研究者詳細 - 田中　伸之

論文 - 田中　伸之

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Prognostic impact and landscape of cellular CXCR5 chemokine receptor expression in clear-cell renal cell carcinoma.

Arai M, Tanaka N, Takamatsu K, Murakami T, Mikami S, Imamura T, Nakamura K, Nishihara H, Oya M

Cancer immunology, immunotherapy : CII 74 （ 5 ） 166 2025年04月

ISSN 0340-7004

CXCR5 is a chemokine receptor that promotes B cell follicular formation and antibody production. Indeed, CXCR5 has been found to be expressed in a variety of cancers; however, the role of CXCR5 expression in clear-cell renal cell carcinoma (ccRCC) remains unclear. We aimed to determine the impact of cellular CXCR5 expression on cancer outcomes, the PD-1/PD-L1 axis, and genetic states in patients with ccRCC. First, multiplex immunofluorescence staining for CXCR5, CD4, CD8, and AE1/AE3, along with automated single-cell counting, was performed to assess cellular CXCR5 expression in ccRCC and its association with prognosis. Second, the tumour microenvironment (TME) was analysed, with a focus on the relationship between the PD-1/PD-L1 axis and CXCR5 expression. Finally, an integrated analysis of CXCR5 expression and genomic mutation information was conducted to reveal the genetic background underlying CXCR5 expression. A total of 105 ccRCC patients were included. Among the 696,964 cells analysed, the distribution of CXCR5-expressing cells was as follows: 30% CXCR5+CD4+ cells, 9% CXCR5+CD8+ cells, and 26% CXCR5+AE1/AE3+ cells. Survival analysis revealed that tumours with low-CXCR5+CD8+ cells had a poor prognosis; TME analysis revealed a relationship between low-CXCR5+CD8+ status and a highly suppressive PD-L1-positive immune environment. Genomic analysis revealed a correlation between low-CXCR5+CD8+ status and high rates of alterations in chromatin remodelling genes, including PBRM1. This study highlights the significance of CXCR5+CD8+ cells in ccRCC, demonstrating their clinical implications and revealing the immunogenomic landscape underlying CXCR5 expression.

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Genomic characterization of metastatic patterns in prostate cancer using circulating tumor DNA data from the SCRUM-Japan MONSTAR SCREEN project.

Shiota M, Matsubara N, Kato T, Eto M, Osawa T, Abe T, Shinohara N, Nishimoto K, Yasumizu Y, Tanaka N, Oya M, Fujisawa T, Horasawa S, Nakamura Y, Yoshino T, Nonomura N

The journal of liquid biopsy 7 100282 2025年03月

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Increased Expression of AXL and c-MET in High-Grade Clear Cell Renal Cell Carcinoma and Its Association With VEGFR-TKI Treatment and PD-L1 Expression

Mikami S., Mizuno R., Tanaka N., Hakozaki K., Takamatsu K., Oya M.

Pathology International 2025年

ISSN 13205463

Cabozantinib, a newly developed vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI), is an effective treatment for advanced renal cell carcinoma (RCC). However, the molecular mechanisms responsible for the superior effectiveness of cabozantinib to other drugs remain unclear. Since cabozantinib inhibits AXL and c-MET in addition to VEGFR, the expression of these molecules was immunohistologically examined in 110 cases of primary clear cell RCC (ccRCC) and eight of sunitinib (VEGFR-TKI)-treated primary ccRCC. AXL expression correlated with the primary tumor stage, while c-MET expression correlated with distant metastasis, the histological grade, and overall survival. Furthermore, the number of programmed death-ligand 1 (PD-L1)-positive tumor-infiltrating immune cells was higher in ccRCC tissues with high c-MET expression than in those with low c-MET expression. The expression of AXL and c-MET was higher in sunitinib-treated ccRCC tissues than in untreated tissues. These results suggest that AXL and c-MET play important roles in the progression of ccRCC and resistance to sunitinib. Furthermore, c-MET may modify the immune microenvironment by inducing PD-L1 expression in immune cells within RCC tissues. These molecular pathways may be related to responses to cabozantinib.

