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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．

The next treatment strategy after drug holidays following docetaxel (DTX) therapy for patients with castration-resistant prostate cancer (CRPC) is unclear. This study investigated the relationship between the duration of drug holidays and prognosis after DTX therapy. This study retrospectively assessed 26 patients treated with DTX in our hospital. Overall survival duration was significantly longer in the long-term withdrawal group (duration of drug holidays ≥6 months) than in the short-term withdrawal group (duration of drug holidays ＜6 months) (P＝0.015). Similarly, progression-free survival duration was significantly longer in the long-term withdrawal group than in the short-term withdrawal group (P＝0.008). The short-term withdrawal group had a significantly lower body mass index (P＝0.009) and higher prostate-specific antigen (PSA) (P＝0.017) at the initiation of DTX therapy, higher PSA nadir during DTX therapy (P＝0.009), and higher PSA at the end of DTX therapy (P＝0.022), compared to the long-term withdrawal group. This study suggests that the optimal opportunity to introduce DXT therapy is when the patients with CRPC are physically able to tolerate chemotherapy and their tumor volume remains a lower burden. This may provide a clinical benefit, longer drug holidays, and a better prognosis.

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.

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.

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

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/).

Aims: To examine the circadian expression changes in bladder clock genes in Dahl salt-sensitive rats following high salt intake. Main methods: Eighteen rats were divided into three groups: the high-salt diet group (HS group), the normal-salt diet group (NS group), and the salt-load interruption group (from a 4 % salt diet to a normal diet; salt-load interruption group [SI group]). Each rat was placed in an individual metabolic cage for 24 h twice weekly. Water intake, urine production, voiding frequency, and voided volume per micturition were recorded. Furthermore, 108 control rats were prepared. Bladders were harvested every 4 h at six time points. Furthermore, the mRNA expression of clock genes and mechanosensors was analyzed. Key findings: In the HS group, the bladder clock genes showed lower mRNA levels than in the NS group. The amplitude of circadian expression changes in bladder clock genes in the HS group was lower than that in the NS group. However, after changing from a 4 % salt diet to a normal diet, the waveforms of the clock gene expression in the SI group were closer to those of the NS group. The 24-h water intake and urinary volume of the SI group decreased to levels comparable to those of the NS group. Significance: Reduced salt intake partially restored the circadian rhythms of bladder clock genes., 博士（医学）・甲第857号・令和4年12月22日, Copyright © 2022 Elsevier Inc. All rights reserved.

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.