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Article ; Online: Clinical features and oncological outcomes of bladder cancer microsatellite instability.

Nagakawa, Shohei / Shiota, Masaki / Takamatsu, Dai / Tsukahara, Shigehiro / Mastumoto, Takashi / Blas, Leandro / Inokuchi, Junichi / Oda, Yoshihiro / Eto, Masatoshi

International journal of urology : official journal of the Japanese Urological Association

2024 Volume 31, Issue 4, Page(s) 438–445

Abstract: Objectives: Excellent anticancer effect for solid tumors with microsatellite instability (MSI)-high by anti-PD-1 antibody has been reported. In this study, we investigated the clinical impact of MSI status in bladder cancer.: Methods: This study ... ...

Abstract	Objectives: Excellent anticancer effect for solid tumors with microsatellite instability (MSI)-high by anti-PD-1 antibody has been reported. In this study, we investigated the clinical impact of MSI status in bladder cancer. Methods: This study included 205 Japanese patients who underwent transurethral resection for bladder cancer between 2005 and 2021. The prevalence rates of microsatellite stable (MSS), MSI-low (MSI-L), and MSI-high (MSI-H) were determined using molecular testing. We examined the association of MSI status (MSS versus MSI-L/H) with clinicopathological characteristics and oncological outcomes. Results: MSI-L/H tumors were associated with higher T-category in non-muscle invasive bladder cancer (NMIBC). Additionally, MSI-L/H tumors were associated with a higher risk of intravesical recurrence in NMIBC patients treated with intravesical bacillus Calmette-Guérin (BCG) but not with non-BCG therapy. Conclusions: This study suggested that the MSI status might serve as a predictive marker for intravesical recurrence after BCG intravesical therapy in NMIBC and highlighted an unmet need for an alternative treatment in patients with MSI-L/H tumors.
MeSH term(s)	Humans ; BCG Vaccine/therapeutic use ; Microsatellite Instability ; Non-Muscle Invasive Bladder Neoplasms ; Adjuvants, Immunologic ; Administration, Intravesical ; Urinary Bladder Neoplasms/therapy ; Urinary Bladder Neoplasms/drug therapy ; Neoplasm Invasiveness/pathology ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/drug therapy
Chemical Substances	BCG Vaccine ; Adjuvants, Immunologic
Language	English
Publishing date	2024-01-09
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1328401-0
ISSN	1442-2042 ; 0919-8172
ISSN (online)	1442-2042
ISSN	0919-8172
DOI	10.1111/iju.15370
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Zs.A 4460: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 278: Show issues

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Article ; Online: TFE3-immunopositive papillary renal cell carcinoma: A clinicopathological, immunohistochemical, and genetic study.

Takamatsu, Dai / Kohashi, Kenichi / Kiyozawa, Daisuke / Kinoshita, Fumio / Ieiri, Kosuke / Baba, Masaya / Eto, Masatoshi / Oda, Yoshinao

Pathology, research and practice

2023 Volume 242, Page(s) 154313

Abstract: It is possible that PRCCs may still contain a variety of unknown histologic subtypes. Some PRCCs express high expression of TFE3 protein without TFE3 gene rearrangement, but no reports have investigated the significance of this. Here we attempted to ... ...

Abstract	It is possible that PRCCs may still contain a variety of unknown histologic subtypes. Some PRCCs express high expression of TFE3 protein without TFE3 gene rearrangement, but no reports have investigated the significance of this. Here we attempted to examine clinicopathological and molecular significance of the TFE3-immunopositive PRCC. We reviewed the histology and immunohistochemistry in 58 PRCCs. TFE3 immunoexpression was recognized in 7 cases. Because TFE3 immunostaining shows false-positive, to ensure the integrity of TFE3 immunostaining, the immunostaining was performed under strict control of internal controls and western blotting was performed on 2 positive cases and 5 negative cases, and differences in protein expression between two groups were confirmed. Significant immunohistochemical expressions of autophagy/lysosome proteins were observed in TFE3-positive group. No TFE3 gene arrangement was detected in all positive cases by fluorescence in situ hybridization. Whole-exome sequencing was performed on 6 TFE3-positive and 2 TFE3-negative cases. Gain of chromosome 7 was found in five of 6 TFE3-positive cases (83%). TFE3-positive group was correlated significantly with higher pTstage, cNstage, WHO/ISUP nuclear grade, and decreased OS. TFE3-immunopositive PRCC group had a poorer prognosis than TFE3-negative PRCC group and showed correlation with expressions of autophagy/lysosome proteins, suggesting that enhancement of autophagy/lysosome function drives an environment of energy metabolism that is favorable for cancer. It is necessary to recognize that there is TFE3-immunopositive group without TFE3 gene rearrangement within PRCC. Because of its aggressive biological behaviour, TFE3 can act as a biomarker in PRCC; moreover, autophagy-inhibiting drugs may have therapeutic effects on TFE3-immunopositive PRCC.
MeSH term(s)	Humans ; Carcinoma, Renal Cell/pathology ; Kidney Neoplasms/pathology ; In Situ Hybridization, Fluorescence ; Transcription Factors/genetics ; Translocation, Genetic ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics
Chemical Substances	Transcription Factors ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; TFE3 protein, human
Language	English
Publishing date	2023-01-16
Publishing country	Germany
Document type	Review ; Journal Article
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2023.154313
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Article ; Online: Interstitial pneumonia after regression by olaparib for neuroendocrine prostate cancer with

