担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated. METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated renal tumours and sporadic renal tumours. FINDINGS: RNA-seq analysis revealed that BHD-associated renal tumours and sporadic renal tumours have totally different expression profiles. Sporadic ChRCCs were clustered into two distinct clusters characterized by L1CAM and FOXI1 expressions, molecular markers for renal tubule subclasses. Increased mitochondrial DNA (mtDNA) copy number with fewer variants was observed in BHD-associated renal tumours compared to sporadic ChRCCs. Cell-of-origin analysis using WGS data demonstrated that BHD-associated renal tumours and sporadic ChRCCs may arise from different cells of origin and second hit FLCN alterations may occur in early third decade of life in BHD patients. INTERPRETATION: These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. FUNDING: This study was supported by JSPS KAKENHI Grants, RIKEN internal grant, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research.

DOI： 10.1016/j.ebiom.2023.104596

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Patients with end-stage renal disease (ESRD) or receiving dialysis have a much higher risk for renal cell carcinoma (RCC), but carcinogenic mechanisms and genomic features remain little explored and undefined. This study's goal was to identify the genomic features of ESRD RCC and characterize them for associations with tumor histology and dialysis exposure. In this study, we obtained 33 RCCs, with various histological subtypes, that developed in ESRD patients receiving dialysis and performed whole-genome sequencing and transcriptome analyses. Driver events, copy-number alteration (CNA) analysis and mutational signature profiling were performed using an analysis pipeline that integrated data from germline and somatic SNVs, Indels and structural variants as well as CNAs, while transcriptome data were analyzed for differentially expressed genes and through gene set enrichment analysis. ESRD related clear cell RCCs' driver genes and mutations mirrored those in sporadic ccRCCs. Longer dialysis periods significantly correlated with a rare mutational signature SBS23, whose etiology is unknown, and increased mitochondrial copy number. All acquired cystic disease (ACD)-RCCs, which developed specifically in ESRD patients, showed chromosome 16q amplification. Gene expression analysis suggests similarity between certain ACD-RCCs and papillary RCCs and in TCGA papillary RCCs with chromosome 16 gain identified enrichment for genes related to DNA repair, as well as pathways related to reactive oxygen species, oxidative phosphorylation and targets of Myc. This analysis suggests that ESRD or dialysis could induce types of cellular stress that impact some specific types of genomic damage leading to oncogenesis.

DOI： 10.1093/hmg/ddac180

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment.

DOI： 10.1016/j.isci.2022.104463

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recently, the effectiveness of anti-programmed death 1 (PD-1) antibody therapy in the treatment of renal cell carcinoma (RCC) has been established. Nevertheless, efficacy has been reported to be limited to only 10-30% of patients. To develop more effective immunotherapy for RCC, we analyzed the immunological characteristics in RCC tissues by immunohistochemistry (IHC). We prepared a tissue microarray that consisted of tumor tissue sections (1 mm in diameter) from 83 RCC patients in Kanagawa Cancer Center between 2006 and 2015. IHC analysis was performed with antibodies specific to immune-related (CD8 and Foxp3) and immune checkpoint (programmed death ligand 1 (PD-L1) and 2 (PD-L2), B7-H4 and galectin-9) molecules. The numbers and proportions of positively stained tumor cells or immune cells were determined in each section. From multivariate analysis of all 83 patients, higher galectin-9 expression was detected as a factor associated with worse overall survival (OS) (P = 0.029) and that higher stage and higher B7-H4 expression were associated with worse progression-free survival (PFS) (P < 0.001 and P = 0.021, respectively). Similarly, in multivariate analysis of 69 patients with clear cell RCC, though not statistically significant, there was a trend for association between higher galectin-9 expression and worse OS (P = 0.067), while higher stage was associated with worse PFS (P < 0.001). This study suggests that higher galectin-9 expression is an independent adverse prognostic factor of OS in RCC patients. Therefore, to develop more effective personalized immunotherapy to treat RCC, it may be important to target not only PD-1/PD-L1, but also other immune checkpoint molecules such as galectin-9.

