研究等業績 - 原著論文 - 羽渕　友則

Lymphovascular invasion is significantly associated with biochemical relapse after radical prostatectomy even in patients with pT2N0 negative resection margin

K. Mitsuzuka, S. Narita, T. Koie, Y. Kaiho, N. Tsuchiya, T. Yoneyama, N. Kakoi, S. Kawamura, T. Tochigi, C. Ohyama, T. Habuchi, Y. Arai

Prostate Cancer and Prostatic Diseases   18 ( 1 ) 25 - 30   2015年03月

研究論文（学術雑誌）  

BACKGROUND: The significance of lymphovascular invasion (LVI) remains controversial, and the association of LVI with biochemical relapse was investigated in men treated with radical prostatectomy according to pathological results. METHODS: Data from 1268 patients undergoing radical prostatectomy between 2000 and 2009 were retrospectively reviewed. Clinicopathological variables were compared between LVI-negative and LVI-positive patients. Multivariate analyses by Cox proportional hazard model and Kaplan-Meier method were performed to identify risk factors for biochemical relapse in all patients, patients with pT2N0 and pT2N0 negative resection margin (RM). RESULTS: LVI information was available in 1160 cases, and LVI was seen in 121 cases (10.4%). Clinicopathological variables were significantly worse in LVI-positive patients than in LVI-negative patients. On multivariate analyses, PSA ≥ 10 ng ml-1, pathological Gleason score ≥ 8, pathological T stage ≥ 3, lymph node metastasis, positive RM and LVI were independent predictors for biochemical relapse in all patients. In patients with pT2N0, PSA ≥ 10 ng ml-1, pathological Gleason score ≥ 8, positive RM and LVI were independent predictors for biochemical relapse. In patients with pT2N0 negative RM, LVI and pathological Gleason score ≥ 8 were independent predictors for biochemical relapse (LVI; hazard ratio 3.809, 95% confidence interval 1.900-7.635, P-value < 0.001, Gleason score ≥ 8; hazard ratio 2.189, 95% confidence interval 1.199-3.999, P-value = 0.011). With a median follow-up of 50 months, 5-year biochemical relapse-free survival in patients with pT2N0 negative RM was 95.7% in those with negative LVI in comparison to 85.3% in those with positive LVI (P < 0.001, log rank). CONCLUSIONS: LVI was consistently a significant predictor for biochemical relapse after radical prostatectomy in not only all patients but also in patients with pT2N0 and pT2N0 negative RM. These results strongly support the significance of LVI as a predictor for biochemical relapse.

DOI PubMed

Prostate-specific antigen density predicts extracapsular extension and increased risk of biochemical recurrence in patients with high-risk prostate cancer who underwent radical prostatectomy.

Takuya Koie, Koji Mitsuzuka, Takahiro Yoneyama, Shintaro Narita, Sadafumi Kawamura, Yasuhiro Kaiho, Norihiko Tsuchiya, Tatsuo Tochigi, Tomonori Habuchi, Yoichi Arai, Chikara Ohyama, Tohru Yoneyama, Yuki Tobisawa

International journal of clinical oncology   20 ( 1 ) 176 - 81   2015年02月

研究論文（学術雑誌）  

BACKGROUND: Patients with advanced local-stage, high-grade prostate cancer (Pca) and high pretreatment prostate-specific antigen (PSA) levels have inferior outcomes compared to their counterparts with more favorable clinical characteristics. However, some patients exhibit favorable pathological features or experience long-term PSA-free survival after radical prostatectomy (RP). We retrospectively examined the ability of preoperative characteristics to predict pathological and oncological outcomes in high-risk Pca patients who underwent RP. METHODS: We examined data of 1,268 consecutive Pca patients treated with RP alone at 4 hospitals from the Michinoku Urological Cancer Study Group database. Preoperative predictors included age, PSA level, biopsy Gleason score, clinical T stage, and PSA density (PSAD). The outcome measures pathological T stage and PSA-free survival were evaluated by multivariate analysis. RESULTS: We identified 380 high-risk Pca patients, of which 44 % patients had extracapsular extension. Logistic regression analysis indicated that PSAD was an independent predictor of adverse pathologic stage. The 5-year PSA-free survival rates were 82.9 % for patients with PSAD ≤0.468 ng mL(-1) cm(-2) and 50.7 % for those with PSAD >0.468 ng mL(-1) cm(-2) (P < 0.0001). Multivariate analyses revealed that PSAD, cT, and the number of preoperative high-risk Pca criteria were independent predictors of PSA-free survival. CONCLUSIONS: PSAD may be an independent predictor of advanced pathological features and biochemical recurrence in high-risk Pca patients treated with RP alone. PSAD may be used for further risk stratification of high-risk Pca patients.

