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Sarcopenia is a known predictor of overall survival in several diseases. We investigated the relationship between sarcopenia and outcome of treatment with cabazitaxel (CBZ) for castration-resistant prostate cancer (CRPC) by a retrospective analysis of 37 patients, who were given cabazitaxel at our hospital, from December 2014 to November 2020. The skeletal muscle mass was evaluated using the Psoas Muscle Mass Index (PMI: psoas major muscle area at the level of the third lumber vertebra (cm²)/height x height (m²)) through computed tomography images. The severe sarcopenia group (PMI＜4.96) showed lower levels of serum albumin, in comparison with the non-severe sarcopenia group (PMI≥4.96). Multivariate analysis identified PMI (odds ratio＝3.7; P＝0.023) as an independent factor associated with prostate specific antigen response to CBZ therapy. However, there was no significant difference in the overall survival between the severe and the non-severe sarcopenia groups (P＝0.1). Skeletal muscle mass might be closely correlated to the therapeutic response to CBZ, but not to the prognosis of patients with CRPC. Nutritional rehabilitation and exercises targeting sarcopenia for patients with prostate cancer should be considered., 本論文の要旨は，第109回日本泌尿器科学会総会で発表を行った．

Patients who contract severe renal infections often suffer from urosepsis. Therefore, early diagnosis and treatment are required. Sometimes, the treatment with antibiotics is not enough for control of the infections. Most of the patients also require surgical interventions including transurethral drainage and nephrectomy. Twenty-two patients with severe renal infections treated between April 2010 and October 2019 at our institute were evaluated retrospectively. Eleven patients had undergone nephrectomy. Open nephrectomy was performed on 10 patients. Laparoscopic nephrectomy was attempted in the other patient but was converted to open nephrectomy because severe adhesion was found around the tissues. Nephrectomy was performed by the retroperitoneal approach on 9 patients and by the transperitoneal approach on 2 patients. The reteroperitoneal approach was used on two patients who suffered postoperative colon perforation. Inflammatory involvement of renal pelvis, hilum and adjacent structures leads to dense fibrotic reaction and obliteration of tissue planes, which makes the nephrectomy procedure challenging. Therefore, it is important to choose the most appropriate nephrectomy procedure for each patient when they have contracted severe renal infections.

Yosuke Morizawa, Katsuya Aoki, Shunta Hori, Daisuke Gotoh, Makito Miyake, Yasushi Nakai, Kazumasa Torimoto, Nobumichi Tanaka, Kiyohide Fujimoto Department of Urology, Nara Medical University, Kashihara, Nara, JapanCorrespondence: Kiyohide FujimotoDepartment of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, JapanTel +81-744-22-3051Fax +81-744-22-9282Email kiyokun@naramed-u.ac.jpPurpose: To determine the clinical efficacy of endoscopic transurethral incision (TUI) for boys with refractory daytime incontinence due to a posterior urethral valve with or without nocturnal enuresis.Patients and Methods: A total of 20 boys with daytime incontinence were assessed. Twelve boys underwent TUI (TUI+ group) and eight boys continued receiving oral drugs (TUI- group). The primary endpoint was the cure rate associated with TUI or NE in both groups.Results: Only two boys achieved daytime continence 6 months after TUI, but no boys were cured of nocturnal enuresis 6 months after TUI. The median time to daytime continence was significantly longer in the TUI+ than in the TUI- group (52 vs 27 months, respectively; log rank P = 0.041) and the median time to dry nights was significantly longer in the TUI+ than in the TUI- group (56 vs 36 months, respectively; log rank P = 0.021).Conclusion: TUI might be not effective in boys with refractory daytime incontinence.Keywords: pediatric, daytime incontinence, enuresis, TUI

Aims: There is accumulating evidence that excessive salt intake contributes to nocturnal polyuria. We aimed to investigate the relationship between salt intake, leg edema, and nocturnal urine volume (NUV) to assess the etiology of nocturnal polyuria. Methods: A total of 56 men aged ≥60 years who were hospitalized for benign prostatic hyperplasia or with suspected prostatic cancer were enrolled. Urine frequency-volume charts of the patients were maintained, and they underwent bioelectrical impedance analysis twice daily (at 5:00 pm and 6:00 am) and examination of blood (brain natriuretic peptide levels) and urine (sodium and creatinine levels and osmotic pressure) samples once daily (at 6:00 am). Free-water clearance, solute clearance, and sodium clearance at night were measured, and daily salt intake was estimated. Results: The data of 52 patients were analyzed. Daily salt intake positively correlated with leg edema at 5:00 pm, differences in leg extracellular fluid levels between 5:00 pm and 6:00 am, and NUV, but not with diurnal urine volume. Partial correlation coefficients showed that salt intake was a factor of the correlation between NUV and change in extracellular volume in the legs between 5:00 pm and 6:00 am. A multivariate logistic model showed that sleep duration and sodium clearance were independent predictive factors for nocturnal polyuria. Conclusions: Sodium intake correlates with diurnal leg edema and NUV in elderly men. These results provide evidence supporting sodium restriction as an effective treatment for nocturnal polyuria., 博士（医学）・乙第1507号・令和3年3月15日, © 2020 Wiley Periodicals LLC., This is the peer reviewed version of the following article: https://onlinelibrary.wiley.com/doi/10.1002/nau.24401, which has been published in final form at https://doi.org/10.1002/nau.24401. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

