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Background and Aims: Tumor growth and progression are affected by interactions between tumor cells and stromal cells within the tumor microenvironment. We previously showed that the expression of an integral membrane protein, called stomatin, was increased in cancer cells following their association with stromal cells. Additionally, stomatin impaired the Akt signaling pathway to suppress tumor growth. However, it remains unclear how stomatin expression is regulated. To explore this, we examined the cell surface molecules that can transduce the intercellular communication signals between cancer cells and stromal cells. Results: Among these molecules, EphA3 and EphA7 receptors and their ligand ephrin‐A5 were found to be expressed in prostate cancer cells, but not in prostate stromal cells. Cell‐to‐cell contact of prostate cancer cells through the EphA–ephrin‐A interaction suppressed stomatin expression, while knockdown of EphA3/7 or ephrin‐A5 increased stomatin expression. This increase contributed to an inhibition of prostate cancer cell proliferation. Intracellularly, the binding of ephrin‐A to EphA attenuated extracellular signaling‐regulated kinase (ERK) activation that promoted stomatin expression. Furthermore, ELK1 and ELK4, which are Ets family transcription factors phosphorylated by ERK, were involved in the induction of stomatin expression. We also found that higher Gleason score prostate cancer tissue samples had increased activation of EphA, while the stomatin expression and activated ERK and ELK levels were all low. In the mouse xenograft tumor samples generated by implantation of prostate cancer cells, EphA3 phosphorylation was attenuated and the ERK–ELK signaling and stomatin expression were enhanced in the area where stromal cells infiltrated the tumor. Conclusion: The EphA‐mediated signaling suppresses the ERK–ELK pathway, leading to the reduction of stomatin expression that affects prostate cancer malignancy. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) in humans is characterized by alterations in the TP53 gene. In mice, loss of p53 triggers OS development, for which c‐Myc (Myc) oncogenicity is indispensable. However, little is known about which genes are targeted by Myc to promote tumorigenesis. Here, we examined the role of γ‐glutamylcyclotransferase (Ggct) which is a component enzyme of the γ‐glutamyl cycle essential for glutathione homeostasis, in human and mouse OS development. We found that GGCT is a poor prognostic factor for human OS, and that deletion of Ggct suppresses p53‐deficient osteosarcomagenesis in mice. Myc upregulates Ggct directly by binding to the Ggct promoter, and deletion of a Myc binding site therein by genome editing attenuated the tumorigenic potential of p53‐deficient OS cells. Taken together, these results show a rationale that GGCT is widely upregulated in cancer cells and solidify its suitability as a target for anticancer drugs. [ABSTRACT FROM AUTHOR]

At present, the combination of immune checkpoint inhibitors (ICIs) or an ICI and a tyrosine kinase inhibitor (TKI) are the main treatment options as first-line therapy for metastatic renal cell cancer (mRCC). Among them, pembrolizumab plus lenvatinib was recently launched in Japanese clinical practice. In this review, the efficacies and safety profiles of pembrolizumab plus lenvatinib for mRCC between Japanese and global populations are compared. In addition, lenvatinib is currently available for the treatment of not only mRCC but also of endometrial, thyroid, thymic, and hepatocellular cancers. We briefly summarized the characteristics of pembrolizumab plus lenvatinib or lenvatinib monotherapy for these malignancies. Finally, the characteristics of pembrolizumab plus lenvatinib for mRCC in the Japanese population are briefly elucidated. In order to develop optimal personalized treatment for mRCC patients, it is necessary for physicians who treat mRCC patients to possess in-depth knowledge of not only the efficacy and safety profile of the respective therapies but also of the interpatient heterogeneities between Japanese and global populations. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have made an appearance in clinical practice, and the treatment outcome of metastatic renal cell cancer (mRCC) has dramatically improved as a result. Currently, most patients are treated with a combination of ICIs or a combination of ICI and tyrosine kinase inhibitors (TKIs). These new therapeutic tools need to be organized and summarized in order to realize and advance personalized therapy for mRCC. In this review, the characteristics of five regimens (nivolumab plus ipilimumab, pembrolizumab plus axitinib, avelumab plus axitinib, and nivolumab plus cabozantinib and pembrolizumab plus lenvatinib) are briefly elucidated and their efficacies and safety profiles are compared. For ICI-unfit patients, the current choices are examined. In addition, the potential second-line regimens after these combination therapies are introduced as sequential treatment. Finally, in the future direction section, ongoing clinical trials are also introduced. ICIs are rapidly being introduced for the treatment of mRCC. Currently, most patients are treated with a combination of ICIs or a combination of ICI and TKIs. In order to develop optimal personalized treatment for our patients, it is necessary for the physicians who treat mRCC patients to possess in-depth knowledge of these new therapeutic tools. [ABSTRACT FROM AUTHOR]

