論文 - 佐藤　泰憲

Pregnancy and neonatal outcomes of small follicle–derived blastocyst transfer in modified natural cycle in vitro fertilization

Teramoto S., Osada H., Sato Y., Shozu M.

Fertility and Sterility （Fertility and Sterility）  111 （ 4 ） 747 - 752 2019年04月

ISSN  00150282

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© 2018 The Authors Objective: To compare the efficacy and safety of blastocyst transfer derived from small follicles (SF; ≤10 mm) and large follicles (LF; ≥11 mm). Design: Retrospective cohort study. Setting: Private clinic. Patient(s): Patients (n = 1,072) 30–40 years old who underwent blastocyst transfer (BT; n = 1,247) between January 2012 and December 2014. Intervention(s): Oocytes retrieved during a modified natural cycle from both LF and SF were fertilized by a conventional method or intracytoplasmic sperm injection. The blastocysts were frozen, thawed, and transferred one by one in the following spontaneous ovulatory cycles or hormone replacement cycles. Main Outcome Measure(s): BT resulted in live births and major congenital anomalies. Result(s): SF-derived BTs (n = 597) yielded 55 chemical abortions (9.2%), 73 clinical abortions (12.2%), and 261 live births (43.8%), whereas LF-derived BTs (n = 650) yielded 71 chemical abortions (10.9%), 73 clinical abortions (11.2%), and 311 live births (47.9%). These incidences were not statistically different between SF- and LF-derived BTs. The incidence of abnormal karyotypes was also not statistically different between SF- and LF-derived spontaneous abortions (71% [39/55] vs. 72% [40/55], respectively). The incidence of major congenital anomalies in neonates did not differ between SF- and LF-derived pregnancies (1.5% and 1.3%, respectively; relative risk = 1.10, 95% confidence interval [0.55–3.21]). Conclusion(s): SF-derived BT is as efficacious and safe as LF-derived BT.

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Validity of a Recently-Proposed Prognostic Grading Index, Brain Metastasis Velocity, for Brain Metastasis Patients Undergoing Multiple Radiosurgical Procedures

Yamamoto M, Aiyama H, Koiso T, Watanabe S, Kawabe T, Sato Y, Higuchi Y, Kasuya H, Barfod BE

Int J Radiat Oncol Biol Phys 103 （ 3 ） 631 - 637 2019年03月

研究論文（学術雑誌）, 共著, 査読有り

Postsurgical Salvage Radiosurgery for Nonfunctioning Pituitary Adenomas Touching/Compressing the Optic Chiasm: Median 13-Year Postirradiation Imaging Follow-up Results

Yamamoto M, Aiyama H, Koiso T, Watanabe S, Kawabe T, Sato Y, Higuchi Y, Barfod BE, Kasuya H

Neurosurgery 49 （ 2 ） 80 - 86 2019年02月

研究論文（学術雑誌）, 共著, 査読有り

Proposal of new clinical diagnostic criteria for POEMS syndrome

Suichi T., Misawa S., Sato Y., Beppu M., Sakaida E., Sekiguchi Y., Shibuya K., Watanabe K., Amino H., Kuwabara S.

Journal of Neurology, Neurosurgery and Psychiatry （Journal of Neurology, Neurosurgery and Psychiatry）  90 （ 2 ） 133 - 137 2019年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00223050

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© Author(s) (or their employer(s)) 2019. Objective To propose the optimal diagnostic criteria for polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome using appropriate statistical methods and disease controls. Methods This retrospective cohort study included 104 consecutive patients with suspected POEMS syndrome, among whom a gold standard group of 60 patients with definitive POEMS syndrome diagnosis were followed for at least 12 months to strictly exclude other disorders mimicking POEMS syndrome and to confirm response to POEMS syndrome-specific treatment. Thirty patients with chronic inflammatory demyelinating polyradiculoneuropathy (demyelinating polyradiculoneuropathy controls) and 30 with multiple myeloma or immunoglobulin light chain amyloidosis (monoclonal plasma cell proliferation controls) were also included. Logistic regression analyses were performed to determine optimal combination of clinical and laboratory abnormalities, characteristic of POEMS syndrome. Results The diagnostic criteria were statistically defined as the presence of the three major criteria (polyneuropathy (typically demyelinating), monoclonal plasma cell proliferative disorder and elevated vascular endothelial growth factor) and at least two of the four minor criteria (oedema/effusion, skin changes, organomegaly and sclerotic bone lesions), based on best performance by area under the receiver operating characteristic curve analyses. The sensitivity and specificity were 100% and 100%, respectively; the diagnostic accuracy of the proposed criteria was equivalent to somewhat complicated previous criteria. Conclusions The statistically defined, simple diagnostic criteria for POEMS syndrome could accelerate early diagnosis and treatment, thereby contribute to better outcome in patients with this serious disease. Prospective larger studies are required to confirm the validity.

