Details of a Researcher - Matsumoto, Kazuhiro

Papers - Matsumoto, Kazuhiro

Division display 1 - 20 of about 141 ／ All the affair displays >>

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

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.

Access to Document (DOI)

　 Previous page - Next page 　