論文 - 大家　基嗣

Overall Survival Analysis From a Randomized Phase II Study of Axitinib With or Without Dose Titration in First-Line Metastatic Renal Cell Carcinoma

大家 基嗣

CLINICAL GENITOURINARY CANCER 14 （ 6 ） 499 - 503 2016年12月

研究論文（学術雑誌）,  ISSN  1558-7673

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Influence of physician years on urological journal publication productivity among Japanese urologists

大家 基嗣

SPRINGERPLUS 5   134 - 139 2016年11月

研究論文（学術雑誌）,  ISSN  2193-1801

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Plasma fibrinogen level

Obata Jun, Tanaka Nobuyuki, Mizuno Ryuichi, Kanao Kent, Mikami Shuji, Matsumoto Kazuhiro, Kosaka Takeo, Kikuchi Eiji, Jinzaki Masahiro, Oya Mototsugu

BJU International 118 （ 4 ） 598 - 603 2016年10月

ISSN  1464-4096

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<p>Objectives: To investigate the impact of perioperative plasma fibrinogen level as a biomarker of oncological outcome in localised renal cell carcinoma (RCC). Patients and methods: We consecutively identified 601 patients with localised RCC who underwent curative surgery at a single institution. Subsequent disease recurrence and cancer-specific survival (CSS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, multivariate analysis was performed for these outcomes. Results: Using the defined threshold level of preoperative plasma fibrinogen of ≥420 mg/dL as elevated, we found 56 patients (9.3%) with an elevated plasma fibrinogen level preoperatively. In Kaplan–Meier analysis, there was a significant difference in disease-free survival and CSS rates between patients with and without preoperative plasma fibrinogen levels of ≥420 mg/dL. Multivariate analysis showed that elevated preoperative plasma fibrinogen level was an independent predictor of subsequent disease recurrence and cancer-specific mortality. In a subgroup analysis of the elevated preoperative plasma fibrinogen level group, postoperative normalisation of plasma fibrinogen level was significantly associated with CSS, showing that patients with non-normalised plasma fibrinogen levels tended to have a higher incidence of cancer-specific mortality after surgery. Conclusion: Patients with elevated preoperative plasma fibrinogen levels could be significantly predicted to have subsequent tumour metastasis and cancer-specific mortality, while there was a significant difference in CSS between patients in the normalised and non-normalised postoperative plasma fibrinogen groups. While these are hypothesis generating results, plasma fibrinogen levels may be a useful biomarker due to its low cost and ease of assessment.</p>

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The Preoperative Neutrophil-to-lymphocyte Ratio is a Novel Biomarker for Predicting Worse Clinical Outcomes in Non-muscle Invasive Bladder Cancer Patients with a Previous History of Smoking

Ogihara Koichiro, Kikuchi Eiji, Yuge Kazuyuki, Yanai Yoshinori, Matsumoto Kazuhiro, Miyajima Akira, Asakura Hirotaka, Oya Mototsugu

Annals of Surgical Oncology    1 - 9 2016年09月

ISSN  1068-9265

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<p>Purpose: We speculated that a heterogeneous population of non-muscle invasive bladder cancer (NMIBC) patients with a previous history of smoking may be more precisely stratified by a biomarker associated with tumor aggressiveness and then focused on the preoperative neutrophil-to-lymphocyte ratio (pre-NLR), which is a simple index of systemic inflammation. Methods: Our study population comprised 605 patients initially diagnosed with NMIBC at our 3 institutions between 1995 and 2013. We analyzed the relationships between pre-NLR levels and clinical outcomes in NMIBC. A pre-NLR level of ≥2.2 was defined as elevated according to a calculation by a receiver-operating curve analysis. Results: In overall, a total of 296 patients (48.9 %) had pre-NLR ≥ 2.2, and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. Among 344 patients with a previous history of smoking, 184 (53.5 %) had pre-NLR ≥ 2.2 and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. The 5-year recurrence-free survival and progression-free survival rates in patients with pre-NLR &lt; 2.2 were 66.3 and 97.5 %, respectively, which were significantly higher than those in their counterparts (31.7 and 90.4 %, p &lt; 0.001). In either subgroup of patients who were current smokers (N = 175) or former smokers (N = 169), the pre-NLR level was the only independent risk factor for tumor recurrence. The pre-NLR level was not associated with tumor recurrence or stage progression in 261 nonsmoking patients. Conclusions: Pre-NLR levels may be a useful marker for identifying worse clinical outcomes in NMIBC patients, particularly those with a previous history of smoking.</p>