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Displacement of the hyoid bone by muscle paralysis and lung volume increase: effects of obesity and obstructive sleep apnea

Kohno A, Kitamura Y, Kato S, Imai H, Masuda Y, Sato Y, Isono S

Sleep 42 （ 1 ）  2019年01月

研究論文（学術雑誌）, 共著, 査読有り

大きな脳転移に対するガンマナイフによる三期的および二期的照射の治療成績の比較　後ろ向き多施設共同研究(JLGK1601)最終報告

芹澤 徹, 樋口 佳則, 山本 昌昭, 松永 成生, 永野 修, 佐藤 泰憲, 青柳 京子, 四方 聖二, 小磯 隆雄, 長谷川 俊典, 中崎 清之, 森木 章人, 近藤 威, 長友 康, 岡本 久代, 光田 幸彦, 河合 秀哉, 志藤 里香, 柴崎 徹, 尾上 信二, 祁内 博行, 井上 明, 森 久恵

定位的放射線治療 （日本定位放射線治療学会）  23   25 - 35 2019年01月

ISSN  1342-9930

　概要を見る

腫瘍体積が10ml以上の大きな脳転移に対するガンマナイフによる三期的および二期的照射の治療成績を比較検討した。本試験参加19施設において総計1441例のガンマナイフによる段階的照射が施行され、このうち335例(三期114例、二期的照射221例)が登録された。生存期間中央値は三期群15.1ヵ月、二期群12.0ヵ月と三期群の方が長い傾向にあったが有意差を認めなかった。その他のすべての副次評価項目において両群間に有意差を認めなかった。Propensity score matchを用いて最終的に212例(両群106例)を選択し評価したところ、生存期間中央値は三期群15.9ヵ月、二期群11.7ヵ月と三期群の方が長い傾向にあったが有意差を認めなかった。1年における累積腫瘍増大発生頻度は三期群21.6%、二期群16.7%で有意差を認めなかった。その他、腫瘍再発、放射線壊死、神経死、有害事象においても両群間に有意差を認めなかった。

Addition of canagliflozin to insulin improves glycaemic control and reduces insulin dose in patients with type 2 diabetes mellitus: A randomized controlled trial

Torimoto K., Okada Y., Goshima Y., Tokutsu A., Sato Y., Tanaka Y.

Diabetes, Obesity and Metabolism （Diabetes, Obesity and Metabolism）  21 （ 9 ） 2174 - 2179 2019年

ISSN  14628902

　概要を見る

© 2019 John Wiley & Sons Ltd The aim of this study was to evaluate the efficacy of canagliflozin in reducing the required insulin dose and the risk of hypoglycaemia in type 2 diabetes (T2D). This study was conducted in patients with T2D treated with insulin. They were randomly assigned to the control (n = 17) and canagliflozin (n = 17, plus 100 mg/day canagliflozin) groups. In both groups, a defined insulin dose adjustment protocol was applied to achieve the same level of glycaemic control. The change from baseline in daily insulin dose was significantly smaller in the canagliflozin group (3.9 units/day) than in the control group (13.4 units/day; P = 0.040). Low blood glucose index and predicted % of blood glucose (BG) <70 mg/dL, which are hypoglycaemia-related variables, worsened significantly in the control group but both remained unchanged in the canagliflozin group. The standard deviation for night-time BG levels improved significantly only in the canagliflozin group. Supplementation of insulin therapy with 100 mg canagliflozin in patients with T2D reduced the required insulin dose and hypoglycaemic risk and flattened night-time glycaemic fluctuations while maintaining the same level of glycaemic control.

