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INTRODUCTION: Robotic-assisted techniques are widespread in urology. However, prolonged preparation time for robotic cases hinders operating room (OR) efficiency and frustrates robotic surgeons. Pre-operative times are an opportunity for quality improvement (QI) and enhancing OR throughput. We have previously shown that pre-operative times in robotic cases are highly variable and that increasing patient complexity was associated with longer times. Our objective was to characterize set-up times in robotic urology cases and to determine whether prolongation was due to robot set-up, in particular. MATERIALS AND METHODS: Patients undergoing robotic-assisted urology procedures at our academic institution had routine peri-operative collection of demographic data and OR time stamps. Following IRB approval, we retrospectively reviewed set-up times from an OR database. Multivariable analysis was used to assess the influence of independent patient variables-gender (M/F), smoking history, age, BMI, American Society of Anesthesiologists (ASA) Physical Status Classification, and Charlson Comorbidity Index (CCI)-on robot set-up times. Institutional factors including procedure, surgeon, and case year were also assessed. RESULTS: A total of 808 patients undergoing 816 robotic-assisted procedures from 2013 to 2018 met inclusion criteria. Robot set-up times varied only by gender (F > M) but not by general patient complexity. Age, BMI, smoking status, ASA, and CCI did not play a role in prolonging robot set-up times. There was marked variability of robot set-up times, even within procedure type. Robot set-up times generally improved over time for a given surgeon. CONCLUSIONS: Robot set-up time is not affected by patient complexity, in contrast to pre-operative time. It is affected by procedure type and does improve with experience. There is wide variability of robot set-up times and this is an important target for surgical QI.

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Vitamin D3 and its receptor are responsible for controlling energy expenditure in adipocytes and have direct roles in the transcriptional regulation of energy metabolic pathways. This phenomenon also has a significant impact on the etiology of prostate cancer (PCa). Using several in vitro models, the roles of vitamin D3 on energy metabolism and its implication in primary, early, and late invasive PCa were investigated. BODIPY staining and qPCR analyses show that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates de novo lipogenesis in PCa cells by orchestrating transcriptional regulation that affects cholesterol and lipid metabolic pathways. This lipogenic effect is highly dependent on the interaction of several nuclear receptors and their corresponding ligands, including androgen receptor (AR), vitamin D receptor (VDR), and retinoid X receptor (RXR). In contrast, inhibition of peroxisome proliferator-activated receptor alpha (PPARα) signaling blocks the induction of the lipogenic phenotype induced by these receptors. Furthermore, 1,25(OH)2D3, T, and 9 cis-retinoic acid (9-cis RA) together redirect cytosolic citrate metabolism toward fatty acid synthesis by restoring normal prostatic zinc homeostasis that functions to truncate TCA cycle metabolism. 1,25(OH)2D3, T, and 9-cis RA also exert additional control of TCA cycle metabolism by down-regulating SLC25A19, which limits the availability of the co-factor thiamine pyrophosphate (TPP) that is required for enzymatic catalyzation of citrate oxidation. This extensive metabolic reprogramming mediated by 1,25(OH)2D3, T, and 9-cis RA is preserved in all in vitro cell lines investigated. These data suggest that 1,25(OH)2D3 and T are important regulators of normal prostatic energy metabolism. Based on the close association between energy metabolism and cancer progression, supplementation of vitamin D3 and testosterone can restrict the energy production that is required to drive PCa progression by maintaining proper zinc homeostasis and inhibiting TCA cycle activity in PCa cells.

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INTRODUCTION: Although not traditionally examined, the nonoperative time a patient spends in the operating room is potentially significant. We determined the role of patient and procedure specific characteristics in nonoperative times in urology cases. METHODS: All patients at our tertiary institution had routine preoperative collection of patient and procedure specific data. Following institutional review board approval, we retrospectively reviewed the time landmarks of preoperative operating room time (the time from when the patient enters the room until the procedure starts) and postoperative operating room time (the time from the procedure end until the patient exits the room). Study inclusion criteria consisted of ASA™ (American Society of Anesthesiologists™) class I-IV and those cases with complete available data. Emergency cases (ASA score greater than 4) were excluded from analysis. Multivariable regression was used to assess the influence of patient and procedure variables on preoperative and postoperative operating room time. RESULTS: A total of 1,488 patients undergoing 1,786 urology procedures during a 9-month period (January to September 2016) met inclusion criteria. Following multivariable analysis, ASA class and Charlson comorbidity index were significantly associated with an increase in preoperative time. The only variable that had a significant association with preoperative and postoperative times was location (hospital vs ambulatory). Procedure type also had a significant effect on perioperative operating room times. CONCLUSIONS: Our analysis is a novel approach to assessing operating room efficiency by characterizing the nonoperative time a patient spends in the operating room. Robotic cases have longer nonoperative times and increasing patient complexity prolongs preoperative time in the operating room. Better preparation of complex cases preoperatively will allow better use of constrained operating room resources.

