Fujita Health University Research Articles

Computational Fluid Dynamics in Unruptured Intracranial Aneurysms

Abstract Introduction and Objective: Intracranial aneurysm, also known as brain aneurysm, is a cerebrovascular disorder in which weakness in the wall of a cerebral artery causes a localized dilation or ballooning of the blood vessel. There is no objective way, device or tools, of predicting rupture of aneurysm so far. Computational fluid dynamics (CFDs) was proposed as a tool to identify the rupture risk. Purpose of study: To reveal the correlation of CFD findings with intraoperative microscopic findings and prove the relevance of CFDin the prediction of rupture risk and in the management of unruptured intracranial aneurysms. Subjects and Methods: A prospective cohort study was conducted inNeurosurgery department of Fujita Health University Banbuntane Hotokukai Hospital, Nagoya, Japanduring a 3‑month period in 2018,from January to March, Ten patientswere diagnosed unruptured intracranial aneurysms (UIA). In diagnosis computed tomography (CT) angiogram, CFD and digital subtraction angiogram were included. Intraoperatively microscopic examination of the aneurysm wall was carried out and images recorded. The correlation between microscopic dome morphology and CFD information was performed. Results: Nine cases were found intraoperatively to have a higher risk of rupture based on the thinning of the wall. One cases had an atherosclerotic wall. All cases had low wall shear stress (WSS). In 90 % of cases Low WSS was able to predict the potency rupture risk in the near future. Conclusions: This study of CFD and its correlation with intraoperativefindings of the aneurysm suggested that low WSS of the aneurysm wall is associated with thin wall aneurysm and hence increased risk of aneurysm rupture. Thus CFD can be used to predict the risk of rupture of unruptured aneurysm and for planning of its treatment.

Early experience with robot-assisted radical cystectomy and intracorporeal ileal conduit urinary diversion at Fujita Health University School of Medicine

Early experience with robot-assisted radical cystectomy and intracorporeal ileal conduit urinary diversion at Fujita Health University School of Medicine

Scattering Transform of Heart Rate Variability for the Prediction of Ischemic Stroke in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is an identified risk factor for ischemic strokes (IS). AF causes a loss in atrial contractile function that favors the formation of thrombi, and thus increases the risk of stroke. Also, AF produces highly irregular and complex temporal dynamics in ventricular response RR intervals. Thus, it is hypothesized that the analysis of RR dynamics could provide predictors for IS. However, these complex and nonlinear dynamics call for the use of advanced multiscale nonlinear signal processing tools. The global aim is to investigate the performance of a recently-proposed multiscale and nonlinear signal processing tool, the scattering transform, in predicting IS for patients suffering from AF. The heart rate of a cohort of 173 patients from Fujita Health University Hospital in Japan was analyzed with the scattering transform. First, p-values of Wilcoxon rank sum tests were used to identify scattering coefficients achieving significant (univariate) discrimination between patients with and without IS. Second, a multivariate procedure for feature selection and classification, the Sparse Support Vector Machine (S-SVM), was applied to predict IS. Groups of scattering coefficients, located at several time-scales, were identified as significantly higher (p-value < 0.05) in patients who developed IS than in those who did not. Though the overall predictive power of these indices remained moderate (around 60 %), it was found to be much higher when analysis was restricted to patients not taking antithrombotic treatment (around 80 %). Further, S-SVM showed that multivariate classification improves IS prediction, and also indicated that coefficients involved in classification differ for patients with and without antithrombotic treatment. Scattering coefficients were found to play a significant role in predicting IS, notably for patients not receiving antithrombotic treatment. S-SVM improves IS detection performance and also provides insight on which features are important. Notably, it shows that AF patients not taking antithrombotic treatment are characterized by a slow modulation of RR dynamics in the ULF range and a faster modulation in the HF range. These modulations are significantly decreased in patients with IS, and hence have a good discriminant ability.

