Impact of oral antithrombotic agents on urinary continence recovery following robot-assisted radical prostatectomy: a retrospective cohort study.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is a preferred minimally invasive surgical treatment for prostate cancer. The number of elderly patients and those with cardiovascular and/or cerebrovascular issues undergoing surgery is increasing, and many of them are taking antithrombotic (AT) agents. However, the effect of AT agents on postoperative urinary recovery has not been adequately studied. In this study, we analyzed the differences in the postoperative recovery of urinary continence and oncological outcomes in patients undergoing RARP for localized prostate cancer between AT agent adherents and non-adherents. METHODS: A total of 394 patients who underwent conventional anterior RARP between February 2015 and February 2021 were categorized into two groups: those taking oral AT agents (AT group) and the control group. Urinary continence recovery, complications, and oncological outcomes were compared between the groups. A Cox proportional hazards analysis was performed to identify clinical factors that affect urinary continence recovery. RESULTS: The background data and bleeding complications did not differ significantly between the groups. The recovery of continence was significantly poorer in the AT group in terms of complete pad free (HR: 0.53 [95% CI: 0.39-0.71]) and use of ≤ 1 safety pad (HR: 0.74 [95% CI: 0.59-0.94]). The rate of anastomotic leakage on cystography was significantly higher in the AT group (20.9% vs. 6.7%). A univariate analysis revealed that taking antithrombotic agents, higher prostate-specific antigen levels, and a more advanced clinical stage were associated with a poor urinary continence recovery; a multivariate analysis showed that taking AT agents was an independent factor negatively associated with urinary continence recovery. There was no significant difference between the groups in the positive surgical margin rate (19.0% vs. 23.8%) or the biochemical-recurrence-free rate. CONCLUSION: Taking oral AT agents may be associated with poor urinary continence recovery after RARP.

Prognostic significance of inflammatory markers in patients with advanced renal cell carcinoma receiving nivolumab plus ipilimumab.

BACKGROUND: A useful biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in advanced renal cell carcinoma (RCC) has not yet been established. This study aims to investigate whether inflammatory markers are associated with the efficacy of nivolumab plus ipilimumab therapy before and during treatment. METHODS: Data from patients with advanced clear cell RCC who received a combination treatment of nivolumab plus ipilimumab were retrospectively analyzed. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels were assessed at baseline and 3, 6, and 9 weeks after treatment initiation. The correlation between these inflammatory markers and the patient's prognosis was investigated. RESULTS: Eighty-four patients were identified. The multivariate analysis identified NLR at week 3, CRP at week 6, and NLR and CRP at week 9 as the consistent predictor associated with poor overall survival (OS) at each time point. The survival analysis and receiver operating characteristic (ROC) curve analysis revealed that an NLR of ≥ 2.4 at week 3, CRP of ≥ 1.4 mg/dL at week 6, and NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 were associated with worse OS (hazard ratios (HR) = 5.70, P = 0.008, HR = 3.23, P = 0.004, HR = 7.38, P < 0.001 and HR = 3.55, P = 0.002). CONCLUSIONS: Both NLR and CRP were considered useful biomarkers for understanding the prognosis during nivolumab plus ipilimumab therapy. Furthermore, an NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 are helpful in reconsidering treatment continuation.

A novel anterior approach toward robotic radical prostatectomy is associated with earlier continence recovery than the conventional approach.