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INTRODUCTION: Delayed bladder perforation is a well-described complication after augmentation cystoplasty. Although the frequency, risk factors, and diagnostic challenges are well documented, discussions regarding management strategies are sparse. OBJECTIVE: We evaluated our experience of managing augmented bladder perforation to interrogate the hypothesis that non-operative management can be used effectively. STUDY DESIGN: We retrospectively evaluated the management of 10 patients with augmented bladder perforations over a 16-year period (Jan 2000-Jan 2016). Patients who demonstrated clinical deterioration, severe peritonitis, or extensive extravasation on imaging underwent exploratory laparotomy and primary closure. Clinically stable patients with minimal extravasation were managed non-operatively with maximal bladder drainage, and those with loculated fluid collections in feasible locations for drainage underwent an image-guided percutaneous drain placement. RESULTS: Underlying diagnoses included four patients with myelomeningocele, three with sacral agenesis, two with spinal cord injuries, and one with bladder exstrophy. Three of the four patients with myelomeningocele had concomitant ventriculoperitoneal shunts. Six patients had continent catheterizable channel creation and two patients had bladder neck reconstructions during the original operation. Four patients were managed with exploratory laparotomy and primary closure. Among the six patients managed non-operatively, three underwent image-guided drain placement in addition to maximal bladder drainage. Four patients developed re-perforation. Two of the four surgically managed patients developed re-perforation. Two of the three patients managed only with maximal bladder drainage developed re-operation. None of the patients managed non-operatively with drain placement suffered from re-perforation. Four perforation episodes were alcohol-related, two occurred after high-impact sporting activity, and two patients reported non-compliant catheterization. DISCUSSION: Non-operative management with maximal bladder drainage and selective image-guided drain placement can be successfully deployed in clinically stable patients with limited extravasation. Ensuring low intraluminal detrusor pressures and empty bladder with maximal drainage is critical for spontaneous sealing of the perforation site. Exploratory laparotomy and primary closure remains our approach for those presenting with clinical deterioration or significant extravasation on imaging. The majority of our perforations and re-perforation episodes seemed to stem from preventable behavioral risk factors. CONCLUSIONS: Our findings support the hypothesis that non-operative management with maximal bladder drainage and image-guided drain placement can be effective in stable patients with limited extravasation.

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PURPOSE: We sought to gain insight into the outcomes of nontunical orchiopexy through assessment of elective and emergent orchiopexies performed by a single surgeon from 1985 to 2014. We demonstrate that successful orchiopexy does not require a fixation suture that pierces the tunica albuginea. MATERIALS AND METHODS: We retrospectively analyzed 1,104 orchiopexies in patients 1 day to 25 years old performed by a single urologist during a 29-year period. A total of 155 procedures were performed in 101 patients to remedy torsion, and 949 procedures were performed in 778 patients for undescended testes. The orchiopexy method for all patients was the same, involving no transparenchymal fixation suture. Operative notes, followup appointments and long-term testicular condition were analyzed. Appropriate testicular size and position were considered successful outcomes. Testicular atrophy, suprascrotal location, torsion and long-term pain were considered undesired outcomes. RESULTS: Of the 1,104 orchiopexy cases evaluated 1,090 were deemed successful, with normal testicular position and size postoperatively. A total of 14 testes in 8 patients showed undesired outcomes (postoperative atrophy in 4 testes, long-term pain in 2 and failure to retain appropriate position postoperatively in 8). CONCLUSIONS: Orchiopexy avoiding transparenchymal suturing through the tunica albuginea is a successful approach for fixation of the testis in the scrotum. Considering the high rate of favorable outcomes with this technique, and assuming that tunical invasion negatively impacts spermatogenesis, we consider a tunical suture unnecessary.