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Risk score system for late aortic events in patients with uncomplicated type B aortic dissection

Matsushita A., Tabata M., Mihara W., Shimamoto T., Komiya T., Takanashi S., Tobaru T., Nakao T., Nakamura S., Sato Y.

Journal of Thoracic and Cardiovascular Surgery （Journal of Thoracic and Cardiovascular Surgery）  2019年

ISSN  00225223

　概要を見る

© 2019 The American Association for Thoracic Surgery Objective: Several risk factors for late aortic events in patients with uncomplicated type B aortic dissection (UTBAD) have been reported; however, they remain controversial. We developed and validated a new risk prediction score system for late aortic events in patients with UTBAD. Methods: We reviewed 187 consecutive patients diagnosed with UTBAD from 2004 to 2017 at 2 centers (derivation cohort) and 219 consecutive patients diagnosed with UTBAD from 2012 to 2016 in 4 other centers (validation cohort). We explored predictors of late aortic events using Fine-Gray generalization of the proportional hazards model, then developed a risk prediction score model and determined the test reliability using time-dependent receiver operating characteristic analyses. Finally, we validated the model using external multicenter data. Results: The risk prediction score system was developed using the following independent predictors: initial aortic diameter of ≥40 mm (2 points), false lumen diameter larger than true lumen diameter (2 points), ulcer-like projection (1 point), and age ≥70 years (1 point). Receiver operating characteristic analysis showed that a cut-off total additive score of 2 points. In the validation cohort, the low-risk group (score, 0-1 point) demonstrated lower 1- and 3-year incidence rates of late aortic events than the high-risk group (score, 2-6 points) (0.9% vs 32.5% and 0.9% vs 47.1%, respectively; P < .0001). Conclusions: We developed a simple risk prediction score system for late aortic events in patients with UTBAD. High-risk patients can be identified using our model, and they should be closely monitored and considered for interventions at the appropriate timing.

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Stereotactic radiosurgery for patients with 10 or more brain metastases

Yamamoto M., Higuchi Y., Sato Y., Aiyama H., Kasuya H., Barfod B.

Progress in Neurological Surgery （Progress in Neurological Surgery）  34   110 - 124 2019年

ISSN  00796492

　概要を見る

© 2019 S. Karger AG, Basel The JLGK0901 study showed the non-inferiority of stereotactic radiosurgery (SRS) alone as the initial treatment for 5-10 as compared to 2-4 brain metastases (BM) in terms of overall survival and most secondary endpoints [Lancet Oncol 2014;15:387-395]. A trend for patients with 5-10 tumors to undergo SRS alone has since become apparent. The next step is to reappraise whether results of SRS treatment alone for tumor numbers ≥10 differ from those for 2-9 tumors. During the past 2 decades, several retrospective studies have demonstrated the SRS alone treatment strategy to have certain benefits for carefully selected patients with ≥10 BM, i.e., a sufficiently long survival period with lower incidences of neurological death, neurological deterioration, local recurrence, and SRS-related complications. Herein, we introduce our Mito experiences with SRS for ≥10 BM, employing a case-matched study on 934 patients, 467 each in groups with 2-9 BM and ≥10 BM. Post-SRS treatment results, i.e., median survival time, neurological death-free survival time and cumulative incidences of local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-related complications, were not inferior for patients with ≥10 BM as compared to those with 2-9 BM. We conclude that patients with ≥10 tumors are not unfavorable candidates for SRS alone.

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Validation of the accuracy of self-reported abo blood types in the Japan nurses' health study

Alkebsi L., Ohnishi H., Nakajima-Shimada J., Onizuka Y., Ideno Y., Sato Y., Hayashi K.

Asian Pacific Journal of Cancer Prevention （Asian Pacific Journal of Cancer Prevention）  20 （ 3 ） 789 - 793 2019年

