A.E. Canda

Robot-assisted nerve-sparing radical cystectomy with bilateral extended pelvic lymph node dissection (PLND) and intracorporeal urinary diversion for bladder cancer: initial experience in 27 cases.

Study Type – Therapy (case series)

Physiology and pharmacology of the human ureter: basis for current and future treatments.

Introduction: This article sets out to be a review regarding agents that affect contraction and relaxation of the ureter in order to establish a basis for current and future treatments for upper urinary tract obstruction. Material and Methods: A complete review of the English literature using MEDLINE was performed between 1960 and 2007 on ureter physiology and pharmacology with special emphasis on signal transduction mechanisms involved in the contractile regulation of the human ureter. Results: Activation of muscarinic and adrenergic receptors increases the amplitude of ureteral contractions. The sympathetic nerves modulate the contractions by α-adrenoceptors and relaxation by β-adrenoceptors. The purinergic system is important in sensory/motor functions and ATP is an important non-adrenergic non-cholinergic (NANC) agent causing contraction. Nitric oxide (NO) is a major inhibitory NANC neurotransmitter causing relaxation. Serotonin causes contraction. Prostaglandin-F2α contracts whereas prostaglandin-E1/E2 relaxes the ureter. Phosphodiesterases (PDE) and the Rho-kinase pathway have recently been identified in the human ureter. PDE-IV inhibitors, K+ channel openers, calcium antagonists, α1-adrenoceptor antagonists and NO donors seem to be promising drugs in relieving obstruction and facilitating stone passage. Conclusions: Further understanding of the ureteral function and pharmacology may lead to the discovery of promising new drugs that could be useful in relieving ureteral colic, facilitating spontaneous stone passage, preparing the ureter for ureteroscopy as well as acting adjunctive to extracorporeal shock-wave lithotripsy.

Pharmacologic targets on the female urethra.

Introduction: This article reviews the mechanisms affecting contraction and relaxation of the urethra in order to establish a basis for current and future treatments for urinary incontinence in women. Material and Methods: A review of the English literature using MEDLINE was performed between 1970 and 2008 on female urethra pharmacology, urinary incontinence, and mechanisms involved in contraction and relaxation of the female human urethra. Results: α-Adrenoceptors (ARs) cause contraction and β-ARs cause relaxation. Use of selective α-agonist and β-AR blocker agents might have potential for the treatment of stress urinary incontinence. Tolerable doses of cholinergic agonists did not have significant effects on intraurethral pressure. Nitric oxide seems to be the major nonadrenergic-noncholinergic inhibitory transmitter causing relaxation. c-kit-positive interstitial cells seem to regulate urethral tone. The roles of adenosine triphosphate and carbon monoxide have not been fully investigated in humans. Neuropeptides function similarly to the urinary bladder. Prostanoids cause urethral contraction and relaxation depending on their subtypes. Serotonin enhances the strength of urethral sphincteric contractions. The Rho-kinase pathway also appears to be modulating smooth muscle contraction in the urethra. Conclusions: Understanding of the urethral function and pharmacology may lead to the development of promising new agents which might be useful in the management of urinary incontinence in women.

Robot-assisted laparoscopic nerve-sparing radical cystoprostatectomy with bilateral extended lymph node dissection and intracorporeal studer pouch construction: outcomes of first 12 cases.

PURPOSE We report our initial experience with robot-assisted laparoscopic neurovascular bundle (NVB) sparing radical cystoprostatectomy (RALRC), bilateral extended lymph node dissection (BELND) with intracorporeal Studer pouch construction for invasive bladder cancer. PATIENTS AND METHODS After initially performing >50 cases of robot-assisted laparoscopic radical prostatectomies (RALRP), between December 2009 and April 2010, we performed 12 RALRC procedures with BELND. Bilateral (n=10) and unilateral (n=1) intrafascial NVB preservation was performed in 11 patients; nonnerve-sparing RALRC was performed in 1 patient. RESULTS Patient characteristics and surgical and postoperative parameters were mean patient age (y): 60 (43-80); American Society of Anesthesiologists score: 2 (1-3); body mass index (kg/m(2)): 24.5 (19.3-31.2); preoperative International Index of Erectile Function (IIEF) score: 25 (5-65); operative time (h): 10 (8.1-11.5); intraoperative blood loss (mL): 455 (100-700); lymph node (LN) yield: 21.3 (8-38); hospital stay (d): 10.7 (9-16); lodge drain removal (d): 10 (9-15). Five patients received neoadjuvant chemotherapy. Surgical margins were negative in all patients. Postoperative pathologic stages were: pT(0) (n=2), pT(1) (n=1), pT(2a) (n=2), pT(2b) (n=2), pT(3a) (n=4), and pT(4a) (n=1). Positive LNs and incidental prostate cancer were detected in five and three patients, respectively. Perioperative death rate was zero. Right external iliac vein injury occurred in one patient during the performance of BELND; surgery was converted to an open procedure and the injury was repaired. Colonic fistula developed in one patient at postoperative day 40; the patient died from cardiac disease at day 60. At a mean follow-up of 7.1 ± 2.3 months, three patients died from metastatic disease. Of the available seven patients, six were fully continent and one had mild daytime incontinence. CONCLUSIONS Although RALRC with bilateral intrafascial NVB preservation, BELND, and intracorporeal Studer pouch formation is a complex procedure, it can be performed with excellent short-term surgical and pathological outcomes and satisfactory functional results after considerable experience gained with RALRP procedures.

