-sided chi-square test, p = 0.068), though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.071), and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.112). Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in postmenopausal patients and patients with triple-negative breast cancer. Further investigation is warranted.

DOI： 10.1371/journal.pone.0143643

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To define the effects of body mass index (BMI) on operative outcomes for both gastroenterological and cardiovascular surgery, using the National Clinical Database (NCD) of the Japanese nationwide web-based database.
The subjects of this study were 288,418 patients who underwent typical surgical procedures between January 2011 and December 2012. There were eight gastroenterological procedures, including esophagectomy, distal gastrectomy, total gastrectomy, right hemicolectomy, low anterior resection, hepatectomy of &gt; 1 segment excluding the lateral segment, pancreaticoduodenectomy, and surgery for acute diffuse peritonitis (n = 232,199); and five cardiovascular procedures, including aortic valve replacement, total arch replacement (TAR), descending thoracic aorta replacement (descending TAR), and on- or off-pump coronary artery bypass grafting (n = 56,219). The relationships of BMI with operation time and operative mortality for each procedure were investigated, using the NCD.
Operation times were longer for patients with a higher BMI. When a BMI cut-off of 30 was used, the operation time for obese patients was significantly longer than that for non-obese patients, for all procedures except esophagectomy (P &lt; 0.01). The mortality rate based on BMI revealed a U-shaped distribution, with both underweight and obese patients having high mortality rates for almost all procedures.
This Japanese nationwide study provides solid evidence to reinforce that both obesity and excessively low weight are factors that impact operative outcomes significantly.

DOI： 10.1007/s00595-015-1231-2

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Unidirectional K+ transport across the lateral cochlear wall contributes to the endocochlear potential (EP) of +80 mV in the endolymph, a property essential for hearing. The wall comprises two epithelial layers, the syncytium and the marginal cells. The basolateral surface of the former and the apical membranes of the latter face the perilymph and the endolymph, respectively. Intrastrial space (IS), an extracellular compartment between the two layers, exhibits low [K+] and a potential similar to the EP. This IS potential (ISP) dominates the EP and represents a K+ diffusion potential elicited by a large K+ gradient across the syncytial apical surface. The K+ gradient depends on the unidirectional K+ transport driven by Na+,K+-ATPases on the basolateral surface of each layer and the concomitant Na+,K+,2Cl(-)-cotransporters (NKCCs) in the marginal cell layer. The NKCCs coexpressed with the Na+,K+-ATPases in the syncytial layer also seem to participate in the K+ transport. To test this hypothesis, we examined the electrochemical properties of the lateral wall with electrodes measuring [K+] and potential. Blocking NKCCs by perilymphatic perfusion of bumetanide suppressed the ISP. Unexpectedly and unlike the inhibition of the syncytial Na+,K+-ATPases, the perfusion barely altered the electrochemical properties of the syncytium but markedly augmented [K+] of the IS. Consequently, the K+ gradient decreased and the ISP declined. These observations resembled those when the marginal cells' Na+,K+-ATPases or NKCCs were blocked with vascularly applied inhibitors. It is plausible that NKCCs in the marginal cells are affected by the perilymphatically perfused bumetanide, and these transporters, but not those in the syncytium, mediate the unidirectional K+ transport.

DOI： 10.1007/s00424-014-1597-9

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist that is approved for the treatment of prostate cancer. GnRH antagonists bind directly to and block GnRH receptors, without causing the initial testosterone surge associated with GnRH agonists. A pivotal phase El study indicated that degarelix induced significantly faster reduction of testosterone and prostate-specific antigen level than GnRH agonist does. In addition, its 5-year extension trial suggested that patients could be safely switched from GnRH agonist to degarelix treatment with sustained efficacy, as measured by biochemical markers. Possible benefits of GnRH antagonists over agonists were suggested especially in patients with advanced prostate cancer with metastatic and symptomatic disease. Moreover, the recent reports including pooled data analyses on degarelix suggest improved disease control, quality of life, and lower urinary tract symptoms and decreased risk of cardiovascular diseases when compared with GnRH agonists. However, interpretation of these reports should be conducted cautiously because of the potential biases involved. This article critically reviews the results of the clinical trials and subsequent analyses and evaluates the points and counterpoints of the conclusions. (C) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.urolonc.2015.04.013

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Language：English   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.SABCS14-P6-01-02

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TOHOKU UNIV MEDICAL PRESS  

Hemodialysis patients in Japan are aging and thus more patients need support for attending hemodialysis facilities. This study aimed to clarify how dialysis patients utilize the services covered by Japan's public long-term care insurance (LTCI) system. This cross-sectional study was based on LTCI data of March 31, 2009, the latest available data provided by Niigata City, located on the northwest coast of Honshu. Among 30,349 LTCI users in Niigata City, there were 234 dialysis patients. To clarify the characteristics of the dialysis patients, we compared the utilization of LTCI services between the dialysis patients (234 users) and randomly selected 765 non-dialysis users. We also calculated the annual transportation service costs per patient for dialysis patients who continued home care (home care group) and those who switched to long-term hospital care at LTCI care levels 4 and 5 (hospital admission group). These care levels indicate difficulty in walking or maintaining a sitting posture without assistance. The dialysis group more frequently utilized home care and equipment services, such as renting or purchasing care-support products and support for home equipment repair, and utilized facility services and short-stay services (respite care) less frequently (both p &lt; 0.001). Cost per patient was higher in the home care group than in the hospital admission group, because the transportation services for dialysis patients at care levels 4 and 5 involve higher costs. These findings indicate that LTCI services usable for dialysis patients were limited. Therefore, instead of merely subsidizing transportation expenses, transportation services must be improved. (C) 2015 Tohoku University Medical Press

DOI： 10.1620/tjem.236.9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BAISHIDENG PUBLISHING GROUP INC  

AIM: To establish a prognostic formula that distinguishes non-hypervascular hepatic nodules (NHNs) with higher aggressiveness from less hazardous one.
METHODS: Seventy-three NHNs were detected in gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) study and confirmed to change 2 mm or more in size and/or to gain hypervascularity. All images were interpreted independently by an experienced, board-certified abdominal radiologist and hepatologist; both knew that the patients were at risk for hepatocellular carcinoma development but were blinded to the clinical information. A formula predicting NHN destiny was developed using a generalized estimating equation model with thirteen explanatory variables: age, gender, background liver diseases, Child-Pugh class, NHN diameter, T1-weighted imaging/T2-weighted imaging detectability, fat deposition, lower signal intensity in arterial phase, lower signal intensity in equilibrium phase, alpha-fetoprotein, des-gamma-carboxy prothrombin, alpha-fetoprotein-L3, and coexistence of classical hepatocellular carcinoma. The accuracy of the formula was validated in bootstrap samples that were created by resampling of 1000 iterations.
RESULTS: During a median follow-up period of 504 d, 73 NHNs with a median diameter of 9 mm (interquartile range: 8-12 mm) grew or shrank by 68.5% (fifty nodules) or 20.5% (fifteen nodules), respectively, whereas hypervascularity developed in 38.4% (twenty eight nodules). In the fifteen shrank nodules, twelve nodules disappeared, while 11.0% (eight nodules) were stable in size but acquired vascularity. A generalized estimating equation analysis selected five explanatories from the thirteen variables as significant factors to predict NHN progression. The estimated regression coefficients were 0.36 for age, 6.51 for lower signal intensity in arterial phase, 8.70 or 6.03 for positivity of hepatitis B virus or hepatitis C virus, 9.37 for des-gamma- carboxy prothrombin, and -4.05 for fat deposition. A formula incorporating the five coefficients revealed sensitivity, specificity, and accuracy of 88.0%, 86.7%, and 87.7% in the formulating cohort, whereas these of 87.2% +/- 5.7%, 83.8% +/- 13.6%, and 87.3% +/- 4.5% in the bootstrap samples.
CONCLUSION: These data suggest that the formula helps Gd-EOB-DTPA-MRI detect a trend toward hepatocyte transformation by predicting NHN destiny.

DOI： 10.3748/wjg.v21.i15.4583

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OBJECTIVE: We investigated the relationships between body weight (BWt) and metabolic syndrome (MS) risk factors to elucidate the effect of BWt (?BWt) change and body mass index (BMI) on these factors in the Japanese population. METHODS: Data were collected on MS-related parameters measured during two annual examinations of 16,640 men (mean age: 41.7±11.6 years) and 10,184 women (mean age: 45.0±12.2 years) without prior treatment of hypertension, diabetes mellitus, or dyslipidemia in 2006 and 2011 in Fukuoka, Japan. The subjects were divided into three groups according to BMI in 2006 (low, middle and high BMI) and into three groups according to change in BMI between 2006 and 2011 (decreased, stable, and increased BMI). Mean values for blood pressure (BP), systolic BP (SBP), diastolic BP (DBP), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), hemoglobin A1c (HbA1c), and fasting blood glucose (FBG) for each group were determined by sex and subjected to statistical analysis for comparison. RESULTS: High BMI (>26) was associated with higher SBP, LDL-C, FBG, and TG in both sexes. An increase≥1.1 BMI units in 5 years was associated with increased DBP, LDL-C, TG, HbA1c, and FBG and decreased HDL-C. In contrast, decreased BMI was associated with decreased BP and LDL-C and increased HDL-C in both sexes, and decreased TG in men and FBG in women. CONCLUSIONS: Maintaining a desirable weight or losing weight may help prevent hypertension and MS, even in non-obese individuals.

DOI： 10.5539/gjhs.v7n5p159

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DOI： 10.4172/2157-7420.1000180

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Gastroenterological Surgery  

DOI： 10.5833/jjgs.48.2015.sr001

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DOI： 10.4236/health.2015.75070

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Other Link： http://file.scirp.org/xml/56482.xml

Language：Japanese   Publisher：(一社)日本神経学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: Hematogenous recurrences of esophageal squamous cell carcinoma (ESCC) have dismal prognoses, but prognostic heterogeneity exists in this disease. The objectives of this study were to clarify the prognosis in this disease with regard to the initial recurrence site and to define the prognostic factors. Methodology: We retrospectively reviewed the cases of 67 consecutive patients with hematogenous recurrence in major organs after esophagectomy for ESCC of the thoracic esophagus and the esophagogastric junction. We analyzed clinicopathological characteristics, survival probability and potential prognostic factors. Results: Lung, liver, bone, and multiple-organ metastases occurred in 24, 19, 14, and 10 patients, respectively. Twenty-seven patients simultaneously had locoregional recurrence (combined recurrence). Among all 67 patients, the median disease-free interval (DFI) was 9.7 months, and the median survival time after the initial recurrence was 4.9 months. The patients with initial lung metastasis had most favorable prognosis with the median survival time of 9.8 months. A multivariate analysis identified that initial recurrence site, DFI, combined recurrence, and anticancer therapy were independent prognostic factors. Conclusions: The initial recurrence site contributes to the prognostic heterogeneity of patients with hematogenous recurrence of ESCC. The prognostic factors identified in this study are useful to optimize the management of these patients.

DOI： 10.5754/hge13171

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Self-stigma, defined by a negative attitude toward oneself combined with the consciousness of being a target of prejudice, is a critical problem for psychiatric patients. Self-stigma studies among psychiatric patients have indicated that high stigma is predictive of detrimental effects such as the delay of treatment and decreases in social participation in patients, and levels of self-stigma should be statistically evaluated. In this study, we developed the Workplace Social Distance Scale (WSDS), rephrasing the eight items of the Japanese version of the Social Distance Scale (SDSJ) to apply to the work setting in Japan. We examined the reliability and validity of the WSDS among 83 psychiatric patients. Factor analysis extracted three factors from the scale items: "work relations," "shallow relationships," and "employment." These factors are similar to the assessment factors of the SDSJ. Cronbach's alpha coefficient for the WSDS was 0.753. The split-half reliability for the WSDS was 0.801, indicating significant correlations. In addition, the WSDS was significantly correlated with the SDSJ. These findings suggest that the WSDS represents an approximation of self-stigma in the workplace among psychiatric patients. Our study assessed the reliability and validity of the WSDS for measuring self-stigma in Japan. Future studies should investigate the reliability and validity of the scale in other countries.

DOI： 10.5539/gjhs.v7n3p46

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with the cognitive severity of Alzheimer's disease (AD). To identify genes relevant to NFT expansion defined by the Braak stage, we conducted whole-genome exon array analysis with an exploratory sample set consisting of 213 human post-mortem brain tissue specimens from the entorinal, temporal and frontal cortices of 71 brain-donor subjects: Braak NFT stages 0 (N = 13), I-II (N = 20), III-IV (N = 19) and V-VI (N = 19). We identified eight genes, RELN, PTGS2, MYO5C, TRIL, DCHS2, GRB14, NPAS4 and PHYHD1, associated with the Braak stage. The expression levels of three genes, PHYHD1, MYO5C and GRB14, exhibited reproducible association on real-time quantitative PCR analysis. In another sample set, including control subjects (N = 30), and in patients with late-onset AD (N = 37), dementia with Lewy bodies (N = 17) and Parkinson disease (N = 36), the expression levels of two genes, PHYHD1 and MYO5C, were obviously associated with late-onset AD. Protein-protein interaction network analysis with a public database revealed that PHYHD1 interacts with MYO5C via POT1, and PHYHD1 directly interacts with amyloid beta-peptide 42. It is thus likely that functional failure of PHYHD1 and MYO5C could lead to AD development.

DOI： 10.1038/tp.2014.35

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003).
Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set.
Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P &lt; 0.001). Moreover, calibration was accurate.
We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

DOI： 10.1093/annonc/mdu125

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: The stigma of schizophrenia constitutes a major barrier to early detection and treatment of this illness. Anti-stigma education has been welcomed to reduce stigma among the general public. This study examined the factors associated with the effectiveness of a web-based educational program designed to reduce the stigma associated with schizophrenia.
Methods: Using Link's Devaluation-Discrimination Scale to measure stigma, the effect of the program was measured by the difference in pre-and post-program tests. In the present study, we focused on program participants whose stigma towards schizophrenia had considerably improved (a reduction of three points or more between pre-and post-program tests) or considerably worsened (an increase of three points or more). The study participants were 1,058 parents of middle or high school students across Japan, including 508 whose stigma had significantly decreased after the program and 550 whose stigma had significantly increased. We used multiple logistic regression analysis to predict a considerable reduction in stigma (by three or more points) using independent variables measured before exposure to the program. In these models, we assessed the effects of demographic characteristics of the participants and four measures of knowledge and views on schizophrenia (basic knowledge, Link's Devaluation-Discrimination Scale, ability to distinguish schizophrenia from other conditions, and social distance).
Results: Participants' employment status, occupation, basic knowledge of schizophrenia, pre-program Link's Devaluation-Discrimination Scale score, and social distance were significant factors associated with a considerable decrease in the stigma attached to schizophrenia following the educational program. Specifically, full-time and part-time employees were more likely to experience reduced stigma than parents who were self-employed, unemployed, or had other employment status. Considerable decreases in stigma were more likely among parents working in transportation and communication or as homemakers than among other occupational groups. In addition, parents with higher pre-program levels of stigma, lower basic knowledge, or lower social distance were more likely to have reduced levels of stigma.
Conclusions: Based on the regression analysis results presented here, several possible methods of reducing stigma were suggested, including increasing personal contact with people with schizophrenia and the improvement of law and insurance systems in primary and secondary industries.

DOI： 10.1186/1471-2458-14-258

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The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other immune-mediated disorders, and nine patients with 'idiopathic' variety. Myeloperoxidase-ANCA-positive hypertrophic pachymeningitis was characterized by: (i) an elderly female predominance; (ii) 82% of patients diagnosed with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) according to Watts' algorithm; (iii) a high frequency of patients with lesions limited to the dura mater and upper airways, developing headaches, chronic sinusitis, otitis media or mastoiditis; (iv) a low frequency of patients with the 'classical or generalized form' of granulomatosis with polyangiitis involving the entire upper and lower airways and kidney, or progressing to generalized disease, in contrast to proteinase 3-ANCA-positive hypertrophic pachymeningitis; (v) less severe neurological damage according to the modified Rankin Scale and low disease activity according to the Birmingham Vasculitis Activity Score compared with proteinase 3-ANCA-positive hypertrophic pachymeningitis; (vi) increased levels of CXCL10, CXCL8 and interleukin 6 in cerebrospinal fluids, and increased numbers of T cells, neutrophils, eosinophils, plasma cells and monocytes/macrophages in autopsied or biopsied dura mater with pachymeningitis, suggesting T(H)1-predominant granulomatous lesions in hypertrophic pachymeningitis, as previously reported in pulmonary or renal lesions of granulomatosis with polyangiitis; and (vii) greater efficacy of combination therapy with prednisolone and cyclophosphamide compared with monotherapy with prednisolone. Proteinase 3-ANCA may be considered a marker for more severe neurological damage, higher disease activity and a higher frequency of the generalized form compared with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. However, categorization into 'granulomatosis with polyangiitis' according to Watts' algorithm and immunological or pathological features were common in both proteinase 3- and myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. These data indicate that most patients with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis should be categorized as having the central nervous system-limited form of ANCA-associated vasculitis, consistent with the concept of ophthalmic-, pulmonary- or renal-limited vasculitis.

