Tokyo Women's Medical Research Articles

Knowledge regarding Proper Use Guidelines for Benzodiazepines

Benzodiazepines (BZs) work by agonising gamma-aminobutyric acid (GABA)-BZ-receptor complex and thereby produce sedation and anti-anxiety effects. BZs are commonly used in several clinical areas as hypnotics or anti-anxiety drugs. However, these drugs once supplied by medical institutions often lead to abuse and dependence. Thus it is important for institutions to supply and manage BZs properly. At Tokyo Women's Medical University Hospital educational activities about proper use of BZs are performed by not only medical doctors but also pharmacists. We coordinate distribution of leaflets and run an educational workshop. As a result of these activities, the number of patients receiving BZ prescriptions was reduced. Performing these activities, pharmacists were required to work for patients, doctors, and nurses; they acquired knowledge about BZs such as action mechanisms, efficacy, adverse effects, problems about co-prescription, and methods of discontinuing BZs, as well as information on coping techniques other than medication. The most important point to attend the patients is to answer their anxieties.

Photodynamic Therapy for Malignant Brain Tumors.

Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women’s Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area.

Mechanical stretching induced alternation of cell attachment and detachment character of poly(N-isopropylacrylamide) gel grafted PDMS surface

Event Abstract Back to Event Mechanical stretching induced alternation of cell attachment and detachment character of poly(N-isopropylacrylamide) gel grafted PDMS surface Yoshikatsu Akiyama1, Miki Matsuyama2, Naoya Takeda2, Masayuki Yamato1 and Teruo Okano1 1 Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Japan 2 Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Japan Introduction: Temperature-responsive cell culture surface, poly(N-isopropylacrylamide) (PIPAAm) hydrogel grafted tissue culture polystyrene (PIPAAm-TCPS), has been utilized for cell-sheet based tissue-engineering. PIPAAm-TCPS shows temperature-dependent cell attachment and detachment character, which is one of characteristics of PIPAAm-TCPS[1]. Based on a hypothesis that thickness of graft PIPAAm hydrogel layer were altered by applying mechanical stress to PIPAAm gel grafted substrate (Fig. 1), we modified PDMS surfaces with ultra-thin PIPAAm hydrogel (PIPAAm-PDMS) and characterized stretched and unstretched PIPAAm-PDMS surfaces as a new stretchable temperature-responsive cell culture surfaces. Experimental Methods: PIPAAm-PDMS was prepared referring to a previous report[2]. IPAAm monomer dissolved in 2-propanol (monomer concentration, 40 wt%) was spread onto 4-well PDMS cell culture surfaces (each chamber size was 16 mm square), which was purchased from STREX, Inc., followed by O2 plasma and (3-aminoproyl)trimethoxysilane (APTMS) treatments. And then, the surface was subjected to EB irradiation. During EB irradiation, polymerization and grafting polymer on PDMS surface occurred simultaneously. PIPAAm-PDMS was characterized by FT-IR / ATR, XPS analysis, contact angle measurement and cell detachment / attachment assay. For the cell attachment and detachment assay, PIPAA-PDMS with about 10.0 ug/cm2 of PIPAAm graft density was used. Uniaxial mechanical-stress was applied to the PIPAAm-PDMS surfaces with a special device (purchased from STEX, Inc.). In this experiment, 20% of stretch ratio was used for the characterization of stretched PIPAAm-PDMS surface. Results: To prove a hypothesis, PDMS was selected as a model elastic substrate in this experiment. Uniaxially stretched and unstretched PIPAAm-PDMS surfaces were evaluated by a variety of surface analysis methods. By modifying PDMS with PIPAAm hydrogel, contact angle decreased from 110º (unstretched PDMS) to 78º (unstretched PIPAAm-PDMS) at 37ºC (Fig. 2). The stretched and unstrethced PIPAAm-PDMS surfaces showed temperature-dependent contact angles alternation. However, by applying 20% of uniaxial mechanical stretching stress to PIPAAm-PDMS, the contact angles increased form 78º (unstretched PIPAAm-PDMS) to 83º (stretched PIPAAm-PDMS). AFM image of PIPAAm-PDMS surface showed PIPAAm nano-particles, which uniformly covered PDMS surface. The thickness of the graft PIPAAm hydrogel layer decreased from 700 nm to 480 nm (Fig. 3). Considering that temperature-responsive cell culture surfaces with thinner PIPAAm hydrogel layer shows more hydrophobic property, that PIPAAm-PDMS surface properties were altered by the applied mechanical stretching stress. Cell attachment assay also suggested that the stretched PIPAAm-PDMS was more cells adhesive. These results possibly suggest that PIPAAm-PDMS surface properties are controllable by the degree of applied mechanical stress. Grant-in-Aid for Scientific Research (No. 23106009) in Innovative Areas "Bio Assembler" from MEXT

Longitudinal PBL in Undergraduate Medical Education Develops Lifelong-Learning Habits and Clinical Competencies in Social Aspects.