The Klotho (KL) gene was first identified as a potent aging suppressor. The KL family currently comprises of three proteins: α-Klotho (KLA), β-Klotho (KLB), and γ-Klotho (KLG). Many studies have shown that KLA and KLB participate in tumor progression or suppression, depending on the type of cancer; however, the relationship between KLG and prostate cancer has not yet been studied. Some studies have claimed that KL is correlated to sensitivity to chemotherapy. Here, we investigated the oncogenic potential of KLG in castration-resistant prostate cancer (CRPC). Immunohistochemical analysis using prostate biopsy specimens revealed that patients with high KLG expression in primary prostate cancer tissue had a significantly poor prognosis for overall survival. In addition, the prostate-specific antigen response rate after docetaxel (DTX) therapy in patients with high KLG expression was lower than that in patients with low KLG expression. To evaluate the potential of KLG as a therapeutic target in human prostate cancer, we generated a xenograft model of human CRPC cell line (PC-3) in male athymic mice. The animals were randomly divided into four groups as follows: i) control group (vehicle only); ii) DTX group (intraperitoneal administration); iii) small interfering RNA targeting KLG (KLG siRNA) group (intratumoral administration); and iv) a combination group (DTX plus KLG siRNA). After 3 weeks of treatment, the tumor weight and tumor Ki-67 labeling index were significantly lower in the KLG siRNA group and the combination group than in the control group. Sensitivity to DTX was increased upon treatment with KLG siRNA. These findings suggest that KLG expression in primary prostate cancer lesions is associated with resistance to DTX in CRPC and has potential as a diagnostic and therapeutic target for patients with CRPC., 博士（医学）・甲第740号・令和2年3月16日, Copyright: © Onishiet al. This is an open access article distributed under theterms of CreativeCommons Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/).

Additional file 1. Table S1. Causes of death in patients treated with SEED-BT and RP.

Renal cell carcinoma (RCC) is an immunogenic tumor and pathological specimen generally contain large quantities of tumor-infiltrating lymphocytes (TILs). Numerous cell types and cytokines could affect the immune escape mechanism of tumor cells. The aim of the present study was to investigate the prognostic impact of TILs and the associated circulating cytokines on localized clear cell RCC following radical nephrectomy. A total of 87 patients who had undergone radical nephrectomy and were pathologically diagnosed with localized clear cell RCC were included. The present study evaluated the profile of TILs with immunohistochemical analysis of tumor specimens using a panel of antibodies [cluster of differentiation (CD)-4, CD8, CD80, CD86, CD276, and Forkhead box p3 (Foxp3)]. Counts of each TIL were compared with clinicopathological variables. Based on the results of immunohistochemical analyses, putative cytokines, including interleukin (IL)-6, IL-10, IL-17, interferon-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β, were selected, and their levels in preoperative serum were measured by ELISA. The levels were compared with TIL counts in tumor specimens. High counts of the CD276+ and Foxp3+ TILs were identified as independent factors for poor prognosis for metastasis and local recurrence following radical nephrectomy (P=0.033 and 0.006, respectively). A high CD276+ TIL count was associated with preoperative serum levels of TNF-α and IFN-γ (P=0.027 and P=0.035, respectively), whereas a high count of Foxp3+ TILs was associated with preoperative serum levels of TGF-β (P=0.021). High levels of TNF-α and TGF-β were associated with recurrence-free survival (P=0.035 and P=0.031, respectively). Topical intra-tumoral immunoreaction and systemic immune status may be associated with patients with localized RCC. The topical induction of the CD276+ and Foxp3+ TILs was suggested to be associated with high levels of serum TNF-α and IFN-γ. Preoperative serum levels of TNF-α and TGF-β could be simple and non-invasive biomarkers for risk stratification before radical surgery., 博士（医学）・甲第741号・令和2年3月16日, Copyright © Spandidos Publications 2019. All rights reserved., Articles from Oncology Letters are provided here courtesy of Spandidos Publications.

Additional file 1 : Table S1. Clavien classification of surgical complications.

AIM: We investigated the role of the bladder wall in permeating water, focusing on aquaporins. METHODS: Female Sprague-Dawley rats weighing 300 g were used to investigate the role of the bladder wall in saline permeation. Changes in intravesical fluid volume and sodium concentration were measured in the desmopressin acetate hydrate-loaded and control groups 3 h after administration. Bladders were resected to measure aquaporin-1, 2, and 3 gene expression using qRT-PCR. Additionally, the change of aquaporin-2 expression was measured using Western blotting and immunohistochemistry in intravesical aquaporin-2 siRNA-treated and control groups. RESULTS: Although the intravesical fluid volume and sodium concentration significantly decreased from 0 to 3 h (1.00 ± 0.00 vs 0.83 ± 0.08 mL, 157.80 ± 1.30 vs 146.8 ± 1.92 mEq/mL, P, 博士（医学）・甲第697号・平成31年3月15日, © 2018 Wiley Periodicals, Inc., This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/nau.23715], which has been published in final form at [http://dx.doi.org/10.1002/nau.23715]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

A 66-year-old man underwent nephrectomy for right renal cell carcinoma (cT3bNOMl (PUL)). Thereafter, he was treated with sunitinib for lung metastasis as the first-line therapy for 5 months and then axitinib as the second-line therapy for 2 months. Because lung metastasis progressed despite molecular targeted therapies, nivolumab was used as the third-line treatment. Three months later, he complained of painful stiffness in hands and wrist joints symmetrically. He was diagnosed as having rheumatoid arthritis. Treatment with nivolumab was discontinued and prednisolone and methotrexate were started. Although the painful stiffness in joints was improved l month later, synovitis remained partially 6 months after starting treatment of disease with anti-rheumatic drugs. Therefore, treatment for rheumatoid arthritis was continued. On the other hand, because the lung lesion had progressed 2 months after discontining nivolumab, everolimus was used as the fourth-line therapy.

