Radical prostatectomy using the Hinotori robot-assisted surgical system: Docking-free design may contribute to reduction in postoperative pain.

BACKGROUND: The docking-free design of the Japanese Hinotori surgical robotic system allows the robotic arm to avoid trocar grasping, thereby minimising excessive abdominal wall stress. The aim of this study was to evaluate the safety and efficacy of robotic-assisted radical prostatectomy (RARP) using the Hinotori system and to explore the potential contribution of its docking-free design to postoperative pain reduction. METHODS: This study reviewed the clinical records of 94 patients who underwent RARP: 48 patients in the Hinotori group and 46 in the da Vinci Xi group. RESULTS: Hinotori group had significantly longer operative and console times (p = 0.030 and p = 0.029, respectively). Perioperative complications and oncologic outcomes did not differ between the two groups. On postoperative day 4, the rate of decline from the maximum visual analogue scale score was marginally significant in the Hinotori group (p = 0.062). CONCLUSIONS: The docking-free design may contribute to reducing postoperative pain.

Efficacy of educational stepwise robot-assisted radical prostatectomy procedure for urology residents.

OBJECTIVE: To evaluate the effectiveness of an educational stepwise robot-assisted radical prostatectomy (RARP) procedure for urology residents. METHODS: We performed a detailed evaluation of 42 RARP procedures performed by a single urology resident from July 2019 to February 2022. The RARP procedures were divided into the following nine steps: (1) bladder dissection, (2) endopelvic fascia dissection, (3) bladder neck dissection, (4) seminal vesicle dissection, (5) Denonvilliers' fascia dissection, (6) dorsal vascular complex ligation, (7) dissection of the prostatic apex, (8) posterior anastomosis, and (9) urethro-vesical anastomosis. The procedures were further subcategorized as anatomical understanding, spatial recognition, and technical skills for evaluation of resident training. The surgeries were divided into first and second halves, and patient characteristics and operative outcomes were statistically analyzed. The operative time of each of the nine steps and the reasons for proctor intervention were compared. RESULTS: Among 42 patients, there were no significant differences in operative outcomes between the two groups. The median operative time was 169 min (164 vs. 179 min, p = .12), and the median console time was 128 min (127 vs. 130 min, p = .74). Although there were no significant differences in the time of the nine steps, the resident significantly overcame (7) dissection of the prostatic apex and (8) posterior anastomosis based on the evaluation of the proctored reasons for intervention. CONCLUSIONS: Urology residents can safely perform and efficiently learn RARP with this stepwise educational system. This educational stepwise RARP procedure can effectively help residents to develop their skills.

Robot-assisted intracorporeal ileal conduit urinary diversion: A two-center comparative study of Bricker versus Wallace ureteroileal anastomosis.

INTRODUCTION: This study was performed to evaluate the differences in the perioperative results, renal function, and incidence of hydronephrosis over time between the use of Bricker anastomosis and Wallace anastomosis for robot-assisted intracorporeal ileal conduit urinary diversion (RICIC). METHODS: Fifty-five patients who underwent RICIC at two institutions were evaluated (Bricker, n = 23; Wallace, n = 32). We investigated changes in estimated glomerular filtration rate and hydronephrosis before surgery and at 3, 6, and 12 months after surgery. RESULTS: The patients in the Bricker group were significantly older than those in the Wallace group. The urinary diversion time was significantly longer in the Bricker group. No significant difference in postoperative renal function was observed. Additionally, no significant difference was observed in the incidence of postoperative hydronephrosis. However, the incidence of right hydronephrosis tended to be high overall, especially in the Wallace group. No patients in either group required repair surgery or ureteral stent placement. CONCLUSIONS: In patients undergoing RICIC, there was no difference in postoperative renal function or the incidence of hydronephrosis between Wallace and Bricker anastomosis. Symptomatic hydronephrosis was not observed in either group. The present study showed that each method was equally effective and safe.

A novel treatment strategy for bladder hypoplasia: A case of megaureter in a functional solitary kidney.