DOI： 10.1007/s00262-020-02608-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer, which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming toward upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics that are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.

DOI： 10.1093/hmg/ddy181

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Clinical reasoning skills are essential competencies for medical students; therefore, effective, evidence-informed teaching methodologies are needed worldwide. This study investigated the benefits of team-based learning (TBL) for developing the skills in medical students. METHOD: A mixed-methods sequential explanatory design was used to investigate the effectiveness of TBL for medical students acquiring clinical reasoning skills. The study participants comprised 92 fourth-year medical students at Yokohama City University School of Medicine, participating in TBL sessions that covered 10 major clinical symptoms identified in the core curriculum. Each session lasted 240 min. Before and after the educational intervention, student performance was measured using the script concordance test (SCT) on a 30-point scale, and self-assessed clinical reasoning competency was measured on a 7-point Likert scale. The SCT included pre-tests and post-tests of 30 questions each, with students randomly assigned to one of two test sets. Following the quantitative evaluation, a qualitative content analysis was conducted to explore the advantages of TBL for learning clinical reasoning skills. The analytic categories were set according to the six levels of Fink's taxonomy of significant learning. RESULT: Student performance improved significantly after the educational intervention (A test: 16.5 ± 4.4 to 18.7 ± 4.5, p = 0.019; B test: 18.1 ± 3.7 to 19.8 ± 4.4, p = 0.028). After the educational intervention, self-assessed clinical reasoning competency was significantly higher in "recalling appropriate physical examination and tests on clinical hypothesis generation," "recalling appropriate differential diagnosis from patient's chief complaint," "verbalizing points that fit/don't fit the recalled differential diagnosis appropriately," "verbalizing and reflecting appropriately on own mistakes," "selecting keywords from the whole aspect of the patient," and "practicing the appropriate clinical reasoning process" (all p < 0.001). The content analysis extracted 23 subcategories and 233 codes of the advantages of TBL for learning clinical reasoning skills, covering all six levels of Fink's taxonomy of significant learning: Foundational knowledge (7 codes); Application (40 codes); Integration (69 codes); Human dimension (89 codes); Caring (8 codes); and Learning how to learn (20 codes). CONCLUSION: This study demonstrates that TBL supports the acquisition of critical clinical reasoning skills among medical students.

DOI： 10.1186/s12909-025-06784-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3-rearranged renal cell carcinoma (TFE3-RCC) remain poorly understood. TFE3-RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC-TFE3 induced a hypoxia-related signature by transcriptionally upregulating HIF1α and HIF2α. The upregulation of HIF1α by PRCC-TFE3 led to increased cellular ATP production by enhancing glycolysis, which also supplied substrates for the TCA cycle while maintaining mitochondrial oxidative phosphorylation. We crossed TFE3-RCC mouse models with Hif1α and/or Hif2α knockout mice and found that Hif1α, rather than Hif2α, is essential for tumor development in vivo. RNA-seq and metabolomic analyses of the kidney tissues from these mice revealed that ketone body production is inversely correlated with tumor development, whereas de novo lipid synthesis is upregulated through the HIF1α/SREBP1-dependent mechanism in TFE3-RCC. Our data suggest that the coordinated metabolic shift via the PRCC-TFE3/HIF1α/SREBP1 axis is a key mechanism by which PRCC-TFE3 enhances cancer cell metabolism, promoting tumor development in TFE3-RCC.

