研究等業績 - その他 - 羽渕 友則
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ロボット支援根治的前立腺全摘術と恥骨後式根治的前立腺全摘術の治療成績の比較
大久保 鉄平, 三塚 浩二, 小泉 淳, 成田 伸太郎, 古家 琢也, 川村 貞文, 栃木 達夫, 大山 力, 羽渕 友則, 荒井 陽一
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 105回 PP60 - 06 2017年04月
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CONTRIBUTION OF GENETIC POLYMORPHISMS RELATED TO AXITINIB PHARMACOKINETICS TO THE CLINICAL SAFETY AND EFFICACY IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA
Ryoma Igarashi, Norihiko Tsuchiya, Takamitsu Inoue, Nobuhiro Fujiyama, Kazuyuki Numakura, Hiroshi Tsuruta, Hideaki Kagaya, Atsushi Maeno, Mitsuru Saito, Shintaro Narita, Takenori Nioka, Masatomo Miura, Shigeru Sato, Tomonori Habuchi
JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC ) 197 ( 4 ) E182 - E182 2017年04月
研究発表要旨（国際会議）
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Kobayashi M.
Acta Urologica Japonica ( Acta Urologica Japonica ) 63 ( 3 ) 111 - 114 2017年03月
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巨大腎血管筋脂肪腫自然破裂を契機に発見された結節性硬化症の1例
小林 瑞貴, 齋藤 満, 秋濱 晋, 熊澤 光明, 五十嵐 龍馬, 山本 竜平, 高山 孝一朗, 鶴田 大, 井上 高光, 成田 伸太郎, 土谷 順彦, 佐藤 滋, 羽渕 友則
泌尿器科紀要 ( 泌尿器科紀要刊行会 ) 63 ( 3 ) 111 - 114 2017年03月
A woman in her 30s was admitted with abdominal pain and nausea. CT scan revealed a spontaneous rupture of the right giant renal angiomyolipoma, and trans-arterial embolization was performed successfully. With further examination, she was found to be affected with tuberous sclerosis complex (TSC) and she finally wastreated with everolimusfor prevention of recurrent spontaneous-rupture of renal angiomyolipoma.
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巨大腎血管筋脂肪腫自然破裂を契機に発見された結節性硬化症の1例
小林 瑞貴, 齋藤 満, 秋濱 晋, 熊澤 光明, 五十嵐 龍馬, 山本 竜平, 高山 孝一朗, 鶴田 大, 井上 高光, 成田 伸太郎, 土谷 順彦, 佐藤 滋, 羽渕 友則
泌尿器科紀要 ( 泌尿器科紀要刊行会 ) 63 ( 3 ) 111 - 114 2017年03月
30歳代女性。20歳頃より前医にて両側腎の腎血管筋脂肪腫(AML)の経過観察中であった。今回、腹痛と嘔吐を主訴に前医へ救急搬送され、CT所見より右腎AMLの自然破裂と診断された。緊急で動脈塞栓術(TAE)が施行されたが、貧血が進行したため精査目的で当院へ搬送された。入院時所見ではAMLから腫瘍内出血が持続しており、右腎部分切除は困難と考え、mTOR阻害薬投与を開始した。投与18週後にAMLは約30%の縮小を認め、現在も内服中であるしている。
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Ishikawa T.
International Journal of Molecular Sciences ( International Journal of Molecular Sciences ) 18 ( 2 ) 2017年02月
The low specificity of the prostate-specific antigen (PSA) for early detection of prostate cancer (PCa) is a major issue worldwide. The aim of this study to examine whether the serum PCa-associated α2,3-linked sialyl N-glycan-carrying PSA (S2,3PSA) ratio measured by automated micro-total immunoassay systems (μTAS system) can be applied as a diagnostic marker of PCa. The μTAS system can utilize affinity-based separation involving noncovalent interaction between the immunocomplex of S2,3PSA and Maackia amurensis lectin to simultaneously determine concentrations of free PSA and S2,3PSA. To validate quantitative performance, both recombinant S2,3PSA and benign-associated α2,6-linked sialyl N-glycan-carrying PSA (S2,6PSA) purified from culture supernatant of PSA cDNA transiently-transfected Chinese hamster ovary (CHO)-K1 cells were used as standard protein. Between 2007 and 2016, fifty patients with biopsy-proven PCa were pair-matched for age and PSA levels, with the same number of benign prostatic hyperplasia (BPH) patients used to validate the diagnostic performance of serum S2,3PSA ratio. A recombinant S2,3PSA- and S2,6PSA-spiked sample was clearly discriminated by μTAS system. Limit of detection of S2,3PSA was 0.05 ng/mL and coefficient variation was less than 3.1%. The area under the curve (AUC) for detection of PCa for the S2,3PSA ratio (%S2,3PSA) with cutoff value 43.85% (AUC; 0.8340) was much superior to total PSA (AUC; 0.5062) using validation sample set. Although the present results are preliminary, the newly developed μTAS platform for measuring %S2,3PSA can achieve the required assay performance specifications for use in the practical and clinical setting and may improve the accuracy of PCa diagnosis. Additional validation studies are warranted.