OBJECTIVES: To advance robotic radical prostatectomy, we developed a novel anterior approach that uses a peritoneal incision created between the umbilical ligaments to develop the Retzius space and thus spares vessels that surround the bladder and prostate, with the space being closed after prostatectomy and vesicourethral anastomosis. This approach may improve continence recovery. We investigated continence recovery following the novel anterior approach compared to after the conventional anterior approach. METHODS: We retrospectively reviewed 516 patients who underwent robotic radical prostatectomy from January 2019 to July 2023. We compared continence recovery following our novel anterior approach (N = 282) to that after conventional anterior approach (N = 234), and we compared the oncological outcomes and safety profiles of the two groups. RESULTS: Patient demographics did not differ significantly between the two groups. Continence recovery in patients undergoing the novel anterior approach was significantly better than that of patients treated via the conventional approach (hazard ratio: 1.651, 95% confidence interval: 1.325-2.057, p < 0.0001). Use of the novel anterior approach in addition to nerve sparing and preservation of the detrusor apron independently predicted continence, and the mixture of these three techniques afforded excellent continence recovery (1- and 2-year total continence rate of 81.1% and 93.7%). Neither the biochemical recurrence-free survival nor the complication rate differed significantly between the two groups. CONCLUSION: Our novel anterior approach may improve continence recovery compared to the conventional anterior approach, without compromising the oncological outcomes. Prospective comparative studies are necessary to confirm the benefits of this approach.

Real-world outcomes of avelumab plus axitinib as first-line therapy in patients with advanced renal cell carcinoma in Japan: A multicenter, retrospective, observational study (J-DART).

OBJECTIVES: In the phase 3 JAVELIN Renal 101 trial in patients with advanced renal cell carcinoma (aRCC), objective response rate (ORR) and progression-free survival (PFS) were significantly improved in patients treated with first-line avelumab plus axitinib vs sunitinib. Here we evaluate real-world outcomes with first-line avelumab plus axitinib in Japanese patients with aRCC. METHODS: In this multicenter, noninterventional, retrospective study, clinical data from patients with aRCC treated with first-line avelumab plus axitinib between December 2019 and December 2020 in Japan were reviewed. Endpoints included ORR and PFS per investigator assessment, and time to treatment discontinuation (TTD). RESULTS: Data from 48 patients (median age, 69 years) from 12 sites were analyzed. Median follow-up was 10.4 months (range, 2.6-16.5), and median duration of treatment was 7.4 months (range, 0.5-16.5). International Metastatic RCC Database Consortium risk category was favorable, intermediate, or poor in 16.7%, 54.2%, and 29.2% of patients, respectively. The ORR was 48.8% (95% CI, 33.3%-64.5%), including complete response in 3/43 patients (7.0%). Thirteen patients (27.1%) had disease progression or died, and median PFS was 15.3 months (95% CI, 9.7 months - not estimable). At data cutoff, 24 patients (50.0%) were still receiving avelumab plus axitinib, and median TTD was 15.2 months (95% CI, 7.4 months - not estimable). Three patients (6.3%) received high-dose corticosteroid treatment for immune-related adverse events, and 8 (16.7%) received treatment for infusion-related reactions. CONCLUSIONS: We report the first real-world evidence of the effectiveness and tolerability of first-line avelumab plus axitinib in Japanese patients with aRCC. Results were comparable with the JAVELIN Renal 101 trial.

Association between immune-related adverse events and survival in patients with renal cell carcinoma treated with nivolumab plus ipilimumab: immortal time bias-corrected analysis.

BACKGROUND: Immune-related adverse events (irAEs) in patients treated with immune check inhibitors are associated with favourable response rate and survivals in multiple cancers, including renal cell carcinoma (RCC). The aim of this study was to investigate how irAEs were associated with improved survivals in advanced RCC patients treated with nivolumab plus ipilimumab. MATERIALS AND METHODS: This retrospective study included patients who received nivolumab plus ipilimumab at six centres, institutions, or hospitals between September 2018 and February 2022. We assessed associations of the development and the number of irAEs with overall survival (OS) and progression-free survival (PFS). To eliminate immortal time bias, landmark analysis and a Cox model with time-dependent variables were used. RESULTS: This study included 129 patients with a median follow-up of 12.3 months. The 2-year OS and PFS rates were 55% and 42%, respectively. Ninety six patients experienced irAEs. The development of irAEs was positively associated with OS and PFS rates (hazard ratio [HR] 0.328, 95% confidence interval [CI] 0.165-0.648, p = 0.001; HR 0.334, 95% CI 0.151-0.737, p = 0.007). Patients who experienced multiple irAEs had longer OS (HR 0.507, 95% CI 0.235-1.097, p = 0.085 or HR 0.245, 95% CI 0.110-0.544, p < 0.001) and PFS (HR 0.572, 95% CI 0.316-1.036, p = 0.085 or HR 0.267, 95% CI 0.113-0.628, p = 0.002) compared with those who experienced single or zero irAE. CONCLUSIONS: Developing irAEs, particularly multiple irAEs, is associated with favourable survivals in advanced RCC patients treated with nivolumab plus ipilimumab.