DOI： 10.1093/brain/awt314

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Language：English   Publisher：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/jco.2014.32.3_suppl.564

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Background: This study attempted to determine the therapeutic dosage of irinotecan and S-1 (IRIS) as a second-line treatment for colorectal cancer (CRC). Methods: S-1 was administered on days 1-14 of a 28-day cycle. Irinotecan was administered on days 1 and 15. The irinotecan dose was then escalated to determine the maximum-tolerated dose and the recommended dose at a fixed dosage of S-1 (80 or 65 mg·m-2·day-1). The S-1 dose was reduced to 65 mg·m-2·day-1 when dose-limiting toxicities were observed at 80 mg·m-2· day-1 and the irinotecan dose was increased. Results: The recommended dose was 65 mg/m2 for S-1 and 75 mg/m2 for irinotecan. Twenty-one patients were treated at the recommended dose. The overall response rate was 28.6%. Conclusion: This modified IRIS regimen is considered effective with acceptable toxicities for advanced CRC resistant to treatment with 5-fluorouracil/leucovorin or uracil and tegafur/leucovorin. © 2014 S. Karger AG, Basel.

DOI： 10.1159/000358482

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DOI： 10.4236/health.2014.621336

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Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002-0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.

DOI： 10.3233/JAD-140225

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Scientific Research Publishing, Inc.  

DOI： 10.4236/ojgas.2014.42011

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Other Link： http://www.scirp.org/journal/doi.aspx?DOI=10.4236/ojgas.2014.42011

Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J00990&link_issn=&doc_id=20140317220017&doc_link_id=%2Fdg3nigta%2F2013%2Fs12711%2F010%2F0638-0638%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2013%2Fs12711%2F010%2F0638-0638%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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DOI： 10.3892/mco.2013.142

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Stigma toward schizophrenia is an important area of research as it is frequently a barrier to early intervention. This study attempted to identify factors underlying stigma in Japan. Because even adolescents can develop schizophrenia, 357 Japanese parents of high school students were enrolled. All parents lived outside the areas affected by the Tohoku earthquake that occurred on March 11, 2011 (ie, parts of Iwate, Miyagi, and Fukushima prefectures). Factor analysis using the Link Devaluation-Discrimination Measure identified two factors: comparison with an able-bodied person and non-comparison with an able-bodied person. Regression analysis revealed that family structure had independent effects on factor 2 (p <0.05), and ANOVA showed that education had independent effects on factor 2 (p<0.05). These results suggest that education programs that seek to counteract stigma should target curricula in high schools and vocational schools.

DOI： 10.5539/gjhs.v5n6p46

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim The aim of this study was to compare the growth of Japanese infants that were exclusively breastfed to those of national references and World Health Organization (WHO) standards.
Methods Mothers, who delivered a normal term baby and had been exclusively breastfeeding for at least 4months, were enrolled. The lengths, body weights and head circumferences of 647 children, aged 0-24months, were obtained and compared to national references and WHO standards.
Results Comparisons of the national references for both length and body weight indicated that breastfed infants were significantly shorter and lighter almost throughout the first 24months. Conversely, head circumferences of breastfed infants were significantly larger at 1 and 6months of age in boys and 6months in girls. Compared to WHO standards, similar trends to the comparisons with national references were found.
Conclusion There were significant differences identified between the growth of breastfed infants and existing national references and WHO standards.

DOI： 10.1111/apa.12262

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Mild cognitive impairment and Alzheimer's disease (AD) are associated with changes in γ-secretase activity in the brain, producing an amyloid β-protein-42-lowering γ-modulator-like effect. We show here that this modulation occurs at the stage of amyloid deposition, presumably decades earlier than the onset of AD. In addition, γ-secretase modulator-1, a γ-modulator, altered γ-secretase activity in the AD brain but to a lesser extent than in the normal brain. These findings suggest that γ-modulators have limited efficacy against amyloid deposition and AD. © 2013 Elsevier Inc.

DOI： 10.1016/j.neurobiolaging.2012.08.017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: Combination therapy with infliximab (IFX) and azathioprine (AZA) is significantly more effective for treatment of active Crohn's disease (CD) than IFX monotherapy. However, AZA is associated with an increased risk of lymphoma in patients with inflammatory bowel disease.
Aim: To evaluate the cost-effectiveness of combination therapy with IFX plus AZA for drug-refractory CD.
Methods: A decision analysis model is constructed to compare, over a time horizon of 1 year, the cost-effectiveness of combination therapy with IFX plus AZA and that of IFX monotherapy for CD patients refractory to conventional non-anti-TNF-alpha therapy. The treatment efficacy, adverse effects, quality-of-life scores, and treatment costs are derived from published data. One-way and probabilistic sensitivity analyses are performed to estimate the uncertainty in the results.
Results: The incremental cost-effectiveness ratio (ICER) of combination therapy with IFX plus AZA is 24,917 GBP/QALY when compared with IFX monotherapy. The sensitivity analyses reveal that the utility score of nonresponding active disease has the strongest influence on the cost-effectiveness, with ICERs ranging from 17,147 to 45,564 GBP/QALY. Assuming that policy makers are willing to pay 30,000 GBP/QALY, the probability that combination therapy with IFX plus AZA is cost-effective is 0.750.
Conclusions: Combination therapy with IFX plus AZA appears to be a cost-effective treatment for drug-refractory CD when compared with IFX monotherapy. Furthermore, the additional lymphoma risk of combination therapy has little significance on its cost-effectiveness. (C) 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.crohns.2012.04.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Background The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registration in 2008.
Methods From 208 participating hospitals, 53 items including surgical procedures, pathological diagnosis, and survival outcomes of 13,626 patients with primary gastric cancer treated in 2002 were collected retrospectively. Data were entered into the JGCA database according to the JGCA classification (13th edition) and UICC TNM classification (5th edition) using an electronic data collecting system. Finally, data of 13,002 patients who underwent laparotomy were analyzed.
Results The 5-year follow-up rate was 83.3 %. The direct death rate was 0.48 %. UICC 5-year survival rates (5YEARSs)/JGCA 5YEARSs were 92.2 %/92.3 % for stage IA, 85.3 %/84.7 % for stage IB, 72.1 %/70.0 % for stage II, 52.8 %/46.8 % for stage IIIA, 31.0 %/28.8 % for stage IIIB, and 14.9 %/15.3 % for stage IV, respectively. The proportion of patients more than 80 years old was 7.8 %, and their 5YEARS was 51.6 %. Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed.
Conclusions Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed.

DOI： 10.1007/s10120-012-0163-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Objective: Neuromyelitis optica spectrum disorder (NMOsd) is an inflammatory and demyelinating syndrome characterized by optic neuritis and myelitis. Several magnetization transfer magnetic resonance imaging (MRI) studies have revealed abnormalities in normal-appearing gray matter in NMOsd. The aim of this study is to elucidate the characteristics and pathogenesis of cognitive impairment and neurodegeneration in NMOsd brains.
Methods: Fourteen Japanese patients with serologically verified NMOsd, 17 patients with multiple sclerosis (MS), and 37 healthy controls were assessed with the Rao's Brief Repeatable Battery of Neuropsychological Tests (BRBN). Using 128 tissue blocks from 6 other cases of NMOsd, 3 cases of MS, and 4 controls without central nervous system involvement, we performed quantitative analysis of cortical neuronal loss and layer-specific changes in NMOsd.
Results: In BRBN assessments, 57% of NMOsd patients and 47% of MS patients had impaired performance on at least 3 cognitive tests. Cognitive impairment in NMOsd was common even in the limited form of disease, indicating that NMOsd may progress insidiously from early stages of disease. Neuropathological assessments showed neuronal loss in cortical layers II, III, and IV, with nonlytic reaction of aquaporin-4 (AQP4)-negative astrocytes in layer I, massive activated microglia in layer II, and meningeal inflammation in NMOsd brains. All NMO cases showed no evidence of cortical demyelination.
Interpretation: We demonstrate cognitive impairment and substantial cortical neuronal loss with unique AQP4 dynamics in astrocytes in NMOsd. These data indicate pathological processes consisting not only of inflammatory demyelinating events characterized by pattern-specific loss of AQP4 immunoreactivity but also cortical neurodegeneration in NMOsd brains. ANN NEUROL 2013;73:65-76

DOI： 10.1002/ana.23721

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OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOsd) is an inflammatory and demyelinating syndrome characterized by optic neuritis and myelitis. Several magnetization transfer magnetic resonance imaging (MRI) studies have revealed abnormalities in normal-appearing gray matter in NMOsd. The aim of this study is to elucidate the characteristics and pathogenesis of cognitive impairment and neurodegeneration in NMOsd brains. METHODS: Fourteen Japanese patients with serologically verified NMOsd, 17 patients with multiple sclerosis (MS), and 37 healthy controls were assessed with the Rao&#039;s Brief Repeatable Battery of Neuropsychological Tests (BRBN). Using 128 tissue blocks from 6 other cases of NMOsd, 3 cases of MS, and 4 controls without central nervous system involvement, we performed quantitative analysis of cortical neuronal loss and layer-specific changes in NMOsd. RESULTS: In BRBN assessments, 57% of NMOsd patients and 47% of MS patients had impaired performance on at least 3 cognitive tests. Cognitive impairment in NMOsd was common even in the limited form of disease, indicating that NMOsd may progress insidiously from early stages of disease. Neuropathological assessment

DOI： 10.1002/ana.23721

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

SORL1 was shown to be genetically associated with late-onset Alzheimer's disease (LOAD) in a large-scale genome-wide association study (GWAS) involving clinically verified subjects. Here, we attempted to replicate the association of SORL1 in Japanese neuropathologically characterized brain donor subjects (LOAD, 213; control, 370) through a single-nucleotide polymorphism (SNP)-based genetic study involving 19 SNPs: 11 SNPs were selected from the initial study reported by Rogaeva et al. (2007), and the other eight were from our GWAS. Among these SNPs, five exhibited a significant association with LOAD after multiple test correction (p &lt; 2.63E-03 [=0.05/19]), which was supported by means of multiple logistic regression analysis with adjustment for age, gender, and carrier status of the APOE epsilon 4 allele. Three of these SNPs (rs985421, rs12364988 [Rogaeva's SNP 7], and rs4598682) were encompassed by a 5' linkage disequilibrium (LD) region, and the remaining two (rs3781834 and rs3781836) by a 3' LD region. Strong LD among SNPs was observed within each LD region, implying that there are two genomic regions showing association with LOAD in SORL1. Case-control haplotype analysis demonstrated that some haplotypes are associated with LOAD in both LD regions. Our replication study strongly supports the preceding evidence that SORL1 is likely one of the genes associated with LOAD.

DOI： 10.3233/JAD-122395

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DOI： 10.4236/health.2013.57147

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：W B SAUNDERS CO LTD  

Objectives: To preoperatively determine candidates at definitive risk of postoperative delirium (POD), we identified relevant factors in patients with arteriosclerosis obliterans who underwent bypass surgery.
Design: A prospective cohort study.
Patients and methods: 299 patients (age &gt;= 60 years) who underwent bypasses in 1995-2006 were enrolled. Cognitive impairment was assessed by the Revised Hasegawa Dementia Scale, the Confusion Assessment Method was also used, and severity was graded as Grade I Ill (mild to severe) based on the Delirium Rating Scale. All patients were followed for 3 years.
Results: POD occurred in 88 patients (29%), with a median age of 75 (10) years (IQR). Onset was 2 (1)days postoperatively, and a duration of 2 (2) days was observed. POD was hyperactive in 89% and was Grade II, and III in 11%, 68%, and 21% respectively. Multiple logistic regression analysis identified the following risk factors for POD: age &gt;= 72 years (&lt;0.0001), end-stage renal failure (0.001), multiple occlusive lesions (&lt;0.0001), cognitive impairment (0.003), and critical limb ischaemia (0.034). The 3-year survival rate was similar when comparing POD and non-POD patients (84% vs. 88%, NS).
Conclusions: This study identified 5 risk factors for POD in patients undergoing bypasses for limb ischaemia. Long-term outcomes were similar when comparing the patients who experienced POD with those who did not. (C) 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejvs.2012.06.028

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HUMANA PRESS INC  

Survival in patientswith advanced non-small-cell lung cancer (NSCLC) has substantially improved. Long-term chemotherapy with epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) and other agents has been associated with long survival. We retrospectively examined the associations between overall survival (OS) and clinical variables in patients with advanced NSCLC who received at least one dose or course of outpatient chemotherapy in our institution. Of 360 patients who received first-line chemotherapy between January 1, 2004 and December 31, 2007, 185 subsequently received additional outpatient chemotherapy and 175 underwent inpatient chemotherapy only. Of the 185 patients, 147 (79.5%), 96 (51.9%), and 60 (32.4%) received second-line, third-line, and fourth-line chemotherapy, respectively. Patients who received outpatient chemotherapy had significantly longer median OS (22.3 months) than did those undergoing inpatient chemotherapy only (7.6 months; P &lt; 0.0001). In univariate analysis of the 185 patients, sex, performance status (PS), smoking status, stage, best response to first-line chemotherapy, use of docetaxel, and EGFR-TKIs were significantly associated with OS (P values: 0.0019, 0.0066, 0.0001, 0.0231, 0.0011, 0.0250, and 0.0023, respectively). In multivariate analysis, PS, stage, best response to first-line chemotherapy, and use of docetaxel were significantly associated with OS (P values: 0.0272, 0.0030, 0.0022, and 0.0376, respectively). Survival was significantly longer among patients who responded to docetaxel and/or EGF-RTKIs. Long-term chemotherapy did not increase cumulative hospitalization. In patients with advanced NSCLC, an effective long-termchemotherapy regimen might prolong survival in responders to first-line chemotherapy.

DOI： 10.1007/s12032-011-0034-6

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/01.hjh.0000420041.58403.cd

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/01.hjh.0000420020.30587.de

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Language：English   Publisher：Scientific Research Publishing  

DOI： 10.4236/health.2012.47061

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Effects of systemic sitafloxacin on periodontal infection control in elderly patients
Objective: To evaluate the microbiological and clinical effects of the systemic administration of sitafloxacin (STFX) on periodontal pockets in elderly patients receiving supportive periodontal therapy (SPT).
Background: Periodontitis is a risk factor for atherosclerosis. Better periodontal health contributes to reduce atherosclerosis-related diseases in elderly population.
Materials and methods: Forty-four patients undergoing SPT were randomly assigned to two groups: a test group took 100 mg/day of STFX for five consecutive days, or a control group received scaling and root planing (SRP) under local anaesthesia. Microbiological and clinical parameters were examined at baseline and at 1 and 3 months after therapy.
Results: The presence of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia was significantly reduced at 1 month after treatment in both groups. The median reductions of the bacteria between the baseline and 1 month were 3.08 and 2.54% in the STFX- and SRP-treated groups, respectively. Both treatments significantly decreased the probing depth at 1 and 3 months compared to the baseline.
Conclusion: The systemic administration of STFX is effective at improving periodontal health during SPT and could be an alternative to SRP for elderly patients who cannot undergo anaesthesia or are at risk of tissue injury.

DOI： 10.1111/j.1741-2358.2011.00605.x

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Objective: The cost-effectiveness of renal replacement therapy (RRT) is affected by the composition of treatment. This study aimed to estimate the costs and outcomes associated with changing the composition of RRT modality over time. Methods: By using clinical and cost data from a systematic review, a Markov model was developed to assess the costs and benefits of the four main treatments available for RRT in Japan. The model included direct health service costs and quality-adjusted life years (QALY). Sensitivity analyses were performed to assess the robustness of the results. Results: Over the 15-year period of the model, the current composition of RRT (i.e., the base composition of RRT) was $84,008/QALY. The most cost-effective treatment was when the likelihood of a living donor transplant was increased by 2.4-times ($70,581/QALY). Compared with the base composition of RRT, dominant treatments with respect to cost-effectiveness were when the likelihood of a deceased donor transplant was increased by 22-times and when the likelihood of a pre-emptive living donor transplant was increased by 2.4-times. Little difference was found between these two treatments. One-way sensitivity analysis did not change the cost effectiveness except for costs of chronic hemodialysis and a living donor transplant in subsequent years. Limitations: It is difficult to increase the rate of transplant overall in the shorter term nationally and internationally. Conclusions: Appropriate distribution of all transplant options and hemodialysis is necessary to achieve the most cost-effective solution. © 2012 Informa UK Ltd All rights reserved.