DOI PubMed

Capability of utilizing CYP3A5 polymorphisms to predict therapeutic dosage of tacrolimus at early stage post-renal transplantation.

Takenori Niioka, Hideaki Kagaya, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura

International journal of molecular sciences   16 ( 1 ) 1840 - 54   2015年01月

研究論文（学術雑誌）  

While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78-1.17) vs. 0.59 (0.45-0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.

DOI PubMed

Effects of functional genetic polymorphisms in the CYP19A1 gene on prostate cancer risk and survival.

Sohei Kanda, Norihiko Tsuchiya, Shintaro Narita, Takamitsu Inoue, Mingguo Huang, Syuji Chiba, Susumu Akihama, Mitsuru Saito, Kazuyuki Numakura, Hiroshi Tsuruta, Shigeru Satoh, Seiichi Saito, Chikara Ohyama, Yoichi Arai, Osamu Ogawa, Tomonori Habuchi

International journal of cancer   136 ( 1 ) 74 - 82   2015年01月

研究論文（学術雑誌）  

CYP19 catalyzes the conversion of androgens to estrogens and is a critical enzyme affecting the sex hormone milieu. In this study, we investigated the functions of CYP19A1 polymorphisms and their associations with prostate cancer risk and clinical outcome. This case-control study evaluated the effects of three single nucleotide polymorphisms (SNPs) in CYP19A1 on the risk of prostate cancer in 330 prostate cancer patients and 354 normal controls. The associations between each SNP and sex hormone levels were evaluated in 164 healthy male patients. The functions of the SNPs were determined by reporter gene assays in PC3 and DU145 cell lines. Prostate-specific antigen nadir was evaluated in 142 patients with metastatic prostate cancer treated with androgen deprivation therapy. Cancer-specific survival (CSS) was determined in 166 patients with metastatic prostate cancer, to evaluate the influence of the three SNPs. Each variant allele of the three SNPs significantly decreased the risk of prostate cancer. Haplotype analysis showed that the T-A-G haplotype (corresponding to rs2470152-rs10459592-rs4775936) increased the risk of prostate cancer, while the C-C-A haplotype decreased the risk. The estrone/androstenedione ratio was significantly higher in men with the C allele of rs2470152, the C allele of rs10459592, and the A allele of rs4775936 in a gene-dosage-dependent manner. Patients with the variant allele at rs4775936 had significantly shorter CSS. These results indicate that CYP19A1 polymorphisms may influence prostate cancer risk and survival by modifying promoter activity, with subsequent effects on the sex hormone milieu.

DOI PubMed

Efficiency of pretreatment risk stratification systems for prostate cancer in a Japanese population treated with radical prostatectomy.

Takuya Koie, Koji Mitsuzuka, Shintaro Narita, Takahiro Yoneyama, Sadafumi Kawamura, Norihiko Tsuchiya, Tatsuo Tochigi, Tomonori Habuchi, Yoichi Arai, Chikara Ohyama

International journal of urology : official journal of the Japanese Urological Association   22 ( 1 ) 70 - 3   2015年01月

研究論文（学術雑誌）  

OBJECTIVE: To determine whether the currently available pretreatment risk classification systems are applicable in Japanese prostate cancer patients. METHODS: Using data obtained from 1264 consecutive patients with prostate cancer treated with radical prostatectomy at four hospitals in Japan, biochemical recurrence-free survival rates were estimated and compared between the D'Amico, the National Institute for Health and Clinical Excellence, the Cancer of the Prostate Strategic Urological Research Endeavor, the National Comprehensive Cancer Network, and the European Society of Medical Oncology risk groups by using the Kaplan-Meier method and log-rank test. RESULTS: The 5-year biochemical recurrence-free survival rates in the D'Amico low-, intermediate-, and high-risk groups were 88.3%, 84.7% and 66.9%, respectively (low and intermediate risk vs high risk, P < 0.001). The 5-year biochemical recurrence-free survival rates in the National Institute for Health and Clinical Excellence, National Comprehensive Cancer Network, and European Society of Medical Oncology low-, intermediate- and high-risk groups were 88.3%, 84.3%, and 60.3%, respectively (low and intermediate risk vs high risk, P < 0.001). The 5-year biochemical recurrence-free survival rates in the Cancer of the Prostate Strategic Urological Research Endeavor low-, intermediate-, and high-risk groups were 90%, 83.5% and 60.3%, respectively (low and intermediate risk vs high risk, P < 0.001). Low- and intermediate-risk groups according to any of the risk stratification systems did not show significant differences in biochemical recurrence-free survival. CONCLUSION: Current risk stratification systems do not discriminate between low- and intermediate-risk groups in the Japanese population. A novel, pretreatment risk stratification system including other prognostic factors is necessary for an adequate prostate cancer risk assessment in the Japanese population.