Kaitsumaru, Masashi / Shiota, Masaki / Takamatsu, Dai / Blas, Leandro / Matsumoto, Takashi / Inokuchi, Junichi / Oda, Yoshinao / Eto, Masatoshi

International cancer conference journal

2023 Volume 12, Issue 2, Page(s) 131–136

Abstract: A 67-year-old man with metastatic prostate cancer was treated with leuprorelin and enzalutamide, but presented radiographic progression after 1 year. Although docetaxel chemotherapy was initiated, liver metastasis appeared with elevation of nerve- ... ...

Abstract	A 67-year-old man with metastatic prostate cancer was treated with leuprorelin and enzalutamide, but presented radiographic progression after 1 year. Although docetaxel chemotherapy was initiated, liver metastasis appeared with elevation of nerve-specific enolase in serum. Pathological findings of needle biopsy of lymph node metastasis in the right inguinal region showed neuroendocrine carcinoma. FoundationOne CDx
Language	English
Publishing date	2023-01-03
Publishing country	Singapore
Document type	Case Reports
ISSN	2192-3183
ISSN (online)	2192-3183
DOI	10.1007/s13691-022-00592-5
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Article ; Online: Prognostic impact of CD73/adenosine 2A receptor (A2AR) in renal cell carcinoma and immune microenvironmental status with sarcomatoid changes and rhabdoid features.

Takamatsu, Dai / Kiyozawa, Daisuke / Kohashi, Kenichi / Kinoshita, Fumio / Toda, Yu / Ishihara, Shin / Eto, Masatoshi / Oda, Yoshinao

Pathology, research and practice

2023 Volume 244, Page(s) 154423

Abstract: One of the most aggressive forms of kidney cancer is renal cell carcinoma (RCC) with sarcomatoid changes and rhabdoid features (S/R). Adenosine produced via CD73 binds to adenosine 2 A receptor (A2AR) and suppress antitumor immunity. Here, we attempted ... ...

Abstract	One of the most aggressive forms of kidney cancer is renal cell carcinoma (RCC) with sarcomatoid changes and rhabdoid features (S/R). Adenosine produced via CD73 binds to adenosine 2 A receptor (A2AR) and suppress antitumor immunity. Here, we attempted to analyze the expression of CD73/A2AR in S/R RCC and examined its relationships with other immune microenvironments and prognostic effect. Sixty cases of S/R RCC were selected. CD73/A2AR expression levels were graded in the tumor cells or infiltrating immune cells on a score of 0-3 and divided into low (0 or 1) or high (2 or 3) groups. PD-L1 results were defined by the tumor proportion score (TPS). We counted the numbers of CD8
MeSH term(s)	Humans ; Carcinoma, Renal Cell/pathology ; Prognosis ; Kidney Neoplasms/pathology ; Signal Transduction ; Soft Tissue Neoplasms ; Adenosine ; Tumor Microenvironment
Chemical Substances	Adenosine (K72T3FS567)
Language	English
Publishing date	2023-03-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2023.154423
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Article ; Online: NR5A2/HSD3B1 pathway promotes cellular resistance to second-generation antiandrogen darolutamide.

Shiota, Masaki / Ushijima, Miho / Tsukahara, Shigehiro / Nagakawa, Shohei / Blas, Leandro / Takamatsu, Dai / Kobayashi, Satoshi / Matsumoto, Takashi / Inokuchi, Junichi / Eto, Masatoshi

Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy

2023 Volume 70, Page(s) 100990

Abstract: This study investigated cellular mechanisms in steroidogenesis responsible for treatment resistance to the novel antiandrogen agent darolutamide in prostate cancer. HSD3B1 was overexpressed in darolutamide-resistant cells and induced by darolutamide ... ...