Fluorescence image‐guided surgery has improved intraoperative identification of anatomic structures including visualization of vascular anatomy. Herein, indocyanine green (ICG) fluorescence imaging was applied to identify of a recurrent small tumor of renal cell carcinoma (RCC) during laparoscopic surgery. The patient underwent left laparoscopic radical nephrectomy via the retroperitoneal approach for RCC (clear cell carcinoma, pT1bN0M0) at the age of 39 years. A solitary retroperitoneal mass (14 mm in diameter) was identified in a computed tomography scan 6 years after surgery. We performed laparoscopic resection with the application of the ICG angiography, because RCC is recognized as one of the most hypervascular cancers. The tumor was clearly visualized by fluorescence. Histopathological diagnosis of the resected tumor was recurrent RCC (low grade, G1). The patient remained free of disease at 2 years after surgery. The ICG fluorescence imaging would be a useful method for identification of metastatic small lesions of RCC during laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the efficacy of a single instillation of pirarubicin with a short retention time for preventing intravesical recurrence of low-risk non-muscle-invasive bladder cancer. Patients and Methods: We analyzed 165 patients with low-risk non-muscle-invasive bladder cancer who underwent transurethral surgery. Single instillation of pirarubicin with 15-min retention time immediate after surgery was performed in 47 (28%) patients. The other patients (118, 72%) were treated without instillation therapy. The primary endpoint was recurrence-free survival. Results: Median overall follow-up was 50 (range=6-134) months. Recurrence-free survival at 1 and 5 years was 91% and 72%, and 79% and 54% in the group treated with pirarubicin, and that treated with surgery alone, respectively (p=0.031). Cox’s hazard analysis revealed lack of instillation and larger tumor size (>10 mm) as significant factors for risk of recurrence. No adverse events regarding intravesical chemotherapy were observed. Conclusion: Pirarubicin instillation with 15-min retention time can prevent intravesical recurrence of low-risk bladder tumors. [ABSTRACT FROM AUTHOR]

BACKGROUND: To overcome the unfavorable issues associated with conventional anti-adhesive HA/CMC film, we developed an anti-adhesive thermally cross-linked gelatin film. OBJECTIVE: We tried to clarify the re-attachability of the film and the required properties concerning the film thickness, stiffness and anti-adhesion effect. METHODS: To determine the optimal thickness, 5 kinds of the thickness of gelatin film and the conventional film were analyzed by the tensile test, shearing test, buckling test and tissue injury test. Finally, using the optimal film thickness, we tried to clarify the anti-adhesion effect of the reattached film. RESULTS: The tensile and shearing test showed gelatin films ≥30 μm thick had greater tensile strength and a smaller number of film fractures, than the conventional film. The buckling and tissue injury test showed gelatin films ≥60 μm thick had higher buckling strength and worse injury scores than the conventional film. The anti-adhesive effect of re-attached gelatin film using optimal thickness (30–40 μm) found the anti-adhesion score was significantly better than that of the control. CONCLUSIONS: Provided it has an optimal thickness, gelatin film can be reattached with enough physical strength not to tear, safety stiffness not to induce tissue injury, and a sufficient anti-adhesion effect. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the perioperative outcomes of off‐clamp tumor excision using soft coagulation in laparoscopic and robotic partial nephrectomy. Methods: We retrospectively analyzed the data from 78 patients who underwent minimally invasive partial nephrectomy, using soft coagulation, at the Shiga University of Medical Science, between September 2013 and April 2017. Tumor excision and hemostasis without renal arterial clamping was performed using soft coagulation. Collecting system repair and renorrhaphy with arterial clamping were carried out only if the collecting system had been opened. Results: Forty‐three of the 78 patients underwent laparoscopic partial nephrectomy using soft coagulation and the other 35 patients underwent robotic partial nephrectomy using soft coagulation. The median estimated total blood loss was 73 (0‐1140) mL and no patient needed a blood transfusion. No cases featured postoperative hemorrhagic events. Six patients with urinary fistula needed prolonged ureteral stenting. The median percentage change of the estimated glomerular filtration rate was −7.2 at one to 3 months after surgery. Conclusion: The off‐clamp soft coagulation technique in laparoscopic partial nephrectomy and robotic partial nephrectomy is a safe and feasible approach to excise kidney tumors. This procedure may reduce the incidence of perioperative hemorrhagic complications. [ABSTRACT FROM AUTHOR]