DOI： 10.1111/gtc.13195

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

TFE3-rearranged Renal Cell Carcinoma (TFE3-RCC) is an aggressive subtype of RCC characterized by Xp11.2 rearrangement, leading to TFE3 fusion proteins with oncogenic potential. Despite advances in understanding its molecular biology, effective therapies for advanced cases remain elusive. This study investigates the role of ARID2, a component of the SWI/SNF chromatin remodeling complex, in TFE3-RCC. Through a series of in vitro and in vivo experiments, we confirmed that ARID2 acts as a tumor suppressor in TFE3-RCC. ARID2 knockout (KO) enhanced TFE3-RCC cell migration, proliferation, and tumor growth. Transcriptomic analysis revealed ERBB3 as a key target gene regulated by both PRCC-TFE3 and ARID2. Chromatin immunoprecipitation (ChIP) assays demonstrated that PRCC-TFE3 directly binds to and upregulates ERBB3 expression, with ARID2 KO further enhancing this effect. TFE3-RCC ARID2 KO cells exhibited significant gene expression enrichment in MAPK and ERBB3 signaling pathways. These cells also showed increased activation of ERBB3, EGFR, and selective activation of SRC and MAPK. TFE3-RCC ARID2 KO cells demonstrated heightened sensitivity to the ERBB3 inhibitor AZD8931 compared to their wild-type counterparts, exhibiting significantly reduced migration and proliferation rates. These findings suggest that the PRCC-TFE3-ARID2-ERBB3 axis plays a critical role in TFE3-RCC pathogenesis and highlights the potential of targeting ERBB3 in ARID2-deficient TFE3-RCC as a therapeutic strategy. This study provides new insights into the molecular mechanisms of TFE3-RCC and suggests avenues for precision treatment of this aggressive cancer.

DOI： 10.3390/cimb46120817

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: Complete endophytic renal tumors (CERTs) are the most challenging for robot-assisted partial nephrectomy (RAPN). This study aimed to determine the impact of CERT on outcomes of RAPN. Methods: All RAPN cases for localized renal tumor undertaken at Yokohama City University Hospital between 2016 and 2023 were enrolled. Tumor characteristics and surgical, functional, and oncologic outcomes of RAPN were compared between CERT and non-CERT groups. Results: Consecutive 666 patients were enrolled, and 76 (11.4%) were identified as CERT (3 points of "E" score). CERT showed smaller tumor diameters (p < 0.001), more predominant hilar tumor (p = 0.029), higher "N" scores (p < 0.001) and "L" scores (p = 0.006) than non-CERT. The CERT group showed longer warm ischemia times (p < 0.001), more frequent positive surgical margins (p = 0.028), and relatively lower trifecta achievement rates (p = 0.101) than the non-CERT group. In multivariable analysis, the CERT was an independent predictor for trifecta achievement but not for pentafecta achievement. Conclusions: CERT was associated with longer warm ischemia time, positive surgical margin, and lower trifecta achievement, but not with surgical complication and pentafecta achievement in RAPN. This study suggested that CERT had limited influence on long-term renal functional preservation; however, it had strong impacts on short-term surgical outcome.

DOI： 10.1089/end.2023.0608

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The influence of chronic kidney disease stage on robot-assisted partial nephrectomy outcomes remains underexplored. This study aimed to assess the impact of chronic kidney disease stage on functional and surgical outcomes of robot-assisted partial nephrectomy and identify preoperative predictors of significant postoperative 1-year renal-function loss (RFL). Clinical data of 408 patients who underwent robot-assisted partial nephrectomy at Yokohama City University Hospital between 2016 and 2023 were retrospectively reviewed. The da Vinci Surgical System was applied in all patients, and outcomes assessed included surgical parameters, postoperative estimated glomerular filtration rate, trifecta and pentafecta achievements, and complications. Significant RFL was defined as estimated glomerular filtration rate reduction ≥ 25% from baseline. Higher chronic kidney disease stages correlated with older age, hypertension, diabetes, and solitary kidneys. Postoperative estimated glomerular filtration rate decline was most pronounced in patients with chronic kidney disease stages 4-5. Although the chronic kidney disease stage did not significantly affect most surgical parameters, pentafecta achievement was higher in patients with chronic kidney disease stage 3 than in those with stages 4-5. Two patients required hemodialysis after robot-assisted partial nephrectomy. Multivariable logistic regression analysis showed that preoperative hemoglobin level and maximum tumor diameter were significant predictive factors for significant RFL. In conclusion, preoperative CKD stage did not influence on surgical outcome except for pentafecta achievement. RAPN may be feasible for patients with CKD stages 4-5 because of no rapid progression to hemodialysis induction and no procedure-related mortality. Preoperative hemoglobin levels and tumor diameter emerged as predictors of significant RFL.