Introduction: We report a case of megaureter in a functional solitary kidney in which surgery was performed after bladder capacity was increased by home bladder cycling. Case presentation: A 6-day-old girl with a left megaureter, a right multicystic dysplastic kidney, and bladder hypoplasia underwent percutaneous left nephrostomy for obstructive renal failure. At 8 months, home bladder cycling was initiated to increase bladder capacity before the planned ureterocystoneostomy. Surgery was performed after bladder capacity increased. The left ureter was compressed by the left umbilical ligament, so ureteral end-to-end anastomosis was performed at 1 year and 4 months. At 2 years and 8 months, cystometry showed age-appropriate bladder capacity and improved bladder compliance. Conclusion: To the best of our knowledge, this is the first report of bladder hypoplasia treated by home bladder cycling.

Impact of lymph node dissection on surgical and oncological outcomes in patients undergoing robot-assisted radical cystectomy for bladder cancer: a multicenter retrospective study.

This study was performed to clarify the therapeutic and diagnostic roles of lymph node dissection (LND) by examining the impact of LND and lymph node yield (LNY) on oncological outcomes in patients undergoing robot-assisted radical cystectomy (RARC). Between 2014 and 2021, 216 patients underwent LND during RARC at Tokushima University Hospital and affiliated hospitals. Among the 216 patients, we compared 115 patients with an LNY of ≥ 20 and 101 with an LNY of < 20 to investigate the impact of LNY on surgical and oncological outcomes. Furthermore, we investigated the impact of LNY and the extent of LND on oncological outcomes by dividing the extent of LND into two groups (standard and extended). The 3-year rates of overall survival (OS) (p = 0.256), cancer-specific survival (CSS) (p = 0.791), and recurrence-free survival (RFS) (p = 0.953) did not differ between the two groups divided by the LNY. A higher LNY was associated with a significantly higher lymph node positivity rate (p = 0.020). The incidence of LND-related major complications was not significantly different between the two groups (p = 0.910). The 3-year survival rates did not differ between the two groups divided by the extent of LND: OS (p = 0.366), CSS (p = 0.814), and RFS (p = 0.689). The LNY and extent of LND were not associated with oncological outcomes in patients undergoing LND during RARC, whereas a higher LNY was associated with lymph node positivity. In the era of adjuvant therapy with immune checkpoint inhibitors, LND during RARC has an important diagnostic role in the detection of pathological node positivity.

The importance of laparoscopic surgery for young urologists remains unwavering even in the era of robot-assisted surgery.

Robot-assisted surgery (RAS) cannot be achieved without the performance of laparoscopic surgical techniques by a patient-side surgeon (PSS). In many medical institutions in Japan, young urologists often take on the role of a PSS. Participating in RAS as a PSS provides a good opportunity to acquire not only the knowledge necessary for surgery, but also skills in laparoscopic surgical techniques. Learning laparoscopic surgery as a PSS may contribute to improving the quality of RAS. Furthermore, it will lead to skill improvement as an operator in laparoscopic surgery. However, notably, opportunities for young urologists to perform laparoscopic surgery are decreasing in the current era of RAS. Under these circumstances, we believe that cadaver surgical training will become increasingly important in the future. We believe that performance of cadaver surgical training will contribute to increased motivation, enhance the understanding of surgical procedures, and facilitate the acquisition of surgical techniques.

Real-world prostate-specific antigen response and progression to castration-resistant prostate cancer among men with metastatic castration-sensitive prostate cancer treated with apalutamide: a multi-institutional study in the Chu-shikoku Japan Urological Consortium.