Problem-based learning (PBL) is popular in medical education in Japan. We wished to understand the influence of PBL on the clinical competence of medical residents, using self-assessment and observer assessment. Tokyo Women's Medical University (TWMU) implemented PBL longitudinally (long-time) for four years, and on this basis we analyzed whether long-time PBL education is useful for clinical work. A self-assessment questionnaire was sent to junior and senior residents who were alumni of several schools, and an observation-based assessment questionnaire to senior doctors instructing them. Respondents were asked if they had used the PBL process in daily clinical tasks, and if so in what processes. Senior doctors were asked whether TWMU graduates perform differently from graduates of other schools. TWMU graduates answered "used a lot" and "used a little" with regard to PBL at significantly higher rates than other graduates. As useful points of PBL, they mentioned extracting clinical problems, solving clinical problems, self-directed leaning, positive attitude, collaboration with others, presentation, doctor-patient relations, self-assessment, and share the knowledge with doctors at lower levels and students. Observer assessments of TWMU graduates by senior doctors represented them as adaptive, good at presenting, good at listening to others' opinions, practical, selfish, and eager in their instructional practice. Longitudinal PBL can be a good educational method to develop lifelong-learning habits and clinical competencies especially in terms of the social aspect.

Differences in mortality and morbidity according to gestational ages and birth weights in infants with trisomy 18.

The aim of this study was to clarify the effects of gestational age and birth weight on outcomes of the infants. Medical records of 36 infants with trisomy 18 admitted to Tokyo Women's Medical University Hospital from 1991 to 2012 were reviewed retrospectively. We compared clinical characteristics between term infants (n = 15) and preterm infants (n = 21). There were one very‐low‐birth‐weight (VLBW) term infant (5%) and 12 VLBW preterm infants (80%). Although there were no significant differences in clinical characteristics and provided management between the two groups, none of the preterm infants achieved survival to discharge. On the other hand, 6 of 21 term infants (29%) achieved survival to discharge (P < 0.05). Similar results were obtained for comparisons between the VLBW infants and non‐VLBW infants. Multiple logistic regression analysis revealed that shorter gestational age had a more negative impact than lower birth weight to survival to discharge in infants with trisomy 18. In both preterm and term groups, the infants who died before 30 days commonly died of respiratory failure or apnea. Whereas, the infants who survived more than 30 days mostly died of heart failure. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Early unclamping might reduce the risk of renal artery pseudoaneurysm after robot-assisted laparoscopic partial nephrectomy.

To determine the influence of the early unclamping technique on the risk of renal artery pseudoaneurysm during robot-assisted laparoscopic partial nephrectomy. From January 2013 to October 2014, 96 patients underwent robot-assisted laparoscopic partial nephrectomy for renal masses at Tokyo Women's Medical University Hospital, Tokyo, Japan. Computed tomography angiography was carried out 3-4 days after surgery. Early in the series, renal hilum was left unclamped and renorrhaphy was subsequently carried out (conventional unclamping technique). An early unclamping technique has been used since November 2013. A total of 61 patients underwent robot-assisted laparoscopic partial nephrectomy with early unclamping, and 35 patients underwent robot-assisted laparoscopic partial nephrectomy with conventional unclamping. Ischemia time was significantly shorter in the early unclamping group (16.5 vs. 23.1 min; P < 0.01). The early unclamping group showed a significantly lower incidence of asymptomatic renal artery pseudoaneurysm relative to the conventional unclamping group (11.4% vs. 28.6%; P = 0.03). Multivariate analysis showed that the early unclamping technique was a significant independent factor in reducing the risk of renal artery pseudoaneurysm (hazard ratio 0.27; P = 0.01). The present findings suggest that an early unclamping technique might reduce ischemic time and risk of renal artery pseudoaneurysm. The absence of arterial bleeding before renorrhaphy is likely to be a key step in preventing renal artery pseudoaneurysm during robot-assisted laparoscopic partial nephrectomy.