DOI： 10.1007/s11701-024-01873-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: In December 2021, enfortumab vedotin (EV), an antibody-drug conjugate directed against nectin-4, was approved in Japan as a new treatment after platinum-containing chemotherapy and PD-1/PD-L1 inhibitors. This study evaluated, using real-world data, the efficacy and safety of EV therapy in patients with metastatic urothelial carcinoma (mUC). MATERIALS AND METHODS: Fifty-five patients with mUC who discontinued pembrolizumab therapy due to disease progression between June 2018 and April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of the 55 patients, 25 received EV therapy (EV group) and 30 did not (non-EV group). All patients who underwent EV therapy were diagnosed with disease progression after the approval of EV in Japan. RESULTS: The median (range) follow-up period after pembrolizumab discontinuation was 6.3 (0.7-31.1) months. There were eight (32.0%) deaths due to cancer in the EV group and 27 (90.0%) in the non-EV group. The overall survival (OS) after pembrolizumab discontinuation was not reached in the EV group versus 2.6 months in the non-EV group (p < 0.001). A multivariate analysis revealed that EV therapy (EV vs. non-EV group; hazard ratio 0.26; 95% confidence interval 0.16-0.41; p < 0.001) was an independent prognostic factor for OS. CONCLUSION: EV prolonged OS in mUC following pembrolizumab therapy in real-world data.

DOI： 10.1111/iju.15437

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The human mitochondrial genome (mtDNA) is a circular DNA molecule with a length of 16.6 kb, which contains a total of 37 genes. Somatic mtDNA mutations accumulate with age and environmental exposure, and some types of mtDNA variants may play a role in carcinogenesis. Recent studies observed mtDNA variants not only in kidney tumors but also in adjacent kidney tissues, and mtDNA dysfunction results in kidney injury, including chronic kidney disease (CKD). To investigate whether a relationship exists between heteroplasmic mtDNA variants and kidney function, we performed ultra-deep sequencing (30,000×) based on long-range PCR of DNA from 77 non-tumor kidney tissues of kidney cancer patients with CKD (stages G1 to G5). In total, this analysis detected 697 single-nucleotide variants (SNVs) and 504 indels as heteroplasmic (0.5% ≤ variant allele frequency (VAF) < 95%), and the total number of detected SNVs/indels did not differ between CKD stages. However, the number of deleterious low-level heteroplasmic variants (pathogenic missense, nonsense, frameshift and tRNA) significantly increased with CKD progression (p < 0.01). In addition, mtDNA copy numbers (mtDNA-CNs) decreased with CKD progression (p < 0.001). This study demonstrates that mtDNA damage, which affects mitochondrial genes, may be involved in reductions in mitochondrial mass and associated with CKD progression and kidney dysfunction.

DOI： 10.3390/ijms242417212

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Lymphoepithelioma-like carcinoma (LELC) of the ureter is very rare and only 14 previous cases have been reported. Here, we report a case of LELC of the ureter. A 76-year-old woman was admitted to our hospital complaining of gross hematuria. Left ureteral cancer was suspected by the imaging examination, and laparoscopic left total nephroureterectomy was performed. Histopathological examination showed pure type of LELC in the ureter. She is alive without disease recurrence at fifteen months after surgery.

