Papers - Oya, Mototsugu

Do you avoid prostate biopsy in patients with negative findings by mpMRI?

Mototsugu Oya

WORLD JOURNAL OF UROLOGY (SPRINGER)  37 ( 6 ) 1226 - 1226 2019.06

Single Work,  ISSN  0724-4983

TVT術後の難治性切迫性尿失禁に対して仙骨神経電気刺激療法が有効であった1例

篠島 利明, 茂田 啓介, 田中 伸之, 大家 基嗣

日本排尿機能学会誌 ((一社)日本排尿機能学会)  29 ( 2 ) 460 - 463 2019.06

ISSN  1347-6513

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症例は53歳女性。尿パッドを1日10枚必要とする尿失禁にて当科紹介。ストレステスト、Qチップテストともに強陽性だが、OABSSは5点と過活動膀胱症状は軽度であった。腹圧性尿失禁を主とする混合性尿失禁に対して保存的治療を行うも有効でなくTVT手術を施行した。術後にストレステストは陰性化したが切迫性尿失禁が顕著となった。メッシュ露出、尿路感染や残尿を認めず、テープによる尿道の屈曲や圧排等の閉塞所見も明らかでなかった。ウロダイナミクス検査では排尿筋過活動、ならびに低尿流率かつ高排尿筋圧の所見を認めた。過活動膀胱治療薬による症状の改善は乏しい上、抗コリン剤は副作用で継続困難であった。OABSSは14点、切迫性尿失禁の回数は1位平均3回以上であった。また膀胱内圧検査では排尿筋過活動の所見を認めた。TVT術後9ヵ月目に仙骨神経電気刺激療法のリード留置術を施行したところ試験刺激により切迫性失禁が消失、刺激装置植え込み術後も有害事象を認めず、本症例では有効な治療法であった。(著者抄録)

Making Valuable Digital Connections a Priority

Mototsugu Oya

WORLD JOURNAL OF UROLOGY (SPRINGER)  37 ( 6 ) 1226 - 1226 2019.06

Single Work,  ISSN  0724-4983

Are there any significant impacts of patient age and prior treatment profile with docetaxel on the efficacy of cabazitaxel in patient with castration-resistant prostate cancer?

Takeo Kosaka, Hiroshi Hongo, Ryuichi Mizuno, Nobuyuki Tanaka, Toshikazu Takaeda, Kazuhiro Matshumoto, Mototsugu Oya

JOURNAL OF CLINICAL ONCOLOGY (AMER SOC CLINICAL ONCOLOGY)  37 ( 15 )  2019.05

Joint Work,  ISSN  0732-183X

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Efficacy of systemic therapy for metastatic renal cell carcinoma in patients over 75 years of age.

Ryuichi Mizuno, Kimiharu Takamatsu, Nozomi Hayakawa, Takeo Kosaka, Nobuyuki Tanaka, Mototsugu Oya

JOURNAL OF CLINICAL ONCOLOGY (AMER SOC CLINICAL ONCOLOGY)  37 ( 15 )  2019.05

Joint Work,  ISSN  0732-183X

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Physical Parameters, Use of Specific Medical Treatments, Nursing Levels, and Activities of Daily Living Are Potential Indicators for Forgoing Maintenance Hemodialysis.

Yamaguchi N, Yoshida T, Oba M, Nakano R, Saito M, Hirokawa M, Shinmi T, Urasawa C, Oya M

