Details of a Researcher - Tanaka, Nobuyuki

Papers - Tanaka, Nobuyuki

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Appropriate definition of non-metastatic castration-resistant prostate cancer (nmCRPC) and optimal timing of androgen receptor signaling inhibitor (ARSI)

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

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 29 ( 8 ) 1198 - 1203 2024

ISSN 13419625

Background: Defined by rising PSA levels under androgen deprivation therapy (ADT) despite no visible metastases on conventional imaging, non-metastatic castration-resistant prostate cancer (nmCRPC) represents a complex clinical challenge. A significant subset of these patients rapidly develops metastatic disease, negatively impacting survival. We examined the difference in prognosis of nmCRPC patients according to the timing of therapeutic interventions with androgen receptor signaling inhibitor (ARSI). Methods: We examined 102 nmCRPC patients treated with ARSI. We divided patients according to their PSA levels when ARSI was administered: Cohort A (PSA 0.5–2.0 ng/mL), Cohort B (PSA 2.0–4.0 ng/mL), and Cohort C (PSA > 4.0 ng/mL). Utilizing the Kaplan–Meier method for survival analysis, our analytical starting point was the moment when PSA levels exceeded 0.5 ng/mL post-ADT nadir, ensuring a fair comparison and minimizing lead-time bias. Results: After excluding 5 patients whose PSA nadir after ADT > 0.5 ng/mL, patient distribution across Cohort A, Cohort B, and Cohort C was 32, 24, and 41 patients, respectively. Kaplan–Meier survival analysis highlighted a 2-year metastasis-free survival rate of 97% for Cohort A, 87% for Cohort B, and 73% for Cohort C. A marked statistical difference emerged when comparing Cohort A with Cohorts B and C, with a p-value of 0.043. Conclusion: The timely initiation of ARSI is paramount in nmCRPC management. Our findings strongly advocate for consideration of ARSI administration in nmCRPC patients before their PSA levels exceed 2.0 ng/mL. Our results indicated a PSA threshold of 1.0 ng/mL for nmCRPC definition which is more reasonable to administer ARSI without delay.

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AUGMENTED ONLAY BUCCAL MUCOSAL GRAFT URETEROPLASTY FOR URETERAL STRICTURE: A CASE REPORT

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

Japanese Journal of Urology 115 ( 1 ) 37 - 41 2024

ISSN 00215287

A 14-year-old boy developed hydronephrosis and worsening renal function due to fibroepithelial polyps of the bladder and left ureter at the age of 12 years. The endoscopic treatment of ureteral polyps was attempted by his previous doctor; however urethral stricture and ureteral stricture developed and was untreatable. Therefore, he was referred to our hospital for further reconstructive treatment. He underwent Palminteri urethroplasty with penile skin graft for urethral stricture at the age of 13 years, followed by ureteroplasty at the age of 14 years. The stenotic ureter was minimally resected, with only complete obstruction and residual polyps, and augmented onlay ureteroplasty with a buccal mucosa graft was performed. Nephrostomy was removed 13 days after surgery, followed by the ureteral stent 4 months after surgery. Retrograde pyelography and ureteroscopy were performed 1 year and 2 years postoperatively, and neither recurrent strictures nor polyps were observed. The patient is doing well 3 years postoperatively.

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進行性尿路上皮癌に対するペムブロリズマブ投与中に副腎皮質刺激ホルモン単独欠損症をきたした血液透析患者の1例

北岡壮太郎, 水野隆一, 吉田理, 高橋遼平, 安水洋太, 田中伸之, 森田伸也, 大家基嗣

泌尿器外科 (医学図書出版(株)) 36 ( 11 ) 1258 - 1261 2023.11

ISSN 0914-6180

症例は79歳女性。右腎盂癌(pT1N0M0)にて右腎尿管全摘除術を施行後の約1年後に血液透析導入となった。術後2年で多発肺転移にて再発し,救援化学療法を2コース施行するもPDであったため,2次化学療法としてペムブロリズマブを開始した。6コース投与後に持続する発熱,倦怠感,脱力,意識障害にて当院に入院し,ACTH単独欠損症の診断となりirAEと考えられた。維持透析下でヒドロコルチゾンを補充し症状は改善,そのままペムブロリズマブを投与再開し,9ヵ月間PRを維持できた。(著者抄録)