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Ito R.
PLoS ONE ( PLoS ONE ) 12 ( 2 ) e0171615 2017年02月
Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this "obesity paradox" is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin. Overweight and obese patients had significantly lower grade cancers than normal patients in all patients and in those without metastasis (p = 0.003 and p = 0.027, respectively). Cancer-specific survival was significantly longer in overweight and obese patients than in normal patients in all patients (p = 0.035). There was a weak inverse correlation between sAd level and BMI in RCC patients (r = -0.344, p = 0.002). Tumor size was slightly correlated with sAd level, and high sAd was significantly associated with poor overall survival rates in patients with non-metastatic RCC (p = 0.035). Adiponectin levels in perinephric adipose tissue and intratumoral AdipoR1/R2 expression were not correlated with RCC aggressiveness or survival. Proliferation significantly increased in 786-O and Caki-2 cells exposed to exogenous adiponectin, whereas cell invasion and migration were unaffected. In addition, exogenous adiponectin significantly inhibited starvation- and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels. In summary, low BMI and high adiponectin levels are associated with aggressive cell behaviors and poor survival in surgically-treated RCC patients. The effects of adiponectin on proliferation and apoptosis might underlie the "obesity paradox" of RCC.
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Patients with metastatic renal cell carcinoma who have benefit from axitinib dose titration: Analysis from a randomized, double-blind, axitinib dose titration phase II study.
Yoshihiko Tomita, Hirotsugu Uemura, Mototsugu Oya, Nobuo Shinohara, Tomonori Habuchi, Yosuke Fujii
JOURNAL OF CLINICAL ONCOLOGY ( LIPPINCOTT WILLIAMS & WILKINS ) 35 ( 6 ) 2017年02月
研究発表要旨（国際会議）
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【メタボリック症候群と腎泌尿器疾患-疾患予防への挑戦-】泌尿器がんとメタボリックシンドローム
成田 伸太郎, 井上 高光, 羽渕 友則
腎臓内科・泌尿器科 ( (有)科学評論社 ) 5 ( 2 ) 133 - 139 2017年02月
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Numakura K.
Anti-Cancer Drugs ( Anti-Cancer Drugs ) 28 ( 1 ) 97 - 103 2017年01月
Although sunitinib is a well-established chemotherapeutic for metastatic renal cell carcinoma (mRCC), there are no robust markers that predict efficacy and toxicity. We analyzed the effect of single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics on clinical outcomes in Japanese patients with mRCC. We analyzed the effect of SNPs in genes involved in sunitinib pharmacokinetics on the clinical outcome in mRCC patients in a Japanese population. We evaluated seven SNPs in four candidate genes, the transport proteins ATP-binding cassette (ABC) B1 (rs1045642, rs1128503, rs2032582, and rs7779562) and ABCG2 (rs2231142), and the metabolic proteins cytochrome P450 (CYP) 3A4 (rs35599367) and CYP3A5 (rs776746) in 70 patients. No significant association was observed between the genotypes of each SNP and time to dose reduction, progression-free survival, overall survival, and best objective response. Meanwhile, the incidence of grade 2 or greater hypertension and hand-foot syndrome, and multiple adverse events (>3), was significantly higher in patients carrying the ABCB1 rs2032582 GG genotype [odds ratio (OR): 5.37, 95% confidence interval (CI) 1.02-14.63, P=0.035; OR: 3.17, 95% CI 1.06-9.52, P=0.036, OR: 3.35; 95% CI 1.14-9.84; P=0.025, respectively]. In conclusion, our data showed that the ABCB1 rs2032582 GG genotype was associated with individual adverse events' susceptibility among Japanese patients treated with sunitinib in routine clinical settings.
