Details of a Researcher - Matsumoto, Kazuhiro

Papers - Matsumoto, Kazuhiro

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Anemia in patients ≥ 75 years with metastatic clear cell renal cell carcinoma: an important poor prognostic factor in the international metastatic renal cell carcinoma database consortium model

Mizuno R., Yasumizu Y., Tanaka N., Takeda T., Morita S., Matsumoto K., Kosaka T., Asanuma H., Oya M.

BMC Urology (BMC Urology) 24 ( 1 ) 2024.12

Background: Due to an increase in life expectancy, the incidence of metastatic renal cell carcinoma (mRCC) in patients aged ≥75 years has been increasing. In this study we investigated the characteristics before treatment and the outcomes of systemic therapies for patients aged ≥75 years with mRCC and compared the results with those for patients aged < 75 years in order to determine whether differences in age influenced survival. Methods: A total of 206 consecutive Japanese patients with mRCC, including 47 patients aged ≥75 years, who received systemic therapy were included. Clinical data from medical records were retrieved and analyzed retrospectively. Survival analyses were determined using a Kaplan–Meier method, and analyzed with a log-rank test. Results: Elderly patients categorized as favorable risk group based on the International Metastatic RCC Database Consortium (IMDC) stratification system were significantly lower. Among IMDC risk factors, the rate of anemia was significantly higher in elderly patients. No statistically significant benefit in progression free survival for first and second line treatment was observed, whereas improvements in overall survival as well as cancer specific survival were seen in patients aged < 75 years. Conclusions: For mRCC patients aged ≥75 years, a higher proportion of base line anemia, which resulted in higher rates of IMDC intermediate/poor risk, would be responsible for shorter OS/CSS. Furthermore, mRCC patients aged ≥75 years tend to receive BSC instead of second line active treatment. Overcoming under-treatment in elderly patients might help to prolong survival in mRCC.

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Prognostic significance of serum testosterone level in patients with castration-resistant prostate cancer treated with cabazitaxel

Fujiwara S., Kosaka T., Nishimoto Y., Kamisawa K., Watanabe K., Baba Y., Takeda T., Matsumoto K., Oya M.

Prostate (Prostate) 84 ( 1 ) 25 - 31 2024.01

ISSN 02704137

Background: Serum testosterone level is a potential prognostic marker for castration-resistant prostate cancer. However, its role as a prognostic marker in cabazitaxel chemotherapy remains unclear. This study aimed to elucidate the clinical significance of serum testosterone levels before cabazitaxel chemotherapy. Methods: This single-institution, retrospective study included 47 patients with metastatic castration-resistant prostate cancer (mCRPC) who received cabazitaxel therapy. Serum testosterone levels were measured before the initiation of cabazitaxel therapy. Results: Progression-free survival and overall survival (OS) were not significantly different between patients with high and low serum testosterone levels. Analysis of patients aged <70 years revealed that those with high serum testosterone levels (total testosterone level > 0.055 ng/mL) had significantly longer OS than those with low serum testosterone levels (total testosterone level < 0.055 ng/mL, p = 0.012). Multivariate analysis revealed that low serum testosterone levels (hazard ratio [HR] = 11.874, 95% confidence interval [CI] 2.076–67.953, p = 0.005) and high prostate-specific antigen levels (HR = 18.051, 95% CI 2.462–132.347, p = 0.004) in the pretreatment phase were independent prognostic factors for OS in patients receiving cabazitaxel therapy. Conclusions: Serum testosterone level may be a prognostic marker for cabazitaxel therapy in patients with mCRPC who are younger than 70 years, and high serum testosterone levels may lead to longer survival.

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Prognostic impact of tumor ureteral invasion on recurrence after radical cystectomy

Saito T., Matsumoto K., Tanaka N., Fukumoto K., Yasumizu Y., Takeda T., Morita S., Kosaka T., Mizuno R., Asanuma H., Hara S., Oya M.

International Urology and Nephrology (International Urology and Nephrology) 56 ( 1 ) 129 - 135 2024.01

ISSN 03011623

Purpose: Several preoperative factors have been suggested to be risk factors of disease recurrence after radical cystectomy. There is no study focusing on the impact on prognosis of bladder tumor ureteral invasion in preoperative imaging. Methods: The study population consisted of 136 patients, all of whom underwent radical cystectomy during the period between 2007–2019. We excluded patients with concurrent or a history of upper tract urothelial carcinoma and who underwent radical cystectomy for other cancers or nononcologic reasons. The starting point of this study was the timing of neoadjuvant chemotherapy or radical cystectomy and the endpoint was the timing of disease recurrence. To identify the factors influencing recurrence, univariate and multivariate analyses were performed using the Cox proportional hazard model. Recurrence-free survival curves were constructed using the Kaplan–Meier method. Results: Ureteral invasion was observed in 20 (14.7%) patients. Disease recurrence was observed in 11 (55.0%) of 20 ureteral invasion positive patients and 35 (30.2%) of 116 ureteral invasion negative patients, respectively. In the ureteral invasion positive group, clinical T and N stage were higher and hydronephrosis were more common than in the ureteral invasion negative group. According to the multivariate analysis, ureteral invasion (hazard ratio: 2.307, p = 0.016) and clinical N stage ≥ 1 (hazard ratio: 2.140, p = 0.028) were independent risk factors for postoperative recurrence. In the ureteral invasion positive group, more local recurrences were observed. Conclusion: This study suggested that ureteral invasion in preoperative imaging is a significant risk factor for postoperative recurrence.

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ASO Visual Abstract: Long-Term Prognosis and Treatment Strategy of Persistent PSA After Radical Prostatectomy

Komori T., Matsumoto K., Kosaka T., Takeda T., Kamitani R., Yasumizu Y., Tanaka N., Morita S., Mizuno R., Asanuma H., Oya M.

Annals of surgical oncology (Annals of surgical oncology) 30 ( 11 ) 2023.10

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Long-Term Prognosis and Treatment Strategy of Persistent PSA After Radical Prostatectomy

Komori T., Matsumoto K., Kosaka T., Takeda T., Kamitani R., Yasumizu Y., Tanaka N., Morita S., Mizuno R., Asanuma H., Oya M.

Annals of Surgical Oncology (Annals of Surgical Oncology) 30 ( 11 ) 6936 - 6942 2023.10

ISSN 10689265

Purpose: Prostate-specific antigen (PSA) is thought to be undetectable (< 0.1 ng/mL) after radical prostatectomy (RP), and persistent PSA (≥ 0.1 ng/mL) is considered a failure of curative treatment. Materials and Methods: The study population consisted of 135 patients, all of whom underwent RP for localized prostate cancer, and developed persistent PSA. We set the starting point at the timing of RP, and the endpoints were the development of castration-resistant prostate cancer (CRPC) and cancer-specific survival. Results: Salvage radiation therapy (RT) and androgen deprivation therapy (ADT) were performed in 53 (39.3%) and 64 (47.4%) patients, respectively. Eighteen (13.3%) patients didn't receive any salvage treatment. During the median follow-up of 10.1 years, CRPC was observed in 23 patients, and 6 patients died due to prostate cancer. Kaplan-Meier curves demonstrated the 15-year CRPC-free and cancer-specific survivals were 79.5% and 92.7%, respectively. Cox multivariate analysis demonstrated that seminal vesicle invasion (SVI) (p = 0.007) and nadir PSA ≥1.0 ng/mL (p = 0.002) were independent risk factors for CRPC. Salvage RT demonstrated better cancer control (the 10-and 15-year CRPC-free survival was 94.1% and 94.1%) compared to ADT (75.9% and 58.5%, p = 0.017) after 1:1 propensity score matching. Conclusions: SVI and nadir PSA ≥1.0 ng/mL are independent risk factors for CRPC in patients with persistent PSA after RP. Salvage RT is considered to be the optimal treatment for this condition.

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Factors affecting the selection of eligible candidates for focal therapy for prostate cancer

Takeda T., Narita K., Yasumizu Y., Tanaka N., Matsumoto K., Morita S., Kosaka T., Mizuno R., Asanuma H., Jinzaki M., Oya M.

World Journal of Urology (World Journal of Urology) 41 ( 7 ) 1821 - 1827 2023.07

ISSN 07244983

Purpose: Focal therapy (FT) is a treatment modality for prostate cancer that aims to reduce side effects. However, it remains difficult to select eligible candidates. We herein examined eligibility factors for hemi-ablative FT for prostate cancer. Methods: We identified 412 patients who were diagnosed with unilateral prostate cancer by biopsy and had undergone radical prostatectomy between 2009 and 2018. Among these patients, 111 underwent MRI before biopsy, had 10–20 core biopsies performed, and did not receive other treatments before surgery. Fifty-seven patients with prostate-specific antigen ≥ 15 ng/mL and biopsy Gleason score (GS) ≥ 4 + 3 were excluded. The remaining 54 patients were evaluated. Both lobes of the prostate were scored using Prostate Imaging Reporting and Data System version 2 on MRI. Ineligible patients for FT were defined as those with ≥ 0.5 mL GS6 or GS ≥ 3 + 4 in the biopsy-negative lobe, ≥ pT3, or lymph node involvement. Selected predictors of eligibility for hemi-ablative FT were analyzed. Results: Among our cohort of 54 patients, 29 (53.7%) were eligible for hemi-ablative FT. A multivariate analysis identified a PI-RADS score < 3 in the biopsy-negative lobe (p = 0.016) as an independent predictor of eligibility for FT. Thirteen out of 25 ineligible patients had GS ≥ 3 + 4 tumors in the biopsy-negative lobe, half of whom (6/13) also had a PI-RADS score < 3 in the biopsy-negative lobe. Conclusion: The PI-RADS score in the biopsy-negative lobe may be important in the selection of eligible candidates for FT. The findings of this study will help reduce missed significant prostate cancers and improve FT outcomes.

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Prognostic role of the innate immune signature CD163 and “eat me” signal calreticulin in clear cell renal cell carcinoma

Anno T., Tanaka N., Takamatsu K., Hakozaki K., Kufukihara R., Baba Y., Takeda T., Matsumoto K., Morita S., Kosaka T., Mikami S., Nishihara H., Mizuno R., Oya M.

Cancer Immunology, Immunotherapy (Cancer Immunology, Immunotherapy) 72 ( 6 ) 1779 - 1788 2023.06

ISSN 03407004

The effects of the innate immune status on patients with clear cell renal cell carcinoma (ccRCC) currently remain unknown. We herein provided more extensive information about the inner landscape of immunobiology of ccRCC. In total, 260 ccRCC samples from three different cohorts consisting of 213 primary tumors and 47 metastases were obtained. We focused on five representative innate immune signatures, CD68, CD163, the “eat me” signal calreticulin, the “don't eat me” signal CD47, and signal regulatory protein α, and examined the role of each signature by quantitative immunohistochemistry. We then conducted an integrated genome mutation analysis by next-generation sequencing. Among the five markers, high CD163 and low calreticulin expression levels were prognostic in ccRCC. The application of a new risk model based on CD163 and calreticulin levels, named the innate immune risk group (high risk: high-CD163/low calreticulin, intermediate risk: high-CD163/high calreticulin or low CD163/low calreticulin, low risk: low-CD163/high calreticulin), enabled the sequential stratification of patient prognosis and malignancy. Although organ-specific differences were observed, metastases appeared to have a higher innate immune risk, particularly in the lungs, with 50% of ccRCC metastases being classified into the high-risk group according to our risk score. An analysis of genomic alterations based on the innate immune risk group revealed that alterations in the TP53/Cell cycle pathway were highly prevalent in high-risk ccRCC patients according to two innate immune signatures CD163 and calreticulin. The present results provide insights into the immune-genomic biology of ccRCC tumors for innate immunity and will contribute to future therapies focused on the innate immune system in solid cancers.

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Strategy for PSA progression in patients undergoing salvage radiation for biochemical recurrence after radical prostatectomy

Saito T., Matsumoto K., Kosaka T., Yasumizu Y., Tanaka N., Takeda T., Morita S., Mizuno R., Asanuma H., Oya M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 28 ( 5 ) 707 - 715 2023.05

ISSN 13419625

Background: The treatment strategy for prostate-specific antigen (PSA) progression in patients who receive salvage radiation therapy (RT) for biochemical recurrence (BCR) after radical prostatectomy (RP) is salvage androgen deprivation therapy (ADT). However, its optimal timing is highly controversial. Methods: The study sample consisted of 77 men who underwent RP, received salvage RT against BCR, and underwent salvage ADT for PSA progression. The endpoint of this study was development to castration-resistant prostate cancer (CRPC), from the start of salvage RT. Results: The median follow-up time was 9.5 years, and 20 patients experienced CRPC. The multivariable analysis identified PSA-doubling time (PSA-DT) ≤ 12 months (hazard ratio, 3.5) and seminal vesicle invasion (SVI) (hazard ratio, 4.4) as independent risk factors. We defined the high-risk and low-risk groups as those with one or two risk factors and no risk factors, respectively. In the high-risk group, a significant difference in time to CRPC was observed between patients who received salvage ADT at PSA ≤ 1.0 ng/mL (n = 8) and at > 1.0 ng/mL (n = 27) (10-year non-CRPC rate: 100.0% vs. 46.3%, respectively). In contrast, in the low-risk group, no significant difference in CRPC-free survival was observed between patients who received salvage ADT at PSA ≤ 1.0 ng/mL (n = 14) and at > 1.0 ng/mL (n = 28) (10-year non-CRPC rate: 86.4% vs. 80.8%, respectively). Conclusion: In high-risk patients (PSA-DT ≤ 12 months and/or SVI), salvage ADT for PSA progression after salvage RT should be started before the PSA levels exceed 1.0 ng/mL.

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Single-Cell Phenotyping of CD73 Expression Reveals the Diversity of the Tumor Immune Microenvironment and Reflects the Prognosis of Bladder Cancer

Izawa M., Tanaka N., Murakami T., Anno T., Teranishi Y., Takamatsu K., Mikami S., Kakimi K., Imamura T., Matsumoto K., Oya M.

Laboratory investigation; a journal of technical methods and pathology (Laboratory investigation; a journal of technical methods and pathology) 103 ( 4 ) 2023.04

The cutting edge of cancer immunotherapy extends to ecto-5'-nucleotidase (CD73), a cell membrane enzyme that targets the metabolism of extracellular adenosine. We herein focused on the expression of CD73 to clarify the state of CD73 positivity in cancer immunity and tumor microenvironment, thereby revealing a new survival predictor for patients with bladder cancer (BCa). We used clinical tissue microarrays of human BCa and simultaneously performed the fluorescent staining of cell type-specific markers (CD3, CD8, Foxp3, programmed cell death protein 1, and programmed death-ligand 1 [PD-L1]) and CD73 together with DAPI for nuclear staining. In total, 156 participants were included. Multiplexed cellular imaging revealed a unique interaction between CD73 expression and CD8+ cytotoxic T cells (CTLs) and Foxp3+ regulatory T (Treg) cells in human BCa, showing the high infiltration of CD8+CD73+ CTLs and Foxp3+CD73+ Treg cells in tumors to be associated with tumorigenesis and poor prognosis in BCa. Interestingly, from a biomarker perspective, the high infiltration of CD73+ Treg cells in tumors was identified as an independent risk factor for overall survival in addition to clinicopathologic features. Regarding the relationship between immune checkpoint molecules and CD73 expression, both CD73+ CTLs and CD73+ Treg cells tended to coexpress programmed cell death protein 1 as tumor invasiveness and nuclear grade increased. Additionally, they may occupy a spatial niche located distantly from PD-L1+ cells in tumors to interfere less with the cancerous effects of PD-L1+ cells. In conclusion, the present results on the status of CD73 in cancer immunity suggest that CD73 expression on specific T-cell types has a negative immunoregulatory function. These findings may provide further insights into the immunobiological landscape of BCa, which may be translationally linked to improvements in future immunotherapy practice.

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IDH2 stabilizes HIF-1α-induced metabolic reprogramming and promotes chemoresistance in urothelial cancer

Shigeta K., Hasegawa M., Hishiki T., Naito Y., Baba Y., Mikami S., Matsumoto K., Mizuno R., Miyajima A., Kikuchi E., Saya H., Kosaka T., Oya M.

EMBO Journal (EMBO Journal) 42 ( 4 ) 2023.02

ISSN 02614189

Drug resistance contributes to poor therapeutic response in urothelial carcinoma (UC). Metabolomic analysis suggested metabolic reprogramming in gemcitabine-resistant urothelial carcinoma cells, whereby increased aerobic glycolysis and metabolic stimulation of the pentose phosphate pathway (PPP) promoted pyrimidine biosynthesis to increase the production of the gemcitabine competitor deoxycytidine triphosphate (dCTP) that diminishes its therapeutic effect. Furthermore, we observed that gain-of-function of isocitrate dehydrogenase 2 (IDH2) induced reductive glutamine metabolism to stabilize Hif-1α expression and consequently stimulate aerobic glycolysis and PPP bypass in gemcitabine-resistant UC cells. Interestingly, IDH2-mediated metabolic reprogramming also caused cross resistance to CDDP, by elevating the antioxidant defense via increased NADPH and glutathione production. Downregulation or pharmacological suppression of IDH2 restored chemosensitivity. Since the expression of key metabolic enzymes, such as TIGAR, TKT, and CTPS1, were affected by IDH2-mediated metabolic reprogramming and related to poor prognosis in patients, IDH2 might become a new therapeutic target for restoring chemosensitivity in chemo-resistant urothelial carcinoma.

