Robot-assisted partial nephrectomy in younger versus older adults with renal cell carcinoma: a propensity score-matched analysis.

PURPOSE: Our study aimed to compare the surgical outcomes of robot-assisted partial nephrectomy (RAPN) between younger and older patients after adjusting for their background differences. We particularly assessed RAPN outcomes and safety in older patients. METHODS: We retrospectively evaluated 559 patients clinically diagnosed with T1 renal cell carcinoma (RCC) and treated with RAPN between 2013 and 2022 at five institutions in Japan. The patients were classified into two groups according to their age during surgery (younger group: < 75 years, older group: ≥ 75 years). Propensity score matching (PSM) was performed to adjust for the differences in the backgrounds between younger and older patients, and surgical outcomes were compared. RESULTS: Among the 559 patients, 422 (75.5%) and 137 (24.5%) were classified into the younger and older groups, respectively; 204 and 102 patients from the younger and older groups were matched according to PSM, respectively. Subsequently, patient characteristics other than age were not significantly different between the two groups. In the matched cohort, the older group had more patients with major complications (younger, 3.0%; older, 8.8%; P = 0.045). CONCLUSION: Surgical outcomes of RAPN in older patients with RCC were comparable with those in younger patients, although older patients experiencedsignificantly more complications than younger patients. These results suggest the need for further detailed preoperative evaluation and appropriate postoperative management in older patients receiving RAPN.

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.

Comparison of robot-assisted partial nephrectomy with soft coagulation and double-layer technique for complex and non-complex tumors.

OBJECTIVES: To compare the postoperative outcomes of robot-assisted partial nephrectomy when only the inner layer is sutured (single-layer technique with soft coagulation) with those when sutures are placed in the inner and outer layers (double-layer technique) in patients with and without complex renal tumors. METHODS: This retrospective three-institution study included 371 patients with renal tumors who underwent robot-assisted partial nephrectomy with a double-layer technique or a single-layer technique with soft coagulation. Tumors that were cT1b, completely embedded, located in the renal portal, or had a RENAL score of ≥10 were considered complex. Relevant data were collected from hospital records. Propensity score matching was performed to minimize selection bias. RESULTS: Propensity score matching created 83 patient pairs with non-complex tumors and 32 with complex tumors. Regardless of tumor complexity, there was no significant difference in operation time, console time, warm ischemia time, positive surgical margin rate, or length of hospital stay between the double-layer and single-layer groups. Although Clavien-Dindo grade I-II urinomas not requiring intervention were significantly more common in the single-layer group regardless of tumor complexity, there was no significant between-group difference in the rate of decline in renal function or grade III-IV complications. CONCLUSION: Single-layer suturing with soft coagulation achieves renal function and perioperative outcomes comparable to those of double-layer suturing regardless of complexity.

Morin improves dexamethasone-induced muscle atrophy by modulating atrophy-related genes and oxidative stress in female mice.

This study investigated the effect of morin, a flavonoid, on dexamethasone-induced muscle atrophy in C57BL/6J female mice. Dexamethasone (10 mg/kg body weight) for 10 days significantly reduced body weight, gastrocnemius and tibialis anterior muscle mass, and muscle protein in mice. Dexamethasone significantly upregulated muscle atrophy-associated ubiquitin ligases, including atrogin-1 and MuRF-1, and the upstream transcription factors FoxO3a and Klf15. Additionally, dexamethasone significantly induced the expression of oxidative stress-sensitive ubiquitin ligase Cbl-b and the accumulation of the oxidative stress markers malondialdehyde and advanced protein oxidation products in both the plasma and skeletal muscle samples. Intriguingly, morin treatment (20 mg/kg body weight) for 17 days effectively attenuated the loss of muscle mass and muscle protein and suppressed the expression of ubiquitin ligases while reducing the expression of upstream transcriptional factors. Therefore, morin might act as a potential therapeutic agent to attenuate muscle atrophy by modulating atrophy-inducing genes and preventing oxidative stress.

A propensity score matching study on robot-assisted radical cystectomy for older patients: comparison of intracorporeal ileal conduit and cutaneous ureterostomy.