Clinical outcomes of nivolumab plus ipilimumab in patients with metastatic non-clear cell renal cell carcinoma: Real-world data from a Japanese multicenter retrospective study.

OBJECTIVES: Although nivolumab plus ipilimumab has become a standard treatment regimen for metastatic clear cell renal cell carcinoma (ccRCC), its efficacy in non-clear cell carcinoma (nccRCC) has not been fully examined. In the current study, we evaluated the clinical outcomes of nivolumab plus ipilimumab in nccRCC compared with ccRCC. METHODS: We retrospectively analyzed 22 patients with metastatic and/or locally advanced unresectable nccRCC who received nivolumab plus ipilimumab as a first-line therapy and compared them with 107 patients with ccRCC. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity were compared between the nccRCC and ccRCC groups. RESULTS: The histology of nccRCC included eight papillary, six unclassified, three chromophobe, two collecting duct carcinoma, and three other subtypes. Best objective response in nccRCC patients included three complete responses and five partial responses, resulting in an ORR of 36%, while that in ccRCC patients was 50% (p = 0.22). With a median follow-up of 11.9 months, OS was significantly shorter in patients with nccRCC than in those with ccRCC (median 20.8 months vs. not reached, p = 0.04), while there was no significant difference in PFS (median 6.3 vs. 10.8 months, p = 0.21). Treatment-related adverse events occurred in 14 (64%) nccRCC patients and 81 (76%) ccRCC patients. CONCLUSIONS: Combination treatment with nivolumab and ipilimumab demonstrated modest clinical efficacy in patients with nccRCC compared with patients with ccRCC, suggesting it could be a therapeutic option for metastatic nccRCC patients.

[A Case of Left Renal Cell Carcinoma with Renal Arteriovenous Fistula and Multiple Vascular Malformation Undergoing Nephrectomy].

A 69-year-old woman was referred to our hospital for the treatment of a left renal tumor found by computed tomography (CT) during examination for microscopic hematuria. Contrast-enhanced CT showed a 5 cm tumor in the inferior pole of the left kidney. Left renal cell carcinoma (RCC) (cT1bN0M0) was suspected. In addition, the left renal and gonadal veins were dilated and enhanced in an arterial phase; renal arteriovenous fistula (RAVF) was suspected. Moreover, there were multiple focal arterial dilatations, suggesting the presence of multiple vascular malformation. Hereditary aortic disease, including vascular Ehlers-Danlos syndrome (vEDS), was a concern. In general, surgery is not recommended for patients with vEDS, due to vascular fragility. As such, a panel analysis of genes for hereditary aortic diseases, including vEDS, was performed; no pathogenic variants in candidate genes including COL3A1 were identified. After detailed discussions with the patient, she underwent a left nephrectomy, following transcatheter arterial embolization (TAE) of the left renal artery. We prepared a balloon catheter for aortic occlusion as a preventative measure for massive bleeding; this was not the case, as only a small amount of intraoperative bleeding occurred. Thus, the nephrectomy was performed successfully without using the balloon catheter. The patient recovered uneventfully and was discharged on day 8. Pathological examination showed clear-cell RCC (pT1a) and a RAVF near the tumor. Herein we report this case of left RCC with RAVF and multiple arterial malformation, which was successfully managed by evaluating preoperative risks with a genetic test, followed by TAE of the renal artery and open nephrectomy.

Hypereosinophilia is a predictive biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma.