DOI： 10.3111/13696998.2011.653512

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

We investigated why the cerebrospinal fluid (CSF) concentrations of A beta 42 are lower in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. Because A beta 38/42 and A beta 40/43 are distinct product/precursor pairs, these four species in the CSF together should faithfully reflect the status of brain gamma-secretase activity, and were quantified by specific enzyme-linked immunosorbent assays in the CSF from controls and MCI/AD patients. Decreases in the levels of the precursors, A beta 42 and 43, in MCI/AD CSF tended to accompany increases in the levels of the products, A beta 38 and 40, respectively. The ratios A beta 40/43 versus A beta 38/42 in CSF (each representing cleavage efficiency of A beta 43 or A beta 42) were largely proportional to each other but generally higher in MCI/AD patients compared to control subjects. These data suggest that gamma-secretase activity in MCI/AD patients is enhanced at the conversion of A beta 43 and 42 to A beta 40 and 38, respectively. Consequently, we measured the in vitro activity of raft-associated gamma-secretase isolated from control as well as MCI/AD brains and found the same, significant alterations in the gamma-secretase activity in MCI/AD brains.

DOI： 10.1002/emmm.201200214

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC CANCER RESEARCH  

Purpose: High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients.
Experimental Design: In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high-and low-risk ovarian cancer groups.
Results: An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 x 10(-20)). We validated its predictive ability with five other data sets using multivariate analysis (Tothill's data set, P = 1 x 10(-5); Bonome's data set, P = 0.0033; Dressman's data set, P = 0.0016; TCGA data set, P = 0.0027; Japanese data set B, P = 0.021). Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response-related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients.
Conclusions: This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients. Clin Cancer Res; 18(5); 1374-85. (C)2012 AACR.

DOI： 10.1158/1078-0432.CCR-11-2725

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TOHOKU UNIV MEDICAL PRESS  

The incidence of esophageal squamous cell carcinoma (ESCC), which is the eighth most common malignancy worldwide, is highest in China. The purpose of this study was to investigate the association between nitrogen compounds in drinking water with the incidence of ESCC by geographical spatial analysis. The incidence of ESCC is high in Shexian county, China, and environmental factors, particularly nitrogen-contaminated drinking water, are the main suspected risk factors. This study focuses on three nitrogen compounds in drinking water, namely, nitrates, nitrites, and ammonia, all of which are derived mainly from domestic garbage and agricultural fertilizer. The study surveyed 48 villages in the Shexian area with a total population of 54,716 (661 adults with ESCC and 54,055 non-cancer subjects). Hot-spot analysis was used to identify spatial clusters with a high incidence of ESCC and a high concentration of nitrogen compounds. Logistic regression analysis was used to detect risk factors for ESCC incidence. Most areas with high concentrations of nitrate nitrogen in drinking water had a high incidence of ESCC. Correlation analysis revealed a significant positive relationship between nitrate concentration and ESCC (P = 0.01). Logistic regression analysis also confirmed that nitrate nitrogen has a significantly higher odds ratio. The results indicate that nitrate nitrogen is associated with ESCC incidence in Shexian county. In conclusion, high concentrations of nitrate nitrogen in drinking water may be a significant risk factor for the incidence of ESCC.

DOI： 10.1620/tjem.226.11

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Canadian Center of Science and Education  

DOI： 10.5539/gjhs.v4n4p42

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Language：Japanese   Publisher：新潟大学災害・復興科学研究所  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：VERSITA  

We conducted an integrated study of cell growth parameters, product formation, and the dynamics of intracellular metabolite concentrations using Escherichia coli with genes knocked out in the glycolytic and oxidative pentose phosphate pathway (PPP) for glucose catabolism. We investigated the same characteristics in the wild-type strain, using acetate or pyruvate as the sole carbon source. Dramatic effects on growth parameters and extracellular and intracellular metabolite concentrations were observed after blocking either glycolytic breakdown of glucose by inactivation of phosphoglucose isomerase (disruption of pgi gene) or pentose phosphate breakdown of glucose by inactivation of glucose-6-phosphate dehydrogenase (disruption of zwf gene). Reducing power (NADPH) was mainly produced through PPP when the pgi gene was knocked out, while NADPH was produced through the tricarboxylic acid (TCA) cycle by isocitrate dehydrogenase or NADP-linked malic enzyme when the zwf gene was knocked out. As expected, when the pgi gene was knocked out, intracellular concentrations of PPP metabolites were high and glycolytic and concentrations of TCA cycle pathway metabolites were low. In the zwf gene knockout, concentrations of PPP metabolites were low and concentrations of intracellular glycolytic and TCA cycle metabolites were high.

DOI： 10.2478/s11756-011-0136-9

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Objective: In 2005, the University of California, San Francisco developed the Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score as a new risk stratification tool. The UCSF-CAPRA, which ranges from 0 to 10 points, consists of five clinical variables, prostate-specific antigen, Gleason score, T stage, percent of positive biopsies and age. The aim of this study was to validate the UCSF-CAPRA score for Japanese prostate cancer patients receiving radical prostatectomy using the contemporary Gleason grading.
Methods: From 1999 to 2010, 211 men who underwent radical prostatectomy were used for validation. Biochemical progression-free survival was calculated using the Kaplan-Meier method and the UCSF-CAPRA and D&apos;Amico risk categories were compared using the log-rank method. The concordance index (c-index) for the UCSF-CAPRA and D&apos;Amico risk classification was calculated.
Results: Using the UCSF-CAPRA score, 85 (40.3%), 106 (50.2%) and 20 (9.5%) subjects were stratified as 0-2 points (low risk), 3-5 points (intermediate risk) and 6-10 points (high risk). Using the D&apos;Amico risk criteria, 66 (31.3%), 89 (42.2%) and 56 (26.5%) were stratified as low-, intermediate- and high-risk groups, respectively. The Kaplan-Meier analysis showed that the UCSF-CAPRA divided the patients significantly into each risk category. There was no significant difference between low and intermediate in the D&apos;Amico risk classification. The c-index of the UCSF-CAPRA and D&apos;Amico classification was 0.755 and 0.713, respectively.
Conclusion: The UCSF-CAPRA is an acceptable risk category tool comparable to that of the D&apos;Amico risk classification for Japanese prostate cancer patients receiving radical prostatectomy in the contemporary Gleason grading era.

DOI： 10.1093/jjco/hyr136

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registry in 2008. Approximately 50 data items, including surgical procedures, pathological diagnoses, and survival outcomes, for 12004 patients with primary gastric cancer treated in 2001 were collected retrospectively from 187 participating hospitals. Data were entered into the JGCA database according to the JGCA Classification of gastric carcinoma, 13th edition and the International Union Against Cancer (UICC) TNM Classification of malignant tumors, 5th edition by using an electronic data collecting system. Finally, data of 11261 patients with gastric resection were analyzed. The 5-year follow-up rate was 83.5%. The direct death rate was 0.6%. TNM 5-year survival rates (5YSRs)/JGCA 5YSRs were 91.8/91.9% for stage IA, 84.6/85.1% for stage IB, 70.5/73.1% for stage II, 46.6/51.0% for stage IIIA, 29.9/33.4% for stage IIIB, and 16.6/15.8% for stage IV. The proportion of patients more than 80 years old was 7.0%, and their 5YSR was 48.7%. Compared to the JGCA archived data, though the follow-up rate needs to be improved, these data suggest that the postoperative results of patients with primary gastric carcinoma have improved in those with advanced disease and in the aged population in Japan.

DOI： 10.1007/s10120-011-0085-6

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This study was intended to compare the prognostic power of the number of positive lymph nodes with that of the lymph node ratio in patients with ampullary carcinoma.
A retrospective analysis was conducted of the medical records of 71 consecutive patients with ampullary carcinoma who underwent pancreaticoduodenectomy with regional lymph node dissection. A total of 2151 lymph nodes were dissected (median: 28 nodes per patient) and examined histologically. Cutoff points were determined for both the number of positive nodes and the lymph node ratio using chi(2) scores calculated with the Cox proportional hazards regression model.
Lymph node metastasis was found in 34 patients. The best cutoff point for the number of positive nodes was identified as three nodes, and that for the lymph node ratio was identified as 10%. Univariate analysis revealed both the number of positive nodes (0, 1-3, or a parts per thousand yen4; P &lt; 0.0001) and the lymph node ratio (0%, 0-10%, or &gt; 10%; P &lt; 0.0001) as significant prognostic factors. Multivariate analysis identified the number of positive nodes as an independent prognostic factor (P &lt; 0.001), whereas the lymph node ratio failed to remain as an independent variable. The cumulative 5-year survival rates were 85% for patients with 0 positive nodes, 63% for patients with 1-3 positive nodes, and 0% for patients with a parts per thousand yen4 positive nodes (P &lt; 0.0001).
The number of positive lymph nodes better predicts the outcome after resection than the lymph node ratio in patients with ampullary carcinoma.

DOI： 10.1007/s00268-011-1175-7

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Language：Japanese   Publisher：(一財)厚生労働統計協会  

目的 本研究では,介護支援専門員の基礎資格を看護系と介護系に分けて,主治医とのコミュニケーションのとり方に違いがあるかどうかを,アンケート調査に基づき統計学的に分析した。方法 アンケートの調査時期は2006年11月であり,対象地域は1県4市の合計5ヶ所である。対象者は居宅介護支援事業所の介護支援専門員であり,その基礎資格を看護系と介護系の2種に大別した。群間における主治医との連携の違いを調べるために,アンケート調査票の中で「主治医との連携」に関連のある4項目を選び比較検討を行った。結果 ケアマネジメント業務での相談相手としては,看護系,介護系ともに「サービス事業者」と「職場の上司・同僚」が高率であった。「主治医」との相談は看護系で有意に高かった。サービス担当者会議に関しては,その開催にあたり「参加を呼びかけた人」は,両群ともに「サービス事業者」「家族」「利用者」が高率であった。また,看護系において有意に高かった項目は,「主治医」であった。さらに,開催にあたり困難を感じる理由としては,両群ともに「サービス事業者との日程調整」の割合が高かった。「主治医が出席できない」を理由として挙げた人の割合は介護系で有意に高かった。介護系の介護支援専門員が考える,医師がサービス担当者会議に参加しない理由としては,「介護支援専門員自身が主治医に出席を呼びかけていない」「介護支援専門員と主治医との信頼関係が確立されていない」「主治医と連絡がつかない」の3項目であった。結論 看護系と介護系の2群間で主治医との連携には大きな違いがあることがわかった。両群ともに,医療との連携が十分とはいえないが,看護系は介護系に比べ主治医との連携が良好であった。このことは,各介護支援専門員の基礎資格,すなわち,それぞれの異なる教育課程や経験に起因するものと考えられる。看護系の介護支援専門員が減少し,介護系の介護支援専門員が増加している現状を踏まえ,基礎資格別の教育システムの導入が必要と考える。同時に医療関係者の介護保険制度に対する認識を深める施策も重要である。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Rationale and Objectives: To evaluate reconstruction image quality at the systolic and diastolic cardiac phases and determine the optimal phase for reconstruction according to heart rate when using dual-source computed tomography (CT) with 75 ms temporal resolution.
Materials and Methods: We retrospectively reviewed the CT datasets of 35 patients with regular heartbeats who underwent coronary CT angiography. Images were reconstructed in 2% steps between 32 and 78% of the beat-to-beat interval. Two experienced radiologists determined the reconstruction interval with the fewest motion artifacts and the motion score of each vessel for the systolic and diastolic phases. Subgroup analysis was performed in patients having heart rates of &lt;70,70-80, and &gt;80 beats per minute (bpm).
Results: In the subgroup with heart rates of &lt;70 bpm, the diastolic phase reconstruction image quality was significantly better than for the systolic phase (P &lt; .01). In the 70-80 bpm and &gt;80 bpm subgroups, no significant difference was observed. In the diastolic phase, the image quality of the &lt;70 bpm subgroup was significantly better than for the &gt;80 bpm subgroup (P &lt; .05). In all systolic phase subgroups and other diastolic phase subgroups, no significant difference was observed.
Conclusions: Using a DSCT scanner with 75 ms temporal resolution, reconstruction at the diastolic phases should be used for patients with heart rates &lt;70 bpm. For heart rates &gt;70 bpm, larger studies are necessary to determine whether reconstruction at the systolic, diastolic, or both phases should be used.

DOI： 10.1016/j.acra.2011.01.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TOHOKU UNIV MEDICAL PRESS  

The incidence of esophageal adenocarcinoma has been rising in many countries, while esophageal squamous cell carcinoma has remained stable or even declined in the same populations over the identical periods. These differences in trends indicate that these cancer subtypes may have a different etiology, which may be caused by lifestyle factors such as alcohol consumption and cigarette smoking. Therefore, a matched case-control study to clarify the risk factors of alcohol and tobacco intake on the development of esophageal adenocarcinoma was collected in Hebei Province of China. The life expectancy of the study area was around 70 years old. In the present study, 98 patients younger than 65 years who were diagnosed with esophageal adenocarcinoma and had initial surgeries (cases) were matched with 294 healthy adults (controls) at a ratio of 1:3 according to sex and age. We found the proportions of drinkers and smokers among cases were 48.0% and 60.2%, respectively, versus 21.2% and 43.5% among controls. Univariate conditional logistic regression analyses revealed that the odds ratios (ORs) showed a nearly monotonic increase for the duration of alcohol consumption and duration of tobacco smoking. Multivariate conditional logistic regression analysis indicated that only alcohol consumption was a significant risk factor for esophageal adenocarcinoma. Additional analysis of the combination of amount and duration of alcohol consumption indicated that heavy drinkers (&gt; 30 ml/day) had significantly higher ORs, irrespective of the duration of alcohol consumption. In conclusion, heavy alcohol consumption increases the risk for esophageal adenocarcinoma independent of the duration of such consumption.

DOI： 10.1620/tjem.224.21

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Early detection and intervention in schizophrenia are important in improving quality of life after treatment and are major issues in psychiatric care. Therefore, it is necessary to increase knowledge of schizophrenia among the general public. Among parents of junior and senior high school students in Japan, we compared rates of correct answers for items on knowledge of schizophrenia and ability to discriminate this psychosis from other disorders on questionnaires given before and after viewing a web-based education program.
Methods: Questionnaires were distributed to 2,690 parents. The program was developed to help parents obtain a basic understanding of schizophrenia and to emphasize the necessity of early detection.
Results: Before the program, the rate of correct answers was 77% for items concerning basic knowledge of schizophrenia, 47% for "discrimination of schizophrenia symptoms," and 30% for "discrimination of prodromal symptoms." The program resulted in an improvement in basic knowledge of schizophrenia, discrimination of schizophrenia symptoms, and discrimination of prodromal symptoms (P &lt; 0.001 for all).
Conclusions: Our web-based education program was useful in helping parents acquire a basic knowledge of schizophrenia and discriminate correctly the symptoms of schizophrenia.

DOI： 10.1186/1471-2458-11-323

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INFORMA HEALTHCARE  

Background. Total and antigen-specific IgE levels vary greatly with age; however, it is unclear whether they are more closely related to patient age or birth cohort. Objective. To determine whether birth cohort or age was more strongly correlated with total and specific IgE levels. Methods. We retrospectively examined the medical records of 5136 asthma patients who were treated at the Niigata Allergic Disease Research Institute Outpatient Clinic during the period from 1997 to 2005. The subjects were divided into four birth cohorts based on their year of birth: the first cohort was born in 1935 or earlier, the second in 1936--1955, the third in 1956--1975, and the fourth in 1976 or later. Their total IgE level and mite-, cedar-, and Candida albicans (Candida)-specific IgE levels were measured using the CAP RAST fluoroenzyme immunoassay test. Results. Univariate analysis revealed that total IgE level and mite-, cedar-, and Candida-specific IgE levels significantly decreased (p &lt; .001) with advancing age. In addition, there were significantly higher IgE levels in later birth cohorts (p &lt; .01). On multivariate analysis, there were associations of total IgE level and mite- and cedar-specific IgE levels with both age and birth cohort. However, there was no significant association between Candida-specific IgE antibody level and either age or birth cohort. Conclusions. The associations of total and specific IgE levels with age and birth cohort were different. Thus, in comparing the results of IgE antibody testing done in different years, even for patients of the same age, the possibility of a birth cohort effect on IgE levels should be considered.&lt;/.