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Urinary pH Levels are Strongly Associated with Bladder Recurrence After Nephroureterectomy in Upper Tract Urothelial Carcinoma Patients with a Smoking History

Ide Hiroki, Kikuchi Eiji, Hagiwara Masayuki, Hayakawa Nozomi, Hongo Hiroshi, Miyajima Akira, Oya Mototsugu

Annals of Surgical Oncology    1 - 10 2016年09月

ISSN  1068-9265

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<p>Purpose: Aromatic amines, well-known bladder carcinogens, derived from cigarette smoke are activated by acidic urine. We herein determined whether urinary pH levels are associated with bladder recurrence in upper tract urothelial carcinoma patients with a positive smoking history. Methods: A total of 256 upper tract urothelial carcinoma patients who were surgically treated at our institution between 1990 and 2013 were included. Urinary pH levels were defined as the median of at least two consecutive measurements within 1 month of surgery. Results: Ninety-six patients (37.5 %) had pH &lt;5.5 and 160 (62.5 %) had pH ≥5.5, and urinary pH levels were identified as one of the significant predictors for bladder recurrence in univariate but not multivariate Cox regression analysis in overall. In patients with a positive smoking history among those without a history of bladder tumor (N = 110), the 5-year bladder recurrence-free survival rate was 52.5 % in patients with pH ≥5.5, which was significantly higher than that in those with pH &lt;5.5 (25.9 %, p = 0.032). In the multivariate analysis, urinary pH &lt;5.5 (p = 0.022, HR; 1.86) was independently associated with bladder recurrence. No significant difference for bladder recurrence was observed between these two groups in patients with no smoking history among them. Conclusions: Urinary pH &lt;5.5 is associated with an increased risk of bladder recurrence in upper tract urothelial carcinoma patients with a positive smoking history among those without a history of bladder tumor. Modifications to pH for urine alkalization may prevent bladder recurrence.</p>

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Successful low-dose leflunomide treatment for ganciclovir-resistant cytomegalovirus infection with high-level antigenemia in a kidney transplant

Morita Shinya, Shinoda Kazunobu, Tamaki Satoshi, Kono Hidaka, Asanuma Hiroshi, Nakagawa Ken, Oya Mototsugu

Journal of Clinical Virology 82   133 - 138 2016年09月

ISSN  1386-6532

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<p>Ganciclovir-resistant cytomegalovirus infection is sometimes life-threatening for organ transplant recipients. Foscarnet is an alternative, although it may potentially worsen the preexistent impaired renal function. Here we report the case of a successful low-dose leflunomide treatment in a kidney transplant recipient with very high viral replication, who underwent kidney transplantation 10 years before. Administering 10 mg leflunomide daily for 5 months without a loading dose completely cleared the ganciclovir-resistant cytomegalovirus strains.</p>

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Successful low-dose leflunomide treatment for ganciclovir-resistant cytomegalovirus infection with high-level antigenemia in a kidney transplant: A case report and literature review

大家 基嗣

JOURNAL OF CLINICAL VIROLOGY 82   133 - 138 2016年09月

研究論文（学術雑誌）,  ISSN  1386-6532

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Tumor budding, a novel prognostic indicator for predicting stage progression in T1 bladder cancers

大家 基嗣

CANCER SCIENCE 107 （ 9 ） 1338 - 1344 2016年09月

研究論文（学術雑誌）,  ISSN  1347-9032

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External Validation of the MSKCC and IMDC Risk Models in Patients Treated with Targeted Therapy as a First-line and Subsequent Second-line Treatment

Tanaka Nobuyuki, Mizuno Ryuichi, Ito Keiichi, Shirotake Suguru, Yasumizu Yota, Masunaga Ayako, Ito Yujiro, Miyazaki Yasumasa, Hagiwara Masayuki, Kanao Kent, Mikami Shuji, Nakagawa Ken, Momma Tetsuo, Masuda Takeshi, Asano Tomohiko, Oyama Masafumi, Oya Mototsugu