Objectives : To evaluate the clinical benefit of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) in patients with muscle-invasive bladder cancer treated with radical cystectomy and to identify patients who may benefit from neoadjuvant chemotherapy and predictors of therapeutic response to it. Methods : In this prospective study, we enrolled 37 patients with muscle-invasive bladder cancer (cT2-4aNanyM0). The primary endpoint was the pathological response rate at cystectomy after receiving neoadjuvant GC chemotherapy. Univariable and multivariable analyses were used to determine predictive factors of pT0N0 and ≦pT1N0. The secondary endpoints were adverse events during chemotherapy, surgical complications, as well as overall, disease-specific, and recurrence-free survival. Results : A mean of 2.7 cycles of neoadjuvant GC was administered. Pathological complete response (pT0N0), partial response (pTisN0/pT1N0), and pathological response (≦pT1N0) rates were 24.3%, 27.0%, and 5l.3%, respectively. Grade 3 or 4 non-hematologic adverse events were rare. Three-year overall, disease-specific, and recurrence-free survival rates were 70.7%, 8l.3%, and 63.9%, respectively. Patients with pathological response (≦pT1N0) demonstrated a significantly improved 3-year overall survival rate (94.7% vs. 42.8%), disease-specific survival rate (94.7% vs.62.9%), and recurrence-free survival rate (80.6% vs.45.5%), compared with pathological non-responders (≦pT2Nany). Clinical stage cT2 and low pre-chemotherapy platelet-to-lymphocyte ratios were significant indicators of favorable pathological response to neoadjuvant Gc. Conclusions : Neoadjuvant chemotherapy using GC is safe and effective in patients with muscle-invasive bladder cancer, Pretreatment clinical T2 stage and low platelet-to-lymphocyte ratios were predictive markers for successful neoadjuvant treatment of muscle-invasive bladder cancer with GC.

AIMS: To investigate the effect of tadalafil on bladder blood flow and lower urinary tract function in a rat model of diabetes. MATERIALS AND METHODS: We studied female Sprague-Dawley rats and induced diabetes in some using a single intraperitoneal injection of streptozotocin. We divided the rats into nondiabetes (ND), diabetes (D), and diabetes with tadalafil (DT) groups. The rats were raised for an additional 7 weeks after diabetes induction. The DT group received oral tadalafil (2 mg/kg/day) for 7 days before the experiments. At 7 weeks after diabetes induction, we performed cystometry, resected the bladders for immunohistochemistry (hypoxia-inducible factor-1α [HIF-1α] and 8-oxo-2'-deoxyguanosine [8-OHdG] staining), and measured bladder blood supply using a laser blood flow meter. RESULTS: The opening pressure, when the urethra opens and urine flow starts, was significantly lower in the DT group than in the D group (24.9 ± 5.9 vs 43.6 ± 12.3 cmH2 O). The inter-contraction interval was significantly longer in the D group than in the ND and DT groups (1566.2 ± 168.7 vs 702.9 ± 165.2 and 787.4 ± 148.8 s). Immunohistochemistry showed positive staining of the urothelial layer for both HIF-1α and 8-OHdG in the D group, but not in the ND or DT groups. Bladder blood flow was significantly lower in the D group than in the ND or DT groups. CONCLUSIONS: Tadalafil improves bladder blood supply and lower urinary tract function in diabetic rats. Tadalafil may be a promising drug that restores lower urinary tract dysfunction in the early phase of diabetes., 博士（医学）・甲第677号・平成30年3月15日, © 2017 Wiley Periodicals, Inc., This is the peer reviewed version of the following article : which has been published in final form at http://dx.doi.org/10.1002/nau.23372. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Here, we report a case of papillary renal cell carcinoma in a 47-year-old woman. In 1970 (at 5 years old), she was diagnosed with Wilms tumor in her right kidney, and underwent surgery. However, nephrectomy was not possible. Consequently, she received radiation therapy (61. 5 Gy) at the former hospital. Thereafter, the patient regularly visited her physician and had no further problems. In 1998 (at 33 years old), blood was detected in her urine, and renal cell carcinoma was suspected. A computed tomography (CT)-guided biopsy was performed, but tissue collection was difficult due to calcification of the renal parenchyma after radiation treatment. The patient was followed closely without treatment. Since 2003, the patient on her own volition stopped visiting the hospital. Her symptoms gradually worsened and in October 2012 (at 47 years old), she was admitted to our hospital. Based on the imaging findings, a right renal pelvic tumor was suspected. Despite various examinations, including retrograde pyelography, a definitive diagnosis could not be made. Following detailed examinations, we observed that the tumor had developed bone metastases. We started chemotherapy consisting of gemcitabine and cisplatin, but the tumor was resistant to the treatment. Renal cell carcinoma was suspected based on the biopsy results for bone metastasis, and consequently, targeted therapy (pazopanib) was started. However, the patient died in August 2014 (at 49 years old) because of progression of the disease. An autopsy revealed the definitive diagnosis to be papillary renal cell carcinoma type 2.