DOI： 10.14989/ActaUrolJap_67_5_205

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Radical prostatectomy and radiotherapy are currently the main treatment options for localized prostate cancer. However, no large cohort study comparing surgery and radiation has been performed in Japan or Asia. The objective of the current study was to compare the survival outcomes of patients with clinically localized prostate cancer and in elderly and young patients receiving surgery and radiotherapy. The survival outcomes of patients with localized prostate cancer (age at diagnosis ≤79 years, clinical T1-3) initially treated with surgery or radiotherapy were retrospectively analyzed. Data were collected from the population-based cancer registry of the Kanagawa Prefecture, Japan. A 1:1 coarsened exact matching of age at diagnosis, clinical T stage and cancer differentiation was performed between the two treatment groups. Patients were also categorized into two subgroups by age using a cutoff of 70 years for analysis. The cohort comprised 4,810 patients aged 50-79 years. No significant difference in cancer-specific survival (CSS) was observed between the two groups (P=0.612). However, the surgery group had significantly better overall survival (OS; P=0.004). When stratified for age, similar tendencies were observed in the elderly group (aged 70-79 years; CSS, P=0.961 and OS, P=0.007). No significant difference in either CSS or OS was identified in the younger group (P=0.550 and P=0.408, respectively). Intrinsic deaths were more likely to occur in elderly patients treated with radiotherapy than those undergoing surgery (69.3 vs. 78.2%; P=0.128). The results indicated that surgery provided significantly better OS than radiotherapy, particularly among the elderly. However, no significant difference was observed in CSS. These results should be interpreted with caution, given that some important factors were unavailable in the present study, such as prostate-specific antigen values and Gleason scores. Prospective trials evaluating these therapies are warranted.

DOI： 10.3892/ol.2020.12013

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

FLCN is a tumor suppressor gene which controls energy homeostasis through regulation of a variety of metabolic pathways including mitochondrial oxidative metabolism and autophagy. Birt-Hogg-Dubé (BHD) syndrome which is driven by germline alteration of the FLCN gene, predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas, pulmonary cysts and less frequently, salivary gland tumors. Here, we report metabolic roles for FLCN in the salivary gland as well as their clinical relevance. Screening of salivary glands of BHD patients using ultrasonography demonstrated increased cyst formation in the salivary gland. Salivary gland tumors that developed in BHD patients exhibited an upregulated mTOR-S6R pathway as well as increased GPNMB expression, which are characteristics of FLCN-deficient cells. Salivary gland-targeted Flcn knockout mice developed cytoplasmic clear cell formation in ductal cells with increased mitochondrial biogenesis, upregulated mTOR-S6K pathway, upregulated TFE3-GPNMB axis and upregulated lipid metabolism. Proteomic and metabolite analysis using LC/MS and GC/MS revealed that Flcn inactivation in salivary gland triggers metabolic reprogramming towards the pentose phosphate pathway which consequently upregulates nucleotide synthesis and redox regulation, further supporting that Flcn controls metabolic homeostasis in salivary gland. These data uncover important roles for FLCN in salivary gland; metabolic reprogramming under FLCN deficiency might increase nucleotide production which may feed FLCN-deficient salivary gland cells to trigger tumor initiation and progression, providing mechanistic insight into salivary gland tumorigenesis as well as a foundation for development of novel therapeutics for salivary gland tumors.

DOI： 10.1016/j.bbrc.2019.11.184

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A computer-assisted diagnostic system for analyzing bone scans (BONENAVI) calculates the automated bone scan index (aBSI). Here we evaluated the aBSI as a prognostic imaging biomarker for men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. METHODS: We retrospectively analyzed 48 patients who received cabazitaxel for mCRPC and evaluated the ability of the aBSI to predict overall survival (OS). The Cox proportional hazards model was used to investigate the associations between baseline aBSI at cabazitaxel treatment and OS with the clinical variables as follows: age, number of cycles of docetaxel, serum prostate-specific antigen, hemoglobin (Hb), lactate dehydrogenase (LDH), and alkaline phosphatase. We determined the C-index to evaluate the discriminatory ability of our models when we included or excluded the aBSI from the analyses. RESULTS: The median OS after cabazitaxel treatment was 10.0 months, and patients with aBSI ≤1% achieved significantly longer OS compared with patients with aBSI ≥1%. Multivariate analysis showed that age, Hb, LDH, and aBSI were independent prognostic factors of OS. Adding aBSI to the base model increased the C-index from 0.78 to 0.80. CONCLUSIONS: The aBSI may serve as a useful imaging biomarker for predicting OS among men with mCRPC treated with cabazitaxel. Prospective studies are required to establish the value of aBSI as prognostic imaging biomarker.