DOI： 10.3109/02770903.2011.558152

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Background: Neoadjuvant chemotherapy (NAC) is one of the main strategies for patients with locally advanced breast cancer. In our previous study, biological markers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2 were essential predictors of the effectiveness of NAC to help individualize treatment. This study examined the effect of NAC on the disease-free survival (DFS) of breast cancer patients. Furthermore, the study was expanded by adding Ki-67 as a biological marker, and examined the correlation between Ki-67 and the prognosis. Patients and Methods: Between September 2005 and September 2007, 43 patients with breast cancer received NAC and surgery. Four cycles of DC (doxorubicin: 60 mg/m(2), and cyclophosphamide: 500 mg/m2) were administered intravenously (i.v.) on day 1 every 21 days, followed by 12 cycles of paclitaxel i.v. (80 mg/m2) every 7 days, prior to surgery. The primary endpoint was the pathological complete response (pCR) rate and the secondary endpoint was DFS; the pCR rate was estimated for each groups stratified by the presence or absence of different factors (PcR, ER/PgR, and Ki-67). Results: The clinical response (cCR+cPR) rate was 81.0%, and the pCR rate was 25.6%. The pCR rate was 75, 50, 9 and 0% in HER2(+)/ER(-), HER2(+)/ER(+), HER2(-)/ER(-), and HER2(-)/ER(+) patients, respectively. The 4-year DFS rate was estimated at 78% for all patients. The HER2 status was an independent predictor of pathological complete response (pCR). The DFS rate of patients with lower Ki-67 values (&lt; 15%) was higher than that of patients with higher Ki-67 values (&gt;= 15%). The treatment-related adverse events were manageable: the majority were mild, but five patients experienced grade 3 (neutropenia and sensory neuropathy) adverse events. Conclusion: DC followed by weekly paclitaxel is an active and manageable preoperative regimen for breast cancer patients. HER2 overexpression may be a good predictive marker of pCR, and the Ki-67 value after NAC may be a prognostic factor for DFS.

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BACKGROUND: Total and antigen-specific IgE levels vary greatly with age; however, it is unclear whether they are more closely related to patient age or birth cohort. OBJECTIVE: To determine whether birth cohort or age was more strongly correlated with total and specific IgE levels. METHODS: We retrospectively examined the medical records of 5136 asthma patients who were treated at the Niigata Allergic Disease Research Institute Outpatient Clinic during the period from 1997 to 2005. The subjects were divided into four birth cohorts based on their year of birth: the first cohort was born in 1935 or earlier, the second in 1936-1955, the third in 1956-1975, and the fourth in 1976 or later. Their total IgE level and mite-, cedar-, and Candida albicans (Candida)-specific IgE levels were measured using the CAP RAST fluoroenzyme immunoassay test. RESULTS: Univariate analysis revealed that total IgE level and mite-, cedar-, and Candida-specific IgE levels significantly decreased (p &lt; .001) with advancing age. In addition, there were significantly higher IgE levels in later birth cohorts (p &lt; .01). On multivariate analysis, there were associations of total IgE level and mite- and cedar-spec

DOI： 10.3109/02770903.2011.558152

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: This study aimed to evaluate the usefulness of immunohistochemical combinations for discrimination between intraepithelial ductal spread of colorectal carcinoma liver metastasis (CRLM) and that of intrahepatic cholangicarcinoma (ICC).
Methodology: A retrospective analysis of resected specimens from 151 patients with CRLM and 28 patients with ICC was conducted. Intraepithelial ductal spread along the bile ducts was judged positive when tumor cells spreading along the intact basement membranes of intrahepatic bile ducts. We evaluated immunoreactivity of cytokeratin (CK) 7, CK20, CDX2, MUC2, MUC5AC and human gastric mucin (HGM).
Results: Of the 151 patients with CRLM, 21 had intrahepatic bile duct involvement verified histologically. Intraepithelial ductal spread was detected in 17 of 21 (81%) patients with CRLM with bile duct involvement, whereas it was detected in 22 of 28 (79%) patients with ICC. CK20-positive/CK7-negative immunophenotype demonstrated a high accuracy of 95% for evaluation of intraepithelial ductal spread from CRLM. CK7-positive/CK20-negative immunophenotype demonstrated the highest accuracy of 85% for evaluation of intraepithelial ductal spread from ICC.
Conclusion: Intraepithelial ductal spread is a common feature of CRLM with bile duct involvement. Immunohistochemical combination of CK7 and CK20 is useful for discrimination between intraepithelial ductal spread of CRLM and that of ICC.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Objectives:
The aim of the current study was to establish the predictive accuracy of the Kattan postoperative nomogram for non-metastatic renal cell carcinoma (RCC) in a Japanese population.
Methods:
A total of 211 patients with stage T1-3N0M0 clear cell RCC who underwent radical nephrectomy or nephron-sparing surgery between 1991 and 2004 were included in this analysis. Median follow up was 81 months (range: 4-208). Univariate and multivariate analyses were performed, and the influence of age, sex, clinical presentation, T stage, histological tumor size, grade, and microvascular invasion on disease recurrence-free survival (RFS) was determined. For each patient, the prognostic score for 5-year RFS was calculated using the Kattan nomogram. The discriminating ability of this model was assessed by the concordance index, and bootstrapping was used to evaluate confidence intervals.
Results:
The 5-year RFS rate for all patients calculated using the Kaplan-Meier method was 80.6%. In multivariate analysis, the statistically significant prognostic factors for 5-year RFS were high-grade tumors (P = 0.019) and symptomatic disease (P = 0.017). The concordance index for RFS predicted by the Kattan nomogram was 0.735 (95% confidence interval: 0.734-0.736). There was a slight discrepancy between the RFS predicted by the Kattan nomogram and the likelihood of being recurrence-free at 5 years according to the Cox analysis in the current patient population.
Conclusion:
These findings suggest the necessity of constructing a more useful nomogram for predicting the prognosis of Japanese patients with non-metastatic RCC.

DOI： 10.1111/j.1442-2042.2010.02693.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Canadian Center of Science and Education  

DOI： 10.5539/gjhs.v4n1p33

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DOI： 10.4236/health.2011.34042

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ASIAN PACIFIC ORGANIZATION CANCER PREVENTION  

Aim: Geographic variation of upper gastrointestinal carcinomas (UGIC) was assessed in a high-risk region in northern China. Methods: Shexian, Linzhou, Yangcheng and Cixian are four counties with world age-standardized incidence rates (ASR) of esophageal cancer as high as 124.9, 99.5, 160.1, and 164.9 per 100,000 respectively for males, and 70.8, 68.8, 92.1, and 104.6 for females for 1998 to 2002. Geographically, Shexian is entirely mountainous, Linzhou and Yangcheng are mostly mountainous, and Cixian is one-third mountains, one-third hills, and the other third plains. The corresponding populations is 382,000, 982,000, 395,000 and 625,000 as in 2000. In the present analyses, the world ASRs of esophageal squamous cell carcinoma (ESCC), adenocarcinoma of the esophagogastric junction (AEG), gastric non-cardia carcinoma (GNCC), and the percentages of these in overall tumor ASRs for 1998 to 2002 were compared across the four counties to show geographic variation and clustering. Additionally, site-specific detection rates of precursors and cancers in our population-based endoscope surveys with local 40- to 69-year-old residents were also compared between a Cixian commune (2,013 surveyed) and a Shexian commune (1,514). Results: ASRs for ESCC, AEG, and GNCC combined amount to 210.5 to 325.8 per 100,000 in men and 117.5 to 185.7 in women, accounting for respectively 70.6 to 82.1% and 53.4 to 77.0 % of the all ASRs. In geographic distribution, the percentages of AEG and GNCC in UGICs increased from Cixian (males 32.8%, females 22.1%) to Yangcheng (50.7%, 38.6%) and Linzhou (52.7%, 41.4%), and further to Shexian (61.7%, 61.9); while that of ESCC decreased in the same direction from Cixian, to Yangcheng and Linzhou, and further to Shexian (67.2%, 77.9%; 49.3%, 61.4% and 47.3%, 58.6%; to 38.3%, 38.1%). Similarly, the detection rates of low-and high-grade intraepithelia neoplasia as well as cancers of the esophagus were significantly higher in the Cixian commune than the Shexian commune (8.7, 4.4, 0.7% vs 7.0, 3.2, 0.4% P=0.004); but the rates for the esophagogastric junction were systematically and significantly lower in the Cixian than in the Shexian commune (2.2, 0.5, 0.8 % Vs 3.3, 0.9, 1.7 %, P=0.001). Conclusions: Clustering of upper gastrointestinal carcinomas may suggest the existence of common risk factors, while geographic variation in topography/histology may be related to regional differences in carcinogen exposure. These observations identify a need for environment improvement, such as programs to improve drinking water conditions. To study high susceptibility in a historically low mobile population, international collaborative research in this region may prove to be very fruitful.

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Background: Stigma toward schizophrenia is a substantial barrier to accessing care and adhering to treatment. Provisions to combat stigma are important, but in Japan and other developed countries there are few such provisions in place that target parents of adolescents. The attitudes of parents are important to address as first schizophrenic episodes typically occur in adolescence. In overall efforts to develop an education program and provisions against stigma, here we examined the relationship between stigma toward schizophrenia and demographic characteristics of parents of junior and senior high school students in Japan. The specific hypothesis tested was that contact and communication with a person with schizophrenia would be important to reducing stigma. A questionnaire inquiring about respondent characteristics and which included a survey on stigma toward schizophrenia was completed by 2690 parents. Results: The demographic characteristics significantly associated with the Devaluation- Discrimination Measure were family income, occupation, presence of a neighbor with schizophrenia, and participation in welfare activities for people with mental illness (p &lt
0.05). The mean ±SD score was 32.74 ± 5.66 out of a maximum of 48 points on the Link Devaluation- Discrimination Measure. Conclusions: Stigma toward schizophrenia among parents of junior and senior high school students was in fact significantly stronger among members of the general public who had had contact with individuals with schizophrenia. In addition, stigma was associated with family income. © 2011 Yoshii et al
licensee BioMed Central Ltd.

DOI： 10.1186/1756-0500-4-558

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Language：Japanese  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

The effects of alcohol consumption and tobacco smoking on the prevalence of esophageal cancer vary considerably by country, race and lifestyle. Few data exist on the effect of the interaction between the amount and duration of alcohol consumption and tobacco smoking on the incidence of esophageal cancer. In this case-control study, the cases included patients with histologically confirmed esophageal squamous cell carcinoma (ESCC) younger than 60 years of age and recruited between January 1, 2002 and December 31, 2006. The controls had no abnormality during a medical checkup. A total of 835 pairs were created by pairing each case to a gender- and age-matched control. Conditional logistic regression analysis was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals. Univariate conditional logistic regression analyses revealed that the ORs according to both duration of alcohol consumption and tobacco smoking increased monotonically. Alcohol consumption and tobacco smoking may have a synergistic effect on the incidence of ESCC. Conditional logistic regression analysis using a forward stepwise selection procedure revealed that the incidence of ESCC was associated with the duration of tobacco smoking, the interaction between the amount and duration of alcohol consumption, and a family history of cancer. In particular, groups with a long duration of alcohol consumption and high alcohol intake had much higher ORs than those with short duration and low intake, which highlights the importance of the interaction between the amount and duration of alcohol intake. This study confirmed the significance of the interaction between alcohol consumption and tobacco smoking in esophageal cancer. This interaction between amount and duration is an accurate indicator for estimating the risk of esophageal cancer attributable to alcohol consumption and tobacco smoking. These findings suggest that decreasing the number of young and middle-aged drinkers and smokers will reduce the incidence of esophageal cancer.

DOI： 10.3892/etm.2010.152

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

Neuronal growth cones migrate directionally under the control of axon guidance molecules, thereby forming synapses in the developing brain. The signal transduction system by which a growth cone detects surrounding guidance molecules, analyzes the detected signals, and then determines the overall behavior remains undetermined. In this study, we describe a novel stochastic model of this behavior that utilizes multiple sensors on filopodia to respond to guidance molecules. Overall growth cone behavior is determined by using only the concentration gradients of guidance molecules in the immediate vicinity of each sensor. The detected signal at each sensor, which is treated as a vector quantity, is sent to the growth cone center and then integrated to determine axonal growth in the next step by means of a simple vector operation. We compared the results of computer simulations of axonal growth with observations of actual axonal growth from co-culture experiments using olfactory bulb and septum. The probabilistic distributions of axonal growth generated by the computer simulation were consistent with those obtained from the culture experiments, indicating that our model accurately simulates growth cone behavior. We believe that this model will be useful for elucidating the as yet unknown mechanisms responsible for axonal growth in vivo. (c) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jtbi.2010.07.036

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE CIRCULATION SOC  

Background: Erythropoietin (EPO) has been found to have anti-apoptotic and tissue protective effects on the myocardium. The aim of the present pilot study was to observe the safety and efficacy of EPO administration for patients with acute myocardial infarction (AMI).
Methods and Results: Patients admitted with AMI had all undergone successful percutaneous coronary intervention (PCI). Patients were randomly assigned to 2 groups (control and EPO groups), and given 12,000 IU EPO iv or saline after PCI. The primary endpoints were the difference between the acute phase and chronic phase (6 months after the attack) regarding left ventricular function as measured on electrocardiogram-gated single-photon emission computed tomography. Thirty-six patients (control 16, EPO 20) were eligible for analysis. Left ventricular ejection fraction (LVEF) significantly increased in the EPO group (from 51.0 +/- 19.6% to 58.5 +/- 15.0%, P=0.0238), but not in the control group. Further analysis was separately undertaken in patients with occlusion in the left anterior descending artery (LAD) and others (non-LAD). LVEF was &lt;50% in most patients in the LAD subgroup, and LVEF significantly increased in the EPO group (37.5 +/- 13.0 to 52.7 +/- 15.8, P=0.0049), but not in the control group. EPO administration did not trigger any adverse clinical events.
Conclusions: EPO administration is a promising treatment for AMI. (Circ J 2010; 74: 1415-1423)

DOI： 10.1253/circj.CJ-10-0109

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER THORACIC SOC  

Rationale: Inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) is a promising therapy for pulmonary alveolar proteinosis (PAP) but has not been adequately studied.
Objectives: To evaluate safety and efficacy of inhaled GM-CSF in patients with unremitting or progressive PAP.
Methods: We conducted a national, multicenter, self-controlled, phase II trial at nine pulmonary centers throughout japan. Patients who had lung biopsy or cytology findings diagnostic of PAP, an elevated serum GM-CSF antibody level, and a Pa(O2) of less than 75 mm Hg entered a 12-week observation period. Those who improved (i.e., alveolar-arterial oxygen difference [A-aDO(2)] decreased by 10 mm Hg) during observation were excluded. The rest entered sequential periods of high-dose therapy (250 mu g Days 1-8, none Days 9-14; x six cycles; 12 wk); low-dose therapy (125 mu g Days 1-4, none Days 5-14; x six cycles; 12 wk), and follow-up (52 wk).
Measurements and Main Results: Fifty patients with PAP were enrolled in the study. During observation, nine improved and two withdrew; all of these were excluded. Of 35 patients completing the high- and low-dose therapy, 24 improved, resulting in an overall response rate of 62% (24/39; intention-to-treat analysis) and reduction in A-aDO(2) of 12.3 mm Hg (95% confidence interval, 8.4-16.2; n = 35, P &lt; 0.001). No serious adverse events occurred, and serum GM-CSF autoantibody levels were unchanged. A treatment-emergent correlation occurred between A-aDO(2) and diffusing capacity of the lung, and high-resolution CT revealed improvement of ground-glass opacity. Twenty-nine of 35 patients remained stable without further therapy for 1 year.
Conclusions: Inhaled GM-CSF therapy is safe, effective, and provides a sustained therapeutic effect in autoimmune PAP.

DOI： 10.1164/rccm.200906-0978OC

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Language：Japanese   Publisher：(一財)厚生労働統計協会  

目的 本研究では,地域包括支援センターの役割とサービス担当者会議の運営方法について,居宅介護支援事業所を対象としたアンケート調査に基づき,問題点と解決策を検討した。方法 アンケートの実施時期は2006年11月9日〜11月30日,対象地域は1県4市の合計5ヶ所である。また,対象者は居宅介護支援事業所の介護支援専門員である。1,487人の回答に基づき,「主任介護支援専門員の業務達成度」「ケアマネジメント業務上での相談相手」「サービス担当者会議に参加すべき人とその開催に関わるべき団体」「サービス担当者会議開催時の地域包括支援センターのサポート体制」および「地域包括支援センターへの期待・要望」について,集計・分析を行った。結果 介護支援専門員による,地域包括支援センターの主任介護支援専門員の役割に対する評価において,多職種協働・連携による長期継続ケアマネジメントの支援については評価が低かった。ケアマネジメント業務を進める上の相談相手としては,職場の上司・同僚(78.5%)サービス事業者(77.1%),についで,地域包括支援センターの職員(47.9%)であった。サービス担当者会議の運営に関しては,地域包括支援センター職員の会議への毎回参加は期待されていない。その一方で,会議開催の旗振り役への期待が57.2%と高率であった。また,サービス担当者会議開催への地域包括支援センターのサポートに,満足している人の割合は,22.4%にとどまった。「大変満足している」人43名と,「まったく満足していない」人182名を対象に,フリーコメントを集計したところ,「地域包括支援センターの職員の経験,専門性,資質の不足」「介護予防ケアプラン作成などの業務量が多く多忙」「居宅介護支援事業所と地域包括支援センターとの連携上の問題」などが挙げられた。結論 居宅介護支援事業所の介護支援専門員からみた地域包括支援センターには,解決すべきいくつかの課題が残されていることがわかった。特に,主任介護支援専門員は指導,助言,相談の役割を求められているが,それらについての介護支援専門員による評価は必ずしも高くはない。また,サービス担当者会議の運営に関して,地域包括支援センターの間接的なサポートの方法にも課題が残されている。これらの解決方法として,地域包括支援センターの組織の改変や職員のキャリアアップ体制の整備が必要と考える。(著者抄録)

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Background: The aim of this study was to identify factors responsible for childhood-onset persistent asthma and childhood-onset asthma relapsing in adulthood. Methods: We compared a number of potential risk factors for asthma among 608 patients with childhood-onset persistent asthma (onset at 15 years of age or younger) and 286'patients with childhood-onset asthma (onset at 20 years or younger) that had relapsed "after a period of remission longer than 2 years. Results: Multiple linear regression analysis revealed that the factors associated with childhood-onset persistent asthma were a past or present history of allergic rhinitis (p = 0.001) and high serum total IgE concentration (≥300IU/ml
p = 0.007). The factors associated, with relapse of childhood-onset asthma were female sex {p = 0.001), younger onset age (p = 0.036), and smoking (current or former: p&lt
0.001). Conclusion: Our findings indicate that a past or present history of allergic rhinitis and high serum IgE level are significant risk factors for childhood-onset persistent asthma, and that female sex and a history of smoking are risk factors for relapse of childhood-onset asthma Fortunately, exposure to r tobacco smoke is a controllable risk factor. © 2010 Japanese Society of Allergology.