Objective: We previously developed genitourinary (GU) cancer-specific scoring system for prediction of survival in patients with bone metastasis (the Bone-Fujimoto-Owari-Miyake [B-FOM] scoring model) based on five prognostic factors: the type of primary tumor (prostate cancer (PCa) vs renal cell carcinoma (RCC) and PCa vs urothelial carcinoma (UC)), poor performance status (PS), visceral metastasis, high Glasgow-prognostic score (GPS), elevated neutrophil-to-lymphocyte ratio (NLR). The aim of this study was to externally validate and further improve the performance of the B-FOM score. Methods: The external validation cohort comprised 309 patients with GU cancer with bone metastasis from multiple institutions. Clinical factors were analyzed using Kaplan-Meier method and COX regression hazard model. Performance of a modified B-FOM score was compared to that of other scoring models by the Kaplan-Meier method and the area under the curve (AUC) of receiver operating characteristic curves. Results: The median follow-up period of development and validation cohort were 25 and 17 months, respectively. Kaplan-Meier curve demonstrated that the type of primary tumor (RCC and UC vs PCa), poor PS, presence of visceral metastasis, high GPS, elevated NLR were significantly associated with shorter cancer-specific survival. Risk groups were successfully stratified by the modified B-FOM score classification. Moreover, the AUC of the modified B-FOM scoring model for predicting mortality at 6, 12, and 24 months were 0.895, 0.856, and 0.815, respectively, which were the highest among evaluated models. Conclusions: The B-FOM scoring model is a simple and accurate prediction tool. By using this scoring model at the time of the diagnosis of bone metastasis in patients with GU cancers, an individualized optimal treatment strategy can be selected., 博士（医学）・甲第835号・令和4年3月15日, © 2020 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license(https://creativecommons.org/licenses/by-nc-nd/4.0/).

Heparan sulfate proteoglycan syndecan-1, CD138, is known to be associated with cell proliferation, adhesion, and migration in malignancies. We previously reported that syndecan-1 (CD138) may contribute to urothelial carcinoma cell survival and progression. We investigated the role of heparanase, an enzyme activated by syndecan-1 in human urothelial carcinoma. Using human urothelial cancer cell lines, MGH-U3 and T24, heparanase expression was reduced with siRNA and RK-682, a heparanase inhibitor, to examine changes in cell proliferation activity, induction of apoptosis, invasion ability of cells, and its relationship to autophagy. A bladder cancer development mouse model was treated with RK-682 and the bladder tissues were examined using immunohistochemical analysis for Ki-67, E-cadherin, LC3, and CD31 expressions. Heparanase inhibition suppressed cellular growth by approximately 40% and induced apoptosis. The heparanase inhibitor decreased cell activity in a concentration-dependent manner and suppressed invasion ability by 40%. Inhibition of heparanase was found to suppress autophagy. In N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer mice, treatment with heparanase inhibitor suppressed the progression of cancer by 40%, compared to controls. Immunohistochemistry analysis showed that heparanase inhibitor suppressed cell growth, and autophagy. In conclusion, heparanase suppresses apoptosis and promotes invasion and autophagy in urothelial cancer., 博士（医学）・乙第1506号・令和3年3月15日, © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB., 博士（医学）・甲第768号・令和3年3月15日, © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Shunta Hori, Tatsuki Miyamoto, Keiichi Sakamoto, Takuto Shimizu, Kazuki Ichikawa, Yosuke Morizawa, Daisuke Gotoh, Yasushi Nakai, Makito Miyake, Tatsuo Yoneda, Nobumichi Tanaka, Katsunori Yoshida, Kiyohide Fujimoto Department of Urology, Nara Medical University, Kashihara, Nara 634-8522, Japan Background: Transplant renal vein thrombosis (TRVT) is a severe vascular complication and is caused by various factors, including recipient factors, donor factors, immunosuppression regimens, and surgical techniques. Despite adequate interventions, including thrombolytic therapy or surgical thrombectomy, successful salvage of the allograft is often difficult. We observed a case of TRVT induced by compression of the renal vein immediately after intraoperative abdominal closure.Case presentation: A 41-year-old male underwent ABO-compatible living kidney transplantation. The donor was his 45-year-old sister, and her right kidney was donated. The allograft had a single artery and vein. One of the preoperative recipient problems was obesity (body mass index, 33.4kg/m2). Intraoperative Doppler ultrasonography (US) revealed sufficient blood flow throughout the allograft, and urine output was also observed. After surgery, hematuria was observed; the urine output decreased and serum creatinine levels increased to 7.0mg/dL. Doppler US showed a decrease in diastolic flow and an elevated resistive index, which were similar findings to those noted in acute rejection. Although steroid pulse therapy was initiated, allograft dysfunction was worsening. On postoperative day 4, surgical exploration revealed TRVT; consequently, thrombectomy was performed. The urine output increased, and serum creatinine levels decreased to 1.8mg/dL. The cause of TRVT development may be that the transplant renal vein was relatively short, due to the right kidney being compressed by surrounding tissues after abdominal closure, and that TRVT was gradually developing due to stagnant blood flow.Conclusion: Although TRVT is induced by multiple factors, an accurate diagnosis is often difficult. Understanding these factors, including obesity, and considering TRVT as a cause of allograft dysfunction are important during the pre-, peri-, and postoperative periods. Knowledge of TRVT can lead to early and accurate diagnosis and intervention, resulting in better outcomes for the patients with allograft dysfunction. Keywords: kidney transplantation, surgical exploration, transplant renal vein thrombosis, thrombectomy&nbsp