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Site-Specific Differences in PD-1 Blockade Success and Biomarkers in Urothelial Carcinoma Treated with Pembrolizumab

Umeda K., Tanaka N., Yasumizu Y., Takeda T., Matsumoto K., Morita S., Kosaka T., Mizuno R., Oya M.

Clinical Genitourinary Cancer (Clinical Genitourinary Cancer) 21 ( 1 ) 128 - 135 2023.02

ISSN 15587673

Introduction: Since tumors in different human organs may have different tumor microenvironments, we evaluate time-course changes in all tumor locations after pembrolizumab treatment in urothelial carcinoma (UC) to examine the differences in efficacy of pembrolizumab per organ. Further, we uncover the usefulness of inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), CRP, and kinetics of these markers to predict pembrolizumab success and relation to overall survival (OS) in UC. Patients and Methods: A total of 115 cancerous lesions from 44 UC patients were measurable based on RECIST 1.1 criteria. The serum CRP and NLR levels were measured at baseline prior to pembrolizumab treatment and at least every 3 weeks just prior to pembrolizumab administration. Results: Site-specific success (ie, patients with CR/PR/SD by RESIST 1.1) rates for pembrolizumab treatments were as follows: primary tumors: 67%, lymph node: 70%, lung: 44%, liver: 40%, and peritoneal metastasis: 56%. Focusing on the major metastasis sites, lymph nodes and lungs, we examined the relationships between NLR, CRP, or that kinetics and pembrolizumab success. In lymph nodes, both early NLR kinetics (P = .005) and CRP kinetics (P = .035) was a predictor for pembrolizumab success. On the other hand, none of 4 was not in lung metastases. Regarding to the mortality, the multivariate analysis revealed that early NLR kinetics was a prognostic biomarker for OS among the 4, independent of performance status and liver metastasis. Conclusion: We revealed that site-specific pembrolizumab success in UC. Early NLR kinetics was a predictor for lymph node pembrolizumab success and OS in our cohorts.

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Androgen deprivation therapy duration is significantly associated with Testosterone recovery in Japanese patients with prostate cancer

Arai M., Kosaka T., Yasumizu Y., Takeda T., Matsumoto K., Oya M.

International Journal of Urology (International Journal of Urology) 30 ( 2 ) 235 - 239 2023.02

ISSN 09198172

Objective: Due to the fear generated by COVID-19 in Spring 2020, many patients postponed their scheduled outpatient visits. To differentiate those patients with prostate cancer (PCa) whose androgen deprivation therapy (ADT) injection treatment can be postponed, we investigated the characteristics of testosterone (T) recovery in Japanese patients after they received combined ADT and radiation therapy (RT). Methods: We included 81 patients with PCa treated with ADT and RT at Keio University Hospital from January 2013 to December 2018. T-recovery was defined as the time interval between the last ADT injection and 3–6 months after T-normalization. The Kaplan–Meier method was used to estimate time to T-recovery. Cox proportional hazards models identified T-recovery predictors. Results: The 50% cumulative incidence of T-recovery was 7.0 months for the 6-short-term group (defined as patients having ≤6 months of ADT therapy) versus 13.0 months for the 6-long-term group (>6 months of therapy) (p < 0.001). The incidence was 7.0 months for the 12 short-term-ADT (ST) group versus 18.0 months for the 12 long-term-ADT (LT) group (p < 0.001). Multivariate analysis revealed that a shorter duration of ADT was associated with a shorter time to T-recovery (hazard ratio, 0.253; 95% CI, 0.138–0.465; p < 0.001). No other factors were significant predictors of T-recovery. Conclusion: Androgen deprivation therapy duration is significantly associated with T-recovery in Japanese patients with PCa. If a patient undergoes ADT for more than 6 or 12 months, it is possible to postpone their outpatient visits for 13 and 18 months, respectively.

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Predictors of urinary function recovery after laparoscopic and robot-assisted radical prostatectomy

Hakozaki K., Takeda T., Yasumizu Y., Tanaka N., Matsumoto K., Morita S., Kosaka T., Mizuno R., Asanuma H., Oya M.

International Braz J Urol (International Braz J Urol) 49 ( 1 ) 50 - 60 2023.01

ISSN 16775538

Introduction: Even in the era of laparoscopic radical prostatectomy (LRP) and robot- -assisted laparoscopic radical prostatectomy (RALP), we sometimes encounter patients with severe urinary incontinence after surgery. The aim of the present study was to identify predictors of urinary continence recovery among patients with urinary incontinence immediately after surgery (UIIAS). Materials and Methods: We identified 274 patients with clinically localized prostate cancer who underwent LRP and RALP between 2011 and 2018. UIIAS was defined as a urine loss ratio > 0.15 on the first day of urethral catheter removal. Urinary continence recovery was defined as using ≤ 1 pad/day one year after surgery. In the present study, we evaluated factors affecting urinary function recovery one year after surgery among patients with urinary incontinence immediately after LRP and RALP. Results: UIIAS was observed in 191 out of 274 patients (69.7%). A multivariate analysis identified age (< 65 years, p = 0.015) as an independent predictor affecting immediate urinary continence. Among 191 incontinent patients, urinary continence one year after surgery improved in 153 (80.1%). A multivariate analysis identified age (< 65 years, p = 0.003) and estimated blood loss (≥ 100 mL, p = 0.044) as independent predictors affecting urinary continence recovery one year after surgery. Conclusion: The present results suggest that younger patients and patients with higher intraoperative blood loss recover urinary continence one year after surgery even if they are incontinent immediately after surgery.

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Evaluation of prognostic factors and treatment options for renal angiosarcoma: A retrospective analysis of 113 reported cases

Kamitani R., Matsumoto K., Takeda T., Mizuno R., Oya M.

European Journal of Surgical Oncology (European Journal of Surgical Oncology) 49 ( 1 ) 263 - 270 2023.01

ISSN 07487983

Background: Primary renal angiosarcoma (PRA) is an extremely rare and aggressive neoplasm. Indeed, due to its rarity, established clinical guidelines for PRA have not yet been established. In this study, we attempted to investigate its prognostic factors and treatment options. Methods: We systematically searched for articles describing PRA that had been published up until December 2021. The final cohort included 113 patients in 103 articles. The starting point of this study was the time of diagnosis and the end point was the time of recurrence and disease-specific mortality. Results: Metastasis at diagnosis was associated with poorer disease-specific survival (DSS) (p = 0.001). Tumors of more than 5 cm had poorer DSS than tumors of 5 cm or less (p < 0.001). Multivariate analysis demonstrated that primary metastatic status, and tumor size were independent prognostic factors. In cases of localized PRA, tumor sizes exceeding 5 cm had also prognostic significance for recurrence-free survival (RFS) and DSS. Surgical margins, postoperative radiation, and postoperative systemic therapy were not associated with prognoses. However, in a subgroup analysis of tumors exceeding 5 cm, postoperative radiation therapy improved RFS and DSS (p = 0.022 and p = 0.031, respectively). In cases of metastatic PRA, systemic therapy improved DSS (p < 0.001). Conclusion: We identified several prognostic factors for PRA. Among them, primary metastatic status and tumor size exceeding 5 cm were selected as independent prognostic factors. Postoperative radiation therapy for large, localized PRA and systemic therapy for recurrent and metastatic PRA might be a treatment option.

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Predictors of renal function after adrenalectomy in patients with Cushing or subclinical Cushing syndrome

Kufukihara R., Takeda T., Hakozaki K., Yasumizu Y., Tanaka N., Matsumoto K., Morita S., Kosaka T., Mizuno R., Asanuma H., Miyashita K., Kurihara I., Oya M.

International Journal of Urology (International Journal of Urology) 29 ( 12 ) 1447 - 1454 2022.12

ISSN 09198172

Purpose: The postoperative course of renal function remains unclear in Cushing syndrome. We examined changes in renal function after adrenalectomy in patients with Cushing syndrome and attempted to identify predictors of renal impairment. Methods: The study population comprised 76 patients who underwent adrenalectomy for Cushing and subclinical Cushing syndrome between 2001 and 2018. Renal function and other factors were evaluated pre-operation, at 1 postoperative month, and 1 postoperative year. We defined a ≥10% decrease in the estimated glomerular filtration rate at 1 postoperative year as renal impairment, and predictors associated with this reduction were investigated. The relationship between renal function and steroid replacement after surgery was also examined. Results: Mean pre-operative estimated glomerular filtration rate was 82.2 ml/min/1.73 m2. While mean estimated glomerular filtration rate was significantly lower at 1 postoperative month than the pre-operative value (71.7 ml/min/1.73 m2 [89.1%], p < 0.001), no significant differences were observed between 1 postoperative year and pre-operation (79.5 ml/min/1.73 m2 [97.6%], p = 0.108). Twenty-six patients (34.2%) developed renal impairment. A multivariate analysis identified a low pre-operative adrenocorticotropic hormone level as an independent predictor of renal impairment (odds ratio 6.30, p = 0.031). Among 43 patients with available records of steroid replacement history, 18 (41.9%) developed renal impairment. The ratio of patients with a reduced steroid replacement dose at 1 postoperative month was significantly lower among patients with renal impairment than those without (22.2% vs. 56.0%, p = 0.027). Conclusions: The pre-operative adrenocorticotropic hormone level was a predictor of renal function after adrenalectomy in patients with Cushing or subclinical Cushing syndrome.

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Characterizing cyclin-dependent kinase 12(CDK12)-altered aggressive prostate cancer: a twelve-case series

Iwasawa T., Kosaka T., Yasumizu Y., Hongo H., Yanai Y., Baba Y., Matsumoto K., Nakamura K., Nishihara H., Oya M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 27 ( 12 ) 1867 - 1873 2022.12

ISSN 13419625

Background: Prostate cancer harboring cyclin-dependent kinase 12 (CDK12) abnormalities is a hot topic due to its distinctive clinical features, such as sensitivity to immune checkpoint inhibitors. In the last few years, precision medicine using comprehensive genome sequencing has become familiar, and the era of precision oncology has arrived in the field of prostate cancer. This study aimed to present the demographic characteristics of patients with CDK12 alterations. Methods: In 12 patients with detected CDK12 alterations in our hospital between 2015 and 2021, we evaluated their genomic features and clinical course. CDK12 allelic status was classified into three groups: monoallelic loss, potentially biallelic loss, and biallelic loss based on the genome analyses. Results: Seven patients already had metastatic cancer at the time of diagnosis, and all 12 patients had Gleason grade ≥ 4. Most cases of biallelic loss or potentially biallelic loss were metastatic cancers at the initial staging, and all these cases were categorized into Gleason grade 5. Two of the 12 patients had BRCA2/RB1 co-loss, and the other two had whole genome duplication. Five patients had a long-term survival of > 6 years, but two patients died within 4 years of diagnosis. Conclusion: This is the first Japanese prostate cancer case series with CDK12 alterations. CDK12-altered prostate cancer is a heterogeneous disease, and accumulating cases with detailed information leads to precision oncology.

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Optimal surgical treatment for paratesticular leiomyosarcoma: retrospective analysis of 217 reported cases

Kamitani R., Matsumoto K., Takeda T., Mizuno R., Oya M.

BMC Cancer (BMC Cancer) 22 ( 1 ) 2022.12

Background: Paratesticular leiomyosarcoma (LMS) is a rare tumor. Conventionally, tumor resection by high inguinal orchiectomy is performed as the preferred treatment approach for paratesticular sarcoma. On the other hand, testis-sparing surgery has recently attracted attention as a less-invasive treatment option for paratesticular sarcoma. However, the prognostic predictors and optimal treatment strategy for paratesticular LMS remain unclear because of its rarity. In this study, we systematically reviewed previously reported cases of paratesticular LMS to evaluate the prognostic factors and establish the optimal treatment strategy. Methods: A systematic search of Medline, Web of Science, Embase, and Google was performed to find articles describing localized paratesticular LMS published between 1971 and 2020 in English. The final cohort included 217 patients in 167 articles. The starting point of this study was the time of definitive surgical treatment, and the end point was the time of local recurrence (LR), distant metastasis (DM), and disease-specific mortality. Results: Patients with cutaneous LMS had a slightly better LR-free survival, DM-free survival, and disease-specific survival than those with subcutaneous LMS (p = 0.745, p = 0.033, and p = 0.126, respectively). Patients with higher grade tumors had a significantly higher risk of DM and disease-specific mortality (Grade 3 vs Grade 1 p < 0.001, and Grade 3 vs Grade 1 p < 0.001, respectively). In addition, those with a microscopic positive margin had a significantly higher risk of LR and DM than those with a negative margin (p < 0.001, and p = 0.018, respectively). Patients who underwent simple tumorectomy had a slightly higher risk of LR than those who underwent high inguinal orchiectomy (p = 0.067). Subgroup analysis of cutaneous LMS demonstrated that the difference in LR between simple tumorectomy and high inguinal orchiectomy was limited (p = 0.212). On the other hand, subgroup analysis of subcutaneous LMS revealed a significant difference in LR (p = 0.039). Conclusions: Our study demonstrated that subcutaneous LMS and high-grade tumors are prognostic factors for paratesticular LMS. For subcutaneous LMS, tumorectomy with high inguinal orchiectomy should be the optimal treatment strategy to achieve a negative surgical margin.

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Predictors of Survival in Favorable Risk Patients with Metastatic Renal Cell Carcinoma Treated with a Single-Agent First-Line Therapy

Mizuno R., Takamatsu K., Yasumizu Y., Tanaka N., Takeda T., Morita S., Matsumoto K., Kosaka T., Asanuma H., Mikami S., Oya M.

Urologia Internationalis (Urologia Internationalis) 106 ( 11 ) 1145 - 1149 2022.11

ISSN 00421138

Introduction: The aim of this retrospective study was to elucidate predictors of survival in metastatic renal cell carcinoma (mRCC) patients in an International Metastatic Renal Cell Carcinoma Database Consortium favorable risk group treated with frontline therapy without immune checkpoint inhibitors. Methods: A total of 238 patients with mRCC were reviewed. Among them, 55 patients in favorable risk group treated with single-agent systemic therapy were retrospectively analyzed. Clinical and pathological data were retrieved and analyzed retrospectively. The prognostic effect of each marker on overall survival (OS) was investigated with univariate and multivariate Cox's proportional hazards regression models. Results: After a median follow-up of 46.2 months after first-line treatment initiation, the median progression-free survival (PFS) was 29.3 months, and the median OS has not been reached. The estimated percentage of patients who were alive at 12 and 24 months were 96.1 and 94.1%, respectively. Multivariate analysis revealed that the long-term duration of first-line treatment (hazard ratio [HR]: 0.972, 95% confidence interval [CI]: 0.944-0.997, p = 0.0299) and the metastases limited to lung (HR: 3.852, 95% CI: 1.080-24.502, p = 0.0361) were independent predictors for longer OS in favorable risk mRCC patients. Conclusion: First-line systemic therapy for favorable risk mRCC patients with a single agent resulted in relatively longer PFS and OS. A longer duration of first-line treatment and lung only metastases are correlated with longer OS.

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A low subcutaneous fat mass is a risk factor for the development of inguinal hernia after radical prostatectomy

Umeda K., Takeda T., Hakozaki K., Yasumizu Y., Tanaka N., Matsumoto K., Morita S., Kosaka T., Mizuno R., Asanuma H., Oya M.

Langenbeck's Archives of Surgery (Langenbeck's Archives of Surgery) 407 ( 7 ) 3107 - 3112 2022.11

ISSN 14352443

Purpose: Inguinal hernia (IH) after radical prostatectomy (RP) is a complication that impairs quality of life; however, the factors contributing to IH after RP remain unclear. Therefore, we herein attempted to identify the factors responsible for the development of IH after RP. Methods: We reviewed 622 patients who underwent laparoscopic or robot-assisted laparoscopic RP at our hospital between December 2011 and April 2020. The total fat area and visceral fat area were calculated at the level of the umbilicus using computed tomography, and the subcutaneous fat area (SFA) was calculated by subtracting the visceral fat area from the total fat area. The psoas muscle area was measured at the third lumbar vertebrae level using computed tomography to calculate the psoas muscle mass index, which is used in sarcopenia as an index of muscle mass. We investigated the risk factors for IH after laparoscopic or robot-assisted laparoscopic RP. Results: IH developed in 88 patients (16.7%). Fifty-seven of these patients underwent hernia repair at our hospital, and 56 (98.2%) had indirect hernias. A multivariate analysis identified SFA (odds ratios: 0.383, p < 0.001) as an independent predictor for the development of IH. Two-year IH-free survival rates were 77.3% in the small SFA group (SFA < 123 cm2) and 88.7% in the large SFA group (SFA ≥ 123 cm2) (p < 0.001). Conclusion: Subcutaneous fat was associated with the development of IH, particularly indirect IH, after laparoscopic or robot-assisted laparoscopic RP. An indirect IH prevention technique needs to be considered, particularly for patients with less subcutaneous fat.

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Influence of response to prior docetaxel on sensitivity to cabazitaxel in prostate cancer patients with PTEN alterations

Kamisawa K., Kosaka T., Nakamura K., Yasumizu Y., Hongo H., Takeda T., Matsumoto K., Nishihara H., Oya M.