Clinical and pathological analyses of chronic vascular rejection after kidney transplantation.

We discuss the clinicopathological analysis of cases of chronic vascular rejection (CVR) cases after renal transplantation and clarify the mechanisms underlying the development and prognostic significance of CVR. CVR was diagnosed in 46 renal allograft biopsy specimens (BS) obtained from 34 renal transplant patients being followed up at the Department of Urology, Tokyo Women's Medical University, between January 2009 and December 2013. CVR was diagnosed at a median of 47.4 months post-transplant. Among the 36 patients, 23 had a history of acute rejection. Among the 46 BS showing evidence of CVR, the CVR was mild (cv1 in Banff's classification) in 23, moderate (cv2) in 17, and severe (cv3) in 6. Of the 40 samples obtained at the time of the biopsy and assayed with plastic beads coated with HLA antigen, 31 (78%) showed circulating ant-HLA alloantibody, and 15 (38%) showed donor-specific antibodies. We then classified the 46 BS showing evidence of CVR by their overall histopathological features, as follows; cv alone was seen in 16 (35%) BS, cv + antibody-mediated rejection (AMR) in 26 (56%), and cv + T-cell-mediated rejection in 9 (19%). Loss of the renal allograft occurred during the observation period in nine of the patients (26%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 11 patients (32%). The results of our study suggest that AMR may underlie CVR in many cases, while T cell-mediated rejection may play an important role in some cases.

PP.14.06

Objective: Postprandial hypotension is a common disorder of blood pressure regulation in the elderly, associated with falls and syncope. The pathophysiological mechanism is thought to be related to impaired vascular compensation for splanchnic blood pooling after a meal. Several studies have suggested that caffeine, acarbose, and Guar gum can improve reduction of postprandial blood pressure (BP). However, these treatments may not necessarily be effective in the patients with symptomatic PPH. Recently, we first experienced the effect of Theophylline on PPH which categorized as xanthine like caffeine. In this study, we investigated the mechanism of action of Theophylline.Design and method: The case is an 92-year-old man under outpatient care for hypertension was admitted to Aoyama Hospital, Tokyo Women's Medical University, Tokyo, Japan, for the investigation and treatment of faintness after breakfast in December 2014. Ambulatory BP monitoring (ABPM) over a 24 hours period showed a decrease in systolic BP of more than 20 mmHg within 2 hours after meal, leading to the diagnosis of PPH. We performed meal test during two days hospitalization. Measurement items were blood pressure, blood test including plasma levels of glucose, insulin, noradrenaline (NA) and renin activity (PRA) before and after breakfast. At the first day, we tested in control (without Theopylline). Next day, we evaluate the effects of Theopylline on PPH. Four hundred mg of Theopylline was given at once before going to sleep at the first day Results: In control, the systolic blood pressure (SBP) decreased from 134mmHg to 97mmHg at 90 minutes after eating. Surprisingly, Theophylline maintained to the drop of SBP from 114mmHg to 97mmHg. Serum NA and PRA levels showed marked elevation under Theophylline administration. Moreover, after taking Theophylline, the patient's symptoms had disappeared Conclusions: We report a case of postprandial hypotension improved by theophylline administration. The part of mechanism may involve the effects of Theopylline as an Adenosine receptor antagonist.

Professor Yukio Fukuyama (福山幸夫教授)

Professor Yukio Fukuyama (Figure), an excellent clinician, accomplished scientist, prolific organizer, respected mentor, and exemplary leader died at his home in Tokyo on July 17, 2014. He was Emeritus Professor of Neurology at Tokyo Women's Medical College and the Director of the Child Neurology Institute. He is survived by his wife, Madam Ayako Fukuyama. His accolades were earned over nearly 60 years from the dawn of modern pediatric neurology. His were unique and independent contributions that marked a proud and distinctive heritage for his beloved country.

