'Pseudo' pseudoaneurysm following robotic assisted partial nephrectomy.

A 65-year-old female presented to clinic requesting follow up for a history of right robotic partial nephrectomy done at an outside institution 2 years prior. Initial pathology demonstrated a grade 2/4 3.4 cm clear cell renal cell carcinoma with negative margins. There was no tumor necrosis, sarcomatoid differentiation, or lymphovascular invasion. High quality follow up imaging initially revealed a pseudoaneurysm in the central portion of the right kidney. The patient was sent to interventional radiology for angioembolization. Angiography identified the abnormality to be a recurrent or residual mass in the renal hilum. MRI confirmed these findings, and the patient ultimately required a laparoscopic radical nephrectomy for definitive treatment. Final pathology showed grade 2/4 clear cell renal cell carcinoma with negative margins and no tumor necrosis or sarcomatoid differentiation. The tumor did involve sinus fat and sinus vessels, but not perinephric fat.

Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on tyrosine hydroxylase and alpha-synuclein in human neuroblastoma SH-SY5Y cells.

Evidence suggests that environmental and dietary factors may contribute to the pathogenesis of Parkinson's disease (PD). High dietary intake of cholesterol is such a factor that has been shown to increase or decrease the risk of PD. However, because circulating cholesterol does not cross the blood-brain barrier, the mechanisms linking dietary cholesterol to the pathogenesis of PD remain to be understood. In contrast to cholesterol, the oxidized cholesterol metabolites (oxysterols), 24S-hydroxycholesterol (24-OHC) and 27-hydroxycholesterol (27-OHC), can cross the blood-brain barrier and may place the brain at risk of degeneration. In this study, we incubated the human neuroblastoma SH-SY5Y cells for 24 h with 24-OHC, 27-OHC, or a mixture of 24-OHC plus 27-OHC, and have determined effects on tyrosine hydroxylase (the rate-limiting enzyme in dopamine synthesis) levels, alpha-synuclein levels, and apoptosis. We demonstrate that while 24-OHC increases the levels of tyrosine hydroxylase, 27-OHC increases levels of alpha-synuclein, and induces apoptosis. Our findings show for the first time that oxysterols trigger changes in levels of proteins that are associated with the pathogenesis of PD. As steady state levels of 24-OHC and 27-OHC are tightly regulated in the brain, disturbances in these levels may contribute to the pathogenesis of PD.

Hypercholesterolemia-induced Abeta accumulation in rabbit brain is associated with alteration in IGF-1 signaling.

Hypercholesterolemia increases levels of beta-amyloid (Abeta), a peptide that accumulates in Alzheimer's disease brains. Because cholesterol in the blood does not cross the blood brain barrier (BBB), the link between circulating cholesterol and Abeta accumulation is not understood. In contrast to cholesterol, the oxidized cholesterol metabolite 27-hydroxycholesterol can cross the BBB, potentially increasing Abeta levels. However, the mechanisms by which cholesterol or 27-hydroxycholesterol regulate Abeta levels are not known. The insulin-like growth factor-1 (IGF-1) regulates the glycogen-synthase kinase-3alpha (GSK-3alpha) and the insulin degrading enzyme (IDE). While GSK-3alpha increases Abeta production, IDE is a major Abeta-degrading enzyme. We report here that feeding rabbits with a cholesterol-enriched diet increases Abeta levels in the hippocampus, an effect that is associated with reduced IGF-1 levels. 27-hydroxycholesterol also increases Abeta and reduces IGF-1 levels in organotypic hippocampal slices from adult rabbits. We suggest that hypercholesterolemia-induced Abeta accumulation may be mediated by 27-hydroxycholesterol, involving IGF-1 signaling.

Regulation of beta-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease.