Cancer Science (Cancer Science) 113 ( 9 ) 3161 - 3168 2022.09

ISSN 13479032

The purpose of this study was to investigate factors predicting the sensitivity to cabazitaxel therapy in metastatic castration-resistant prostate cancer (mCRPC) patients with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) alterations. This single-institution, retrospective study included 12 mCRPC patients with PTEN alterations who had received cabazitaxel therapy. Five patients (41%) responded to cabazitaxel therapy with a prostate-specific antigen (PSA) level decline of ≥30% from baseline, and all of them had responded to prior docetaxel therapy with a PSA decline of ≥30%. None of the patients with a poor response to prior docetaxel therapy responded well to cabazitaxel therapy. Of the seven patients who did not respond to cabazitaxel and whose PSA declined from baseline was <30%, five (71%) were also refractory to prior docetaxel therapy. The PSA responses to docetaxel and cabazitaxel were significantly correlated (p = 0.027). Kaplan–Meier analysis revealed that progression-free survival (PFS) for cabazitaxel was significantly shorter for prior docetaxel nonresponders (3.3 versus 9.1 months, p = 0.028). Multivariate analysis revealed that a poor response to prior docetaxel (PSA decline < 30%) (hazard ratio [HR] = 6.382, 95% confidence interval [CI] 1.172–34.750, p = 0.032) and baseline PSA of ≥20 ng/ml (HR = 33.584, 95% CI 2.332–483.671, p = 0.010) were independent prognostic factors for PFS with cabazitaxel therapy. These results demonstrate cross-resistance between docetaxel and cabazitaxel. The response to prior docetaxel therapy can influence the sensitivity to cabazitaxel therapy in mCRPC patients with PTEN alterations.

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Management and outcomes of hydronephrosis in patients with metastatic extramammary Paget’s disease: A retrospective analysis

Fusumae T., Fukuda K., Hirai I., Nakamura Y., Kobayashi K., Tanese K., Matsumoto K., Iwata T., Funakoshi T.

Journal of Dermatology (Journal of Dermatology) 49 ( 8 ) 787 - 791 2022.08

ISSN 03852407

Hydronephrosis in extramammary Paget’s disease (EMPD) with distant metastasis (metastatic EMPD) has been observed in medical practice; however, its prognosis remains unclear. Retrospective analyses were performed to assess the management and outcomes of hydronephrosis in metastatic EMPD. During a follow-up of 44 patients with metastatic EMPD, 13 (30%) developed hydronephrosis. Ten (77%) of the 13 patients with hydronephrosis had impaired renal function (estimated glomerular filtration rate: <60 ml/min/1.73 m2), and ureteral stents were placed in every patient with impaired renal function. The stent was placed successfully in all 10 patients, and their renal function recovered within a median period of 7 days. Importantly, each of these patients continued chemotherapy, and none of them experienced stent failure. The median overall survival time (OS) in patients with metastatic EMPD and hydronephrosis (n = 13) was 7.8 months. Treatment for hydronephrosis was not a significant factor for OS, and median OS in patients who underwent ureteral stent replacement (n = 10) was 14.7 months. Collectively, our results indicate that hydronephrosis is relatively common, and ureteral stent placement should be considered in cases of metastatic EMPD with hydronephrosis to maintain renal function and continue chemotherapy toward a better prognosis.

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Endoscopic vaporization of benign prostatic hyperplasia using a contact 980 nm diode laser under antithrombotic therapy: A prospective survey

Sanjo T., Tanaka N., Shinojima T., Yasumizu Y., Takeda T., Matsumoto K., Morita S., Kosaka T., Mizuno R., Asanuma H., Oya M.

Asian Journal of Endoscopic Surgery (Asian Journal of Endoscopic Surgery) 15 ( 3 ) 585 - 590 2022.07

ISSN 17585902

Introduction: To prospectively clarify whether endoscopic contact laser vaporization of the prostate (CVP) can be safely performed even in patients undergoing antithrombotic therapy. Methods: Fifty-five patients treated with CVP were enrolled. Patients were assigned to: (i) the antithrombotic therapy group (n = 21, 38%); or (ii) control group without antithrombotic therapy (n = 34, 62%). All patients in the antithrombotic therapy group continued all antithrombotic agents during the perioperative period and thereafter. Results: No difference was noted in patient background between the two groups. In primary endpoints, decreases in the postoperative hemoglobin level were remarkable in the antithrombotic therapy group, while no serious effects were noted in either group. The control and antithrombotic therapy groups did not show a significant difference in the occurrence of catheter obstruction due to blood clots or serious hematuria following catheter removal. During follow-up, transurethral coagulation for hemostasis was needed only in the antithrombotic therapy group, with a frequency of transurethral coagulation of up to 14%. In secondary endpoints, no difference in the occurrence of perioperative or late-onset complications after surgery was noted between the two groups. Finally, no difference was noted in improvements in the International Prostate Symptom Score (IPSS), IPSS quality of life score, overactive bladder symptom score, maximum flow rate, or post-voiding residual urine volume between the two groups throughout the follow-up period. Conclusions: CVP can be performed safely and effectively in patients undergoing continuous antithrombotic therapy. However, the possibility of secondary bleeding after discharge in a subset of patients, such as those undergoing antithrombotic therapy, may be noted.

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Profiling the Biological Characteristics and Transitions through Upper Tract Tumor Origin, Bladder Recurrence and Muscle-Invasive Bladder Progression in Upper Tract Urothelial Carcinoma

Shigeta K., Matsumoto K., Tanaka N., Mikami S., Kosaka T., Yasumizu Y., Takeda T., Mizuno R., Kikuchi E., Oya M.

International Journal of Molecular Sciences (International Journal of Molecular Sciences) 23 ( 9 ) 2022.05

ISSN 16616596

To evaluate biological characteristics and transitions of upper tract urothelial carcinoma (UTUC) through metachronous bladder tumors after radical nephroureterectomy (RNU), we con-ducted immunohistochemical (IHC) staining of tumor specimens of UTUC tumor origin, non-mus-cle-invasive bladder cancer (NMIBC) and MIBC progressed after intravesical recurrence (IVR), and bladder primary MIBC. Fibroblast growth factor receptor 3 (FGFR3), p53, cytokeratin 5/6 (CK5/6), and CK20 were stained to examine expression rates. After expression assessment with heatmap clustering, the overexpression of four biomarkers from UTUC origin to metachronous MIBC progression was analyzed with clinicopathological variables. We found that high CK20 and low CK5/6 expression were both observed in UTUC tumor origin and subsequent NMIBC after RNU. By in-vestigating molecular expression in the IVR specimen, we observed that low pT stage bladder recurrence occupied the majority of CK20 high CK5/6 low expression, but would change to CK20 low CK5/6 high expression as it progressed to MIBC. UTUC metachronous MIBC has different characteristics compared with bladder primary MIBC, which comprises favorable biological features such as high FGFR3 expression, and follows favorable prognosis compared to those without FGFR3 ex-pression. The present study demonstrated that the biological characteristics of UTUC tumor origin shifts from luminal to basal-like features with progression to MIBC, but FGFR3 expression taken over from UTUC origin may comprise a favorable entity compared to primary MIBC.

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Does neoadjuvant chemotherapy have therapeutic benefit for node-positive upper tract urothelial carcinoma? Results of a multi-center cohort study

Shigeta K., Matsumoto K., Ogihara K., Murakami T., Anno T., Umeda K., Izawa M., Baba Y., Sanjo T., Shojo K., Tanaka N., Takeda T., Morita S., Kosaka T., Mizuno R., Arita Y., Akita H., Jinzaki M., Kikuchi E., Oya M.

Urologic Oncology: Seminars and Original Investigations (Urologic Oncology: Seminars and Original Investigations) 40 ( 3 ) 105.e19 - 105.e26 2022.03

ISSN 10781439

Objective: The indications of neoadjuvant chemotherapy (NAC) for lymph node-positive upper tract urothelial carcinoma (UTUC) have not been investigated regarding improved survival outcomes. Our specific aim was to compare the clinical outcomes of clinically node-positive UTUC patients who were treated by NAC followed by radical nephroureterectomy (RNU) or upfront RNU followed by adjuvant chemotherapy (AC). Materials and methods: Among 966 UTUC patients, we identified 89 with clinical nodal involvement who received either NAC before RNU nor AC after upfront RNU. Cox proportional hazard models were employed to evaluate the impact of chemotherapy modality on the oncological outcomes. Results: Of the patient cohort, 36 (40.4%) received NAC followed by RNU, whereas 53 (59.6%) underwent RNU followed by AC. Multivariate analysis revealed that tumor size ≥3 cm, clinical T4, and gemcitabine and cisplatin regimen were independent risk factors for disease recurrence, whereas NAC followed by RNU was an independent factor for favorable RFS. Furthermore, regarding cancer-specific survival (CSS), NAC followed by RNU remained an independent factor for favorable CSS. According to Kaplan-Meier analysis, the 1-year and 2-year RFS were 67.9% and 47.0%, respectively, in the NAC+RNU group, which were significantly higher than those in the RNU+AC group (43.9% and 24.6%, respectively, P = 0.006). Moreover, the 1-year and 2-year CSS were 80.5% and 64.2%, respectively, in the NAC+RNU group, which were higher than those in the RNU+AC group (68.6% and 48.2%, respectively, P = 0.016). Conclusion: For node-positive UTUC patients, NAC followed by RNU was more clinically beneficial than RNU followed by AC.

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The Significance of PARP1 as a biomarker for Predicting the Response to PD-L1 Blockade in Patients with PBRM1-mutated Clear Cell Renal Cell Carcinoma

Hagiwara M., Fushimi A., Matsumoto K., Oya M.

European Urology (European Urology) 81 ( 2 ) 145 - 148 2022.02

ISSN 03022838

Immune checkpoint inhibitors (ICIs) have become key agents in the management of clear cell renal cell carcinoma (ccRCC), but their benefits are limited and responders remain unidentified. We investigated the significance of PARP1 in ccRCC using RNA sequencing data for 311 tumors from patients enrolled in prospective clinical trials of PD-1 blockade. Among patients treated with nivolumab (n = 181), overall survival (OS) was significantly higher in the PARP1-low group than in the PARP1-high group (p = 0.006), and PARP1 status was significantly associated with OS (hazard ratio [HR] 1.7; p = 0.007). By contrast, for patients treated with everolimus (n = 130) there was no significant difference by PARP1 status for progression-free survival (PFS; p = 0.9) or OS (p = 0.38). In subgroup analysis for PBRM1-mutated ccRCC, PFS (p = 0.016) and OS (p = 0.004) were significantly longer in the group with PARP1-low status and PBRM1 mutation in comparison to the other groups. In addition, PARP1 status was significantly associated with PFS (HR 2.6; p = 0.007) and OS (HR 3.5; p = 0.016) among patients with PBRM1-mutated ccRCC treated with nivolumab. Our study suggests that PARP1 can be used as a biomarker for predicting response to ICI treatment for patients with PBRM1-mutated ccRCC. Patient summary: Immune checkpoint inhibitors (ICIs) are key agents in the treatment of multiple cancers. We found that expression of the PARP1 protein was associated with survival after ICI treatment and with the response to ICI treatment in patients with clear cell kidney cancer who have a mutation of the PBRM1 gene.

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Hybridisation chain reaction-based visualisation and screening for lncRNA profiles in clear-cell renal-cell carcinoma

Kufukihara R., Tanaka N., Takamatsu K., Niwa N., Fukumoto K., Yasumizu Y., Takeda T., Matsumoto K., Morita S., Kosaka T., Aimono E., Nishihara H., Mizuno R., Oya M.

British Journal of Cancer (British Journal of Cancer) 2022

ISSN 00070920

Background: Analysis of long noncoding RNA (lncRNA) localisation at both the tissue and subcellular levels can provide important insights into the cell types that are important for their function. Methods: By applying new fluorescent in situ hybridisation technique called hybridisation chain reaction (HCR), we achieved a high-throughput lncRNA visualisation and evaluation of clinical samples. Results: Assessing 1728 pairs of 16 lncRNAs and clear-cell renal-cell carcinoma (ccRCC) specimens, three lncRNAs (TUG1, HOTAIR and CDKN2B-AS1) were associated with ccRCC prognosis. Furthermore, we derived a new lncRNA risk group of ccRCC prognosis by combining the expression levels of these three lncRNAs. Examining genomic alterations underlying this classification revealed prominent features of tumours that could serve as potential biomarkers for targeting lncRNAs. We then derived combination of HCR with expansion microscopy and visualised nanoscale-resolution HCR signals in cell nuclei, uncovering intracellular colocalization of three lncRNA (TUG1, HOTAIR and CDKN2B-AS1) signals such as those located intra- or out of the nucleus or nucleolus in cancer cells. Conclusion: LncRNAs are expected to be desirable noncoding targets for cancer diagnosis or treatments. HCR involves plural probes consisting of small DNA oligonucleotides, clinically enabling us to detect cancerous lncRNA signals simply and rapidly at a lower cost.

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CD8-positive T cells and CD204-positive M2-like macrophages predict postoperative prognosis of very high-risk prostate cancer

Yanai Y., Kosaka T., Mikami S., Hongo H., Yasumizu Y., Takeda T., Matsumoto K., Miyauchi J., Kitano S., Oya M.

Scientific Reports (Scientific Reports) 11 ( 1 ) 2021.12

To stratify the heterogeneity of prostate cancer (PCa) with seminal vesicle invasion (SVI) immunologically after radical prostatectomy focusing on the tumor microenvironment. We retrospectively reviewed the clinicopathological data of 71 PCa patients with SVI, which is known as a factor of very high-risk PCa. Preoperative clinical variables and postoperative pathological variables were evaluated as predictors of biochemical recurrence (BCR) with a multivariate logistic regression. Immune cell infiltration including the CD8-positive cell (CD8+ cell) and CD204-positive M2-like macrophage (CD204+ cell) was investigated by immunohistochemistry. The cumulative incidence and risk of BCR were assessed with a Kaplan–Meier analysis and competing risks regression. A higher CD8+ cell count in the SVI area significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). A lower CD204+ cell count in the SVI area also significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). Furthermore, the combination of the CD8+ and CD204+ cell infiltration ratio of the SVI area to the main tumor area was a significant factor for BCR in the patients with the PCa with SVI (p = 0.001). In PCa patients with SVI, the combination of CD8+ and CD204+ cell infiltration is useful to predict the prognosis.

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Risk factors for haemodynamic instability and its prolongation during laparoscopic adrenalectomy for pheochromocytoma

Takeda T., Hakozaki K., Yanai Y., Masuda T., Yasumizu Y., Tanaka N., Matsumoto K., Morita S., Kosaka T., Mizuno R., Kurihara I., Asanuma H., Itoh H., Oya M.

Clinical Endocrinology (Clinical Endocrinology) 95 ( 5 ) 716 - 726 2021.11

ISSN 03000664

Objective: Pheochromocytoma is a rare neuroendocrine tumour that secretes catecholamines and originates in the adrenal gland. Although surgical resection is the only curative therapy for pheochromocytoma, it is associated with a risk of haemodynamic instability (HDI), such as extremely high blood pressure and/or post tumour removal hypotension and shock. We investigated the risk factors for HDI during pheochromocytoma surgery. Design and Patients: Eighty-two patients who underwent laparoscopic adrenalectomy for pheochromocytoma between July 2002 and February 2020 were examined. We excluded 3 patients with bilateral disease and 11 without detailed 24 h urinary data. We defined HDI as systolic blood pressure ≥ 200 or <80 mmHg. We investigated the risk factors for HDI during laparoscopic adrenalectomy for pheochromocytoma. Results: There were 29 males and 39 females with a median age of 50.5 years. Tumours were localised on the right adrenal gland in 28 patients and on the left in 40. The median tumour diameter was 37.5 mm and the median pneumoperitoneum time was 93.5 min. Twenty-five out of sixty-eight patients (37%) developed HDI. A multivariate analysis identified diabetes mellitus (DM; odds ratio: 3.834; 95% confidence interval: 1.062–13.83; p =.04) as an independent predictor of HDI. In terms of hormonal data, median 24 h urinary epinephrine levels (p =.04) and metanephrine levels (p =.01) were significantly higher in the HDI group. DM was also considered as a risk factor for prolonged HDI (p =.02). Conclusion: Surgeons and anaesthesiologists need to be aware of the risk of HDI and its prolongation during laparoscopic adrenalectomy for pheochromocytoma for DM patients.

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Negative impact of neoadjuvant hormonal therapy on detecting biochemical recurrence after radical prostatectomy

Matsumoto K., Niwa N., Kosaka T., Takeda T., Yasumizu Y., Tanaka N., Morita S., Mizuno R., Shinojima T., Asanuma H., Oya M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 26 ( 9 ) 1722 - 1728 2021.09

ISSN 13419625

Background: Routine use of neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP) is not recommended, but it is sometimes performed to reduce the prostate size and tumor volume or to prevent tumor progression during the wait times for surgery in clinical practice. On the other hand, the impact of NHT on the pattern of biochemical recurrence (BCR) is unknown. Methods: We retrospectively examined 1749 consecutive patients who underwent RP between 1996 and 2017. Among the patients who met the inclusion criteria, BCR developed in 240 of non-NHT patients and in 120 of NHT patients during the mean follow-up period of 6.9 years. We examined the impact of NHT on the PSA-doubling time (DT) following BCR at different times after RP. Results: The median PSA-DTs in non-NHT patients who experienced BCR in the first year after surgery, between 1 and 2 years, between 2 and 3 years, between 3 and 4 years, between 4 and 5 years, and at > 5 years were 5.5, 8.8, 11.3, 17.7, 18.2, and 18.4 months, respectively. On the other hand, those in NHT patients were 1.4, 4.1, 9.1, 13.4, 27.2, and 19.3 months, respectively. The differences of PSA-DTs in the first year after surgery (p < 0.001) and between 1 and 2 years (p = 0.005) were significant between non-NHT and NHT patients. Conclusion: Patients who received NHT had a higher risk of a rapid PSA increase when they experienced BCR, especially within 2 years after RP. In order to not miss the optimal timing of salvage treatment for BCR, intensive PSA follow-up is necessary.