Fujita Health University Core for Comprehensive Community Care

Fujita Health University Core for Comprehensive Community Care

A retrospective study of the efficacy of ramelteon for insomnia: relevance of dose and timing of administration

The objective of the study was to investigate the efficacy of ramelteon for insomnia, particularly with circadian disturbance, focusing on the relevance of dose and timing of administration. We reviewed the chart data of 145 continuous patients who received ramelteon for insomnia for the first time at the sleep clinic of the Department of Psychiatry, Fujita Health University Hospital (Aichi, Japan) between October 2010 and May 2014. Treatment efficacy was assessed using the Clinical Global Impression of Improvement (CGI-I) scale and this relationship with the dose and timing of administration was further analyzed. Symptoms in 56.6% of patients were improved (CGI-I ≦ 3). In a subgroup of 114 patients, especially aiming for phase advance, the ratio of improvement was 64.0%. The ratio of patients reporting symptom improvement tended to be great in the low-dose (1 or 2 mg) group and the low-dose + early administration (> 5 h before habitual bedtime) group, as compared with the remaining group; however, this difference was not statistically significant. Significantly fewer cases in the low-dose group reported carry-over effects. In our specialized sleep clinic, there were many refractory cases of insomnia; however, ramelteon was effective in about half of such patients. Particularly, ramelteon tended to be more effective for patients with insomnia and circadian disturbances, although differences among groups were not statistically significant. The effectiveness of the low-dose administration or the combination of low-dose and early-administration was equal or slightly better and acceptability tended to be better than other modes of administration.

No Viral Spreading After Rotavirus Vaccination in NICU

BackgroundPreterm and low birth weight infants are considered to be high risk for severe rotavirus gastroenteritis. However, it has been demonstrated that many infants are ineligible for receiving rotavirus vaccine due to over the age limitation within the neonatal intensive care unit (NICU). We sought to elucidate the safety of rotavirus (RV) vaccination in NICU by assessing vaccine virus transmission from vaccine recipients in NICU.MethodsThis study was designed as the prospective study conducted at the NICU of Fujita Health University hospital and Konan Kosei Hospital. This study was approved by the ethical committee in our university. Premature age-eligible infants were recruited to administer rotavirus vaccine. Stool samples were serially collected from unvaccinated infants (UVI) and vaccinated infants (VI) who received either the pentavalent rotavirus vaccine (RV5) or monovalent rotavirus vaccine (RV1). During October 10, 2014 and December 25, 2015, 19 VIs and 49 UVIs were enrolled in this study. Contact precaution was carried out in NICU. All stool samples were analyzed by real-time RT-PCR for detection of RV5, RV1, and wild-type strain’s genomes.ResultsTotal of 676 stool samples (89 samples collected from the 9 RV5 vaccinated infants, 110 samples collected from the 10 RV1 vaccinated infants, and 477 samples collected from the 49 UVIs) were analyzed in this study. Nineteen VIs received with first dose of vaccine demonstrated persistent shedding of rotavirus vaccine genome during 1–8 days after the first dose of the vaccine. Meanwhile, in comparison to VIs received with first dose of vaccine, the detection of viral genome in stool samples decreased gradually in there VIs after second dose of vaccine. In contrast to the VI, no vaccine genome was detected in any of the stool samples collected from the UVIs.ConclusionThis study suggests that RV vaccine may be safe for administration of preterm and low birth weight infants in NICU. Accordingly, the contact precaution measures may play an important role in prevention of vaccine virus transmission between VIs and UVIs.Disclosures All authors: No reported disclosures.

EXTRACORPOREAL BLOOD Aβ REMOVAL SYSTEM (EBARS) REDUCED SOLUBLE Aβ IN THE BRAIN BY TRIGGERING INFLUX INTO THE BLOOD: RAT STUDIES