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Prognostic significance of circulating tumor DNA alterations in advanced renal cell carcinoma from SCRUM-Japan MONSTAR-SCREEN: a nationwide genomic profiling project: Genetics and Genomics

Kato T., Shiota M., Nishimoto K., Matsubara N., Osawa T., Abe T., Yasumizu Y., Tanaka N., Yamamoto Y., Ishizuya Y., Abutani H., Bando H., Fujisawa T., Nakamura Y., Oya M., Shinohara N., Eto M., Yoshino T., Nonomura N.

British Journal of Cancer 133 （ 1 ） 111 - 120 2025年

ISSN 00070920

Background: Circulating tumor DNA (ctDNA) is a promising tool for diagnosing and predicting cancer prognosis. However, its clinical utility in metastatic renal cell carcinoma (mRCC) remains unclear, particularly in terms of clinical prognosis. Methods: We enrolled 124 patients with mRCC in the MONSTAR-SCREEN study (UMIN 000036749) between August 2019 and February 2022, a national observational ctDNA-based screening study, and performed ctDNA sequencing before and at the time of resistance to systemic therapy. Results: ctDNA were assessed in 178 samples containing 432 mutations. The most frequently altered genes at baseline were VHL (25.0%), PBRM1 (10.9%), TERT2 (8.7%), BAP1 (8.7%), and MTOR (7.6%). Patients receiving first-line therapy with tumor fraction (TF) < 1.2% showed significantly better progression-free survival than those with TF ≥ 1.2% (Hazard ratio (HR) = 0.467; 95% CI 0.229–0.979; p = 0.0425). BAP1 mutational status of ctDNA at baseline led to poor OS (HR = 0.4867; 95% CI 0.322–0.736; p = 0.0003). Serial ctDNA analysis showed that 46.8% of patients developed new ctDNA mutations at disease progression, which was linked to shorter time to progression (p = 0.046). Conclusions: Our findings demonstrated that ctDNA profiling is feasible in mRCC and can predict disease progression after treatment.

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Prediction of pathological up-staging after radical nephroureterectomy in patients with upper tract urothelial carcinoma

Shojo K., Takeda T., Akita H., Suzuki T., Mikami S., Shigeta 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） 42 （ 1 ） 192 2024年12月

ISSN 07244983

Purpose: The diagnostic accuracy of computed tomography urography for upper tract urothelial carcinoma is high; however, difficulties are associated with precisely assessing the T stage. Preoperative tumor staging has an impact on treatment options for upper tract urothelial carcinoma. We herein attempted to identify preoperative factors that predict pathological tumor up-staging, which will facilitate the selection of treatment strategies. Materials and methods: We retrospectively identified 148 patients with upper tract urothelial carcinoma who underwent computed tomography urography preoperatively followed by radical nephroureterectomy without preoperative chemotherapy at our institution between 2000 and 2021. Preoperative factors associated with cT2 or lower to pT3 up-staging were examined using a multivariate logistic regression analysis. Results: Ninety out of 148 patients were diagnosed with cT2 or lower, and 22 (24%) were up-staged to pT3. A multivariate analysis identified a positive voided urine cytology (HR 4.69, p = 0.023) and tumor length ≥ 3 cm (HR 6.33, p = 0.003) as independent predictors of pathological tumor up-staging. Conclusions: Patients diagnosed with cT2 or lower, but with preoperative positive voided urine cytology and/or tumor diameter ≥ 3 cm need to be considered for treatment as cT3.