Early Oncologic Failure after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

Purpose: We sought to investigate the prevalence and variables associated with early oncologic failure. Materials and Methods: We retrospectively reviewed the IRCC (International Radical Cystectomy Consortium) database of patients who underwent robot‐assisted radical cystectomy since 2003. The final cohort comprised a total of 1,894 patients from 23 institutions in 11 countries. Early oncologic failure was defined as any disease relapse within 3 months of robot‐assisted radical cystectomy. All institutions were surveyed for the pneumoperitoneum pressure used, breach of oncologic surgical principles, and techniques of specimen and lymph node removal. A multivariate model was fit to evaluate predictors of early oncologic failure. The Kaplan‐Meier method was applied to depict disease specific and overall survival, and Cox proportional regression analysis was used to evaluate predictors of disease specific and overall survival. Results: A total of 305 patients (22%) experienced disease relapse, which was distant in 220 (16%), local recurrence in 154 (11%), peritoneal carcinomatosis in 17 (1%) and port site recurrence in 5 (0.4%). Early oncologic failure developed in 71 patients (5%) at a total of 10 institutions. The incidence of early oncologic failure decreased from 10% in 2006 to 6% in 2015. On multivariate analysis the presence of any complication (OR 2.87, 95% CI 1.38–5.96, p = 0.004), pT3 or greater disease (OR 3.73, 95% CI 2.00–6.97, p <0.001) and nodal involvement (OR 2.14, 95% CI 1.21–3.80, p = 0.008) was a significant predictor of early oncologic failure. Patients with early oncologic failure demonstrated worse disease specific and overall survival (23% and 13%, respectively) at 1 and 3 years compared to patients who experienced later or no recurrences (log rank p <0.001). Conclusions: The incidence of early oncologic failure following robot‐assisted radical cystectomy has decreased with time. Disease related rather than technical related factors have a major role in early oncologic failure after robot‐assisted radical cystectomy.

Robot-assisted radical cystectomy and intracorporeal neobladder formation: on the way to a standardized procedure

BackgroundRobot-assisted radical cystectomy (RARC) with intracorporeal diversion has been shown to be feasible in a few centers of excellence worldwide, with promising functional and oncologic outcomes. However, it remains unknown whether the complexity of the procedure allows its duplication in other non-pioneer centers. We attempt to address this issue by presenting our cumulative experience with RARC and intracorporeal neobladder formation.MethodsWe retrospectively identified 62 RARCs in 50 men and 12 women (mean age 63.6 years) in two tertiary centers. Intracorporeal Studer neobladders were created, duplicating the steps of standard open surgery. Perioperative and postoperative variables and complications were analyzed using standardized tools. Functional and oncological results were assessed.ResultsThe mean operative time was 476.9 min (range, 310 to 690) and blood loss was 385 ml (200 to 800). The mean hospital stay was 16.7 (12 to 62) days with no open conversion. Perioperative complications were grade II in 15, grade III in 11, and grade IV in 5 patients. The mean nodal yield was 22.9 (8 to 46). Positive margins were found in in 6.4%. The 90- and 180-day mortality rates were 0% and 3.3%. The average follow-up was 37.3 months (3 to 52). Continence was achieved in 88% of patients. The cancer-specific survival rate and overall survival rate were 84% and 71%, respectively.ConclusionsA RARC with intracorporeal neobladder creation is safe and reproducible in ‘non-pioneer’ tertiary centers with robotic expertise with acceptable operative time and complications. Further standardization of RARC with intracorporeal diversion is a prerequisite for its widespread use.