BACKGROUND: This study aimed to evaluate whether hypereosinophilia is a clinical biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma treated with nivolumab plus ipilimumab. METHODS: This was a retrospective cohort study conducted at Jichi Medical University Saitama Medical Center between January 2018 and December 2020. In total, 12 patients with renal cell carcinoma who presented with immune checkpoint inhibitor-induced hypopituitarism were enrolled in this study. The clinical parameters and symptoms at baseline, last visit, and onset of hypopituitarism were analyzed. RESULTS: The median period from the initial treatment with immune checkpoint inhibitors to the onset of hypopituitarism was 82.5 (range: 56-196) days. Most patients developed hypopituitarism within 6 months. One patient presented with hypophysitis and 11 patients presented with isolated adrenocorticotropic hormone deficiency. The major symptoms noted at onset were fatigue (66.7%) and loss of appetite (41.7%). None of the patients had symptoms during the last visit. However, four developed hypereosinophilia. Eosinophil fraction (%) and eosinophil count (/µL) increased during the last visit and at the onset of hypopituitarism, respectively. The serum sodium and plasma glucose levels were similar. CONCLUSIONS: The eosinophil count increased before the onset of hypopituitarism. Thus, hypereosinophilia can be an early predictor of hypopituitarism.

Prostate-specific antigen level, biopsy grade group, and tumor-capsular contact length on magnetic resonance imaging are independently associated with an extraprostatic extension.

OBJECTIVE: To define the clinicopathological and radiological factors independently associated with the existence of an extraprostatic extension in radical prostatectomy specimens. METHODS: A total of 202 patients who underwent robotic prostatectomy following biparametric magnetic resonance imaging were assessed. We evaluated the clinicopathological and magnetic resonance imaging variables. We performed receiver-operating characteristic curve analyses to identify factors associated with extraprostatic extension. We engaged in multivariate analysis to identify factors independently associated with such extension. RESULTS: Extraprostatic extensions were apparent in the final prostatectomy specimens of 62 patients (31%). The areas under the curves of the prostate-specific antigen level, the biopsy grade group, and the tumor-capsular contact length on magnetic resonance imaging were 0.76, 0.71, and 0.70, respectively, in receiver-operating characteristic analysis when used to predict extraprostatic extension; thus, higher than the areas under the curves of the other variables (0.61-0.68). The prostate-specific antigen level (odds ratio 1.090, p = 0.004), the biopsy grade group (odds ratios 2.678 and 6.358, p = 0.017 and p < 0.001 for grade group 3-4 and 5), and the tumor-capsular contact length (odds ratio 1.079, p = 0.001) were independently associated with extraprostatic extension. When the three factors were combined, the area under the receiver-operator characteristic curve increased to 0.79. CONCLUSIONS: The prostate-specific antigen level, the biopsy grade group, and the tumor-capsular contact length on magnetic resonance imaging were independently associated with extracapsular extension.

Combination of biparametric magnetic resonance imaging with prostate-specific antigen density to stratify the risk of significant prostate cancer: Initial biopsy and long-term follow-up results.

OBJECTIVES: To assess whether the combination of biparametric magnetic resonance imaging with prostate-specific antigen density can properly stratify the risk of significant prostate cancer in patients undergoing prostate biopsies and how this approach affects the detection of prostate cancer during follow-up in patients who do not undergo prostate biopsy. METHODS: In total, 411 biopsy-naïve patients who had elevated prostate-specific antigen levels and then underwent biparametric magnetic resonance imaging for suspicious prostate cancer were analyzed: 203 patients underwent prostate biopsies, whereas 208 patients did not. Significant prostate cancer detection rates stratified by the combination of Prostate Imaging Reporting and Data System score and prostate-specific antigen density were assessed in patients who underwent prostate biopsies. The cumulative incidence of prostate cancer detection during the follow-up was assessed in patients who omitted biopsy. RESULTS: The negative predictive value for significant prostate cancer was 89% for Prostate Imaging Reporting and Data System scores 1-3, which increased to 97% when prostate-specific antigen density <0.15 ng/ml/cm3 was combined. Among patients who did not undergo biopsy, patients with Prostate Imaging Reporting and Data System scores 1-3 plus prostate-specific antigen density <0.15 ng/ml/cm3 included significantly less cases in which significant prostate cancer was detected during the follow-up, compared with the others (3.2% versus 17% at 36 months). CONCLUSIONS: Restriction of prostate biopsies to patients with Prostate Imaging Reporting and Data System scores 4-5 or prostate-specific antigen density ≥0.15 ng/ml/cm3 proved to be the good biopsy strategy, effectively balancing risks and benefits.