Rapid removal of Aβ from the blood by an extra-corporeal system may act as a peripheral sink from the brain. We have reported that 1) several medical materials including hemodialyzers are able to remove Aβ effectively, 2) the concentrations of blood Aβs decreased and Aβ influx into blood were triggered during hemodialysis in humans, 3) Aβ deposition in the brain of hemodialysis patients was significantly lower than controls. Here, the effect of removing blood Aβ on blood and cerebrospinal fluid (CSF) concentrations of Aβ was investigated in rats. This study was approved by the Institutional Animal Care and Use Committee in Education and Research Center of Fujita Health University. The blood of normal SD male rats (9–11weeks, n=8) was treated for 60 minutes extracorporeally with mini-columns of hexadecyl-alkylated cellulose beads (HDC) as Aβ removers. Blood was collected at pre/post of the HDC-columns and CSF from Cisterna magna. The Aβ1–40 and Aβ1–42concentrations were measured by sandwich ELISAs (WAKO, Japan). The removal efficiencies of the blood Aβs by HDC-columns were 98% at 30min and 83% at 60min for Aβ1–40, 96% at 30min and 94% at 60min for Aβ1–42 during blood purification. Despite such high removal efficiencies, the blood Aβ concentrations at the end of blood Aβs removal (60min) in the whole body circulation significantly “increased” up to 153% for Aβ1–40 and 187% for Aβ1–42 (both, p=0.0003) compared with those just before the treatment. Further, Aβ concentrations in CSF decreased to 77% for Aβ1–40 (p=0.022) and 90% for Aβ1–42 (p=0.27). The decrease tendency of CSF Aβs continued another 60min; 64% for Aβ1–40 (p=0.071) and 77% for Aβ1–42 (p=0.25) compared with those before the treatment. Removal blood Aβ may trigger the influx from the brain into the blood. This might explain few Aβ depositions in the brains of hemodialysis patients. Therefore, Extracorporeal Blood Aβ Removal Systems may be potential therapeutic systems for Alzheimer's Disease. Acknowledgment: The authors thank Mrs. Kota Watanabe, Hiroki Aoki, and Ms. Yuri Sakakibara for their technical assistance. This work was partly supported by KAKENHI (2350531, 26282126) and Smoking Research Foundation.

Usefulness of Interprofessional Education (Tsurumai-Meijo IPE) in Program Collaborating with Simulated Patients.

Collaboration with multiple healthcare professionals is important to provide safer and higher quality care. Interprofessional education (IPE) promotes the practice of team-based care. The establishment of Tsurumai-Meijo IPE, including interprofessional education and practice (IPEP) and video-teaching materials, was conducted in collaboration with school of medicine/nursing in Nagoya University and Fujita Health University, because Meijo University does not have its own clinical settings and faculties except for pharmacy. In the established Tsurumai-Meijo IPE, pharmacy, medicine, and nursing students interviewed simulated patients (SP) together or separately and practiced team-based care through Tsurumai-Meijo IPEP. Students could learn in advance and on their own about each professional's knowledge related to patient care by using video-teaching materials from the Meijo IPE homepage. Using a questionnaire survey at the end of program, this study was examined whether Tsurumai-Meijo IPEP, and video-teaching materials were useful for understanding importance of team-based care. More than 83% of students indicated that Tsurumai-Meijo IPE is useful on future clinical practice. This suggests that the program and materials are beneficial to the medical student education. In the optional survey of some clinical pharmacists, who had participated in Tsurumai-Meijo IPE before graduation, they utilized it in their work and it facilitated their work related to team-based care. Tsurumai-Meijo IPE collaborating with SP is likely to contribute to provide high quality and safe team-based care by taking advantage of specialized professional ability of healthcare professionals.

Abstract P5-15-10: Eribulin mesylate (eribulin) showed inhibitory effects on epithelial-mesenchymal transition (EMT) in tumors of metastatic breast cancer patients. -First preliminary report of a prospective study-