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：Japanese   Publisher：(一社)日本医療情報学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

The case fatality rate is an important indicator of the severity of a disease, and unbiased and accurate estimates of it during an outbreak are important in the study of epidemic diseases, including severe acute respiratory syndrome (SARS). In this paper, estimation methods are developed using a constant cure-death hazard ratio. A semiparametric model is presented, in which the cure-death hazard ratio is a parameter of interest, and a profile likelihood-based technique is proposed for estimating the case fatality rate. An extensive simulation was carried out to investigate the performance of this technique for small and medium sample sizes, using both summary and individual data. The results show that the performance depends on the model validity but is not heavily dependent on the sample size. The method was applied to summary SARS data obtained from Hong Kong and Singapore.

DOI： 10.1007/s10985-009-9119-3

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Language：Japanese   Publisher：THE JAPANESE SOCIETY OF PEDIATRIC ALLERGY AND CLINICAL IMMUNOLOGY  

Background:<BR>The demographic characteristics of asthma patients in Japan are not known in detail. The investigation of regional differences in prevalence of asthma is useful to identify factors that might predispose individuals to asthma. <BR>Methods:<BR>We examined data from the Ministry of Health, Labour and Welfare "Vital Statistics" and "Patient Survey" reports of 1999, 2002, and 2005.<BR>The number of patients with asthma per 1000 population stratified by age, sex and prefecture was analyzed.<BR>Results:<BR>Although the total number of patients with asthma reported in 1999, 2002, and 2005 did not significantly differ, there was a significant increase over time in the number of asthmatic boys aged 0 to 14 years and the number of asthmatic girls aged 0 to 4 years. There were also significant differences in asthma prevalence by prefecture: prevalence was higher in Hokkaido and in the area adjacent to the Sea of Japan in the Tohoku region, and lower in Okinawa prefecture and the Kinki region in 1999, 2002, and 2005. <BR>Conclusion:<BR>In Hokkaido, the prevalence of asthma was consistently high, and consecutively increased, from 1999 through 2005.

DOI： 10.3388/jspaci.23.303

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Other Link： http://search.jamas.or.jp/link/ui/2009353602

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

Objective:
Microscopic portal vein invasion (PVI) by cancer cells is a poor prognostic factor after hepatic resection for hepatocellular carcinoma (HCC). The aim of this study is to predict PVI preoperatively in patients with HCC.
Methods:
We studied 46 hepatectomized patients who had HCC without any portal venous invasion detected during preoperative radiographic evaluation. We defined the portal perfusion defect area ratio (PPDAR) as the following: the quotient of the maximal portal perfusion defect area, on computed tomography during arterio-portography (CTAP) is divided by the maximal tumor area on magnetic resonance imaging (MRI) or CT.
Results:
The median PPDAR was 1.3 (mean 1.4 +/- 1.1; ranged from 0.7 to 5.8). The incidence of PVI was 4.5% in patients with a PPDAR &lt; 1.3, 35.7% in those with a PPDAR of 1.3-1.6, 70% in those with a PPDAR &gt;= 1.6 (P = 0.0005). When analyzing the preoperative value of different cut-off points for the PPDAR, the lowest P-value by Fisher&apos;s exact test was achieved when the PPDAR threshold was 1.6 (P = 0.0012). The sensitivity was 58%, and specificity was 91% with this cut-off value. On univariate analyses, factors that significantly correlated with PVI were PPDAR (P = 0.0012), serum levels of des-gamma-carboxy prothrombin (P = 0.033), and tumor size (P = 0.0126). On multivariate analysis, PPDAR was the only significant independent predictor of PVI.
Conclusion:
Our study shows that PPDAR is a new concept, which is useful in predicting PVI and that a value &gt;= 1.6 is predictive of PVI.

DOI： 10.1111/j.1440-1746.2009.05847.x

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BACKGROUND AND PURPOSE Three-dimensional anisotropy contrast (3DAC) based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) sequence on a 3.0T system is a new magnetic resonance imaging technique capable of providing images with significantly high anatomical resolution. The purpose of this study was to confirm whether this technique can characterize the degenerative processes in the brainstem of patients with spinocerebellar degeneration (SCD). METHODS 3DAC images of 13 patients with multiple system atrophy with predominant cerebellar symptoms (MSA-C) and seven International Cooperative Ataxia Rating Scale (ICARS) score-matched patients with Machado-Joseph disease (MJD) were created using a diffusion-weighted PROPELLER sequence on a 3.0T system. The section of the middle pons was chosen for morphometric and diffusivity analyses. RESULTS The above analyses showed that atrophy and increased diffusivity of the ventral portion of the pons indicated MSA-C, whereas atrophy and increased diffusivity of the pontine tegmentum indicated MJD. Furthermore, ICARS scores significantly correlated with both the severities of the pontine atrophy and the mean diffusivity values of the ventral pontocerebellar tracts. CONCLUSIONS This study demonstrated that 3DAC PROPELLER on a 3.0T system enables in vivo "tract by tract" quantitative analysis of pontine degeneration in SCD. J Neuroimaging 2009
19:220-226. © 2008 by the American Society of Neuroimaging.

DOI： 10.1111/j.1552-6569.2008.00273.x

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Language：Japanese   Publisher：新潟医学会  

静脈血栓塞栓症(VTE)は、発症しても臨床症状に乏しく早期診断が困難であること、また重篤な場合は死に至ることから予防が重要とされている。本研究の目的は、人工股関節置換術(THA)と人工膝関節置換術(TKA)を受けた入院患者を対象とし、予防の実施状況、VTEの発症率、および、理学的・薬物的予防効果を推定することである。本院において2005年1月から2006年3月までに、THAおよびTKAを受けた97例を対象とした。解析に用いたデータ項目は、診察所見、検査、手術に関するデータの13項目である。理学的予防、薬物的予防の実施率は、それぞれ100%、19.6%であった。97例におけるVTE発症率は23.7%であったが、VTE既往歴の有無で層別したときの発症率は、それぞれ、42.3%、16.9%であった。ロジスティック回帰分析の結果、VTE発症に関与する危険因子はVTE既往歴のみが選択された。VTEの既往歴で層別したそれぞれの層において、薬物的予防実施群と非実施群のVTE発症率を比較した。その結果、いずれの層でも実施群のVTE発症率が非実施群に比べて低かった。また合併症指標として薬物的予防実施群と非実施群でのヘモグロビン値と血小板数を比較した結果、有意な差は認められなかった(P=0.864、P=0.255)。本研究において、理学的・薬物的予防がVTEの発症率を下げることを示唆した。これらの予防効果に関する探索的な推定値を使い、確証的な予防効果を得るための臨床試験を行うことが必要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J00990&link_issn=&doc_id=20091124040005&doc_link_id=%2Fdg3nigta%2F2009%2F012307%2F005%2F0357-0362%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2009%2F012307%2F005%2F0357-0362%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：TOHOKU UNIV MEDICAL PRESS  

Hepcidin, a key iron-regulator secreted from the liver, consists of 25 amino acids (hepcidin-25), blocks iron release from macrophages via internalization and degradation of cellular iron exporter ferroportin, and restrains the use of iron in organs. Hepcidin mRNA and protein are also expressed in the human heart. A short form of hepcidin that lacks 5 amino-acid residues in the N-terminus (hepcidin-20) has been found in human serum, although its physiological role is unknown. Here, we successfully measured the serum levels of hepcidin-25 and hepcidin-20 in 12 patients with acute myocardial infarction (AMI) using surface-enhanced laser desorption ionization time of flight mass spectrometry. Among the selected 10 patients, whose blood samples were taken within 4 hours after a heart attack, all the patients showed elevated serum levels of hepcidin-20 [between 31.7 and 285.1 arbitrary unit (AU); normal level &lt; 9.3 AU], while 8 patients showed high levels of hepcidin-25 (9.3-271.4; normal &lt; 25.5 AU). The hepcidin-20 level was decreased to nearly the normal level on day 7 (range of 2.9 to 12.5 AU) in the 12 patients, whereas the hepcidin-25 level remained high on day 7 in 8 patients. Furthermore, the elevated levels of hepcidin-25 and hepcidin-20 were not correlated with the serum levels of markers for inflammation, interleukin-6 and C-reactive protein, in the patients with AMI. In conclusion, the serum hepcidin-20 is transiently elevated in response to acute cardiac ischemia. Measurement of serum hepcidin-20, rather than hepcidin-25, is helpful for diagnosis of acute myocardial infarction.

DOI： 10.1620/tjem.218.93

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Language：English   Publisher：AMER ASSOC CANCER RESEARCH  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

The epsilon 4 allele of the apolipoprotein E gene (APOE) is unequivocally recognized as a genetic risk factor for late-onset Alzheimer&apos;s disease (LOAD). Recently, single-nucleotide polymorphisms (SNPs) of the GRB2-associated binding protein 2 gene (GAB2) were shown to be associated with LOAD in Caucasians carrying the APOE-epsilon 4 allele through a genome-wide association study. Here, we attempted to replicate the finding by genotyping these SNPs in a large clinical cohort of Japanese. We observed no association of any of the SNPs with LOAD. GAB2 may not be a disease susceptibility gene for LOAD in Japanese.

DOI： 10.1038/ejhg.2008.181

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J01175&link_issn=&doc_id=20090323230701&doc_link_id=10.5980%2Fjpnjurol.100.303_4&url=https%3A%2F%2Fdoi.org%2F10.5980%2Fjpnjurol.100.303_4&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Motivation: A two-stage association study is the most commonly used method among multistage designs to efficiently identify disease susceptibility genes. Recently, some SNP studies have utilized more than two stages to detect disease genes. However, there are few available programs for calculating statistical powers and positive predictive values (PPVs) of arbitrary n-stage designs.
Results: We developed programs for a multistage case-control association study using R language. In our programs, input parameters include numbers of samples and candidate loci, genome-wide false positive rate and proportions of samples and loci to be selected at the k-th stage (k = 1,..., n). The programs output statistical powers, PPVs and numbers of typings in arbitrary n-stage designs. The programs can contribute to prior simulations under various conditions in planning a genome-wide association study.

DOI： 10.1093/bioinformatics/btn616

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Although the age of onset of childhood bronchial asthma is known to be decreasing, the age of onset of adult-onset asthma has yet to be comprehensively investigated. Methods: We examined the records of 5067 asthma patients (2047 males) aged 16 years or older who visited our clinic during a recent 9-year period (1997 through 2005). The definition of adult-onset asthma (ie, new-onset persistent asthma developing at 20 years or older) was based on the Akiyama classification. We analyzed the associations between a number of putative risk factors and age of onset Results: Although the age of onset of adult-onset asthma did not change significantly in males (43.0 ± 13.8 [mean ± SD] years in 1997 vs 44.5 ± 15.2 years in 2005), a significant increase was observed in females (40.6 ± 15.3 years in 1997 vs 43.5 ± 16.1 years in 2005, p&lt
0.001). Conclusion: Our data indicate that, during a recent 9-year period, the age of onset of adult-onset asthma appears to be increasing in females, most likely because the numbers of female asthmatics who smoke, have a high total serum IgE level (IgE ≥300IU/ml), have a high mite-specific IgE antibody score (RAST.score &gt
2), and have complications from or a past history of allergic rhinitis have declined. © 2009 Japanese Society of Allergology.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Inhaled corticosteroid (ICS) has played an important role in the management of asthma. Although several kinds of ICSs are currently available, there is no established strategy for ICS selection. Methods: Using the data from the 2004 questionnaire surveys by the Niigata Asthma Treatment Study Group, we analyzed relationships between each patient and the ICS employed on the basis of patient background, asthma control and treatment, and indicated characteristics of ICS selection by the physician. Results: Of 2852 cases, 2279 (79.9%) were ICS users, and 1513 (66.4% of ICS users) were classified as being in the fluticasone propionate (FP) group, 438 (19.2%) in the budesonide (BUD) group, and 240 (10.5%) in the hydrofluoroalkane-beclometasone (HFA-BDP) group, indicating that FP was a standard ICS in this study. The mean age was significantly lower in the BUD group (52.3+/-18.2 years) and was significantly higher in the HFA-BDP group (59.9+/-17.0 years) than that in the FP group (55.8+/-16.6 yaers). The proportion of female patients was significantly higher not in the HFA-BDP (46.5%) but in the BUD group (59.0%) than in the FP group (51.1%). These results indicated that BUD was frequently prescribed to young female and HFA-BDP was employed in the elderly patients irrespective of gender compared with FP. Conclusions: Our study indicates that ICS selection is reasonably adapted to each patient's background at least in the surveyed area. We need to elucidate the characteristics of ICS selection further in the future as new ICS and devices are developed. ©2009 Japanese Society of Allergology.

DOI： 10.2332/allergolint.08-OA-0077

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

The relationship between suicide and disaster is an important problem but it&apos;s not clear. We conducted this study to determine whether a natural disaster affects suicide rates.
We collected data on suicides during the 84 months before and the 60 months after the earthquake and compared the suicide rate in Kobe to that in Japan as a whole. We also examined what groups were significantly affected.
Compared with Japan as a whole, the suicide rates in Kobe significantly decreased in the 2 years after the earthquake.
An influence on suicide rate after the disaster clearly appeared in middle-aged men.

DOI： 10.1111/j.1440-1819.2009.01942.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

Although it has been well documented that loss of human chromosome 11q is frequently observed in primary neuroblastomas, the smallest region of overlap (SRO) has not yet been precisely identified. Previously, we performed array-comparative genomic hybridization (array-CGH) analysis for 236 primary neuroblastomas to search for genomic aberrations with high-resolution. In our study, we have identified the SRO of deletion (10-Mb or less) at 11q23. Within this region, there exists a TSLC1/IGSF4/CADM1 gene (Tumor suppressor in lung cancer I/Immunoglobulin superfamily 4/Cell adhesion molecule 1), which has been identified as a putative tumor suppressor gene for lung and some other cancers. Consistent with previous observations, we have found that 35% of primary neuroblastomas harbor loss of heterozygosity (LOH) on TSLC1 locus. In contrast to other cancers, we could not detect the hypermethylation in its promoter region in primary neuroblastomas as well as neuroblastoma-derived cell lines. The clinicopathological analysis demonstrated that TSLC1 expression levels significantly correlate with stage, Shimada's pathological classification, MYCN amplification status, TrkA expression levels and DNA index in primary neuroblastomas. The immunohistochemical analysis showed that TSLC1 is remarkably reduced in unfavorable neuroblastomas. Furthermore, decreased expression levels of TSLC1 were significantly associated with a poor prognosis in 108 patients with neuroblastoma. Additionally, TSLC1 reduced cell proliferation in human neuroblastoma SH-SY5Y cells. Collectively, our present findings suggest that TSLC1 acts as a candidate tumor suppressor gene for neuroblastoma. (c) 2008 Wiley-Liss, Inc.

DOI： 10.1002/ijc.23776

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim: This study was undertaken 5 months after the 2004 Niigata-Chuetsu earthquake in Japan to assess factors that impacted on psychological distress and its recovery.
Methods: Three thousand and twenty-six adult victims who lived in temporary shelter and in seriously damaged areas were evaluated by questionnaire. The questionnaire queried subject profile, degree of house damage, health status, and psychological distress using a 5-point scale before, immediately and 5 months after the earthquake.
Results: Immediately after the earthquake, 59.3% of the subjects had psychological distress. At 5 months after the earthquake, however, this percentage decreased to 21.8%. The psychological distress immediately after the earthquake was significantly serious in victims who: (i) were female; (ii) felt stronger fear of the earthquake and the aftershocks; (iii) lived at home or office after the earthquake; and (iv) were injured due to the earthquake or suffered from sickness after the earthquake. In contrast, the factors impairing psychological recovery 5 months after the earthquake were as follows: (i) being with unfamiliar member(s) during the night after the earthquake; (ii) serious house damage; (iii) living in temporary shelter or at a relative&apos;s home after the earthquake; and (iv) physical illness after the earthquake.
Conclusion: Despite differences between disasters, these results were consistent with those in some previous studies and may be useful for long-term mental care support.