BACKGROUND: Japanese men receiving apalutamide often experience skin-adverse events (AEs), possibly requiring treatment interruption or dose reduction. However, concerns have arisen regarding the impact of these adjustments on the efficacy of apalutamide. Our study evaluated the efficacy, safety, and persistence of apalutamide in men with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: We retrospectively reviewed the medical records of 108 men with mCSPC from 14 Japanese institutions. The primary outcomes were the efficacy of apalutamide: prostate-specific antigen (PSA) response (50%, 90% and < 0.2 decline) and progression to castration-resistant prostate cancer (CRPC). The secondary outcomes were the skin-AE and compliance of apalutamide. RESULTS: PSA50%, PSA90% and PSA < 0.2 declines were observed in 89.8, 84.3 and 65.7%, and the median time to CRPC progression was not reached. PSA < 0.2 decline and an initial full dose of apalutamide were significantly associated with a longer time to CRPC. The most common AE was skin-AE (50.9%), and there was no association between the occurrence of skin-AE and the time to CRPC (P = 0.72). The median apalutamide persistence was 29 months, which was longer in the initial full dose recipients than in the reduced dose recipients. The dosage is reduced in about 60% of patients within the first year of treatment in the initial full dose recipients. CONCLUSIONS: Our findings indicate the effectiveness of apalutamide in Japanese men with mCSPC, despite a substantial portion requiring dose reduction within a year among the initial full dose recipients.

A case of laparoscopically assisted transperineal repair of anterior enterocele dehiscence with small bowel evisceration after robot-assisted radical cystectomy.

We herein report a case of successful laparoscopically assisted transperineal repair of anterior enterocele dehiscence with small bowel evisceration after robot-assisted radical cystectomy. A 75-year-old woman underwent robot-assisted radical cystectomy with anterior vaginectomy and urethrectomy for bladder cancer (pTisN0M0). Vaginal reconstruction was performed using the posterior vaginal wall. Four months after surgery, she presented with small bowel evisceration due to anterior enterocele dehiscence. She underwent laparoscopically assisted transperineal repair. The anterior enterocele dehiscence did not occur at the vaginal closure site but instead between the vaginal wall and posterior pubic bone. No recurrence had developed at 2 months postoperatively.

Impact of early urinary catheter removal on successful voiding and physical function in stroke patients.

OBJECTIVE: The aim of the present study was to identify factors related to the success of trial without catheter (TWOC) in patients with stroke and to examine the effect of the timing of urinary catheter removal on the course of stroke. METHODS: Patients who were admitted to the Stroke Care Unit of our institution between March 2018 and October 2021 were included. To identify factors related to success of TWOC, a multivariate analysis was performed on the patient's condition at admission and catheter indwelling time. The patients were divided into two groups by the timing of catheter removal, and we assessed the relationship between the timing of catheter removal successful TWOC and recovery of physical function. RESULTS: A total of 118 patients were included. The presence of comorbidities and scores of severity and function at admission were not predictors of successful voiding. The time to achieve voiding sussess was significantly shorter in the early catheter removal group than in the later group (p<0.005). Interestingly, the early group also showed better improvements in physical function. CONCLUSION: Early removal of catheters may lead to early recovery of bladder function, improvement of physical function, and lower risk of complications in patients with stroke. J. Med. Invest. 70 : 436-442, August, 2023.

The suppression of the differentiation of adipocytes with Mallotus furetianus is regulated through the posttranslational modifications of C/EBPß.

Obesity is a major risk factor for various chronic diseases, especially lifestyle-related diseases. Therefore, finding a protective substance against obesity and elucidating its molecular mechanism is one of the most important problems for improving human health. In this study, we investigated the antiobesity effect of Mallotus furetianus extract (MFE). The aim of the study was to examine the in vivo and in vitro effects of MFE on lipid synthesis. We examined the effect using an in vivo experimental system with obesity model mice and an in vitro experimental system with 3T3-L1 preadipocytes. We found that the treatment of MFE significantly suppressed the increase in body weight and adipose tissue weight and morphological changes in the liver and adipose tissue of the obesity model mice. In the in vitro experimental system, we revealed that MFE treatment suppressed the expression of transcription factors such as C/EBPα, C/EBPß, and PPARγ, which are involved in the early differentiation of 3T3-L1 preadipocytes. As a result, the ability to synthesize triacylglycerol was suppressed. An interesting finding in this study was the clarification that MFE decreases the expression of C/EBPß through post-translation modifications (PTMs), followed by the transcriptional suppression of PPAR𝛾 and C/EBP𝛼.