MP57-17 COMPARISON OF SURVIVAL RATES IN STAGE ONE RENAL CELL CARCINOMA BETWEEN PARTIAL NEPHRECTOMY AND RADICAL NEPHRECTOMY PATIENTS ACCORDING TO AGE DISTRIBUTION

You have accessJournal of UrologyKidney Cancer: Surgical Therapy II1 Apr 2015MP57-17 COMPARISON OF SURVIVAL RATES IN STAGE ONE RENAL CELL CARCINOMA BETWEEN PARTIAL NEPHRECTOMY AND RADICAL NEPHRECTOMY PATIENTS ACCORDING TO AGE DISTRIBUTION Toshio Takagi, Tsunenori Kondo, Kenji Omae, Junpei Iizuka, Hirohito Kobayashi, Yasunobu Hashimoto, and Kazunari Tanabe Toshio TakagiToshio Takagi More articles by this author , Tsunenori KondoTsunenori Kondo More articles by this author , Kenji OmaeKenji Omae More articles by this author , Junpei IizukaJunpei Iizuka More articles by this author , Hirohito KobayashiHirohito Kobayashi More articles by this author , Yasunobu HashimotoYasunobu Hashimoto More articles by this author , and Kazunari TanabeKazunari Tanabe More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2005AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients undergoing PN had lower rates of cardiovascular events and better survival rates than those with radical nephrectomy (RN) in previous retrospective study. However, a randomized study (EORTC 30904) could not demonstrate the superiority of PN over RN in either survival rates or kidney function. Although that study has some limitations, we should discuss what type of patients with small renal tumors are likely to benefit more from PN than from RN. Thus, we compared the effects of PN and RN on overall survival in patients with localized renal cell carcinoma (RCC) according to age and analyzed what age groups benefit most from PN. METHODS This study comprises 989 patients with Stage 1 RCC who underwent PN or RN at Tokyo Women's Medical University Hospital. Patients are divided into three groups according to age: Group 1(≤ 54 years), Group 2(55-64) and Group 3(≥65). We compared overall survival(OS), patient characteristics including the presence of hypertension(HT), diabetes mellitus(DM), and preoperative eGFR between PN and RN among the three groups. RESULTS Group 1 included 340 patients(PN: 205, RN:123); Group 2, 318(PN:201, RN 117); and Group 3, 331(PN:209, RN:122). Older groups have significantly lower preoperative eGFR values and higher rates of HT and DM(all p<0.0001). However, these characteristics are similar between PN and RN in each group. In addition, PN can preserve more renal function than RN in all groups, despite a bit worse preoperative eGFR in the PN group than in RN. In Group 2 and Group 3, there is a significant difference in OS between PN and RN(Group2 5-yr PN: 98% RN: 89% p=0.0125, Group3 PN: 91% RN: 82% p=0.0098), whereas, a significant difference is not seen in Group 1(PN: 100% RN: 96% p=0.182). CONCLUSIONS Our study demonstrated that PN has significantly better survival rates than RN in older patients, but not in younger ones, suggesting that patients with comorbidities may receive more benefit from PN than those without. We propose that patients should not avoid PN only because of their advanced age. We also recommend PN for young patients with T1 RCC despite no significant overall survival difference between surgical approaches because of the other, important benefits it offers, including avoiding treatment for benign tumors and keeping other options open. Group 1 (n=340) Group 2 (n=318) Group 3 (n=331) p Age (year), mean, IQR 45 (40-51) 60 (57-62) 72 (67-76) <0.0001 BMI (kg/m2), mean (IQR) 24 (22-26) 24 (22-26) 24(22-26) 0.4334 Gender, male, n (%) 253 (74) 232 (73) 229 (69) 0.3008 HT, n (%) 50 (15) 133 (42) 166 (50) <0.0001 DM, n (%) 20 (6) 60 (19) 81 (25) <0.0001 Preop eGFR, mean(IQR) 81 (69-91) 70 (59-81) 62 (50-73) <0.0001 Postop eGFR, mean(IQR) 67 (54-79) 56 (45-67) 50 (37-62) <0.0001 Tumor size (cm), mean, IQR 3.5 (2.4-4.5) 3.5 (2.3-4.6) 3.3 (2.3-4.2) 0.1306 Follow up (month), mean (IQR) 78 (24-111) 62 (20-81) 51 (21-67) 0.0002 © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e696 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Toshio Takagi More articles by this author Tsunenori Kondo More articles by this author Kenji Omae More articles by this author Junpei Iizuka More articles by this author Hirohito Kobayashi More articles by this author Yasunobu Hashimoto More articles by this author Kazunari Tanabe More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

How to prevent contamination with Candida albicans during the fabrication of transplantable oral mucosal epithelial cell sheets.