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Grading of Multifocal Prostate Cancer Cases in which the Largest Volume and the Highest Grade Do Not Coincide within One Lesion

Matsumoto K., Omura M., Takeda T., Kosaka T., Hashiguchi A., Takamatsu K., Yasumizu Y., Tanaka N., Morita S., Mizuno R., Asanuma H., Oya M.

Journal of Urology (Journal of Urology) 206 ( 2 ) 338 - 345 2021.08

ISSN 00225347

Purpose:In general, the index lesion of prostate cancer has the largest tumor volume, the highest Grade Group (GG), and the highest stage (concordant cases). However, these factors sometimes do not coincide within one lesion (discordant cases). In such discordant cases, the largest tumor may not be of biological significance and the secondary tumor may more greatly impact the prognosis.Materials and Methods:We retrospectively reviewed the medical records of patients who underwent radical prostatectomy, and we identified 580 (85.3%) concordant cases and 100 (14.7%) discordant cases. The end point of this study was biochemical recurrence, and median followup was 4.2 years.Results:Among discordant cases in which GGs of the largest tumor and the highest GG tumor differed, the majority (67 patients) had the largest tumor of GG 2, and we set them as the study cohort. On the other hand, we regarded 212 concordant cases with an index tumor of GG 2 as the control cohort. The study cohort comprised 48 (71.6%) patients with a secondary tumor of GG 3 and 19 (28.4%) with a secondary tumor of GG 4/5. Kaplan-Meier curves revealed that the 5-year biochemical recurrence-free survival rates were 76%, and 67%, respectively. The 5-year biochemical recurrence-free survival rate of the control cohort was 91%, which was significantly better than that of the study cohort (p=0.013 and p=0.014, respectively).Conclusions:Our study suggests that the prognosis of discordant cases is better determined by the secondary cancer lesion with the highest GG instead of the largest lesion.

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On-treatment C-reactive protein control could predict response to subsequent anti-PD-1 treatment in metastatic renal cell carcinoma

Takamatsu K., Mizuno R., Baba Y., Yasumizu Y., Tanaka N., Shirotake S., Takeda T., Morita S., Matsumoto K., Kosaka T., Asanuma H., Oyama M., Mikami S., Oya M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 26 ( 8 ) 1500 - 1505 2021.08

ISSN 13419625

Objective: The aim of this study was to evaluate the clinical significance of the on-treatment C-reactive protein (CRP) status during systemic treatment as the predictive marker for the response of subsequent nivolumab monotherapy in patients with refractory metastatic renal cell carcinoma (mRCC). Patients and methods: A total of 73 mRCC patients treated with nivolumab were retrospectively reviewed. We evaluated the serum CRP levels before and after molecular-targeted treatments. Patients whose CRP did not exceed baseline value were defined as the CRP-control group and the others were defined as the CRP-progression group. The clinical impact of CRP-control on the efficacy of nivolumab was assessed. Results: Twenty-four patients (33%) were categorized into the CRP-control group. The CRP-control group patients (median PFS not reached) had significantly longer PFS than the CRP-progression group (median PFS 11.9 months, 95% confidence interval, CI 4.1–19.8, p = 0.038). The CRP-control group had a tendency of longer OS from nivolumab initiation than the CRP-progression group (p = 0.071). By multivariate analysis, the on-treatment CRP-control was the independent predictive factor for PFS (hazard ratio HR 0.37, 95% CI 0.14–0.99, p = 0.047). Conclusion: The on-treatment CRP-control could be the predictive factor for the efficacy of nivolumab in refractory mRCC patients.

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Long-term follow-up comparing salvage radiation therapy and androgen-deprivation therapy for biochemical recurrence after radical prostatectomy

Matsumoto K., Niwa N., Hagiwara M., Kosaka T., Takeda T., Yasumizu Y., Tanaka N., Morita S., Mizuno R., Shinojima T., Hara S., Asanuma H., Oya M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 26 ( 4 ) 744 - 752 2021.04

ISSN 13419625

Background: The salvage treatments for biochemical recurrence (BCR) include local external beam radiation therapy (RT) and systemic androgen-deprivation therapy (ADT). Methods: We reviewed patients who underwent radical prostatectomy (RP) and developed BCR at three institutions. After excluding patients whose nadir prostate-specific antigen (PSA) was higher than 0.2 ng/mL, those who received neoadjuvant/adjuvant therapy, and those whose BCR was not treated until their PSA exceeded 4.0 ng/mL, the remaining 335 patients comprised the cohort of this study. Salvage RT and ADT were performed for 154 and 181 patients, respectively. After the failure of salvage RT, all patients received subsequent ADT. The starting point of this study was the timing of BCR and the endpoint was the development of castration-resistant prostate cancer (CRPC). Results: During the mean follow-up period of 8.5 years after BCR, CRPC was observed in 13 patients administered RT and 24 patients administered ADT. Kaplan–Meier curves demonstrated no significant difference in CRPC-free survival between the RT and ADT groups (10-year CRPC-free survival 89.9 vs. 86.3%, p = 0.199). On the other hand, we found a significant difference in CRPC-free survival between the RT and ADT groups in 50 high-risk patients with two risk factors of Grade Group ≥ 4 and PSA-doubling time < 6 months (10-year CRPC-free survival 73.4 vs. 40.3%, p = 0.040). Conclusion: This study revealed that salvage RT increases the CRPC-free survival rate compared with salvage ADT in high-risk patients with Grade Group ≥ 4 and PSA-doubling time < 6 months.

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The clinicopathological characteristics of muscle-invasive bladder recurrence in upper tract urothelial carcinoma

Shigeta K., Matsumoto K., Ogihara K., Murakami T., Anno T., Umeda K., Izawa M., Baba Y., Sanjo T., Shojo K., Tanaka N., Takeda T., Kosaka T., Mizuno R., Mikami S., Kikuchi E., Oya M.

Cancer Science (Cancer Science) 112 ( 3 ) 1084 - 1094 2021.03

ISSN 13479032

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.

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Can random bladder biopsies be eliminated after bacillus Calmette–Guérin therapy against carcinoma in situ?

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

International Urology and Nephrology (International Urology and Nephrology) 53 ( 3 ) 465 - 469 2021.03

ISSN 03011623

Purpose: Intravesical bacillus Calmette–Guérin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy. Methods: We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6–8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens. Results: According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p = 0.116, and p < 0.001, respectively). The sensitivity (Sen.), specificity (Spe.), positive predictive value (PPV), and negative predictive value (NPV) of voiding cytology were 50%, 68%, 39%, and 77%, respectively. The values for cystoscopy findings were as follows: Sen.: 87%, Spe.: 57%, PPV: 46%, and NPV: 91%. The values for their combination (having either of them) were as follows: Sen.: 100%, Spe.: 44%, PPV: 43%, and NPV: 100%. Conclusion: RBB after BCG therapy for patients with negative voiding cytology and negative cystoscopy may be omitted because their risk of BCG-unresponsive disease is significantly low (NPV: 100%).

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Laparoscopic surgery training at the robotic surgery era

Matsumoto K., Takeda T.

Japanese Journal of Clinical Urology (Japanese Journal of Clinical Urology) 75 ( 10 ) 722 - 725 2021

ISSN 03852393

Three-dimensional single-cell imaging for the analysis of RNA and protein expression in intact tumour biopsies

Tanaka N., Kanatani S., Kaczynska D., Fukumoto K., Louhivuori L., Mizutani T., Kopper O., Kronqvist P., Robertson S., Lindh C., Kis L., Pronk R., Niwa N., Matsumoto K., Oya M., Miyakawa A., Falk A., Hartman J., Sahlgren C., Clevers H., Uhlén P.

Nature Biomedical Engineering (Nature Biomedical Engineering) 4 ( 9 ) 875 - 888 2020.09

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Microscopy analysis of tumour samples is commonly performed on fixed, thinly sectioned and protein-labelled tissues. However, these examinations do not reveal the intricate three-dimensional structures of tumours, nor enable the detection of aberrant transcripts. Here, we report a method, which we name DIIFCO (for diagnosing in situ immunofluorescence-labelled cleared oncosamples), for the multimodal volumetric imaging of RNAs and proteins in intact tumour volumes and organoids. We used DIIFCO to spatially profile the expression of diverse coding RNAs and non-coding RNAs at the single-cell resolution in a variety of cancer tissues. Quantitative single-cell analysis revealed spatial niches of cancer stem-like cells, and showed that the niches were present at a higher density in triple-negative breast cancer tissue. The improved molecular phenotyping and histopathological diagnosis of cancers may lead to new insights into the biology of tumours of patients.

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Umbilical closure using 2-octyl cyanoacrylate in transumbilical laparoscopic adrenalectomy: A randomized controlled trial

Fukumoto K., Miyajima A., Matsumoto K., Kobayashi H., Niwa N., Hongo H., Kurihara I., Kikuchi E., Oya M.

International Journal of Urology (International Journal of Urology) 27 ( 8 ) 670 - 675 2020.08

ISSN 09198172

© 2020 The Japanese Urological Association Objectives: To evaluate postoperative pain and esthetic outcomes in patients undergoing transumbilical laparoscopic adrenalectomy with wound closure using 2-octyl cyanoacrylate. Methods: A total of 26 patients who underwent laparoscopic adrenalectomy with the transumbilical approach and agreed to participate in this study were included. Patients were randomly divided into two groups: the 2-octyl cyanoacrylate group (Glue group) or the non-use group (non-Glue group). A single surgeon (AM) carried out all procedures between 2014 and 2017. Results: There were no significant differences in the clinical background of the Glue and non-Glue groups. The number of patients with moderate or high levels of pain in the resting/moving period on postoperative days 1, 2 and 3 was 6/10 (46%/77%), 6/9 (46%/69%) and 3/5 (23%/38%) in the non-Glue group, and 5/7 (38%/54%), 2/7 (15%/54%) and 1/3 (8%/23%) in the Glue group. These differences were not significant. In the subgroup analysis of patients aged <50 years, the numbers were 4/6 (57%/86%), 5/7 (71%/100%) and 3/5 (43%/71%) in the non-Glue group, and 3/4 (33%/44%), 1/4 (11%/44%) and 0/1 (0%/11%) in the Glue group in the resting/moving period. On postoperative days 2 and 3, these differences were significant (P = 0.035 and 0.037 in the resting period, and P = 0.017 and 0.013 in the moving period). Conclusions: 2-octyl cyanoacrylate can be used safely for laparoscopic adrenalectomy with the transumbilical approach, and might be useful for reducing postoperative pain in patients aged <50 years.

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External validation of the "optimal PSA follow-up schedule after radical prostatectomy” in a new cohort

Yanai Y., Matsumoto K., Kosaka T., Takeda T., Tanaka N., Morita S., Mizuno R., Shinojima T., Asanuma H., Oya M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 25 ( 7 ) 1393 - 1397 2020.07

ISSN 13419625

© 2020, Japan Society of Clinical Oncology. Background: Biochemical recurrence (BCR) after radical prostatectomy (RP) is most commonly diagnosed by detecting an increase in asymptomatic prostate-specific antigen (PSA). We previously reported the “optimal PSA follow-up schedule after RP”. The aim of this study was to confirm the usefulness and safety of that follow-up schedule in another cohort. Methods: We retrospectively reviewed the clinicopathological data of 798 consecutive patients who underwent radical prostatectomy between 2009 and 2017. We examined all PSA values measured during follow-up. Furthermore, we estimated the PSA value when we observed the “optimal PSA follow-up schedule” at each timing in the virtual follow-up. BCR was defined as an elevation of PSA to greater than 0.2 ng/ml, and the ideal PSA range for detection of BCR was regarded to be 0.2–0.4 ng/ml. Results: During the mean follow-up period of 5.8 years, BCR occurred in 115 (14.9%) patients and the frequency of virtual follow-up was significantly lower than the actual frequency. However, overlooking of BCR (detecting BCR when PSA exceeded 0.4 ng/ml) was observed in 17 patients, which is higher than the actual frequency of overlooking (12 patients). Therefore, we modified the follow-up schedule, which could achieve the lower follow-up frequency and a limited number of overlooking of BCR (7 patients). Conclusion: This external validation study revealed that the "modified optimal PSA follow-up schedule after RP" can reduce the frequency of PSA measurement with a limited risk of overlooking BCR.

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Type of patients in whom biochemical recurrence after radical prostatectomy can be observed without salvage therapy

Matsumoto K., Niwa N., Hagiwara M., Kosaka T., Tanaka N., Takeda T., Morita S., Mizuno R., Shinojima T., Hara S., Asanuma H., Oya M.

World Journal of Urology (World Journal of Urology) 38 ( 7 ) 1749 - 1756 2020.07

ISSN 07244983

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: To examine the prognosis after BCR with and without salvage therapy, including radiation and/or androgen deprivation. Methods: The study population consisted of 431 patients, all of whom underwent radical prostatectomy and developed BCR (PSA > 0.2 ng/mL). According to the two risk factors [Gleason score ≥ 8 and PSA-doubling time (DT) < 6 months], we divided the patients into two groups. The high/intermediate-risk group consisted of patients with both or one risk factor. On the other hand, patients with neither factor were in the low-risk group. We set the starting point at the timing of BCR, and the endpoints were development to castration-resistant prostate cancer (CRPC) and cancer-specific death. Results: During the mean follow-up period of 8.3 years after BCR, CRPC was observed in 49 patients (11.4%), and 21 patients (4.9%) died due to prostate cancer. We first divided the 191 high/intermediate-risk patients according to the PSA level (PSA < 1.0 ng/mL, PSA 1.0–4.0, and PSA > 4.0 or no therapy) at the initiation of salvage therapy, including radiation and/or androgen deprivation. We found that delayed (PSA > 4.0 ng/mL) or no salvage therapy was significantly associated with CRPC and cancer-specific death. In the 240 low-risk patients, Kaplan–Meier curves demonstrated no significant difference in CRPC-free survival or cancer-specific survival within 10 years from the timing of BCR. Conclusions: Observation after BCR without salvage therapy or delayed administration may be an option for low-risk patients with a Gleason score ≤ 7 and PSA-DT ≥ 6 months when their life expectancy is within 10 years.

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Appropriate timing for a biochemical evaluation after adrenalectomy for unilateral aldosterone-producing adenoma

Takamatsu K., Takeda T., Hattori S., Tanaka N., Morita S., Matsumoto K., Kosaka T., Mizuno R., Shinojima T., Kikuchi E., Asanuma H., Kurihara I., Itoh H., Oya M.

Clinical Endocrinology (Clinical Endocrinology) 92 ( 6 ) 503 - 508 2020.06

ISSN 03000664

© 2020 John Wiley & Sons Ltd Context: The oversecretion of plasma aldosterone by unilateral aldosterone-producing adenoma (APA) can be cured by adrenalectomy. However, the time needed for the endocrine environment to normalize remains unclear. Objective: To clarify adequate timing for a biochemical evaluation in unilateral APA patients after adrenalectomy. Design and patients: A total of 166 unilateral APA patients were retrospectively reviewed. We evaluated the plasma aldosterone concentration (PAC) (pg/mL), active renin concentration (ARC) (pg/mL), aldosterone-renin ratio (ARR; PAC/ARC), serum potassium concentration and estimated glomerular filtration rate (eGFR) at 1, 3 and 6 postoperation months (POM). Results: PAC was significantly lower at 1POM than at presurgery (presurgery; 407.2, 1 POM; 90.0 pg/mL, P <.001). ARC did not increase from baseline at 1POM, but significantly increased at 3POM (presurgery; 4.43, 1POM; 4.87, 3POM; 11.3 pg/mL, P <.001). ARR significantly decreased at 1POM (presurgery; 146.9, 1 POM; 26.3, P <.001) although ARC did not increase at 1POM. Among the 34 patients who had hypokalaemia presurgery, it was resolved in 28 (82%) at 1POM and in all (100%) at 3POM. The biochemical outcomes at 1POM were 131 (79%) complete, 20 (12%) partial and 15 (9%) absent successes, while at 3POM, 147 (89%) were complete, 9 (5%) partial and 10 (6%) absent. Twenty-three (14%) patients were reclassified into different biochemical outcomes between 1 and 3POM, whereas only 5 (3%) changed between 3 and 6POM. Conclusion: The appropriate timing for a biochemical evaluation of unilateral APA patients treated with laparoscopic adrenalectomy appears to be 3 months or more after surgery.

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The efficacy of the TachoSil binding suturing technique in laparoscopic partial nephrectomy to prevent the development of pseudoaneurysm

Shigeta K., Matsumoto K., Abe T., Komatsuda A., Takeda T., Mizuno R., Kikuchi E., Asanuma H., Arita Y., Akita H., Jinzaki M., Miyajima A., Oya M.