Effect of Positive Biopsy Core Rate on Low-dose-rate Brachytherapy Outcomes in Intermediate-risk Prostate Cancer.

BACKGROUND/AIM: Intermediate-risk prostate cancer (PCa) is a highly heterogeneous disease. Although low-dose-rate brachytherapy (LDR-BT) is mainly used for low- to intermediate-risk PCa, limited reports have evaluated the detailed differences in outcomes, including differences between patients with ISUP grade group (GG) 2 and GG3 intermediate-risk PCa. This study aimed to investigate the differences in outcomes between intermediate-risk Japanese patients with GG2 and GG3 PCa who underwent LDR-BT. PATIENTS AND METHODS: This single-center retrospective study included 342 consecutive patients with intermediate-risk PCa; 232 patients with GG2 and 110 with GG3 were treated with LDR-BT at Tokushima University Hospital between July 2004 and December 2019. RESULTS: No significant difference in 5-year biochemical progression-free survival and cancer-specific survival was observed between patients with GG2 and those with GG3 (p=0.649 and p=0.633, respectively). Multivariate analysis showed that radiation doses up to 90% of the prostate volume (D90) and the percentage of positive cores were predictors of recurrence in all patients with intermediate-risk PCa. Group analyses showed that D90 was a predictor for recurrence in patients with GG2. In contrast, a high percentage of positive cores was a significant risk factor for recurrence in patients with GG3. CONCLUSION: Positive core ratios observed on prostate biopsy correlated with higher recurrence rates after LDR-BT. This indicates that the proportion of positive cores in the biopsy may be an important factor in predicting the likelihood of recurrence, especially for patients with GG3 PCa.

Lymph node dissection during radical cystectomy for bladder cancer: A two-center comparative study of robotic versus open surgery.

INTRODUCTION: This study was performed to evaluate the safety and efficacy of lymph node dissection (LND) during robot-assisted radical cystectomy (RARC) compared with open radical cystectomy (ORC). METHODS: From October 2003 to December 2021, 122 patients underwent LND during RARC and 103 patients underwent LND during ORC at Tokushima University Hospital and Tokushima Prefectural Central Hospital. We investigated the safety and efficacy of LND during RARC by comparing the surgical and oncological outcomes between the two groups. RESULTS: The patients were significantly older in the RARC than the ORC group. The operative time was significantly shorter and the estimated blood loss was significantly lower in the RARC than the ORC group. Although the lymph node yield was significantly higher in the RARC than the ORC group, there was no significant difference in lymph node positivity between the groups. There was no significant difference in the incidence of local recurrence or distant metastasis between the two groups. The 5-year survival rates (overall survival, cancer-specific survival, and recurrence-free survival) were not different between the RARC and ORC groups. CONCLUSION: This study suggests that the surgical and oncological safety and efficacy of LND during RARC are greater than those of LND during ORC. We believe that LND during RARC is a higher-quality procedure than LND during ORC.

Kaempferia galanga L. extract and its main component, ethyl p-methoxycinnamate, inhibit the proliferation of Ehrlich ascites tumor cells by suppressing TFAM expression.

Kaempferia galanga L. shows anti-cancer effects; however, the underling mechanism remains unclear. In this study, we explored the underlying mechanism of the anti-cancer effects of Kaempferia galanga L. Kaempferia galanga L. rhizome extracts (KGEs) suppressed Ehrlich ascites tumor cell (EATC) proliferation by inhibiting S-phase progression. The main component of KGE is ethyl p-methoxycinnamate (EMC), which exhibits the same anti-proliferative effect as KGE. Furthermore, EMC induced the downregulation of cyclin D1 and upregulation of p21. EMC also decreased the expression of mitochondrial transcription factor A (TFAM) but did not significantly change mitochondrial DNA copy number and membrane potential. Phosphorylation at Ser62 of c-Myc, a transcription factor of TFAM, was decreased by EMC treatment, which might be due to the suppression of H-ras expression. These results indicate that EMC is the active compound responsible for the anti-cancer effect of KGE and suppresses EATC proliferation by regulating the protein expression of cyclin D1 and p21; TFAM may also regulate the expression of these genes. In addition, we investigated the anticancer effects of KGE and EMC in vivo using EATC bearing mice. The volume of ascites fluid was significantly increased by intraperitoneal administration of EATC. However, the increase in the volume of ascites fluid was suppressed by oral administration of EMC and KGE. This study provides novel insights into the association between the anti-cancer effects of natural compounds and TFAM, indicating that TFAM might be a potential therapeutic target.