ISSN  15137368

　概要を見る

© 2019 Asian Pacific Journal of Cancer Prevention. Background: The associations between ABO blood type and risk of diseases including cancer have been reported from epidemiological studies. Self-reporting is one of the most widely used methods of collecting the ABO blood type information. Verifying the accuracy of self-reporting is important to consider measurement errors. We aimed to conduct validation of self-reported ABO blood types in the Japan Nurses' Health Study (JNHS), which is a large prospective cohort study. Methods: The concordance rate between self-reported and serologically or genetically inferred ABO blood groups was investigated for a subsample of 41 subjects from the Gunma Nurses' Health Study, which was a pilot cohort study that preceded the JNHS. The presence of antibodies to A or B antigens in serum (serological test) and allele types of the ABO gene (genotyping test) were determined by using frozen blood samples that were preserved for approximately 7 years. ABO blood types were determined from these tests and compared with self-reported data. Results: All of the nurses reported that their ABO blood groups were concordant with those determined by a serological and/or genotyping test. Self-reported ABO blood types of 35 of 38 (92.1%) participants were consistent with the results from serological typing, while the answers of three participants were not. In these three participants, ABO genotypes that were inferred from genotyping of three single nucleotide polymorphisms in ABO loci perfectly matched with their self-reported ABO types, and all of these were O-type. Conclusions: Japanese health professionals report their blood type with a high degree of accuracy. Special attention should be paid to the O-type group in serological analysis of blood samples that have been preserved for several years in longitudinal studies.

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The Effect of Grandmothers' Presence on the Provision of Multidisciplinary Perinatal Support for Pregnant and Postpartum Women with Psychosocial Problems.

Ogawa M, Hashimoto T, Tanaka M, Tachibana M, Seki R, Sato A, Okayama J, Endo M, Saito N, Sato Y, Watanabe H, Nakazato M, Mori E, Shozu M, Iyo M

Journal of multidisciplinary healthcare 12   1033 - 1041 2019年

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A pilot and feasibility study of a cognitive behavioural therapy-based anxiety prevention programme for junior high school students in Japan: a quasi-experimental study.

Ohira I, Urao Y, Sato Y, Ohtani T, Shimizu E

Child and adolescent psychiatry and mental health 13 （ 1 ） 40 2019年

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Prognostic grading system specifically for elderly patients with brain metastases after stereotactic radiosurgery: A 2-institution study

Yamamoto M., Serizawa T., Higuchi Y., Nagano O., Aiyama H., Koiso T., Watanabe S., Kawabe T., Sato Y., Kasuya H.

Journal of Neurosurgery （Journal of Neurosurgery）  129   95 - 102 2018年12月

ISSN  00223085

　概要を見る

©AANS 2018. OBJECTIVE With the aging of the population, increasing numbers of elderly patients with brain metastasis (BM) are undergoing stereotactic radiosurgery (SRS). Among recently reported prognostic grading indexes, only the basic score for brain metastases (BSBM) is applicable to patients 65 years or older. However, the major weakness of this system is that no BM-related factors are graded. This prompted the authors to develop a new grading system, the elderly-specific (ES)–BSBM. METHODS For this IRB-approved, retrospective cohort study, the authors used their prospectively accumulated database comprising 3267 consecutive patients undergoing Gamma Knife SRS for BMs during the 1998–2016 period at the Mito GammaHouse. Among these 3267 patients, 1789 patients ≥ 65 years of age were studied (Yamamoto series [Y-series]). Another series of 1785 patients ≥ 65 years of age in whom Serizawa and colleagues performed Gamma Knife SRS during the same period (Serizawa series [S-series]) was used for validity testing of the ES-BSBM. RESULTS Two factors were identified as strongly impacting longer survival after SRS by means of multivariable analysis using the Cox proportional hazard model with a stepwise selection procedure. These factors are the number of tumors (solitary vs multiple: HR 1.450, 95% CI 1.299–1.621; p < 0.0001) and cumulative tumor volume (≤ 15 cm3 vs > 15 cm3: HR 1.311, 95% CI 1.078–1.593; p = 0.0067). The new index is the addition of scores 0 and 1 for these 2 factors to the BSBM. The ES-BSBM system is based on categorization into 3 classes by adding these 2 scores to those of the original BSBM. Each ES-BSBM category has 2 possible scores. For the category ES-BSBM 4–5, the score is either 4 or 5; for ES-BSBM 2–3, the score is either 2 or 3; and for ES-BSBM 0–1, the score is either 0 or 1. In the Y-series, the median survival times (MSTs, months) after SRS were 17.5 (95% CI 15.4–19.3) in ES-BSBM 4–5, 6.9 (95% CI 6.4–7.4) in ES-BSBM 2–3, and 2.8 (95% CI 2.5–3.6) in ES-BSBM 0–1 (p < 0.0001). Also, in the S-series, MSTs were, respectively, 20.4 (95% CI 17.2–23.4), 7.9 (95% CI 7.4–8.5), and 3.2 (95% CI 2.8–3.6) (p < 0.0001). The ES-BSBM system was shown to be applicable to patients with all primary tumor types as well as to those 80 years or older. CONCLUSIONS The authors found that the addition of the number of tumors and cumulative tumor volume as scoring factors to the BSBM system significantly improved the prognostic value of this index. The present study is strengthened by testing the ES-BSBM in a different patient group.