Asian Journal of Surgery (Asian Journal of Surgery) 43 ( 6 ) 668 - 675 2020.06

ISSN 10159584

© 2019 Objective: Our specific aim was to introduce the TachoSil binding suturing technique for renal cell carcinoma (RCC) patients when closing the parenchymal defect after tumor excision during laparoscopic partial nephrectomy (LPN), which is a novel technique for reducing the risk of developing subsequent pseudoaneurysm (PA). Methods: We identified 113 pT1aN0M0 RCC patients who underwent LPN at our institution. Eighty-one (72%) patients underwent the suturing procedure without binding TachoSil, whereas 32 (28%) patients underwent renorraphy with the renal defect closed together with TachoSil. The vascular complications were evaluated by computed tomography or magnetic resonance imaging with enhanced contrast material at the first visit after LPN. We conducted Fischer's exact test to determine risk factors for transcatheter arterial embolization (TAE). Results: The median age was 55 (36–86) years old and the median follow-up time was 65 (12–147) months. In the overall population, there were 11 (11%) patients who underwent TAE because they developed PA. All 11 patients exhibited the imaging findings of PA, and were all from the conventional suturing group. In contrast, no patients for whom the TachoSil binding method was used had any significant findings on imaging (14% vs. 0%). Based on the analysis to determine risk factors for TAE due to PA development, the TachoSil binding suturing technique was one of the significant indicators for reducing the risk of developing PA. Conclusions: Our study demonstrated that the TachoSil binding suturing technique might reduce the development of PA after LPN. Prospective randomized study and comparison to the standard 2 or 3–layer renorrhaphy is needed to prove its actual value.

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The pretreatment neutrophil-to-lymphocyte ratio is a novel biomarker for predicting clinical responses to pembrolizumab in platinum-resistant metastatic urothelial carcinoma patients

Ogihara K., Kikuchi E., Shigeta K., Okabe T., Hattori S., Yamashita R., Yoshimine S., Shirotake S., Nakazawa R., Matsumoto K., Mizuno R., Hara S., Oyama M., Masuda T., Niwakawa M., Oya M.

Urologic Oncology: Seminars and Original Investigations (Urologic Oncology: Seminars and Original Investigations) 38 ( 6 ) 602.e1 - 602.e10 2020.06

ISSN 10781439

© 2020 Elsevier Inc. Purpose: We investigated the relationship between pretreatment neutrophil-to-lymphocyte ratio (pre-NLR) levels just before the initiation of treatment with pembrolizumab and clinical outcomes in platinum-resistant metastatic urothelial carcinoma (UC) patients treated with pembrolizumab. Methods: Our study population comprised 78 patients diagnosed with metastatic UC and treated with pembrolizumab after platinum-based chemotherapy at our institutions between December 2017 and April 2019. We examined the relationships between pre-NLR levels just before pembrolizumab treatment and clinical outcomes. A pre-NLR level of ≥3.35 was defined as elevated according to a calculation by a receiver-operating curve analysis. Results: The high pre-NLR group consisted of 33 patients (42.3%). Overall, 29.5% of patients had a clinical response and the sum of the target lesion longest diameter was decreased in 18.8% of the high pre-NLR group, which was significantly lower than that in the low pre-NLR group (58.1%, P = 0.005). Six-month progression-free survival and cancer-specific survival rates for the high pre-NLR group were 9.1 and 58.0%, which were significantly lower than those for their counterpart (45.9 and 89.1%, P < 0.001 and P = 0.002, respectively). The pre-NLR level was an independent indicator of disease progression and cancer-specific death (P < 0.001 and P = 0.003). Furthermore, patients with a postpembrolizumab NLR level that had decreased ≥25% from the pre-NLR level had significantly lower disease progression and cancer-specific death rates than their counterparts (P = 0.01 and P = 0.022, respectively). Conclusions: Elevated pre-NLR may be a novel biomarker for identifying poor responders to pembrolizumab among platinum-resistant metastatic UC patients.

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Bacillus Calmette–Guérin-unresponsive non-muscle-invasive bladder cancer: Its definition and future therapeutic strategies

Kikuchi E., Hayakawa N., Fukumoto K., Shigeta K., Matsumoto K.

International Journal of Urology (International Journal of Urology) 27 ( 2 ) 108 - 116 2020.02

ISSN 09198172

© 2019 The Japanese Urological Association Bacillus Calmette–Guérin induction with or without maintenance is the gold standard therapy for intermediate-/high-risk non-muscle-invasive bladder cancer; however, one-third of patients treated with adequate bacillus Calmette–Guérin therapy do not achieve sufficient responses, and this is referred to as “bacillus Calmette–Guérin failure.” The term, bacillus Calmette–Guérin failure, is ambiguous and includes a very heterogeneous population of patients. By strictly focusing on patients who are unlikely to benefit from additional bacillus Calmette–Guérin therapy and who need to be treated with radical cystectomy, the new concept of “bacillus Calmette–Guérin unresponsive” was recently proposed, and might accelerate the development of novel therapeutic options for bacillus Calmette–Guérin-unresponsive disease. A promising therapeutic strategy for bacillus Calmette–Guérin-unresponsive disease is the blockade of the programmed cell death-1/programmed cell death-ligand 1 pathway, which is considered to be activated by bacillus Calmette–Guérin therapy. Several large clinical trials have been carried out to assess the potential of programmed cell death-1/programmed cell death-ligand 1 blockade in bacillus Calmette–Guérin-naïve high-risk non-muscle-invasive bladder cancer and bacillus Calmette–Guérin-unresponsive disease. Furthermore, clinical trials that are targeting bacillus Calmette–Guérin-unresponsive disease with other strategies, such as vaccines, gene therapy, and targeted and cytotoxic therapies, are ongoing. The findings of these trials are awaited in order to establish appropriate bladder-sparing approaches for patients with bacillus Calmette–Guérin-unresponsive disease.

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Reduced recurrence of low-risk non-muscle-invasive bladder cancer is associated with low urine-specific gravity

Iwasawa T., Niwa N., Matsumoto K., Komatsuda A., ide H., Oya M.

International Journal of Urology (International Journal of Urology) 2020

ISSN 09198172

© 2020 The Japanese Urological Association Objective: To investigate the association between urine-specific gravity and oncological outcomes in patients with non-muscle-invasive bladder cancer. Methods: We identified 433 primary non-muscle-invasive bladder cancer patients who underwent transurethral resection between 2002 and 2016. The association between urine-specific gravity and tumor recurrence was statistically evaluated. Results: A total of 211 (48.7%) patients received adjuvant bacillus Calmette–Guérin therapy. During the median follow-up period of 60 months, 155 (35.8%) patients experienced at least one tumor recurrence. Of them all, 95 (21.9%) and 338 (78.1%) patients had high (>1.020) and low (≤1.020) urine-specific gravity, respectively. The Kaplan–Meier curve suggested that recurrence-free survival was significantly lower in patients with a high urine-specific gravity; however, the multivariate analysis failed to show that urine-specific gravity is significantly associated with tumor recurrence. In 222 (51.3%) patients who had not received bacillus Calmette–Guérin therapy, the Kaplan–Meier curve also suggested that recurrence-free survival was significantly lower in patients with a high urine-specific gravity. Multivariate analysis showed that age >70 years (hazard ratio 1.69, P = 0.02), grade 3 tumor (hazard ratio 1.81, P = 0.03) and high urine-specific gravity (hazard ratio 1.87, P < 0.01) were independent risk factors for tumor recurrence. Conclusion: High urine-specific gravity is an independent risk factor for tumor recurrence in non-muscle-invasive bladder cancer patients who have not received bacillus Calmette–Guérin therapy. Our results suggest that hydration status might have some clinical impacts on bladder tumor recurrence.

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Optimal treatment strategy for paratesticular liposarcoma: retrospective analysis of 265 reported cases

Kamitani R., Matsumoto K., Takeda T., Mizuno R., Oya M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 2020

ISSN 13419625

© 2020, Japan Society of Clinical Oncology. Background: Liposarcoma is one of the most common subtypes of soft tissue sarcoma. Although the standard treatment for localized liposarcoma is surgical resection with negative margins, a treatment specific to paratesticular liposarcoma has yet to be quantitatively evaluated. Methods: A systematic search of Medline, Web of Science, Embase, and Google was performed to find articles describing localized paratesticular liposarcoma published between 1979 and 2018 in English. The final cohort included 265 patients in 183 articles. The starting point was the time of surgical treatment, and the endpoint was the time of recurrence, including local recurrence, or distant metastasis. Results: The median patient age was 62 years and the median tumor size was 9.5 cm. In total, 178 patients underwent high inguinal orchiectomy and 40 underwent simple tumorectomy. Based on the Kaplan–Meier curves, recurrence-free survival rates were significantly higher for those who underwent high inguinal orchiectomy than for those who underwent tumorectomy. Moreover, those with microscopic positive margins had a higher risk of recurrence than those with negative margins, but adjuvant radiation therapy after resection had no statistically significant effect on recurrence-free survival, even in subgroup analysis of patients with positive margins. Regarding the pathological subtypes, dedifferentiated, pleomorphic, and round-cell liposarcoma had a higher risk of recurrence than well-differentiated or myxoid liposarcoma. In the multivariate analysis, high inguinal orchiectomy greatly affected recurrence-free survival. The tumor size and histological subtype were independent risk factors for recurrence. Conclusion: Complete resection with high inguinal orchiectomy is the optimal treatment for paratesticular liposarcoma.

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Evaluation of Gleason Grade Group 5 in a Contemporary Prostate Cancer Grading System and Literature Review

Kamitani R., Matsumoto K., Kosaka T., Takeda T., Hashiguchi A., Tanaka N., Morita S., Mizuno R., Shinojima T., Asanuma H., Oya M.

Clinical Genitourinary Cancer (Clinical Genitourinary Cancer) 19 ( 1 ) 69 - 75.e5 2020

ISSN 15587673

© 2020 Elsevier Inc. Introduction: The aim of this study was to validate contemporary grading systems, in particular, the Gleason grade group (GGG) 5. Patients and Methods: We retrospectively reviewed the clinicopathologic data of 176 patients who underwent radical prostatectomy and whose pathologic results were GGG 4 or 5. The endpoints were biochemical recurrence (BCR) and castration-resistant prostate cancer (CRPC). Results: The GGG 4 group was composed of 69 patients. The GGG 5 group consisted of 78 patients with GS 4+5 and 29 patients with GS 5+4 or higher. The 5-year BCR-free survival rates for men with GGG 4, GS 4+5, and GS 5+4 or higher were 59%, 54%, and 20%, respectively, and the 5-year CRPC-free survival rates were 98%, 100%, and 88%, respectively. Both the BCR- and CRPC-free survival rates were significantly higher in GS 4+5 than in GS 5+4 or higher (P < .001 and P = .002, respectively), but there were no significant differences between GGG 4 and GS 4+5 (P = .702 and P = .803, respectively). The multivariate analysis demonstrated that GS 5+4 or higher (hazard ratio, 3.4; P = .002) and lymphovascular invasion (hazard ratio, 3.4; P < .001) greatly affected BCR. Conclusion: Our follow-up study revealed that men with GS 4+5 and those with GGG 4 had a similar prognosis. However, there was a significant discrepancy in prognosis between GS 4+5 and GS 5+4 or higher. This suggested that GGG 4 and 5 in the contemporary prostate cancer grading system should be reviewed. Furthermore, lymphovascular invasion may be useful to subgroup these pathologically high-risk patients.

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Evaluating the Oncological Outcomes of Pure Laparoscopic Radical Nephroureterectomy Performed for Upper-Tract Urothelial Carcinoma Patients: A Multicenter Cohort Study Adjusted by Propensity Score Matching

Shigeta K., Matsumoto K., Takeda T., Hattori S., Kaneko G., Matsushima M., Abe T., Tanaka N., Mizuno R., Asanuma H., Kikuchi E., Oya M.

Annals of Surgical Oncology (Annals of Surgical Oncology) 28 ( 1 ) 465 - 473 2020

ISSN 10689265

© 2020, Society of Surgical Oncology. Purpose: To evaluate the oncological feasibility of pure laparoscopic radical nephroureterectomy (p-LRNU) for upper tract urothelial carcinoma (UTUC) compared with conventional LRNU (c-LRNU) using a propensity-adjusted multi-institutional collaboration dataset. Methods: Among the 503 UTUC patients who underwent RNU, we identified 219 who underwent c-LRNU (laparoscopic nephrectomy with open bladder cuff resection) and 72 who underwent p-LRNU (dissecting the kidney, ureter, and bladder cuff under complete laparoscopy). We adopted a propensity score (PS) matching method to achieve homogeneity with respect to patient backgrounds. PS matching-adjusted Cox-regression analysis was performed to evaluate the risk factors that influenced oncological outcomes. Results: Sixty-eight p-LRNU and 68 c-LRNU patients were matched. Overall, 51 (37.0%) developed intravesical recurrence (IVR), 21 (15.4%) had disease recurrence, and 20 (14.7%) died. Patients who underwent p-LRNU had a significantly shorter operation time and less blood loss than those who underwent c-LRNU. Although no significant differences in 3-year recurrence-free survival were found between the two methods, atypical recurrence sites were observed in the p-LRNU group, including the brain, sigmoid colon, vagina, and peritoneum. Regarding IVR, the 3-year IVR-free survival rate was 41.8% in the p-LRNU group, which was significantly lower than that in the c-LRNU group (66.6%, p = 0.004). Multivariate analysis demonstrated that a history of bladder cancer, ureteral cancer, and p-LRNU were independent risk factors for subsequent IVR. Conclusion: Although p-LRNU is less invasive, the current technique may increase the incidence of atypical disease recurrence and subsequent IVR due to extravesical and intravesical tumor dissemination.

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A first Japanese case of neuroendocrine prostate cancer accompanied by lung and brain metastasis with somatic and germline BRCA2 mutation

Kosaka T., Hongo H., Aimono E., Matsumoto K., Hayashida T., Mikami S., Nishihara H., Oya M.

Pathology International (Pathology International) 69 ( 12 ) 715 - 720 2019.12

ISSN 13205463

© 2019 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd Germline mutations and copy number changes in DNA damage repair (DDR) genes such as BRCA2 are associated with aggressive forms of prostate cancer (PCa). Although the prevalence of BRCA2 variants in PCa is increasing in Japan, the genomic and biological implications in Japanese patients are unclear. An 81-year-old male presented with prostatic adenocarcinoma with neuroendocrine differentiation accompanied by metastatic lung nodule and brain metastases. Platinum-based doublet chemotherapy combined with etoposide resulted in partial and complete remissions of brain and lung metastases, respectively. Next-generation sequencing of biopsy and peripheral blood samples demonstrated a somatic BRCA2 mutation at c.7008-2A>C and a germline mutation at p.E2877*. The patient's son had been diagnosed with breast cancer 2.5 years ago and was found to have the same germline BRCA2 mutation. BRCA2 mutation increases the risks of aggressive PCa and other cancer types in Japanese males. These forms may be highly responsive to platinum-based chemotherapy.

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

Ogihara K., Kikuchi E., Okazaki S., Hagiwara M., Takeda T., Matsumoto K., Kosaka T., Mikami S., Saya H., Oya M.

Cancer Science (Cancer Science) 110 ( 4 ) 1431 - 1441 2019.04

ISSN 13479032

© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. 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-p38 MAPK 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-p38 MAPK 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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The clinical implication of gamma globulin levels in patients with nonmuscle-invasive bladder cancer

Niwa N., Matsumoto K., Ide H.

Urologic Oncology: Seminars and Original Investigations (Urologic Oncology: Seminars and Original Investigations) 37 ( 4 ) 291.e1 - 291.e7 2019.04

ISSN 10781439

© 2019 Objective: The production of antibody, also referred immunoglobulin, is the principal functions of B cells. Gamma globulin fraction determined by serum protein electrophoresis is composed almost entirely of immunoglobulin. This study aimed to investigate the association between gamma globulin level and oncological outcomes in patients with nonmuscle-invasive bladder cancer (NMIBC). Patients and methods: A total of 274 patients with NMIBC who underwent transurethral surgery between 2000 and 2015 were identified. One hundred forty-four patients (52.6%) had received adjuvant intravesical bacillus Calmette-Guérin. Gamma globulin fraction (%) was determined by serum protein electrophoresis, and gamma globulin level (mg/dl) was calculated by multiplying the total protein level (mg/dl) by the gamma globulin fraction (%). The association between gamma globulin levels and oncological outcomes was statistically evaluated. Results: During a median follow-up period of 39 months, 99 (36.1%) patients experienced at least 1 tumor recurrence and 16 (5.8%) patients had disease progression. The median (interquartile range) gamma globulin level was 1.2 (1.0–1.3) mg/dl. Recurrence-free survival rate of patients with gamma globulin levels of ≥1.4 mg/dl was significant lower than that of patients with gamma globulin levels of <1.4 mg/dl (P < 0.01). There was no significant difference in progression-free survival between the 2 groups (P = 0.17). Multivariate analysis revealed that gamma globulin level of ≥1.4 mg/dl is significantly associated with higher recurrence rate (hazard ratio = 1.83, P < 0.01). Conclusion: Gamma globulin level is significantly associated with tumor recurrence. Our results suggest that B cell immunity may be involved in tumor recurrence in patients with NMIBC.

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Prediction of extraprostatic extension by MRI tumor contact length: difference between anterior and posterior prostate cancer

Matsumoto K., Akita H., Narita K., Hashiguchi A., Takamatsu K., Takeda T., Kosaka T., Mizuno R., Kikuchi E., Oya M., Jinzaki M.