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Laparoendoscopic single-site surgeries: A multicenter experience of 469 cases in Japan
Sato F.
International Journal of Urology ( International Journal of Urology ) 24 ( 1 ) 69 - 74 2017年01月
OBJECTIVE: To report on a multi-institutional series of non-robotic urological laparoendoscopic single-site surgery in Japan. METHODS: Consecutive cases of laparoendoscopic single-site surgery carried out between February 2009 and December 2012 at nine academic institutions were included. We examined the surgical outcomes, including conversion and complications rates. RESULTS: Four hundred and sixty-nine cases were included in the analysis. The most common procedure was adrenalectomy (n = 177) and the second most common procedure was radical nephrectomy (n = 143). The procedures also included nephroureterectomy (n = 40), living donor nephrectomy (n = 40), pyeloplasty (n = 30), urachal remnant excision (n = 9), simple nephrectomy (n = 7), radical prostatectomy (n = 6) and others (n = 17). The access sites included umbilicus (n = 248, 53%) and other sites (n = 221, 47%). A transperitoneal approach was used in 385 cases (82%), and retroperitoneal approach in 84 cases (18%). The median operation time of all procedures was 198 min. Conversion to reduced port surgery, conventional laparoscopy, or open surgery was noted in 27 cases (5.8%), 12 cases (2.6%), and two cases (0.4%), respectively, with an overall conversion rate of 8.7%. Intraoperative complications occurred in 10 cases (2.1%). Post-operative complications were noted in 29 cases (6.2%), including five major complications (1.1%). No mortality was recorded in this series. CONCLUSIONS: Non-robotic laparoendoscopic single-site surgery is technically feasible and safe for various urologic diseases in Japan. Furthermore, urological laparoendoscopic single-site surgery is a promising minimally invasive surgical option that is feasible for experienced urological surgeons in intermediate-volume centers as well as high-volume centers.
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Narita T.
Medical Oncology ( Medical Oncology ) 34 ( 1 ) 1 - 1 2017年01月
The optimal treatment for high-risk prostate cancer (Pca) remains to be established. The current guidelines recommend extended pelvic lymph node dissection (e-PLND) for selected intermediate- and high-risk patients treated with RP. However, the indications, optimal extent, and therapeutic benefits of e-PLND remain unclear. The aim of this study was to assess whether e-PLND confers an oncological benefit for high-risk Pca compared to neoadjuvant luteinizing hormone-releasing hormone and estramustine (LHRH + EMP). The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at four institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The outcome measure was BRFS. The 5-year biochemical recurrence-free survival rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9 and 54.7%, respectively (P < 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Although the present study was not randomized, neoadjuvant LHRH + EMP therapy followed by RP might reduce the risk of biochemical recurrence.
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ABO血液型不適合生体腎移植後、抗体関連型拒絶反応治療中に併発した急性T細胞性拒絶反応の1例
山本 竜平, 齋藤 満, 鶴田 大, 前野 淳, 井上 高光, 成田 伸太郎, 土谷 順彦, 佐藤 滋, 羽渕 友則
腎移植・血管外科 ( 腎移植・血管外科研究会 ) 27 ( 1 ) 68 - 74 2017年01月
症例は59歳男性。悪性関節リウマチのため20年以上プレドニゾロン(PSL)10mg/dayを内服していた。妻をドナーとするABO血液型不適合腎移植を施行され、血清クレアチニン(SCr)は術後11日目に1.3mg/dlまで低下した。術後28日目から当科プロトコルに従い、PSL7.5mg/dayに減量した。術後30日のプロトコル生検で病理学的に急性抗体関連型拒絶反応を認め、血漿交換、低用量免疫グロブリン投与、methyl PSL(mPSL)semi-pulse療法(250mg)を施行した。しかしSCrのさらなる上昇を認め、再度移植腎生検を施行したところ、急性T細胞性拒絶反応の併発を認めた。血漿交換、低用量免疫グロブリン投与に加え、通常doseでのmPSL、pulse療法(500mg、3days)を追加し、その後PSLをtaperingした。治療後、SCrは1.8-2.0mg/dlで安定した。PSLを長期間内服していた症例に腎移植療法を施行する場合、免疫抑制効果としてのPSLの必要量が高まっている可能性があり、PSLの漸減には注意が必要である。(著者抄録)
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泌尿器系悪性腫瘍の下大静脈伸展に対する手術の問題と対策
田中 郁信, 角浜 孝行, 山浦 玄武, 千田 佳史, 高木 大地, 桐生 健太郎, 荒井 岳史, 山本 浩史, 齋藤 満, 羽渕 友則
静脈学 ( 日本静脈学会 ) 28 ( 1 ) 79 - 80 2017年01月
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Kagaya H.