DOI PubMed

Characterization of clinical and genetic risk factors associated with dyslipidemia after kidney transplantation.

Kazuyuki Numakura, Hideaki Kagaya, Ryohei Yamamoto, Naoki Komine, Mitsuru Saito, Tsuruta Hiroshi, Susumu Akihama, Takamitsu Inoue, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi, Takenori Niioka, Masatomo Miura, Shigeru Satoh

Disease markers   2015   179434 - 179434   2015年

研究論文（学術雑誌）  

We determined the prevalence of dyslipidemia in a Japanese cohort of renal allograft recipients and investigated clinical and genetic characteristics associated with having the disease. In total, 126 patients that received renal allograft transplants between February 2002 and August 2011 were studied, of which 44 recipients (34.9%) were diagnosed with dyslipidemia at 1 year after transplantation. Three clinical factors were associated with a risk of having dyslipidemia: a higher prevalence of disease observed among female than male patients (P = 0.021) and treatment with high mycophenolate mofetil (P = 0.012) and prednisolone (P = 0.023) doses per body weight at 28 days after transplantation. The genetic association between dyslipidemia and 60 previously described genetic polymorphisms in 38 putative disease-associated genes was analyzed. The frequency of dyslipidemia was significantly higher in patients with the glucocorticoid receptor (NR3C1) Bcl1 G allele than in those with the CC genotype (P = 0.001). A multivariate analysis revealed that the NR3C1 Bcl1 G allele was a significant risk factor for the prevalence of dyslipidemia (odds ratio = 4.6; 95% confidence interval = 1.8-12.2). These findings may aid in predicting a patient's risk of developing dyslipidemia.

DOI PubMed

Clinical benefits of tubeless umbilical cutaneous ureterostomy.

Kazuyuki Numakura, Norihiko Tsuchiya, Makoto Takahashi, Hiroshi Tsuruta, Susumu Akihama, Mitsuru Saito, Takamitsu Inoue, Shintaro Narita, Mingguo Huang, Shigeru Satoh, Tomonori Habuchi

Canadian Urological Association journal = Journal de l'Association des urologues du Canada   9 ( 5-6 ) E379-83 - E383   2015年

研究論文（学術雑誌）  

INTRODUCTION: We assess a novel technique of tubeless bilateral cutaneous ureterostomy, with a single umbilical stoma, for bladder cancer patients with short ureters after cystectomy. The benefit of cutaneous ureterostomy is equal to other incontinent urinary diversions, when the tubeless procedure is successfully achieved. This simple technique makes it easy to monitor the upper urinary tract (UUT) and is beneficial to patients with a high risk of UUT recurrence. METHODS: This old and new surgical technique was used to perform total cystectomy and urinary diversion on three patients with bladder cancer at a high risk of UUT recurrence. RESULTS: Two men and one woman (mean age: 73 years) underwent this surgery and the mean follow-up period was 8.3 years. The surgical approaches were laparotomy (n = 2) and laparoscopy (n = 1). One case developed para-stomal erosion, whereas another developed ureteral stenosis requiring catheter reinsertion. Although postoperative hydronephrosis was observed in all cases, the mean preoperative and postoperative serum creatinine levels were 0.70 and 0.76, respectively. UUT recurrence was not observed during the follow-up period. CONCLUSION: This tubeless umbilical cutaneous ureterostomy procedure greatly improves the outcome of urinary diversion for cancer patients with short ureters at a high risk of UUT recurrence. The benefits are equivalent to other urinary diversions when the tubeless procedure is successfully achieved.

