Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo.

Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

Calculated insulin resistance correlates with stone-forming urinary metabolic changes and greater stone burden in high-risk stone patients.

AIMS: Metabolic syndrome and diabetes are associated with nephrolithiasis. Proposed mechanisms of lithogenesis include insulin resistance causing low urine pH and hyperinsulinemia leading to hypercalciuria. Herein, we sought to determine whether insulin resistance was associated with differences in stone burden and lithogenic changes on 24-hour urine samples. MATERIALS AND METHODS: All patients that underwent comprehensive metabolic workup including 24-hour urine samples and fasting insulin levels were included. Insulin resistance was defined as a homeostasis model assessment of insulin resistance value > 5 (HOMA-IR = (glucose×insulin)/405). Patients on active metabolic therapy were excluded or the 24-hour urine sample predating treatment was utilized for analysis. Stone burden was determined by totaling the maximal diameter of all stones noted on CT. RESULTS: 18 of 30 patients (60.0%) had HOMA-IR > 5. Among patients with calculated insulin resistance, stone burden was greater (17.6 mm vs. 6.3 mm, p = 0.002) and 24-hour urine samples revealed higher urine calcium (293 mg/d vs. 159 mg/d, p = 0.02) and lower urine pH and citrate (454 mg/d vs. 639 mg/d, p = 0.04 and 5.83 vs. 6.33, p = 0.04, respectively). CONCLUSIONS: Previous studies have demonstrated a correlation between metabolic syndrome, diabetes, and nephrolithiasis. This report demonstrates a quantitative increase in stone burden among patients with calculated insulin resistance. The pathway for this greater stone burden may be related to the urinary metabolic changes noted among patients with insulin resistance. In the future, targeting reduction of fasting insulin levels may represent a key element of stone disease prevention.

Evaluation of post-flexible cystoscopy urinary tract infection rates.

PURPOSE: The risk of urinary tract infection (UTI) development after flexible cystoscopy (FC) is not well described. It remains difficult to assess the role of pre-FC antimicrobial prophylaxis to reduce UTI risk. METHODS: In fall 2017, the urology service at the Providence Veterans Affairs Medical Center implemented routine oral antimicrobial prophylaxis in its outpatient FC clinic. Outpatients were randomly selected for a retrospective chart review to compare patients who received pre-FC antimicrobials (cefuroxime 500 mg tablet or sulfamethoxazole/trimethoprim [800 mg/160 mg] tablet) and those who underwent FC prior to fall 2017 and did not receive prophylaxis. The primary outcome was presence of symptomatic UTI within 30 days post FC. Secondary outcomes included symptomatic UTI that met colony-forming unit (CFU)/mL guideline requirements, and UTI treatment received. Potential risk factors for UTI were also assessed. RESULTS: A total of 296 patients were included in the final analysis: 139 who did not receive and 157 who received a prophylactic antimicrobial before FC. Rates of symptomatic UTI, symptomatic UTI meeting CFU/mL guideline requirements, and postprocedure treatment for UTI were similar with and without antimicrobial prophylaxis (2.5% vs 2.2% [P > 0.99], 1.9% vs 1.4% [P > 0.99], and 2.5% vs 4.3% [P = 0.53], respectively). The mean number of days from FC to the start of UTI treatment was 7.9 (range, 1-18 days). Age over 65 years was the only risk factor present in all patients with a post-FC UTI, irrespective of antimicrobial prophylaxis. CONCLUSION: The rate of post-FC symptomatic UTI was lower than rates previously described in the literature. The role of antimicrobial prophylaxis prior to FC warrants further exploration.

Examining Trends in Underrepresented Minorities in Urology Residency.

OBJECTIVE: To examine trends in underrepresented minority (URM) representation in urology residency. Comparison is made between URM representation in urology residency and URM representation in other surgical fields as well as all medical fields. We hypothesized that percentage of URM in urology has been limited when compared to both surgical fields and all other fields. MATERIAL AND METHODS: Data on the race and ethnicity of residents were collected from ACGME Data Resource Books from 2012 to 2017. We defined URM as the aggregate of Asian or Pacific Islander, Hispanic, Black, Native America/Alaskan and Other. The proportion of URM was compared to the proportion of White in urology vs other surgical specialties and all fields of medicine. Analysis consisted of chi-square testing for each year and for all years combined. RESULTS: In total, 5005 urology residents, 67,699 surgical residents, and 367,440 residents in all fields were identified. Comparative analysis demonstrated a significantly lower proportion of URM trainees in urology (30.8%) than surgery (33.6%) and all fields (42.3%), P <.001 for both analyses. Similar trends were observed in year-over-year analysis. Subanalyses of Hispanic, Black, Native American/Alaskan and Other representation as well as Asian representation in urology demonstrated comparable results as that found in the primary analysis (P <.001 for comparison between both surgical fields and all medical fields). CONCLUSION: The findings demonstrate that URM representation in urology trainees lags behind other fields. Recruitment and selection policies which take into account diversity are needed to improve inclusion of URM into the urologic pipeline and workforce.

Predicting the Impacted Ureteral Stone with Computed Tomography.

OBJECTIVE: To evaluate whether preoperative computed tomography (CT) findings could predict the presence of an impacted stone. Preoperative identification of an impacted ureteral stone may influence patient preparation and operative decisions. Factors predicting ureteral stone impaction have not been clearly identified. METHODS: We identified all patients from June 2014 to July 2016 that underwent ureteroscopic treatment of an impacted ureteral stone. Patients that had ureteral prestenting or previous treatment for their stone were excluded. Noncontrast CT images were reviewed to calculate stone size, stone volume, degree of hydronephrosis (0-3), and Hounsfield units (HU) of the stone as well as the ureter distal and proximal to the stone. These were compared with a control group of patients that had nonimpacted stones. RESULTS: Patients with impacted stones had a greater stone size, volume, HU of the ureter under the stone, HU under/above ratio, and degree of hydronephrosis on univariate analysis. Multivariate analysis demonstrated that HU under the stone was a significant predictor of ureteral stone impaction (odds ratio 1.17; 95% confidence interval 1.11-1.25). Distal ureteral density above 27 HU demonstrated a sensitivity of 85%, specificity of 85%, positive predictive value of 89%, and negative predictive value of 81% for ureteral stone impaction. CONCLUSION: Impacted stones are associated with ureteral density cut-off value of 27 HU or greater. Measuring this value on preoperative noncontrast CT may help predict which patients are more likely to have impacted stones.

A Randomized, Double-Blind, Sham-Controlled Study Assessing Electroacupuncture for the Management of Postoperative Pain after Percutaneous Nephrolithotomy.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the gold standard procedure for large renal calculi but postoperative (PO) pain remains a concern. Modifications of the PCNL technique and intraoperative and PO strategies have been tested to reduce pain. PO pain control reducing risk of long-term pain medication and narcotic use is of considerable importance. Acupuncture is a common medical procedure shown to alleviate PO pain. Some benefits are that it is nonpharmacologic, easy to administer, and safe. The purpose of this study was to evaluate the effects of electroacupuncture (EA) on PO pain in patients undergoing PCNL. MATERIALS AND METHODS: This was a randomized, double-blind, sham-controlled study. The study was Institutional Review Board approved and performed under standard ethical guidelines. Fifty-one patients undergoing PCNL by a single surgeon were randomized to one of the three groups: true EA (n = 17), sham EA (SEA, n = 17), and no acupuncture (control, n = 17). The EA and SEA were performed by a single licensed acupuncturist <1 hour before operation. PCNL was performed without the use of intraoperative nerve block(s) or local anesthetic. Pain scores (visual analog scale [VAS]), narcotic use (morphine equivalents), and side effects were recorded at set intervals postoperatively. RESULTS: Mean VAS scores for flank and abdomen pain were lower at all time periods in the EA compared with the SEA and control groups. Mean cumulative opioid usage was lower in the EA group immediately postoperatively compared with both SEA and control groups. Two patients in the EA group did not require any PO narcotics. No differences between groups were found for PO nausea and vomiting. No adverse effects of EA or SEA were noted. CONCLUSIONS: EA significantly reduced PO pain and narcotic usage without any adverse effects after PCNL. This promising treatment for managing PO pain warrants further investigation.

Beta blockers exposure and traumatic brain injury: a literature review.

Traumatic brain injury (TBI) continues to carry a significant public health burden and is anticipated to worsen worldwide over the next century. Recently the authors of several articles have suggested that exposure to beta blockers may improve mortality rates following TBI. The exact mechanism through which beta blockers mediate this effect is unknown. In this paper, the authors review the literature regarding the safety of beta blockers in patients with TBI. The findings of several recent retrospective cohort studies are examined and implications for future investigation are discussed. Future questions to be addressed include: the specific indications for the use of beta blockers in patients with TBI, the optimal type and dose of beta blocker given, the end point of beta blocker therapy, and the safety of beta blockers in cases of severe TBIs.

Recurrent Kidney Stone Episodes Leading to a Diagnosis of Occult Acromegaly.

The association between nephrolithiasis and acromegaly has been previously described. Although the mechanism has been established, the urological literature sparsely discusses clinically suspecting that patients with recurrent nephrolithiasis could have acromegaly and subsequently referring them for accurate diagnosis and treatment. We present a case of occult acromegaly secondary to a pituitary tumor discovered 20 years after the patient's first stone episode.

Emergency Ureteral Stone Treatment Score Predicts Outcomes of Ureteroscopic Intervention in Acute Obstructive Uropathy Secondary to Urolithiasis.

INTRODUCTION: Immediate ureteroscopic treatment for patients presenting to the emergency room with symptomatic ureterolithiasis is more commonly being utilized. Recent reports demonstrate good efficacy for emergency ureteroscopy (URS); however, preoperative predictors of treatment success have not been described. In this study, we report our multicenter experience with emergency URS and identify predictors of successful treatment. We also describe the Emergency Ureteral Stone Treatment (EUST) score, which integrates these predictors and stratifies patients into those that are likely and unlikely to have successful treatment. MATERIALS AND METHODS: Laboratory and radiographic data for all patients who underwent emergency URS for acute symptomatic ureterolithiasis from 2010 to 2015 were reviewed. Statistical difference among parameters for patients who were stone free (SF) and not SF was assessed with the Student's t-test. Cutoff values for significant predictors were determined using sensitivity and specificity analysis. The EUST score was determined based on the number of cutoffs a patient was below. RESULTS: Two hundred two of 247 patients (81.8%) were SF. Two complications (ureteral perforation) occurred. Stone size, duration of symptoms before presentation, and serum white blood count at presentation did not affect SF rates. 95.5% of the treatment failures were attributed to a tight ureter preventing stone access. Patients who received alpha blockers before treatment were more likely to be SF (98.0% vs 55.5%, p < 0.01). Periureteral density (PUD) was lower in SF patients (2.8 HU vs 19.6 HU, p < 0.01), whereas the increase in serum creatinine from baseline (ΔCr) was greater in non-SF patients (0.44 mg/dL vs 0.20 mg/dL, p < 0.01). EUST score of 0, 1, and 2 correlated with SF rates of 20.6%, 81.9%, and 99.2%, respectively. CONCLUSIONS: Combined consideration of PUD and ΔCr with the EUST score can assist in selecting optimal candidates for immediate ureteroscopic management. Administration of alpha blockers before surgery may improve success rates by providing preoperative ureteral dilation.

Prone Percutaneous Nephrolithotomy: Does Bolster Orientation Matter?

OBJECTIVE: To assess whether horizontal vs vertical bolster orientation affects kidney position during prone percutaneous nephrolithotomy as this could impact the need for supracostal access and therefore the likelihood of pleural injury. MATERIALS AND METHODS: In a prospective trial, 10 subjects with 20 renal units underwent magnetic resonance imaging in prone position with standard cylindrical bolsters oriented vertically and then horizontally. Vertical bolsters were placed along the lateral aspect of the chest. Horizontal bolsters were placed at the xiphoid and symphysis pubis. The position of the kidney relative to the pleura was assessed by measuring distances from the kidney upper pole to diaphragm, to the top of the first lumbar vertebra, and inferior-most rib. Nephrostomy tract length and tract proximity to adjacent organs were also measured. RESULTS: Right and left kidney-to-diaphragm distance significantly increased with horizontal vs vertical bolsters by 3.44 cm and 1.86 cm, respectively (P = .02, P = .01). Right kidney-to-rib distance significantly increased by 2.4 cm (P = .025); left kidney-to-rib distance increased by 0.5 cm (P = .123). Right kidney-to-vertebral distance significantly increased by 2.16 cm (P = .007); left kidney-to-vertebral distance increased by 0.9 cm (P = .059). There was no significant difference in maximum access angle, overall tract length, or colon position between horizontal and vertical bolsters. CONCLUSION: Orienting bolsters horizontally results in caudal kidney displacement without affecting access angle, overall tract length, or colon position. In comparison with vertical orientation, this may improve safety of percutaneous nephrolithotomy by decreasing the need for supracostal access and increasing the safety of supracostal access when required.

Triple D Score is a reportable predictor of shockwave lithotripsy stone-free rates.

PURPOSE: Over the last decade, shockwave lithotripsy (SWL) success rates have been correlated with stone density, skin-to-stone distance (SSD), and stone diameter. However, time constraints and the technical challenge of manual measurement often preclude utilization of these parameters. In this study, we describe a scoring system that accurately predicts SWL stone-free rates, is simple to calculate, and can be easily included in the radiology report. MATERIALS AND METHODS: Two hundred thirty-five patients who underwent SWL from 2011 to 2014 were evaluated. One hundred thirty-three had available preoperative imaging. Stone density, SSD, ellipsoid stone volume (ESV), and stone-free rates were determined. Receiver operator characteristic (ROC) curves were generated to determine cutoff values for each parameter. The Triple D Score was calculated based upon the number of cutoff values a stone fell below. RESULTS: One hundred forty of the 235 patients (59.5%) who underwent SWL were stone free after single-session treatment. Seventy-six of the 133 (57.1%) patients with available preoperative imaging were stone free. ESV, SSD, and stone density were significant predictors of SWL success. Based upon the ROC curves, cutoffs of <150 µL for ESV, <12 cm for SSD, and <600 HU for stone density were established. A Triple D Score of 0, 1, 2, and 3 correlated with SWL success rates of 21.4%, 41.3%, 78.7%, and 96.1%, respectively. CONCLUSIONS: Readily available predictive tools are necessary to enhance SWL cost-effectiveness. The Triple D Score is simple to calculate and can be reported by radiologists. Incorporation of the Triple D Score into preoperative planning may increase the overall SWL success rates.