DOI： 10.1111/j.1440-1819.2008.01842.x

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Language：Japanese   Publisher：(一社)日本血栓止血学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Background: This study sought to clarify the distribution of intrahepatic micrometastases and elucidate an adequate hepatectomy margin for colorectal carcinoma liver metastases.
Methods: Intrahepatic micrometastases in resected specimens from 90 patients who underwent hepatectomy for colorectal carcinoma liver metastases were examined retrospectively. Intrahepatic micrometastases were defined as microscopic lesions spatially separated from the gross tumor. Distances from these lesions to the hepatic tumor borders were measured histologically, and the density of intrahepatic micrometastases (number of lesions/mm(2)) calculated relative to the advancing tumor border in a zone &lt; 1 cm from the border (close) or &gt;= 1 cm away (distant). Median follow-up time was 127 months.
Results: A total of 294 intrahepatic micrometastases were detected in 52 (58%) patients; 95% of these occurred in the close zone. The density of intrahepatic micrometastases was significantly higher in the close zone (mean 74.8 x 10(-4) lesions/mm(2)) than in the distant zone (mean 7.4 x 10(-4) lesions/mm(2); P &lt; 0.001). Hepatectomy margin status was positive by 0 cm in 10 patients or negative by &lt; 1 cm in 51, and by &gt;= 1 cm in 29 patients. The median survival times were 18, 33, and 89 months in patients with hepatectomy margins 0 cm, &lt; 1 cm, and &gt;= 1 cm, respectively. Hepatectomy margin status independently influenced survival (P &lt; 0.001) and disease-free survival (P &lt; 0.001).
Conclusion: The currently recommended &gt;= 1 cm hepatectomy margin should remain the goal for resections of colorectal carcinoma liver metastases, based on the distribution of intrahepatic micrometastases and survival risk.

DOI： 10.1245/s10434-008-0023-y

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DOI： 10.1111/j.1744-618X.2008.00088.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Background This study aimed to define the role of combined major hepatectomy and pancreaticoduodenectomy in the surgical management of biliary carcinoma and to identify potential candidates for this aggressive procedure.
Methods A retrospective analysis was conducted on 28 patients who underwent a combined major hepatectomy and pancreaticoduodenectomy for extrahepatic cholangiocarcinoma (n = 17) or gallbladder carcinoma (n = 11). Major hepatectomy was defined as hemihepatectomy or more extensive hepatectomy. Altogether, 11 patients underwent a Whipple procedure, and 17 had a pylorus-preserving pancreaticoduodenectomy. The median follow-up time was 169 months.
Results Morbidity and in-hospital mortality were 82% and 21%, respectively. Overall cumulative survival rates after resection were 32% at 2 years and 11% at 5 years (median survival time 9 months). The median survival time was 6 months with a 2-year survival rate of 0% in 11 patients with residual tumor, whereas the median survival time was 26 months with a 5-year survival rate of 18% in 17 patients with no residual tumor (P = 0.0012). Residual tumor status was the only independent prognostic factor of significance (relative risk 4.65; P = 0.003). There were three 5-year survivors (two with diffuse cholangiocarcinoma and one with gallbladder carcinoma with no bile duct involvement) among the patients with no residual tumor.
Conclusions Combined major hepatectomy and pancreaticoduodenectomy provides survival benefit for some patients with locally advanced biliary carcinoma only if potentially curative (R0) resection is feasible. Patients with diffuse cholangiocarcinoma and gallbladder carcinoma with no bile duct involvement are potential candidates for this aggressive procedure.

DOI： 10.1007/s00268-007-9393-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TOHOKU UNIV MEDICAL PRESS  

In Japan, the national screening for the hepatitis C virus (HCV) has been started for both the general population and the high-risk groups. Our cost-effectiveness analysis was based on the result of the screening program including 99,001 people among the general population and 42,538 people among the high risk group from 2003 to 2006. The screening was performed using the three steps of the semi-quantitative HCV antibody test, the HCV core antigen test and the HCV-PCR test. A Markov model for HCV infected patients was constructed to estimate the future clinical benefits and the lifetime cost and the cost-effectiveness analysis was performed considering the recent treatment with peginterferon plus ribavirin. In the cost-effectiveness analysis, the cohort, in which the screening was implemented (= screening strategy), was compared with the similar cohort without the screening (= no-screening strategy) in both the general population and the high-risk group, stratified by age. The infection rates of the general population and the high-risk group were 0.36% and 0.81%, respectively. The incremental cost-effectiveness ratio (ICER), a measure of cost-effectiveness, of the general population and the high-risk group was calculated to be from 848 to 4,825 and - 749 to 2,297 $/life expectancy gained, respectively. The treatment effectiveness, transition probabilities and the infection rate varied in the one-way sensitivity analyses, but the superiority of the screening strategy regarding the cost-effectiveness was unchanged. In conclusion, the screening strategy in both the general population and the high-risk group therefore appears to be more cost-effective than a no-screening strategy.

DOI： 10.1620/tjem.215.33

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

A two-stage association study is the most commonly used method to efficiently identify disease susceptibility genes. However, some recent single nucleotide polymorphism (SNP) studies recently utilized three-stage designs. The purpose of this study was to investigate the practical properties of statistical powers and positive predictive values (PPVs) of replication-based analysis (RBA) and the joint analysis (JA) in multistage designs. For this purpose, a program for multistage designs was developed to calculate these performance indicators under various conditions of the number of samples, alleles of candidates, alleles remaining in the final stage, and genotypings. The results showed that the powers and PPVs of RBA and JA in three-stage designs were higher than those in two-stage designs in the range of a smaller proportion of sample size than 0.5 at the first stage. This tendency was more remarkable in JA. In conclusion, researchers who perform SNP studies for identifying disease susceptibility genes need to take account of three-stage case-control association studies, corresponding to study conditions such as the total numbers of samples, alleles, and genotypings. Furthermore, the program developed in this study is useful for estimating powers and PPVs in planning multistage association studies.

DOI： 10.1007/s10038-008-0258-2

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Background In Japan, a nationwide programme between 1984 and 2003 screened all infants for urinary catecholamine metabolites as a marker for neuroblastoma. Before 1989, this was done by qualitative spot tests for vanillylmandelic acid in urine, and subsequently by quantitative assay with high-performance liquid chromatography (HPLC). However, the Japanese government stopped the mass-screening programme in 2003, after reports that it did not reduce mortality due to neuroblastoma. We aimed to assess the effectiveness of the programme, by comparing the rates of incidence and mortality from neuroblastomas diagnosed before 6 years of age in three cohorts.
Methods We did a retrospective population-based cohort study on all children born between 1980 and 1998, except for a 2-year period from 1984. We divided these 22 289 695 children into three cohorts: children born before screening in 1980-83 (n=6 130 423); those born during qualitative screening in 1986-89 (n=5 290 412); and those born during quantitative screening 1990-98 (n=10 868 860). We used databases from hospitals, screening centres, and national cancer registries. Cases of neuroblastoma were followed up for a mean of 78.7 months.
Findings 21.56 cases of neuroblastorna per 100 000 births over 72 months were identified in the qualitatively screened group (relative risk [RR] 1 . 87, 95% Cl 1 . 66-2. 10), and 29.80 cases per 100 000 births over 72 months in the quantitatively screened group (RR 2.58, 2.33-2.86). The cumulative incidence of neuroblastorna in the prescreening cohort (11 . 56 cases per 100 000 births over 72 months) was lower than that in other cohorts (p&lt;0 . 0001 for all comparisons), but more neuroblastomas were diagnosed after 24 months of age in this cohort (p=0 . 0002 for qualitative screening vs prescreening, p&lt;0 . 0001 for quantitative screening vs prescreening). Cumulative mortality was lower in the qualititative screening (3.90 cases per 100 000 livebirths over 72 months) and quantitative screening cohorts (2.83 cases) than in the prescreening cohort (5.38 cases). Compared with the prescreening cohort, the relative risk of mortality was 0 . 73 (95% Cl 0 . 58-0.90) for qualitative screening, and 0 . 53 (0.42-0.63) for quantitative screening. Mortality rates for both the qualitative and quantitative screening groups were lower than were those for the prescreening cohort (p=0 . 0041 for prescreening vs qualitative screening, p&lt;0. 0001 for prescreening vs quantitative screening).
Interpretation More infantile neuroblastomas were recorded in children who were screened for neuroblastoma at 6 months of age than in those who were not. The mortality rate from neuroblastoma in children who were screened at 6 months was lower than that in the prescreening cohort, especially in children screened by quantitative HPLC. Any new screening programme should aim to decrease mortality but also to minimise overdiagnosis of turnours with favourable prognoses (eg, by screening children at 18 months).

DOI： 10.1016/S0140-6736(08)60523-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

Objectives: Simultaneous dealing of hundreds of thousands of single nucleotide polymorphisms (SNPs) in genome-wide association studies is laborious. The aim of our study is to develop a method to decrease the number of candidate SNPs prior to the genotyping of study subjects.
Methods. We created virtual genotype data on case and control subjects from data of the International HapMap Project by using haplotype-based simulation method. We repeated virtual case-control association studies and selected candidate SNPs. We applied the selected SNPs to previously published genetic case-control studies. Sensitivity to detect association with causative genes using our method was compared to the original studies and results using tag SNPs.
Results. We found a discrete distribution pattern of SNPs, which was able to produce significant results in case-control association studies. The number of candidate SNPs that we selected was 24.7% of the number of the original set of SNPs, We applied this method to previously published genetic case-control studies and found that the use of candidate SNPs improved the sensitivity for detecting significant alleles, both compared to the original studies and to the use of tag SNPs. The results were not affected by the difference of the diseases and genes involved.
Conclusions. Our simulation-based approach has advantages of reducing costs and improving performance to detect significant alleles. This method can be used without considering the specific disease and genes involved.

DOI： 10.3414/ME9129

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Niigata University  

Several integrated scoring systems for hepatocellular carcinoma (HCC) have recently been proposed, but there is still no consensus regarding their validity. The present study developed a new scoring system to obtain a better model for predicting the survival of patients with HCC. Data obtained from 1,070 patients with HCC diagnosed at 31 hospitals affiliated with the Niigata Liver Disease Study Group from January 1993 through December 2003 were retrospectively analyzed. The significant factors, which affected the survival of the patients were analyzed, and the best fitting model for the patients' survival was constructed. Fourteen factors were identified based on a univariate analysis, and those factors were used in a multivariate analysis as the candidate prognostic factors. The first Cox's analysis revealed that the Cancer of the Liver Italian Program (CLIP) score, tumor diameter, metastasis (N factor and/or M factor) based on the Liver Cancer Study Group of Japan (LCSGJ), and Japan Integrated Staging (JIS) score were all significant factors. Since the results suggested that both the CLIP and JIS scores were insufficient for the prediction of survival, the Japan Integrated Triform system (JITs) score was designed by removing tumor morphology and portal vein thrombosis from the CLIP score and by adding T factor and metastasis of the LCSGJ. An evaluation by the Akaike information criteria (AIC) showed the JITs score to be a good-fitting model in the present study population. JITs score may hopefully be useful for physicians in determining the appropriate management options.

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Other Link： http://search.jamas.or.jp/link/ui/2009186907

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Alzheimer's disease (AD), the most common form of dementia in the elderly, was found to exhibit a trend toward a higher risk in females than in males through epidemiological studies. Therefore, we hypothesized that gender-related genetic risks could exist. To reveal the ones for late-onset AD (LOAD), we extended our previous genetic work on chromosome 10q (genomic region, 60-107 Mb), and single nucleotide polymorphism (SNP)-based genetic association analyses were performed on the same chromosomal region, where the existence of genetic risk factors for plasma Abeta42 elevation in LOAD was implied on a linkage analysis. Two-step screening of 1140 SNPs was carried out using a total of 1408 subjects with the APOE-epsilon3*3 genotype: we first genotyped an exploratory sample set (LOAD, 363; control, 337), and then genotyped some associated SNPs in a validation sample set (LOAD, 336; control, 372). Seven SNPs, spanning about 38 kb, in intron 9 of CTNNA3 were found to show multiple-hit association with LOAD in females, and exhibited more significant association on Mantel-Haenszel test (allelic P-values(MH-F) = 0.000005945-0.0007658). Multiple logistic regression analysis of a total of 2762 subjects (LOAD, 1313; controls, 1449) demonstrated that one of the seven SNPs directly interacted with the female gender, but not with the male gender. Furthermore, we found that this SNP exhibited no interaction with the APOE-epsilon4 allele. Our data suggest that CTNNA3 may affect LOAD through a female-specific mechanism independent of the APOE-epsilon4 allele.

DOI： 10.1093/hmg/ddm244

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Language：Japanese   Publisher：(一社)日本医療情報学会  

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Language：English   Publisher：WILEY-LISS  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

An accurate diagnosis of acute appendicitis in the early stage is often difficult, and decision support tools to improve such a diagnosis might be required. This study compared the levels of accuracy of artificial neural network models and logistic regression models for the diagnosis of acute appendicitis. Data from 169 patients presenting with acute abdomen were used for the analyses. Nine variables were used for the evaluation of the accuracy of the two models. The constructed models were validated by the ".632+ bootstrap method". The levels of accuracy of the two models for diagnosis were compared by error rate and areas under receiver operating characteristic curves. The artificial neural network models provided more accurate results than did the logistic regression models for both indices, especially when categorical variables or normalized variables were used. The most accurate diagnosis was obtained by the artificial neural network model using normalized variables.

DOI： 10.1007/s10916-007-9077-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective Recent studies have reported the effectiveness of shorter courses of treatment with peginterferon alpha-2b plus ribavirin for patients with chronic hepatitis C, who achieved a rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV-) RNA at week 4. The aim of this study was to evaluate the cost-effectiveness of the new protocol for treatment, from the perspective of RVR.
Methods A cost-effectiveness analysis based on the rate of sustained virologic response was performed. A Markov cohort model of hepatitis C was constructed to demonstrate the clinical states on the basis of the assigned transition probabilities over 30 years. The treatment strategies were classified into five subgroups taking into consideration the viral genotypes, viral load, and RVR. The lifetime costs and quality-adjusted life years (QALYs) were compared between the new and standard protocols for treatment.
Results Genotype 1-infected patients in the new protocol for treatment compared with the standard one could prolong OALYs by 0.33 and reduce lifetime cost by (sic) 5993. Genotype 2 or 3-infected patients in the new protocol for treatment compared with the standard one could prolong QALYs by 0.02 and reduce lifetime cost by (sic)2851.
Conclusion Treatment strategies that consider viral load and RVR for patients with a low viral load infected with genotype 1 and those infected with genotype 2 or 3 are more cost-effective compared with the standard protocol for treatment.

DOI： 10.1097/MEG.0b013e3282748f1f

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Background: This work aimed to examine the predictive value for death of various clinical variables after long-term hemodialysis (HD). Design, s etting, participants, and measurements: A total of 947 patients (597 men and 350 women, aged 21 to 93 yr) who were undergoing maintenance HD in Niigata, Japan, were stratified into two cohorts: Those with &gt
10 yr of prior HD at study enrollment (n = 391) and those with ≤10 yr of previous therapy (n = 556). The survival of patients was examined for up to 40 mo (1999 to 2003) with the Cox proportional hazards model. Baseline clinical and dialysis data and serum biochemistries were used as independent variables. For adjustment for bias in patient selection, patient survival in either cohort was analyzed separately. Results: In patients with &gt
10 yr of HD, high pulse pressure, cerebrovascular disease, low serum creatinine, and low Kt/V values were the mortality risk predictors, whereas for those with ≤10 yr of HD, age and cerebrovascular disease were independent risk predictors for death. Diabetes, coronary artery disease, serum albumin, and C-reactive protein were NS predictors in those with long-term HD. Conclusions: Providing a dequate dosage of dialysis and achieving a better control of pulse pressure may further improve survival in selected patients who had undergone HD for &gt
10 yr. Copyright © 2007 by the American Society of Nephrology.