PURPOSE:The change in functional renal volume (FRV) has an absolute influence on renal function after nephrectomy (Nx) or nephron-sparing surgery (NSS). In this study, we prospectively examined whether the postoperative renal function following Nx and NSS could be accurately predicted and assessed the reproducibility of our newly developed 3-D image reconstruction system (Kashihara) to measure the FRV. METHODS:We enrolled 98 patients who underwent Nx and 41 patients who underwent NSS from April 2006 to September 2009 to predict postoperative FRV and renal function. FRV was measured before and after (1 month and 1 year) renal surgery. The postoperative estimated glomerular filtration rate (eGFR) was predicted from the preoperative eGFR calculated from the serum creatinine (sCr) level and the ratio of the postoperative/preoperative FRV. To assess the reproducibility and accuracy of our newly developed 3-dimensional (3-D) image reconstruction system, FRV was measured by five examiners using images obtained by CT (five cases) and MRI (five cases). RESULTS:Significant correlation was found both for FRV and for renal function between the predictive values and the actually measured values at 1 month and 1 year after surgery, not only in the Nx group, but also in the NSS group. The accuracy and reproducibility could be confirmed both with CT and MRI studies. CONCLUSIONS:The postoperative FRV and renal function could be predicted preoperatively using a 3-D image reconstructive system, preoperative routine diagnostic imaging, and preoperative sCr level., 博士（医学）・乙第1369号・平成27年11月27日, © Springer-Verlag Berlin Heidelberg 2015, The final publication is available at Springer via http://dx.doi.org/10.1007/s00345-014-1470-7

A 68-year-old man underwent radical nephrectomy for renal cell carcinoma of the right kidney 12 years ago. He was diagnosed as having a recurrent tumor of the contralateral kidney and a single metastatic pulmonary lesion by diagnostic imaging on the annual checkup. He visited us in order to receive nephron sparing surgery. Since the preoperative abdominal computed tomography showed tumor thrombus invading intothe intrarenal vein, ex vivo partial nephrectomy and auto-transplantation was performed. Although he received transit hemodialysis during the postoperative 10 days, his renal function, thereafter became stable without hemodialysis. Eighty-seven days later he underwent right lower lobectomy. At postoperative 6 months he has no local recurrence or distant metastasis and maintains well-preserved renal function.

OBJECTIVE: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria. MATERIALS AND METHODS: One hundred six men with nocturia aged ≥ 60 years underwent full-night polysomnography to determine whether they had OSAS. Blood count, standard chemistry panel, BNP, urinary ADH, urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 AM, and a frequency volume chart was recorded on the same day that polysomnography was performed. RESULTS: We evaluated 83 patients after excluding 18 with mild OSAS and 5 with nocturnal polyuria index, 博士（医学）・乙第1349号・平成26年12月3日, Copyright © 2014 Elsevier Inc. All rights reserved.

OBJECTIVE: To assess whether the phosphorylated Fas-associated death domain protein (FADD) at 194 serine (p-FADD) is valuable as a marker of biochemical recurrence in hormone-naive patients who had undergone radical prostatectomy. MATERIALS AND METHODS: We used radical prostatectomy specimens from 106 patients. None of the patients had received neoadjuvant or adjuvant therapy. The percentage of positive p-FADD cells (nuclear staining) was immunohistochemically evaluated. The correlation between FADD phosphorylation and the clinicopathologic parameters was assessed. The correlation between the biochemical recurrence-free rate and the p-FADD expression level was analyzed using the Kaplan-Meier method. RESULTS: Overall, 39 patients developed biochemical recurrence. We investigated the expression of p-FADD in 106 patients with prostate cancer using immunohistochemistry. We compared our findings with the clinicopathologic parameters, including the follow-up data. Patients with a greater positive p-FADD rate had a significantly lower biochemical recurrence rate than those with a lower positive p-FADD rate (P < .001). A significant inverse correlation was found between the positive p-FADD rate and the Gleason score. CONCLUSION: A low expression of p-FADD could be a predictor of biochemical recurrence in hormone-naive patients who have undergone radical prostatectomy., 博士（医学）・乙第1313号・平成25年5月29日

We report a case of prostate cancer and left ectopic ureter opening to seminal vesicle with left renal agenesis. A 62-year-old man was admitted to our hospital for treatment of prostate cancer with cyst formation. On the rectal examination, a cystic tumor was palpable on the left side of prostate. The left kidney was not detected by intravenous pyelography and ultrasonography. Magnetic resonance imaging revealed a retrovesical cystic lesion in the left side. Total prostatectomy and left ureterectomy were performed under the diagnosis of clinical T1cN0M0 prostate cancer and left ectopic ureter opening to seminal vesicle with left renal agenesis. The pathological findings showed well differentiated adenocarcinoma, Gleason score 3 + 3, and left ectopic ureter entering into the seminal vesicle and left renal agenesis. The patient was well 39 months after the total prostatectomy and left ureterectomy without evidence of recurrence. There have been no cases of the association of this urogenital anomaly, such as ectopic ureter opening to seminal vesicle with renal agenesis and prostate cancer and the combined management of both. Our case seems to be first case in the Japanese literature., 62歳男。PSA高値を指摘され、他院で経直腸的前立腺生検を受けた際、超音波で前立腺左側近傍に嚢胞性腫瘤を認めて紹介となった。画像所見で左腎尿管への造影剤の排泄を認めず、左腎あるいはその痕跡を示唆する所見を認めなかった。骨盤MRIで嚢状腫瘤は内部に出血または高粘稠な液体貯留が疑われた。また、嚢状腫瘤の頭側では連続した管腔状の組織を認め、嚢状腫瘤に異所開口する尿管と診断した。前医の前立腺精検結果 (well differentiated adenocarcinoma)等により、左無形成腎および精嚢への尿管異所開口を伴った前立腺癌と術前診断し、手術を施行した。術中所見は術前診断に一致し、開口部の精嚢は嚢腫様に腫大していた。左尿管を頭側に剥離していくと、尿管は総腸骨動静脈分岐部で盲端に終わっており、左腎は同定できなかった。術後経過は良好で、39ヵ月を経過する現在、再発転移は認めなかった。