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Three-stage Gamma Knife treatment for metastatic brain tumors larger than 10 cm³: A 2-institute study including re-analyses of earlier results using competing risk analysis

Yamamoto M., Higuchi Y., Serizawa T., Kawabe T., Nagano O., Sato Y., Koiso T., Watanabe S., Aiyama H., Kasuya H.

Journal of Neurosurgery （Journal of Neurosurgery）  129   77 - 85 2018年12月

ISSN  00223085

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©AANS 2018. OBJECTIVE The results of 3-stage Gamma Knife treatment (3-st-GK-Tx) for relatively large brain metastases have previously been reported for a series of patients in Chiba, Japan (referred to in this study as the C-series). In the current study, the authors reappraised, using a competing risk analysis, the efficacy and safety of 3-st-GK-Tx by comparing their experience with that of the C-series. METHODS This was a retrospective cohort study. Among 1767 patients undergoing GK radiosurgery for brain metastases at Mito Gamma House during the 2005–2015 period, 78 (34 female, 44 male; mean age 65 years, range 35–86 years) whose largest tumor was > 10 cm3, treated with 3-st-GK-Tx, were studied (referred to in this study as the M-series). The target volumes were covered with a 50% isodose gradient and irradiated with a peripheral dose of 10 Gy at each procedure. The interval between procedures was 2 weeks. Because competing risk analysis had not been employed in the published C-series, the authors reanalyzed the previously published data using this method. RESULTS The overall median survival time after 3-st-GK-Tx was 8.3 months (95% CI 5.6–12.0 months) in the M-series and 8.6 months (95% CI 5.5–10.6 months) in the C-series (p = 0.41). Actuarial survival rates at the 6th and 12th post–3-st-GK-Tx months were, respectively, 55.1% and 35.2% in the M-series and 62.5% and 26.4% in the C-series (HR 1.175, 95% CI 0.790–1.728, p = 0.42). Cumulative incidences at the 12th post–3-st-GK-Tx, determined by competing risk analyses, of neurological deterioration (14.2% in C-series vs 12.8% in M-series), neurological death (7.2% vs 7.7%), local recurrence (4.8% vs 6.2%), repeat SRS (25.9% vs 18.0%), and SRS-related complications (2.3% vs 5.1%) did not differ significantly between the 2 series. CONCLUSIONS There were no significant differences in post–3-st-GK-Tx results between the 2 series in terms of overall survival times, neurological death, maintained neurological status, local control, repeat SRS, and SRS-related complications. The previously published results (C-series) are considered to be validated by the M-series results.

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Clinical significance of conformity index and gradient index in patients undergoing stereotactic radiosurgery for a single metastatic tumor

Aiyama H., Yamamoto M., Kawabe T., Watanabe S., Koiso T., Sato Y., Higuchi Y., Ishikawa E., Yamamoto T., Matsumura A., Kasuya H.