The Keio journal of medicine (KEIO JOURNAL MEDICINE)  69 ( 1 ) 16 - 25 2019.05

Research paper (scientific journal), Joint Work,  ISSN  0022-9717

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Maintenance hemodialysis (HD) therapy is essential for survival in patients with end-stage renal disease (ESRD); however, HD can also be life-threatening in the final stages of ESRD. Currently, no clear indicators and/or biomarkers exist regarding when HD should be forgone. In the present study, we examined temporal changes in multiple clinical parameters, including biochemical data, physical data, the use of specific medical treatments, nursing care levels, and the activities of daily living (ADL) in 47 ESRD patients who underwent maintenance HD and who died in our hospital. We also investigated the status of informed consents regarding the forgoing of HD in these patients. We found that while biochemical parameters were unaltered, physical parameters such as consciousness levels and blood pressure gradually deteriorated during hospitalization. The use of the following specific medical treatments significantly increased over time: vasopressor use, O2 inhalation, and ventilator use. The need for nursing care increased and the ADL levels decreased toward the time of death. Medical doctors gave information regarding forgoing HD to patients and/or their family/relatives in 55% of cases, obtained agreement to forego HD in 45% of cases, and HD was actually foregone in 38% of cases. Most clinical parameters were not significantly different between the patients whose HD sessions were forgone versus those in whom HD was continued, indicating that HD was foregone in the very last stages of life. The results suggest that physical parameters, the use of specific medical treatments, the levels of nursing care, and ADL are potential indicators for forgoing HD in the final stages of ESRD.

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Preserved Kidney Volume, Body Mass Index, and Age Are Significant Preoperative Factors for Predicting Estimated Glomerular Filtration Rate in Living Kidney Donors at 1 Year After Donation.

Kazunobu Shinoda, Shinya Morita, Hirotaka Akita, Fuyuki Washizuka, Satoshi Tamaki, Ryohei Takahashi, Hideyo Oguchi, Kei Sakurabayashi, Toshihide Mizutani, Yusuke Takahashi, Yoji Hyodo, Yoshihiro Itabashi, Masaki Muramatsu, Takeshi Kawamura, Hiroshi Asanuma, Eiji Kikuchi, Masahiro Jinzaki, Nobuyuki Shiraga, Ken Nakagawa, Mototsugu Oya, Seiichiro Shishido, Ken Sakai

Transplantation proceedings (ELSEVIER SCIENCE INC)  51 ( 5 ) 1306 - 1310 2019.05

Research paper (scientific journal), Joint Work,  ISSN  0041-1345

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BACKGROUND: Securing postdonation renal function in the lifetime of donors is a consequential subject for physicians, and precise prediction of postdonation renal function would be considerably beneficial when judging the feasibility of kidney donation. The aim of this study was to investigate the optimum model for predicting eGFR at 1 year after kidney donation. METHODS: We enrolled 101 living-related kidney donors for the development cohort and 44 for the external validation cohort. All patients in each cohort underwent thin-sliced (1 mm) enhanced computed tomography (CT) scans. We excluded individuals with diabetes, glucose intolerance, or albuminuria from this study. We evaluated preoperative factors including age, sex, hypertension, body mass index (BMI), serum uric acid, baseline eGFR, and body surface area (BSA)-adjusted preserved kidney volume (PKV) by using 3-dimensional reconstruction of thin-sliced enhanced CT images. To detect independent predictors, we performed multivariable regression analysis. RESULTS: The multivariable regression analysis revealed that age, BMI, predonation eGFR, and BSA-adjusted PKV were independent predictors of eGFR at 1 year after kidney donation (correlation coefficient: -0.15, -0.476, 0.521, 0.127, respectively). A strong correlation between predicted eGFR and observed eGFR was obtained in the development cohort (r = 0.839, P < .0001). The significance of this predictive model was also confirmed with the external validation cohort (r = 0.797, P < .0001). CONCLUSIONS: Age, BMI, predonation eGFR, and BSA-adjusted PKV may be useful for precisely predicting eGFR at 1 year after living kidney donation and be helpful to determine the feasibility of kidney donation from marginal donors.

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Sub-classification of patients with intermediate-risk metastatic renal cell carcinoma treated with targeted therapy.

Go Kaneko, Suguru Shirotake, Koshiro Nishimoto, Yasumasa Miyazaki, Keiichi Ito, Yujiro Ito, Masayuki Hagiwara, Kent Kanao, Ken Nakagawa, Tetsuo Momma, Tomohiko Asano, Nobuyuki Tanaka, Ryuichi Mizuno, Mototsugu Oya, Masafumi Oyama

Japanese journal of clinical oncology (OXFORD UNIV PRESS)  49 ( 8 ) 780 - 785 2019.05