European Urology Focus 2 （ 3 ） 303 - 309 2016年08月

ISSN  2405-4569

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<p>Background Two risk models, the Memorial Sloan Kettering Cancer Center (MSKCC) model and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, have been studied in metastatic renal cell carcinoma (mRCC) treated with targeted therapy. Objective To validate externally the predictive accuracies of the MSKCC and IMDC models for prognosis in mRCC patients treated with first-line and subsequent second-line targeted therapy. Design, setting, and participants A total of 311 patients were assessed retrospectively. Intervention All patients underwent targeted therapy. Outcome measurements and statistical analysis Survival outcomes were assessed using Kaplan-Meier analysis. The predictive ability was evaluated using the c-index. Results and limitations Regarding to the first-line targeted therapy, the 3-yr overall survival (OS) rates of the MSKCC (p &lt; 0.001) and IMDC models (p &lt; 0.001) were 76.2% and 77.3%, respectively, in the favorable-risk group; 46.7% and 47.9%, respectively, in the intermediate-risk group; and 13.4% and 15.6%, respectively, in the poor-risk group. The c-indexes were 0.68 for the MSKCC model and 0.69 for the IMDC model in a first-line setting. Regarding the second-line targeted therapy, the 1-yr OS rates of the MSKCC (p &lt; 0.001) and IMDC models (p &lt; 0.001) were 80.9% and 90.5%, respectively, in the favorable-risk group; 71.4% and 70.6%, respectively, in the intermediate-risk group; and 31.7% and 24.6%, respectively, in the poor-risk group. The c-indexes were 0.66 for the MSKCC model and 0.65 for the IMDC model in the second-line setting. The study is limited by its retrospective nature. Conclusions The results may assist physicians in providing more appropriate patient counseling and imply the need for a future prognostic tool in mRCC treated with targeted therapy. Patient summary Both risk models were useful for the risk stratification in metastatic renal cell carcinoma (mRCC) patients treated with first-line and second-line targeted therapy; however, it might be necessary to further update or optimize the models for our Japanese cohort of mRCC patients.</p>

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Clinical practice patterns for upper tract urothelial carcinoma

Kikuchi Eiji, Oya Mototsugu

Japanese Journal of Clinical Oncology 46 （ 8 ） 768 - 774 2016年08月

ISSN  0368-2811

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<p>Objective: A comprehensive survey has not yet been conducted to investigate care patterns by urologists for the management of upper tract urothelial carcinoma.Methods: We conducted a nationwide survey for urologists treating upper tract urothelial carcinoma patients. The questionnaire was approved by the Japanese Urological Association and sent by mail in February 2014 to 1119 institutes in Japan. We identified 627 responders for this study.Results: Our survey demonstrated that (i) the mean number of radical nephroureterectomy cases per institution in 2013 was 7.6, (ii) the main detecting tool for upper tract urothelial carcinoma is contrast-enhanced computed tomography, (iii) the need for ureteroscopic evaluations is highly dependent on voiding urine cytology results, (iv) 67% of urologists always or often perform radical nephroureterectomy by laparoscopic surgery, (v) more than half of the urologists do not aggressively perform lymph node dissection, (vi) 75% of the urologists perform bladder cuff incision through an extravesical approach, (vii) urologists perform kidney-sparing surgery following various indications, (viii) 59% of the urologists always perform adjuvant systemic chemotherapy for high-risk upper tract urothelial carcinoma patients, (ix) the combination of gemcitabine and cisplatin is the most frequent chemo-regimen for metastatic upper tract urothelial carcinoma, and gemcitabine and cisplatin with dose reductions is also the first choice even in patients with impaired renal function and (x) 10.5% of urologists always or sometimes perform single intravesical chemotherapy immediately after radical nephroureterectomy.Conclusions: The management strategy for upper tract urothelial carcinoma has changed with the introduction of new devices and development of instruments. The lack of clear evidence for relatively uncommon upper tract urothelial carcinoma affects the consistency of its treatment strategies.</p>

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High Absolute Monocyte Count Predicts Poor Clinical Outcome in Patients with Castration-Resistant Prostate Cancer Treated with Docetaxel Chemotherapy

Shigeta Keisuke, Kosaka Takeo, Kitano Shigehisa, Yasumizu Yota, Miyazaki Yasumasa, Mizuno Ryuichi, Shinojima Toshiaki, Kikuchi Eiji, Miyajima Akira, Tanoguchi Hitoshi, Hasegawa Shintaro, Oya Mototsugu