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Prediction of undetectable circulating tumor DNA by comprehensive genomic profiling assay in metastatic prostate cancer: the SCRUM-Japan MONSTAR SCREEN project

Shiota M., Matsubara N., Kato T., Eto M., Osawa T., Abe T., Shinohara N., Nishimoto K., Yasumizu Y., Tanaka N., Oya M., Fujisawa T., Horasawa S., Nakamura Y., Yoshino T., Nonomura N.

World Journal of Urology 42 （ 1 ） 526 2024年12月

ISSN 07244983

Background: Undetectable circulating tumor DNA (ctDNA) is an obstacle to performing comprehensive genomic profiling in daily practice to identify genomic alterations. We investigated the associations between clinicopathological factors and undetectable ctDNA using a commercially available comprehensive genomic profiling assay in metastatic prostate cancer. Patients and methods: Patients treated with systemic treatment for metastatic prostate cancer were included. ctDNA was analyzed by FoundationOne®Liquid CDx at enrollment. The associations between clinicopathological characteristics and ctDNA detection were analyzed. Results: The number of bone metastasis was associated with ctDNA detection (odds ratio [95% confidence interval], 13.6 [1.71–108], P = 0.014). An algorithm predicting ctDNA detection using clinicopathological parameters was created. If ≥ 4 bone metastases were observed, ctDNA detection was estimated to be 98.9%. Among the patients with < 4 bone metastases, if two or three features among ISUP grade group 5, PSA level ≥ 10 ng/ml, and castration resistance were present, the ctDNA detection rate was 96.7% while the ctDNA detection rate was 86.3% if no or only one feature was present. Conclusions: An algorithm created in this study is helpful in determining when to undertake comprehensive genomic profiling assay using blood.

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Tumor immune microenvironment dynamics and outcomes of prognosis in non-muscle-invasive bladder cancer.

Kamitani R, Tanaka N, Anno T, Murakami T, Masuda T, Yasumizu Y, Takeda T, Morita S, Kosaka T, Mikami S, Matsumoto K, Oya M

Cancer science 115 （ 12 ） 3963 - 3972 2024年10月

ISSN 1347-9032

Agents that target PD-1 and PD-L1 have been developed in the treatment of bladder cancer (BC). However, the diversity of immune cell infiltration in non-muscle-invasive BC (NMIBC) and the dynamics of the microenvironment as it progresses to muscle-invasive/metastatic disease remains unknown. To assess tumor immune activity, hierarchical clustering was applied to 159 BC samples based on cellular positivity for the defined immune cellular markers (CD3/CD4/CD8/FOXP3/CD20/PD-1/PD-L1/LAG3/TIGIT), divided into two clusters. There was a “hot cluster” (25%) consisting of patients with a high expression of these markers and a “cold cluster” (75%) comprising those without. The expression of CD39, CD44, CD68, CD163, IDO1, and Ki67 was significantly higher in tumors in the hot cluster. Immunologically, high-grade T1 tumors were significantly hotter, whereas tumors that had progressed to muscle invasion turned cold. However, a certain number of high-grade NMIBC patients were in the cold cluster, and these patients had a significantly higher risk of disease progression. Using an externally available TCGA dataset, RB1 and TP53 alterations were more frequently observed in TCGA hot cluster; rather FGFR3, KDM6A, and KMT2A alterations were common in TCGA cold/intermediate cluster. Analyses of recurrent tumors after BCG therapy revealed that tumor immune activity was widely maintained before and after treatment, and high FGFR3 expression was detected after recurrence in tumors initially classified into the cold cluster. Collectively, we revealed the dynamics of the tumor microenvironment in BC as a whole and identified candidate molecules as therapeutic targets for recurrent NMIBC, e.g., after BCG therapy.