Xenobiotica ( Xenobiotica ) 47 ( 10 ) 916 - 922 2017年
1. The objective of this study was to examine the association of UGT1A9, SLCO, and ABCC polymorphisms with mycophenolic acid (MPA) pharmacokinetics in ABO blood type (ABO) incompatible patients with severe renal dysfunction pre-transplantation. 2. In all patients, on day 14 after beginning mycophenolate mofetil (MMF) treatment (1 week before transplantation) and on day 28 after renal transplantation, samples were collected just prior to and 1, 2, 3, 4, 6, 9, and 12 h after oral MMF administration. 3. The median dose-adjusted AUC0-12 of MPA after renal transplantation was significantly lower than before transplantation (57.9 versus 76.5 μg h/mL, respectively, p = 0.002). 4. Although the enterohepatic circulation of MPA pre-transplantation was extremely high (57.6%), this level was significantly reduced after renal transplantation (34.6%). 5. In the multivariate analysis, pre-transplantation, patients with the SLCO1B3 334T allele (p = 0.003), higher alanine aminotransferase (p = 0.002), and lower body weight were independently predictive for a higher dose-adjusted AUC0-12 of MPA. 6. In patients with severe renal dysfunction pre-transplantation, MPA is excreted mainly to bile from the liver, and as a consequence, the SLCO1B3 334T > G polymorphism was found to be significantly associated with MPA exposure.
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Huang M.
Oncotarget ( Oncotarget ) 8 ( 67 ) 111780 - 111794 2017年
Fatty acid binding protein 4 (FABP4) is an abundant protein in adipocytes, and its production is influenced by high-fat diet (HFD) or obesity. The prostate stromal microenvironment induces proinflammatory cytokine production, which is key for the development and progression of prostate cancer (PCa). Here, we show that high FABP4 expression and its secretion by PCa cells directly stimulated PCa cell invasiveness by upregulating matrix metalloproteinases through phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. In addition, prostate stromal cells augmented PCa cell invasiveness by secreting interleukin-8 and -6 in response to FABP4. This was abrogated by the FABP4 specific inhibitor, BMS309403. Furthermore, a mouse xenograft experiment showed HFD enhanced PCa metastasis and invasiveness by the upregulation of FABP4 and interleukin-8. Clinically, the serum level of FABP4 was significantly associated with an aggressive type of PCa rather than obesity. Taken together, FABP4 may enhance PCa progression and invasiveness by upregulating matrix metalloproteinases and cytokine production in the PCa stromal microenvironment, especially under HFD or obesity.
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Narita S.
Surgical Laparoscopy, Endoscopy and Percutaneous Techniques ( Surgical Laparoscopy, Endoscopy and Percutaneous Techniques ) 27 ( 4 ) e69 - e73 2017年
PURPOSE: The purpose of this study is to assess the risk factors and characteristics of adherent perinephric fat (APF) in healthy individuals. PATIENTS AND METHODS: Men who underwent laparoscopic donor nephrectomy were included. Video review was used to divide patients on the basis of APF severity. Relationship between APF scores and clinical and radiographic features was evaluated. RESULTS: Of the 92 patients, 43 (46.7%) and 8 (8.7%) were categorized as APF and severe APF, respectively. The median total operative time was significantly associated with APF severity. Sex, body mass index, and perinephric fat area, stranding, and thickness were significantly associated with severe APF. In the multivariate analysis, perinephric fat areas and stranding were independent risk factors for severe APF (HR, 1.189 and 14.450, respectively). In the 44 analyzed cytokines, levels of sIL-6R in the perinephric adipose tissue-conditioned medium were significantly higher for APF group than that for non-APF group (P=0.049). CONCLUSIONS: Host-related risk factors for APF could predict surgical difficulty in patients undergoing partial nephrectomy.