Accumulation of beta-amyloid (Abeta) peptide in the brain is a major hallmark of Alzheimer's disease (AD). Hypercholesterolemia is a risk factor for AD and has been shown by laboratory studies to cause Abeta accumulation. Abeta levels in the brain are governed by its generation from amyloid precursor protein by beta-secretase (BACE1), degradation by the insulin degrading enzyme (IDE), clearance from the brain by the low density lipoprotein receptor-related protein (LRP-1), and transport from circulation into the brain by receptor for advanced glycation end products (RAGE). However, the mechanisms by which hypercholesterolemia causes Abeta accumulation in the brain and contributes to the pathogenesis of AD are still to be determined. In the present study, we determined the extent to which hypercholesterolemia-induced Abeta accumulation is associated with alterations in BACE1, IDE, LRP-1, and RAGE expression levels. We show that hypercholesterolemia increases Abeta production, an effect that is associated with increased levels of BACE1 and RAGE and reduced levels of IDE and LRP-1. These results suggest that reducing Abeta accumulation in the brain may require strategies that combine reduction of generation and transport of Abeta in addition to acceleration of degradation and clearance of this peptide.

Diffusion of Robotic Technology Into Urologic Practice has Led to Improved Resident Physician Robotic Skills.

OBJECTIVE: To investigate whether propagation of robotic technology into urologic practice and training programs has improved baseline urology resident trainee robotic skills. DESIGN: Questionnaires were completed by each urology resident trainee participating in a training course and asked about access to robotic simulation, robot experience, and console time. Baseline resident trainee scores on the Mimic Robotic Simulator (Mimic Technologies, Inc., Seattle, WA) from 27 participants of 2012 course were compared with the 2015 scores of 34 trainees on 4 standard Mimic exercises using Wilcoxon rank-sum tests. p = 0.05 or less were considered statistically significant. PARTICIPANTS AND SETTING: Totally, 34 resident trainees from 17 programs in the Southeast Section of the American Urological Association participated in an annual 2-day robotic training course. RESULTS: Overall score, economy of motion score, and time to complete exercise were all significantly better in the 2015 trainee group compared with the 2012 trainee group (p < 0.001) for the Peg Board 1, Camera Targeting 2, and Energy Dissection exercises. Overall scores for needle targeting improved between 2012 and 2015 (p = 0.04). Trainee access to a simulator was not associated with overall score on any of the 4 exercises in the 2015 group. In the 2015 group, actual robotic console time was associated with better overall scores in Camera Targeting 2 (p = 0.02) and Peg Board 1 (p = 0.04). CONCLUSIONS: Baseline resident trainee performance on basic robotic simulator exercises has improved over the past 3 years irrespective of robotic simulator access or console time.

Impact of Resident Involvement on Robot-Assisted Radical Prostatectomy Outcomes.

OBJECTIVE: This study examines perioperative outcomes of resident involvement during various steps of robot-assisted radical prostatectomy (RARP). METHODS: The RARP procedure was divided into seven steps: bladder takedown (BTD), endopelvic fascia, bladder neck (BN), seminal vesicle/vas deferens, pedicle/nerve sparing, apex, and anastomosis. Three hundred seventy-two RARPs performed by a single surgeon were analyzed. Resident console time during each of the seven steps was recorded. Perioperative variables were compared to surgeon-only cases. RESULTS: Residents performed on the console for 232 of 372 cases (62.4%). Estimated blood loss (p = 0.09), transfusion (p = 0.11), and complications (p = 0.33) were no different between surgeon-only and resident-involved cases. Mean operating room time (ORT) was less for the surgeon-only cases (190.4 vs 206.4 minutes, p = 0.003). There was no difference in positive margins (p = 0.79), length of stay (LOS) (p = 0.30), catheter days (p = 0.17), readmission (p = 0.33), or reoperation (p = 0.73) when comparing surgeon-only to resident-involved cases. Residents performing the BN step had no effect on BN margins (p = 0.73) or prolonged catheterization (p = 0.62). ORT was significantly prolonged if BTD was performed by a resident (233.0 vs 191.7 minutes, p < 0.0001). Residents performing anastomosis had no effect on prolonged catheter time (p = 0.62) or LOS (p = 0.20). Residents were more likely to be involved in at least one portion of RARP following the purchase of a Mimic simulator (Mimic Technologies, Inc., Seattle, WA) in January 2012. CONCLUSIONS: Supervised resident console involvement in RARP does not affect perioperative outcomes, although, it prolongs ORT, with the BTD step having the most effect on ORT.