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Multiplexed Spatial Imaging at the Single-Cell Level Reveals Mutually Exclusive Expression of B7 Family Proteins

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

Laboratory Investigation 104 （ 10 ） 102131 2024年10月

ISSN 00236837

Targeting novel inhibitory ligands beyond anti-PD-1 and PD-L1 and CTLA-4 therapies is essential for the next decade of the immunotherapy era. Agents for the B7 family molecules B7-H3, B7-H4, and B7-H5 are emerging in clinical trial phases; therefore, further accumulation of evidence from both clinical and basic aspects is vital. Here, we applied a 7-color multiplexed imaging technique to analyze the profile of B7 family B7-H3/B7-H4/B7-H5 expression, in addition to PD-L1, and the spatial characteristics of immune cell infiltrates in urothelial carcinoma (UC). The results revealed that B7-H3 and B7-H4 were mainly expressed on tumor cells and B7-H5 on immune cells in UC, and most of the B7-H3/B7-H4/B7-H5-positive cells were mutually exclusive with PD-L1-positive cells. Also, the expression of B7-H4 was elevated in patients with advanced pathologic stages, and high B7-H4 expression was a significant factor affecting overall mortality following surgery in UC. Furthermore, spatial analysis revealed that the distance from the B7-H4+ cells to the nearest CD8+ cells was markedly far compared with other B7 family-positive tumor cells. Interestingly, the distance from B7-H4+ cells to the nearest CD8+ cells was significantly farther in patients dying from cancer after surgery or immune checkpoint inhibitors compared with cancer survivors; thus, high B7-H4 expression in tumor cells may inhibit CD8 infiltration into the tumor space and that B7-H4-positive cells form a specific spatial niche. In summary, we performed a comprehensive evaluation of B7 family member expression and found that the spatial distribution of B7-H4 suggests the potentially useful role of combination blockade with both B7-H4 and the current anti-PD-1/PD-L1 axis in the treatment of UC.

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多発病変の中の小さな最高grade病変は,MRIで検出できるのか

松本一宏, 秋田大宇, 橋口明典, 武田利和, 小坂威雄, 福本桂資郎, 安水洋太, 田中伸之, 森田伸也, 水野隆一, 浅沼宏, 大家基嗣, 陣崎雅弘

泌尿器外科（医学図書出版(株)） 37 （ 8 ） 942 - 944 2024年08月

ISSN 0914-6180

Three-dimensional imaging of upper tract urothelial carcinoma improves diagnostic yield and accuracy

Fukumoto K., Kanatani S., Jaremko G., West Z., Li Y., Takamatsu K., Al Rayyes I., Mikami S., Niwa N., Axelsson T.A., Tanaka N., Oya M., Miyakawa A., Brehmer M., Uhlén P.

JCI Insight 9 （ 14 ） 2024年07月

Upper tract urothelial carcinoma (UTUC) is a rare form of urothelial cancer with a high incidence of recurrence and a low survival rate. Almost two-thirds of UTUCs are invasive at the time of diagnosis; therefore, improving diagnostic methods is key to increasing survival rates. Histopathological analysis of UTUC is essential for diagnosis and typically requires endoscopy biopsy, tissue sectioning, and labeling. However, endoscopy biopsies are minute, and it is challenging to cut into thin sections for conventional histopathology; this complicates diagnosis. Here, we used volumetric 3-dimensional (3D) imaging to explore the inner landscape of clinical UTUC biopsies, without sectioning, revealing that 3D analysis of phosphorylated ribosomal protein S6 (pS6) could predict tumor grade and prognosis with improved accuracy. By visualizing the tumor vasculature, we discovered that pS6+ cells were localized near blood vessels at significantly higher levels in high-grade tumors than in low-grade tumors. Furthermore, the clustering of pS6+ cells was associated with shorter relapse-free survival. Our results demonstrate that 3D volume imaging of the structural niches of pS6 cells deep inside the UTUC samples improved diagnostic yield, grading, and prognosis prediction.

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Volumetric imaging of the tumor microvasculature reflects outcomes and genomic states of clear cell renal cell carcinoma.