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 2023.09

ISSN 0301-1623

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 ) 6945 2023.07

ISSN 1068-9265

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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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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 ) 100040 2023.01

ISSN 0023-6837

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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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 : official journal of the Brazilian Society of Urology (International braz j urol : official journal of the Brazilian Society of Urology) 49 ( 1 ) 50 - 60 2023.01

ISSN 1677-5538

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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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

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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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

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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Surgical Treatment for Metastatic Brain Tumor in the Cerebellar Hemisphere from Small-cell Neuroendocrine Carcinoma of the Urinary Bladder: A Case Report and Review of the Literature.

Sogano J, Takahashi S, Tanaka N, Kubo H, Okita H, Oya M, Toda M

NMC case report journal 10 235 - 239 2023

ISSN 2188-4226

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IMAGENE trial: multicenter, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy of niraparib with PD-1 inhibitor in solid cancer patients with homologous recombination repair genes mutation

Kato T., Matsubara N., Shiota M., Eto M., Osawa T., Abe T., Shinohara N., Yasumizu Y., Tanaka N., Oya M., Nishimoto K., Hayashi T., Nakayama M., Kojima T., Namikawa K., Fujisawa T., Okano S., Hida E., Nakamura Y., Bando H., Yoshino T., Nonomura N.

BMC Cancer (BMC Cancer) 22 ( 1 ) 1292 2022.12

Background: Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis. Methods: Key eligibility criteria for this trial includes HRR gene-mutated tumor determined by any cancer gene tests; progression after previous ICI treatment; and Eastern Cooperative Oncology Group Performance Status ≤ 1. The primary endpoint is the confirmed objective response rate (ORR) in all patients. The secondary endpoints include the confirmed ORR in patients with HRR gene-mutation of ctDNA using the Caris Assure (CARIS, USA). The target sample size of the IMAGENE trial is 57 patients. Biomarker analyses will be performed in parallel using the Caris Assure, proteome analysis, and T cell repertoire analysis to reveal tumor immunosurveillance in peripheral blood. Expected outcome: Our trial aims to confirm the clinical benefit of PARPi plus ICI combination therapy in ICI-resistant patients. Furthermore, through translational research, our trial will shed light on which patients would benefit from the targeted combination therapy for patients with HRR gene-mutated tumor even after the failure of ICIs. Trial registration: The IMAGENE trial: jRCT, Clinical trial no.: jRCT2051210120, Registered date: November 9, 2021.

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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 : official journal of the Japanese Urological Association (International Journal of Urology) 29 ( 12 ) 1447 - 1454 2022.08

ISSN 0919-8172

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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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 2022.08

ISSN 1558-7673

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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Principal component analysis of early immune cell dynamics during pembrolizumab treatment of advanced urothelial carcinoma

Teshima T., Kobayashi Y., Kawai T., Kushihara Y., Nagaoka K., Miyakawa J., Akiyama Y., Yamada Y., Sato Y., Yamada D., Tanaka N., Tsunoda T., Kume H., Kakimi K.