Journal of Neurosurgery （Journal of Neurosurgery）  129   103 - 110 2018年12月

ISSN  00223085

　概要を見る

©AANS 2018. OBJECTIVE Although the conformity index (CI) and the gradient index (GI), which were proposed by Paddick and colleagues, are both logically considered to correlate with good posttreatment results after stereotactic radiosurgery (SRS), this hypothesis has not been confirmed clinically. The authors’ aim was to reappraise whether high CI values correlate with reduced tumor progression rates, and whether low GI values correlate with reduced complication incidences. METHODS This was an institutional review board–approved, retrospective cohort study conducted using a prospectively accumulated database including 3271 patients who underwent Gamma Knife SRS for brain metastases (BMs) during the 1998–2016 period. Among the 3271 patients, 925 with a single BM at the time of SRS (335 women and 590 men, mean age 66 [range 24–93] years) were studied. The mean/median CIs were 0.62/0.66 (interquartile range [IQR] 0.53–0.74, range 0.08–0.88) and the mean/median GIs were 3.20/3.09 (IQR 2.83–3.39, range 2.27–11.4). RESULTS SRS-related complications occurred in 38 patients (4.1%), with a median post-SRS interval of 11.5 (IQR 6.0–25.8, maximum 118.0) months. Cumulative incidences of post-SRS complications determined by a competing risk analysis were 2.2%, 3.2%, 3.6%, 3.8%, and 3.9% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed that only two clinical factors (i.e., peripheral doses and brain volume receiving ≥ 12 Gy) correlated with complication rates. However, neither CIs nor GIs impacted the incidences of complications. Among the 925 patients, post-SRS MRI was performed at least once in 716 of them, who were thus eligible for local progression evaluation. Among these 716 patients, local progression was confirmed in 96 (13.4%), with a median post-SRS interval of 10.8 (IQR 6.7–19.5, maximum 59.8) months. Cumulative incidences of local progression determined by a competing risk analysis were 7.7%, 12.6%, 14.2%, 14.8%, and 15.3% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed neurological symptoms, extracerebral metastases, repeat SRS, and CIs to correlate with incidences of local progression, whereas GIs had no impact on local tumor progression. Particularly, cumulative incidences of local progression were significantly lower in patients with CIs < 0.65 than in those with CIs ≥ 0.65 (adjusted hazard ratio 1.870, 95% confidence interval 1.299–2.843; p = 0.0034). CONCLUSIONS To the authors’ knowledge, this is the first analysis to focus on the clinical significance of CI and GI based on a large series of patients with BM. Contrary to the majority opinion that dose planning with higher CI and lower GI results in good post-SRS outcomes (i.e., low local progression rates and minimal complications), this study clearly showed that the lower the CIs were, the lower the local progression rates were, and that the GI did not impact complication rates.

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Multiinstitutional prospective observational study of stereotactic radiosurgery for patients with multiple brain metastases from non–small cell lung cancer (JLGK0901 study–NSCLC)

Shuto T., Akabane A., Yamamoto M., Serizawa T., Higuchi Y., Sato Y., Kawagishi J., Yamanaka K., Jokura H., Yomo S., Nagano O., Aoyama H.

Journal of Neurosurgery （Journal of Neurosurgery）  129   86 - 94 2018年12月

ISSN  00223085

　概要を見る

©AANS 2018. OBJECTIVE Previous Japanese Leksell Gamma Knife Society studies (JLGK0901) demonstrated the noninferiority of stereotactic radiosurgery (SRS) alone as the initial treatment for patients with 5–10 brain metastases (BMs) compared with those with 2–4 BMs in terms of overall survival and most secondary endpoints. The authors studied the aforementioned treatment outcomes in a subset of patients with BMs from non–small cell lung cancer (NSCLC). METHODS Patients with initially diagnosed BMs treated with SRS alone were enrolled in this prospective observational study. Major inclusion criteria were the existence of up to 10 tumors with a maximum diameter of less than 3 cm each, a cumulative tumor volume of less than 15 cm3, and no leptomeningeal dissemination in patients with a Karnofsky Performance Scale score of 70% or better. RESULTS Among 1194 eligible patients, 784 with NSCLC were categorized into 3 groups: group A (1 tumor, n = 299), group B (2–4 tumors, n = 342), and group C (5–10 tumors, n = 143). The median survival times were 13.9 months in group A, 12.3 months in group B, and 12.8 months in group C. The survival curves of groups B and C were very similar (hazard ratio [HR] 1.037; 95% CI 0.842–1.277; p < 0.0001, noninferiority test). The crude and cumulative incidence rates of neurological death, deterioration of neurological function, newly appearing lesions, and leptomeningeal dissemination did not differ significantly between groups B and C. SRS-induced complications occurred in 145 (12.1%) patients during the median post-SRS period of 9.3 months (IQR 4.1–17.4 months), including 46, 54, 29, 11, and 5 patients with a Common Terminology Criteria for Adverse Events v3.0 grade 1, 2, 3, 4, or 5 complication, respectively. The cumulative incidence rates of adverse effects in groups A, B, and C 60 months after SRS were 13.5%, 10.0%, and 12.6%, respectively (group B vs C: HR 1.344; 95% CI 0.768–2.352; p = 0.299). The 60-month post-SRS rates of neurocognitive function preservation were 85.7% or higher, and no significant differences among the 3 groups were found. CONCLUSIONS In this subset analysis of patients with NSCLC, the noninferiority of SRS alone for the treatment of 5–10 versus 2–4 BMs was confirmed again in terms of overall survival and secondary endpoints. In particular, the incidence of neither post-SRS complications nor neurocognitive function preservation differed significantly between groups B and C. These findings further strengthen the already-reported noninferiority hypothesis of SRS alone for the treatment of patients with 5–10 BMs.