An 11-year-old boy underwent every-5-mm Nd:YAG laser irradiation for endophytic VM of the glans penis, 12 mm in size. GLO:FRY/01nov21:iju14662-fig-0001.jpg PHOTO (COLOR): 1 Preoperative and postoperative appearance of VM of the glans penis. gl Because there were no relapses of VM after this irradiation therapy, additional treatments were unnecessary. Abbreviations & Acronyms Nd:YAG neodymium:yttrium-aluminum-garnet VM venous malformation Vascular anomalies of the male genitalia are rare, and there is no consensus on classification, cause, or treatment.1 Such anomalies include hemangiomas and vascular malformations. [Extracted from the article]

The present study evaluated the impact of nedaplatin-containing chemotherapy on renal function in 35 patients with urothelial carcinoma (UC) between 2001 and 2014 who were unfit for cisplatin treatment. As comparative controls, the present study also examined 35 patients with the same disease who underwent cisplatin-containing chemotherapy during the same period. The changes in the estimated glomerular filtration rate (eGFR) prior to and following the administration of nedaplatin during each cycle of chemotherapy was investigated. The present study also reported the overall response rates and adverse events in each group. A total of 31 cycles of the gemcitabine/nedaplatin regimen and 66 cycles of the methotrexate/epirubicin/nedaplatin regimen were administered. In the nedaplatin group, the mean eGFRs prior to and following chemotherapy were 45.4 and 47.8 ml/min/1.73 m2, respectively. The eGFR of the post-chemotherapy group was significantly increased (P<0.001). On the other hand, in the cisplatin group, the eGFR following chemotherapy was significantly lower than the rate prior to chemotherapy (P<0.001). The overall response rates were 30.4 and 66.7% in the nedaplatin and cisplatin groups, respectively. In the two groups, myelosuppression was the most common side effect, but the occurrence rates in both groups were similar, and these adverse events were manageable. With regard to nephrotoxicity, nedaplatin-containing chemotherapy for cisplatin-unfit patients with UC is a safe treatment modality. [ABSTRACT FROM AUTHOR]

Voiding cystourethrography is the most important fluoroscopic examination in pediatric urology for the investigation of lower urogenital tract diseases, such as vesicoureteral reflux or urethral stricture. However, this invasive procedure imposes a significant burden on children and their parents, and recently there has been a paradigm shift in the diagnosis and treatment of vesicoureteral reflux. In the 2011 revision, the American Academy of Pediatrics guidelines on urinary tract infection recommended abandoning routine voiding cystourethrography after the first febrile urinary tract infection. In 2014, the randomized intervention for children with vesicoureteral reflux study recommended discontinuation of routine continuous antibiotic prophylaxis for vesicoureteral reflux. The time is now ripe to radically reconsider indications for voiding cystourethrography and the procedure itself. [ABSTRACT FROM AUTHOR]