Oncology Letters (Oncology Letters) 24 ( 2 ) 265 2022.08

ISSN 17921074

Immune checkpoint inhibitors have been approved as second-line therapy for patients with advanced urothelial carcinoma (UC). However, which patients will obtain clinical benefit remains to be determined. To identify predictive biomarkers for the pembrolizumab (PEM) response early during treatment, the present study investigated 31 patients with chemotherapy-resistant recurrent or metastatic UC who received 200 mg PEM intravenously every 3 weeks. Blood was taken just before the first dose and again before the second dose, and the peripheral blood mononuclear cells of all 31 pairs of blood samples were immune phenotyped by flow cytometry. Data were assessed by principal component analysis (PCA), correlation analysis and Cox proportional hazards modeling in order to comprehensively determine the effects of PEM on peripheral mononuclear immune cells. Absolute counts of CD45RA+CD27-CCR7- terminally differentiated CD8+ T cells and KLRG1+CD57+ senescent CD8+ T cells were significantly increased after PEM administration (P=0.042 and P=0.043, respectively). Senescent and exhausted CD4+ and CD8+ T cell dynamics were strongly associated with each other. By contrast, counts of monocytic myeloid-derived suppressor cells (mMDSCs) were not associated with other immune cell phenotypes. The results of PCA and non-hierarchical clus-tering of patients suggested that excessive T cell senescence and differentiation early during treatment were not neces-sarily associated with a survival benefit. However, decreased mMDSC counts after PEM were associated with improved overall survival. In conclusion, early on-treatment peripheral T cell status was associated with response to PEM; however, it was not associated with clinical benefit. By contrast, decreased peripheral mMDSC counts did predict improved overall survival.

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射精機能温存の接触式レーザー前立腺蒸散術が施行された患者の治療成績

田中伸之, 三條丹星, 大家基嗣

日本排尿機能学会誌 ((一社)日本排尿機能学会) 32 ( 2 ) 429 - 433 2022.07

ISSN 1347-6513

目的:前立腺肥大症に対する接触式レーザー前立腺蒸散術(CVP)は,980nmダイオードレーザーで肥大した前立腺組織を気化・除去する.一方,通常の前立腺肥大症手術では,逆行性射精が合併する.この問題の解決に我々は,射精機能を温存するCVPに取り組んでいる.方法:当院で施行された射精機能温存CVPについて,周術期・術後アウトカムの臨床的検討を行った.前立腺レーザー蒸散は,中葉〜精丘付近〜側葉の順に蒸散を行った.射精機能を温存する場合は,精丘から7mm以上を肉眼的所見でのマージンとし,可能な限り低出力で周囲を蒸散した.結果:射精機能温存を行ったCVP患者12例においては,手術関連の重篤な合併症は認められず,術後排尿機能の改善も著明であった.射精機能は術後6ヵ月の時点で,12例中10例(83%)で保持されていた.結論:射精機能温存を試みたCVP施行12例の周術期・術後アウトカムを報告した.約8割の症例で順行性射精が可能であった.(著者抄録)

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 2022.06

ISSN 1435-2443

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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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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【腹部の最新画像情報2022】症例　術後早期に遠隔転移を認めた表在性膀胱小細胞癌の2例

竹下諒, 有田祐起, 秋田大宇, 三上修治, 田中伸之, 奥田茂男, 大家基嗣, 陣崎雅弘

臨床放射線 (金原出版(株)) 67 ( 5 ) 505 - 510 2022.05

ISSN 0009-9252

症例1は60歳代女性。主訴は肉眼的血尿であった。MRI T2強調像で膀胱左側壁に21mm大の広基性腫瘤を認め、経尿道的膀胱腫瘍切除術を行った。病理学的に膀胱小細胞癌と診断した。2年後のFDG-PETで右腋窩・右側腹部の皮下腫瘤、左腸骨動脈リンパ節にFDGの強い集積亢進を認め、膀胱小細胞癌の転移と考えられた。症例2は60歳代男。主訴は肉眼的血尿であった。MRI T2強調像で膀胱前壁に12mm大の広基性腫瘤を認め、経尿道的膀胱腫瘍切除術、その後膀胱全摘術を行った。病理学的に膀胱小細胞癌と診断した。1年後のCTで両肺に多発する増大傾向の結節を認め、膀胱小細胞癌の転移と考えられた。

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