Research paper (scientific journal), Joint Work,  ISSN  0368-2811

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BACKGROUND: International Metastatic Renal Cell Carcinoma Database Consortium model predicts the outcomes of metastatic renal cell carcinoma stratified into favorable, intermediate, and poor risk groups (FG, IG, and PG, respectively), with approximately 50% of patients being classified as IG. We aimed to generate better risk model based on the sub-classification of IG. METHODS: We analyzed records of 213 consecutive patients receiving molecular targeted therapy. Age, gender, histology, type of initial molecular targeted therapy, serum laboratory data, previous nephrectomy and immunotherapy, and metastatic sites were used for IG sub-stratification. Modified and original models were compared using a concordance correlation coefficient analysis. RESULTS: Median follow-up was 17.8 months. Serum albumin, serum C-reactive protein, and bone metastases were independent predictors of overall survival (OS) in IG. IG was sub-classified into low-, middle-, and high-risk IG according to the number of predictors. The following modified model was developed: modified FG (FG & low-risk IG), modified IG (middle-risk IG), and modified PG (PG & high-risk IG). Concordance indices for original and modified models were 0.68 and 0.73, respectively (P < 0.001). OS was significantly longer in modified PG treated with mammalian target of rapamycin inhibitors as second-line therapy than with tyrosine kinase inhibitors, whereas this was not observed in the original model. CONCLUSIONS: We successfully developed modified IMDC model using a two-step process: the original IMDC plus an IG sub-stratification, and demonstrated that it predicts outcomes more accurately than original model.

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Prognostic value of serum C-reactive protein level prior to second-line treatment in intermediate risk metastatic renal cell carcinoma patients.

Takamatsu K, Mizuno R, Tanaka N, Takeda T, Morita S, Matsumoto K, Kosaka T, Shinojima T, Kikuchi E, Asanuma H, Oyama M, Mikami S, Oya M

International journal of clinical oncology (SPRINGER JAPAN KK)  24 ( 9 ) 1069 - 1074 2019.05

Research paper (scientific journal), Joint Work,  ISSN  1341-9625

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BACKGROUND: The later-line treatment of metastatic renal cell carcinoma (mRCC) has been drastically changing by the development of immune-oncology drugs and molecular targeted treatment in recent years. Although the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is useful for second-line setting, this model has the problem that over 50% patients are classified as intermediate risk group. The aim of this study is to evaluate whether the serum C-reactive protein (CRP) levels prior to second-line treatment could divide intermediate risk group patients. METHODS: We retrospectively reviewed 82 consequent intermediate-risk mRCC patients who received second-line molecular targeted therapy. We classified patients who had serum CRP higher than 0.5 mg/dl in elevated CRP group because the median baseline serum CRP level before second-line treatment was 0.51 mg/dl. We assessed the prognostic impact of serum CRP levels prior to second-line treatment initiation to predict overall survival (OS). RESULTS: Thirty-three out of 82 (40%) patients demonstrated elevated baseline CRP levels. The median OS of elevated and non-elevated CRP group was 11.5 (95% CI 5.4-17.5) and 29.4 (95% CI 25.5-33.5) months, respectively (p = 0.001). The serum CRP elevation could predict prognosis in intermediate risk patients treated with second-line treatment (HR 2.5, 95% CI 1.4-4.2, p = 0.001). CONCLUSIONS: The serum CRP levels after first-line treatment termination could divide intermediate risk group mRCC patients into two prognostic subgroups in second-line targeted treatment setting.

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Castration-resistant prostate cancer patients who had poor response on first androgen deprivation therapy would obtain certain clinical benefit from early docetaxel administration.

Shigeta K, Kosaka T, Hongo H, Yanai Y, Matsumoto K, Morita S, Mizuno R, Shinojima T, Kikuchi E, Oya M

International journal of clinical oncology (SPRINGER JAPAN KK)  24 ( 5 ) 546 - 553 2019.05