DOI： 10.1186/s12885-018-4401-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The pituitary production of human chorionic gonadotropin (hCG) can cause false-positive results during or after germ cell tumor (GCT) treatment. Because hypogonadism leads to pituitary hCG production, testosterone administration test (TAT) has been recommended for pituitary hCG diagnosis. However, little is known about its efficacy for the discrimination of pituitary hCG as detected by currently used hCG assays in treatment of GCT. We conducted a retrospective multicenter study to determine the usefulness of TAT. MATERIALS AND METHODS: The study included 60 patients who underwent TAT for the discrimination of pituitary hCG. In principle, serum hCG levels were measured 1 week after testosterone enanthate administration (250 mg). When the serum hCG levels decreased below the normal upper range, the results of TAT were determined positive. In this case, the elevated hCG was considered to be derived from pituitary and not from GCT. RESULTS: Serum hCG levels were normalized after TAT in 36 of 60 patients (60%). Before TAT, the hCG levels were below 1.0 IU/L in 13 patients (36%), 1.0-1.9 IU/L in 11 (31%), 2.0-2.9 IU/L in 7 (19%), and >3.0 IU/L in 5 (14%) of TAT-positive patients. Of them, 28 (78%) patients were successfully managed without further treatment with chemotherapy after TAT. Pituitary hCG was associated with higher levels of LH and not necessarily associated with low levels of testosterone. CONCLUSION: Determining the TAT status of patients was effective in discriminating pituitary hCG production.

DOI： 10.1007/s00432-017-2520-5

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記述言語：英語  

A 56-year-old man was admitted to our hospital for urachal carcinoma with peritoneal dissemination. He received first-line chemotherapy with gemcitabine and cisplatin. After the fifth cycle, a computed tomography (CT) scan revealed abdominal fluid, and his serum tumor marker levels were increased. The patient was started on second-line therapy with FOLFIRI. After 11 cycles, his tumor decreased in size and no new metastatic lesions were detected. The patient underwent complete tumor resection with partial cystectomy and pelvic lymph node dissection. The tumor was removed, along with adhering surrounding organs, including the omentum, peritoneum, abdominal rectus muscle, and vermiform appendix. Although pathological examination confirmed peritoneal dissemination, his tumor markers normalized soon after surgery. The patient has survived 62 months after surgery without any adjuvant therapy and with no evidence of recurrence. To our knowledge, this is the longest duration of survival without recurrence of a patient with urachal carcinoma with peritoneal dissemination who received multimodal therapy.

DOI： 10.1155/2018/9836154

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 34-year-old man presented with scrotal pain and slight fever. The scrotal pain was improved by the treatment of antibiotics, but the slight fever remained and an abdominal protuberance appeared. Computed tomography showed a 22 cm abdominal tumor with lipid density. He was then referred to our hospital. He was diagnosed as retroperitoneal liposarcoma and a surgical resection was performed for retroperitoneal tumor and surrounding organs. Histopathological diagnosis was dedifferentiated liposarcoma. 3 months after surgery, a PET/CT scan showed multiple lung metastases. We treated the patient with AI therapy by doxorubicin and ifosfamide. After 6 courses were performed, a complete response was achieved. 30months after the initial surgery, a PET/CT scan showed there was just one metastasis which was in the left lung. Thoracoscopic lung tumor resection was performed. Histopathological diagnosis was metastatic dedifferentiated liposarcoma. As adjuvant therapy, we treated with IE therapy by ifosfamide and VP-16. 3 courses were performed. 3 years and 6 months after the first surgery, he has had no recurrence up to the present day.