DOI PubMed

[Treatment for high-risk localized prostate cancer].

Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi

Nihon rinsho. Japanese journal of clinical medicine   72 ( 12 ) 2212 - 6   2014年12月

研究論文（学術雑誌）  

High-risk localized prostate cancer encompasses a significant heterogeneity and the treatment strategy for this group of prostate cancer patients remains controversial. The definition of high-risk localized prostate cancer is not consistent in that which clinicopathological parameters are included as risk factors. Therefore, we need to be careful in comparing the treatment outcome of each report. Recently, there have been significant improvements in the radiotherapeutic and surgical management. High radiation dose levels, long-term androgen deprivation therapy, and the combination of brachytherapy may contribute to the improvement of radiation-based treatment. Although some patients can be cured by standard surgical approach, extended lymph node dissection and multimodal treatment with radiation and chemohormonal therapy may improve surgical outcome. This review focuses on the recent treatment strategy for high-risk localized prostate cancer.

PubMed

De novo renal cell carcinoma in an allograft kidney treated with nephron-sparing surgery: a case report.

Kazuyuki Numakura, Shigeru Satoh, Norihiko Tsuchiya, Mitsuru Saito, Taketoshi Nara, Mingguo Huang, Hiroshi Tsuruta, Susumu Akihama, Takamitsu Inoue, Shintaro Narita, Tomonori Habuchi

Progress in transplantation (Aliso Viejo, Calif.)   24 ( 4 ) 328 - 31   2014年12月

研究論文（学術雑誌）  

The development of primary malignant tumors is a distressing complication of organ transplant. However, the emergence of de novo renal cell carcinoma from a kidney allograft is rare. A 60-year-old man underwent living kidney transplant from a spousal donor. Six years after the transplant surgery, computed tomographic evaluation confirmed the presence of a 2.8-cm-diameter solid mass in the lower pole of the allograft. Partial allograft nephrectomy was performed, and the margin surrounding the normal parenchyma was resected. The serum level of creatinine did not decrease. Here, we report a case of renal cell carcinoma in an allograft kidney that was successfully treated with nephron-sparing surgery.

DOI PubMed

Progress in cancer diagnosis and therapy using new imaging technologies

Tomonori Habuchi

Drug Delivery System   29 ( 4 ) 271   2014年12月

研究論文（学術雑誌）  

DOI

Reliability of laparoscopic skills assessment on video: 8-year results of the endoscopic surgical skill qualification system in Japan.

Tadashi Matsuda, Hiroomi Kanayama, Yoshinari Ono, Akihiro Kawauchi, Hiroaki Mizoguchi, Ken Nakagawa, Masatsugu Iwamura, Masanobu Shigeta, Tomonori Habuchi, Toshiro Terachi

Journal of endourology   28 ( 11 ) 1374 - 8   2014年11月

研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: The Japanese Urological Association and Japanese Society of Endourology established a urologic laparoscopic skills qualification system called the Endoscopic Surgical Skill Qualification (ESSQ) System in Urological Laparoscopy in 2004. The reliability of video assessments by referees was evaluated. MATERIALS AND METHODS: Videos of nephrectomies or adrenalectomies performed by the applicants were assessed by two referees selected among a pool of 42 referees. From 2004 to 2011, 1308 urologists applied and 60.2% were qualified after video assessments. The results of skills assessments on 1220 videos that had fixed points by two referees were analyzed statistically. RESULTS: The average number of videos that each referee assessed was 58.1, with a range of 16 to 87. The accordance rate of the results of the video assessment, pass or fail, by the two referees was 68.9%. The scores of the video assessment by each referee averaged 62.7±2.4 (standard deviation) (full score was set at 75 points and ≥60 points was needed to pass). There was a statistically significant difference in the average video assessment score among the referees (P<0.001), and five referees showed significantly higher or lower average scores than the other referees. The percentage qualification of the final decision made by the Referee Committee on the videos originally assessed by each referee showed no significant differences among the 42 referees. The accordance rate of the results from the video assessment by each referee with the final decision by the committee showed a statistically significant positive correlation with the number of videos assessed by each referee (r=0.404, P=0.0080). CONCLUSIONS: The ESSQ system showed moderate reliability for the video assessments by the referees. It was concluded that the video assessments by the referees were fair for all applicants, because the final qualification rates showed no significant differences among the referees.