Prostate Cancer and Prostatic Diseases (Prostate Cancer and Prostatic Diseases) 22 ( 4 ) 539 - 545 2019

ISSN 13657852

© 2019, Springer Nature America, Inc. Background: Tumor contact length (TCL) is defined as the extent of contact between prostate cancer and the prostatic capsule, and its predictive value for microscopic extraprostatic extension (EPE) has been reported. However, the impact of the zonal origin (anterior or posterior tumor) of the tumor on the diagnosis of EPE is controversial. Methods: We retrospectively analyzed the records of 233 consecutive patients who underwent preoperative MRI and radical prostatectomy. We designated their tumors as anterior or posterior, and evaluated the correlation between the TCL measured by MRI and microscopic EPE in the radical prostatectomy specimen. Then, we created the predicted probability curves for EPE versus TCL for anterior and posterior prostate cancer. Results: There were 109 patients (47%) with an anterior tumor and 124 patients (53%) with a posterior tumor. Postoperative pathological analysis confirmed pT3 in 18 patients (17%) with an anterior tumor and in 53 patients (43%) with a posterior tumor. Multivariate analysis demonstrated that the zonal origin of the tumor was an independent predictive factor for EPE. We developed separate probability curves of EPE versus TCL for anterior and posterior prostate cancer, which revealed that anterior tumors were less likely to invade the extraprostatic tissues. Among patients whose TCL was 10–20 mm, 9/32 patients (28%) with an anterior tumor had EPE compared with 24/45 patients (53%) with a posterior tumor (p = 0.036). The decision curve of this EPE predictive model had high clinical efficacy. Conclusions: Our results indicate that anterior tumors have more favorable pathological characteristics than posterior tumors with the same TCL measured by MRI. We constructed two separate predicted probability curves for EPE after discriminating anterior and posterior tumors, which will be useful for decision making in clinical practice.

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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.

Int J Clin Oncol. 2019

Research paper (scientific journal), Accepted

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.

Int J Clin Oncol. (International Journal of Clinical Oncology) 24 ( 9 ) 1069 - 1074 2019

Research paper (scientific journal), Accepted, ISSN 13419625

© 2019, Japan Society of Clinical Oncology. 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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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: Seminars and Original Investigations (Urologic Oncology: Seminars and Original Investigations) 37 ( 9 ) 575.e19 - 575.e25 2019

ISSN 10781439

© 2019 Elsevier Inc. 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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Selection of patients who would not require long-term prostate-specific antigen monitoring after low-dose-rate brachytherapy

Niwa N., Matsumoto K., Nishiyama T., Yagi Y., Ozu C., Nakamura K., Saito S., Oya M.

Brachytherapy (Brachytherapy) 17 ( 6 ) 899 - 905 2018.11

ISSN 15384721

© 2018 American Brachytherapy Society Purpose: To identify patients at extremely low risk of biochemical recurrence (BCR) of prostate cancer after low-dose-rate brachytherapy (LDR-BT) to determine when prostate-specific antigen (PSA) monitoring can be stopped. Methods and Materials: We retrospectively reviewed clinicopathologic data of patients with prostate cancer who underwent LDR-BT between 2003 and 2011. Of 1569 patients reviewed, 689 (43.9%) received combination external beam radiotherapy, and 970 (61.8%) had neoadjuvant hormonal therapy. We stratified patients according to risk factors identified by multivariate analysis and assessed the factors for an association with BCR (defined as ≥2 ng/mL higher than the nadir). Results: The median followup was 96 months. Of 1531 patients who were BCR-free at 3 years after treatment, 76 subsequently developed BCR; of 1500 who were BCR-free at 5 years, 45 eventually had BCR. On multivariate analysis, independent risk factors for BCR were the National Comprehensive Cancer Network risk group at diagnosis and PSA levels at 3 or 5 years after radiotherapy. In the low-risk group, no patient with a PSA level ≤0.2 ng/mL at 3 years after radiotherapy subsequently developed BCR. In the intermediate-risk group, no patients with a PSA level ≤0.2 ng/mL at 5 years subsequently developed BCR. Conclusions: The National Comprehensive Cancer Network risk group at diagnosis and PSA values at 3 and 5 years after LDR-BT are independently associated with a risk of later BCR. Using these two factors may help to select patients for whom PSA monitoring could be stopped because they have an extremely low risk of later BCR.

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Genomic abnormalities of bladder cancer and potential as a target for novel treatments

Matsumoto K.

Japanese Journal of Clinical Urology (Japanese Journal of Clinical Urology) 72 ( 11 ) 906 - 909 2018.10

ISSN 03852393

Incidence and timing of inadvertent nephrostomy catheter displacement in patients with ureteral obstruction

Niwa N., Matsumoto K., Kikuchi E., Yazawa S., Takeda T., Morita S., Kosaka T., Shinoda K., Mizuno R., Shinojima T., Asanuma H., Oya M.

Clinical Nephrology (Clinical Nephrology) 90 ( 2 ) 112 - 116 2018.08

ISSN 03010430

© 2018 Dustri-Verlag Dr. K. Feistle. Introduction: To evaluate nephrostomy catheter displacement, we assessed the cumulative nephrostomy catheter displacement rate in patients with percutaneous nephrostomy and compared the nephrostomy displacement rates between pigtail and balloon catheters. Materials and methods: Between 2003 and 2011, 87 patients who underwent percutaneous nephrostomy catheter placement and more than one subsequent catheter replacement were retrospectively identified. We evaluated their inadvertent nephrostomy catheter displacement. Results: 20 patients (23.0%) experienced incidental nephrostomy catheter displacement during the follow-up period. Kaplan-Meier analysis revealed that the 1-year nephrostomy catheter displacement-free survival rate was 62 ± 9%. No significant independent risk factors for predicting nephrostomy catheter displacement were identified, including the type of catheter. The median time from initial placement to displacement of pigtail catheters was shorter than that of balloon catheters. Conclusion: There were no significant differences in the nephrostomy catheter displacement-free survival rates between the two types of catheters. Regardless of the type of catheter, our results indicated that careful handling and guiding during catheter placement are important for all patients because of the high risk of inadvertent events.

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Clinical Role of Programmed Cell Death-1 Expression in Patients with Non-muscle-invasive Bladder Cancer Recurring After Initial Bacillus Calmette–Guérin Therapy

Fukumoto K., Kikuchi E., Mikami S., Hayakawa N., Matsumoto K., Niwa N., Oya M.

Annals of Surgical Oncology (Annals of Surgical Oncology) 25 ( 8 ) 2484 - 2491 2018.08

ISSN 10689265

© 2018, Society of Surgical Oncology. Background: The programmed cell death-1 (PD-1) pathway has been suggested to play an important role in tumor immune escape. We evaluated changes in PD-1 expression before and after Bacillus Calmette–Guérin (BCG) therapy and its prognostic significance in non-muscle-invasive bladder cancer (NMIBC) patients. Methods: We examined 78 paired tissue samples of NMIBC in tumors just before BCG therapy and BCG-relapsing tumors, defined as recurrence after achieving disease-free status by initial BCG instillations for 6 months. We counted PD-1-positive cells, and PD-1 expression was defined as high when the number of PD-1-positive cells was more than 18 under ×200 magnification. Results: The median number of PD-1-positive cells in tumors just before BCG therapy was 3.5, significantly lower than that in BCG-relapsing tumors (17.0, p < 0.001). High PD-1 expression was observed in 20 tumors just before BCG therapy (25.6%) and 36 BCG-relapsing tumors (46.2%). Fifty-two cases (66.6%) showed an increase in the number of PD-1-positive cells in BCG-relapsing tumors. High PD-1 expression in BCG-relapsing tumors was independently associated with subsequent tumor recurrence (p = 0.011) and stage progression (p = 0.033). The 5-year recurrence-free and progression-free survival rates were 40.7 and 74.1% in patients with high PD-1 expression in BCG-relapsing tumors, significantly lower than those in their counterparts (72.9 and 94.1%, respectively). Conclusions: PD-1 was induced by BCG therapy, and its expression in BCG-relapsing tumors may be an important indicator for predicting worse clinical outcomes in NMIBC patients treated with BCG therapy.

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Prognostic Value of Baseline Serum C-Reactive Protein Level in Intermediate-Risk Group Patients With Metastatic Renal-Cell Carcinoma Treated by First-Line Vascular Endothelial Growth Factor–Targeted Therapy

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

Clinical Genitourinary Cancer (Clinical Genitourinary Cancer) 16 ( 4 ) e927 - e933 2018.08

ISSN 15587673

© 2018 Elsevier Inc. Because accumulating evidence underlines the association of systemic inflammation with metastatic renal-cell carcinoma (mRCC) progression, we evaluated baseline C-reactive protein (CRP) levels as a prognostic marker in 107 intermediate-risk mRCC patients treated with first-line targeted therapy. Baseline CRP could be a biomarker correlated with overall survival in the intermediate-risk group. Its cost efficacy and availability make CRP a helpful tool for reclassifying the intermediate-risk group. Background: Almost half of patients with metastatic renal-cell carcinoma (mRCC) are classified as intermediate risk by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. The aim of this study was to evaluate whether baseline C-reactive protein (CRP) levels predict overall survival (OS) in intermediate-risk group mRCC patients. Patients and Methods: Data from 107 intermediate-risk group mRCC patients receiving first-line targeted therapy were retrospectively reviewed. We evaluated the correlation between baseline CRP levels as well as other indices and OS. Results: Of the 107 patients with intermediate-risk disease, 46 patients (43%) were classified as having elevated CRP levels. The elevation of pretreatment serum CRP levels was the independent prognostic factor of OS in patients with intermediate risk (hazard ratio, 4.609; P =.001). The 1- and 3-year survival rates of patients with intermediate–nonelevated CRP were 90.0% and 64.7% compared to the favorable-risk group, at 92.1% and 68.5%, respectively. In contrast, the 1- and 3-year survival rates of patients with intermediate–elevated CRP were 80.5% and 37.4% compared to the poor-risk group, at 65.2% and 24.2%, respectively. Conclusion: Baseline CRP levels could divide mRCC patients in the intermediate-risk group into 2 prognostic subgroups.

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Establishment of the optimal follow-up schedule after radical prostatectomy

Matsumoto K., Niwa N., Hattori S., Takeda T., Morita S., Kosaka T., Mizuno R., Shinojima T., Kikuchi E., Asanuma H., Oya M.

Urologic Oncology: Seminars and Original Investigations (Urologic Oncology: Seminars and Original Investigations) 36 ( 7 ) 341.e9 - 341.e14 2018.07

Doctoral thesis, ISSN 10781439

© 2018 Elsevier Inc. Purpose: Monitoring the serum level of prostate specific antigen (PSA) is indispensable for surveillance after radical therapy, and the aim of this study was to establish the optimal follow-up schedule. Materials and methods: We retrospectively reviewed the clinicopathological data of 1,010 consecutive patients who underwent radical prostatectomy. After excluding patients who received neoadjuvant or adjuvant therapy and those without a nadir PSA level<0.2 ng/ml, the remaining 779 patients were enrolled. Biochemical recurrence (BCR) was defined as elevation of PSA to >0.2 ng/ml. We investigated the PSA doubling time (PSA-DT) following BCR at various times after surgery. Results: During a mean follow-up of 8.8 years, BCR occurred in 180/779 patients. The annual BCR rate was 6% in the first year after surgery, 6% between 1 and 2 years, 3% between 2 and 3 years, 3% between 3 and 5 years, and 2% at >5 years postoperatively. During these periods, the minimum PSA-DT after BCR was 1.6, 2.4, 3.1, 6.1, and 6.4 months, respectively. These minimum PSA-DTs were used to determine the optimal follow-up interval during each period after surgery. If the baseline level is 0.1 ng/ml, PSA should be measured at approximately 3-month intervals for the first year, at 4-month intervals between 1 and 2 years, at 6-month intervals between 2 and 3 years, and annually thereafter to definitely detect BCR before the serum PSA level exceeds 0.4 ng/ml. Conclusion: The PSA-DT following BCR varies according to the time after surgery. Our data on minimum PSA-DT values after BCR are useful for setting the optimal follow-up schedule.

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Does switching the bacillus Calmette-Guérin strain affect clinical outcome in patients with recurrent non–muscle-invasive bladder cancer after initial bacillus Calmette-Guérin therapy?

Niwa N., Kikuchi E., Matsumoto K., Kosaka T., Mizuno R., Oya M.

Urologic Oncology: Seminars and Original Investigations (Urologic Oncology: Seminars and Original Investigations) 36 ( 6 ) 306.e1 - 306.e8 2018.06

ISSN 10781439

© 2018 Elsevier Inc. Purpose: It is still unknown whether switching the bacillus Calmette-Guérin (BCG) strain at the second induction course of BCG therapy has a therapeutic benefit in patients with tumor recurrence after the initial BCG therapy (BCG-relapsing tumor). Materials and methods: We retrospectively reviewed the clinicopathological features of 97 patients treated with a second induction course of BCG therapy between 1986 and 2014. Among the patients initially treated with BCG Tokyo-172, the second course was either BCG Tokyo-172 in 56 (57.8%) or BCG Connaught in 15 (15.5%). Among those who were initially treated with BCG Connaught, the corresponding numbers were 13 (13.4%) or 13 (13.4%), respectively. Twenty-eight (28.9%) patients were given a different BCG strain at the 2 BCG therapies (switching group), and 69 (71.1%) patients were given the same BCG strain (non-switching group). Result: The 5-year recurrence-free survival rate of the switching group was 64.7 ± 9.6%, which was not significantly different from that of the non-switching group (54.8 ± 6.9%, P = 0.427). Switching or not switching the BCG strain was not significantly associated with tumor recurrence after the second BCG therapy. The 5-year progression-free survival rate of the switching group was 95.4 ± 2.6%, which was also not significantly different from that of the non-switching group (96.0 ± 3.9%, P = 0.674). Patients treated with BCG Tokyo-172 to Tokyo-172 had significantly higher incidences of side effects during the second BCG therapy. Conclusions: The results of this study indicate that in patients with a BCG-relapsing tumor after the initial BCG therapy, the same BCG strain as that administered at the initial BCG therapy could be utilized effectively for the second BCG therapy. Patients treated with BCG Tokyo-172 for an initial tumor had a higher incidence of side effects during the second BCG therapy using the same strain.

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Prognostic Value of Pretreatment Albumin-to-Globulin Ratio in Patients With Non–Muscle-Invasive Bladder Cancer

Niwa N., Matsumoto K., Ide H., Nagata H., Oya M.

Clinical Genitourinary Cancer (Clinical Genitourinary Cancer) 16 ( 3 ) e655 - e661 2018.06

ISSN 15587673

© 2018 Elsevier Inc. In an investigation of the relationship between albumin-to-globulin ratio (AGR) and oncologic outcomes in 364 non–muscle-invasive bladder cancer (NMIBC) patients, those with AGR < 1.6 had significantly poorer recurrence-free and progression-free survival than those with AGR ≥ 1.6. Multivariate analysis revealed that AGR < 1.6 is significantly associated with tumor recurrence. Low AGR is an independent risk factor for recurrence in NMIBC patients. Purpose: To investigate the relationship between albumin-to-globulin ratio (AGR) and oncologic outcomes in patients with non–muscle-invasive bladder cancer (NMIBC). Patients and Methods: We identified 364 patients with primary NMIBC who underwent transurethral surgery between 2000 and 2015. The association between pretreatment AGR and clinicopathologic variables, including oncologic outcomes, was statistically evaluated. Results: One hundred twenty patients (33.0%) experienced at least one tumor recurrence, and 23 (6.3%) developed muscle-invasive disease. The median (interquartile range) pretreatment AGR was 1.73 (1.53-1.89). The Kaplan-Meier curve revealed that tumor recurrence was strongly predicted in patients with pretreatment AGR < 1.6, and similar results were observed for disease progression (P <.01 and P <.01, respectively). On multivariate analysis, we found that pretreatment AGR < 1.6 is an independent risk factor for tumor recurrence (hazard ratio, 0.53; P <.01). On univariate analysis, pretreatment AGR < 1.6 was also associated with disease progression (hazard ratio, 0.24; P <.01). Conclusion: Low pretreatment AGR is an independent risk factor for tumor recurrence and is one risk factor for disease progression in NMIBC patients. This inexpensive and easily accessible biomarker may become useful in selecting patients with NMIBC with higher risk of recurrence and progression.

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Purified Protein Derivative Skin test prior to bacillus Calmette-Guérin Therapy May have Therapeutic Impact in Patients with Nonmuscle Invasive Bladder Cancer

Niwa N., Kikuchi E., Matsumoto K., Kosaka T., Mizuno R., Oya M.

Journal of Urology (Journal of Urology) 199 ( 6 ) 1446 - 1451 2018.06

ISSN 00225347

© 2018 American Urological Association Education and Research, Inc. Purpose: We investigated the clinical impact of the purified protein derivative skin test prior to bacillus Calmette-Guérin therapy in patients with nonmuscle invasive bladder cancer treated with adjuvant bacillus Calmette-Guérin therapy. Materials and Methods: A total of 498 patients with nonmuscle invasive bladder cancer treated with adjuvant bacillus Calmette-Guérin were included in study, of whom 320 underwent the purified protein derivative skin test 1 to 2 weeks prior to therapy. Oncologic outcomes and the rate of bacillus Calmette-Guérin related side effects were statistically evaluated. Results: The mean ± SD 5-year recurrence-free survival rate in patients who did vs did not undergo the purified protein derivative skin test was 66.6% ± 2.8% and 59.1% ± 4.1%, respectively, which was significantly different (p = 0.048). No significant difference was observed in the progression-free survival rate between patients who did vs did not undergo the test. Multivariate Cox regression analysis revealed that a history of recurrence (HR 1.59, p = 0.02), multiple tumors (HR 1.95, p <0.01), the bacillus Calmette-Guérin Connaught strain (HR 0.71, p = 0.04), 7 or more bacillus Calmette-Guérin instillations (HR 0.70, p = 0.04) and undergoing the purified protein derivative skin test (HR 0.72, p = 0.04) were independently associated with tumor recurrence. Major bacillus Calmette-Guérin related side effects were noted in 77 of the 320 patients (24.1%) who did vs 27 of the 178 (15.2%) who did not undergo the test, which was significantly different (p = 0.02). Conclusions: The purified protein derivative skin test prior to bacillus Calmette-Guérin treatment enhances the therapeutic effects of this treatment and potentially results in a higher incidence of major bacillus Calmette-Guérin related side effects. Combination therapy with bacillus Calmette-Guérin using the purified protein derivative skin test may improve the oncologic outcomes of that therapy.