Kaneko Y, Masuda T, Takamatsu K, Mikami S, Nakamura K, Nishihara H, Mizuno R, Tanaka N, Oya M

The journal of pathology. Clinical research （Journal of Pathology: Clinical Research） 10 （ 4 ） e12388 2024年07月

Tumor structure is heterogeneous and complex, and it is difficult to obtain complete characteristics by two-dimensional analysis. The aim of this study was to visualize and characterize volumetric vascular information of clear cell renal cell carcinoma (ccRCC) tumors using whole tissue phenotyping and three-dimensional light-sheet microscopy. Here, we used the diagnosing immunolabeled paraffin-embedded cleared organs pipeline for tissue clearing, immunolabeling, and three-dimensional imaging. The spatial distributions of CD34, which targets blood vessels, and LYVE-1, which targets lymphatic vessels, were examined by calculating three-dimensional density, vessel length, vessel radius, and density curves, such as skewness, kurtosis, and variance of the expression. We then examined those associations with ccRCC outcomes and genetic alteration state. Formalin-fixed paraffin-embedded tumor samples from 46 ccRCC patients were included in the study. Receiver operating characteristic curve analyses revealed the associations between blood vessel and lymphatic vessel distributions and pathological factors such as a high nuclear grade, large tumor size, and the presence of venous invasion. Furthermore, three-dimensional imaging parameters stratified ccRCC patients regarding survival outcomes. An analysis of genomic alterations based on volumetric vascular information parameters revealed that PI3K-mTOR pathway mutations related to the blood vessel radius were significantly different. Collectively, we have shown that the spatial elucidation of volumetric vasculature information could be prognostic and may serve as a new biomarker for genomic alterations. High-end tissue clearing techniques and volumetric immunohistochemistry enable three-dimensional analysis of tumors, leading to a better understanding of the microvascular structure in the tumor space.

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Detection of the Highest-Grade Lesion in Multifocal Discordant Prostate Cancer by Multiparametric Magnetic Resonance Imaging

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

Clinical Genitourinary Cancer （Clinical Genitourinary Cancer） 22 （ 3 ） 102084 2024年06月

ISSN 15587673

Purpose: Prostate cancer generally occurs multifocally. The lesions of the largest size and highest-grade are often concordant, and defined as an index tumor. However, these factors sometimes do not coincide within one lesion. In such discordant cases, not the largest size lesion but the highest-grade lesion is known to determine the prognosis. We focused on the multiparametric magnetic resonance imaging (mpMRI) detectability of the highest-grade tumors in discordant cases. Materials and Methods: We investigated the detectability of the highest-grade tumor using preoperative mpMRI in 50 discordant patients who underwent radical prostatectomy. The radiologist was informed of the tumor location on the pathological tumor map, and mpMRI interpretation for each tumor was performed. Results: Prostate Imaging-Reporting and Data System (PI-RADS) scores of 1, 2, 3, 4, and 5 on preoperative mpMRI were assigned to 13, 1, 9, 16, and 11 of the largest tumors, respectively. On the other hand, scores of 1, 2, 3, 4, and 5 were assigned to 23, 0, 7, 19, and 1 of the highest-grade tumors, respectively. The difference between them was statistically significant (p=0.007). We also found that the largest anterior tumor frequently hid the ipsilateral posterior highest-grade tumor; the detection rate of the highest-grade tumor in this pattern was 42.1% (8 of 19 cases) Conclusion: We found that mpMRI detectability of the highest-grade tumor in discordant cases was inferior to that of the largest tumor with low malignant potential. Our results suggest that the risk of high-grade tumors which determine patient prognosis being overlooked.

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Risk factors for postoperative fever after laparoscopic adrenalectomy focusing on hormones produced: a case control study.

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

BMC urology 24 （ 1 ） 90 2024年04月

Background: Laparoscopic adrenalectomy is widely performed for a number of hormone-producing tumors and postoperative management depends on the hormones produced. In the present study, we conducted a retrospective analysis to clarify the risk factors for postoperative complications, particularly postoperative fever after laparoscopic adrenalectomy. Methods: We analyzed 406 patients who underwent laparoscopic adrenalectomy at our hospital between 2003 and 2019. Postoperative fever was defined as a fever of 38 °C or higher within 72 h after surgery. We investigated the risk factors for postoperative fever after laparoscopic adrenalectomy. Results: There were 188 males (46%) and 218 females (54%) with a median age of 52 years. Among these patients, tumor pathologies included 188 primary aldosteronism (46%), 75 Cushing syndrome (18%), and 80 pheochromocytoma (20%). Postoperative fever developed in 124 of all patients (31%), 30% of those with primary aldosteronism, 53% of those with pheochromocytoma, and 8% of those with Cushing syndrome. A multivariate logistic regression analysis identified pheochromocytoma and non-Cushing syndrome as independent predictors of postoperative fever. Postoperative fever was observed in 42 out of 80 cases of pheochromocytoma (53%), which was significantly higher than in cases of non-pheochromocytoma (82/326, 25%, p < 0.01). In contrast, postoperative fever developed in 6 out of 75 cases of Cushing syndrome (8%), which was significantly lower than in cases of non-Cushing syndrome (118/331, 35.6%, p < 0.01). Conclusion: Since postoperative fever after laparoscopic adrenalectomy is markedly affected by the hormone produced by pheochromocytoma and Cushing syndrome, it is important to carefully consider the need for treatment.

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Genomic profiling and clinical utility of circulating tumor DNA in metastatic prostate cancer: SCRUM-Japan MONSTAR SCREEN project.

Shiota M, Matsubara N, Kato T, Eto M, Osawa T, Abe T, Shinohara N, Nishimoto K, Yasumizu Y, Tanaka N, Oya M, Fujisawa T, Horasawa S, Nakamura Y, Yoshino T, Nonomura N

BJC reports 2 （ 1 ） 28 2024年04月

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Impact of prostatic shape on the difficulty of robot-assisted laparoscopic radical prostatectomy.

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

Asian journal of endoscopic surgery （Asian Journal of Endoscopic Surgery） 17 （ 2 ） e13291 2024年04月

ISSN 1758-5902

Introduction: To investigate the impact of prostatic shape observed on preoperative magnetic resonance imaging (MRI) on the difficulty of robot-assisted laparoscopic radical prostatectomy (RALP). Methods: We retrospectively reviewed the operative records of 211 patients who underwent RALP. We excluded patients who received neoadjuvant therapy. All surgeries in this study were performed by two surgeons. Each patient clinicopathological and surgical data were reviewed. Prostate sphericity was evaluated by measuring the roundness of the prostate at the largest axial slice by MRI. The console time was adopted as an objective indicator for assessing surgical difficulty. Results: The mean prostate volume was 34 cc (range 14–88) and the mean prostate roundness was 0.55 (range 0.24–0.90). The mean console time was 194 min (range 95–296). To assess the relationship between prostate volume and console time, scatter plot analysis was performed. The prostate volume had a weak positive correlation with the console time (r =.165, p =.016). Similarly, scatter plot analysis between the prostate roundness and console time demonstrated a weak positive correlation (r =.167, p =.015). Next, we performed subgroup analysis of 56 patients with a large prostate volume (≥40 cc), and the positive correlation between the prostate volume and the console time disappeared (r =.142, p =.296). On the other hand, the prostate roundness was more strongly correlated with the console time (r =.439, p =.001). Conclusions: The spherical shape of the prostate is associated with the surgical difficulty of RALP, especially in patients with a large prostate volume.

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Profiling Fibroblast Growth Factor Receptor 3 Expression Based on the Immune Microenvironment in Upper Tract Urothelial Carcinoma.