DOI PubMed

Renal subcapsular fluid collection caused by penetration of a pancreatic pseudocyst.

Soki Kashima, Takamitsu Inoue, Mitsuru Chiba, Naoki Komine, Ryuichi Ito, Kazuyuki Numakura, Hiroshi Tsuruta, Mitsuru Saito, Susumu Akihama, Shintaro Narita, Norihiko Tsuchiya, Shigeru Satoh, Hirohide Onishi, Tomonori Habuchi

Urology   84 ( 5 ) e23-4 - e24   2014年11月

研究論文（学術雑誌）  

A 63-year-old man presented with left flank pain and spiked fever. Computed tomography revealed a pancreatic cyst and left renal subcapsular fluid collection that appeared to be connected to the cyst. High levels of amylase and lipase were observed in a test puncture of renal fluid collection. The cause of the fluid collection was diagnosed as penetration of the pancreatic pseudocyst. Endoscopic nasobiliary drainage was used to drain the pancreatic pseudocyst and renal subcapsular fluid collection. The present case demonstrated that renal subcapsular fluid collection may be caused by penetration of a pancreatic pseudocyst.

DOI PubMed

Serum tri- and tetra-antennary N-glycan is a potential predictive biomarker for castration-resistant prostate cancer.

Yusuke Ishibashi, Yuki Tobisawa, Shingo Hatakeyama, Tetsu Ohashi, Masakazu Tanaka, Shintaro Narita, Takuya Koie, Tomonori Habuchi, Shin-Ichiro Nishimura, Chikara Ohyama, Tohru Yoneyama

The Prostate   74 ( 15 ) 1521 - 9   2014年11月

研究論文（学術雑誌）  

BACKGROUND: The U.S. FDA has approved several novel systemic agents including abiraterone acetate and taxoid cabazitaxel for metastatic castration-resistant prostate cancer (CRPC) result in a complicated decision-making while selecting an appropriate treatment. Therefore, a predictive biomarker for CRPC would provide useful information to physicians. The aim of this study is to evaluate the diagnostic potential of serum N-glycan profiling in CRPC. METHODS: Serum N-glycomics was performed in 80 healthy volunteers and 286 benign prostatic hyperplasia, 258 early-stage PC, 46 PC with androgen deprivation therapy (ADT), and 68 CRPC patients using the glycoblotting method. A total of 36 types of N-glycan levels in each patient were analyzed using logistic regression analysis and receiver operating characteristic curves. We also examined the expression of N-glycan branching enzyme genes in PC cell lines using quantitative RT-PCR. RESULTS: We observed that tri- and tetra-antennary N-glycans were significantly higher in CRPC patients than in any other groups. The longitudinal follow-up of tri- and tetra- antennary N-glycan levels revealed that one PC with ADT patient showed an increase that was more than the cut-off level and two consecutive increases in tri- and tetra-antennary N-glycan levels 3 months apart; resulted in biochemical recurrence despite the castrate level of testosterone, and the patient was defined as CRPC. Expression of N-glycan branching enzyme genes were significantly upregulated in CRPC cell lines. CONCLUSIONS: These results suggest that the overexpression of tri- and tetra-antennary N-glycan may be associated with the castration-resistant status in PC and may be a potential predictive biomarker for CRPC.

DOI PubMed

Reassessment of prognostic heterogeneity of pT3 renal pelvic urothelial carcinoma: analysis in terms of proposed pT3 subclassification systems.

Jinsung Park, Tomonori Habuchi, Youichi Arai, Chikara Ohyama, Takamitsu Inoue, Shingo Hatakeyama, Seong Soo Jeon, Ghee Young Kwon, Cheol Kwak, Kyung Chul Moon, Choung-Soo Kim, Hanjong Ahn