Annals of Surgical Oncology    1 - 8 2016年06月

ISSN  1068-9265

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<p>Background: The association of peripheral monocyte count and prostate cancer progression is not well characterized. Objective: Our aim was to investigate the prognostic value of absolute monocyte count (AMC), which is thought to modulate immune response in the tumor microenvironment, in castration-resistant prostate cancer (CRPC) patients treated with docetaxel chemotherapy. Methods: We retrospectively reviewed the medical records of 214 CRPC patients who received docetaxel therapy and were used as the training and validation set. Docetaxel at a dose of 75 mg/m² was administered every 3 or 4 weeks. Clinicopathological factors and laboratory data were collected to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). Results: In the training set, the median age was 73.0 years, and the median prostate-specific antigen (PSA) value was 31.7 ng/ml at initial treatment. The median OS and PFS were 23.0 months (range 1.20–84.0) and 11.2 months (range 3.6–78.0), respectively. According to multivariable Cox regression analysis, AMC ≥400/uL, PSA level ≥20 ng/ml, and Hb </p>

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Testicular torsion

Asanuma Hiroshi, Oya Mototsugu

  355 - 358 2016年06月

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<p>Testicular torsion occurs most often in the neonatal period and around puberty. Perinatal testicular torsion mostly occurs extravaginally in the prenatal period. On the other hand, pubertal torsion usually occurs intravaginally and requires prompt surgical treatment. The degree of cord twisting and the time between onset of symptoms and detorsion are most important factors to decide early salvage rate of the testis. In order to revive blood supply until operation, consider manual detorsion by rotation from within outward in pubertal boys with intravaginal torsion. If the color of the testis recovers after untwisting it, orchiopexy is performed in the dartos pouch with at least three places of fixation using nonabsorbable sutures. In all cases, contralateral orchiopexy should be done to prevent future torsion. Patients would need a long-term follow-up mainly for fertility and hormonal issues.</p>

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Pyeloplasty

Asanuma Hiroshi, Oya Mototsugu

  301 - 304 2016年06月

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<p>The widespread use of ultrasonography during pregnancy has resulted in a higher detection rate for antenatal hydronephrosis. Ureteropelvic junction obstruction is the most common pathological cause of neonatal hydronephrosis. Surgical indications for this hydronephrosis comprise a decrease of split renal function (&gt;5 %) on renography or increased dilatation on ultrasonography in subsequent studies, or existence symptoms such as breakthrough urinary tract infection or the abdominal pain during follow-up. The Anderson-Hynes dismembered method has been adopted most widely now. It is available in any cases with ureteropelvic junction obstruction due to intrinsic or extrinsic stenosis or high insertion. It is key point for the success of pyeloplasty to anastomose the apex of caudal angle of the renal pelvis and the crotch of the spatulated ureter with five sutures as knock stitch and come the funnel shape with the double pigtail stent finally. Remove the stent 2-3 months postoperatively under cystoscopy. Evaluate renal pelvic dilatation and split renal function 6 months postoperatively. Success pyeloplasty should be defined as no symptom, reduced pelvic dilatation, and stable or improved split renal function compared to preoperative condition.</p>

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Suprapubic cystostomy and vesicocutaneostomy

Asanuma Hiroshi, Oya Mototsugu

  315 - 319 2016年06月

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<p>Suprapubic cystostomy and vesicocutaneostomy continue to be used frequently as temporary vesical diversion in pediatric patients who develop urethral obstruction (posterior urethral valves, cloacal anomalies, urethral trauma), recurrent urinary tract infection with severe vesicoureteral reflux, or neurogenic bladder associated with spina bifida not responsive to clean intermittent catheterization. Vesicocutaneostomy is more appropriate for long-term usage because of no catheter. Suprapubic cystostomy is usually inserted into the bladder using Seldinger method in young children. Blocksom's method is easier and has been widely used in vesicocuta- neostomy. It is important to evaluate bladder capacity and superior border of full bladder for adequate stoma marking and not to place the stoma in a position which is too large and too low to prevent bladder prolapse. The decision to close a vesicocutaneostomy should be made only once the bladder function has been assessed and permanent therapy has been planned.</p>

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Patient age was an independent predictor of cancer-specific survival in male patients with upper tract urothelial carcinoma treated by radical nephroureterectomy

Kobayashi Hiroaki, Kikuchi Eiji, Tanaka Nobuyuki, Shirotake Suguru, Miyazaki Yasumasa, Ide Hiroki, Obata Jun, Hoshino Katsura, Matsumoto Kazuhiro, Kaneko Gou, Hagiwara Masayuki, Kosaka Takeo, Oyama Masafumi, Nakajima Yosuke, Oya Mototsugu