DOI： 10.5980/jpnjurol.109.25

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 74-year-old man underwent transurethral resection for a bladder tumor (TURBT). The pathological diagnosis was urothelial carcinoma, grade 3 pT2 at least. He desired preservation of the bladder. Thus, MEC (methotrexate 100-150 mg/body (day 1), etoposide 100 mg/m2 (day 2-4), cisplatin 20 mg/m2 (day 2-6)) chemotherapy was administered for 2 courses. The next year, he had a relapse in the bladder, and the pathological diagnosiswasurothelial carcinoma, grade 2 pTa and pTis. He underwent Calmette-Guerin Bacillus (BCG) immunotherapy for 6 courses that resulted in a complete response without recurrence for 6 years. Six months after the latest examination, he complained of difficulty in voiding. An 8 cm tumor in the bladder and enlargement of obturator lymph node were detected. The pathological diagnosis by TURBT was small cell carcinoma. He rejected cystectomy, so we applied MEC therapy again. After 2 courses of MEC therapy, the bladder tumor and lymphadenopathy markedly shrunk in image and almost disappeared subsequently. The patient refused further therapy, but he had been followed without recurrence for 48 monthsafter the chemotherapy.

DOI： 10.14989/ActaUrolJap_63_6_245

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We describe a case of testicular tumor with multiple metastasis to the lung,retoroperitoneal lymph node, and brain. After chemotherapy the retroperitoneal lymph node and brain metastasis disappeared,but the multiple pulmonary metastases but not disappear,although they were reduced in size. Since the human chorionic gonadotoropin (HCG) was persistently dected at a low level,we performed a testosterone tolerance test. The HCG level became undetectable for a while,but was detected at a low level again. Then the patient underwent residual tumor removal of some of the residual pulmonary disease,which was diagnosed as tumor necrosis. The patient has been followed on an ambulatory basis after surgery for 12 months without recurrence. In this case a definitive diagnosis was difficult,because of the low positive level of HCG.

DOI： 10.14989/ActaUrolJap_63_3_119

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION AND OBJECTIVES: An elevated neutrophil-to-lymphocyte ratio (NLR) has been suggested to be associated with a poor prognosis in several cancers. We evaluated the utility of an elevated NLR as a biomarker to predict the prognosis of metastatic castration-resistant prostate cancer (mCRPC) patients treated with cabazitaxel (CBZ). METHODS: We analyzed 47 patients who received CBZ chemotherapy for mCRPC in our institutions. The NLR was calculated using the neutrophil and lymphocyte counts before CBZ chemotherapy. We determined the NLR cut-off value based on the sensitivity and specificity levels derived from area under the receiver operator characteristic curves for death. A multivariate analysis was performed to investigate the association between the NLR and the prognosis. RESULTS: The median overall survival (OS) after CBZ was 10.0 months (range: 6.3-13.2). The median OS was shorter in patients with a high NLR (≥3.83) than in those with a low NLR (<3.83) (5.8 versus 13.2 months, p = 0.018). In the multivariate analysis, the NLR, patient age, and lymph node (LN) metastasis were independent predictors of the OS (hazard ratio 3.01, p = 0.030; hazard ratio 3.10, p = 0.029; hazard ratio 12.38, p = 0.001, resp.). CONCLUSIONS: NLR might be a useful prognostic biomarker in mCRPC patients treated with CBZ.

DOI： 10.1155/2017/7538647

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 70-year-old man underwent left partial nephrectomy for renal cell carcinoma (pT1aN0M0). One year after the surgery, he presented with hematuria and fatigue. Computed tomography showed a left 8 cm renal tumor and multiple liver and lung metastases. We performed percutaneous renal and liver biopsy with echo guidance. The diagnosis of both kidney and liver was urothelial carcinoma. He died 3 weeks after the diagnosis. Ipsilateral occurrence of the pelvic renal carcinoma after partial nephrectomy for renal cell carcinoma is extremely rare. To our knowledge, this case is the first to be reported in Japan and elsewhere.