The Journal of urology   192 ( 4 ) 1064 - 71   2014年10月

研究論文（学術雑誌）  

PURPOSE: We determined whether the 3 pT3 subclassification systems reported by the Asan, Cornell and Nagoya groups provide an accurate estimation of patient prognosis. We also determined which subclassification is most predictive of the heterogeneous oncological outcomes of pT3 renal pelvic urothelial carcinoma. MATERIALS AND METHODS: Using a Korea-Japan multi-institutional, retrospective database 250 pT3 renal pelvic urothelial carcinomas treated with radical nephroureterectomy were assigned to the 3 pT3 subcategories by tumor location and depth of parenchymal invasion after pathological reevaluation. Recurrence-free and cancer specific survival was assessed according to the 3 pT3 subclassifications. Predictive accuracy for survival in 4 models (baseline and each of the 3 pT3 subclassifications) was quantified and predictive accuracy increments for each model were compared. RESULTS: In the baseline multivariate Cox regression model nodal metastasis and high grade were significant for survival. On multivariate analysis including the pT3 subclassifications the 3 subclassifications remained significantly associated with survival rates. Of the 3 pT3 subclassification systems the Cornell subclassification had the highest predictive accuracy for discriminating the heterogeneous prognosis of pT3 renal pelvic urothelial carcinoma, followed by the Nagoya subclassification. Compared with the baseline model adding the Cornell subclassification significantly increased predictive accuracy for recurrence-free survival from 0.687 to 0.742 (p = 0.029) and for cancer specific survival from 0.713 to 0.758 (p = 0.047). CONCLUSIONS: The criteria of microscopic vs macroscopic parenchymal invasion and/or peripelvic fat invasion provide the most accurate differential classification of the prognostic heterogeneity of pT3 renal pelvic urothelial carcinoma. Further studies should be performed to determine the need to modify the current pT3 renal pelvic urothelial carcinoma staging system.

DOI PubMed

Antiemetic efficacy and safety of a combination of palonosetron, aprepitant, and dexamethasone in patients with testicular germ cell tumor receiving 5-day cisplatin-based combination chemotherapy.

Shota Hamada, Shiro Hinotsu, Koji Kawai, Shigeyuki Yamada, Shintaro Narita, Tomomi Kamba, Hiroyuki Nishiyama, Yoichi Arai, Tomonori Habuchi, Osamu Ogawa, Koji Kawakami

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer   22 ( 8 ) 2161 - 6   2014年08月

研究論文（学術雑誌）  

PURPOSE: This study aimed to determine the antiemetic efficacy and safety of a combination of palonosetron, aprepitant, and dexamethasone in patients with testicular germ cell tumor (TGCT) receiving 5-day cisplatin-based combination chemotherapy. METHODS: An open-label, single-arm, multicenter study was performed in patients with TGCT who were scheduled to receive 5-day cisplatin-based combination chemotherapy. The antiemetic therapy consisted of palonosetron 0.75 mg on day 1, aprepitant 125 mg on day 1 and 80 mg on days 2 to 5, and dexamethasone 9.9 mg on day 1 and 6.6 mg on days 2 to 8. The primary endpoint was complete response (CR) rate, which was defined as no vomiting and no rescue medication, in the overall period (0 to 216 h) in the first chemotherapy course. Incidence and severity of nausea were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) and a subjective rating scale completed by patients. RESULTS: Thirty patients were included in the analysis. CR was achieved in 90.0% of the patients in the first chemotherapy course, and high CR rates were also observed in the second and third courses (82.1 and 78.3%, respectively). The incidence of nausea peaked on days 4 to 6 in about 50% of the patients. The reported adverse drug reactions were hiccups (13.3%), anorexia (3.3%), and stomach pain (3.3%). None of these were unexpected and none were grade 3 or 4. CONCLUSIONS: The combination antiemetic therapy examined in this study was highly effective and well-tolerated in patients with TGCT receiving 5-day cisplatin-based combination chemotherapy.

DOI PubMed

Pharmacokinetic and CYP3A5 pharmacogenetic differences between once- and twice-daily tacrolimus from the first dosing day to 1 year after renal transplantation.

Shigeru Satoh, Takenori Niioka, Hideaki Kagaya, Kazuyuki Numakura, Takamitsu Inoue, Mitsuru Saito, Naoki Komine, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi, Masatomo Miura