Early Recurrence Patterns Following Totally Intracorporeal Robot-assisted Radical Cystectomy: Results from the EAU Robotic Urology Section (ERUS) Scientific Working Group

Recurrence following radical cystectomy often occurs early, with >80% of recurrences occurring within the first 2 yr. Debate remains as to whether robot-assisted radical cystectomy (RARC) negatively impacts early recurrence patterns because of inadequate resection or pneumoperitoneum. We report early recurrence patterns among 717 patients who underwent RARC with intracorporeal urinary diversion at nine different institutions with a minimum follow-up of 12 mo. Clinical, pathologic, radiologic, and survival data at the latest follow-up were collected. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method, and Cox regression models were built to assess variables associated with recurrence. RFS at 3, 12, and 24 mo was 95.9%, 80.2%, and 74.6% respectively. Distant recurrences most frequently occurred in the bones, lungs, and liver, and pelvic lymph nodes were the commonest site of local recurrence. We identified five patients (0.7%) with peritoneal carcinomatosis and two patients (0.3%) with metastasis at the port site (wound site). We conclude that unusual recurrence patterns were not identified in this multi-institutional series and that recurrence patterns appear similar to those in open radical cystectomy series. PATIENT SUMMARY In this multi-institutional study, bladder cancer recurrences following robotic surgery are described. Early recurrence rates and locations appear to be similar to those for open radical cystectomy series.

Role of Rho-kinase in contractions of ureters from rabbits with unilateral ureteric obstruction

To investigate the expression of two isoforms of Rho‐kinase (ROCK) and its functional role in the pathophysiological control of smooth muscle contraction in rabbits with unilateral ureteric obstruction (UUO).

Open versus robotic radical cystectomy with intracorporeal Studer diversion.

Background and Objectives: To compare open versus totally intracorporeal robotic-assisted radical cystectomy, bilateral extended pelvic lymph node dissection, and Studer urinary diversion in bladder cancer patients. Methods: A retrospective comparison of open (n = 42) versus totally intracorporeal (n = 32) robotic-assisted radical cystectomy, bilateral extended pelvic lymph node dissection, and Studer urinary diversion was performed concerning patient demographic data, operative and postoperative parameters, pathologic parameters, complications, and functional outcomes. Results: Patient demographic data and the percentages of patients with pT2 disease or lower and pT3–pT4 disease were similar between groups (P > .05). Positive surgical margin rates were similar between the open (n = 1, 2.4%) and robotic (n = 2, 6.3%) groups (P > .05). Minor and major complication rates were similar between groups (P > .05). Mean estimated blood loss was significantly lower in the robotic group (412.5 ± 208.3 mL vs 1314.3 ± 987.1 mL, P < .001). Significantly higher percentages of patients were detected in the robotic group regarding bilateral neurovascular bundle–sparing surgery (93.7% vs 64.3%, P = .004) and bilateral extended pelvic lymph node dissection (100% vs 71.4%, P = .001). The mean lymph node yield was significantly higher in the robotic group (25.4 ± 9.7 vs 17.2 ± 13.5, P = .005). The number of postoperative readmissions for minor complications was significantly lower in the robotic group (0 vs 7, P = .017). Better trends were detected in the robotic group concerning daytime continence with no pad use (84.6% vs 75%, P > .05) and severe daytime incontinence (8.3% vs 16.6%, P > .05). No significant differences were detected regarding postoperative mean International Index of Erectile Function scores between groups (P > .05). Conclusions: Robotic surgery has the advantages of decreased blood loss, better preservation of neurovascular bundles, an increased lymph node yield, a decreased rate of hospital readmissions for minor complications, and a better trend for improved daytime continence when compared with the open approach.

Does diabetes affect the intensity of staining of interstitial cells and neuronal tissue in the bladder, prostate and urethra of rabbits?

We compared the intensity of staining of interstitial cells (ICs) and neural tissue in the lower urinary tract of rabbits with diabetes with the intensity in normal subjects. Diabetes was induced by injecting alloxane (65mg/kg) in adult male rabbits. After 3 days, rabbits with a blood glucose level >300 mg/dL were considered to have diabetes. After 8 weeks, the rabbits were killed, and tissue specimens from the bladder, prostate and urethra were obtained. ICs were stained with anti-human CD117 (c-kit) rabbit polyclonal antibody, and neural tissue was stained with synaptophysin. The streptavidin-biotin method was used for immunohistochemical staining. The intensity of c-kit and synaptophysin staining were scored as negative (0), weak (+), moderate (++), and strong (+++). Staining intensity of ICs and neural tissue was assessed and compared in tissues obtained from rabbits with diabetes (n=8) and from control subjects (n=7). Although staining intensity of both ICs and neural tissue was found to be significantly decreased in the bladder tissue of rabbits with diabetes compared to that in the control group (p=0.0001 [ICs] and p=0.021 [neural tissue]), no significant differences in staining intensity of ICs and neural tissue in the urethra and in the prostate was found when rabbits with diabetes were compared to the control group. Diabetes may cause dysfunction of the lower urinary tract, particularly in the urinary bladder, as shown by the staining intensity of ICs and neural tissue.