Patients with a history of non-muscle-invasive bladder cancer sometimes have recurrence of tumors after transurethral resection of bladder tumor treatment. To find factors related to the recurrence of non-muscle-invasive bladder cancer, we examined tissue specimens taken at transurethral resection of bladder tumor as an initial treatment. We revealed the association between prognosis of non-muscle-invasive bladder cancer and infiltration of Foxp3+ T cells that suppress anti-tumor immunity in 115 primary non-muscle-invasive bladder cancer patients retrospectively identified and followed for at least 3 months after primary transurethral resection. In immunohistological staining, we counted the number of cells positive for CD3 and positive for CD3 and Foxp3 together and calculated the percentage of Foxp3+ T cells among the CD3+ T cells. The recurrence-free survival rate was calculated by the Kaplan-Meier method, and a Cox regression analysis of recurrence factors was performed. The median (interquartile range) percentage of Foxp3+ T cells in all cases was 17.1% (11.9, 11.4–23.3%). Compared by risk stratification, it was 11.4% (10.4, 7.8–18.2%) in the low-risk group (n = 32), 16.8% (12.6, 11.6–24.2%) in the intermediate-risk group (n = 45), and 22.0% (9.7, 16.4–26.1%) in the high-risk group (n = 38). The Kaplan-Meier survival analysis indicated that the Foxp3+ T cell high group (≥ 17.1%) had a worse RFS rate than did the low group (< 17.1%) (P = 0.006). In multivariate analysis, the percentage of Foxp3+ T cells was an independent risk factor for intravesical recurrence (hazard ratio 2.25). Thus, peritumoral Foxp3+ T cell infiltration was correlated to risk stratification and recurrence-free survival. Therefore, the percentage of Foxp3+ T cells in tumor specimens may predict a risk for intravesical recurrence. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Renal cell carcinoma (RCC) is the urological malignancy with the highest mortality rate and is increasing in incidence. The prognostic and predictive biomarkers are highly desired. This study aims to investigate the significance of superoxide dismutase 2 (SOD2) as a clinical biomarker in patients with renal cell carcinomas. METHODS: A cohort of 97 patients with RCC was analyzed retrospectively using various clinical parameters and SOD2 expression by immunohistochemistry. RESULTS: Cases with stronger SOD2 positivity of the tumor in comparison to the adjacent normal renal tubule by immunohistochemistry were categorized as high SOD2 and were associated with worse overall survivals ( p = 0.005). In particular, in cases with metastatic RCC, high SOD2 expression in the tumors was significantly associated with a worse overall survival ( p = 0.001), and the maximum critical risk. Treatment with current molecular targeting therapies did not improve the prognoses of cases with metastatic or recurrent RCC. CONCLUSIONS: High SOD2 expression can be predictive of a poor clinical outcome and be clinically useful in the follow-up of metastatic RCC. Therapeutics for metastatic RCCs require further improvement, such as supplementary administration of agents targeting mitochondrial SOD2. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the current status of urological laparoendoscopic single‐site and reduced port surgery in Japan. Methods: Of the 152 institutions to which councilors of the Japanese Society of Endourology belong, 42 (28%) have carried out laparoendoscopic single‐site and reduced port surgery. A total of 32 of these institutions agreed to participate in this survey. Patients who had undergone surgery between January 2008 and March 2014 were included in the present study. Results: Overall, 1145 cases of laparoendoscopic single‐site and reduced port surgery were recorded during the study period. The most frequent procedures were adrenalectomy and radical nephrectomy. Laparoendoscopic single‐site and reduced port surgery represented 12% (872/7311) of all laparoscopic procedures carried out at participating institutions. The number of patients who underwent pyeloplasty, donor nephrectomy and simple nephrectomy tended to increase, whereas those who underwent adrenalectomy, radical nephrectomy and nephroureterectomy peaked in 2012, and then tended to decrease in 2013. The rates of conversion, perioperative and postoperative complications, were 2.7%, 2.2% and 4.5%, respectively. Conclusions: The number of laparoendoscopic single‐site and reduced port urological surgeries in Japan has increased for benign indications, such as pyeloplasty, donor nephrectomy and simple nephrectomy. In contrast, procedures such as adrenalectomy and radical nephrectomy are trending down after reaching a peak in 2012. Overall, laparoendoscopic single‐site and reduced port urological surgery in Japan is being safely carried out when compared with other reported series of laparoendoscopic single‐site surgery and conventional laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of a new laparoscopic varicocelectomy technique using indocyanine green (ICG) angiography.Methods: Laparoendoscopic single-site (LESS) varicocelectomy using ICG angiography was performed in a single institution on 11 patients with a grade 2 or 3 varicocele. Adult men (N = 9, 82%) who were apparently infertile and had a varicocele, as well as prepubertal boys (N = 2, 18%) with testicular growth retardation, underwent a LESS varicocelectomy using ICG angiography. After the separation of testicular veins, arteries, and lymphatics, ICG was injected intravenously, and arterial and venous blood flows were observed by ICG fluorescence. Spermatic veins were cauterized by bipolar forceps and cut. The spermatic artery and lymphatics were preserved.Results: The mean time to the arterial phase (AP) from the ICG injection was 34.9 seconds and the mean time to the venous phase was 58.3 seconds. The mean interval from the arterial phase to the venous phase was 23.3 seconds, and in all cases, this time interval facilitated the identification of arteries and veins. The rates of residual varicocele 3 and 6 months after surgery were 9.1% and 0%, respectively. Serious postoperative complications were not observed nor were adverse events induced by ICG.Conclusion: ICG angiography appears to be safe and appears to facilitate the detection of artery and veins during LESS varicocelectomy. Continuing investigations of efficacy are required of this new and promising procedure in a larger number of patients. [ABSTRACT FROM AUTHOR]