BACKGROUND: Robot-assisted radical cystectomy (RARC) and intracorporeal urinary diversion are less invasive than conventional procedures. However, for older patients, cutaneous ureterostomy (CUS) may be preferred because urinary diversion using the intestine has a high incidence of perioperative complications and is highly invasive. The purpose of this study was to demonstrate the safety and efficacy of intracorporeal ileal conduit (ICIC) compared with CUS in patients aged 75 years or older who underwent RARC. METHODS: From October 2014 to December 2021, 82 patients aged 75 years or older who underwent RARC at Tokushima University Hospital, Tokushima Prefectural Central Hospital, or Ehime Prefectural Central Hospital were retrospectively reviewed. Of these, 52 and 25 patients who underwent ICIC and CUS, respectively, were included. After adjusting the patients' characteristics using propensity score-matching, surgical results and prognoses were retrospectively compared. The propensity score was based on age, Eastern Cooperative Oncology Group Performance Status Scale (ECOG-PS), American Society of Anesthesiologists physical status classification (ASA-PS), clinical tumor stage, and neoadjuvant chemotherapy. RESULTS: The median age was lower in the ICIC group compared with the CUS group, and the proportion of high-risk cases (ECOG-PS ≥ 2 or ASA-PS ≥ 3) did not differ. The median operation time was longer in the ICIC group, and estimated blood loss was higher, compared with the CUS group. There were no significant differences in the incidence of complications within the first 30 postoperative days, incidence of complications 30-90 days after surgery, 2-year overall survival, 2-year cancer-specific survival, and 2-year recurrence-free survival. The stent-free rate was significantly lower in the CUS group than that in the ICIC group. CONCLUSION: In older patients, the ICIC group showed non-inferior surgical and oncological outcomes compared with the CUS group. Urinary diversion following RARC in older patients should be carefully selected by considering not only the age but also the general condition (including comorbidities) of the patient.

Appropriate management reduces radiation exposure in daily urological practice.

OBJECTIVES: To identify and raise awareness of the radiation exposure of urologists due to X-ray fluoroscopic procedures in daily practice. METHODS: This was a single-center, cohort study of 30 consecutive patients who underwent periodic percutaneous or transurethral replacements of urinary tract catheters. A total of 55 replacements every 3 months with cases aligned were performed by a single urologist. The urologist's radiation exposure and the incident dose to patients per case were measured with thermoluminescent dosimeters. In the latter 3-month period, the pulse fluoroscopy condition was changed from 15 to 7.5 pulses per second, and collimation was added to the field of view. RESULTS: In the analysis of all patients, the use of a modified pulse rate and collimation did not affect the fluoroscopy time, but it did significantly reduce the air kerma and dose area product; in addition, with respect to the medical exposure dose during percutaneous catheter replacement, fluoroscopy time was longer, but air kerma and dose area product showed significant decreases. As with decreases in medical exposure of patients, the equivalent dose for eye lenses of the urologist decreased from 1.2 mSv in the first 3-month period to 0.2 mSv in the second 3-month period. Similarly, the exposure dose for the extremities also decreased significantly, from 33.9 mSv to 8.1 mSv. CONCLUSIONS: Urologists are exposed to non-negligible amounts of radiation due to fluoroscopy. Appropriate management such as modified pulse fluoroscopy condition and precautions are required.

[A Case of Pappilary Renal Cell Caircinoma which Responded Well to the Combination Therapy of Ipilimumab and Nivolumab --A CASE REPORT-].

We report a case of papillary renal cell carcinoma that responded well to the combination of ipilimumab and nivolumab. The patient was a 68-year-old male who was being followed up for a small left renal mass without treatment. Two years later, computed tomography (CT) showed enlarged cervical and para-aortic lymph nodes, and lymph node biopsy suggested metastases of the cancer. After resection of the renal tumor, we performed pararenal aortic lymph node biopsy, and we diagnosed the case as papillary renal cell carcinoma type 1 with lymph node metastasis. The combination of ipilimumab and nivolumab each metastatic site showed regression on CT. Since immune-related adverse events occurred during the therapy nivolumab was discontinued, but partial response of the metastases was maintained.

[Two Cases of Robot-Assisted Total Pelvic Exenteration and Intracorporeal Ileal Conduit for Locally Advanced Rectal Cancer].