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Vulnerable combinations of functional polymorphisms to the late-onset treatment resistant schizophrenia

Oishi K, Kanahara N, Takase M, Oda Y, Nakata Y, Niitsu T, Ishikawa M, Sato Y and Iyo M

PLOS ONE 13 （ 11 ） e0207133 2018年11月

研究論文（学術雑誌）, 共著, 査読有り

Differences of recovery from rocuronium-induced deep paralysis in response to small doses of sugammadex between elderly and nonelderly patients

Muramatsu T., Isono S., Ishikawa T., Nozaki-Taguchi N., Okazaki J., Kitamura Y., Murakami N., Sato Y.

Anesthesiology （Anesthesiology）  129 （ 5 ） 901 - 911 2018年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00033022

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© 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved. Anesthesiology 2018; 129:901-11 Background: Complete recovery from rocuronium-induced muscle paralysis with sugammadex is reported to be delayed in elderly patients. The authors tested a hypothesis that recovery from deep neuromuscular block with low-dose sugammadex is slower (primary hypothesis) and incidence of recurarization is higher (secondary hypothesis) in elderly patients than in nonelderly patients. Methods: In anesthetized elderly (n = 20; 76.9 ± 5.0 yr of age) and nonelderly patients (n = 20; 53.7 ± 12.8 yr of age) under deep paralysis with rocuronium, change of train-of-four ratio per minute (primary outcome variable) was measured with an accelero-myograph neuromuscular monitor during spontaneous recovery from rocuronium-induced muscle paralysis (0.6 mg/kg) and after infusion of low-dose sugammadex (50 µg · kg-1 · min-1). Recurarization was defined as the negative change of train-of-four ratio. Results: Spontaneous train-of-four ratio recovery rate was significantly slower in the elderly group (median [25th percentile, 75th percentile]: 1.89 [1.22, 2.90] %/min) than in the nonelderly group (3.45 [1.96, 4.25] %/min, P = 0.024). Train-of-four ratio change rate in response to low-dose sugammadex was significantly slower in elderly (0.55 [-0.29, 1.54] %/min) than in the nonelderly group (1.68 [0.73, 3.13] %/min, P = 0.024). Incidence of recurarization was significantly higher in the elderly group than in the nonelderly group (35% vs. 5%, P = 0.044). Multiple linear regression analyses indicate that slower spontaneous train-of-four ratio recovery rate and impaired renal function are two major contributing factors that decrease train-of-four ratio change rate in response to low-dose sugammadex. Conclusions: Elderly patients are at greater risk for recurarization and residual muscle paralysis when low-dose sugammadex is administered.

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Vulnerable combinations of functional dopaminergic polymorphisms to late-onset treatment resistant schizophrenia

Oishi K., Kanahara N., Takase M., Oda Y., Nakata Y., Niitsu T., Ishikawa M., Sato Y., Iyo M.