Insulin receptor expression to predict resistance to axitinib and elucidation of the underlying molecular mechanism in metastatic renal cell carcinoma.

BACKGROUND: The study aimed to examine the significance of insulin receptor (INSR) expression in predicting resistance to axitinib in clear cell renal cell carcinoma (ccRCC). METHODS: Clinicopathological data were collected from 36 consecutive patients with metastatic RCC who received axitinib. Thirty-three primary tumours were obtained for immunohistochemistry. Patient-derived xenograft (PDX) models were created by transplanting primary tumours into immunodeficient mice, establishing axitinib-resistant PDX models. RCC cell lines were co-cultured with human renal glomerular endothelial cells (HGECs) treated with siRNA of INSR (HGEC-siINSR). Gene expression alteration was analysed using microarray. RESULTS: The patients with low INSR expression who received axitinib had a poorer outcome. Multivariate analysis showed that INSR expression was the independent predictor of progression-free survival. INSR expression decreased in axitinib-resistant PDX tumours. RCC cell lines showed upregulated interferon responses and highly increased interferon-ß levels by co-culturing with HGEC-siINSR. HGECs showed decreased INSR and increased interferon-ß after axitinib administration. RCC cell lines co-cultured with HGEC-siINSR showed high programmed death-ligand 1 (PD-L1) expression, which increased after interferon-ß administration. CONCLUSIONS: Decreased INSR in RCC could be a biomarker to predict axitinib resistance. Regarding the resistant mechanism, vascular endothelial cells with decreased INSR in RCC may secrete interferon-ß and induce PD-L1.

The impact of nutritional status and changes of body composition on the prognosis of metastatic renal cell carcinoma patients.

PURPOSE: This study aimed to analyze the impact of patients' nutritional status and changes in body composition on the prognosis of metastatic renal cell carcinoma (mRCC) patients who received systemic therapy with tyrosine kinase inhibitors (TKIs). METHODS: A total of 57 mRCC patients who received systemic therapy with TKIs as first-line therapy at our facility between November 2004 and October 2018 were included. The Prognostic Nutritional Index (PNI) was used to evaluate their nutritional status. The volumes of skeletal muscle mass and fat tissue were calculated using the SYNAPSE VINCENT system. The effects of nutritional status and body composition of mRCC patients on progression-free survival (PFS) and overall survival (OS) were analyzed using Cox regression methods. RESULTS: Low PNI at the start of systemic therapy was a significant prognostic predictor for OS (HR 3.807 [95% CI 1.205-12.027], P=0.046), and it was related to loss of muscle mass three months after systemic therapy. Although the loss of muscle mass at the start of systemic therapy was not associated with OS, loss of muscle mass during treatment predicted worse OS. CONCLUSIONS: Nutritional status of mRCC patients may predict changes in body composition and be associated with their prognosis. J. Med. Invest. 70 : 80-87, February, 2023.

Efficacy of fresh-frozen cadaveric surgical training for arteriovenous fistula in vascular access.