DOI： 10.14989/ActaUrolJap_62_10_535

PubMed

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記述言語：日本語   出版者・発行元：(一社)腎癌研究会  

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記述言語：英語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

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記述言語：英語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)腎癌研究会  

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記述言語：日本語   出版者・発行元：(一社)腎癌研究会  

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記述言語：日本語   出版者・発行元：(一社)腎癌研究会  

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記述言語：日本語   出版者・発行元：(一社)腎癌研究会  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

J-GLOBAL

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

症例は66歳男性。左腎細胞癌cT1bN0M0に対し体腔鏡下腎摘除術を施行、病理組織診断は淡明細胞癌、G2、pT1bであった。術前よりCTで右副腎に径15mmの腫瘤を認められていたが画像から腺腫と診断し、経過観察となった。術後4年目にCTで右副腎腫瘤は径25mmに増大傾向を認め、体腔鏡下右副腎摘除術を施行、病理組織診断は淡明細胞癌、G2であり、腎細胞癌からの転移と診断された。腎細胞癌が同時性に孤立性対側副腎転移をきたし、診断、治療に至った報告は稀である。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：日本語   出版者・発行元：泌尿器科紀要刊行会  

74歳男。排尿困難を主訴とした。2006年に浸潤性膀胱癌に対して経尿道的膀胱腫瘍切除術(TURBT)を行い、病理組織は尿路上皮癌、grade 3、pT2≦で小細胞癌を疑う所見はなかった。患者が膀胱温存を強く希望したため、メソトレキセート、エトポシド、シスプラチンによる多剤併用療法(MEC療法)を行い、1回の表在性再発を除いて約7年間無再発であったが、2013年に頻尿を自覚し、画像検査所見で急速に進行する再発性膀胱癌と右閉鎖リンパ節の腫大を認めた。膀胱癌cT3bN1M0と診断してTURBTを行い、腫瘍病理はpure typeの小細胞癌であったが、小細胞癌のマーカーはすべて陰性であり、追加治療としてMEC療法2コースを行ったところ、重篤な副作用を認めることなく残存腫瘍とリンパ節腫大はほぼ消失した。MEC療法施行後48ヵ月現在、再発は認めていない。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01269&link_issn=&doc_id=20170710470005&doc_link_id=1390290699820941952&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390290699820941952&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：日本語   出版者・発行元：泌尿器科紀要刊行会  

36歳男性。胸痛を主訴に前医を受診し、精査の結果、右精巣腫瘍、多発肺・後腹膜リンパ節・左頭頂葉転移と診断された。前医では高位精巣摘除術が施行され、病理結果は絨毛癌、stage IIIc、IGCCCはpoor prognosisであった。術後、加療目的で当院へ紹介となり、転移性精巣腫瘍に対してmodified BEP療法を行った後、通常のBEP療法を3コース施行した。その後、EP療法を1コース追加したが、腫瘍マーカーでHCGの低下が緩徐になったため、レジメンをTIP療法に変更し4コース施行した。更にNI療法を適応したが、HCGは低値陽性が持続した。NI療法4コース終了時点で肺転移、後腹膜リンパ節転移は消失したが、多発肺転移が残存するため、胸腔鏡下腫瘍摘出術を施行した。病理結果はいずれも壊死組織であり、病理組織学的完全寛解が確認された。肺手術後はHCGが陰性化し、術後12ヵ月現在、再発はみられていない。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01269&link_issn=&doc_id=20170414400005&doc_link_id=1390572174797440768&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390572174797440768&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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会議種別：口頭発表（招待・特別）  

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会議種別：シンポジウム・ワークショップ パネル（指名）  

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会議種別：シンポジウム・ワークショップ パネル（指名）  

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