The impact of cardiopulmonary exercise testing (CPET) and Charlson comorbidity index (CCI) in a large contemporary cohort of patients undergoing robot-assisted radical cystectomy and intracorporeal urinary diversion (RARC-ICUD).

Objective: The aim of this study was to investigate whether pre-operative comorbidity status measured by the Charlson comorbidity index (CCI) or cardiopulmonary exercise testing (CPET) is associated with postoperative complications and length of stay (LOS) in patients undergoing robot-assisted radical cystectomy and intracorporeal urinary diversion (RARC-ICUD). Patients and methods: We conducted a retrospective study of a prospectively maintained database of 428 consecutive patients who underwent RARC-ICUD at a tertiary referral centre between 2011 and 2019. CCI was correlated with peri-operative outcomes including postoperative LOS, Clavien-Dindo (CD) complications and survival. A planned subgroup analysis was performed to evaluate the relationship between pre-operative CPET, and the same outcomes utilising the threshold of anaerobic threshold (AT) ≥ 11/ <11 ml/kg/min were analysed. Results: Of the total cohort, 350 patients undergoing RARC-ICUD with complete data were included in the final analysis. A CCI score ≥5 was associated with a higher rate of CD III-V complications at 30-day incidence rate ratio (IRR) = 3.033, (p = 0.02) and at 90-day IRR 2.495, (p = 0.04) postsurgery. LOS was not associated with CCI; the strongest association with LOS was a CD complication of any grading. CCI did not predict readmission or mortality rates after surgery. Subanalyses of patients who underwent pre-operative CPET found that CPET <11 ml/kg/min did not predict for LOS, CD complications or death within 1 year of surgery. Conclusions: CCI score is a simple, reliable and cost-effective way of identifying patients at increased risk of complication after RARC-ICUD. Surgeons performing radical cystectomy should consider utilising CCI to augment pre-operative patient counselling prior to RARC-ICUD.

Expanding the indications of robotic surgery in urology: A systematic review of the literature.

OBJECTIVES: To evaluate the recent developments in robotic urological surgery, as the introduction of robotic technology has overcome many of the difficulties of pure laparoscopic surgery enabling surgeons to perform complex minimally invasive procedures with a shorter learning curve. Robot-assisted surgery (RAS) is now offered as the standard for various surgical procedures across multiple specialities. METHODS: A systematic search of MEDLINE, PubMed and EMBASE databases was performed to identify studies evaluating robot-assisted simple prostatectomy, salvage radical prostatectomy, surgery for urolithiasis, distal ureteric reconstruction, retroperitoneal lymph node dissection, augmentation ileocystoplasty, and artificial urinary sphincter insertion. Article titles, abstracts, and full text manuscripts were screened to identify relevant studies, which then underwent data extraction and analysis. RESULTS: In all, 72 studies evaluating the above techniques were identified. Almost all studies were retrospective single-arm case series. RAS appears to be associated with reduced morbidity, less blood loss, reduced length of stay, and comparable clinical outcomes in comparison to the corresponding open procedures, whilst having a shorter operative duration and learning curve compared to the equivalent laparoscopic techniques. CONCLUSION: Emerging data demonstrate that the breadth and complexity of urological procedures performed using the da Vinci® platform (Intuitive Surgical Inc., Sunnyvale, CA, USA) is continually expanding. There is a gaining consensus that RAS is producing promising surgical results in a wide range of procedures. A major limitation of the current literature is the sparsity of comparative trials evaluating these procedures.

Concurrent upper and lower urinary tract robotic surgery: A case series.

The da Vinci Surgical System (Intuitive Surgical Inc.) continues to develop as a platform in urological surgery. Synchronous upper and lower urinary tract tumours requiring extirpative surgery are not uncommon. We report the first case robotic series of combined complex upper and lower urinary tract surgery. Six high-risk anaesthetic patients with a median age of 71 years and apparent synchronous upper and lower urinary tract pathologies underwent concurrent robotic surgery. Five underwent robotic nephroureterectomy and robotic-assisted radical cystectomy (RARC); 1 had combined robotic nephroureterectomy and robotic-assisted radical prostatectomy (RALP). The mean length of stay was 10 days, with an average blood loss of 416.7 mL. The median console time for nephroureterectomy, RALP and RARC was 90, 90 and 210 minutes, respectively. Four patients had intra-corporeal ileal conduit urinary diversion. There were no Clavien grade 3, 4, or 5 complications. In all patients, 30- and 90-day mortality was nil. Margins were clear in the entire cohort. We concluded that combined upper and lower urinary tract robotic surgery is safe and technically feasible with acceptable complications and oncological outcomes.

Enhanced recovery after surgery (ERAS) protocols: Time to change practice?

Radical cystectomy with pelvic lymph node dissection remains the standard treatment for patients with muscle invasive bladder cancer. Despite improvements in surgical technique, anesthesia and perioperative care, radical cystectomy is still associated with greater morbidity and prolonged in-patient stay after surgery than other urological procedures. Enhanced recovery after surgery (ERAS) protocols are multimodal perioperative care pathways designed to achieve early recovery after surgical procedures by maintaining preoperative organ function and reducing the profound stress response following surgery. The key elements of ERAS protocols include preoperative counselling, optimization of nutrition, standardized analgesic and anesthetic regimens and early mobilization. Despite the significant body of evidence indicating that ERAS protocols lead to improved outcomes, they challenge traditional surgical doctrine, and as a result their implementation has been slow.The present article discusses particular aspects of ERAS protocols which represent fundamental shifts in surgical practice, including perioperative nutrition, management of postoperative ileus and the use of mechanical bowel preparation.