Research paper (scientific journal), Joint Work,  ISSN  1341-9625

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BACKGROUND: Our specific aim was to investigate the prognostic value of effective duration of first androgen deprivation therapy (ADT) and to evaluate the clinical impact on early docetaxel administration with oncological outcomes in castration-resistant prostate cancer (CRPC) patients treated with docetaxel. METHODS: We identified 148 mCRPC patients who were treated with 75 mg/m2 docetaxel. We defined 16 months as the threshold for the effective duration of ADT, and defined 12 months as the cut-off time for starting docetaxel from the onset of CRPC. Univariate and multivariate analyses were conducted to investigate the prognostic indicators that influenced the survival outcomes. RESULTS: Overall, 81 (54.7%) patients died. The median 1st ADT response was 22.2 months and the median time interval from CRPC onset to docetaxel treatment was 11.7 months. Multivariate analysis indicated that visceral metastasis, bone metastasis extent of disease (EOD) ≥ 2, and effective duration of ADT < 16 months were the independent prognostic indicators for progression-free survival (PFS). Referring to cancer-specific survival (CSS), besides visceral metastasis and effective duration of ADT < 16 months, late docetaxel treatment ≥ 12 months became as the predictors for poor prognosis. Among the ADT poor-responder group (ADT < 16 months), Kaplan-Meier method showed that 1-year and 2-year CSS rates were 96.0% and 80.0% in the patients who introduced docetaxel in early setting (< 12 months), which were significantly higher than those who introduced in late settings (93.6% and 30.8%, respectively, p < 0.001). CONCLUSION: CRPC patients who had poor response during 1st ADT would obtain survival benefit by introducing docetaxel treatment in early stage.

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Correction to: Castration-resistant prostate cancer patients who had poor response on first androgen deprivation therapy would obtain certain clinical benefit from early docetaxel administration.

Shigeta K, Kosaka T, Hongo H, Yanai Y, Matsumoto K, Morita S, Mizuno R, Shinojima T, Kikuchi E, Oya M

International journal of clinical oncology (SPRINGER JAPAN KK)  24 ( 5 ) 554 - 556 2019.05

Research paper (scientific journal), Joint Work,  ISSN  1341-9625

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The original article can be found online.

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Estimation of fuel particle balance in steady state operation with hydrogen barrier model

Hanada K., Yoshida N., Takagi I, Hirata T., Hatayama A., Okamoto K., Oya Y., Shikama T., Wang Z., Long H., Huang C., Oya M., Idei H., Nagashima Y., Onchi T., Hasegawa M., Nakamura K., Zushi H., Kuroda K., Kawasaki S., Higashijima A., Nagata T., Shimabukuro S., Takase Y., Murakami S., Gao X., Liu H., Qian J., Raman R., Ono M.

NUCLEAR MATERIALS AND ENERGY 19   544 - 549 2019.05

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Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma.

Mikami S, Mizuno R, Kondo T, Shinohara N, Nonomura N, Ozono S, Eto M, Tatsugami K, Takayama T, Matsuyama H, Kishida T, Oya M, Japanese Society of Renal Cancer

Cancer science (WILEY)  110 ( 6 ) 1820 - 1828 2019.04

Research paper (scientific journal), Joint Work,  ISSN  1347-9032

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Recently, immunotherapy based on blocking immune checkpoints with programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) Abs has been introduced for the treatment of advanced clear cell renal cell carcinoma (ccRCC), especially tumors resistant to vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs), but the significance of their expression in the tumor microenvironment is unclear. We investigated these immune checkpoint markers in tumor cells and tumor-infiltrating immune cells (TIIC) in the tumor microenvironment of 100 untreated and 25 VEGF-TKI-treated primary ccRCC tissues. Upregulated expression of PD-1 and PD-L1 by TIIC, and PD-L1 by tumor cells was associated with the histological grade and unfavorable prognosis of RCC patients. High PD-1 and PD-L1 expression by TIIC was associated with a poorer response to VEGF-TKI, whereas PD-L1 expression by tumor cells did not affect the efficacy of the treatment. Furthermore, increased PD-1-positive TIIC and PD-L1-positive TIIC were observed in tumors treated with VEGF-TKIs compared with those in untreated tumors. Our data suggest that PD-1 and PD-L1 expression by TIIC in the tumor microenvironment is involved in treatment resistance, and that sequential therapy with immune checkpoint inhibitors could be a promising therapeutic strategy for ccRCC resistant to VEGF-TKI treatment.

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The prognostic value of zonal origin and extraprostatic extension of prostate cancer for biochemical recurrence after radical prostatectomy.