Abstract	This study investigated cellular mechanisms in steroidogenesis responsible for treatment resistance to the novel antiandrogen agent darolutamide in prostate cancer. HSD3B1 was overexpressed in darolutamide-resistant cells and induced by darolutamide treatment and AR knockdown. Inversely, HSD3B1 knockdown increased cellular sensitivity to darolutamide. Similarly, its upstream regulator NR5A2 was up-regulated in darolutamide-resistant cells and induced by darolutamide treatment and AR knockdown. Inversely, NR5A2 knockdown and NR5A2 inhibitor ML180 decreased expression of various steroidogenic enzymes including HSD3B1, leading to increased cellular sensitivity to darolutamide. The NR5A2/HSD3B1 pathway promoted cellular resistance to darolutamide and targeting NR5A2/HSD3B1 pathway is a promising therapeutic strategy to overcome darolutamide resistance.
MeSH term(s)	Humans ; Male ; Androgen Antagonists/pharmacology ; Androgen Antagonists/therapeutic use ; Androgen Receptor Antagonists/pharmacology ; Androgen Receptor Antagonists/therapeutic use ; Multienzyme Complexes/metabolism ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism
Chemical Substances	Androgen Antagonists ; Androgen Receptor Antagonists ; darolutamide ; Multienzyme Complexes ; NR5A2 protein, human ; Receptors, Cytoplasmic and Nuclear
Language	English
Publishing date	2023-07-17
Publishing country	Scotland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1474513-6
ISSN	1532-2084 ; 1368-7646
ISSN (online)	1532-2084
ISSN	1368-7646
DOI	10.1016/j.drup.2023.100990
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Zs.A 5099: Show issues

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Article ; Online: Comparative analyses of tumour immune microenvironment between collecting duct carcinoma and fumarate hydratase-deficient renal cell carcinoma.

Kiyozawa, Daisuke / Kohashi, Kenichi / Takamatsu, Dai / Umekita, Shinya / Eto, Masatoshi / Kinjo, Mitsuru / Nishiyama, Kenichi / Taguchi, Kenichi / Oshiro, Yumi / Kuboyama, Yusuke / Oda, Yoshinao

Journal of clinical pathology

2024 Volume 77, Issue 2, Page(s) 105–110

Abstract: Aims: Collecting duct carcinoma (CDC) and fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) have similar histological morphologies and both show a poor prognosis. Programmed death ligand 1 (PD-L1) inhibitor has been approved for the ... ...

Abstract	Aims: Collecting duct carcinoma (CDC) and fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) have similar histological morphologies and both show a poor prognosis. Programmed death ligand 1 (PD-L1) inhibitor has been approved for the treatment of RCC. However, tumour-infiltrating neutrophils stimulated by interleukin-8 (IL-8) interfere with PD-L1 inhibitors. Here, we retrospectively analysed PD-L1 and IL-8 expression, and examined its relationship with infiltrating immune cells. Methods: Nine cases of CDC and seven cases of FH-deficient RCC were selected. We defined PD-L1 and IL-8 expression by the Tumour Proportion Score and Combined Positive Score (CPS). We counted the numbers of CD8 Results: A number of CXCR2 Conclusions: Our results suggest the difference of each tumour microenvironment between CDC and FH-deficient RCC, and IL-8 is a potential therapeutic target for treating CDC, but not FH-deficient RCC.
MeSH term(s)	Humans ; Carcinoma, Renal Cell/pathology ; Kidney Neoplasms/pathology ; Fumarate Hydratase ; B7-H1 Antigen ; Interleukin-8 ; Retrospective Studies ; Tumor Microenvironment
Chemical Substances	Fumarate Hydratase (EC 4.2.1.2) ; B7-H1 Antigen ; Interleukin-8
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	80261-x
ISSN	1472-4146 ; 0021-9746
ISSN (online)	1472-4146
ISSN	0021-9746
DOI	10.1136/jcp-2022-208589
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Article ; Online: Salvage robot-assisted radical prostatectomy after carbon ion radiotherapy to the prostate.

Shiota, Masaki / Tsukahara, Shigehiro / Takamatsu, Dai / Tanegashima, Tokiyoshi / Ueda, Shohei / Blas, Leandro / Goto, Shunsuke / Kobayashi, Satoshi / Matsumoto, Takashi / Inokuchi, Junichi / Shioyama, Yoshiyuki / Eto, Masatoshi

Asian journal of endoscopic surgery

2024 Volume 17, Issue 1, Page(s) e13279

Abstract: Purpose: This study presents the surgical and oncological outcomes of salvage robot-assisted radical prostatectomy (RARP) after carbon ion radiotherapy at a single institution.: Methods: Patients who underwent salvage RARP for local recurrence after ... ...