We have utilized patients' own oral mucosa as a cell source for the fabrication of transplantable epithelial cell sheets to treat limbal stem cell deficiency and mucosal defects after endoscopic submucosal dissection of esophageal cancer. Because there are abundant microbiotas in the human oral cavity, the oral mucosa was sterilized and 40 μg/mL gentamicin and 0.27 μg/mL amphotericin B were added to the culture medium in our protocol. Although an oral surgeon carefully checked each patient's oral cavity and although candidiasis was not observed before taking the biopsy, contamination with Candida albicans (C. albicans) was detected in the conditioned medium during cell sheet fabrication. After adding 1 μg/mL amphotericin B to the transportation medium during transport from Nagasaki University Hospital to Tokyo Women's Medical University, which are 1200 km apart, no proliferation of C. albicans was observed. These results indicated that the supplementation of transportation medium with antimycotics would be useful for preventing contamination with C. albicans derived from the oral mucosa without hampering cell proliferation.

Chronological changes in baseline disease activity of patients with rheumatoid arthritis who received biologic DMARDs between 2003 and 2012

Background/Purpose. The use of biologic disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA) has been increasing since 2003. In this study, we evaluated changes in the characteristics of patients receiving biologic DMARDs daily, in Japan.Methods. The characteristics of all RA patients who received any biologic DMARD at the Institute of Rheumatology, Tokyo Women's Medical University, within 1 year after its approval in Japan, were retrospectively evaluated. The periods of patient enrollment for each biologic agent were: infliximab (IFX), 2003–2004; etanercept (ETN), 2005–2006; tocilizumab (TCZ), 2008–2009; adalimumab (ADA), 2008–2009; abatacept (ABT), 2010–2011; and golimumab (GLM), 2011–2012. We retrospectively collected individual patient characteristics, concomitant medication usage, and disease activity assessed by disease activity score 28 (DAS28) at the time of administration, from the medical records. The retention rate for each agent at 6 months after treatment initiation was also assessed.Results. The numbers of patients who received each biologic DMARD at our institute within 1 year after its approval were: IFX, 49; ETN, 50; TCZ, 62; ADA, 52; ABT, 40; and GLM, 77. From 2003 to 2012, the proportion of patients with prior use of any biologic DMARD increased, as did concomitant use and dose of methotrexate (MTX); however, corticosteroid use and doses decreased. DAS28, at the time of treatment initiation, gradually decreased. At the time of IFX administration, 75% and 25% of patients had high and moderate disease activity respectively, compared to 25% and 58% respectively, of patients who received GLM. No significant difference was observed in the retention rate of biologic DMARDs at 6 months (range, 75.0% to 89.6%).Conclusion. Baseline disease activity of RA patients who received biologic DMARDs between 2003 and 2012 has changed from high to moderate in daily practice in Japan.

Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection.

OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status. METHODS One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings demonstrated that EOR was significantly correlated with patient survival; thus, one should aim for maximum tumor resection. In addition, patients with a higher EOR can be safely observed without adjuvant therapy. For patients with partial resection, postoperative chemotherapy should be administered for those with oligodendroglial subtypes, and repeat resection should be considered for those with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be required for patients with a poor prognosis, such as those with diffuse astrocytoma, 1p/19q nondeleted tumors, or IDH1 wild-type oligodendroglial tumors with partial resection.

BM-08 * PROGNOSTIC FACTORS FOR SRS-TREATED PATIENTS WITH CEREBRAL METASTASIS: IMPLICATIONS ON RANDOMIZED CONTROL TRIAL DESIGN AND INTER-INSTITUTIONAL COLLABORATIVE EFFORTS

