Systematic Review and Cumulative Analysis of Oncologic and Functional Outcomes After Robot-assisted Radical Cystectomy

CONTEXT Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly performed. OBJECTIVE To report on a systematic literature review and cumulative analysis of pathologic, oncologic, and functional outcomes of RARC in comparison with ORC and LRC. EVIDENCE ACQUISITION Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy. RARC case series and studies comparing RARC with either ORC or LRC were collected. A cumulative analysis was conducted. EVIDENCE SYNTHESIS The searches retrieved 105 papers, 87 of which reported on pathologic, oncologic, or functional outcomes. Most series were retrospective and had small case numbers, short follow-up, and potential patient selection bias. The lymph node yield during lymph node dissection was 19 (range: 3-55), with half of the series following an extended template (yield range: 11-55). The lymph node-positive rate was 22%. The performance of lymphadenectomy was correlated with surgeon and institutional volume. Cumulative analyses showed no significant difference in lymph node yield between RARC and ORC. Positive surgical margin (PSM) rates were 5.6% (1-1.5% in pT2 disease and 0-25% in pT3 and higher disease). PSM rates did not appear to decrease with sequential case numbers. Cumulative analyses showed no significant difference in rates of surgical margins between RARC and ORC or RARC and LRC. Neoadjuvant chemotherapy use ranged from 0% to 31%, with adjuvant chemotherapy used in 4-29% of patients. Only six series reported a mean follow-up of >36 mo. Three-year disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates were 67-76%, 68-83%, and 61-80%, respectively. The 5-yr DFS, CSS, and OS rates were 53-74%, 66-80%, and 39-66%, respectively. Similar to ORC, disease of higher pathologic stage or evidence of lymph node involvement was associated with worse survival. Very limited data were available with respect to functional outcomes. The 12-mo continence rates with continent diversion were 83-100% in men for daytime continence and 66-76% for nighttime continence. In one series, potency was recovered in 63% of patients who were evaluable at 12 mo. CONCLUSIONS Oncologic and functional data from RARC remain immature, and longer-term prospective studies are needed. Cumulative analyses demonstrated that lymph node yields and PSM rates were similar between RARC and ORC. Conclusive long-term survival outcomes for RARC were limited, although oncologic outcomes up to 5 yr were similar to those reported for ORC. PATIENT SUMMARY Although open radical cystectomy (RC) is still regarded as the standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RCs are becoming more popular. Templates of lymph node dissection, lymph node yields, and positive surgical margin rates are acceptable with robot-assisted RC. Although definitive comparisons with open RC with respect to oncologic or functional outcomes are lacking, early results appear comparable.

Superior functional outcome after radical cystectomy and orthotopic bladder substitution with restrictive intraoperative fluid management: a followup study of a randomized clinical trial

PURPOSE Continuous intraoperative norepinephrine infusion combined with restrictive deferred hydration improves surgical field visibility, and significantly decreases intraoperative blood loss and postoperative complications in patients undergoing radical cystectomy and urinary diversion. We determined whether the intraoperative fluid regimen would affect functional results (continence and erectile function) 1 year after orthotopic ileal bladder substitution. MATERIALS AND METHODS We analyzed a subgroup of 93 patients who received an ileal orthotopic bladder substitute. The subgroup was part of a randomized trial in 167 patients initially allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour initially and 3 ml/kg per hour crystalloid infusion after cystectomy (norepinephrine/low volume group of 51) or a standard crystalloid infusion of 6 ml/kg per hour throughout surgery (42 controls). We prospectively assessed daytime and nighttime continence, and erectile function 1 year postoperatively in the 93-patient subgroup. RESULTS Daytime continence was reported by 44 of 51 patients (86%) in the norepinephrine/low volume group and by 27 of 42 controls (64%) (p = 0.016), and nighttime continence was reported by 38 (75%) and 25 (60%), respectively (p = 0.077). Erectile function recovery was reported by 26 of 33 preoperatively potent patients (79%) in the norepinephrine/low volume group and by 11 of 29 controls (38%) (p = 0.002). CONCLUSIONS Patients who undergo radical cystectomy and orthotopic bladder substitution with continuous norepinephrine infusion and restrictive hydration during surgery have significantly better daytime continence and erectile function 1 year postoperatively.

There is a place for radical cystectomy and urinary diversion, including orthotopic bladder substitution, in patients aged 75 and older: Results of a retrospective observational analysis from a high-volume center