We examined the usefulness of the volume-adjusted prostate-specific antigen (PSA) parameters for prediction of T1c prostate cancer on 210 patients who had abnormal PSA levels but no abnormal findings in digital transrectal examination (DRE) or transrectal ultrasonography (TRUS). PSA, prostate volume (PV), transition zone volume (TZV), PSAD (PSA/PV) and PSATZD (PSA/TZV) were assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Simple and stepwise logistic regression models were used to calculate the odds ratios of these parameters. Fifty-three (25.2%) of all 210 patients and 31 (19.9%) of 156 patients with intermediate PSA levels had biopsy-proved prostate cancer. The ROC curves of all patients revealed that PSA, PV, TZV, PSAD and PSATZD had significant predictive values, while AUCs of PV, PSAD and PSATZD had significant predictive values as compared to that of PSA. In the patients with intermediate PSA levels, the ROC curves revealed that PV, TZV, PSAD and PSATZD had significant predictive values, but there were no significant differences in AUCs among these parameters. The stepwise logistic regression analysis showed that PV and PSATZD were significant predictive parameters in all patients and that PSATZD was the only significant predictive parameter in the patients with intermediate PSA levels. In conclusion, not only PSAD and PSATZD but also PV and TZV had significant predictive values in discriminating prostate cancer. However, the multivariate analysis showed that PSATZD had the strongest predictive value in all patients and in those with intermediate PSA levels., T1c前立腺癌の診断におけるPSA density(PSAD)およびPSA transition zone density(PSATZD)の有用性について, 生検前にPSAのみに異常を認めた210例について検討した。210例中53例(25.2%), 生検前PSA値がグレーゾーン(4.1～10.0ng/ml)を示した156例中31例(19.9%)が癌と診断された。ROC曲線解析では, 全体210例では, PSA, PSAD, PSATZD, 前立腺体積(PV)および移行域体積(TZV)が癌診断の有効なパラメータであった。グレーゾーンを示した156例では, PSAD, PSATZD, PVおよびTZVが癌診断の有効なパラメータであった。多変量解析ではPSATZDが最も有効なパラメータであった。T1c前立腺癌を疑う症例において, PSATZDが最も有用性が高いことが示された。(著者抄録)

A 47-year-old man had a retroperitoneal tumor measuring 18 cm in maximum diameter of the left kidney that was diagnosed with computed tomography (CT)-guided needle biopsy as small cell carcinoma. Microscopically, the tumor cells showed immunohistochemical reaction for neural cell adhesion molecule antibodies. This patient with advanced renal small cell carcinoma and multiple metastatic lesions was treated with the first-line combination chemotherapy of cisplatin, etoposide and ifosphamide, which showed a partial response of primary renal tumor and a complete response of liver metastasis, and with the second-line chemotherapy of cisplatin and irinotecan, which showed a complete response of Virchow's nodal metastasis. Thereafter, in spite of salvage chemotherapy of amurubicin hydrochloride for persistent and refractory renal small cell carcinoma, he died 32 months after the first presentation due to local progression. However, combination chemotherapy of these anticancer agents made his prognosis more favorable than we expected before treatment. The extrapulmonary small cell carcinomas are generally known to be more aggressive and malignant than the lung small cell carcinomas, and small cell carcinoma arising from the kidney is an extremely rare malignant neoplasm, with only 34 cases reported in the English or Japanese literature. The prognosis of renal small cell carcinomas is currently limited as compared with the lung small cell carcinomas, and therefore a cumulative investigation of a larger number of cases treated with multidisciplinary modalities including combination chemotherapy is necessary., 47歳, 男性に左腎由来の最大径18cmの後腹膜腫瘍を認め, CTガイド下針生検にて小細胞癌と診断した。組織診断で, 腫瘍細胞は神経細胞接着分子抗体を用いた免疫染色に陽性であった。多発転移を伴う進行性腎小細胞癌の本患者は, cisplatin, etoposide, ifosphamideによるfirst-lineの多剤併用化学療法を施行され, 腎原発巣のpartial responseと肝転移巣のcomplete responseを得た。さらに, cisplatinとirinotecanを用いたsecond-lineの化学療法にて, Virchowリンパ節転移巣のcomplete responseを得た。その後, 執拗に残存し再燃する腎原発巣に対して, amurubicin hydrochlorideによるsalvage化学療法を施行したが, 初診より32ヵ月後に局所進展のため癌死した。しかし, 本症例については, これらの抗癌剤を用いた化学療法により, 治療前に予想した以上に患者の予後は良好なものとなった。一般的に肺外小細胞癌は, 肺小細胞癌よりも侵襲的で, より悪性度の高い腫瘍として知られている。その中でも, 腎由来の小細胞癌はきわめて稀な悪性新生物であり, 英文あるいは邦文論文報告も僅かに34件である。現況では, 腎小細胞癌の予後は, 肺小細胞癌の予後に比べて不良であり, 何らかの多剤併用化学療法を含めた集学的治療による, より多くの症例での治療経験の集積とその調査が必要である。(著者抄録)

