Preoperative Belladonna and Opium Suppository for Ureteral Stent Pain: A Randomized, Double-blinded, Placebo-controlled Study.

OBJECTIVE: To investigate whether the use of a belladonna and opium (B&O) rectal suppository administered immediately before ureteroscopy (URS) and stent placement could reduce stent-related discomfort. METHODS: A randomized, double-blinded, placebo-controlled study was performed from August 2013 to December 2014. Seventy-one subjects were enrolled and randomized to receive a B&O (15 mg/30 mg) or a placebo suppository after induction of general anesthesia immediately before URS and stent placement. Baseline urinary symptoms were assessed using the American Urological Association Symptom Score (AUASS). The Ureteral Stent Symptom Questionnaire and AUASS were completed on postoperative days (POD) 1, 3, and after stent removal. Analgesic use intraoperatively, in the recovery unit, and at home was recorded. RESULTS: Of the 71 subjects, 65 had treatment for ureteral (41%) and renal (61%) calculi, 4 for renal urothelial carcinoma, and 2 were excluded for no stent placed. By POD3, the B&O group reported a higher mean global quality of life (QOL) score (P = .04), a better mean quality of work score (P = .05), and less pain with urination (P = .03). The B&O group reported an improved AUASS QOL when comparing POD1 with post-stent removal (P = .04). There was no difference in analgesic use among groups (P = .67). There were no episodes of urinary retention. Age was associated with unplanned emergency visits (P <.00) and "high-pain" measure (P = .02) CONCLUSION: B&O suppository administered preoperatively improved QOL measures and reduced urinary-related pain after URS with stent. Younger age was associated with severe stent pain and unplanned hospital visits.

First in Human Clinical Trial of Ultrasonic Propulsion of Kidney Stones.

PURPOSE: Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones. MATERIALS AND METHODS: Subjects underwent ultrasonic propulsion while awake without sedation in clinic, or during ureteroscopy while anesthetized. Ultrasound and a pain questionnaire were completed before, during and after propulsion. The primary outcome was to reposition stones in the collecting system. Secondary outcomes included safety, controllable movement of stones and movement of stones less than 5 mm and 5 mm or greater. Adverse events were assessed weekly for 3 weeks. RESULTS: Kidney stones were repositioned in 14 of 15 subjects. Of the 43 targets 28 (65%) showed some level of movement while 13 (30%) were displaced greater than 3 mm to a new location. Discomfort during the procedure was rare, mild, brief and self-limited. Stones were moved in a controlled direction with more than 30 fragments passed by 4 of the 6 subjects who had previously undergone a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of a large stone at the ureteropelvic junction. In 4 subjects a seemingly large stone was determined to be a cluster of small passable stones after they were moved. CONCLUSIONS: Ultrasonic propulsion was able to successfully reposition stones and facilitate the passage of fragments in humans. No adverse events were associated with the investigational procedure.

Use of the Acoustic Shadow Width to Determine Kidney Stone Size with Ultrasound.

PURPOSE: Ultrasound is known to overestimate kidney stone size. We explored measuring the acoustic shadow behind kidney stones combined with different ultrasound imaging modalities to improve stone sizing accuracy. MATERIALS AND METHODS: A total of 45 calcium oxalate monohydrate stones were imaged in vitro at 3 different depths with the 3 different ultrasound imaging modalities of conventional ray line, spatial compound and harmonic imaging. The width of the stone and the width of the acoustic shadow were measured by 4 operators blinded to the true size of the stone. RESULTS: Average error between the measured and true stone width was 1.4 ± 0.8 mm, 1.7 ± 0.9 mm, 0.9 ± 0.8 mm for ray line, spatial compound and harmonic imaging, respectively. Average error between the shadow width and true stone width was 0.2 ± 0.7 mm, 0.4 ± 0.7 mm and 0.0 ± 0.8 mm for ray line, spatial compound and harmonic imaging, respectively. Sizing error based on the stone width worsened with greater depth (p <0.001) while the sizing error based on the shadow width was independent of depth. CONCLUSIONS: Shadow width was a more accurate measure of true stone size than a direct measurement of the stone in the ultrasound image (p <0.0001). The ultrasound imaging modality also impacted the measurement accuracy. All methods performed similarly for shadow size while harmonic imaging was the most accurate stone size modality. Overall 78% of the shadow sizes were accurate to within 1 mm, which is similar to the resolution obtained with clinical computerized tomography.