Pharmacogenomics   15 ( 11 ) 1495 - 506   2014年08月

研究論文（学術雑誌）  

UNLABELLED: Aim & patients & methods: This study investigated 24-h pharmacokinetic and CYP3A5 pharmacogenetic differences between once-daily tacrolimus (Tac-q.d.) versus twice-daily tacrolimus (Tac-b.i.d.) pretransplantation and at 1 month and 1 year post-transplantaion. RESULTS: The dose-adjusted trough level (Cmin) and area under the blood concentration-time curve from 0 to 24 h (AUC₀₋₂₄) increased twofold within 1 year post-transplantation with both formulations and the two genotypes. Good correlations were observed between the AUC₀₋₂₄ and Cmin for both formulations. However, the dose-adjusted Cmin, but not dose-adjusted AUC₀₋₂₄, was approximately 30% lower for Tac-q.d. than for Tac-b.i.d. Although the dose-adjusted Cmin was lower for Tac-q.d. than for Tac-b.i.d. in both genotypes, the dose-adjusted AUC₀₋₂₄ was approximately 25% lower for Tac-q.d. than for Tac-b.i.d. in CYP3A5 expressers, but not in nonexpressers during the study period. CONCLUSION: These results suggested that the approximately 30% lower Cmin for Tac-q.d. than for Tac-b.i.d. may have achieved the same AUC₀₋₂₄ with both formulations and may be associated with CYP3A5 pharmacogenomic differences, especially in CYP3A5 expressers, between Tac-b.i.d. and Tac-q.d.

DOI PubMed

Successful mammalian target of rapamycin inhibitor maintenance therapy following induction chemotherapy with gemcitabine and doxorubicin for metastatic sarcomatoid renal cell carcinoma.

Kazuyuki Numakura, Norihiko Tsuchiya, Susumu Akihama, Takamitsu Inoue, Shintaro Narita, Mingguo Huang, Shigeru Satoh, Tomonori Habuchi

Oncology letters   8 ( 1 ) 464 - 466   2014年07月

研究論文（学術雑誌）  

This study presents a case of metastatic sarcomatoid renal cell carcinoma (RCC) treated with systemic chemotherapy followed by mammalian target of rapamycin inhibitor maintenance therapy. A 63-year-old male presented with lumbago, and lumbar vertebral tumors were detected by magnetic resonance imaging. Subsequent computed tomography (CT) revealed a right renal tumor and CT-guided biopsy of the right renal and left sacroiliac tumors determined pure sarcomatoid carcinoma without a clear cell component. Two cycles of combination chemotherapy comprising of gemcitabine (1,500 mg/m2 on day one) and doxorubicin (50 mg/m2 on day one) resulted in a 20% reduction in the longest diameter of the right renal tumor. However, due to grade 3 neutropenia, the chemotherapy was discontinued and temsirolimus (25 mg once weekly), which binds to the cytoplasmic protein, FKBP-12, and inhibits mTOR, was administered. Stable disease was maintained for 19 months with temsirolimus and no major adverse events, with the exception of grade 2 nausea, were observed. The patient succumbed to their disease at 30 months following the initiation of treatment. These results suggested that systemic chemotherapy followed by temsirolimus maintenance is a feasible treatment option for patients with metastatic sarcomatoid RCC.

DOI PubMed

Are pathological and oncological outcomes of elderly men treated with radical prostatectomy worse than those of younger men? Matched-pair analysis between patients aged <70 and ≥70 years.

Koji Mitsuzuka, Takuya Koie, Shintaro Narita, Yasuhiro Kaiho, Takahiro Yoneyama, Norihiko Tsuchiya, Narihiko Kakoi, Sadafumi Kawamura, Tatsuo Tochigi, Chikara Ohyama, Tomonori Habuchi, Yoichi Arai

Japanese journal of clinical oncology   44 ( 6 ) 587 - 92   2014年06月

研究論文（学術雑誌）  

OBJECTIVE: To compare oncological outcomes of patients aged ≥70 years treated with radical prostatectomy with those of a clinically matched younger cohort. METHODS: Data from 1268 patients undergoing radical prostatectomy between 2000 and 2009 were retrospectively reviewed. Patients were classified according to age (<70 or ≥70 years) at the time of prostatectomy. After matching pre-operative factors (i.e. prostate specific antigen, positive biopsy cores, Gleason score, clinical stage and D'Amico risk group), 333 patients were chosen from each group. RESULTS: The percentage of pathological stage ≥T3 in those of age <70 and ≥70 years was 30.3 and 33.0%, respectively (P = 0.51). The percentage of pathological Gleason score ≤6, 7 and ≥8 was not significantly different between the two age groups (P = 0.08). The percentage of organ-confined disease in those of age <70 and ≥70 years was 69.4 and 67.0%, respectively (P = 0.56). With a median follow-up of 50 months, 5-year prostate specific antigen recurrence-free survival in those of age <70 and ≥70 years was 83.4 and 80.1%, respectively (log rank, P = 0.199). Five-year cancer-specific survival in those of age <70 and ≥70 years was 100 and 99.4%, respectively (log rank, P = 0.317). Five-year overall survival in those of age <70 and ≥70 years was 98.4 and 96.4%, respectively (log rank, P = 0.228). CONCLUSIONS: Pathological and oncological outcomes in elderly patients (age ≥70 years) treated with radical prostatectomy were not significantly different from those of younger patients (age <70 years). This information will help refine the indications for definitive treatment for localized prostate cancer in elderly men.