Abstract Background: EMT is thought to contribute to metastasis in patients with breast cancer, leading to their poor prognosis. Pivotal phase III trials have demonstrated that eribulin improved overall survival in patients with triple negative metastatic breast cancer (MBC). Preclinical studies have shown that eribulin suppressed EMT and this phenomenon could be one of reason for an improved prognosis of MBC patients treated with eribulin. However, there is no direct clinical data on the effect of eribulin treatment on EMT in tumors of MBC patients. We designed a prospective study to clarify if eribulin treatment suppresses EMT in tumors of MBC patients. Patients and methods: Patients with recurrent or MBC were treated with eribulin (1.4 mg/m2 intravenously on days 1 and 8 of a 21-day cycle). Dose reductions were allowed according to eribulin's prescribing information. Treatment continued until disease progress, unacceptable toxic effects, or discontinuation requests from patients or physicians. Breast cancer tissue samples were obtained from all patients before and on day 15±4 of 1st cycle of eribulin treatment. The quantitative analysis of mRNA levels of EMT markers (E-cadherin, cytokelatin18, cytokelatin19, N-cadherin, vimentin, ZEB1, Slug, Snail, and Twist) were carried out by qPCR. Primary outcome measure was to assess the change from baseline to day 15±4 in mRNA levels of EMT related markers in tumor tissue. This study was approved by the Ethic Committee of Fujita Health University. Results: Eleven patients were enrolled. Median age of the patients was 63 years old (44-72). Of the 11 tumors, 6 were luminal B and 5 were triple negative (TN). Median number of prior chemotherapy regimen for recurrent or metastatic disease was 0 (0-3). Four patients were treated with dose reduced eribulin (1.1 mg/m2) and administration of eribulin on day 8 during 1st cycle of the treatment were skipped in 2 patients. To identify meaningful EMT markers, differences in expression levels of each EMT marker were investigated between TN and luminal B tumors. At baseline mRNA levels of N-cadherin and vimentin were higher in TN tumors than in luminal B tumors, 8.12±10.78 vs 1.02±0.68, 5.13±4.50 vs 0.88±0.47, respectively. After the treatment, a decrease of expression of N-cadherin and vimentin was more frequent in TN tumors (100% and 80%, respectively) than in luminal B tumors (33.3% and 16.7%, respectively). Frequency of a decrease of expression of ZEB1, Slug, Snail, and Twist in TN tumors and luminal B tumors were 80% (TN) vs 83.3% (luminal B), 80% vs 16.7%, 40% vs 66.7%, and 100% vs 50%, respectively. Conclusions: This is the first prospective study to investigate the effect of eribulin treatment on expression of EMT markers in tumors of MBC patients. We demonstrated that eribulin treatment suppressed EMT in tumors. Our results suggested that eribulin showed antitumor effect by improving the tumor microenvironment. In our study, eribulin seems to have different effects on EMT pathway in individual cases. Our findings may provide a light to a scientific basis for solving underlying mechanisms for improvement of overall survival of patients with MBC treated with eribulin. Citation Format: Utsumi T, Hayashi T, Kobayashi N, Hikichi M, Ushimado K, Ri Y, Nakano S, Fujii K, Ando T. Eribulin mesylate (eribulin) showed inhibitory effects on epithelial-mesenchymal transition (EMT) in tumors of metastatic breast cancer patients. -First preliminary report of a prospective study- [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-10.

Efficacy and tolerability of topiramate-augmentation therapy for schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to perform a comprehensive meta-analysis of topiramate-augmentation therapy in patients with schizophrenia receiving antipsychotic agents. Data published up to June 20, 2016 were obtained from the PubMed, PsycINFO, and Cochrane Library databases. Twelve randomized controlled trials comparing topiramate to placebo or antipsychotic only were included (n=676 patients). The primary outcome was change in overall symptoms. Relative risk (RR) and standardized mean difference (SMD), along with 95% confidence intervals, were calculated using random effects model for each outcome. Topiramate-augmentation therapy was superior to the control for decreasing overall symptoms (SMD −0.55, 95% confidence interval −0.86 to −0.24; P=0.001; I2=55%, eight comparisons, n=380), positive symptoms (SMD −0.4), negative symptoms (SMD −0.47), and Positive and Negative Syndrome Scale general subscale scores (SMD −0.67). Furthermore, topiramate-augmentation therapy decreased weight (SMD −0.69) and body mass index (SMD −0.95) compared with the control. Topiramate was similar to the control with respect to discontinuation due to all causes (RR 1.19), inefficacy (RR 1.71), and adverse events (RR 1.09). Topiramate was associated with higher incidence of paresthesia (RR 2.67) and attention difficulty (RR 8.97) compared with the control. Our results seemed to suggest that topiramate-augmentation therapy improves the psychopathology of schizophrenia with good tolerability and has the additional advantage of weight maintenance. However, because there were some limitations (numbers of studies and patients included in the meta-analysis were small, some studies used completer analysis, Chinese studies were included in the meta-analysis, and studies that had a risk of bias were included in the meta-analysis) in this study, we cannot apply the results of this study in daily clinical practice.