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Purified protein derivative skin test reactions are associated with clinical outcomes of patients with nonmuscle invasive bladder cancer treated with induction bacillus Calmette-Guérin therapy

Niwa N., Kikuchi E., Matsumoto K., Kosaka T., Mizuno R., Oya M.

Urologic Oncology: Seminars and Original Investigations (Urologic Oncology: Seminars and Original Investigations) 36 ( 2 ) 77.e15 - 77.e21 2018.02

ISSN 10781439

© 2018 Elsevier Inc. Objectives: To investigate the relationship between purified protein derivative (PPD) skin test reactions before bacillus Calmette-Guérin (BCG) therapy and the clinical outcomes of BCG-naïve nonmuscle invasive bladder cancer patients treated with adjuvant BCG therapy. Materials and methods: A total of 288 nonmuscle invasive bladder cancer patients subjected to the PPD skin test before BCG therapy were included. PPD skin test reactions were categorized into 3 groups: positive, slightly positive, and negative. The presence of an induration was positive. If an induration was absent, erythema of 10 mm or more and less than 10 mm corresponded to slightly positive and negative, respectively. Results: A total of 66 (22.9%), 149 (51.7%), and 73 (25.3%) patients exhibited a positive, slightly positive, and negative to PPD skin test, respectively. The 5-year recurrence-free survival rate of patients with positive PPD skin test reactions was 89.4 ± 4.1%, which was significantly higher than those of patients with slightly positive (65.5 ± 4.2%, P = 0.001) and negative reactions (56.4 ± 6.6%, P<0.001). A multivariate Cox regression analysis revealed that a positive PPD skin test reaction was independently associated with tumor recurrence (hazard ratio of 0.233, P<0.001), but not with stage progression. The incidence of fever persisting for more than 2 days or fever of ≥38°C was significantly higher in patients with a positive PPD skin test reaction (18.2%) than in patients with slightly positive (8.7%) and negative PPD skin test reactions (4.1%). Conclusions: The PPD skin test reactions before BCG therapy may predict clinical outcomes following BCG therapy and help clinicians counsel patients exhibiting strong therapeutic effects with BCG therapy and potentially major BCG-related side effects.

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Vasohibin-1 as a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer

Kobayashi H., Kosaka T., Mikami S., Miyazaki Y., Matsumoto K., Kikuchi E., Miyajima A., Kameyama K., Sato Y., Oya M.

Oncotarget (Oncotarget) 9 ( 12 ) 10203 - 10210 2018

© Kobayashi et al. Background: We previously reported high expression of vasohibin-1 (VASH1), which is specifically expressed in activated vascular endothelial cells, was a prognostic indicator of disease progression in prostate cancer. The aim of this study was to assess whether VASH1 expression at the area of normal prostatic tissue as well as that of intratumoral tissue could reflect the grade of malignancy of prostate cancer. Results: Pathological upgrade of Gleason Score ≥7 by radical prostatectomy was observed in 48 patients (upgraded group). The median VASH1 densities of the intratumoral and normal areas were 9.7 ± 9.5 and 13.3 ± 11.8, respectively, and the median MVDs were 58.6 ± 20.3 and 64.1 ± 23.5, respectively. We detected a strong positive correlation with each other for both VASH1 density (ρ = 0.589, p < 0.001) and MVD (ρ = 0.342, p < 0.001). VASH1 density was significantly higher in the upgreaded group than in the non-upgraded group regardless of prostatic location (intratumoral area: p < 0.001, normal area: p < 0.001). Conclusions: Even if the tumor volume was low in biopsy samples, VASH1 density reflected the grade of malignancy throughout the prostate. These results suggested that VASH1 expression could be a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer. Materials and Methods: Among the 1177 patients who underwent radical prostatectomy, 104 patients diagnosed with Gleason Score ≤6 and positive cores ≤3 were included. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD), and those with activated endothelial cells as VASH1 density using prostatic biopsy samples, and evaluated the association between their expressions and clinicopathological findings.

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Is transperitoneal laparoscopic radical nephrectomy suitable for patients with a history of abdominal surgery?

Yanai Y, Takeda T*, Miyajima A, Matsumoto K, Hagiwara M, Mizuno R, Kikuchi E, Asanuma H, Oya M.

Asian J Endosc Surg. (Asian journal of endoscopic surgery) 12 ( 4 ) 429 - 433 2018

Research paper (scientific journal), Accepted

© 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd. INTRODUCTION: Laparoscopic radical nephrectomy is the gold standard for treatment of renal cell carcinoma. However, previous abdominal surgery is generally regarded as a contraindication to the laparoscopic approach because it causes intraperitoneal adhesions, which are thought to interfere with subsequent laparoscopic procedures inside the abdominal cavity. Few studies have examined the influence of prior surgery on laparoscopic nephrectomy. Therefore, the aim of this study was to evaluate the impact of previous laparotomy on laparoscopic nephrectomy. METHODS: The records of 251 consecutive patients who had undergone laparoscopic nephrectomy for renal cell carcinoma at our hospital between 2005 and 2015 were reviewed retrospectively. RESULTS: Of the 251 laparoscopic nephrectomy patients, 76 patients (30%) had undergone prior abdominal surgery (surgery group), whereas the remaining 175 patients (70%) had not previously had abdominal surgery (control group). There were no significant differences between the control group and the surgery group with regard to pneumoperitoneum time (143 vs 135 min, P = 0.241) or blood loss (39 vs 36 mL, P = 0.763). Next, we divided the patients into two cohorts based on surgeon experience: 98 patients had been treated by an expert (i.e. someone who performs more than 50 laparoscopic procedures per year) and 153 patients had been treated by a non-expert. There was no significant difference in pneumoperitoneum time between the control and surgery groups in each cohort (treated by experts, 108 vs 103 min; treated by non-experts: 162 vs 166 min). CONCLUSION: We conclude that laparoscopic nephrectomy may be feasible after previous abdominal surgery and could be one of the surgical options.

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Evaluation of prostate-specific antigen density in the diagnosis of prostate cancer combined with magnetic resonance imaging before biopsy in men aged 70 years and older with elevated PSA.

Yanai Y, Kosaka T*, Hongo H, Matsumoto K, Shinojima T, Kikuchi E, Miyajima A, Mizuno R, Mikami S, Jinzaki M, Oya M.

Mol Clin Oncol. 9 ( 6 ) 656 - 660 2018

Research paper (scientific journal), Accepted

Laparoscopic vesical diverticulectomy

Shinojima T., Matsumoto K., Oya M.

Japanese Journal of Clinical Urology (Japanese Journal of Clinical Urology) 72 ( 12 ) 1012 - 1017 2018

ISSN 03852393

Novel algorithm for management of acute epididymitis.

Hongo H, Kikuchi E*, Matsumoto K, Yazawa S, Kanao K, Kosaka T, Mizuno R, Miyajima A, Saito S, Oya M.

Int J Urol. 24 ( 1 ) 82 - 87 2017

Research paper (scientific journal), Accepted

The learning curve of laparoendoscopic single-site adrenalectomy: an analysis of over 100 cases.

Fukumoto K, Miyajima A*, Hattori S, Matsumoto K, Abe T, Kurihara I, Jinzaki M, Kikuchi E, Oya M.

Surg Endosc. 31 ( 1 ) 170 - 177 2017

Research paper (scientific journal), Accepted

Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity.

Tanaka N, Kanatani S, Tomer R, Sahlgren C, Kronqvist P, Kaczynska D, Louhivuori L, Kis L, Lindh C, Mitura P, Stepulak A, Corvigno S, Hartman J, Micke P, Mezheyeuski A, Strell C, Carlsonv JW, Moro CF, Dahlstrand H, Östman A, Matsumoto K, Wiklund P, Oya M, Miyakawa A, Deisseroth K, Uhlén P*.

Nature Biomedical Engineering. 1 796 - 806 2017

Research paper (scientific journal), Accepted

Can urologists introduce the concept of "oligometastasis" for metastatic bladder cancer after total cystectomy?

Ogihara K, Kikuchi E*, Watanabe K, Kufukihara R, Yanai Y, Takamatsu K, Matsumoto K, Hara S, Oyama M, Monma T, Masuda T, Hasegawa S, Oya M.

Oncotarget. 8 ( 67 ) 111819 - 111835 2017

Research paper (scientific journal), Accepted

Factors influencing the operating time for single-port laparoscopic radical nephrectomy: focus on the anatomy and distribution of the renal artery and vein.

Matsumoto K, Miyajima A, Fukumoto K, Komatsuda A, Niwa N, Hattori S, Takeda T, Kikuchi E, Asanuma H, Oya M.

Jpn J Clin Oncol. 47 ( 10 ) 976 - 980 2017

Determining when to stop PSA monitoring after radical prostatectomy: the role of ultrasensitive prostate specific antigen.

Matsumoto K, Komatsuda A, Yanai Y, Niwa N, Kosaka T, Mizuno R, Kikuchi E, Miyajima A, Oya M.

J Urol. 197 ( 3 Pt1 ) 655 - 661 2017

Research paper (scientific journal), Accepted

Characterizing intermediate-risk non-muscle-invasive bladder cancer: Implications for the definition of intermediate risk and treatment strategy.

Matsumoto K, Kikuchi E, Yanai Y, Hayakawa N, Ito Y, Maeda T, Nagata H, Miyajima A, Oya M.

Urol Oncol. 35 ( 5 ) 208 - 214 2017

Research paper (scientific journal), Accepted

Simple and practical nomograms for predicting the stone-free rate after shock wave lithotripsy in patients with a solitary upper ureteral stone.

Niwa N, Matsumoto K, Miyahara M, Omura M, Kobayashi H, Kikuchi E, Miyajima A, Miyata K, Oya M.

World J Urol. 35 ( 9 ) 1455 - 1461 2017

Research paper (scientific journal), Accepted

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

Niwa N, Kikuchi E*, Matsumoto K, Miyajima A, Oya M.

Springerplus. 29 ( 5 ) 2040 2016

Research paper (scientific journal), Accepted

Technical Improvement Using a Three-Dimensional Video System for Laparoscopic Partial Nephrectomy.

Komatsuda A, Matsumoto K, Miyajima A, Kaneko G, Mizuno R, Kikuchi E, Oya M.

Asian Pac J Cancer Prev. 17 ( 5 ) 2475 - 2478 2016

Research paper (scientific journal), Accepted

Syndrome of inappropriate antidiuretic hormone secretion in a patient with castration-resistant prostate cancer treated with enzalutamide.

Yanai Y, Matsumoto K*, Niwa N, Kosaka T, Kikuchi E, Miyajima A, Ito H, Oya M.

Acta Oncol. 55 ( 3 ) 399 - 400 2016

Research paper (scientific journal), Joint Work, Accepted

A Case of Gemcitabine and Cisplatin Chemotherapy in a Patient With Metastatic Urothelial Carcinoma Receiving Hemodialysis.

Ezaki T, Matsumoto K, Morita S, Shinoda K, Mizuno R, Kikuchi E, Oya M.

Clin Genitourin Cancer. 14 ( 4 ) e413 - e416 2016

Research paper (scientific journal), Accepted

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 K, Kikuchi E*, Yuge K, Yanai Y, Matsumoto K, Miyajima A, Asakura H, Oya M.

Ann Surg Oncol. 23 ( Suppl 5 ) 1039 - 1047 2016

Research paper (scientific journal), Accepted

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

Fukumoto K, Kikuchi E*, Mikami S, Ogihara K, Matsumoto K, Miyajima A, Oya M.

Cancer Sci. 107 ( 9 ) 1338 - 1344 2016

Doctoral thesis, Accepted

Refraining from Smoking for 15 Years or More Reduced the Risk of Tumor Recurrence in Non-muscle Invasive Bladder Cancer Patients.

Ogihara K, Kikuchi E*, Yuge K, Ito Y, Tanaka N, Matsumoto K, Miyajima A, Asakura H, Oya M.

Ann Surg Oncol. 23 ( 5 ) 1752 - 1759 2016

Research paper (scientific journal), Accepted

Assessment of Prostate Cancer Aggressiveness by Use of the Combination of Quantitative DWI and Dynamic Contrast-Enhanced MRI.

Hötker AM*, Mazaheri Y, Aras Ö, Zheng J, Moskowitz CS, Gondo T, Matsumoto K, Hricak H, Akin O.

AJR Am J Roentgenol. 206 ( 4 ) 756 - 763 2016

Research paper (scientific journal), Accepted

Plasma fibrinogen level: An independent prognostic factor for disease-free survival and cancer-specific survival in patients with localized renal cell carcinoma.

Obata J, Tanaka N, Mizuno R*, Kanao K, Mikami S, Matsumoto K, Kosaka T, Kikuchi E, Jinzaki M, Oya M.

BJU Int. 118 ( 4 ) 598 - 603 2016

Research paper (scientific journal), Accepted

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

Kobayashi H, Kikuchi E*, Tanaka N, Shirotake S, Miyazaki Y, Ide H, Obata J, Hoshino K, Matsumoto K, Kaneko G, Hagiwara M, Kosaka T, Oyama M, Nakajima Y, Oya M.

Jpn J Clin Oncol. 2016

Research paper (scientific journal), Accepted

Should We Try Antiandrogen Withdrawal in Castration-Resistant Prostate Cancer Patients? Insights From a Retrospective Study.

Hongo H, Kosaka T*, Mizuno R, Ezaki T, Matsumoto K, Morita S, Shinoda K, Shinojima T, Kikuchi E, Miyajima A, Oya M.

Clin Genitourin Cancer. 14 ( 6 ) e569 - e573 2016

Research paper (scientific journal), Accepted

Erectile function status is highly associated with prostate-specific antigen bounce in localized prostate cancer patients treated with permanent prostate brachytherapy.

Matsushima M, Kikuchi E*, Matsumoto K, Kosaka T, Mizuno R, Ohashi T, Mikami S, Miyajima A, Shigematsu N, Oya M.

Int J Urol. 23 ( 3 ) 247 - 252 2016

Research paper (scientific journal), Accepted

Preoperative parameters to predict incidental (T1a and T1b) prostate cancer.

Sakamoto H, Matsumoto K, Hayakawa N, Maeda T, Sato A, Ninomiya A, Mukai K, Nakamura S.

Can Urol Assoc J. 8 ( 11-12 ) 815 2015

Research paper (scientific journal), Accepted

Bladder metastasis from renal cell carcinoma: retrospective analysis of 65 reported cases.

Matsumoto K, Hayakawa N, Nakamura S, Oya M.

Clin Exp Metastasis. 32 ( 2 ) 135 2015

Research paper (scientific journal), Accepted

The role of single instillation chemotherapy in patients who receive subsequent bacillus Calmette-Guérin: A retrospective single centre study, and systematic review of the literature.

Matsumoto K, Gondo T, Hayakawa N, Maeda T, Ninomiya A, Nakamura S.

Can Urol Assoc J. 9 ( 7-8 ) 411 2015

Research paper (scientific journal), Accepted

Automatic classification of prostate cancer Gleason scores from multiparametric magnetic resonance images.

Fehr D, Veeraraghavan H*, Wibmer A, Gondo T, Matsumoto K, Vargas HA, Sala E, Hricak H, Deasy JO.

Proc Natl Acad Sci U S A. 112 ( 46 ) E6265 - E6273 2015

Research paper (scientific journal), Accepted

Clinical role of pathological downgrading after radical prostatectomy in patients with biopsy-proven Gleason score 3+4 prostate cancer.

Gondo T, Poon BY, Matsumoto K, Bernstein M, Sjoberg DD, Eastham JA*.

BJU Int. 115 ( 1 ) 81 - 86 2015

Research paper (scientific journal), Accepted

Impact of an adjuvant chemotherapeutic regimen on the clinical outcome in high-risk patients with upper tract urothelial carcinoma: A Japanese multi-institution experience.

Shirotake S, Kikuchi E*, Tanaka N, Matsumoto K, Miyazaki Y, Kobayashi H, Ide H, Obata J, Hoshino K, Kaneko G, Hagiwara M, Kosaka T, Kanao K, Kodaira K, Hara S, Oyama M, Momma T, Miyajima A, Nakagawa K, Hasegawa S, Nakajima Y, Oya M.

J Urol. 193 ( 4 ) 1122 - 1128 2015

Research paper (scientific journal), Accepted

Therapeutic effect of intravesical administration of paclitaxel solubilized with poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) in an orthotopic bladder cancer model.

Tamura K, Kikuchi E*, Konno T, Ishihara K, Matsumoto K, Miyajima A, Oya M.

BMC Cancer. 15 ( 1 ) 317 2015

Doctoral thesis, Accepted

Intravesical dual PI3K/mTOR complex 1/2 inhibitor NVP-BEZ235 therapy in an orthotopic bladder cancer model.