Laparoscopic sacrocolpopexy for pelvic organ prolapse in the elderly: safety and outcomes.

Due to its low postoperative complication rate, vaginal surgery is the preferred intervention for pelvic organ prolapse (POP) in elderly patients. We aimed to assess outcomes and perioperative complication rates associated with laparoscopic sacrocolpopexy (LSC) in elderly women. We retrospectively reviewed the medical records of 74 consecutive patients [52 (70.3%) aged <75 years; 22 (29.7%) aged ≥75 years] with POP who underwent LSC between August 2015 and December 2017. We evaluated preoperative risks using the Charlson Comorbidity Index (CCI) and complications, using the Clavien-Dindo grading (CDG). No between-group differences were observed in CCI. CDG indicated fewer perioperative complications in patients aged >75 years. Anatomical success rates at 15 months were 95.5% and 90.4% in patients aged ≥75 and <75 years, respectively. LSC has a high anatomical correction rate and few perioperative complications regardless of age. Thus, the appropriate surgical intervention method would depend on the patient's health and comorbidities.IMPACT STATEMENTWhat is already known on this subject? Laparoscopic sacrocolpopexy (LSC) is a superior method to vaginal surgery because of its anatomical and functional outcomes, particularly regarding sexual activity.What do the results of this study add? In this single-center study with a 15-month follow-up, we demonstrated that LSC has a high anatomical correction rate and few perioperative complications regardless of age at the time of surgery. Furthermore, there was no significant difference in the rate of complications between the ≥75 and <75 years groups. Thus, LSC may be considered for women aged >75 years. However, in these elderly patients, the surgical method should be determined according to their health status and medical comorbidities.What the implications are of these findings for clinical practice and/or further research? Age should not be the basis for exclusion from laparoscopic procedures. Moreover, LSC is a suitable and valid option for elderly women with POP. As the study population consisted of a homogenous group of Japanese women, it lacks generalisability. Studies evaluating these outcomes are required in other populations.

Retzius-sparing robot-assisted radical prostatectomy: early learning curve experience in three continents.

OBJECTIVE: To assess the effect of surgical experience on peri-operative, functional and oncological outcomes during the first 50 Retzius-sparing robot-assisted radical prostatectomy (RsRARP) cases performed by surgeons naïve to this novel approach. MATERIALS AND METHODS: We retrospectively evaluated the initial cases operated by 14 surgeons in 12 different international centres. Pre-, peri- and postoperative features of the first 50 patients operated by each surgeon in all the participating centres were collected. The effect of surgical experience on peri-operative, functional and oncological outcomes was firstly evaluated after stratification by level of surgical experience (initial [≤25 cases] and expert [>25 cases]) and after using locally weighted scatterplot smoothing to graphically explore the relationship between surgical experience and the outcomes of interest. RESULTS: We evaluated 626 patients. The median follow-up was 13 months in the initial group and 9 months in the expert group (P = 0.002). Preoperative features overlapped between the two groups. Shorter console time (140 vs 120 min; P = 0.001) and a trend towards lower complications rates (13 vs 5.5%; P = 0.038) were observed in the expert group. The relationship between surgical experience and console time, immediate urinary continence recovery and Clavien-Dindo grade ≥2 complications was linear, without reaching a plateau, after 50 cases. Conversely, a non-linear relationship was observed between surgical experience and positive surgical margins (PSMs). CONCLUSIONS: In this first report of a multicentre experience of RsRARP during the learning curve, we found that console time, immediate urinary continence recovery and postoperative complications are optimal from the beginning and further quickly improve during the learning process, while PSM rates did not clearly improve over the first 50 cases.