Takamatsu K, Matsumoto K, Shojo K, Tanaka N, Takeda T, Morita S, Kosaka T, Mizuno R, Shinojima T, Kikuchi E, Asanuma H, Oya M

Urologic oncology (ELSEVIER SCIENCE INC)  37 ( 9 ) 575.e19 - 575.e25 2019.04

Research paper (scientific journal), Joint Work,  ISSN  1078-1439

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OBJECTIVE: To investigate the influence of the zonal origin of prostate cancer and extraprostatic extension on biochemical recurrence (BCR). PATIENTS AND METHODS: We included 638 consecutive patients undergoing radical prostatectomy between 2005 and 2015 who did not receive neoadjuvant/adjuvant therapy. The largest lesion was defined as the index tumor. We categorized each patient into the transition zone (TZ) or peripheral zone (PZ) group based on the lesion where the index tumor existed. Differences in the BCR defined as increasing prostate-specific antigen rate between groups were examined by Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: There were 293 (46%) patients with TZ cancer and 345 (54%) with PZ cancer. TZ cancer was significantly associated with a higher prostate-specific antigen (P = 0.012), lower biopsy positive core rate (P = 0.020), lower pathological Gleason score (P = 0.017), lower pathological stage (P = 0.002), and lower rate of seminal vesicle invasion (P = 0.002). During a median follow-up period of 59 months, 79 patients (12%) developed BCR. In the entire cohort, the PZ origin (hazard ratio: 1.68, P = 0.033) and extraprostatic extension were independent risk factors for BCR. The 3-, 5-, and 7-year BCR-free survival rates of patients with pT3a TZ cancer were 89%, 88%, and 86%, respectively, which were significantly better than those of patients with pT3a PZ cancer (80%, 74%, and 62%, P = 0.012), but were similar to those of the pT2 cancer cohort (92%, 91%, and 90%, P = 0.376). CONCLUSION: TZ cancer had more favorable pathological characteristics and oncological outcome than PZ cancer especially in pT3a cases.

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Small intestinal perforation due to a huge gastrointestinal stromal tumor in a kidney transplant recipient: a case report and literature review.

Ryohei Takahashi, Kazunobu Shinoda, Takashi Ishida, Yasuo Hamamoto, Shinya Morita, Hirotaka Akita, Sotaro Kitaoka, Satoshi Tamaki, Hiroshi Asanuma, Tadashi Yoshida, Masahiro Jinzaki, Kaori Kameyama, Mototsugu Oya

BMC nephrology (BMC)  20 ( 1 ) 120 - 120 2019.04

Research paper (scientific journal), Joint Work,  ISSN  1471-2369

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BACKGROUND: Gastrointestinal stromal tumors (GISTs) in transplant recipients are very rare and only a handful of cases have been reported to date. Here we present the first known case of a huge GIST in a kidney transplant recipient with perforation of small intestine. CASE PRESENTATION: A 64-year-old male presented at our hospital with right colic pain; he had received an ABO incompatible kidney transplant 6 years earlier and was treated with cyclosporine, mycophenolate mofetil, and methylprednisolone. Radiological evaluation revealed a huge (11 cm in diameter) solitary tumor at the small intestine without distant metastasis. The small intestinal wall at the tumor location was perforated one week after diagnosis and the patient underwent emergency surgery. The pathological findings were compatible with GIST and the tumor consisted of spindle cells with positive staining for KIT, CD34, and DOG1 and negative or weak staining for desmin and S-100 protein. A mutation in exon 11 of the c-kit gene was also detected. Cyclosporine was withdrawn and imatinib mesylate (400 mg daily) was introduced. However, thereafter, we needed to decrease the dose at 300 mg daily due to severe hyponatremia. Reduced imatinib treatment was well tolerated and recurrence was not observed for 18 months after surgery. CONCLUSIONS: The occurrence of GISTs in transplant patients is rare, and huge GISTs should be resected immediately after diagnosis because gastrointestinal tract at the tumor site could be perforated. Imatinib treatment is feasible in transplant recipients under immunosuppression, although immunosuppressive drugs metabolized by CYP3A4 should be used at a reduced dosage or withdrawn.