We describe two cases of locally advanced rectal cancer (LARC) treated with robot-assisted total pelvic exenteration (Ra-TPE) and intracorporeal ileal conduit (ICIC). The first case was in a 71-year-old man with LARC (RbP, T4bN2bM0, cStage IIIc). He was started on bevacizumab+S-1/oxaliplatin therapy in July 2019. In April 2020, he developed Fournier's gangrene due to subcutaneous penetration of rectal cancer. Emergency drainage and colostomy were performed simultaneously, and a percutaneous vesical fistula was created. In May 2020, Ra-TPE and ICIC were performed. Histopathological analysis revealed moderately differentiated tubular adenocarcinoma (ypT3N0, RM0). At postoperative 9 months, thoracoscopic right upper lobectomy was performed for a right metastatic lung tumor. At present, ie, at postoperative 12 months, the patient has been free of recurrence and metastasis, with a carcinoembryonic antigen (CEA) level of 1.4 ng/ml and carcinoma antigen (CA) 19-9 level of 11 U/ml. The second case was in a 61-year-old man with fistula-associated anal cancer (PRb, T4N3M1b, cStage IVb). In April 2019, he was started on FOLFOXIRI+cetuximab therapy. In August 2020, Ra-TPE, ICIC, and transperineal total mesenteric excision were performed. Histopathological analysis revealed adenocarcinoma (ypT4N0, RM0). At postoperative 11 months, thoracoscopic left lower lobectomy was performed for a left metastatic lung tumor. At present, ie, at postoperative 12 months, the patient remains free of recurrence and metastasis, with a CEA level of 7.3 ng/ml and CA19-9 level of 12 U/ml. Ra-TPE, which allows transperineal removal of a specimen, can be performed as a minimally invasive surgery in combination with ICIC.

[A Case of Robot-Assisted Radical Cystoprostatectomy for Locally Advanced Prostate Cancer with Bladder Infiltration].

While robot-assisted radical cystoprostatectomy (RARC) for locally advanced prostate cancer (LAPC) may sometimes prove to be excessive treatment, it can significantly reduce the risk of positive surgical margins and lower urinary tract obstruction in some cases. Here, we report a case of LAPC treated with RARC in a patient with right hydronephrosis due to bladder infiltration and left hypoplastic kidney. A 71-year-old man presented with frequent urination in August 2019. Prostate-specific antigen (PSA) level was 8.633 ng/ml, and magnetic resonance imaging led to the suspicion that the prostate cancer extended beyond the prostate capsule without distant metastasis. Prostatic biopsy revealed Gleason score 10 (5＋5) adenocarcinoma in 8 out of 8 specimens. We diagnosed left hypoplastic kidney and LAPC with right hydronephrosis due to bladder infiltration. We performed percutaneous right nephrostomy and started neoadjuvant hormone therapy. RARC and intracorporeal ileal conduit were performed in March 2020. The prostate was adherent to the anterior surface of the rectum and was difficult to remove. At present, five months after the surgery, the patient remains free of recurrence and metastasis with PSA level ＜0.003 ng/ml. RARC for LAPC with bladder infiltration can be an effective therapeutic strategy in some cases.

[A Case of Desmoid Tumor Initially Diagnosed as a Metastasis from Renal Cell Carcinoma --A CASE REPORT-].

We report a case of desmoid tumor that was initially diagnosed as metastasis from renal cell carcinoma. A follow-up computed tomographic (CT) scan after nephrectomy for renal cell carcinoma in a 64-year-old man revealed a right retroperitoneal tumor 3.5 cm in diameter. Though the CT density of the tumor was similar to that of muscles, we first suspected metastasis from renal cell carcinoma or other cancer because the tumor growth was relatively fast. We resected the tumor. The pathological diagnosis was desmoid type fibromatosis. We also review six cases of desmoid tumors after nephrectomy for renal cell carcinoma reported in Japan. Careful followup is required for the patients with desmoid tumors because of frequent recurrence.

[A Case of Pelvic Organ Prolapse and Bladder Diverticulum Surgically Treated at the Same Time].