PLoS ONE （PLoS ONE）  13 （ 11 ）  2018年11月

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© 2018 Oishi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background A significant portion of patients with schizophrenia who respond to initial antipsychotic treatment acquire treatment resistance. One of the possible pathogeneses of treatment-resistant schizophrenia (TRS) is antipsychotic-induced dopamine supersensitivity psychosis (Ai-DSP). Patients with this disease progression might share some genetic vulnerabilities, and thus determining individuals with higher risks of developing Ai-DSP could contribute to preventing iatrogenic development of TRS. Therefore, we decided to examine whether combinations of functional single nucleotide polymorphisms (SNPs) known to affect dopaminergic functions are related to Ai-DSP development. Methods In this case-control study, 357 Japanese participants diagnosed with schizophrenia or schizoaffective disorder were recruited and divided into two groups, those with and without Ai-DSP. As functional SNPs, we examined rs10770141 of the tyrosine hydroxylase gene, rs4680 of the catechol-O-methyltransferase gene, and rs1799732 and rs1800497 of the DRD2 genes, which are known to possess strong directional ties to dopamine synthesis, dopamine degradation and post-synaptic DRD2 prevalence, respectively. Results Among the 357 Japanese patients with schizophrenia or schizoaffective disorder, 130 were classified as Ai-DSP(+) and the other 227 as Ai-DSP(-). Significantly higher proportions of Ai-DSP(+) patients were found to have the SNP combinations of rs10770141/rs4680 (57.9%, OR2.654, 95%CI1.036–6.787, P = 0.048) and rs10770141/rs4680/rs1800497 (64.3%, OR4.230, 95%CI1.306–13.619, P = 0.029). However, no single SNP was associated with Ai-DSP. Conclusions We preliminarily found that carrying particular combinations of functional SNPs, which are related to relatively higher dopamine synthesis and dopamine degradation and lower naïve DRD2, might indicate vulnerability to development of Ai-DSP. However, further studies are needed to validate the present results.

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Comparison of treatment results between 3- and 2-stage Gamma Knife radiosurgery for large brain metastases: a retrospective multi-institutional study

Serizawa, T., Higuchi, Y., Yamamoto, M., Matsunaga, S., Nagano, O., Sato, Y., Aoyagi, K., Yomo, S., Koiso, T., Hasegawa, T., Nakazaki, K., Moriki, A., Kondoh, T., Nagatomo, Y., Okamoto, H., Kohda, Y., Kawai, H., Shidoh, S., Shibazaki, T., Onoue, S., Kenai, H., Inoue, A. and Mori, H.

J Neurosurg    1 - 11 2018年09月

研究論文（学術雑誌）, 共著,  ISSN  0022-3085

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OBJECTIVE In order to obtain better local tumor control for large (i.e., > 3 cm in diameter or > 10 cm(3) in volume) brain metastases (BMs), 3-stage and 2-stage Gamma Knife surgery (GKS) procedures, rather than a palliative dose of stereotactic radiosurgery, have been proposed. Here, authors conducted a retrospective multi-institutional study to compare treatment results between 3-stage and 2-stage GKS for large BMs. METHODS This retrospective multi-institutional study involved 335 patients from 19 Gamma Knife facilities in Japan. Major inclusion criteria were 1) newly diagnosed BMs, 2) largest tumor volume of 10.0-33.5 cm(3), 3) cumulative intracranial tumor volume </= 50 cm(3), 4) no leptomeningeal dissemination, 5) no more than 10 tumors, and 6) Karnofsky Performance Status 70% or better. Prescription doses were restricted to between 9.0 and 11.0 Gy in 3-stage GKS and between 11.8 and 14.2 Gy in 2-stage GKS. The total treatment interval had to be within 6 weeks, with at least 12 days between procedures. There were 114 cases in the 3-stage group and 221 in the 2-stage group. Because of the disproportion in patient numbers and the pre-GKS clinical factors between these two GKS groups, a case-matched study was performed using the propensity score matching method. Ultimately, 212 patients (106 from each group) were selected for the case-matched study. Overall survival, tumor progression, neurological death, and radiation-related adverse events were analyzed. RESULTS In the case-matched cohort, post-GKS median survival time tended to be longer in the 3-stage group (15.9 months) than in the 2-stage group (11.7 months), but the difference was not statistically significant (p = 0.65). The cumulative incidences of tumor progression (21.6% vs 16.7% at 1 year, p = 0.31), neurological death (5.1% vs 6.0% at 1 year, p = 0.58), or serious radiation-related adverse events (3.0% vs 4.0% at 1 year, p = 0.49) did not differ significantly. CONCLUSIONS This retrospective multi-institutional study showed no differences between 3-stage and 2-stage GKS in terms of overall survival, tumor progression, neurological death, and radiation-related adverse events. Both 3-stage and 2-stage GKS performed according to the aforementioned protocols are good treatment options in selected patients with large BMs.

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