DOI： 10.2215/CJN.03160906

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Factor structure of the 12-item General Health Questionnaire (GHQ- 12) was studied by a survey of subjects who had experienced the 2004 Niigata-Chuetsu earthquake (6.8 on the Richter scale) in Japan.
Methods: Psychological distress was measured at two years after the earthquake by using GHQ-12 in 2,107 subjects (99.0% response rate) who suffered the earthquake. GHQ-12 was scored by binary, chronic and Likert scoring method. Confirmatory factor analysis was used to reveal the factor structure of GHQ-12. Categorical regression analysis was performed to evaluate the relationships between various background factors and GHQ-12 scores.
Results: Confirmatory factor analysis revealed that the model consisting of the two factors and using chronic method gave the best goodness-of-fit among the various models for factor structure. Recovery in the scale for the factor 'social dysfunction' was remarkably impaired compared with that of the factor 'dysphoria'. Categorical regression analysis revealed that various factors, including advanced age, were associated with psychological distress. Advanced age affected the impaired recovery of factor 'social dysfunction' score as well as total GHQ score.
Conclusion: The two-factor structure of GHQ-12 was conserved between the survey at five month and that at two years after the earthquake. Impaired recovery in the ability to cope with daily problems in the subjects who had experienced the earthquake was remarkable even at two years after the earthquake.

DOI： 10.1186/1471-2458-7-175

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Language：Japanese   Publisher：日本診療情報管理学会  

病院情報システム更新と同時にプロブレムリストエディタを導入した。導入直後から、必要な病名が病名オーダから登録されていないという事例が多数発生した。そのため、プロブレムリストエディタの作動を止め、病院情報システム上では単なるSOAPに分けた診療録に記載を行っていた。この度、問題志向型診療録に特化したシステムとして修正して、導入し直した。以前の紙媒体での運用時の診療録記載方法を分析し検討を行った。職種や診療科によって記載方法に差異があった。また、いずれもプロブレムリストエディタの使用率が低かった。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

Objectives: We evaluated prostate-specific antigen (PSA) density of the prostatic volume (PSAD) estimated using transrectal ultrasonography (TRUS; TRUS-based PSAD), magnetic resonance imaging (MRI; MRI-based PSAD), and PSA density of the transition zone (TZ) volume (PSATZD) estimated using MRI (MRI-based PSATZD) in the diagnosis of prostate cancer (PCa).
Methods: One hundred and twenty patients, who were suspected to have PCa based on PSA, ranged between 4.1 and 20.0 ng/mL were enrolled in this study.
Results: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI by 11.4% in the patients with PSA levels ranging 4.1-20.0 ng/mL, 7.2% in those 4.1-10.0 ng/mL, and 15.7% in those 10.1-20.0 ng/mL, respectively. PSA levels were correlated with the prostatic volume estimated using TRUS and MRI, and TZ volume estimated using MRI in the patients without PCa; however, the level was not correlated with them in the patients with PCa. The area under the receiver operating characteristic curve of MRI-based PSAD was higher than that of TRUS-based PSAD; however, there was no statistical difference. Stepwise logistic regression analysis for the prediction of PCa by using PSA-related parameters confirmed that MRI-based PSATZD was the most significant predictor in patients with PSA levels in the range of 4.1-20.0 ng/mL (P &lt; 0.001), the range of 4.1-10.0 ng/mL (P=0.002), and the range of 10.1-20.0 ng/mL (P &lt; 0.001), respectively.
Conclusions: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI. MRI-based PSATZD is the most significant predictor in the four parameters.

DOI： 10.1111/j.1442-2042.2007.01686.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Background: This study aimed to evaluate the effect of anatomic resection on long-term outcomes in patients with pathologic T1-T2 (pT1-T2) hepatocellular carcinoma.
Methods: A retrospective analysis of 158 consecutive patients who underwent either anatomic (n = 95) or nonanatomic (n = 63) resection for pT1-T2 hepatocellular carcinoma was conducted. Anatomic resection was defined as the complete removal of at least one Couinaud segment containing the tumor; nonanatomic resection was defined as removal of the tumor plus a rim of nonneoplastic liver parenchyma. The median follow-up time was 83 months.
Results: Patients who underwent anatomic resection were characterized by lower prevalence of cirrhosis (P = .015), more favorable hepatic function (P = .001), larger tumor size (P = .029), and higher prevalence of vascular invasion (P = .008) compared with patients who underwent nonanatomic resection. Anatomic resection provided better survival (median survival time, 122 months) than nonanatomic resection (median survival time, 76 months; P = .0358). Patients who underwent anatomic resection had better disease-free survival (P = .0121). Anatomic resection independently improved both survival (hazard ratio, .46; P = .003) and disease-free survival (hazard ratio, .55; P = .008). When stratified for pT classification, the effectiveness of anatomic resection remained only in patients with pT2 tumors in terms of survival (P = .0012) and disease-free survival (P = .0004).
Conclusions: Anatomic resection independently improves long-term survival in patients with T1-T2 hepatocellular carcinoma, probably because of the clearance of venous tumor thrombi within the resected domain.

DOI： 10.1245/s10434-006-9318-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

The occurrence of significant second-order interactions for group characteristics was examined using real data in a randomized controlled trial (RCT). The interactions exist in all RCTs; they could be easily overlooked when using the simple randomization or stratification methods, but could become more obvious when minimization methods are used. Using real data from an RCT, the minimization method enabled balancing the distributions of the four selected stratified factors. Analyses for three-way second-order interactions including six additional potential confounding variables (for a total of 10 variables) presented 8 significant second-order interactions with the treatment groups. Interaction effects need to be evaluated when treatment effects are examined to maximize the power of the treatment effects in any RCTs. A stepwise regression method with piecewise linear functions would be useful to select the significant variables with interaction effects affecting the treatment outcomes in RCTs. Additional ways to handle interaction effects in RCTs are presented in this paper. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.cmpb.2006.12.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Aim: The nodal status is an established prognostic factor in ampullary carcinoma. The aim of this study was to compare the prognostic power of the anatomic location of positive nodes with that of the number of positive nodes.
Methods: Of 73 consecutive patients treated for ampullary carcinoma, 62 underwent pancreaticoduodenectomy with regional lymphadenectomy. A survival analysis of these 62 patients by nodal status was conducted retrospectively. A total of 1942 lymph nodes taken from the patients were examined histologically for metastasis. The location of positive regional nodes was classified into 4 categories, according to the Japanese staging system. The number of positive regional nodes was recorded for each patient. The median follow-up period was 124 months.
Results: Nodal disease was found in 31 patients, of whom 23 had 1-3 positive regional nodes and 8 had &gt;= 4 positive regional nodes. Univariate analysis revealed that both the location (p &lt; 0.0001) and the number (p &lt; 0.0001) of positive nodes were significant prognostic factors. Multivariate analysis revealed that the number of positive nodes was an independent prognostic factor (p = 0.007), while the location failed to remain as an independent variable. The median survival time was 59 months with a 5-year survival rate of 48% in patients with 1-3 positive nodes, whereas all patients with &gt;= 4 positive nodes died of the disease within 29 months of resection (p = 0.0001).
Conclusion: The number, not the location, of positive regional lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejso.2006.10.008

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.genhosppsych.2006.09.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE PUBLICATIONS INC  

The purpose of this study was to assess the relationship between the clinical findings before starting treatment and the development quotient in children treated for congenital hypothyroidism. Patients with congenital hypothroidism (n = 129) were divided into favorable and unfavorable groups according to intellectual performance. Children with congenital hypothyroidism generally have a similar intellectual outcome to that of healthy children. However, a low birth weight, the presence of complications, and a high serum thyroid-stimulating hormone value are the risk factors for unfavorable cases, who consistently have a development quotient score of less than 100.

DOI： 10.1177/000992280689326

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

Objectives: The diagnosis of acute appendicitis is difficult, and a diagnostic error will often lead to either a perforation or the removal of a normal appendix. In this study, we constructed a Bayesian network model for the diagnosis of acute appendicitis and compared the diagnostic accuracy with other diagnostic models, such as the naive Bayes model, an artificial neural network model, and a logistic regression model.
Methods: The data from 169 patients, who suffered from acute abdominal pain and who were suspected of having an acute appendicitis, were analyzed in this study. Nine variables were used for the evaluation of the accuracy of the four models for the diagnosis of an acute appendicitis. The naive Bayes model, the Bayesian network model, an artificial neural network model, and a logistic regression model were used in this study for the diagnosis of acute appendicitis. These four models were validated by using the ".632 + bootstrap method" for resampling. The levels of accuracy of the four models for diagnosis were compared by the error rates and by the areas under the receiver operating characteristic curves.
Results: Through the course of illness, 50.9% (86 of 169) of the patients were diagnosed as having an acute appendicitis. The error rate was the lowest in the Bayesian network model, as compared with the other diagnostic models. The area under the receiver operating characteristic curve analysis also showed that the Bayesian network model provided the most reliable results.
Conclusion: The Bayesian network model provided the most accurate results in comparison to other models for the diagnosis of acute appendicitis.

DOI： 10.3414/ME9066

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Perimenstrual asthma (PMA) has been documented in 30% to 40% of asthmatic women
the characteristics of PMA have also been well described. However, there have been few epidemiological investigations of PMA in practice. In this study, we analyzed PMA based on a questionnaire survey carried out in Japan and compared the results with those of studies reported previously. Methods: For 8 weeks from September through October 2004, a questionnaire survey was administered to patients with bronchial asthma and their attending physicians. The questionnaire surveyed asthma control, asthma-related emergencies and satisfaction in daily life. The attending physicians were questioned about patient profiles and medications. All female patients who were menstruating during the survey period and who were known to have asthma exacerbation related to menstruation were allocated to the PMA group
those who were not were allocated to the non-PMA group. Results: The rate of PMA in female patients who were menstruating during the survey period was 11.3% in this study. Characteristic features of the PMA group (n = 54) included more severe disease, worsened disease control and more aggressive patient management, including increased oral corticosteroid use compared with the non-PMA group. The rates of emergency episodes in the PMA group were higher than in the non-PMA group. There was a significant increase in aspirin intolerant asthma (AIA, 25.5%) in the PMA group compared with the non-PMA group (8.4%). Conclusions: Attention should be paid to the lack of knowledge regarding PMA in patients with asthma in actual clinical settings. The low rate of PMA reported in this study may be due to the study method using self-reports of PMA by patients without sufficient knowledge, and may not be an accurate representation of the actual incidence of the disease. The clinical similarity of PMA to AIA in this study may also provide a new insight into the mechanism of PMA. ©2007 Japanese Society of Allergology.

DOI： 10.2332/allergolint.O-06-475

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Language：English   Publishing type：Research paper (bulletin of university, research institution)   Publisher：Nova Science Publisher, Inc.  

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DOI： 10.1016/j.healthpol.2005.06.008

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Association for Medical Informatics  

The new inclusive payment system was introduced into acute inpatient care in main hospitals at universities to replace traditional fee-for-service payment system in 2003. The system created incentives to reduce length of stay of inpatients (LOS) and to urge early discharge to aftercare to shorten the LOS. Therefore, strong partnership with other medical facilities became more important for university hospitals. We studied the pattern of reverse referral from a university hospital to aftercare using geographic information system (GIS). We found that GIS is a useful tool to detect the spatial differences in partnership between the university hospital and other medical facilities.

DOI： 10.14948/jami.26.41

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Other Link： http://search.jamas.or.jp/link/ui/2006318622

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: An earthquake measuring 6.8 on the Richter scale struck the Niigata-Chuetsu region of Japan at 5.56 P. M. on the 23rd of October, 2004. The earthquake was followed by sustained occurrence of numerous aftershocks, which delayed reconstruction of community lifelines. Even one year after the earthquake, 9,160 people were living in temporary housing. Such a devastating earthquake and life after the earthquake in an unfamiliar environment should cause psychological distress, especially among the elderly.
Methods: Psychological distress was measured using the 12-item General Health Questionnaire (GHQ-12) in 2,083 subjects (69% response rate) who were living in transient housing five months after the earthquake. GHQ-12 was scored using the original method, Likert scoring and corrected method. The subjects were asked to assess their psychological status before the earthquake, their psychological status at the most stressful time after the earthquake and their psychological status at five months after the earthquake. Exploratory and confirmatory factor analysis was used to reveal the factor structure of GHQ12. Multiple regression analysis was performed to analyze the relationship between various background factors and GHQ-12 score and its subscale.
Results: GHQ-12 scores were significantly elevated at the most stressful time and they were significantly high even at five months after the earthquake. Factor analysis revealed that a model consisting of two factors ( social dysfunction and dysphoria) using corrected GHQ scoring showed a high level of goodness-of-fit. Multiple regression analysis revealed that age of subjects affected GHQ-12 scores. GHQ-12 score as well as its factor 'social dysfunction' scale were increased with increasing age of subjects at five months after the earthquake.
Conclusion: Impaired psychological recovery was observed even at five months after the Niigata-Chuetsu Earthquake in the elderly. The elderly were more affected by matters relating to coping with daily problems.

DOI： 10.1186/1471-2458-6-230

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: Suicide notes (SN) are one of markers of the severity of a suicide attempt and are said to provide a valuable insight into the thinking of suicide victims before the fatal act [Shah, A., De, T., 1998. Suicide and the elderly. Int. J. Psychiat. Clin Pract. 2, 3-18]. To examine whether suicide victims who wrote notes (note writers: NW) differ from those who did not, we investigated the characteristics of a sample of more than 5000 Japanese suicides using multiple logistic regression analysis.
Methods: For all suicide victims (5161 cases), we examined the following information: gender, age, suicide method, reason for suicide, marital status, residential status, history of psychiatric disorders, previous suicidal behavior, physical disease, and content of suicide notes.
Results: Mean incidence of NW was 30.1% (male: 29.7%, female: 30.8%). NW in Japan had the following characteristics; higher proportion in female and living alone, suicide by more lethal methods such as carbon monoxide, hanging or sharp instruments. On the other hand, non-NW had tendencies to commit suicide for reasons of physical illness and psychiatric disorder, and/or history of previous psychiatric disorders.
Limitations: This study is observational and discusses only completed, not attempted, suicide. Medical and psychiatric comorbidity are judged only by the history of diagnosis and the information about the problems in relationships is based not on valid criteria for inclusion.
Conclusions: Although these findings show ethnic differences, it is possible that SN may be considered an indicator of a serious suicide attempt. Further studies of SN are needed to confirm this. (c) 2006 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jad.2006.03.023

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

The apolipoprotein E (APOE) gene has been consistently shown to be a major genetic risk factor; however, all cases of Alzheimer's disease (AD) cannot be attributed to the epsilon 4 variant of APOE, because about half of AD patients have the APOE-epsilon 3*3 genotype. To identify an additional genetic risk factor(s), we performed large-scale single nucleotide polymorphism (SNP)-based association analysis of 1526 late-onset AD patients and 1666 control subjects in a Japanese population. We prepared two independent sets consisting of exploratory and validation samples, respectively, with only the APOE-epsilon 3*3 genotype, and first carried out genotyping for the exploratory set with 1206 SNPs in the region between 60 and 107 Mb on chromosome 10q that is implicated by linkage studies as containing an AD susceptibility locus. Thirty-five SNPs that showed significant values (P &lt; 0.01) were followed-up to detect any association with the validation samples. Finally, six SNPs exhibited replicated significant associations (P=0.000035-0.00048) on meta-analysis of both sets. These SNPs were clustered in a locus spanning 220 kb at genomic position 101 Mb, and three of the six SNPs were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed AD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones (P &lt; 0.0169). Thus, we confirmed the association of DNMBP with AD individuals with the APOE-epsilon 3*3 genotype or lacking the epsilon 4 allele, and DNMBP may be one of the susceptibility genes for AD.

DOI： 10.1093/hmg/ddl142

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Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

MYCN is the most powerful prognostic factor in cases of older children. However, how MYCN is related to the prognosis of infantile cases is not clear. A mass screening program was carried out by measuring urinary catecholamine metabolites (VMA and HVA) from 6-month-old infants. Of 2084 cases detected by the screening program, MYCN amplification (MNA) was examined by Southern blot analyses in 1533 cases from 1987 to 2000. Of the 1533 cases examined, 1500 (97.8%) showed no MNA, 20 cases (1.3%) showed MNA from three to nine copies, and 13 (0.8%) cases showed more than 10 copies. The 4-year overall survival rates of these three groups (99, 89 and 53%, respectively) were significantly different (P &lt; 0.001), indicating that MYCN copy number correlates with the prognosis. Cases with MNA more than 10 copies were more advanced than those without amplification (stage III, IV vs I, II, IVs; P &lt; 0.001). Patients with MNA more than 10 copies had significantly higher serum levels of neuron-specific-enolase (NSE) and ferritin than non-amplified patients (P = 0.049, P = 0.025, respectively). MYCN amplification was strongly correlated with a poor prognosis in infantile neuroblastoma cases. Therefor

DOI： 10.1038/sj.bjc.6603149

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY, INC  

Background. The aim of this study was to clarify whether preoperative squamous cell carcinoma-antigen messenger RNA (SCC-Ag mRNA) level in peripheral blood can be used to predict tumor recurrence after curative resection for esophageal squamous cell carcinoma.
Methods. A prospective analysis was conducted for 46 consecutive patients who underwent curative esophagectomy and who had no residual tumor. The SCC-Ag mRNA level in the peripheral blood of each patient was measured preoperatively by using quantitative reverse transcriptase-polymerase chain reaction. Median follow-up period was 34 months.
Results. Receiver operating characteristic analysis demonstrated that the optimal cutoff level of SCC-Ag mRNA was 40. Patients were divided into the high SCC-Ag mRNA level group (n = 14) and the low SCC-Ag mRNA level group (n = 32). The cumulative probabilities of tumor recurrence were higher in the high SCC-Ag mRNA level group (probability of recurrence was 71% at 2 years) than in the low group (22% at 2 years; P = .0005). SCC-Ag mRNA level (relative risk, 3.00; 95% confidence interval, 1.05-8.54; P = .040) was the strongest independent predictor of recurrence by multivariate analysis.
Conclusions. Preoperative SCC-Ag mRNA levels in the peripheral blood are the best predictive factor for recurrence in patients with esophageal squamous cell carcinoma who undergo curative resection (R0).