Radical prostatectomy for high-risk clinically localized prostate cancer: a prospective single institution series.

OBJECTIVE: The objective of this paper is to report on the pathologic and biochemical progression-free outcomes of patients who underwent radical prostatectomy for high-risk localized prostate cancer. METHODS: Data was collected prospectively from 299 patients who underwent radical prostatectomy for high-risk clinically localized prostate cancer by 2 surgeons at a single institution. High risk was defined as 1 or more of 3 adverse factors: prostate-specific antigen (PSA) >20, biopsy Gleason score 8 to 10 and clinical stage T3. PSA recurrence was defined as PSA >0.4 ng/mL or any salvage therapy. RESULTS: Median age was 63.3 years (46.1-75.9). Median follow-up was 4.7 years (range 0.5-17.3 years). PSA at diagnosis was >20 ng/mL in 31.4%. Biopsy Gleason score was 8 to 10 in 66.9%. Clinical stage was T3 in 24.4%. 81.6% of patients had a single baseline risk factor, 15.7% had 2 risk factors and 2.7% had all 3 risk factors. Neoadjuvant therapy was administered to 184 patients (61.5%). Pathologic stage was organ-confined in 39.6%, specimen-confined in 26%, non-specimen-confined in 26.4%, and 8% had lymph node positive disease. Overall survival, cancer-specific survival and biochemical progression-free survival was 99%, 99.67% and 70.2%, respectively. Univariate analysis showed that PSA at diagnosis, percentage of cores positive and number of risk factors were predictors of PSA recurrence (p < 0.05). Multivariate analysis showed that PSA at diagnosis was an independent predictor of PSA recurrence (p < 0.05). CONCLUSION: Radical prostatectomy is associated with favourable biochemical progression-free, clinical and overall survival in selected men with high-risk localized prostate cancer, and should therefore be considered an option in these patients. Baseline PSA >20 ng/mL is a significant independent predictor of PSA recurrence.

Penicillamine administration reverses the inhibitory effect of hyperhomocysteinaemia on endothelium-dependent relaxation in the corpus cavernosum in the rabbit.

OBJECTIVE: To elucidate the role of copper in mediating the impact of homocysteine on vasculogenic erectile dysfunction (VED), by investigating the effect of dietary supplementation with the copper-chelator penicillamine to rabbits rendered hyperhomocysteinaemic (HHC) with a methionine-rich diet, as a raised plasma level of homocysteine might be a risk factor for VED. MATERIALS AND METHODS: Homocysteine inhibits the nitric oxide (NO)-dependent relaxation of the corpus cavernosum (CC), an effect which appears to be mediated via the generation of superoxide (O2*-), and H2O2. Copper is a catalyst for the generation of H2O2 in the presence of homocysteine and in the presence of copper, H2O2 undergoes reactions resulting in the generation of O2*-, which reacts with NO to produce peroxynitrite (ONOO-), thereby reducing the bioavailability of NO and impairing NO-mediated relaxation of CC. Smooth muscle strips from CC were obtained from two groups of adult New Zealand White rabbits, one rendered HHC with a diet supplemented with methionine (group 1) and another HHC group that had additional dietary supplementation with penicillamine (group 2). Tissue O2*- levels were measured in each group. After pre-contraction with phenylephrine, relaxation responses of CC strips to carbachol were also assessed in both groups. RESULTS: Methionine supplementation led to profound HHC in all rabbits. Penicillamine in group 2 reduced the total plasma Cu2+ compared to group 1. There was a markedly lower carbachol-stimulated relaxation of CC from HHC rabbits in group 1, with a mean (sem) maximum relaxation of 37 (4)% (six samples), than in group 2, at 58 (6)%. CONCLUSION: These data show that elevated levels in vivo of homocysteine in the rabbit markedly impair NO-dependent relaxation of the CC. Furthermore, this effect appears to be augmented by copper. Further clinical studies on homocysteine and copper status in patients with VED are warranted.

Sildenafil inhibits the formation of superoxide and the expression of gp47 NAD[P]H oxidase induced by the thromboxane A2 mimetic, U46619, in corpus cavernosal smooth muscle cells.

OBJECTIVE: To assess the effect of sildenafil on superoxide formation and p47(phox) (the active subunit of NADPH oxidase) expression in cultured corpus cavernosal smooth muscle cells (CVSMCs). MATERIALS AND METHODS: CVSMCs derived from rabbit penis were incubated with U46619 (thromboxane A2 analogue) with or without sildenafil for 1 or 16 h at 37 degrees C. Superoxide dismutase-inhibitable superoxide formation was assessed using the reduction of ferricytochrome c measured spectrophotometrically, and gp47(phox) assessed using Western blot analysis. The role of NAD[P]H oxidase and cGMP was further studied by using specific inhibitors of each. RESULTS: Superoxide formation was significantly greater in cells incubated with U46619 after 1 and 16 h incubation than in controls, an effect blocked by NADP(H) oxidase inhibitors. These effects of U46619 were inhibited by sildenafil (1 and 10 nmol/L), which in turn were negated by the guanylyl cyclase inhibitor, ODQ; 10 nmol/L sildenafil inhibited p47phox expression induced by U46619. CONCLUSIONS: Sildenafil is a potent inhibitor of superoxide formation in CVSMCs. This effect is mediated through the inhibition of PDE-5 which in turn augments the inhibitory action of the NO-cGMP axis on NAD[P]H oxidase expression and activity. This mechanism constitutes a new pharmacological action of sildenafil, consolidates the potential role of superoxide in ED, and indicates that thromboxane A(2) may be an important mediator of intrapenile oxidative stress.