Lower Blood Pressure-Induced Renal Hypoperfusion Promotes Cisplatin-Induced Nephrotoxicity

Background and Aims: Cisplatin-induced nephrotoxicity primarily occurs in the proximal tubules, and tubular injuries reduce glomerular filtration rates. Lower blood pressure causes renal hypoperfusion, which promotes ischemic acute kidney injury (AKI). Our study examined the relationship between lower blood pressure-induced renal hypoperfusion and cisplatin-induced nephrotoxicity. Methods: The relationship between cisplatin use and hypoalbuminemia is not clear. This study consisted of Japanese patients who received cisplatin as the first-line chemotherapy at Fujita Health University Hospital from April 2006 to December 2012. Hypoalbuminemia was defined as serum albumin levels ≤3.5 mg/dl. Results: Patients who experienced lower blood pressure during chemotherapy were included in the lower blood pressure group (n = 229), and those who did not were included in the normal blood pressure group (n = 743). Total cisplatin dose in the normal blood pressure and lower blood pressure groups was 58.9 ± 23.8 and 55.0 ± 20.4 mg/m², respectively. The rate of severe nephrotoxicity was higher and overall survival was shorter in the lower blood pressure group than in the normal blood pressure group. In a multivariable analysis, lower blood pressure significantly correlated with hypoalbuminemia. Conclusions: To prevent ischemic AKI, nutrition and cachexia controlling are important parts of cancer treatment.

Single institution outcomes in the first 3 years of pancreas transplantation from brain dead donors.

A total of 26 pancreas transplants from brain dead donors, including 21 simultaneous pancreas and kidney (SPK) transplantation procedures, have been performed at Fujita Health University Hospital since the new pancreas transplant program was initiated in August 2012. The objective of this study is to investigate the outcomes of pancreatic transplantation in our facility in first 3 years of the program. The background characteristics of the donors and the outcomes of 26 pancreas transplant recipients were analyzed. The mean age of the recipients was 44.0 years, and all recipients had a long-term history of diabetes (mean: 30.2 years). In the SPK cases, the patients also had a long history of hemodialysis (mean: 6.3 years). Although the average donor age was 41.0 years and more than half of the donors were marginal donors (defined according to Kapur's criteria and Troppmann's criteria), the patient survival and pancreatic graft survival rates were 100% and 91.7%, respectively. Unfortunately, two recipients experienced graft failure due to graft thrombosis, which resulted in graft loss. The new pancreas transplant program at Fujita Health University has provided excellent outcomes for patients with type 1 diabetes.

Repeat pulmonary resection for recurrent lung metastases from colorectal cancer: an analysis of prognostic factors

The purpose of this study was to investigate the prognostic factors for repeat lung metastasectomy in patients with colorectal cancer, which may be clinically helpful in defining a subset of patients who are most likely to benefit from repeat lung metastasectomy. In total, 138 patients underwent complete lung resection for the first time due to metastases of colorectal cancer between January 2004 and December 2013 at Fujita Health University School of Medicine. Among them, 33 underwent repeat pulmonary metastasectomy for lung tumour recurrence. Kaplan-Meier survival curves and log-rank tests were used to analyse the survival rates. No patient died as a direct result of surgery, and all patients were discharged after the repeat pulmonary metastasectomy. The 5-year survival rate after the initial pulmonary resection of the 33 patients who underwent repeat lung resection was 64%, which was not significantly different from that of the 105 patients who did not undergo repeat lung resection (5-year survival rate, 61%; P = 0.779). Univariate analysis identified only one significant prognostic factor: preoperative serum carcinoembryonic antigen (CEA) level (P = 0.002). The 5-year survival rates of patients with high preoperative CEA levels and normal CEA levels after repeat metastasectomy were significantly different at 47 and 90%, respectively. Prethoracotomy serum CEA levels affect survival rates after repeat pulmonary resection. The preoperative assessment of serum CEA levels before repeat metastasectomy is important when considering repeat pulmonary resection, and prethoracotomy CEA levels should be taken into account when selecting patients for repeat lung resection.