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ロボット支援腹腔鏡下膀胱全摘術における拡大リンパ節郭清の手技と成績
鶴田 大, 羽渕 友則
Japanese Journal of Endourology ( 日本泌尿器内視鏡学会 ) 30 ( 1 ) 14 - 19 2017年
<p> 筋層浸潤性膀胱癌に対する膀胱全摘術とそれに伴う骨盤内リンパ節郭清術（PLND）は標準治療であるが開放膀胱全摘術（ORC）は侵襲性の高い術式である．近年ロボット手術の泌尿器科領域での適応拡大に伴い保険適応外ではあるがロボット支援腹腔鏡下膀胱全摘術（RARC）が行われる症例が増えてきており当科でも10例に施行している．RARCでは体位ならびに機器の配置はロボット支援腹腔鏡下前立腺全摘術（RALP）に準じ，カメラポートはRALPよりも3-4cm頭側に配置し，さらに第2助手用5mmトロカールを1本追加，計7本のトロカールを配置した．全例で下腸間膜動脈分岐部までの拡大リンパ節郭清を施行した．総手術時間中央値544分（494-639），リンパ節郭清に要した時間の中央値は164分（136-202），摘出リンパ節個数中央値は31個（18-62）であった．本術式は安全に施行可能で，周術期の重篤な合併症の発生はなかった．本稿ではRARCにおける拡大あるいは超拡大PLNDの意義に関して論述する．</p>
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羽渕 友則
Japanese Journal of Endourology ( 日本泌尿器内視鏡学会 ) 30 ( 1 ) 67 - 71 2017年
<p> 腹腔鏡手術における“医療安全”や“危機管理”を確実にするにはどうしたらよいか？“安全”は存在することはなく，“リスクを如何にゼロに近づけるか，というマネージメントとプロセス”と言われています．すなわち，リスクはゼロにはなりません．どんなに“安全な船”を造っても，沈没する確率はゼロにはならないのと同様です．腹腔鏡手術においても“安全な手術”とは患者，家族，社会にとって許容できるレベルまで“不幸な事象”のリスクを下げられた手術だと思います．そのためには，いろんな方面からの“防御壁”が必要でしょう．例えば，術前・術中・術後に分けて対策を立てることも必要ですし，さらには“危険回避のストラテジー”という観点からリスクを最小化することも重要です．また，医療安全における“Tragedy”には様々なパターンがあることも十分知るべきでしょう．“システム型のTragedy”は様々な医療安全管理によって程度も頻度も随分改善されてきましたが，“不幸な境遇型”や“誤認・ご判断型のTragedy”は未だに外科医を悩ます難題と言えるかと思います．腹腔鏡手術を患者，家族，社会にとって，許容できるレベルまで安全に行い，その安全性に継続性を持たせるためには，危機管理の伝承が非常に重要であると考えます．</p>
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【鏡視下腎摘出術の新展開】LESS/RPSドナー腎採取術の現況と展望
井上 高光, 成田 伸太郎, 齋藤 満, 奈良 健平, 神田 壮平, 沼倉 一幸, 佐藤 滋, 羽渕 友則
腎移植・血管外科 ( 腎移植・血管外科研究会 ) 29 ( 3 ) 144 - 152 2017年
本邦の生体ドナー腎採取術の9割以上は腹腔鏡下ドナー腎採取術(laparoscopic donor nephrectomy:LDN)で行われているが、近年、一部の施設で単孔式腹腔鏡手術(Laparoendoscopic single-site surgery:LESS)に代表されるreduced port surgery(RPS)を採用したLDNが推進されてきた。従来法のLDN(Std-LDN)より更に低侵襲性や整容性を高めることは、数少ない生体腎移植ドナー候補に対して提供手術に納得していただくために重要であると考えられる。一方、LDNは健康なボランティアに対する手術であるため、安全性と採取腎の良好な機能が絶対的な要件である。従って、LESS/RPSの術式においては低侵襲性、整容性を担保しつつ同時に安全性も担保するreduced port surgery(RPS)の考え方が重要であると考えられる。腎に対するLESSでは副腎など小さな臓器の場合と異なり、腎摘出に必要な約5cmの単孔ではストレート鉗子のみでの操作で比較的容易に術式の完遂が可能である。また採取対象の腎の大きさは、腫瘍性疾患と異なり、各ドナー間でのばらつきが少ないため、ドナー腎採取術はLESSの良い適応であると考えられる。本稿では、LESSドナー腎採取術(Laparoendoscopic single-site donor nephrectomy:LESSDN)およびRPSを採用したLDNについて、国内外の過去の文献および当科の取り組みを紹介し、今後を展望する。(著者抄録)