Complications and clinical outcomes of laparoscopic sacrocolpopexy for pelvic organ prolapse.

Evidence on laparoscopic sacrocolpopexy (LSC) is lacking. Herein, we describe the complications and outcomes of LSC. This single-centre, retrospective cohort study included women with pelvic organ prolapse (POP) who underwent LSC between 2015 and 2017. Preoperative, intraoperative, postoperative, and demographic data were collected. We evaluated patients using the Pelvic Organ Prolapse Quantification system and questionnaires. The primary outcomes were operative characteristics, perioperative complications, early postoperative complications, and anatomical results at 12 months. Forty-six patients (median age: 71 years) underwent LSC. The median follow-up period was 12.0 ± 5.0 (range: 11-26) months. The perioperative complications were bladder perforation and vaginal injury (2.2%). Two (4.3%) patients required reoperation for port-site hernia. One (2.2%) patient developed a retroperitoneal abscess, and one (2.2%) had worsened stress urinary incontinence after LSC. Three (6.5%) patients presented with recurrence of prolapse. LSC is safe and effective for POP.IMPACT STATEMENTWhat is already known on this subject? Laparoscopic sacrocolpopexy (LSC) has become a widely used intervention strategy during the last decade; nevertheless, few studies have reported its outcomes and complications.What do the results of this study add? We demonstrate that LSC for pelvic organ prolapse (POP) has favourable anatomical and voiding functional results, and few perioperative complications. However, it is important to preoperatively inform patients regarding the incidence of mesh-related postoperative complications, although they are not life-threatening, and secure their informed consent.What are the implications of these findings for clinical practice and/or further research? We believe that the LSC procedure, because of its short-term and functional outcomes in the lower urinary tract discussed here, will be more commonly available in clinical practice as a feasible and safe surgical option for POP. However, prospective, large-sample studies should be performed to verify the efficacy of LSC, as further evaluation of the procedure is required.

[A Case of Metachronous Occurrence of Interstitial Pneumonitis and Hypophysitis Following Nivolumab Plus Ipilimumab for Metastatic Renal Cell Carcinoma].

A 71-year-old man presented with neck pain. He was diagnosed with renal cell carcinoma of the left kidney with lung and bone metastases. After laparoscopic left nephrectomy, nivolumab plus ipilimumab was introduced as a first-line therapy for intermediate risk metastatic renal cell carcinoma based on the IMDC risk classification. After four cycles of nivolumab plus ipilimumab, he experienced dyspnea and was diagnosed with interstitial pneumonitis. Corticosteroid therapy was initiated, after which the symptoms of interstitial pneumonitis subsided. Corticosteroid therapy was tapered and discontinued after two months of treatment. The patient experienced fatigue at one week after the discontinuation of corticosteroid therapy and was diagnosed with isolated ACTH deficiency due to hypophysitis. He recovered after hydrocortisone treatment. This case involved two different immune-related adverse events (irAE), interstitial pneumonitis and hypophysitis, that occurred asynchronously following nivolumab plus ipilimumab therapy. It is important to observe the patient's condition carefully whether additional irAEs arise when corticosteroid therapy is tapered or discontinued.

Roles Played by Biomarkers of Kidney Injury in Patients with Upper Urinary Tract Obstruction.

Partial or complete obstruction of the urinary tract is a common and challenging urological condition caused by a variety of conditions, including ureteral calculi, ureteral pelvic junction obstruction, ureteral stricture, and malignant ureteral obstruction. The condition, which may develop in patients of any age, induces tubular and interstitial injury followed by inflammatory cell infiltration and interstitial fibrosis, eventually impairing renal function. The serum creatinine level is commonly used to evaluate global renal function but is not sensitive to early changes in the glomerular filtration rate and unilateral renal damage. Biomarkers of acute kidney injury are useful for the early detection and monitoring of kidney injury induced by upper urinary tract obstruction. These markers include levels of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein-1, kidney injury molecule 1, N-acetyl-b-D-glucosaminidase, and vanin-1 in the urine and serum NGAL and cystatin C concentrations. This review summarizes the pathophysiology of kidney injury caused by upper urinary tract obstruction, the roles played by emerging biomarkers of obstructive nephropathy, the mechanisms involved, and the clinical utility and limitations of the biomarkers.