Feasibility of a Simplified, Clinically Oriented, Three-dimensional Gait Analysis System for the Gait Evaluation of Stroke Patients.

Although previous studies have evidenced the value of three-dimensional gait analysis (3DGA) for evaluating gait disorder, the time-consuming measurement process and space requirement has hampered its use in the clinical setting. The aim of this study was to examine the feasibility of a simplified 3DGA system for stroke patients. Thirteen pairs of stroke patients and age- (± 1 year), gender-, and gait speed- (± 0.5 m/s) matched controls were drawn from the Fujita Health University gait analysis database. 3DGA was performed using the KinemaTracer® treadmill gait analysis system. Comparisons of the spatiotemporal and kinematic parameters were performed between stroke patients and matched controls. The correlations between items from the Wisconsin Gait Scale (WGS) and 3DGA data in stroke patients were also investigated. 3DGA measurements clearly showed reduced toe clearance, hip flexion, and knee flexion in stroke patients compared with the matched controls. In contrast, significant increases were observed in hip elevation, shoulder elevation, shoulder lateral shift, and step width in stroke patients. For the four items drawn from the WGS, a significant correlation with three 3DGA parameters was observed: stance time on the impaired side, stance width, and knee flexion from toe off to midswing. In this study, significant differences in gait parameters of stroke patients and age-, gender-, and speed-matched controls were found using a simplified 3DGA system. A significant correlation with WGS was also observed. These results support the validity of the clinical measurement of gait parameters using a simplified 3DGA system.

P3-6-4 - Efficacy and safety of etoposide in patients with platinum-pretreated metastatic or recurrent urothelial cancer

Backgroud: Platinum containing regimen is the standard first line chemotherapy in patients with metastatic or recurrent urothelial cancer (UC). Although paclitaxel is one of the second line treatment options, its efficacy is not sufficient.Methods: To evaluate etoposide in patients with UC pretreated with platinum agent, we reviewed the patient records in Japanese Nagoya Daiichi Red Cross hospital and Fujita Health University hospital. Etoposide is administrated as 100mg/m2 injection in day1 to 3 every 3 weeks until documented disease progression, unacceptable toxicities, or patient refusal.Results: From October 2010 to September 2014, 24 patients received etoposide therapy. Two patients were excluded from the analysis due to the histology without UC. The patient characteristics were as follows: median age, 72.5 years (range, 55 to 82); men/women, 12/10; performance status, 0/1/2, 9/12/1; primary site, bladder/ureter/pelvis, 13/7/2; primary site, unresected/resected, 9/13; estimated glomerular filtrating rate (calculated by Cockcroft-Gault formula), median 45.5ml/min (range, 25 to 83); metastatic site, lymph node/lung/liver/bone, 14/4/6/4; and number of previous chemotherapeutic regimen, 1/2 or more, 16/6. At a median follow-up time of 9.8 months (range 2.7 to 44.7 months), response rate, disease control rate, 6-months progression-free survival (PFS) rate, median PFS, and median overall survival were 11%, 50%, 34% [95% confidential interval(CI), 16 to 54 %], 4.3 months [95% CI, 2.3 to 12.3 months], and 9.4 months (95% CI, 6.4 to 22.2 months), respectively. The common grade 3/4 toxicities were neutropenia (68%), anemia (9%), febrile neutropenia (14%), appetite loss (5%), and arterial thrombosis (5%). Treatment related death was not observed.Conclusion: Etoposide was well tolerated for patients with platinum-pretreated UC. The efficacy was almost equal to previous reports of paclitaxel monotherapy. Future evaluation in prospective study is warranted. Backgroud: Platinum containing regimen is the standard first line chemotherapy in patients with metastatic or recurrent urothelial cancer (UC). Although paclitaxel is one of the second line treatment options, its efficacy is not sufficient. Methods: To evaluate etoposide in patients with UC pretreated with platinum agent, we reviewed the patient records in Japanese Nagoya Daiichi Red Cross hospital and Fujita Health University hospital. Etoposide is administrated as 100mg/m2 injection in day1 to 3 every 3 weeks until documented disease progression, unacceptable toxicities, or patient refusal. Results: From October 2010 to September 2014, 24 patients received etoposide therapy. Two patients were excluded from the analysis due to the histology without UC. The patient characteristics were as follows: median age, 72.5 years (range, 55 to 82); men/women, 12/10; performance status, 0/1/2, 9/12/1; primary site, bladder/ureter/pelvis, 13/7/2; primary site, unresected/resected, 9/13; estimated glomerular filtrating rate (calculated by Cockcroft-Gault formula), median 45.5ml/min (range, 25 to 83); metastatic site, lymph node/lung/liver/bone, 14/4/6/4; and number of previous chemotherapeutic regimen, 1/2 or more, 16/6. At a median follow-up time of 9.8 months (range 2.7 to 44.7 months), response rate, disease control rate, 6-months progression-free survival (PFS) rate, median PFS, and median overall survival were 11%, 50%, 34% [95% confidential interval(CI), 16 to 54 %], 4.3 months [95% CI, 2.3 to 12.3 months], and 9.4 months (95% CI, 6.4 to 22.2 months), respectively. The common grade 3/4 toxicities were neutropenia (68%), anemia (9%), febrile neutropenia (14%), appetite loss (5%), and arterial thrombosis (5%). Treatment related death was not observed. Conclusion: Etoposide was well tolerated for patients with platinum-pretreated UC. The efficacy was almost equal to previous reports of paclitaxel monotherapy. Future evaluation in prospective study is warranted.