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INTRODUCTION: While SLN biopsy is recommended for melanoma ≥1 mm in depth, its use among the elderly population is more controversial. We reviewed our experience at the University of Michigan with melanoma patients ≥75 years of age. METHODS: A total of 952 melanoma patients ≥75 years of age from 1996 to 2011 were identified from our institutional review board-approved database. In addition to clinicopathologic features and outcome data, comorbidity data were collected to calculate the Charlson comorbidity index (CCI). Univariate and multivariate Cox regression analysis was performed to characterize predictors of outcome. Kaplan-Meier analysis was used to generate survival curves. RESULTS: Among 553 clinically node-negative patients with melanoma ≥1 mm in Breslow thickness, 213 had wide excision alone, whereas 340 had excision and SLN biopsy, with 83 (24 %) having a positive SLN. SLN biopsy was less likely with older age (p < 0.0001) and H&N location (p = 0.007), but not CCI. SLN involvement was associated with female gender [odds ratio (OR) 2.15, p = 0.009], Breslow thickness [OR 1.23/mm increase, p = 0.004], and satellitosis (OR 4.43, p = 0.004). Distant disease-specific survival was negatively associated with male gender (OR 1.5, p = 0.007), increasing age (OR 1.05/year, p < 0.001), increasing Breslow thickness (OR 1.07/year, p = 0.013), ulceration (OR 1.51, p = 0.004), a positive SLN (OR 2.61, p < 0.001), and not having a SLN biopsy (OR 1.72, p < 0.001). CCI did not predict worse disease-free or melanoma-specific survival. CONCLUSIONS: WLE and SLN biopsy was not only strongly prognostic, but compared with WLE alone was associated with improved outcome, even after factoring for age and comorbidities. If otherwise healthy, SLN biopsy should be strongly considered for this population.

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OBJECTIVE: Ureteroscopic lithotripsy (URSL) is believed to be associated with less risk of symptomatic renal hematoma than extracorporeal shockwave lithotripsy (SWL) and percutaneous nephrolithotomy (PCNL). We sought to document the rate of and risk factors for this rare complication following URSL for renal calculi. METHODS: With Institutional Review Board approval, we reviewed 1087 cases of URSL performed between July 2009 and October 2012 for four surgeons. We identified cases for renal calculi complicated by symptomatic "hematoma" by searching electronic medical records of patients undergoing URSL with a web-based search tool and cross-referencing with a departmental quality improvement database for postoperative complications. Chi-squared tests were used to assess risk factors. RESULTS: Among 877 renal units exposed to URSL for renal calculi, 4 were complicated by symptomatic subcapsular hematomas (SH) and 3 by symptomatic perinephric hematomas (PH), yielding a 0.5% and 0.3% rate for each complication, respectively. Pain was the primary presenting symptom. Almost all cases presented within 24 to 48 hours postop. Two PH patients required postoperative blood transfusion. Four patients (two SH, two PH) were hospitalized for observation. Ureteral sheaths were used in two cases (one PH and one SH). There was no association with age, diabetes, body mass index (BMI), or operative duration (p-values all>0.05). However, hematoma did correlate with female gender, preoperative hypertension, preoperative ureteral stenting, intraoperative ureteral sheath use, and postoperative ureteral stenting (all p-values<0.0001). CONCLUSIONS: While symptomatic hematoma is a complication of URSL, the rate of such outcome (0.8%) is far less than that reported by prior series with SWL and PCNL. This may partially be attributable to collection biases, where subclinical cases are not imaged, or anchoring biases, where clinicians attribute symptoms to another possible etiology. This outcome can be morbid, but can often be conservatively managed with observation.

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Voltage-gated Na(+) channels (VGSCs) are heteromeric membrane protein complexes containing pore-forming α subunits and smaller, non-pore-forming ß subunits. VGSCs are classically expressed in excitable cells, including neurons and muscle cells, where they mediate action potential firing, neurite outgrowth, pathfinding, and migration. VGSCs are also expressed in metastatic cells from a number of cancers. The Na(v)1.5 α subunit (encoded by SCN5A) is expressed in breast cancer (BCa) cell lines, where it enhances migration and invasion. We studied the expression of SCN5A in BCa array data, and tested the effect of the VGSC-blocking anticonvulsant phenytoin (5,5-diphenylhydantoin) on Na(+) current, migration, and invasion in BCa cells. SCN5A was up-regulated in BCa samples in several datasets, and was more highly expressed in samples from patients who had a recurrence, metastasis, or died within 5 years. SCN5A was also overexpressed as an outlier in a subset of samples, and associated with increased odds of developing metastasis. Phenytoin inhibited transient and persistent Na(+) current recorded from strongly metastatic MDA-MB-231 cells, and this effect was more potent at depolarized holding voltages. It may thus be an effective VGSC-blocking drug in cancer cells, which typically have depolarized membrane potentials. At a concentration within the therapeutic range used to treat epilepsy, phenytoin significantly inhibited the migration and invasion of MDA-MB-231 cells, but had no effect on weakly metastatic MCF-7 cells, which do not express Na(+) currents. We conclude that phenytoin suppresses Na(+) current in VGSC-expressing metastatic BCa cells, thus inhibiting VGSC-dependent migration and invasion. Together, our data support the hypothesis that SCN5A is up-regulated in BCa, favoring an invasive/metastatic phenotype. We therefore propose that repurposing existing VGSC-blocking therapeutic drugs should be further investigated as a potential new strategy to improve patient outcomes in metastatic BCa.

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