著者らは直径7cm以下の腎細胞癌症例121例(124腎)に対して, 主に開腹術でマイクロ波組織凝固装置を用いた腎部分切除を施行してきた.その手術成績を評価し, 術後再発等の予後と, 術後の残腎機能を中心に報告した.輸血を要したのは8腎で, 1例は腎摘除術を余儀なくされた.術中に腎盂腎杯の開放を20例に認め, 修復を行ったが, 5例は術後も尿漏を認め, 1例は改善しなかった.術後1ヵ月以内に多発性腎細胞癌, 浸潤型紡錘細胞癌, 前述の長期尿漏遷延の3例に腎摘除術を施行した.他に患側腎での再発のため術後2年目に1例に摘除術を施行した.腎機能は, クレアチニン値, クレアチニンクリアランスの推移からみて良好に温存されていた.単腎症例1例で術後6ヵ月, 嚢胞腎症例1例で術後11年目に腎機能が悪化し, 透析が導入された.局所再発を認めたのは1例, 癌なし生存は107例で, 腎機能に問題のなかった99例は全例癌なし生存であった, Nowadays, partial nephrectomy is often selected for treatment of small renal cell carcinoma (RCC) because T1a RCC shows a favorable prognosis with a 5-year overall-survival rate exceeding 90%. To determine the methodological usefulness and treatment outcome of partial nephrectomy using microwave tissue coagulator (MTC), we evaluated our series of 121 patients (124 kidneys) with T1 RCC who underwent this procedure. Ninety-nine patients were elective and 22 patients were imperative cases. This procedure was indicated for asymptomatic solitary RCC; < or =4 cm in diameter in elective cases or < or =5 cm in imperative cases, expanding outward with a clear capsule, and showing neither renal pelvis nor renal sinus invasion. The median operation time was 150 minutes and the median blood loss was 217 ml. Eight patients needed transfusion, and conservative therapy cured 4 patients of postoperative urine leakage successfully. Three patients underwent early secondary nephrectomy due to multiple RCCs, invasive spindle cell carcinoma, or prolongation of urine leakage. No significant deterioration of renal function by creatinine clearance (Ccr) was observed, and postoperative Ccr could be precisely predicted from preoperative serum creatinine value and the renal parenchymal volume estimated with 3-dimensinal image reconstruction. Five-year overall-survival rate was 91% at the mean follow-up of up to 37.9 months and 107 patients were alive without disease. One patient showed local recurrence 2 years later and underwent radical nephrectomy. We believe that non-ischemic partial nephrectmy using MTC is a simple and reliable nephron-sparing surgery for small RCC in respect of postoperative recurrence and preservation of renal function.

Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model. Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly divided into six groups and treated with chemotherapeutic agents once a week for four weeks. After last treatment, bladder and serum samples were analyzed for cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1) using immunohistochemistry staining. Serum and urine cytokine levels were evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties similar to those of BCG. These included changes in immune cells that resulted in fewer M2 macrophages and regulatory T cells around tumors. This result was compatible with those in human samples. Intravesical chemotherapy also induced systemic changes in cytokines, especially urinary interleukin (IL)-17A and granulocyte colony stimulating factor (G-CSF), as well as in the distribution of blood neutrophils, lymphocytes, and monocytes. Our findings suggest that intravesical treatment with mitomycin C and adriamycin suppresses protumoral immunity while enhancing anti-tumor immunity, possibly through the action of specific cytokines. A better understanding of the immunoreaction induced by chemotherapeutic agents can lead to improved outcomes and fewer side effects in intravesical chemotherapy against NMIBC., 博士（医学）・甲第695号・平成31年3月15日, Copyright: © 2017 Hori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

1993年1月～5年6ヵ月間に前立腺癌と診断された319例のうち, 過去にTUR-Pにより病理組織学的にBPHと診断されていた7例について検討した.PSA高値のため受診した症例が3例で, うち1例はTUR-P前より断続してPSAが高値であった.残る4例もPSAは高値であった.TUR-Pから癌診断迄の期間は22ヵ月から15年であったが, 6例は6年以上であった, From January 1993 to June 1998, 319 cases were histopathologically diagnosed as prostatic cancer. In 7 of the 319 cases (2.2%) transurethral resection of the prostate (TUR-P) had been performed and a diagnosis of benign prostatic hyperplasia had been made with the resected specimens. The interval between TUR-P and the diagnosis of prostatic cancer ranged from 22 months to 15 years. All the cases showed an elevation of the prostate specific antigen (PSA) value (6.4-399 ng/ml, Tandem-R: RIA) at the time of cancer diagnosis. In 2 cases, PSA was measured in cancer screening. The clinical stage was stage B1 in 2 cases, stage B2 in 2 and D2 in 3. Only one case had been regularly followed-up after TUR-P, in which cancer was diagnosed by needle biopsy 22 months after TUR-P, because of the sustained high PSA values. Since most of such patients have an advanced stage of prostate cancer, it is of importance to have periodical follow-up examinations after TUR-P. The measurement of PSA appears the most reliable means in this way.

A case of squamous cell carcinoma of the urinary bladder associated with a bladder stone in a 43-year-old man is reported. Because a 1 cm x 1 cm sized mass was found in the right lateral side of the dome at the time of vesicolithotomy, partial cystectomy was performed. The weight of the stone was 285 g and the tumor was histologically diagnosed as squamous cell carcinoma, grade 2, pT2. Radical cystectomy with ileal conduit was sandwiched by a total of 6 cycles of chemotherapy with PVB. Twelve cases of squamous cell carcinoma of the urinary bladder associated with a bladder stone(s) from the Japanese literature are reviewed, and the relationship between bladder stone, leukoplakia and squamous cell carcinoma discussed.