Utility of robot-assisted radical cystectomy with intracorporeal urinary diversion for muscle-invasive bladder cancer.

Radical cystectomy remains the gold standard for treatment of muscle-invasive bladder cancer. Robot-assisted radical cystectomy has technical advantages over laparoscopic radical cystectomy and has emerged as an alternative to open radical cystectomy. Despite the advancements in robotic surgery, experience with total intracorporeal reconstruction of urinary diversion remains limited. Most surgeons have carried out the hybrid approach of robot-assisted radical cystectomy and extracorporeal reconstruction of urinary diversion, as intracorporeal reconstruction of urinary diversion remains technically challenging. However, intracorporeal reconstruction of urinary diversion might potentially proffer additional benefits, such as decreased fluid loss, reduction in estimated blood loss and a quicker return of bowel function. The adoption of intracorporeal ileal neobladder reconstruction has hitherto been limited to high-volume academic institutions. In the present review, we compare the totally intracorporeal robot-assisted radical cystectomy approach with open radical cystectomy and robot-assisted radical cystectomy + extracorporeal reconstruction of urinary diversion in muscle-invasive bladder cancer patients.

A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study.

Background: Vanin-1 is a novel acute kidney injury (AKI) biomarker that has not been clinically investigated as a biomarker for obstructive nephropathy. This study investigated the diagnostic value of vanin-1 as a biomarker for adult obstructive nephropathy by comparing it to existing AKI biomarkers. Methods: A total of 49 patients, 21 controls, and 28 hydronephrosis (HN) cases were assessed. AKI biomarkers in bladder (BL) urine and renal pelvic (RP) urine in the HN group were compared to each BL marker in the control group. In a subgroup of cases receiving interventions for obstructive nephropathy, the BL values of each biomarker were assessed after the intervention. Results: RP vanin-1 levels were significantly higher while BL vanin-1 levels were marginally higher in the HN group than in the control group. The area under the receiver operating characteristics curve values for RP and BL vanin-1 were 0.9778 and 0.6386, respectively. In multivariate analyses, BL vanin-1 and N-acetyl-ß-D-glucosaminidase (NAG), but not kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL), were independent factors for predicting the presence of HN. In cases receiving interventions, vanin-1 decreased significantly from 1 week after the intervention in cases of moderate to severe obstructive nephropathy compared to RP values at baseline. Conclusion: Urinary vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.

Early urinary biomarkers of renal tubular damage by a high-salt intake independent of blood pressure in normotensive rats.

Dietary sodium intake has been associated with progression to chronic kidney disease (CKD) as well as hypertension. A high-salt intake causes renal damage independent of hypertension. Because traditional renal biomarkers are insensitive, it is difficult to detect renal injury induced by a high-salt intake, especially in normotensive patients. Here, we investigated whether newly developed renal biomarkers could be detected earlier than traditional biomarkers under a high-salt intake, in normotensive rats. Male Wistar Kyoto rats (WKY) received a regular (0.8% NaCl) or salt-loaded (2, 4, and 8% NaCl) diet from 9 to 17 weeks of age. A urine sample was obtained once a week and urinary vanin-1, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (Kim-1) were measured. At 17 weeks of age, 8% salt-loaded WKY showed histopathological renal tubular damage and elevated Rac1 activity in renal tissues. Although there was no significant increase in serum creatinine, urinary albumin, N-acetyl-ß-D-glucosaminidase (NAG), or Kim-1 during the study period among the groups, urinary vanin-1 and NGAL significantly increased in 8% salt-loaded WKY from 10 to 17 weeks of age. These results suggest that urinary vanin-1 and NGAL, which might be induced by salt per se, are potentially earlier biomarkers for renal tubular damage in normotensive rats under a high-salt intake.

