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Background/Aims: Hypoxia Inducible Factor-1α (HIF-1α) is involved in cancer progression and is stabilized by the chaperone HSP90 (Heat Shock Protein 90), preventing degradation. Previously identified HSP90 inhibitors bind to the N-terminal pocket of HSP90, which blocks binding to HIF-1α and induces HIF-1α degradation. N-terminal inhibitors have failed in the clinic as single therapy treatments partially because they induce a heat shock response. SM molecules are HSP90 inhibitors that bind to the C-terminus of HSP90 and do not induce a heat shock response. The effects of these C-terminal inhibitors on HIF-1α are unreported. Methods: HCT116, MDA-MB-231, PC3, and HEK293T cells were treated with HSP90 inhibitors. qRT-PCR and western blotting was performed to assess mRNA and protein levels of HIF-1α, HSPand RACK1-related genes. siRNA was used to knockdown RACK1, while MG262 was used to inhibit proteasome activity. Dimethyloxalylglycine (DMOG) was used to inhibit activity of the prolyl hydroxylases (PHDs). Anti-angiogenic activity of HSP90 inhibitors was assessed using a HUVEC tubule formation assay. Results: We show that SM compounds decrease HIF-1α target expression at the mRNA and protein level under hypoxia in colorectal, breast and prostate cancer cells, leading to cell death, without inducing a heat shock response. Surprisingly, we found that when the C-terminal of HSP90 is inhibited, HIF-1α degradation occurs through the proteasome and prolyl hydroxylases in an oxygen-dependent manner even in very low levels of oxygen (tumor hypoxia levels). RACK1 was not required for proteasomal degradation of HIF-1α. Conclusion: Our results suggest that by targeting the C-terminus of HSP90 we can exploit the prolyl hydroxylase and proteasome pathway to induce HIF-1α degradation in hypoxic tumors. [ABSTRACT FROM AUTHOR]

Objective To assess the efficacy of light-reflectance spectroscopy ( LRS) to detect positive surgical margins ( PSMs) on ex vivo radical prostatectomy ( RP) specimens. Materials and Methods A prospective evaluation of ex vivo RP specimens using LRS was performed at a single institution from June 2013 to September 2014. LRS measurements were performed on selected sites on the prostate capsule, marked with ink, and correlated with pathological analysis. Significant features on LRS curves differentiating malignant tissue from benign tissue were determined using a forward sequential selection algorithm. A logistic regression model was built and randomised cross-validation was performed. The sensitivity, specificity, accuracy, negative predictive value ( NPV), positive predictive value ( PPV), and area under the receiver operating characteristic curve ( AUC) for LRS predicting PSM were calculated. Results In all, 50 RP specimens were evaluated using LRS. The LRS sensitivity for Gleason score ≥7 PSMs was 91.3%, specificity 92.8%, accuracy 92.5%, PPV 73.2%, NPV 99.4%, and the AUC was 0.960. The LRS sensitivity for Gleason score ≥6 PSMs was 65.5%, specificity 88.1%, accuracy 83.3%, PPV 66.2%, NPV 90.7%, and the AUC was 0.858. Conclusions LRS can reliably detect PSMs for Gleason score ≥7 prostate cancer in ex vivo RP specimens. [ABSTRACT FROM AUTHOR]

Purpose: We developed a polyethylene sack (the PercSac) that fits over the shaft of a rigid nephroscope and is deployed into the collecting system to capture a stone and contain fragments during percutaneous nephrolithotomy (PCNL). We previously reported our results using the PercSac in a percutaneous cystolithopaxy model. In this study, we compare the efficiency of stone fragmentation with and without the PercSac in an anatomically correct in vitro PCNL model. Materials and Methods: The PCNL model consisted of a human collecting system model created on a 3D printer. Ten BegoStones made in spherical molds of 2.0 cm diameter, matched for weight, were fragmented in the model using a 24F rigid nephroscope and an ultrasonic lithotripter, including five with and five without the PercSac. The total times for stone fragmentation and complete stone clearance, gross assessment of the stonefree status, and need for flexible nephroscopy to achieve a stone-free state were recorded. Results: The median time for stone fragmentation was significantly shorter in the PercSac group compared with the control group (217 seconds [IQR= 169-255] vs 340 seconds [IQR= 310-356], [p = 0.028]). Likewise, the total time for complete stone clearance from the kidney was significantly shorter for the PercSac group (293 seconds [IQR= 244-347] vs 376 seconds [IQR= 375-480], [p = 0.047]). In one trial with the PercSac, residual dust remained in the kidney, while in all five trials without the PercSac small residual fragments remained. All trials without the PercSac required flexible nephroscopy with basket extraction to become stone free, while none of the trials with the PercSac required flexible nephroscopy for stone clearance. Conclusions: Ultrasonic lithotripsy using the novel PercSac stone entrapment device is more efficient and efficacious than traditional ultrasonic lithotripsy in an in vitro PCNL model. The advantage may be even more pronounced during clinical PCNL where residual fragments migrate into difficult-to-access calices. Further in vivo testing is underway. [ABSTRACT FROM AUTHOR]