INTRODUCTION: Defining key prognostic factors for patients with cerebral metastases who underwent stereotactic radiosurgery (SRS) treatment will greatly facilitate future clinical trial designs. However, these is little agreement in terms of these prognostic factors in the existing literature. METHODS: We adopted a two-phase study design where results from one cohort were validated in a second independent cohort. The exploratory analysis reviewed the survival outcomes of 1017 consecutive patients (with 3610 metastases) who underwent Gamma radiosurgery at the University of California, San Diego (UCSD)/San Diego Gamma Knife Center (SDGKC). Multivariate analysis was performed to identify prognostic factors. Results were validated using data derived from 2253 consecutive patients (with 17,539 metastases) treated with SRS at the Tokyo Women's Medical University (TWMU). RESULTS: For the SDGKC cohort, the median overall survival of patients following SRS was 7 months. Two year follow-up data was available for 85 % of the patients. Multivariable analysis found that patient age, Karnofsky performance score, systemic cancer status, tumor histology, number of metastasis, and cumulative tumor volume independently associated with overall survival (p < 0.001). All statistical associations were validated in multivariate analysis of data derived from the TWMU cohort. CONCLUSIONS: This is the first large scale study that defined prognostic factors for SRS treated patients with cerebral metastasis using an inter-institutional validation study design. The work establishes a model for collaborative interactions between large volume centers and provides prognostic variables that should be incorporated into future clinical trial design.

NT-25 * EARLY JAPANESE EXPERIENCE WITH NovoTTF-100A SYSTEM FOR RECURRENT GBM

BACKGROUND: NovoTTF-100A System is an FDA-approved treatment for recurrent glioblastoma (GBM) and is defined as a device of high unmet medical need in Japan. Subsequently, the device has been made available on a restricted case basis for compassionate use in Japan. Here we report initial experience with 10 patients treated at Tokyo Women's Medical University, Kashiwaba Neurosurgical Hospital and Japanese Red Cross Medical Center. METHODS: Using retrospective chart review, we analyzed patient demographics, tumor size, location, and treatment compliance with NovoTTF-100A System from the device log files. Duration of therapy was estimated using the Kaplan-Meier estimate. Adverse event frequency and severity was also evaluated. RESULTS: Ten (10) patients with supra-tentorial recurrent GBM were treated between July 8, 2013 and June 3, 2014 at 3 Japanese hospitals. 80% were male and 20% female. The median age was 41 years (range 32-66). The average baseline tumor burden was 13.3 cm2. 40% of patients had bi-hemispheric tumors and 30% left hemispheric tumors. The K-M median duration of therapy was 7.8 months. Average daily device compliance was 17.4 hours. This is consistent with prior global studies which have demonstrated average daily device compliance of 70-80%. The device was well-tolerated with no reported serious adverse events. The only device-related adverse events were mild skin irritation. CONCLUSIONS: NovoTTF-100A System was safe and well-tolerated in an initial cohort of Japanese patients with GBM. Device usage and compliance was consistent with that observed in non-Japanese patients.

Trial Use of the Personal Qualities Assessment (PQA) in the Entrance Examination of a Japanese Medical University: Similarities to the Results in Western Countries

Background: The Personal Qualities Assessment (PQA), developed by the University of Newcastle, Australia to assess the aptitude of future medical professionals, has been used in Western countries. Purposes: The objective was to investigate whether the PQA is appropriate for Japanese medical school applicants. Methods: Two of the PQA tests, Libertarian-Dual-Communitarian moral orientations (Mojac) and Narcissism, Aloofness, Confidence, and Empathy (NACE), were translated into Japanese, and administered at the Tokyo Women's Medical University entrance examinations from 2007 to 2009. Results: The distributions of the applicants’ Mojac and NACE scores were close to the normal distribution, and the mean scores did not exhibit a large difference from those in Western countries. The only significant difference was that the mean score of the NACE test was slightly lower than the Western norm. Conclusions: The translated PQA tests may be appropriate for use with Japanese applicants, though further research considering cultural differences is required.

Abstract 3503: Somatic mutations and aberrant expression of RNF43 are recurrently found in intraductal papillary mucinous neoplasms of the pancreas

