Details of a Researcher - Matsumoto, Kazuhiro

Papers - Matsumoto, Kazuhiro

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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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