Purpose: Early urinary control is a major goal for patients undergoing robot-assisted radical prostatectomy (RARP). We report our technique of posterior urethral suspension (PUS) performed at the time of urethrovesical anastomosis. Patients and Methods: We prospectively followed men with localized prostate cancer undergoing RARP by a single surgeon from August 2012 to October 2015. Patients before April 2014 underwent only bladder neck preservation (controls), while patients after April 2014 also underwent PUS. Patients were given a modified Expanded Prostate Cancer Index Composite questionnaire, along with questions depicting objective measures of urinary control (type of pad, number of pads, wetness of pad). Time points queried were preoperatively and postoperatively at weeks 1, 2, 4, and 12. Our primary outcome was pad-free survival. Results: Questionnaire response rate was 52% (56/107) for controls and 43% (36/83) for PUS. There were no differences in baseline demographics, preoperative urinary control, intraoperative variables, or postoperative complications between groups. There were few subjective improvements in urinary control for PUS compared with controls. More notable, PUS patients had significantly improved objective measures of urinary control, including less protective incontinence products at 1 and 2 weeks after catheter removal ( p < 0.03). They also wore fewer pads and had less leakage on each pad that lasted from week 1 to week 4 after catheter removal ( p < 0.01). PUS patients had pad-free rates of 37%, 47%, 54%, and 60% compared with controls 15%, 18%, 24%, and 36%, at weeks 1, 2, 4, and 12 after catheter removal ( p = 0.07). Conclusion: PUS may improve objective measures of early urinary control compared with controls. With no increase in operative time and no change in complication rates, further work in a randomized setting would provide additional weight to our findings. [ABSTRACT FROM AUTHOR]

Background and Purpose: With the extensive documentation afforded by our electronic medical record (EMR), we observed an unusually high number of patient-initiated encounters following ureteroscopy (URS). We sought to quantify and categorize patient encounters following URS to determine if we could identify avoidable common problems. Materials and Methods: Following IRB approval, we reviewed the records of 298 consecutive patients with stones who underwent 314 URS procedures between July 2013 and November 2014. Patient demographics, stone characteristics and operative details, as well as telephone encounters, secure online patient-initiated (MyChart) messages, and emergency department (ED) visits following URS were extracted from our EMR (Epic, Verona, WI). We performed univariate (UVA) and multivariate (MVA) analysis to identify factors predictive of postoperative patient encounters and compared URS patients to a group of 56 patients undergoing transurethral resection of bladder tumor (TURBT) for number and type of encounters. Results: We identified 443 encounters generated by 201 URS patients, including 334 telephone calls, 71 MyChart messages, and 38 ED visits. Among these encounters, 352 (79%) were medically related (pain comprised 45%) and the remainder involved scheduling issues. By UVA age, bilateral versus unilateral URS, stone location (both kidney and ureter), ureteral access sheath size, and total number of stones predicted a postoperative encounter. By MVA, only younger age and larger UAS size were independent predictors. When compared with TURBT patients, URS patients had a 2.5-fold higher risk of having a pain-related postoperative encounter (OR 2.54, 95% CI 1.08-7.04, P = 0.03). Conclusions: Among patients undergoing URS for stones, two-thirds made unprompted contact with a healthcare provider and 80% of contacts involved postoperative pain, a finding that is distinct from another endoscopic procedure that does not involve upper tract manipulation. Patients do not perceive URS as the benign procedure doctors do. [ABSTRACT FROM AUTHOR]