Abstract	Purpose: This study presents the surgical and oncological outcomes of salvage robot-assisted radical prostatectomy (RARP) after carbon ion radiotherapy at a single institution. Methods: Patients who underwent salvage RARP for local recurrence after carbon ion radiotherapy at Kyushu University Hospital between 2020 and 2023 were included. A single surgeon performed salvage RARP with extended pelvic lymph node dissection. Clinicopathological characteristics and perioperative and postoperative outcomes were prospectively collected and electronically recorded. Results: Ten cases were included. The preoperative clinical T-stage was T2, except for one case with T3a. The median console time was 171 min (range, 135-226 min). No severe perioperative or postoperative complications were noted. The pathological T-stage was T2, T3a, and T3b in four, four, and two cases, respectively. Biochemical recurrence was observed in one patient at 31.2 months after surgery. For patients with more than 1 year of follow-up, urinary continence recovery with ≤1 pad was achieved in two cases within 1 year, whereas four cases did not recover urinary continence within 1 year. Conclusions: This case series demonstrated the feasibility of salvage RARP after carbon ion radiotherapy. Although the urinary continence recovery was modest, short-term disease control was favorable.
MeSH term(s)	Male ; Humans ; Prostate/pathology ; Robotics ; Urinary Incontinence/etiology ; Urinary Incontinence/surgery ; Prostatic Neoplasms/radiotherapy ; Prostatic Neoplasms/surgery ; Treatment Outcome ; Robotic Surgical Procedures/adverse effects ; Prostatectomy/adverse effects ; Heavy Ion Radiotherapy/adverse effects
Language	English
Publishing date	2024-01-22
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2503256-2
ISSN	1758-5910 ; 1758-5902
ISSN (online)	1758-5910
ISSN	1758-5902
DOI	10.1111/ases.13279
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Zs.A 6788: Show issues

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Article ; Online: Novel nomogram to predict biochemical recurrence-free survival after radical prostatectomy.

Blas, Leandro / Shiota, Masaki / Takamatsu, Dai / Kinoshita, Fumio / Matsumoto, Takashi / Lee, Ken / Monji, Keisuke / Kashiwagi, Eiji / Inokuchi, Junichi / Eto, Masatoshi

World journal of urology

2022 Volume 41, Issue 1, Page(s) 43–50

Abstract: Purpose: Conditional survival represents the probability of subsequent survival given that patients have already survived a certain length of time. Several models predict biochemical recurrence (BCR) after radical prostatectomy. However, none of them ... ...

Abstract	Purpose: Conditional survival represents the probability of subsequent survival given that patients have already survived a certain length of time. Several models predict biochemical recurrence (BCR) after radical prostatectomy. However, none of them include postoperative prostate-specific antigen (PSA). We aimed to analyze BCR-free survival evolution over time and develop a nomogram incorporating the postoperative PSA value to predict BCR-free survival. Material and methods: We included patients treated with robot-assisted radical prostatectomy (RARP) for prostate cancer between 2009 and 2021 and calculated conditional survival. Cox proportional hazard regression analysis was used to assess the predictive variables of BCR. We developed a nomogram predicting BCR-free survival three and five years after RARP. We used c-index and decision curve analyses to compare the nomogram with the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score. Results: We included 718 patients. The overall 3- and 5-year BCR-free survival rates were 85.1% and 75.7%, respectively. The 5-year BCR-free survival rates increased to 78.9%, 82.9%, 85.2%, and 84.7% for patients surviving 1, 2, 3, and 4 years without BCR, respectively. We developed a nomogram including the pathological Gleason score and T stage, positive surgical margin, PSA ≥ 0.05 ng/mL at one year, and lymph node involvement to predict BCR at 3 and 5 years postoperatively. Our nomogram presented a higher c-index (0.89) than the CAPRA-S score (0.78; p = 0.001) and a positive net benefit at 3 and 5 years postoperatively in the decision curve analyses. Conclusion: The 5-year conditional BCR-free survival increased with survival without BCR. The developed nomogram significantly improved the accuracy in predicting BCR-free survival after RARP.
MeSH term(s)	Male ; Humans ; Nomograms ; Prostate-Specific Antigen ; Prostate/pathology ; Prostatic Neoplasms/pathology ; Prostatectomy/adverse effects ; Neoplasm Recurrence, Local/pathology
Chemical Substances	Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2022-12-17
Publishing country	Germany
Document type	Journal Article
ZDB-ID	380333-8
ISSN	1433-8726 ; 0724-4983
ISSN (online)	1433-8726
ISSN	0724-4983
DOI	10.1007/s00345-022-04245-3
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Zs.A 1832: Show issues

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Article ; Online: Impact of nerve sparing in robot-assisted radical prostatectomy on the risk of positive surgical margin and biochemical recurrence.

Komori, Hiroki / Blas, Leandro / Shiota, Masaki / Takamatsu, Dai / Matsumoto, Takashi / Lee, Ken / Monji, Keisuke / Kashiwagi, Eiji / Inokuchi, Junichi / Eto, Masatoshi

International journal of urology : official journal of the Japanese Urological Association

2022 Volume 29, Issue 8, Page(s) 824–829

Abstract: Objectives: Nerve sparing may increase positive surgical margin rate during radical prostatectomy. Our objective was to analyze the positive surgical margin rate and location as well as its impact on biochemical recurrence according to nerve sparing ... ...

Abstract	Objectives: Nerve sparing may increase positive surgical margin rate during radical prostatectomy. Our objective was to analyze the positive surgical margin rate and location as well as its impact on biochemical recurrence according to nerve sparing procedure in robot-assisted radical prostatectomy. Methods: We included 814 patients treated with robot-assisted radical prostatectomy between 2009 and 2021, and evaluated the impact of nerve sparing on positive surgical margin and biochemical recurrence using logistic regression and Cox models. Results: Unilateral nerve sparing and bilateral nerve sparing were performed in 152 (18.6%) cases and 118 (14.5%) cases, respectively. On multivariable analysis, in addition to nerve sparing, bilateral nerve sparing, but not unilateral nerve sparing was associated with an increased risk of positive surgical margin compared with non-nerve sparing. Positive surgical margin at any location increased the risk of biochemical recurrence. During unilateral nerve sparing, positive surgical margin in nerve sparing side, but not in non-nerve sparing side was associated with increased risk of biochemical recurrence on multivariate analysis. Conclusions: Taken together, surgeons need to notice an increased risk of biochemical recurrence associated with positive surgical margin when performing nerve sparing in robot-assisted radical prostatectomy, and then need to choose the patients suitable for nerve sparing.
MeSH term(s)	Humans ; Male ; Margins of Excision ; Prostate/innervation ; Prostate/surgery ; Prostate-Specific Antigen ; Prostatectomy/adverse effects ; Prostatectomy/methods ; Robotic Surgical Procedures/adverse effects ; Robotic Surgical Procedures/methods ; Robotics ; Urogenital Abnormalities/surgery
Chemical Substances	Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2022-04-11
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1328401-0
ISSN	1442-2042 ; 0919-8172
ISSN (online)	1442-2042
ISSN	0919-8172
DOI	10.1111/iju.14900
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Article ; Online: Validation study on the 2 mm diameter cutoff in lymph node-positive cases following radical prostatectomy in accordance with the AJCC/UICC TNM 8th edition: Real-world data analysis from a Japanese cohort.

International journal of urology : official journal of the Japanese Urological Association

2024

Abstract: Objectives: The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not ... ...

Abstract	Objectives: The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not described. We evaluated LN+ patients' survival after radical prostatectomy (RP) based on the LN maximum tumor diameter (MTD). Methods: Data from 561 LN+ patients after RP and pelvic LN dissection (PLND) treated between 2006 and 2019 at 33 institutions were retrospectively investigated. Patients were stratified by a LN+ MTD cutoff of 2 mm. Outcomes included castration resistance-free survival (CRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Results: In total, 282 patients were divided into two groups (LN+ MTD >2 mm [n = 206] and ≤2 mm [n = 76]). Patients of LN+ status >2 mm exhibited significantly decreased CRFS and MFS, and poorer CSS and OS. No patients developed CRPC in the LN+ status ≤2 mm group when the PLND number was ≥14. Multivariate analysis showed the number of LN removed, RP Gleason pattern 5, and MTD in LN+ significantly predicted CRFS. Conclusions: Patients of LN+ status ≤2 mm showed better prognoses after RP. In all the patients in the ≤2-mm group, the progression to CRPC could be prevented with appropriate interventions, particularly when PLND is performed accurately. Our findings support the utility of the pN substaging proposed by the AJCC/UICC 8th edition; this will facilitate precision medicine for patients with advanced prostate cancer.
Language	English
Publishing date	2024-02-29
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1328401-0
ISSN	1442-2042 ; 0919-8172
ISSN (online)	1442-2042
ISSN	0919-8172
DOI	10.1111/iju.15434
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