DOI： 10.1016/j.surg.2005.09.022

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Although uremia is well known as the most common cause of pruritus, the mechanisms of pruritus in chronic hemodialysis patients remain unclear. The purpose was to characterize uremic pruritus in more detail and to investigate whether severe pruritus is a marker for poor prognosis. A total of 1773 adult hemodialysis patients were studied. A questionnaire was given to each patient to assess the intensity and frequency, as well as pruritus-related sleep disturbance. We analyzed the relationship between clinical and laboratory data and the severity of pruritus in hemodialysis patients and followed them for 24 months prospectively. In total, 453 patients had severe pruritus with a visual analogue scale (VAS) score more than or equal to 7.0. Among them, more than 70% complained of sleep disturbance, whereas the majority of patients with a VAS score of less than 7.0 had no sleep disturbance. Male gender, high levels of blood urea nitrogen, β2-microglobulin (β2MG), hypercalcemia, and hyperphosphatemia were identified as independent risk factors for the development of severe pruritus, whereas a low level of calcium and intact-parathyroid hormone were associated with reduced risk. During the follow-up, 171 (9.64%) patients died. The prognosis of patients with severe pruritus was significantly worse than the others. Moreover, severe pruritus was independently associated with death even after adjusting for other clinical factors including diabetes mellitus, age, β2MG, and albumin. Severe uremic pruritus caused by multiple factors, not only affects the quality of life but may also be associated with poor outcome in chronic hemodialysis patients. © 2006 International Society of Nephrology.

DOI： 10.1038/sj.ki.5000251

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Language：English   Publisher：TAYLOR & FRANCIS AS  

DOI： 10.1080/08035250500411957

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TOHOKU UNIV MEDICAL PRESS  

To realize an effective cost control, a practical and accurate cost accounting system is indispensable in hospitals. In traditional cost accounting systems, the volume-based costing (VBC) is the most popular cost accounting method. In this method, the indirect costs are allocated to each cost object (services or units of a hospital) using a single indicator named a cost driver (e.g., Labor hours, revenues or the number of patients). However, this method often results in rough and inaccurate results. The activity based costing (ABC) method introduced in the mid 1990s can prove more accurate results. With the ABC method, all events or transactions that cause costs are recognized as "activities", and a specific cost driver is prepared for each activity. Finally, the costs of activities are allocated to cost objects by the corresponding cost driver. However, it is much more complex and costly than other traditional cost accounting methods because the data collection for cost drivers is not always easy. In this study, we developed a simplified ABC (S-ABC) costing method to reduce the workload of ABC costing by reducing the number of cost drivers used in the ABC method. Using the S-ABC method, we estimated the cost of the laboratory tests, and as a result, similarly accurate results were obtained with the ABC method (largest difference was 2.64%). Simultaneously, this new method reduces the seven cost drivers used in the ABC method to four. Moreover, we performed an evaluation using other sample data from physiological laboratory department to certify the effectiveness of this new method. In conclusion, the S-ABC method provides two advantages in comparison to the VBC and ABC methods: (1) it can obtain accurate results, and (2) it is simpler to perform. Once we reduce the number of cost drivers by applying the proposed S-ABC method to the data for the ABC method, we can easily perform the cost accounting using few cost drivers after the second round of costing.

DOI： 10.1620/tjem.208.213

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DOI： 10.1111/j.1075-122X.2006.00220.x

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

To investigate risk factors for coronary artery disease (CAD), we analyzed the clinical parameters of patients with a coronary artery bypass graft (CABG) in a case-control study. Eighty-eight patients (75 males and 13 females) who underwent CABG surgery between 2001 and 2002 were compared with age- and sex-matched healthy controls randomly chosen from the registry of Kobari Health Care Center. Wilcoxon's signed rank test and McNemar's test were used for pairwise comparisons. Multivariate logistic regression analysis was used to identify significant risk factors for CABG. Significant differences between the patients and controls were observed in HDL-C (P &lt; 0.001), HbA,c (p &lt; 0.001), Brinkman Index (BI; p &lt; 0.001), body mass index (BMI; p = 0.002), and systolic blood pressure (SBP; p = 0.013). Subjects with an abnormal BMI, HbA(1c), or HDL-C or high BI value made up a significantly higher proportion of the patients who underwent CABG, compared to their age- and sex-matched controls. Multivariate logistic regression analysis identified high levels of HbA(1c), low levels of HDL-C, and high scores on the BI as significant risk factors for needing a CABG. These results demonstrate that, despite the modification of laboratory determinations by antecedent treatment, HDL-C, HbA(1c), BI, BMI, and SBP are significant indicators of risk for CAD.

DOI： 10.5551/jat.13.62

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: In Japan, all citizens are covered by the national insurance system in which universal free access to healthcare services is promised to everybody. There are no general physicians or gatekeepers in the Japanese healthcare system.
Methods: We studied the pattern of referral of inpatients from secondary care hospitals to a tertiary care university hospital and the reverse referral under the situations using a geographic information system (GIS), taking paediatric inpatients as an example.
Results: The results showed that 61.2% of the patients were directly admitted to the hospital without referral from other hospitals or clinics and that 82.8% of the inpatients were referred to the outpatient department of the hospital to which they had been admitted. GIS analysis for the inpatients service area showed the hospital functions as both a secondary care hospital and tertiary care hospital. Patients who lived near the hospital tended to be admitted directly to the hospital, and patients who lived far from the hospital tended to utilize the hospital as a tertiary care provider. There were territorial disputes with other secondary care hospitals. To estimate spatial differences in referral to aftercare, we analyzed the spatial distribution of inpatients with focus on their length of hospital stay (LOS). GIS analysis revealed apparent foci of patients with long LOS and those with low LOS.
Conclusion: These results suggest that the function of university hospital in Japan is unspecialized and that the referral route from the university hospital to aftercare is also unequipped.

DOI： 10.1186/1472-6963-6-11

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Accurate cost estimate and a profit and loss analysis are necessary for health care practice. We performed an actual financial analysis for an intensive care unit (ICU) of a university hospital in Japan, and tried to discuss the health care policy and resource allocation decisions that have an impact on critical intensive care.
Methods: The costs were estimated by a department level activity based costing method, and the profit and loss analysis was based on a break-even point analysis. The data used included the monthly number of patients, the revenue, and the direct and indirect costs of the ICU in 2003.
Results: The results of this analysis showed that the total costs of US$2,678,052 of the ICU were mainly incurred due to direct costs of 88.8%. On the other hand, the actual annual total patient days in the ICU were 1,549 which resulted in revenues of US$2,295,044. However, it was determined that the ICU required at least 1,986 patient days within one fiscal year based on a break-even point analysis. As a result, an annual deficit of US$383,008 has occurred in the ICU.
Conclusion: These methods are useful for determining the profits or losses for the ICU practice, and how to evaluate and to improve it. In this study, the results indicate that most ICUs in Japanese hospitals may not be profitable at the present time. As a result, in order to increase the income to make up for this deficit, an increase of 437 patient days in the ICU in one fiscal year is needed, and the number of patients admitted to the ICU should thus be increased without increasing the number of beds or staff members. Increasing the number of patients referred from cooperating hospitals and clinics therefore appears to be the best strategy for achieving these goals.

DOI： 10.1186/1472-6963-6-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background and Objectives: Because inhaled corticosteroids (ICS) play a central role in the management of asthma, new drug delivery systems for fluticasone propionate, Diskhaler (FPdh) and Diskus (FPdk), were developed. However, few studies have focused on compliance with these drug delivery systems, which can influence drug efficacy. Hence, we compared compliance with FPdk versus that with FPdh. Methods: Data were obtained from a survey of pharmacists dispensing anti-asthmatic drugs to adult asthma patients who visited participating pharmacies between October 2002 and November 2003. Patients were limited to regular users of FPdh or FPdk whose medication and daily administration frequency of ICS were evaluated on the basis of pharmaceutical records. Data on asthma status and various other factors affecting ICS compliance were obtained by questionnaire. Results: Data were acquired on 337 patients. There were no significant differences in gender, age, and duration between the FPdk and FPdh groups. Although FPdk compliance was significantly higher than that of FPdh, conversely there was no significant difference in daily dose and administration frequency between the 2 groups. Furthermore, there was no significant difference in the rate of concomitant drug and in various influencing factors associated with drug compliance. Regarding compliance of concomitant drug, that of oral sustained-released theophylline was significantly lower in FPdk versus FPdh users. Conclusion: In the area of drug compliance, FPdk is superior to FPdh. Although the reason for this is unclear, it is probably due to the characteristics of FPdk itself. Copyright (C) 2006 S. Karger AG, Basel.

DOI： 10.1159/000095313

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Language：English   Publisher：The Japanese Society of Pediatric Surgeons  

DOI： 10.11164/jjsps.42.3_379

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.55.293

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

A prospective payment system based on diagnosis procedure combination (DPC/PPS) was introduced to acute care hospitals in Japan in April 2003. In order to increase hospital income, hospitals must shorten the average Length of stay (ALOS) and increase the number of patients. We constructed a simulation program for evaluating the relationships among ALOS, bed occupation rate (BOR) and hospital income of hospitals in which DPC/PPS has been introduced. This program can precisely evaluate the hospital income by regulating the ALOS and the number of patients for each DPC. By using this program, it is possible to predict the optimum ALOS and optimum number of inpatients for each DPC in order to increase hospital income. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.cmpb.2005.09.003

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DOI： 10.1111/j.1440-1754.2005.00644_1.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

<b>Background:</b> Because bronchial inflammation was recognized as a basic component of bronchial asthma, the strategy for asthma management has changed in the last two decades. In Japan there are few clinico-epidemiological reports of changes in the management of bronchial asthma in actual practice.<br> In this study, we analyzed practical asthma management in Japan, and examined changes in the prevalence of asthma medication and relation between these changes and the level of asthma control and management.<br> <b>Methods:</b> From 1998 to 2002, questionnaires on asthma control, asthma related emergent episodes and satisfaction in daily life. Questionnaires were distributed to adult asthmatic patients. Questionnaires about the patients' profiles and medication were also given to the patients' doctors.<br> <b>Results:</b> The total number of patient responders was approximately 2500—3300 per year. The rate of peak flow meter (PEFM) use was under approximately only 40% and plateaued from 2000 to 2002. The percentage of inhaled corticosteroid use and leukotriene receptor antagonist use increased, from 62.0%, 27.2% to 77.4%, 40.6% respectively. Indicators for asthma control, including presence of attacks and sleep disturbance, were significantly improved. Limited to PEFM users, there was an improvement hospitalization, ambulance use or ED visits and in satisfaction in daily life based on a Quality of Life (QOL) indicator.<br> <b>Conclusions:</b> These results indicate that the prevalence of anti-inflammatory agents, including inhaled corticosteroids and leukotriene receptor antagonist, was associated with an adequate improvement in asthma control in clinical practice. In asthma management in clinical practice, prevalence of PEFM may play an important role in the improvement of asthma related emergent episodes or QOL.<br>

DOI： 10.2332/allergolint.54.555

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

<b>Background:</b> Not only monotherapy with inhaled corticosteroids (ICS) but also the concurrent use of other antiasthmatic agents, including leukotriene receptor antagonists (LTRA), play an important role in the management of asthma. However, few studies have focused on compliance with these drugs and on the relation between drug compliance and drug usage.<br> <b>Methods:</b> Data were derived from a survey of pharmacists dispensing antiasthmatic drugs to adults with asthma who visited participating pharmacies from October through November 2002. The patients were limited to regular users of ICS whose medication had not been changed for at least 6 months before the survey. Drug compliance and the daily administration frequency of antiasthmatic agents were evaluated on the basis of pharmaceutical records.<br> <b>Results:</b> Completed data were received for 322 patients. ICS compliance was lower than compliance with oral sustained-released theophylline (OSRT) and compliance with LTRA. ICS compliance significantly correlated with OSRT compliance and with LTRA compliance. There were no significant differences of ICS compliance among ICS alone, ICS + LTRA, ICS + OSRT and ICS + LTRA + OSRT group, while the daily inhalation frequency in ICS + OSRT or ICS + OSRT + LTRA group were higher than those in ICS alone group. Although there was a significant negative correlation between ICS compliance and daily inhalation frequency, neither OSRT compliance nor LTRA compliance significantly correlated with the tablet or capsule numbers per day. These findings indicate that OSRT may increase the compliance of concomitant ICS, and that the compliance of OSRT or LTRA is independent of the numbers of tablets taken per day.<br> <b>Conclusions:</b> These unique characteristics should be considered in the treatment and guidance of patients with bronchial asthma.<br>

DOI： 10.2332/allergolint.54.547

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

<b>Background:</b> The importance of smoking in bronchial asthma has been thoroughly investigated. Although a high smoking rate has been recognized in Japan, there have been few studies of the relationship between active smoking and bronchial asthma, and little analysis of the gender difference in this relationship. The aims of this study were to examine the contribution of active smoking to asthma and to clarify any gender difference.<br> <b>Methods:</b> For 8 weeks from September through October 2000, a smoking questionnaire survey was performed on adult patients with bronchial asthma, and their attending physicians, in Niigata Prefecture, Japan. The questionnaire surveyed asthma control, asthma-related emergencies and satisfaction in daily life. The attending physicians were questioned about patient profiles and medications. Patients were classified into three groups: non-smokers (NS), ex-smokers (ES) and current smokers (CS). For examination of gender differences, the CS group was compared with the NS group, due to variable duration of smoking and of cessation of smoking in the ES group.<br> <b>Results:</b> Complete data were received from 2947 cases. Of the male patients, 340 (23.0%) were in the CS group, 325 (22.0%) were in the NS group and 812 were in the ES group. Of the female patients, 109 (7.4%) were in the CS group, 1132 (77.4%) were in the NS group, and 229 (7.4%) were in the ES group. The male CS group had more severe asthma-related symptoms in the morning and at night, more sputum and cough in the morning, and more severe sleep disturbance than the male NS group. In the female patients, these differences were not detected. A logistic and multiple regression analysis confirmed these significant differences between male and female asthma patients.<br> <b>Conclusions:</b> The gender differences in the susceptibility of asthma to smoking suggests the need for gender-specific strategies for smoking cessation, although further investigation is required.<br>

DOI： 10.2332/allergolint.54.401

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DOI： 10.1007/s00467-004-1780-x

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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DOI： 10.1016/j.healthpol.2004.10.003

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Language：Japanese   Publisher：(一社)日本医療情報学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BAISHIDENG PUBL GRP CO LTD  

AIM: To assess the validity of our selection criteria for hepatectomy procedures based on indocyanine green disappearance rate (KICG), and to unveil the factors affecting posthepatectomy mortality in patients with hepatocellular carcinoma (HCC).
METHODS: A retrospective analysis of 198 consecutive patients with HCC who underwent partial hepatectomies in the past 14 years was conducted. The selection criteria for hepatectomy procedures during the study period were KICG &gt;= 0.12 for hemihepatectomy, KICG &gt;= 0.10 for bisegm-entectomy, KICG &gt;= 0.08 for monosegmentectomy, and KICG &gt;= 0.06 for nonanatomic hepatectomy. The hepatectomies were categorized into three types: major hepatectomy (hemihepatectomy or a more extensive procedure), bisegmentectomy, and limited hepatectomy. Univariate (Fisher(sic) exact test) and multivariate (the logistic regression model) analyses were used.
RESULTS: Postoperative mortality was 5% after major hepatectomy, 3% after bisegmentectomy, and 3% after limited hepatectomy. The three percentages were comparable (P = 0.876). The platelet count of &lt;= 10104/mL was the strongest independent factor for postoperative mortality on univariate (P = 0.001) and multivariate (risk ratio, 12.5; P = 0.029) analyses. No patient with a platelet count of &gt; 7.3104/mL died of postoperative morbidity, whereas 25% (6/24 patients) of patients with a platelet count of &lt;= 7.3104/mL died (P&lt;0.001).
CONCLUSION: The selection criteria for hepatectomy procedures based on KICG are generally considered valid, because of the acceptable morbidity and mortality with these criteria. The preoperative platelet count independently affects morbidity and mortality after hepatectomy, suggesting that a combination of KICG and platelet count would further reduce postoperative mortality. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.

DOI： 10.3748/wjg.v11.i37.5888

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE