Mechanism of Action of the Transobturator Sling for Post-Radical Prostatectomy Incontinence: A Multi-institutional Prospective Study Using Dynamic Magnetic Resonance Imaging.

OBJECTIVE: To compare the length of the membranous (functional) urethra in male patients who underwent the male transobturator sling (TOS) for postradical prostatectomy urinary incontinence (PPI). The TOS is in established use for treatment of PPI; however, the precise mechanism of action is unknown. MATERIALS AND METHODS: This is a prospective case-controlled study on men undergoing male TOS surgery from 2008 to 2014. The comparison arm included patients without incontinence after radical prostatectomy. All participants underwent dynamic magnetic resonance imaging (MRI) at baseline and this was repeated after TOS placement for those who underwent the procedure. Three standardized points were measured using MRI and compared in both groups in addition to clinical measures. RESULTS: Thirty-nine patients were enrolled and 31 patients completed the protocols. The controls (N = 14) had a longer vesicourethral anastomosis to urethra measured at the penile bulb (functional urethral length) distance compared to the pre-TOS group at rest (1.92 cm controls vs 1.27 cm pre-TOS, P = .0018) and at Valsalva (2.13 cm controls vs 1.72 cm pre-TOS, P = .0371). Placement of the sling (N = 17) increased the functional urethral length distance at rest (1.92 cm control vs 1.53 cm post-TOS, P = .09) and at Valsalva (1.94 cm post-TOS vs 2.13 cm control, P = .61), so that the difference was no longer statistically significant. CONCLUSION: We identified that one possible mechanism in improvement in stress urinary incontinence post-TOS placement is the lengthening of the vesicourethral anastomosis to bulbar-urethra distance. This is the first such study utilizing dynamics MRI in post prostatectomy controls, incontinent pre-TOS, and post-TOS to assess and show these findings.

Evaluation of Novel Ball-Tip Holmium Laser Fiber: Impact on Ureteroscope Performance and Fragmentation Efficiency.

PURPOSE: A novel ball tip (BT) holmium laser fiber has recently been developed, which features a modified rounded tip. The modification is purported to aid in insertion and minimize damage to the ureteroscope working channel. We evaluated this laser fiber with regard to stone comminution, tip degradation, insertional force into the ureteroscope, and impact on ureteroscope deflection. MATERIALS AND METHODS: A 242 µm BT fiber and a standard flat tip (SF) fiber were compared. Four kilojoules was delivered to a BegoStone over a constant surface area using settings of 0.2/50, 0.6/6, 0.8/8, and 1 J/10 Hz. Fiber tip degradation was measured at 1 and 4 kJ. Ureteroscope deflection was measured with the Olympus URF-P5, URF-P6, and URF-V. Insertion force into a 270° angled ureteroscope sheath model was measured. RESULTS: A sample size of five fibers was used for each comminution energy setting. Comminution increased with pulse energy without significant difference between fibers. No significant differences in tip degradation were observed. Both fibers reduced deflection (10°-30°) in all ureteroscopes without significant differences between fibers. Four new fibers paired with new sheath models were used to test insertion force. The BT insertion forces were approximately one-third of the SF. One SF fiber caused significant damage to the sheath and could not be advanced completely. CONCLUSIONS: The BT fiber has comparable comminution, tip degradation, and ureteroscope deflection performance compared with the SF fiber while exhibiting reduced insertion force within an aggressively deflected working sheath. The new tip design is likely protective of the working channel without loss of performance.

Clinical outcomes after ureteroscopic lithotripsy in patients who initially presented with urosepsis: matched pair comparison with elective ureteroscopy.

BACKGROUND AND PURPOSE: The outcomes of ureteroscopy (URS) after urgent decompression and antibiotics for patients who initially present with urosepsis because of obstructive urolithiasis have not been previously evaluated. The aim of this study was to compare the outcomes and complications of URS in patients with a recent history of sepsis with those without sepsis. METHODS: The study included 138 patients who underwent URS for stone removal from January 2004 to September 2011 at a university medical center. A matched-pair analysis was performed using three parameters (age, sex, and race) to compare outcomes and complications between 69 patients who had sepsis vs a matched cohort who did not have sepsis before URS. RESULTS: The study included 138 patients, 88 (64%) females and 50 (36%) males with a median age of 57.5 years (range 18-88 years). Patients with previous sepsis had similar patient characteristics and stone-free rates (81% vs 77%) compared with patients without previous sepsis (P>0.05). Patients with previous sepsis, however, had a significantly higher complications rate (20% vs 7%), longer hospital length of stay (LOS), and longer courses of postoperative antibiotics after URS (P<0.05). Sepsis developed postoperatively in two patients with diabetes (one with and one without previous sepsis), and postoperative fever developed in five patients with previous sepsis. CONCLUSIONS: URS after decompression for urolithiasis-related sepsis has similar success but higher complication rates, greater LOS, and longer course of postoperative antibiotics. This is important in counseling patients who present for definitive URS after urgent decompression for urolithiasis-related sepsis.

Ureteral stenting in laparoscopic colorectal surgery.

BACKGROUND: Few studies have examined the current status of ureteral stent use or the indications for stenting, particularly in laparoscopic colorectal surgery. This study examines current national trends and predictors of ureteral stenting in patients undergoing major colorectal operations and the subsequent effects on perioperative outcomes. METHODS: The 2005-2011 National Surgical Quality Improvement participant user files were used to identify patients undergoing laparoscopic segmental colectomy, low anterior resection, or proctectomy. Trends in stent use were assessed across procedure types. To estimate the predictors of stent utilization, a forward-stepwise logistic regression model was used. A 3:1 nearest neighbor propensity match with subsequent multivariable adjustment was then used to estimate the impact of stents. RESULTS: A total of 42,311 cases were identified, of which 1795 (4.2%) underwent ureteral stent placement. Predictors of stent utilization included diverticular disease, need for radical resection (versus segmental colectomy), recent radiotherapy, and more recent calendar year. After adjustment, ureteral stenting appeared to be associated with a small increase in median operative time (44 min) and a trivial increase in length of stay (5.4%, P<0.001). However, there were no significant differences in morbidity or mortality. CONCLUSIONS: We describe the clinical predictors of ureteral stent usage in this patient population and report that while stenting adds to operative time, it is not associated with significantly increased morbidity or mortality after adjusting for diagnosis and comorbidities. Focused institutional studies are necessary in the future to address the utility of ureteral stents in the identification and possible prevention of iatrogenic injury.

Emergent ureteric stent vs percutaneous nephrostomy for obstructive urolithiasis with sepsis: patterns of use and outcomes from a 15-year experience.

OBJECTIVES: To characterize the use of emergent JJ ureteric stent placement and percutaneous nephrostomy (PCN) for patients with obstructive urolithiasis with sepsis, and to determine whether outcomes differ between the two treatment methods. PATIENTS AND METHODS: A total of 130 patients with obstructive urolithiasis and systemic inflammatory response syndrome criteria were identified retrospectively from a single health system database from 1995 to 2011. Primary outcomes included stone-related and clinical variables which predicted the use of each treatment method. Secondary outcomes included the length of hospital stay, risk of intensive care unit (ICU) admission, and surgical approach used for definitive stone management. RESULTS: The overall rate of failed procedures was 2.3% (3/130), with one in-hospital death (0.8%). Patients treated with PCN had larger stones (10 vs 7 mm, P = 0.031), and were more acutely ill (acute physiology, age, chronic health evaluation [APACHE] II scores of 15 vs 11, P = 0.036) than those treated with JJ stent placement. Patients treated with PCN were more likely to require ICU admission (odds ratio: 3.23, 95% confidence interval [CI]: 1.24-8.41, P = 0.016), and demonstrated longer length of hospital stay (ß: 0.47, 95% CI: 0.20-0.74, P = 0.001), even when adjusting for age, APACHE II score, and Charlson Comorbidity Index score. After resolution of sepsis, patients treated with PCN were more likely to be treated definitively with a percutaneous approach, while patients treated with JJ stent placement were more likely to be treated ureteroscopically. CONCLUSIONS: Both JJ stent placement and PCN drainage appear effective. Patients with larger stones and who are more acutely ill are more likely to be treated with PCN. Additional randomized clinical trials of adequate power are warranted to define the optimum management of these often complex cases.

Increasing dwell time of mitomycin C in the upper tract with a reverse thermosensitive polymer.

UNLABELLED: Abstract Background and Purpose: Topical chemotherapy for urothelial cancer is dependent on adequate contact time of the chemotherapeutic agent with the urothelium. To date, there has not been a reliable method of maintaining this contact for renal or ureteral urothelial carcinoma. We evaluated the safety and feasibility of using a reverse thermosensitive polymer to improve dwell times of mitomycin C (MMC) in the upper tract. MATERIALS AND METHODS: Using a porcine model, four animals were treated ureteroscopically with both upper urinary tracts receiving MMC mixed with iodinated contrast. One additional animal received MMC percutaneously. The treatment side had ureteral outflow blocked with a reverse thermosensitive polymer plug. MMC dwell time was monitored fluoroscopically and intrarenal pressures measured. Two animals were euthanized immediately, and three animals were euthanized 5 days afterward. RESULTS: In control kidneys, drainage occurred at a mean of 5.3±0.58 minutes. Intrarenal pressures stayed fairly stable: 9.7±14.0 cm H20. In treatment kidneys, dwell time was extended to 60 minutes, when the polymer was washed out. Intrarenal pressures in the treatment kidneys peaked at 75.0±14.7 cm H20 and reached steady state at 60 cm H20. Pressures normalized after washout of the polymer with cool saline. Average washout time was 11.8±9.6 minutes. No histopathologic differences were seen between the control and treatment kidneys, or with immediate compared with delayed euthanasia. CONCLUSIONS: A reverse thermosensitive polymer can retain MMC in the upper urinary tract and appears to be safe from our examination of intrarenal pressures and histopathology. This technique may improve the efficacy of topical chemotherapy in the management of upper tract urothelial carcinoma.

Obesity triples the radiation dose of stone protocol computerized tomography.

PURPOSE: Patients with recurrent nephrolithiasis are often evaluated and followed with computerized tomography. Obesity is a risk factor for nephrolithiasis. We evaluated the radiation dose of computerized tomography in obese and nonobese adults. MATERIALS AND METHODS: We scanned a validated, anthropomorphic male phantom according to our institutional renal stone evaluation protocol. The obese model consisted of the phantom wrapped in 2 Custom Fat Layers (CIRS, Norfolk, Virginia), which have been verified to have the same radiographic tissue density as fat. High sensitivity metal oxide semiconductor field effect transistor dosimeters were placed at 20 organ locations in the phantoms to measure organ specific radiation doses. The nonobese and obese models have an approximate body mass index of 24 and 30 kg/m(2), respectively. Three runs of renal stone protocol computerized tomography were performed on each phantom under automatic tube current modulation. Organ specific absorbed doses were measured and effective doses were calculated. RESULTS: The bone marrow of each model received the highest dose and the skin received the second highest dose. The mean ± SD effective dose for the nonobese and obese models was 3.04 ± 0.34 and 10.22 ± 0.50 mSv, respectively (p <0.0001). CONCLUSIONS: The effective dose of stone protocol computerized tomography in obese patients is more than threefold higher than the dose in nonobese patients using automatic tube current modulation. The implication of this finding extends beyond the urological stone population and adds to our understanding of radiation exposure from medical imaging.

In-vitro assessment of a new portable ballistic lithotripter with percutaneous and ureteroscopic models.

BACKGROUND AND PURPOSE: The EMS Swiss LithoBreaker is a new, portable, electrokinetic lithotripter. We compared its tip velocity and displacement characteristics with a handheld, pneumatic lithotripter LMA StoneBreaker.™ We also evaluated fragmentation efficiency using in vitro models of percutaneous and ureteroscopic stone fragmentation. MATERIALS AND METHODS: Displacement and velocity profiles were measured for 1-mm and 2-mm probes using a laser beam aimed at a photo detector. For the percutaneous model, 2-mm probes fragmented 10-mm spherical BegoStone phantoms until the fragments passed through a 4-mm mesh sieve. The ureteroscopic model used 1-mm probes and compared the pneumatic and electrokinetic devices to a 200-µm holmium laser fiber. Cylindrical (4-mm diameter, 4-mm length) BegoStone phantoms were placed into silicone tubing to simulate the ureter; fragmented stones passed through a narrowing in the tubing. RESULTS: For both 1-mm and 2-mm probes, the electrokinetic device had significantly higher tip displacement and slower tip velocity, P<0.01. In the percutaneous model, the electrokinetic device needed an average of 484 impulses over 430 seconds to fragment one BegoStone, while the pneumatic device needed 29 impulses over 122 seconds to fragment one stone. Both clearance times and number of impulses needed for percutaneous stone clearance were significantly different at P<0.01. Ureteroscopically, the mean clearance time was 97 seconds for the electrokinetic lithotripter, 145 seconds for the pneumatic lithotripter, and 304 seconds for the laser. Comparing the pneumatic device with the electrokinetic device ureteroscopically, there was no significant difference in clearance time, P=0.55. Both the pneumatic and electrokinetic lithotripters, however, demonstrated decreased clearance times compared with the laser, P=0.027. CONCLUSIONS: The portable electrokinetic lithotripter may be better suited for ureteroscopy instead of percutaneous nephrolithotomy. It appears to be comparable to the portable pneumatic device in the ureter. Further clinical studies are needed to confirm these findings in vivo.

Outcomes of metallic stents for malignant ureteral obstruction.

PURPOSE: Malignant ureteral obstruction often necessitates chronic urinary diversion and is associated with high rates of failure with traditional ureteral stents. We evaluated the outcomes of a metallic stent placed for malignant ureteral obstruction and determined the impact of risk factors previously associated with increased failure rates of traditional stents. MATERIALS AND METHODS: Patients undergoing placement of the metallic Resonance® stent for malignant ureteral obstruction at an academic referral center were identified retrospectively. Stent failure was defined as unplanned stent exchange or nephrostomy tube placement for signs or symptoms of recurrent ureteral obstruction (recurrent hydroureteronephrosis or increasing creatinine). Predictors of time to stent failure were assessed using Cox regression. RESULTS: A total of 37 stents were placed in 25 patients with malignant ureteral obstruction. Of these stents 12 (35%) were identified to fail. Progressive hydroureteronephrosis and increasing creatinine were the most common signs of stent failure. Three failed stents had migrated distally and no stents required removal for recurrent infection. Patients with evidence of prostate cancer invading the bladder at stent placement were found to have a significantly increased risk of failure (HR 6.50, 95% CI 1.45-29.20, p = 0.015). Notably symptomatic subcapsular hematomas were identified in 3 patients after metallic stent placement. CONCLUSIONS: Failure rates with a metallic stent are similar to those historically observed with traditional polyurethane based stents in malignant ureteral obstruction. The invasion of prostate cancer in the bladder significantly increases the risk of failure. Patients should be counseled and observed for subcapsular hematoma formation with this device.

Optical performance comparison of deflectable laparoscopes for laparoendoscopic single-site surgery.

BACKGROUND AND PURPOSE: Flexible working angles and fine optical visualization are major requisite factors in performing laparoendoscopic single-site (LESS) urologic procedures. Multiple mechanical design approaches have been used to develop deflectable laparoscopes for LESS procedures. We compared the optical characteristics of three such devices using a bench top approach to simulate LESS in straight and deflected positions. MATERIALS AND METHODS: A 10-mm fixed-rod rotating lens device (Storz EndoCameleon) and two 5-mm articulating devices (Olympus EndoEye and Stryker IdealEye) were compared using standard industry testing protocols for image resolution (United States Air Force-1951 test target), distortion (multifrequency grid distortion target), and color reproducibility (Gretag Macbeth color checker). RESULTS: The 10-mm fixed-rod rotating lens system demonstrated the highest image resolution (5.04 line pairs/mm), but also the highest distortion (22.8%). Among the 5-mm flexible articulating laparoscopes, resolution was superior with the Olympus EndoEye (4.00 line pairs/mm) compared with the Stryker IdealEye (3.17 line pairs/mm). Distortion (7.0%) and color reproduction (1.18) were superior with the IdealEye vs the EndoEye (18.8 %, 1.27). Laparoscope deflection resulted in attenuation of resolution by 11% with both articulating models, but not with the fixed rod system. CONCLUSIONS: Definition of these optical characteristics may inform further development and selection of laparoscopic systems optimized for LESS surgery. A narrow but flexible camera can be crucial in the limited working space available during these procedures. Further investigation is warranted to determine if these objective findings translate into improved surgeon performance.

When (and how) to surgically treat asymptomatic renal stones.

Asymptomatic renal stones are identified in 8-10% of screened populations. With the increasing utilization of CT, the number of patients seeking urologic care for incidentally diagnosed renal calculi is likely to increase. Such patients present an important management dilemma: differentiating those to treat surgically from those who can be safely observed. Observational studies have revealed that approximately 50% of asymptomatic stones will progress, but most will not require surgery. Stones >15 mm in diamater and located in the renal pelvis are at highest risk of progression. Although no guidelines exist for the optimal monitoring regimen for asymptomatic stones, follow-up studies may include serum creatinine, plain radiography, ultrasonography, and CT. Shock wave lithotripsy (SWL) does not seem to offer significant benefit over observation for asymptomatic calyceal stones. Percutaneous nephrolithotomy does improve stone-free rates compared to SWL or observation. Additional research is needed to characterize the role of ureteroscopic management of asymptomatic renal stones.