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Sulfasalazine could modulate the CD44v9-xCT system and enhance cisplatin-induced cytotoxic effects in metastatic bladder cancer.

Koichiro Ogihara, Eiji Kikuchi, Shogo Okazaki, Masayuki Hagiwara, Toshikazu Takeda, Kazuhiro Matsumoto, Takeo Kosaka, Shuji Mikami, Hideyuki Saya, Mototsugu Oya

Cancer science (WILEY)  110 ( 4 ) 1431 - 1441 2019.04

Research paper (scientific journal), Joint Work,  ISSN  1347-9032

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The prognostic role of CD44v9, a variant isoform of CD44 and a new cell surface marker of cancer stem cells, remains unclear in bladder cancer (BC) patients. Furthermore, limited information is available on the functional role of sulfasalazine (SSZ), which could modulate the CD44v9-xCT system in order to enhance cisplatin (CDDP)-induced cytotoxicity and inhibit the metastatic potential of BC. CD44v9 protein expression was examined immunohistochemically in 63 muscle invasive BC (MIBC) patients who underwent radical cystectomy. CD44v9 expression was independently associated with disease recurrence and cancer-specific death in MIBC. Cytotoxic effects, glutathione levels, and reactive oxygen species production by SSZ and CD44v9 and phospho-p38MAPK protein expression by SSZ with or without CDDP were assessed in MBT-2V cells with highly metastatic potential. Sulfasalazine exerted cytotoxic effects against MBT-2V cells by inhibiting glutathione levels and inducing the production of reactive oxygen species. Sulfasalazine in combination with CDDP appeared to exert strong cytotoxic effects against MBT-2V cells by inhibiting CD44v9 expression and upregulating phospho-p38MAPK expression. The inhibitory effects of SSZ with or without CDDP were also investigated using an MBT-2V lung metastatic model. In the murine lung metastatic BC model, SSZ significantly prolonged animal survival. Furthermore, the combination of SSZ with CDDP exerted stronger inhibitory effects on the establishment of lung tumor nodules than SSZ or CDDP alone. CD44v9 expression could be a clinical biomarker for predicting poor outcomes in MIBC patients. Sulfasalazine in combination with CDDP has potential as a novel therapy against metastatic BC.

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CD44 VARIANT 9 EXPRESSION IS A NOVEL INDICATOR FOR IDENTIFYING POOR SURVIVAL IN PATIENTS WITH INVASIVE UROTHELIAL CARCINOMA

Koichiro Ogihara, Eiji Kikuchi, Masayuki Hagiwara, Kazuhiro Matsumoto, Shuji Mikami, Hideyuki Saya, Mototsugu Oya

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS)  201 ( 4 ) E899 - E900 2019.04

Joint Work,  ISSN  0022-5347

THE SURVIVAL PREDICTION WITH TIME OF INTRAVESICAL RECURRENCE IN UPPER TRACT UROTHELIAL CARCINOMA

Koichiro Ogihara, Eiji Kikuchi, Keisuke Shigeta, Masayuki Hagiwara, Ryuichi Mizuno, Mototsugu Oya

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS)  201 ( 4 ) E716 - E717 2019.04

Joint Work,  ISSN  0022-5347

SITE SPECIFIC DIFFERENCES IN SURVIVAL AMONG BLADDER, RENAL PELVIC, AND URETERAL UROTHELIAL CARCINOMA PATIENTS TREATED WITH RADICAL SURGERY

Tadatsugu Anno, Eiji Kikuchi, Koichiro Ogihara, Mototsugu Oya

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS)  201 ( 4 ) E720 - E720 2019.04

Joint Work,  ISSN  0022-5347

SIMULATING THE SURVEILLANCE DURATION OF INTRAVESICAL RECURRENCE AFTER RADICAL NEPHROURETERECTOMY: AN INDIVIDUALIZED RISK BASED APPROACH APPLYING THE WEIBULL MODEL

Shigeta Keisuke, Eiji Kikuchi, Masayuki Hagiwara, Takayuki Abe, Koichiro Ogihara, Ryuichi Mizuno, Mototsugu Oya

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS)  201 ( 4 ) E717 - E717 2019.04

Joint Work,  ISSN  0022-5347