Shigeta K, Matsumoto K, Kitaoka S, Omura M, Umeda K, Arita Y, Mikami S, Fukumoto K, Yasumizu Y, Tanaka N, Takeda T, Morita S, Kosaka T, Mizuno R, Hara S, Oya M

European urology oncology 7 （ 6 ） 1338 - 1349 2024年02月

BACKGROUND: Although several studies have shown favorable outcomes in upper tract urothelial carcinoma (UTUC) with fibroblast growth factor receptor 3 (FGFR3) mutations and/or expression, the relationship between immune cell markers and FGFR3 expression remains unknown. OBJECTIVE: To clarify the FGFR3-based immune microenvironment and investigate biomarkers to predict the treatment response to pembrolizumab (Pem) in patients with UTUC. DESIGN, SETTING, AND PARTICIPANTS: We conducted immunohistochemical staining in 214 patients with UTUC. The expression levels of FGFR3, CD4, CD8, CD68, CD163, CD204, and programmed cell death ligand 1 (PD-L1) were examined. INTERVENTION: All UTUC patients underwent radical nephroureterectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the relationship between these immune markers and patient prognosis. RESULTS AND LIMITATIONS: A total of 109 (50.9%) patients showed high FGFR3 expressions and a favorable prognosis compared with the remaining patients. Among the six immune markers, CD8 high expression was an independent favorable factor, whereas CD204 expression was an independent prognostic factor for cancer death. From the FGFR3-based immune clustering, three immune clusters were identified. Cluster A showed low FGFR3 with tumor-associated macrophage-rich components (CD204+) followed by a poor prognosis due to a poor response to Pem. Cluster B showed low FGFR3 with an immune hot component (CD8+), followed by the most favorable prognosis owing to a good response to Pem. Cluster C showed high FGFR3 expression but an immune cold component, followed by a favorable prognosis due to the high FGFR3 expression, but a poor response was confirmed with Pem. CONCLUSIONS: Although most patients exhibit a poor response to Pem, individuals with low FGFR3 expression and immune hot status may benefit clinically from Pem treatment. PATIENT SUMMARY: We conducted immunohistochemical staining to evaluate fibroblast growth factor receptor 3 (FGFR3)-related immune microenvironment by evaluating the expressions of CD4, CD8, CD68, CD163, CD204, and PD-L1 in 214 upper tract urothelial carcinoma patients. We identified three distinct immune clusters based on FGFR3 expressions and found that patients with a low FGFR3 expression but immune hot status received the maximum benefit from an immune checkpoint inhibitor.

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

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

BMC urology （BMC Urology） 24 （ 1 ） 13 2024年01月

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

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尿管狭窄に対して口腔粘膜を用いた拡大onlay法尿管形成術を施行した1例

岩佐俊, 浅沼宏, 高橋遼平, 福本桂資郎, 安水洋太, 田中伸之, 武田利和, 松本一宏, 森田伸也, 小坂威雄, 水野隆一, 大家基嗣

日本泌尿器科学会雑誌（(一社)日本泌尿器科学会） 115 （ 1 ） 37 - 41 2024年01月

ISSN 0021-5287

症例は14歳男子.12歳時に水腎症と腎機能の増悪を認め,近医で膀胱腫瘍,左尿管腫瘍の診断となった.前医で経尿道的膀胱腫瘍切除術,尿管腫瘍生検が施行され,線維上皮性ポリープの診断となった.尿管ポリープに対して経尿道的切除を試みられたが尿道狭窄を併発したため到達困難となり,左腎瘻造設,経皮的レーザー焼灼術が施行された.術後4ヵ月,尿管狭窄もきたし,尿路再建の目的に当院へ紹介となった.尿道狭窄に対して13歳時に包皮利用Palminteri法尿道形成術を施行した.逆行性腎盂造影,腎瘻造影検査で脊椎L4レベルに2cmの尿管狭窄,尿管鏡検査で脊椎L5レベルに残存ポリープを認めた.14歳時に尿管再建術を行った.端々吻合では吻合部の緊張が強いと考えられ,口腔粘膜利用拡大onlay法尿管形成術を行う方針とした.完全閉塞部と残存ポリープ部のみを最小限切除し,緊張のかからない尿管壁同士を一部端々吻合した.吻合部の対側の尿管壁は健常部まで十分にspatulateし,尿管ステントを留置後に15×40mm大の頬粘膜を縫着,頬粘膜のグラフト床として腹腔内から遊離した大網を吻合部に全周性に縫着した.術後13日で腎瘻を抜去,術後4ヵ月で尿管ステントを抜去した.術後1年および2年の逆行性腎盂造影,尿管鏡検査で再狭窄やポリープの再発は認めず,術後3年現在,左側腹部痛,腎盂腎炎,腎盂拡張などを認めず経過良好である.(著者抄録)