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Pembrolizumab has been widely used to treat advanced urothelial carcinoma that has progressed after first-line platinum-based chemotherapy. Because its clinical benefits are limited, biomarkers that can predict a good response to pembrolizumab are required. The prognostic nutritional index (PNI), calculated using the serum albumin level and peripheral lymphocyte count, has been evaluated as a predictive biomarker in cancer immunotherapy. The present study investigated the application of PNI as a predictive biomarker for pembrolizumab response in patients with advanced urothelial cancer. A retrospective study was conducted on 34 patients treated with pembrolizumab at Shiga University of Medical Science Hospital between January 2018 and July 2022. The posttreatment PNI (post-PNI) was calculated within 2 months of starting pembrolizumab. The present study investigated the association between post-PNI and objective response, overall survival (OS) and progression-free survival (PFS). The patient cohort was stratified into two categories, high and low post-PNI groups, with a cutoff value of post-PNI at 40. The higher post-PNI group demonstrated a better disease control rate than the lower post-PNI group (complete response + partial response + stable disease, 75 vs. 21%, P=0.004). Regarding median OS, the higher post-PNI group exhibited a significantly longer survival time than the lower post-PNI group (23.1 vs. 2.9 months, P<0.001). Similarly, the higher post-PNI group exhibited a significantly longer PFS than the lower post-PNI group (10.2 vs.1.9 months, P<0.001). Multivariate analysis showed that a higher post-PNI value was an independent predictor for OS (hazard ratio, 0.04; 95% confidence interval, 0.01–0.14; P<0.001) and PFS (hazard ratio, 0.12; 95% confidence interval, 0.04–0.35; P<0.001). The present study indicated that the post-PNI was a predictor of favorable clinical outcomes in patients treated with pembrolizumab for advanced urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common genitourinary cancer in men. Population-based serum prostate-specific antigen (PSA) testing is used to screen men for the early detection of asymptomatic prostate cancer. The present study compared the features of patients with prostate cancer in Kusatsu City, the only municipality in Shiga Prefecture of Japan to implement organized PSA screening, with those in other municipalities. The target population for organized PSA screening by mail invitation was men ≥50 years. Patients were pathologically diagnosed via prostate biopsy because of elevated serum PSA. This multicenter observational study was subsequently conducted in 14 hospitals. The following information was extracted from patient records: age, reason for PSA testing, initial PSA level, Gleason score, clinical stage, and place of residence. Risk classification was defined as low, intermediate, high, and advanced. Each patient was stratified according to their city/town. A total of 984 patients diagnosed with prostate cancer in Shiga in 2012 and 2017 were analyzed, of which 955 (97%) were opportunistically tested, with the remaining 29 (3%) assessed by organized screening. In Kusatsu, 93 patients were diagnosed, of whom 26 (28%) were detected by organized screening. By contrast, only three of 891 patients (0.3%) were detected by organized screening in other municipalities. Of patients in Kusatsu, cases identified by opportunistic testing had a higher initial PSA value (P=0.010) than those identified by organized screening. However, patients detected through opportunistic testing in Kusatsu City were younger (P=0.034), had a lower PSA value (P=0.001), and improved risk classification (P<0.001) than those in other municipalities. It was concluded that more patients were diagnosed with early-stage cancer by organized PSA screening. Furthermore, population-based PSA screening in Kusatsu City may have indirectly affected early detection, even by opportunistic testing. [ABSTRACT FROM AUTHOR]

The present study aimed to use real-world Japanese data to compare the treatment outcome of conventional hormonal therapy to that of using androgen receptor axis-targeted (ARAT) agents for patients with metastatic castration-resistant prostate cancer. The overall survival between the conventional hormonal therapy group and the ARAT agent therapy group was compared using a group of 75 Japanese patients who were treated for metastatic castration-resistant prostate cancer. A subgroup analysis was carried out and the risk factors that affected overall survival (OS) were determined. The median OS from the time of prostate-specific antigen recurrence was 73.1 months in the ARAT group and 45.2 months in the conventional treatment group (P=0.414). Although OS tended to be slightly longer in the ARAT group, the difference between the groups was not significant. Subgroup analysis suggested that the therapeutic outcome of using ARAT agents tended to be less beneficial in patients who were older, and in those with a higher tumor volume or low Gleason grade. In conclusion, use of ARAT agents did not impart a significant survival benefit to patients with metastatic castration-resistant prostate cancer when compared with survival rates in response to conventional therapy. However, there was some clinical benefit when ARAT agents were used after patients developed castration-resistant prostate cancer. These findings suggest that up-front therapy using ARAT agents at the time of the initial hormone therapy can impart clinical benefit in Japanese patients with metastatic prostate cancer. [ABSTRACT FROM AUTHOR]