DOI PubMed

Measurement of aberrant glycosylation of prostate specific antigen can improve specificity in early detection of prostate cancer.

Tohru Yoneyama, Chikara Ohyama, Shingo Hatakeyama, Shintaro Narita, Tomonori Habuchi, Takuya Koie, Kazuyuki Mori, Kazuya I P J Hidari, Maho Yamaguchi, Takashi Suzuki, Yuki Tobisawa

Biochemical and biophysical research communications   448 ( 4 ) 390 - 6   2014年06月

研究論文（学術雑誌）  

INTRODUCTION: We previously identified prostate cancer (PCa)-associated aberrant glycosylation of PSA, where α2,3-linked sialylation is an additional terminal N-glycan on free PSA (S2,3PSA). We then developed a new assay system measuring S2,3PSA using a magnetic microbead-based immunoassay. We compared the diagnostic accuracy of conventional PSA and percent-free PSA (%fPSA) tests. METHODS: We used MagPlex beads to measure serum S2,3PSA levels using anti-human fPSA monoclonal antibody (8A6) for capture and anti-α2,3-linked sialic acid monoclonal antibody (HYB4) for detection. We determined the cutoff values in a training test and measured serum S2,3PSA levels in 314 patients who underwent biopsy, including 138 PCa and 176 non-PCa patients with PSA of <10.0 ng/ml. Serum S2,3PSA levels were presented as mean fluorescence intensity (MFI). Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of total PSA, %fPSA, and S2,3PSA. RESULTS: We determined an MFI cutoff value of 1130 with a sensitivity of 95.0% and specificity of 72.0% for the diagnosis of PCa in the training test. In the validation study, the area under the curve for the detection of PCa with S2,3PSA was 0.84, which was significantly higher than that with PSA or %fPSA. CONCLUSIONS: Although the present study is small and preliminary, these results suggest that the measurement of serum S2,3PSA using a magnetic microbead-based immunoassay may improve the accuracy of early detection of PCa and reduce unnecessary prostate biopsy.

DOI PubMed

Successful local control of recurrent penile cancer treated with a combination of systemic chemotherapy, irradiation, and mohs' paste: a case report.

Naoki Komine, Shintaro Narita, Teruaki Kigure, Hiroshi Tsuruta, Kazuyuki Numakura, Susumu Akihama, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, Hiroshi Nanjo, Tomonori Habuchi

Case reports in oncology   7 ( 2 ) 522 - 7   2014年05月

研究論文（学術雑誌）  

Penile squamous cell carcinoma (pSCC) is a rare disease, making it difficult to establish a standard of care, particularly in the advanced stage. We report a case of pSCC with advanced lymph node metastasis treated with multimodal therapy consisting of combination chemotherapy, irradiation, and chemosurgery using Mohs' zinc chloride-containing paste. An 80-year-old male with a past history of local treatment for penile cancer presented with a large painful inguinal mass with an ulcer and exudates. The patient underwent multimodal treatment with combination chemotherapy, irradiation, and Mohs' paste. The combination chemotherapy consisted of cisplatin, 5-fluorouracil, and docetaxel. The patient received 50-Gy external-beam radiation therapy to the left inguinal region along with daily local treatment with Mohs' paste. After the initiation of treatment, the pain and bleeding in the inguinal region considerably ameliorated. The wound became dry and flattened 20 days after the initiation of chemotherapy. A CT scan showed that the tumor had decreased 70% in diameter 1 month after the initiation of chemotherapy. After the first course of chemotherapy, the patient and his family decided not to continue treatment because of socio-economic reasons. The patient underwent no additional treatments; nevertheless, he had no local progression of the inguinal tumors for 8 months. We report a case of successful local control of recurrent inguinal pSCC treated with multimodal therapy. Combination treatment with taxane-based chemotherapy, external-beam radiation therapy, and Mohs' paste is an option for the management of recurrent pSCC.

DOI PubMed