Role of HHV-6B Infection in Mesial Temporal Lobe Epilepsy.

Investigators from Fujita Health University, Toyoake, and National Epilepsy Center, Shizuoka, Japan, studied the pathogenic role of HHV-6B in patients with mesial temporal lobe epilepsy (MTLE).

PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients.

AimTo investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients.MethodsTwo hundred and thirty-one patients with CHC were examined for PNPLA3 genotypes, liver stiffness measurements (LSM), and hepatocellular carcinoma (HCC) from May 2010 to October 2012 at Fujita Health University Hospital. The rs738409 single nucleotide polymorphism (SNP) encoding for a functional PNPLA3 I148M protein variant was genotyped using a TaqMan predesigned SNP genotyping assay. LSM was determined as the velocity of a shear wave (Vs) with an acoustic radiation force impulse. Vs cut-off values for cirrhosis were set at 1.55 m/s. We excluded CHC patients with a sustained virological response or relapse after interferon treatment.ResultsPNPLA3 genotypes were CC, CG, and GG for 118, 72, and 41 patients, respectively. Multivariable logistic regression analysis selected older age (OR = 1.06; 95% CI: 1.03–1.09; p < 0.0001), higher body mass index (BMI) (OR= 1.12; 95% CI: 1.03–1.22; p = 0.0082), and PNPLA3 genotype GG (OR = 2.07; 95% CI: 0.97–4.42; p = 0.0599) as the factors independently associated with cirrhosis. When 137 patients without past history of interferon treatment were separately assessed, multivariable logistic regression analysis selected older age (OR = 1.05; 95% CI: 1.02–1.09; p = 0.0034), and PNPLA3 genotype GG (OR = 3.35; 95% CI: 1.13–9.91; p = 0.0291) as the factors independently associated with cirrhosis. Multivariable logistic regression analysis selected older age (OR = 1.12; 95% CI: 1.07–1.17; p < 0.0001), PNPLA3 genotype GG (OR = 2.62; 95% CI: 1.15–5.96; p = 0.0218), and male gender (OR = 1.83; 95% CI: 0.90–3.71); p = 0.0936) as the factors independently associated with HCC.ConclusionPNPLA3 genotype I148M is one of risk factors for developing HCC in Japanese CHC patients, and is one of risk factors for progress to cirrhosis in the patients without past history of interferon treatment.

Twenty years of trans-disciplinary approach development for dysphagia rehabilitation in Japan.