Urology residents experience comparable workload profiles when performing live porcine nephrectomies and robotic surgery virtual reality training modules.

In pursuit of improving the quality of residents' education, the Southeastern Section of the American Urological Association (SES AUA) hosts an annual robotic training course for its residents. The workshop involves performing a robotic live porcine nephrectomy as well as virtual reality robotic training modules. The aim of this study was to evaluate workload levels of urology residents when performing a live porcine nephrectomy and the virtual reality robotic surgery training modules employed during this workshop. Twenty-one residents from 14 SES AUA programs participated in 2015. On the first-day residents were taught with didactic lectures by faculty. On the second day, trainees were divided into two groups. Half were asked to perform training modules of the Mimic da Vinci-Trainer (MdVT, Mimic Technologies, Inc., Seattle, WA, USA) for 4 h, while the other half performed nephrectomy procedures on a live porcine model using the da Vinci Si robot (Intuitive Surgical Inc., Sunnyvale, CA, USA). After the first 4 h the groups changed places for another 4-h session. All trainees were asked to complete the NASA-TLX 1-page questionnaire following both the MdVT simulation and live animal model sessions. A significant interface and TLX interaction was observed. The interface by TLX interaction was further analyzed to determine whether the scores of each of the six TLX scales varied across the two interfaces. The means of the TLX scores observed at the two interfaces were similar. The only significant difference was observed for frustration, which was significantly higher at the simulation than the animal model, t (20) = 4.12, p = 0.001. This could be due to trainees' familiarity with live anatomical structures over skill set simulations which remain a real challenge to novice surgeons. Another reason might be that the simulator provides performance metrics for specific performance traits as well as composite scores for entire exercises. Novice trainees experienced substantial mental workload while performing tasks on both the simulator and the live animal model during the robotics course. The NASA-TLX profiles demonstrated that the live animal model and the MdVT were similar in difficulty, as indicated by their comparable workload profiles.

Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on beta-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells.

BACKGROUND: Activation of the liver x receptors (LXRs) by exogenous ligands stimulates the degradation of beta-amyloid 1-42 (Abeta42), a peptide that plays a central role in the pathogenesis of Alzheimer's disease (AD). The oxidized cholesterol products (oxysterols), 24-hydroxycholesterol (24-OHC) and 27-hydroxycholesterol (27-OHC), are endogenous activators of LXRs. However, the mechanisms by which these oxysterols may modulate Abeta42 levels are not well known. RESULTS: We determined the effect of 24-OHC and/or 27-OHC on Abeta generation in SH-SY5Y cells. We found that while 27-OHC increases levels of Abeta42, 24-OHC did not affect levels of this peptide. Increased Abeta42 levels with 27-OHC are associated with increased levels of beta-amyloid precursor protein (APP) as well as beta-secretase (BACE1), the enzyme that cleaves APP to yield Abeta. Unchanged Abeta42 levels with 24-OHC are associated with increased levels of sAPPalpha, suggesting that 24-OHC favors the processing of APP to the non-amyloidogenic pathway. Interestingly, 24-OHC, but not 27-OHC, increases levels of the ATP-binding cassette transporters, ABCA1 and ABCG1, which regulate cholesterol transport within and between cells. CONCLUSION: These results suggest that cholesterol metabolites are linked to Abeta42 production. 24-OHC may favor the non-amyloidogenic pathway and 27-OHC may enhance production of Abeta42 by upregulating APP and BACE1. Regulation of 24-OHC: 27-OHC ratio could be an important strategy in controlling Abeta42 levels in AD.