Japanese Journal of Clinical Oncology 46 （ 6 ） 554 - 559 2016年06月

ISSN  0368-2811

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<p>Objective: We hypothesized that there may be a prognostic difference in age between the genders and evaluated the influence of gender-adjusted age on prognosis in upper tract urothelial carcinoma patients. Methods: A total of 839 patients with upper tract urothelial carcinoma from a retrospective multi-institutional cohort were included. The patients were divided into four groups consisting of males (N = 610) and females (N = 229) according to age ((i) &lt;60 years, (ii) 60-69.9 years, (iii) 70-79.9 years and (iv) ≥ 80 years), and we evaluated the associations of patient age and gender with clinicopathological features and oncological outcomes following radical nephroureterectomy. The median follow-up duration was 34 months. Results: Disease recurrence occurred in 249 patients and 192 patients died of upper tract urothelial carcinoma. The 3-year cancer-specific survival rates were (i) 84.3%, (ii) 80.2%, (iii) 77.1% and (iv) 71.5% in the entire patient population (P = 0.001); (i) 84.5%, (ii) 81.1%, (iii) 76.8% and (iv) 69.7% in males (P = 0.010); and (i) 83.3%, (ii) 76.9%, (iii) 77.7% and (iv) 72.9% in females (P = 0.287), respectively. No significant differences between disease recurrence and age were found in the male or female population. In multivariate analysis, older age was an independent predictor of cancer-specific survival, in addition to advanced pT stage, the presence of lymphovascular invasion and lymph node involvement in males. In contrast, age was not associated with cancer-specific survival in females, while high grade, advanced pT stage, the presence of lymph node involvement and multifocal tumor were independent predictors. Conclusion: The results indicate that gender-adjusted age might be a new prognostic factor in upper tract urothelial carcinoma patients.</p>

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IJU this issue

Oya Mototsugu

International Journal of Urology 23 （ 6 ） 453 2016年06月

ISSN  0919-8172

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Technical improvement using a three-dimensional video system for laparoscopic partial nephrectomy

Komatsuda Akari, Matsumoto Kazuhiro, Miyajima Akira, Kaneko Gou, Mizuno Ryuichi, Kikuchi Eiji, Oya Mototsugu

Asian Pacific Journal of Cancer Prevention 17 （ 5 ） 2475 - 2478 2016年06月

ISSN  1513-7368

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<p>Background: Laparoscopic partial nephrectomy is one of the major surgical techniques for small renal masses. However, it is difficult to manage cutting and suturing procedures within acceptable time periods. To overcome this difficulty, we applied a three-dimensional (3D) video system with laparoscopic partial nephrectomy, and evaluated its utility. Materials and Methods: We retrospectively enrolled 31 patients who underwent laparoscopic partial nephrectomy between November 2009 and June 2014. A conventional two-dimensional (2D) video system was used in 20 patients, and a 3D video system in 11. Patient characteristics and video system type (2D or 3D) were recorded, and correlations with perioperative outcomes were analyzed. Results: Mean age of the patients was 55.8±12.4, mean body mass index was 25.7±3.9 kg/m², mean tumor size was 2.0±0.8 cm, mean R.E.N.A.L nephrometry score was 6.9±1.9, and clinical stage was T1a in all patients. There were no significant differences in operative time (p=0.348), pneumoperitoneum time (p=0.322), cutting time (p=0.493), estimated blood loss (p=0.335), and Clavien grade of &gt; II complication rate (p=0.719) between the two groups. However, warm ischemic time was significantly shorter in the 3D group than the 2D group (16.1 min vs. 21.2min, p=0.021), which resulted from short suturing time (9.1 min vs. 15.2 min, p=0.008). No open conversion occurred in either group. Conclusions: A 3D video system allows the shortening of warm ischemic time in laparoscopic partial nephrectomy and thus may be useful in improving the procedure.</p>

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A prospective longitudinal survey of erectile function status in symptomatic benign prostatic hyperplasia patients treated with dutasteride

大家 基嗣

AGING MALE 19 （ 2 ） 111 - 116 2016年06月

研究論文（学術雑誌）,  ISSN  1368-5538

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Stem cell biology in prostate cancer

Kosaka Takeo, Oya Mototsugu

Nihon rinsho. Japanese journal of clinical medicine 74   65 - 70 2016年05月

ISSN  0047-1852

Risk factors in localized prostate cancer

Matsumoto Kazuhiro, Miyajima Akira, Oya Mototsugu

Nihon rinsho. Japanese journal of clinical medicine 74   161 - 165 2016年05月

ISSN  0047-1852