Abstract Background: RNF43 encodes ring finger protein 43, an ubiquitin ligase, and is recently uncovered as mutated in intraductal papillary mucinous neoplasms of the pancreas (IPMNs). We studied mutations and aberrant expressions of RNF43 and their associations with molecular and clinicopathological features in IPMNs. Materials and methods: Studied were 178 IPMNs operated upon between 2001 and 2010 at Tokyo Women's Medical University Hospital. Formalin-fixed and paraffin-embedded tissues of the 178 cases and frozen tisssues of 56 of the cases were subjected for immunohistochemical and the next generation semiconducter sequencing analyses, respectively. Detected mutations were validated by Sanger sequencing. Results: Expression of RNF43 was reduced in 60 (33.7%) of the 178 IPMNs. Somatic mutations in RNF43 were found in 10 (17.9%) of the 56 examined cases, in which frameshift mutations, a nonsense mutation, and missense mutations were found in 5, 1, and 4 cases, respectively. These mutations were significantly associated with RNF43 expression (p = 0.008) and GNAS mutation (p = 0.012), however, not associated with tumor grade, histological subtype or prognosis. Conclusion: These results indicate that RNF43 may function as a tumor suppressor and play a role in development of IPMN. Citation Format: Hitomi Sakamoto, Yuko Kuboki, Takashi Hatori, Masakazu Yamamoto, Masanori Sugiyama, Noriyuki Shibata, Kyoko Shimizu, Keiko Shiratori, Toru Furukawa. Somatic mutations and aberrant expression of RNF43 are recurrently found in intraductal papillary mucinous neoplasms of the pancreas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3503. doi:10.1158/1538-7445.AM2014-3503

Long-term outcome of 114 adult JIA patients in a non-pediatric rheumatology institute in Japan

Objective. To evaluate the long-term outcome of patients with juvenile idiopathic arthritis (JIA) using data from a large cohort database, Institute of Rheumatology, Rheumatoid Arthritis, managed by the Tokyo Women's Medical University.Methods. Of 182 patients identified from the database from 2000 to 2013, 114 were verified as having JIA. The transition of medical care and the contributions of biological DMARDs were evaluated.Results. The mean age of the patients (93 females, 81.6%) at the latest examination was 36.6 ± 13.3 years. The mean age at disease onset and mean disease duration were 11.6 ± 3.4 and 25.0 ± 13.3 years, respectively. Of the 114 patients, 106 (93.0%) had poly- or oligoarthritis. Only one-fourth transferred from general pediatricians or pediatric rheumatologists. More patients with recent disease onset were treated with biological DMARDs (16.7% in the 1970s, vs. 80.0% in the 2000s). Disease activity assessed with DAS28 was significantly lower when disease onset was more recent (3.9 ± 1.3 for onset in the 1960s vs. 2.2 ± 1.1 for onset in the 2000s, p = 0.04). The percentage of patients requiring orthopedic surgery has decreased (53.8% before the 1970s vs. 10.0% in the 2000s).Conclusion. Patients with more recent disease onset showed an improved outcome. Establishing and sharing a transition program among pediatric and non-pediatric rheumatologists is desirable.

Assessment of Long-Term Outcomes After Kidney Retransplantation.

[Introduction] In recent years it has become possible to prevent antibody-mediated rejection by performing desensitization with a combination of preoperative plasma exchange, rituximab (RIT), and g-globulin (IVIG).In the present study we assessed the long-term outcome of initial kidney transplantation and retransplantation. [Subjects and Methods] Between 2001 and 2013 kidney transplantation was performed in 1026 cases (initial kidney transplantation: 965 cases; kidney retransplantation: 61 cases) in the Department of Urology of Tokyo Women's Medical University. The assessment was conducted by dividing the cases into an initial kidney transplantation group and a kidney retransplantation group and comparing them. [Results] No significant differences between the groups were seen in their 1-year, 5-year, or 10-year graft survival or patient survival rates, and no significant differences were seen in their serum creatinine values. The pre-transplantation donor-specific antibody (DSA)-positive rate was 169/965 (18%) in the initial transplantation group and 22/61 (36%) in the retransplantation group, and DSA-positive cases tended to be more common in the retransplantation group. The rate of occurrence of chronic antibody-mediated rejection was higher in the retransplantation group, and the difference in rejection rates was significant. The frequency of de novo detection was 31/965 (3%) in the initial transplantation group and 1/61 (2%) in the retransplantation group, and it tended to be higher in the initial transplantation group. [Conclusion] By performing an adequate preoperative immunologic evaluation with flow cytometry crossmatch (FCXM), Luminex, etc., and performing preconditioning when necessary, it appeared possible to achieve outcomes that are not inferior to the outcomes of initial transplantation.

AB0017 Impact of Disease Susceptibility Genes on Progression of Joint Destruction in Japanese Patients with Rheumatoid Arthritis

BackgroundDisease severity of rheumatoid arthritis (RA) is objectively measured by radiographic joint damage, which is reflective of the cumulative burden of inflammation. To date, several genetic risk loci for progression...