We report a case of bladder diverticulum presumably caused by lower urinary tract dysfunction due to pelvic organ prolapse (POP) simultaneously treated with transurethral coagulation (TUC) of the bladder diverticulum and laparoscopic sacrocolpopexy (LSC). A literature search showed this is the first report of bladder diverticulum and POP surgically treated at the same time. A 71-year-old woman was referred to our hospital for the treatment of cystocele. She had both storage and voiding symptoms. She had a POPQ stage III cystocele and stage I uterine prolapse. Ultrasonography and computed tomographic scan showed a large volume of residual urine along with a bladder diverticulum. Since urodynamic studies revealed a low compliance bladder and obstruction, we opined that the lower urinary tract symptoms were induced by the cystocele. TUC of the bladder diverticulum and LSC were performed at the same time. After the operation, clean intermittent catheterization (CIC) was needed once a day for one month. Gradually, residual urine decreased and CIC became unnecessary. The bladder diverticulum disappeared, and there has been no recurrence of POP.

Current knowledge of risk factors for testicular germ cell tumors.

The development of the human gonads is tightly regulated by the correct sequential expression of many genes and hormonal activity. Disturbance of this regulation does not only prevent proper development of the gonads, but it also contributes to the development of testicular germ cell tumors. Recent genetic studies, especially genome-wide association studies, have made great progress in understanding genetic susceptibility. Although there is strong evidence of inherited risks, many environmental factors also contribute to the development of testicular germ cell tumors. Histopathological studies have shown that most testicular germ cell tumors arise from germ cell neoplasia in situ, which is thought to be arrested and transformed primordial germ cells. Seminoma has features identical to germ cell neoplasia in situ or primordial germ cells, whereas non-seminoma shows varied differentiation. Seminomas and embryonic cell carcinomas have the feature of pluripotency, which is thought to be the cause of histological heterogeneity and mixed pathology in testicular germ cell tumors. Testicular germ cell tumors show high sensitivity to chemotherapies, but 20-30% of patients show resistance to standard chemotherapy. In the present review, the current knowledge of the epidemiological and genomic factors for the development of testicular germ cell tumors is reviewed, and the mechanisms of resistance to chemotherapies are briefly mentioned.

[Renal Angiomyolipoma Extending into the Renal Vein --A Case Report-].

We report a case of left renal angiomyolipoma extending into the renal vein. A 67-year-old woman showed a left renal tumor which was 6 cm in diameter and had density equal to fat tissue in computed tomography. We suspected liposarcoma and performed radical nephrectomy and resection of thrombus. The pathological diagnosis was angiomyolipoma with no malignancy. To our knowledge, renal angiomyolipoma with tumor thrombus has been reported in 62 cases, and pulmonary embolism developed in 9 of these cases. We conclude that surgical treatment is effective in treating angiomyolipoma with tumor thrombus.

Clinical Significance of Neoadjuvant Combined Androgen Blockade for More Than Six Months in Patients with Localized Prostate Cancer Treated with Prostate Brachytherapy.

INTRODUCTION: The aim of this study is to clarify the clinical significance of neoadjuvant combined androgen blockade (CAB) for ≥ 6 months in patients with localized prostate cancer. PATIENTS AND METHODS: A total of 431 patients with localized prostate cancer who underwent prostate brachytherapy (BT) with or without neoadjuvant CAB for ≥ 6 months with mean follow-up time of 64.6 months (range 24-108 months) were evaluated retrospectively. Of those 431, 232 patients received BT in combination with neoadjuvant CAB for ≥ 6 months. Biochemical recurrence-free rates (BRFRs) in 364 patients with at least 3 years of follow-up were evaluated by log-rank test. RESULTS: BRFR in patients with low-, intermediate- and high-risk prostate cancer were 98.1, 94.2 and 89.1%, respectively. In patients with intermediate-risk prostate cancer only, neoadjuvant CAB was significantly associated with BRFR (p = 0.0468). Especially in patients with intermediate-risk prostate cancer with radiation dose received by 90% of the prostate (D90) < 180 Gy, neoadjuvant CAB exerted a favorable impact on BRFR (p = 0.0429). On multivariate analyses, neoadjuvant CAB and D90 were independent predictors of BRFR (p = 0.0061 and p < 0.0001, respectively). CONCLUSIONS: Neoadjuvant CAB for ≥ 6 months has a favorable impact on BRFR in patients with intermediate-risk prostate cancer, particularly in patients with relatively low radiation doses of D90.

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.

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.

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.

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.