Cancer detection rate of prebiopsy MRI with subsequent systematic and targeted biopsy are superior to non-targeting systematic biopsy without MRI in biopsy naïve patients: a retrospective cohort study.

BACKGROUND: To determine whether prebiopsy multiparametric magnetic resonance imaging (mpMRI) with subsequent systematic plus targeted biopsies for suspicious lesions improve prostate cancer detection compared with standard non-targeting systematic biopsies without mpMRI in biopsy-naïve patients. METHODS: Patients who underwent their first prostate biopsy due to suspicion of prostate cancer were analyzed retrospectively to compare the biopsy outcomes between patients who received prebiopsy mpMRI (215 patients) and those who did not (281 patients). mpMRI was performed to determine pre-biopsy likelihood of the presence of prostate cancer using a three-point scale (1 = low level of suspicion, 2 = equivocal, and 3 = high level of suspicion). Systematic biopsies were performed in both groups. Targeted biopsies were added for a high level of suspicious lesions on mpMRI. All biopsies were performed by transperineal biopsy technique. After biopsy, Prostate Imaging Reporting and Data System ver. 2 (PIRADS-2) scoring was performed to describe the mpMRI findings and predictive value of PIRADS-2 was evaluated. RESULTS: The detection rate of total and clinically significant prostate cancer was significantly higher in patients who received prebiopsy mpMRI than in those who did not (55.3 and 46.0% vs. 42.0 and 35.2%, respectively; p = 0.004 and p = 0.016). The clinically insignificant prostate cancer detection rate was similar between the two groups (9.3% vs. 6.8%; p = 0.32). Of 86 patients who underwent systematic plus targeted biopsy in the MRI cohort and were diagnosed with prostate cancer, seven patients were detected by addition of targeted biopsy whereas 29 patients were missed by targeted biopsy but detected by systematic biopsy. There was a correlation between the PIRADS-2 and prostate cancer detection rate, and a receiver-operator curve analysis yielded an area under the curve of 0.801 (p <  0.0001). CONCLUSIONS: Prebiopsy mpMRI with subsequent systematic plus targeted biopsies for suspicious lesions can yield a higher cancer detection rate than non-targeting systematic biopsies. PIRADS-2 scoring is useful for predicting the biopsy outcome.

[Metastases of Urothelial Carcinoma with Trophoblastic Differentiation that Responded to Combination Chemotherapy with Gemcitabine and Oxaliplatin : A Case Report].

A 70-year-old man was admitted with complaint of gross hematuria. Cystoscopy and computed tomography (CT) revealed a 2.5 cm nodular tumor in the urinary bladder. Pathological diagnosis after the transurethral resection of bladder tumor (TURBT) was invasive urothelial cancer with trophoblastic differentiation of pT1. The tumor was positively stained with human chorionic gonadotropin (HCG). The serum HCG level was 12.8 IU/l in the fourth week after TURBT, and it increased to 35.7 IU/l in the 20th week after TURBT. However, radiological examination at this point did not reveal tumor recurrence or metastases. Three months later, the patient coughed up bloody sputum. Lung metastases (up to 2.4 cm) were identified, and they were surgically removed. The pathological specimen consisted of syncytiotrophoblastic giant cells with hemorrhage and necrosis, but no urothelial cancer element. Because the lung and lymph node metastases developed soon after surgery, chemotherapy was planned. Because the patient had impaired renal function with a creatinine clearance of 33.7 ml/min, we selected combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) rather than cisplatin -based chemotherapy. CT after two courses of GEMOX showed stable disease, but HCG levels markedly decreased from 1,240 IU/l to 7.9 IU/l. This marker of response continued through six courses of GEMOX. Then, the chemotherapy was discontinued due to grade 2 neuropathy. He died of cancer 12 months after development of metastases. Autopsy revealed only tumor cells with trophoblastic differentiation, but no urothelial carcinoma in multiple metastatic sites.