Lysophosphatidic Acid Stimulates the Proliferation of Ovarian Cancer Cells via the gep Proto-Oncogene Gα(12).

Lysophosphatidic acid (LPA), an agonist that activates specific G protein-coupled receptors, is present at an elevated concentration in the serum and ascitic fluid of ovarian cancer patients. Although the increased levels of LPA have been linked to the genesis and progression of different cancers including ovarian carcinomas, the specific signaling conduit utilized by LPA in promoting different aspects of oncogenic growth has not been identified. Here, we show that LPA stimulates both migration and proliferation of ovarian cancer cells. Using multiple approaches, we demonstrate that the stimulation of ovarian cancer cells with LPA results in a robust and statistically significant proliferative response. Our results also indicate that Gα(12), the gep proto-oncogene, which can be stimulated by LPA via specific LPA receptors, is overtly activated in a large array of ovarian cancer cells. We further establish that LPA stimulates the rapid activation of Gα(12) in SKOV-3 cells and the expression of CT12, an inhibitory minigene of Gα(12) that disrupts LPAR-Gα(12) interaction and potently inhibits such activation. Using this inhibitory molecule as well as the shRNA approach, we show that the inhibition of Gα(12) or silencing of its expression drastically and significantly attenuates LPA-mediated proliferation of ovarian cancer cell lines such as SKOV3, Hey, and OVCAR-3. Together with our findings that the silencing of Gα(12) does not have any significant effect on LPA-mediated migratory response of SKOV3 cells, our results point to a critical role for LPA-LPAR-Gα(12) signaling in ovarian cancer cell proliferation and not in migration. Thus, results presented here for the first time demonstrate that the gep proto-oncogene forms a specific node in LPA-LPAR-mediated mitogenic signaling in ovarian cancer cells.

The microrevolution: applications and impacts of microarray technology on molecular biology and medicine (review).

Microarray is a technique that provides a global analysis of gene expression at the level of transcription. Genetic and epigenetic changes underlie neoplastic transformation, cardiovascular disease, some psychiatric illnesses, and a growing list of disease pathogeneses and therapeutic responses. The profile of genes expressed by different cells (gene up- and downregulation under different conditions) determines their phenotype, and thus provides insights into the molecular basis for health and disease. Microarray technology combines standard molecular techniques with high-throughput screening to monitor the expression of up to 38,500 genes. A single experiment can assay gene expression across the entire genome under experimental or clinical conditions. Microarray therefore extends wide bridges between basic science and clinical medicine. This review describes the principles behind transcriptional profiling, experimental designs, and data analyses in the context of basic and clinical sciences. In addition, we survey the Microrevolutionized field of clinical cancer research by reviewing the most recent and innovative microarray studies of breast carcinoma.

Decreased activation of the lateral geniculate nucleus in a patient with anisometropic amblyopia demonstrated by functional magnetic resonance imaging.

Although postmortem morphological changes in the lateral geniculate nucleus (LGN) have been reported in human amblyopia, LGN function during monocular viewing by amblyopic eyes has not been documented in humans. We used functional magnetic resonance imaging (fMRI) to study monocular visual activation of the LGN in a patient with anisometropic amblyopia. Four normal subjects, a patient with optic neuritis and a patient with anisometropic amblyopia were studied with fMRI at 1.5 T during monocular checkerboard stimulation. Activated areas in the LGN and visual cortex were identified after data processing (motion correction and spatial normalization) with SPM99. In the 4 normal subjects, comparable activation of the LGN and visual cortex was obtained by stimulation of either the right or left eye. In the patient with unilateral optic neuritis, activation of the LGN and visual cortex was markedly decreased when the affected eye was stimulated. Similarly, decreased activation of the LGN as well as the visual cortex by the affected eye was demonstrated in the patient with anisometropic amblyopia. Our preliminary results suggest that activation of the LGN is diminished during monocular viewing by affected eyes in anisometropic amblyopia. fMRI appears to be a feasible method to study LGN activity in human amblyopia.