BACKGROUND: Creation of an arteriovenous fistula (AVF) as vascular access is a basic operation that should be learned by all surgeons involved in renal failure treatment. AVF creation is often challenging for inexperienced young surgeons because it requires comprehensive surgical techniques. For such young surgeons, we introduced cadaveric surgical training (CST) for AVF creation using fresh-frozen cadavers (FFCs). This study was performed to identify the differences in AVF surgical techniques between FFCs and living bodies and to examine the impact of CST on young surgeons. METHODS: Twelve CST sessions were performed for AVF creation at the Clinical Anatomy Education and Research Center of Tokushima University Hospital from March 2021 to June 2022. Seven young surgeons (1st- and 2nd-year) performed the operation, and two surgeons (10th- and 11th-year) supervised it. We conducted an anonymous questionnaire survey using a 5-point Likert scale to examine the impact of CST on young surgeons. RESULTS: Twelve CST sessions were performed on nine FFCs. All training sessions allowed completion of AVF creation with a median operative time of 78.5 min. Although veins and arteries were more difficult to identify than in a living body, other surgical operations could be performed in the same way as in a living body. All the respondents stated that it was good for them to experience CST. In addition, 86% of surgeons responded that CST improved their surgical techniques, and 71% of surgeons responded that they were less anxious about AVF creation. CONCLUSIONS: CST for AVF creation is useful for surgical education because it enables learning of surgical techniques that are almost equivalent to those in living bodies. In addition, this study suggested that CST not only contributes to the improvement of surgical skills of young surgeons but also promotes the reduction of anxiety and stress about AVF creation.

Glyoxylic Acid, an α-Keto Acid Metabolite Derived from Glycine, Promotes Myogenesis in C2C12 Cells.

α-Keto acids may help prevent malnutrition in patients with chronic kidney disease (CKD), who consume protein-restricted diets, because they serve as amino acid sources without producing nitrogenous waste compounds. However, the physiological roles of α-keto acids, especially those derived from non-essential amino acids, remain unclear. In this study, we examined the effect of glyoxylic acid (GA), an α-keto acid metabolite derived from glycine, on myogenesis in C2C12 cells. Differentiation and mitochondrial biogenesis were used as myogenesis indicators. Treatment with GA for 6 d resulted in an increase in the expression of differentiation markers (myosin heavy chain II and myogenic regulatory factors), mitochondrial biogenesis, and intracellular amounts of amino acids (glycine, serine, and alanine) and their metabolites (citric acid and succinic acid). In addition, GA treatment suppressed the 2.5-µM dexamethasone (Dex)-induced increase in mRNA levels of ubiquitin ligases (Trim63 and Fbxo32), muscle atrophy markers. These results indicate that GA promotes myogenesis, suppresses Dex-induced muscle atrophy, and is metabolized to amino acids in muscle cells. Although further in vivo experiments are needed, GA may be a beneficial nutrient for ameliorating the loss of muscle mass, strength, and function in patients with CKD on a strict dietary protein restriction.

Prostate-specific Antigen Levels Following Brachytherapy Impact Late Biochemical Recurrence in Japanese Patients With Localized Prostate Cancer.

BACKGROUND/AIM: Evaluation of long-term outcomes is essential for the successful treatment of localized prostate cancer; however, the risk of late recurrence following brachytherapy is still not clear. This study aimed to evaluate the long-term outcomes of low-dose-rate brachytherapy (LDR-BT) for localized prostate cancer in Japanese patients and identify factors associated with late recurrence after treatment. PATIENTS AND METHODS: This single-center, cohort study included patients who underwent LDR-BT at the Tokushima University Hospital in Japan between July 2004 and January 2015; 418 patients, who were followed-up at least 7 years after LDR-BT, were included in the study. Biochemical progression free survival (bPFS) was defined according to the Phoenix definition (nadir PSA+2 ng/ml) and bPFS and cancer specific survival (CSS) were calculated using Kaplan-Meier survival curves. Univariate and multivariate analyses were performed using Cox proportional hazard regression models. RESULTS: Approximately half of the patients with PSA >0.5 ng/ml at 5 years after LDR-BT had a recurrence within the next 2 years. However, only 1.4% of the patients with a PSA ≤0.2 ng/ml at 5 years post-treatment showed tumor recurrence, including those at high risk of treatment failure according to the D'Amico classification. In multivariate analysis, PSA level at 5 years post-treatment was the only predictor of late recurrence after 7 years of treatment. CONCLUSION: PSA levels at 5 years post-treatment were associated with long-term recurrence of localized prostate cancer, which can help alleviate patient anxiety concerning prostate cancer recurrence if PSA levels remain low at 5 years after LDR-BT.