To the Editor, We are pleased to report on the development and progress of the trans-disciplinary field of Deglutology in Japan as the Japanese Society of Dysphagia Rehabilitation (JSDR) commemorates its 20th year of establishment. The JSDR includes a broad range of disciplines in order to integrate diverse knowledge and expertise and pave the way for the emerging field of Deglutition. The percentage of individuals aged over 65 years reached 25.0 % of the Japanese population in 2013 [1]. With this rapid increase in the elderly, a substantially greater demand for dysphagia rehabilitation comes up. As the progression of dysphagia diminishes both the function of swallowing and the enjoyment of eating, the objective of dysphagia rehabilitation should therefore address both the recovery of swallowing function and the restoration of pleasure while eating. Dysphagia rehabilitation is performed for a wide range of disease stages, from acute medical care to terminal support. Although a team approach is essential for effective rehabilitation, treatment can be challenging because support strategies vary considerably over time and require numerous approaches and caregivers. We normally divide the team approach in dysphagia rehabilitation into three categories according to the relationships among participating disciplines as follows: (1) the multi-disciplinary approach, where disciplines treat patients independently and have little communication with each other, (2) the inter-disciplinary approach, where related disciplines exchange information at team conferences to reach a consensus on treatment, thus promoting inter-disciplinary cooperation, and (3) the trans-disciplinary approach, where participating disciplines complement the scope of others to more efficiently integrate a team approach. The trans-disciplinary approach is particularly suitable for dysphagia rehabilitation because the size and composition of a support team may change significantly over time; complementing the scopes of associated disciplines without establishing a rigid inter-disciplinary border enables seamless care over a wider range of individuals, symptom stages, and circumstances. The JSDR was founded in 1995 under the concept of a trans-disciplinary approach for dysphagia rehabilitation. As the society now celebrates 20 years of progress and innovation, its membership has grown to more than 11,000 medical professionals (11,653 as of August 30, 2014) and involves numerous disciplines (Fig. 1) in line with the original JSDR trans-disciplinary tenets. Recently, the 20th annual conference of the JSDR held in Tokyo in September 2014 featured an international symposium that included 12 E. Saitoh Department of Rehabilitation Medicine I, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan e-mail: esaitoh@fujita-hu.ac.jp

当院における有棘細胞癌に対するSentinel Node Biopsyの検討

当院における有棘細胞癌に対するSentinel Node Biopsyの検討

Iminodibenzyl class antipsychotics for schizophrenia: a systematic review and meta-analysis of carpipramine, clocapramine, and mosapramine.

BackgroundWe conducted a meta-analysis of the iminodibenzyl antipsychotics carpipramine, clocapramine, and mosapramine, which are classified as second-generation antipsychotics (SGAs) for schizophrenia treatment.MethodsWe searched data that had been published in PubMed, the Cochrane Library databases, PsycINFO, CiNii, and the Japan Medical s Society up to August 29, 2014. Randomized controlled trials that compared iminodibenzyl antipsychotics with other antipsychotics in patients with schizophrenia were included. Odds ratios and standardized mean differences were evaluated.ResultsWe included four randomized controlled trials on carpipramine (number of patients [n]=290), six on clocapramine (n=1,048), and five on mosapramine (n=986) in the meta-analysis. There were no significant differences in the response rates or in the discontinuation rates either between carpipramine and the other pooled antipsychotics or between clocapramine and the other pooled antipsychotics. On the Positive and Negative Syndrome Scale, mosapramine’s positive subscale scores were superior to those of the other pooled antipsychotics (standard mean of difference =−0.22); however, on that same scale, there were no significant differences in total scores, negative scores, general subscale scores, response rates, or the discontinuation rates between mosapramine and the other pooled antipsychotics. Furthermore, the incidences of extrapyramidal symptoms and of hyperprolactinemia were significantly greater with mosapramine than with the other pooled antipsychotics.ConclusionThe pharmacological profiles of carpipramine and clocapramine, which are classified as SGAs, were similar to those of first-generation antipsychotics because there were no significant differences in efficacy and safety outcomes. However, mosapramine was associated with a greater risk of extrapyramidal symptoms and hyperprolactinemia than the other SGAs were, although it may be beneficial for the improvement of positive symptoms.