BACKGROUND:Past attempts at detecting prostate cancer (PCa) cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities. To improve the sensitivities, we evaluate the feasibility and clinical utility of photodynamic diagnosis (PDD) of prostate cancer by using 5-aminolevulinic acid (5-ALA) to examine shed prostate cancer cells in voided urine samples. METHODS:One hundred thirty-eight patients with an abnormal digital rectal exam (DRE) and/or abnormal prostate-specific antigen (PSA) levels were recruited between April 2009 and December 2010. Voided urine specimens were collected before prostate biopsy. Urine specimens were treated with 5-ALA and imaged by fluorescence microscopy and reported as protoporphyrin IX (PPIX) positive (presence of cells demonstrating simultaneous PPIX fluorescence) or PPIX negative (lack of cells demonstrating fluorescence). RESULTS:Of the 138 patients, PCa was detected on needle biopsy in 81 patients (58.7%); of these 81 patients with PCa, 60 were PPIX-positive (sensitivity: 74.1%). Although 57 patients did not harbor PCa by conventional diagnostic procedures, 17 of these at-risk patients were found to be PPIX-positive (specificity: 70.2%). PPIX-PDD was more sensitive compared with DRE and transrectal ultrasound and more specific compared with PSA and PSA density. The incidence of PPIX-PDD positivity did not increase with increasing total PSA levels, tumor stage or Gleason score.CONCLUSIONS:To our knowledge, this is the first successful demonstration of PPIX in urine sediments treated with 5-ALA used to detect PCa in a noninvasive yet highly sensitive manner. However, further studies are warranted to determine the role of PPIX-PPD for PCa detection., 博士（医学）・甲第633号・平成27年3月16日, © 2014 Nakai et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

BACKGROUND: To evaluate the clinical usefulness of estimated glomerular filtration rate (eGFR) divided by functional renal volume (FRV) measured by three-dimensional image reconstruction (eGFR/FRV) for the prediction of functional outcomes after nephrectomy. METHODS: Eighty-three patients who underwent nephrectomy were enrolled. The FRV of each patient was measured before surgery. Preoperative medical information on proteinuria, blood pressure, blood glucose level, body mass index (BMI), hemoglobin level and serum cholesterol level were also obtained. We evaluated the relationships between eGFR/FRV and each of these parameters before surgery. We also assessed the potential relationship between eGFR/FRV and the 3-year postoperative eGFR. Stepwise multiple regression analyses were conducted to elucidate independent factors. RESULTS: The median FRV and eGFR were 310.15 cm3 and 79.0 ml/min/1.73 m² before surgery, respectively. The correlation between FRV and eGFR was statistically significant (r = 0.465, P < 0.001). The median eGFR/FRV was 0.24 ml/min/1.73 m²/cm³. Stepwise multiple regression analysis showed that the independent parameters (multiple correlation coefficient, r = 0.389, P = 0.031) associated with eGFR/FRV were proteinuria, BMI, age and hypertension. Proteinuria was statistically associated with eGFR/FRV, and the independent parameters (multiple correlation coefficient, r = 0.694, P < 0.001) associated with the 3-year postoperative eGFR were age, BMI and eGFR/FRV. The eGFR/FRV was statistically associated with the 3-year postoperative eGFR (r = 0.559, P < 0.001). CONCLUSION: The present results demonstrated that patients with proteinuria are expected to have a lower eGFR/FRV than those without proteinuria. The present study also supports the notion that eGFR/FRV is the primary determinant of the long-term functional outcome after nephrectomy. It should be taken into consideration that patients with a low eGFR/FRV may develop chronic kidney disease after nephrectomy., 博士（医学）・乙第1354号・平成27年3月16日, © 2014 Hosokawa et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

A 25-year old man, who had an inferiority of having a small penis and normal potency, underwent intracavernous implantation of hand-made silicone rods by a cosmetic surgeon in order to enlarge his penis. He had pyrexia and swelling of the penis 2 days after the implantation, and penile cavernitis developed. The penile symptoms improved by drainage and strict chemotherapy, and then the silicone rods were removed from his penis. Histopathological findings of the corpus cavernosum showed marked inflammatory and granulomatous changes. The patient lost his potency due to poor blood flow into the cavernous.

BACKGROUND: COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation. METHODS: LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1000 μM diclofenac. Next, a clonogenic assay was performed in which cells were subjected to irradiation (0 to 4 Gy) with or without diclofenac. COX-2 expression and other relevant molecules were measured by real-time PCR and immunohistochemistry after irradiation and diclofenac treatment. In addition, we assessed the tumor volumes of xenograft LNCaP-COX-2 cells treated with topical diclofenac with or without radiation therapy (RT). RESULTS: LNCaP-COX-2 and LNCaP-Neo cell lines experienced cytotoxic effects of diclofenac in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to RT than LNCaP-Neo cells. Furthermore, the addition of diclofenac sensitized LNCaP-COX-2 not but LNCaP-Neo cells to the cytocidal effects of radiation. In LNCaP-COX-2 cells, diclofenac enhanced radiation-induced apoptosis compared with RT alone. This phenomenon might be attributed to enhancement of RT-induced TRAIL expression as demonstrated by real-time PCR analysis. Lastly, tumor volumes of LNCaP-COX-2 cells xenograft treated with diclofenac or RT alone was >4-fold higher than in mice treated with combined diclofenac and radiation (p, 博士（医学）・甲第606号・平成25年11月27日, © 2013 Inoue et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.