下大静脈後尿管を合併した膀胱尿管逆流に対して逆流防止術を施行した2例の比較

岩佐俊, 浅沼宏, 高橋遼平, 安水洋太, 田中伸之, 武田利和, 松本一宏, 森田伸也, 小坂威雄, 水野隆一, 大家基嗣

日本逆流性腎症フォーラム記録集（日本逆流性腎症フォーラム） 30回 19 - 21 2024年01月

ISSN 2435-323X

症例1(26歳女性)。11歳時に右膀胱尿管逆流(VUR)に対しCohen法による逆流防止術が施行された。今回、右水腎症を契機に下大静脈後尿管(RCU)の合併が明らかになり、右尿管尿管吻合術を行った結果、術後4年半経過現在、水腎症は改善している。尚、本症例は逆流防止術前にRCUの診断がされておらず、尿管の対側への牽引がRCUによる腎盂尿管移行部通過障害を悪化させた可能性が考えられた。症例2(19歳女性)。反復する発熱、右水腎症を主訴とした。超音波検査、CT検査、排尿時膀胱尿道造影の所見を踏まえて、RCU合併の右VURと診断された。尿管の牽引を伴わないLich-Gregoir法による逆流防止術を施行した結果、術後は水腎症の増悪なく、良好である。

Concomitant Prostate Needle Biopsy and Laser Vaporization of the Prostate Could Be a Risk of Postoperative Hemoglobin Decline, a Retrospective Study.

Ezaki T, Hongo H, Takamatsu K, Tanaka N, Oya M

Research and reports in urology （Research and Reports in Urology） 16 123 - 129 2024年

ISSN 2253-2447

Purpose: Contact laser vaporization of the prostate (CVP) for benign prostatic hyperplasia is a widely accepted and safe procedure for elderly patients because of its lower bleeding risks. However, CVP lacks a postoperative pathological examination for prostate cancer. Concomitant prostate biopsy and CVP may complement this disadvantage; however, the risk of bleeding associated with this procedure remains unclear. This study aimed to evaluate the safety of a concomitant prostate biopsy and CVP. Patients and Methods: This retrospective study included 106 men who had undergone CVP in Nerima General Hospital. Prostate biopsies and CVP were performed simultaneously on 16 patients. We defined the “hemorrhage group” by a >5% decrease in hemoglobin the day after surgery. Preoperative and operative indices were evaluated based on the association with the hemorrhage group. Results: Participants in the concomitant biopsy group were older (p = 0.001), had larger prostates (p = 0.014), a lower rate of prostate biopsy history (p = 0.046), longer postoperative urinary catheter duration (p = 0.024), and a higher rate of decline in hemoglobin levels the day after surgery (p = 0.023). Patients in the hemorrhage group (n = 20, 18.9%) showed a significantly higher rate of concomitant biopsy and CVP (p = 0.006). Multivariate analysis showed that concomitant prostate biopsy (p = 0.009, odds ratio = 4.61) was the sole statistically significant predictive factor for hemorrhage. Conclusion: Concomitant prostate biopsy and CVP of the prostate may increase the risk of bleeding.

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