Matsushima M, Kikuchi E*, Matsumoto K, Hattori S, Takeda T, Kosaka T, Miyajima A, Oya M.

Int J Oncol. 47 ( 1 ) 377 - 383 2015

Doctoral thesis, Accepted

Comparison of outcomes between ultrasonography and cystoscopy in the surveillance of patients with initially diagnosed TaG1-2 bladder cancers: A matched-pair analysis.

Niwa N, Matsumoto K, Hayakawa N, Ito Y, Maeda T, Akatsuka S, Masuda T, Nakamura S, Tanaka N*.

Urol Oncol. 33 ( 9 ) 386 2015

Research paper (scientific journal), Accepted

Haralick texture analysis of prostate MRI: utility for differentiating non-cancerous prostate from prostate cancer and differentiating prostate cancers with different Gleason scores.

Wibmer A*, Hricak H, Gondo T, Matsumoto K, Veeraraghavan H, Fehr D, Zheng J, Goldman D, Moskowitz C, Fine SW, Reuter VE, Eastham J, Sala E, Vargas HA.

Eur Radiol. 25 ( 10 ) 2840 - 2850 2015

Research paper (scientific journal), Accepted

Improved Intraoperative Visualization of Nerves through a Myelin-Binding Fluorophore and Dual-Mode Laparoscopic Imaging.

Cotero VE, Kimm SY, Siclovan TM, Zhang R, Kim EM, Matsumoto K, Gondo T, Scardino PT, Yazdanfar S, Laudone VP, Tan Hehir CA*.

PLoS One. 10 ( 6 ) e0130276. 2015

Research paper (scientific journal), Accepted

Impact of Combined Use of Blood-based Inflammatory Markers on Patients with Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy: Proposal of a Cumulative Marker Score as a Novel Predictive Tool for Prognosis.

Tanaka N, Kikuchi E*, Kanao K, Matsumoto K, Shirotake S, Miyazaki Y, Kobayashi H, Kaneko G, Hagiwara M, Ide H, Obata J, Hoshino K, Hayakawa N, Kosaka T, Hara S, Nakagawa K, Jinzaki M, Oya M.

Eur Urol Focus 1 ( 1 ) 54 - 63 2015

Research paper (scientific journal), Accepted

Efficacy of tegafur-uracil (UFT) administration in castration-resistant prostate cancer patients with a history of both alternative antiandrogen therapy and estramustine phosphate sodium hydrate therapy.

Hayakawa N, Matsumoto K, Sato A, Sakamoto H, Ezaki T, Maeda T, Ninomiya A, Nakamura S.

Int Urol Nephrol. 46 ( 6 ) 1123 2014

Research paper (scientific journal), Accepted

Survival following primary androgen deprivation therapy for localized intermediate- or high-risk prostate cancer: comparison with the life expectancy of the age-matched normal population.

Matsumoto K, Hagiwara M, Tanaka N, Hayakawa N, Ishida M, Ninomiya A, Nakajima Y, Nakamura S.

Med Oncol. 31 ( 6 ) 979 2014

Research paper (scientific journal), Accepted

Third-line hormonal therapy to treat prostate cancer relapse after initial and second-line hormonal therapy: report of 52 cases and literature review.

Matsumoto K, Hagiwara M, Hayakawa N, Tanaka N, Ito Y, Maeda T, Ninomiya A, Nagata H, Nakamura S.

Asian Pac J Cancer Prev. 15 ( 8 ) 3645 2014

Research paper (scientific journal), Accepted

Optimal timing of hormonal therapy for prostate-specific antigen recurrence after radical prostatectomy.

Matsumoto K, Mizuno R, Tanaka N, Ide H, Hasegawa M, Ishida M, Hayakawa N, Yasumizu Y, Hagiwara M, Hara S, Kikuchi E, Miyajima A, Nakagawa K, Nakajima Y, Nakamura S, Nakashima J, Oya M.

Med Oncol. 31 ( 7 ) 45 2014

Research paper (scientific journal), Accepted

Granulocyte colony-stimulating factor-producing upper urinary tract carcinoma: systematic review of 46 cases reported in Japan.

Matsumoto K, Hayakawa N, Nakamura S.

Clin Oncol (R Coll Radiol). 26 ( 12 ) 781 2014

Research paper (scientific journal), Accepted

Independent Predictors for Bladder Outcomes after Treatment of Intravesical Recurrence following Radical Nephroureterectomy in Patients with Primary Upper Tract Urothelial Carcinoma.

Tanaka N, Kikuchi E*, Kanao K, Matsumoto K, Shirotake S, Kobayashi H, Miyazaki Y, Ide H, Obata J, Hoshino K, Hayakawa N, Hagiwara M, Kosaka T, Oyama M, Miyajima A, Momma T, Nakagawa K, Jinzaki M, Hasegawa S, Nakajima Y, Oya M.

Ann Surg Oncol. 21 ( 9 ) 3151 - 3158 2014

Research paper (scientific journal), Accepted

A Multi-Institutional Validation of the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio for Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy.

Tanaka N, Kikuchi E*, Kanao K, Matsumoto K, Shirotake S, Miyazaki Y, Kobayashi H, Kaneko G, Hagiwara M, Ide H, Obata J, Hoshino K, Hayakawa N, Kosaka T, Hara S, Oyama M, Momma T, Nakajima Y, Jinzaki M, Oya M.

Ann Surg Oncol. 21 ( 12 ) 4041 - 4048 2014

Research paper (scientific journal), Accepted

Metastatic Behavior of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: Association with Primary Tumor Location.

Tanaka N, Kikuchi E*, Kanao K, Matsumoto K, Kobayashi H, Ide H, Miyazaki Y, Obata J, Hoshino K, Shirotake S, Akita H, Kosaka T, Miyajima A, Momma T, Nakagawa K, Hasegawa S, Nakajima Y, Jinzaki M, Oya M.

Ann Surg Oncol. 21 ( 3 ) 1038 - 1045 2014

Research paper (scientific journal), Accepted

The Predictive Value of C-reactive Protein for Prognosis in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy: A Multi-institutional Study.

Tanaka N, Kikuchi E*, Shirotake S, Kanao K, Matsumoto K, Kobayashi H, Miyazaki Y, Ide H, Obata J, Hoshino K, Hayakawa N, Ito Y, Kosaka T, Kodaira K, Oyama M, Miyajima A, Momma T, Nakagawa K, Ueno M, Oya M.

Eur Urol. 65 ( 1 ) 227 - 234 2014

Research paper (scientific journal), Accepted

The predictive value of positive urine cytology for outcomes following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma: A multi-institutional study.

Tanaka N, Kikuchi E*, Kanao K, Matsumoto K, Shirotake S, Kobayashi H, Miyazaki Y, Ide H, Obata J, Hoshino K, Hayakawa N, Kosaka T, Oyama M, Miyajima A, Momma T, Nakagawa K, Jinzaki M, Nakajima Y, Oya M.

Urol Oncol. 32 ( 1 ) 48 2014

Research paper (scientific journal), Accepted

Efficacy of estramustine phosphate sodium hydrate (EMP) monotherapy in castration-resistant prostate cancer patients: report of 102 cases and review of literature.

Matsumoto K*, Tanaka N, Hayakawa N, Ezaki T, Suzuki K, Maeda T, Ninomiya A, Nakamura S.

Med Oncol. 30 ( 4 ) 717 2013

Research paper (scientific journal), Accepted

Positive posterior margin of needle biopsy cores is an independent predictor for extracapsular extension in retropubic radical prostatectomy.

Yamanaka H, Matsumoto K, Obata J, Ninomiya A, Mukai K, Nakamura S.

Urology. 81 ( 5 ) 986 2013

Research paper (scientific journal), Accepted

The type of patients who would benefit from anti-androgen withdrawal therapy: could it be performed safely for aggressive prostate cancer?

Matsumoto K, Tanaka N, Hayakawa N, Ezaki T, Suzuki K, Maeda T, Ninomiya A, Nakamura S.

Med Oncol. 30 ( 3 ) 647 2013

Research paper (scientific journal), Accepted

Who would benefit from solifenacin add-on therapy to tamsulosin for overactive bladder symptoms associated with benign prostatic hyperplasia?

Obata J, Matsumoto K, Yamanaka H, Ninomiya A, Nakamura S.

LUTS. 5 145 2013

Research paper (scientific journal), Accepted

Patient characteristics and outcomes in metastatic upper tract urothelial carcinoma after radical nephroureterectomy: the experience of Japanese multi-institutions.

Tanaka N, Kikuchi E*, Kanao K, Matsumoto K, Kobayashi H, Miyazaki Y, Ide H, Obata J, Hoshino K, Shirotake S, Hayakawa N, Kosaka T, Miyajima A, Momma T, Nakagawa K, Hasegawa S, Nakajima Y, Oya M.

BJU Int. 112 ( 2 ) E28 - E34 2013

Research paper (scientific journal), Accepted

Prognostic value of plasma fibrinogen levels in patients with localized upper tract urothelial carcinoma.

Tanaka N, Kikuchi E*, Matsumoto K, Hayakawa N, Ide H, Miyajima A, Nakamura S, Oya M

BJU Int. 111 ( 6 ) 857 - 864 2013

Research paper (scientific journal), Accepted

C-reactive protein: A biomarker of survival in patients with localized upper tract urothelial carcinoma treated with radical nephroureterectomy.

Obata J, Kikuchi E*, Tanaka N, Matsumoto K, Hayakawa N, Ide H, Miyajima A, Nakagawa K, Oya M.

Urol Oncol. 31 ( 8 ) 1725 - 1730 2013

Research paper (scientific journal), Accepted

Impact of Smoking Status on Bladder Recurrence Following Radical Nephroureterectomy in Patients with Upper Tract Urothelial Carcinoma.

Hagiwara M, Kikuchi E*, Tanaka N, Matsumoto K, Ide H, Miyajima A, Masuda T, Nakamura S, Oya M.

J Urol. 189 ( 6 ) 2062 - 2068 2013

Research paper (scientific journal), Accepted

Risk of subsequent tumour recurrence and stage progression in bacille Calmette-Guérin relapsing non-muscle-invasive bladder cancer.

Matsumoto K, Kikuchi E, Shirakawa H, Hayakawa N, Tanaka N, Ninomiya A, Miyajima A, Nakamura S, Oya M.

BJU Int. 110 ( 11 ) 508 2012

Research paper (scientific journal), Accepted

Prognonstic impact of renin-angiotensin system blockade in localised upper-tract urothelial carcinoma.

Br J Cancer. 106 ( 2 ) 290 - 296 2012

Research paper (scientific journal), Accepted

Surgical and Chemotherapeutic Options for Urachal Carcinoma: Report of Ten Cases and Literature Review.

Yazawa S, Kikuchi E*, Takeda T, Matsumoto K, Miyajima A, Nakagawa K, Oya M.

Urol Int. 88 ( 2 ) 209 - 214 2012

Research paper (scientific journal), Accepted

Prognostic significance of Bacillus Calmette-Guérin failure classification in non-muscle-invasive bladder cancer.

Shirakawa H, Kikuchi E*, Tanaka N, Matsumoto K, Miyajima A, Nakamura S, Oya M.

BJU Int. 110 ( 6 Pt B ) E216 - E221 2012

Research paper (scientific journal), Accepted

Prognostic role of KiSS-1 and possibility of therapeutic modality of metastin, the final peptide of the KiSS-1 gene, in urothelial carcinoma.

Takeda T, Kikuchi E*, Mikami S, Suzuki E, Matsumoto K, Miyajima A, Okada Y, Oya M.

Mol Cancer Ther. 11 ( 4 ) 853 - 863 2012

Doctoral thesis, Accepted

Intravesical interleukin-15 gene therapy in an orthotopic bladder cancer model.

Matsumoto K, Kikuchi E, Horinaga M, Takeda T, Miyajima A, Nakagawa K, Oya M.

Hum Gene Ther. 22 ( 11 ) 1423 2011

Research paper (scientific journal), Accepted

Efficacy of tension-free vaginal tape compared with transobturator tape in the treatment of stress urinary incontinence in women: analysis of learning curve, perioperative changes of voiding function.

Ito H*, Yamanaka H, Hagiwara M, Furuuchi T, Matsumoto K, Kanai K, Kodaira K, Ninomiya A, Nakamura S.

BMC Urol. 11 13 2011

Research paper (scientific journal), Accepted

Benefit of laparoscopic radical nephrectomy in patients with a high BMI.

Hagiwara M, Miyajima A*, Matsumoto K, Kikuchi E, Nakagawa K, Oya M.

Jpn J Clin Oncol. 41 ( 3 ) 400 - 404 2011

Research paper (scientific journal), Accepted

Frequency of tumor recurrence: a strong predictor of stage progression in initially diagnosed nonmuscle invasive bladder cancer.

Tanaka N, Kikuchi E*, Matsumoto K, Miyajima A, Nakagawa K, Oya M.

J Urol. 185 ( 2 ) 450 - 455 2011

Research paper (scientific journal), Accepted

The clinical impact of the classification of carcinoma in situ on tumor recurrence and their clinical course in patients with bladder tumor.

Jpn J Clin Oncol. 41 ( 3 ) 424 - 429 2011

Research paper (scientific journal), Accepted

Could patient age influence tumor recurrence rate in non-muscle-invasive bladder cancer patients treated with BCG immunotherapy?

Yuge K, Kikuchi E*, Matsumoto K, Takeda T, Miyajima A, Oya M.

Jpn J Clin Oncol. 41 ( 4 ) 565 - 570 2011

Research paper (scientific journal), Accepted

Urinary pH is highly associated with tumor recurrence during intravesical mitomycin C therapy for nonmuscle invasive bladder tumor.

Maeda T, Kikuchi E*, Matsumoto K, Miyajima A, Oya M.

J Urol. 185 ( 3 ) 802 - 806 2011

Research paper (scientific journal), Accepted

Neoadjuvant gemcitabine plus cisplatin for muscle-invasive bladder cancer.

Kaneko G, Kikuchi E*, Matsumoto K, Obata J, Nakamura S, Miyajima A, Oya M.

Jpn J Clin Oncol. 41 ( 7 ) 908 - 914 2011

Research paper (scientific journal), Accepted

Contrast-enhanced ultrasonography of the prostate with Sonazoid.

Matsumoto K, Nakagawa K, Hashiguchi A, Kono H, Kikuchi E, Nagata H, Miyajima A, Oya M.

Jpn J Clin Oncol. 40 ( 11 ) 1099 2010

Research paper (scientific journal), Accepted

Late recurrence and progression in non-muscle-invasive bladder cancers after 5-year tumor-free periods.

Matsumoto K, Kikuchi E, Horiguchi Y, Tanaka N, Miyajima A, Nakagawa K, Nakashima J, Oya M.

Urology. 75 ( 6 ) 1385 2010

Research paper (scientific journal), Accepted

Clinical impact of bladder biopsies with TUR-BT according to cytology results in patients with bladder cancer: a case control study.

Matsushima M, Kikuchi E*, Hasegawa M, Matsumoto K, Miyajima A, Oya M.

BMC Urol. 10 12 2010

Research paper (scientific journal), Accepted

The clinical significance of urine cytology after a radical cystectomy for urothelial cancer.

Yoshimine S, Kikuchi E*, Matsumoto K, Ide H, Miyajima A, Nakagawa K, Oya M.

Int J Urol. 17 ( 6 ) 527 - 532 2010

Research paper (scientific journal), Accepted

Gemcitabine and cisplatin chemotherapy induced reversible posterior leukoencephalopathy syndrome in a bladder cancer patient.

Maeda T, Kikuchi E*, Matsumoto K, Yazawa S, Hagiuda J, Miyajima A, Nakagawa K, Fujiwara H, Hoshino H, Oya M.

Int J Clin Oncol. 15 ( 5 ) 508 - 511 2010

Research paper (scientific journal), Accepted

Role of pelvic lymph node dissection in lymph node-negative patients with invasive bladder cancer.

Shirotake S, Kikuchi E*, Matsumoto K, Yazawa S, Kosaka T, Miyajima A, Nakagawa K, Oya M.

Jpn J Clin Oncol. 40 ( 3 ) 247 - 251 2010

Research paper (scientific journal), Accepted

Potent cytotoxic effect of a novel nuclear factor-kappaB inhibitor dehydroxymethylepoxyquinomicin on human bladder cancer cells producing various cytokines.

Kodaira K, Kikuchi E*, Kosugi M, Horiguchi Y, Matsumoto K, Kanai K, Suzuki E, Miyajima A, Nakagawa K, Tachibana M, Umezawa K, Oya M.

Urology. 75 ( 4 ) 805 - 812 2010

Doctoral thesis, Accepted

Discontinuance of bacille Calmette-Guérin instillation therapy for nonmuscle-invasive bladder cancer has negative effect on tumor recurrence.

Takeda T, Kikuchi E*, Yuge K, Matsumoto K, Miyajima A, Nakagawa K, Oya M.

Urology. 73 ( 6 ) 1318 - 1322 2009

Research paper (scientific journal), Accepted

Pharmacokinetics of cisplatin and methotrexate after M-VAC chemotherapy for advanced urothelial cancer in hemodialysis patients.

Matsumoto K

Int J Urol. 15 ( 10 ) 949 2008

Research paper (scientific journal), Accepted

Is interval from an initial biopsy a significant predictor of prostate cancer at repeat biopsies?

Satoh A*, Matsumoto K, Nakamura S.

Int J Urol. 13 ( 3 ) 224 - 227 2006

Research paper (scientific journal), Accepted

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