INTRODUCTION The incidence of cancer increases with age and owing to the changing demographics we are increasingly confronted with treating bladder cancer in old patients. We report our results in patients>75 years of age who underwent open radical cystectomy (RC) and urinary diversion. MATERIAL AND METHODS From January 2000 to March 2013, a consecutive series of 224 old patients with complete follow-up who underwent RC and urinary diversion (ileal orthotopic bladder substitute [OBS], ileal conduit [IC], and ureterocutaneostomy [UCST]) were included in this retrospective single-center study. End points were the 90-day complication rates (Clavien-Dindo classification), 90-day mortality rates, overall and cancer-specific survival rates, and continence rates (OBS). RESULTS Median age was 79.2 years (range: 75.1-91.6); 35 of the 224 patients (17%) received an OBS, 178 of the 224 patients (78%) an IC, and 11 of the 224 patients (5%) an UCST. The 90-day complication rate was 54.3% in the OBS (major: Clavien grade 3-5: 22.9%, minor: Clavien Grade 1-2: 31.4%), 56.7% in the IC (major: 27%, minor: 29.8%), and 63.6% in the UCST group (major: 36.4%, minor: 27.3%); P = 0.001. The 90-day mortality was 0% in the OBS group, 13% in the IC group, and 10% in the UCST group (P = 0.077). The Glasgow prognostic score was an independent predictor of all survival parameters assessed, including 90-day mortality. Median follow-up was 22 months. Overall and cancer-specific survivals were 90 and 98, 47 and 91, and 11 and 12 months for OBS, IC, and UCST, respectively. In OBS patients, daytime continence was considered as dry in 66% and humid in 20% of patients. Nighttime continence was dry in 46% and humid 26% of patients. CONCLUSION With careful patient selection, oncological and functional outcome after RC can be good in old patients. Old age as the sole criterion should not preclude the indication for RC or the option of OBS. In old patients undergoing OBS, satisfactory continence results can be achieved.

CYP17A1 Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based Population Study

BACKGROUND Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17α-hydroxylase (CYP17A1) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family-based population study and estimated the heritability of CYP17A1 activity. METHODS In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed CYP17A1 activities exploring effect modification by urinary sodium excretion. RESULTS Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night CYP17A1 activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 (P values <0.001). CYP17A1 activities, assessed with ratio 1, were lower in older participants. CONCLUSIONS Low apparent CYP17A1 activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of CYP17A1 with BP.

Continuous CO2/CH4/CO measurements (2012–2014) at Beromünster tall tower station in Switzerland

The understanding of the continental carbon budget is essential to predict future climate change. In order to quantify CO₂ and CH₄ fluxes at the regional scale, a measurement system was installed at the former radio tower in Beromünster as part of the Swiss greenhouse gas monitoring network (CarboCount CH). We have been measuring the mixing ratios of CO₂, CH₄ and CO on this tower with sample inlets at 12.5, 44.6, 71.5, 131.6 and 212.5 m above ground level using a cavity ring down spectroscopy (CRDS) analyzer. The first 2-year (December 2012–December 2014) continuous atmospheric record was analyzed for seasonal and diurnal variations and interspecies correlations. In addition, storage fluxes were calculated from the hourly profiles along the tower. The atmospheric growth rates from 2013 to 2014 determined from this 2-year data set were 1.78 ppm yr⁻¹, 9.66 ppb yr⁻¹ and and -1.27 ppb yr⁻¹ for CO₂, CH₄ and CO, respectively. After detrending, clear seasonal cycles were detected for CO₂ and CO, whereas CH₄ showed a stable baseline suggesting a net balance between sources and sinks over the course of the year. CO and CO₂ were strongly correlated (r² > 0.75) in winter (DJF), but almost uncorrelated in summer. In winter, anthropogenic emissions dominate the biospheric CO₂ fluxes and the variations in mixing ratios are large due to reduced vertical mixing. The diurnal variations of all species showed distinct cycles in spring and summer, with the lowest sampling level showing the most pronounced diurnal amplitudes. The storage flux estimates exhibited reasonable diurnal shapes for CO₂, but underestimated the strength of the surface sinks during daytime. This seems plausible, keeping in mind that we were only able to calculate the storage fluxes along the profile of the tower but not the flux into or out of this profile, since no Eddy covariance flux measurements were taken at the top of the tower.

Sleep-wake disorders persist 18 months after traumatic brain injury but remain underrecognized

OBJECTIVE This study is a prospective, controlled clinical and electrophysiologic trial examining the chronic course of posttraumatic sleep-wake disturbances (SWD). METHODS We screened 140 patients with acute, first-ever traumatic brain injury of any severity and included 60 patients for prospective follow-up examinations. Patients with prior brain trauma, other neurologic or systemic disease, drug abuse, or psychiatric comorbidities were excluded. Eighteen months after trauma, we performed detailed sleep assessment in 31 participants. As a control group, we enrolled healthy individuals without prior brain trauma matched for age, sex, and sleep satiation. RESULTS In the chronic state after traumatic brain injury, sleep need per 24 hours was persistently increased in trauma patients (8.1 ± 0.5 hours) as compared to healthy controls (7.1 ± 0.7 hours). The prevalence of chronic objective excessive daytime sleepiness was 67% in patients with brain trauma compared to 19% in controls. Patients significantly underestimated excessive daytime sleepiness and sleep need, emphasizing the unreliability of self-assessments on SWD in trauma patients. CONCLUSIONS This study provides prospective, controlled, and objective evidence for chronic persistence of posttraumatic SWD, which remain underestimated by patients. These results have clinical and medicolegal implications given that SWD can exacerbate other outcomes of traumatic brain injury, impair quality of life, and are associated with public safety hazards.