Objective: Robot-assisted laparoscopic prostatectomy (RALP) with suprapubic tube (SPT), compared to urethral catheter (UC) drainage, has been proposed to improve patient comfort and recovery. We sought to compare short-term outcomes for pain and morbidity after RALP with SPT vs UC drainage. Methods: Between August 2012 and 2014, 159 men underwent a RALP and prospectively completed a questionnaire addressing postoperative pain and satisfaction. Group 1 ( n = 94) underwent a RALP by one surgeon who placed a UC and removed it between postoperative day (POD) 7 and 10. Group 2 ( n = 65) underwent a RALP by a different surgeon who placed an SPT and UC. On POD 1, the UC was removed. On POD 9, the SPT was capped and removed on POD 11 if the patient was voiding adequately. Preoperative and intraoperative data, complications, questionnaires, and patient-reported morbidity, including unplanned telephone calls and emergency department (ED) visits, were compared between groups. Results: Patient characteristics were similar between groups. One week after surgery, the penile pain score was statistically significantly lower in Group 2 compared to Group 1 (56.9% and 79.8%, respectively, reported minimal-to-moderate pain, p = 0.003). Bladder spasms and overall pain were not significantly higher for Group 1 compared to Group 2 ( p > 0.05). When asked 'How big a problem has your urine storage device been?,' 20.2% of patients in Group 1 reported it as a 'moderate-to-big' problem compared to 10.8% in Group 2 ( p > 0.05). The number of catheter-related unplanned telephone encounters did not differ between the two groups ( p = 0.7), however, although not statistically significant, 4.6% of patients in Group 2 presented to the ED with catheter-related issues ( p = 0.07). Conclusion: SPT after RALP was associated with less penile pain compared to UC drainage, and modestly better patient satisfaction. There were no significant differences in bladder spasms, overall pain, and patient-reported morbidity between groups. [ABSTRACT FROM AUTHOR]

Purpose: We developed a novel device to capture stones in vivo in an enclosed bag (PercSac) to prevent dispersion of stone fragments during percutaneous nephrolithotomy (PCNL) or cystolitholapaxy. We report on our initial feasibility trials of the PercSac device. Materials and Methods: PercSac consists of a specially designed polyethylene bag that is fitted over the shaft of a rigid nephroscope. The bag is used to first entrap the target stone, then tighten around it to allow fragmentation within the bag. Matched pairs of 10 canine bladder stones (2.5 cm maximum diameter) were fragmented in a human bladder model using the CyberWand™ (Olympus America, Inc.), and the procedure was assessed for markers of efficiency and effectiveness. Results: Median time to entrap the stone within the PercSac was 67 seconds (range 51-185 sec). Median time for stone fragmentation was significantly shorter with the PercSac than without (182.0 sec [range 108-221] vs 296.5 sec [range 226-398], P=0.004). Overall, however, there was no significant difference in the total time to entrap and fragment the stones between the two groups. A stone-free state was not achieved for any trial without the PercSac, while 9 of 10 trials with the PercSac resulted in a stone-free state. Conclusions: Use of the PercSac in conjunction with stone fragmentation has the potential to reduce the occurrence of residual fragments after PCNL or cystolitholapaxy. Further in vitro testing in a kidney model is planned. [ABSTRACT FROM AUTHOR]

There is limited data regarding hyperbaric oxygen's effectiveness in the treatment of nonhealing arterial insufficiency ulcers. This study was designed to analyze healing rates and amputation rates in patients who underwent adjunctive hyperbaric oxygen for a nonhealing arterial insufficiency ulcer. A retrospective chart review was completed on patients who underwent hyperbaric oxygen for arterial insufficiency ulcers that failed to heal despite standard treatment. Information collected included complete ulcer healing, amputation, and patient characteristics. There were 82 patients identified. A majority did not have diabetes (84.1%). The overall rate of healing was 43.9%. The overall major amputation rate was 17.1%. The amputation rate among those who healed was 0% compared to 42.4% among those not healed ( p < 0.0001). Dialysis was predictive of major amputation ( p = 0.03). Our findings suggest hyperbaric oxygen can play a role in management of arterial insufficiency ulcers that have failed standard treatment. The overwhelming majority of these patients did not have diabetes, which allows this study to be translated to patients with a primary arterial insufficiency ulcer. These results support the use of hyperbaric oxygen for select nonhealing arterial insufficiency ulcers that have failed standard therapy and the need for a prospective pilot study. [ABSTRACT FROM AUTHOR]