Renal Vasoconstriction Occurs Early During Shockwave Lithotripsy in Humans.

INTRODUCTION: In animal models, pretreatment with low-energy shock waves and a pause decreased renal injury from shockwave lithotripsy (SWL). This is associated with an increase in perioperative renal resistive index (RI). A perioperative rise is not seen without the protective protocol, which suggests that renal vasoconstriction during SWL plays a role in protecting the kidney from injury. The purpose of our study was to investigate whether there is an increase in renal RI during SWL in humans. MATERIALS AND METHODS: Subjects were prospectively recruited from two hospitals. All subjects received an initial 250 shocks at low setting, followed by a 2-minute pause. Treatment power was then increased. Measurements of the renal RI were taken before start of procedure, at 250, after 750, after 1500 shocks, and at the end of the procedure. A linear mixed-effects model was used to compare RIs at the different time points. RESULTS: Fifteen patients were enrolled. Average treatment time was 46 ± 8 minutes. Average RI at pretreatment, after 250, after 750, after 1500 shocks, and post-treatment was 0.67 ± 0.06, 0.69 ± 0.08, 0.71 ± 0.07, 0.73 ± 0.07, and 0.74 ± 0.06, respectively. In adjusted analyses, RI was significantly increased after 750 shocks compared with pretreatment (p = 0.05). CONCLUSION: Renal RI increases early during SWL in humans with the protective protocol. Monitoring for a rise in RI during SWL is feasible and may provide real-time feedback as to when the kidney is protected.

Tools to improve the accuracy of kidney stone sizing with ultrasound.

PURPOSE: Ultrasound (US) overestimates stone size when compared with CT. The purpose of this work was to evaluate the overestimation of stone size with US in an in vitro water bath model and investigate methods to reduce overestimation. MATERIALS AND METHODS: Ten human stones (3-12 mm) were measured using B-mode (brightness mode) US by a sonographer blinded to the true stone size. Images were captured and compared using both a commercial US machine and software-based research US device. Image gain was adjusted between moderate and high stone intensities, and the transducer-to-stone depth was varied from 6 to 10 cm. A computerized stone-sizing program was developed to outline the stone width based on a grayscale intensity threshold. RESULTS: Overestimation with the commercial device increased with both gain and depth. Average overestimation at moderate and high gain was 1.9±0.8 and 2.1±0.9 mm, respectively (p=0.6). Overestimation increased an average of 22% with an every 2-cm increase in depth (p=0.02). Overestimation using the research device was 1.5±0.9 mm and did not vary with depth (p=0.28). Overestimation could be reduced to 0.02±1.1 mm (p<0.001) with the computerized stone-sizing program. However, a standardized threshold consistent across depth, system, or system settings could not be resolved. CONCLUSION: Stone size is consistently overestimated with US. Overestimation increased with increasing depth and gain using the commercial machine. Overestimation was reduced and did not vary with depth, using the software-based US device. The computerized stone-sizing program shows the potential to reduce overestimation by implementing a grayscale intensity threshold for defining the stone size. More work is needed to standardize the approach, but if successful, such an approach could significantly improve stone-sizing accuracy and lead to automation of stone sizing.

Preclinical safety and effectiveness studies of ultrasonic propulsion of kidney stones.

OBJECTIVE: To provide an update on a research device to ultrasonically reposition kidney stones transcutaneously. This article reports preclinical safety and effectiveness studies, survival data, modifications of the system, and testing in a stone-forming porcine model. These data formed the basis for regulatory approval to test the device in humans. MATERIALS AND METHODS: The ultrasound burst was shortened to 50 ms from previous investigations with 1-s bursts. Focused ultrasound was used to expel 2- to 5-mm calcium oxalate monohydrate stones placed ureteroscopically in 5 pigs. Additionally, de novo stones were imaged and repositioned in a stone-forming porcine model. Acute safety studies were performed targeting 2 kidneys (6 sites) and 3 pancreases (8 sites). Survival studies followed 10 animals for 1 week after simulated treatment. Serum and urine analyses were performed, and tissues were evaluated histologically. RESULTS: All ureteroscopically implanted stones (6/6) were repositioned out of the kidney in 14 ± 8 minutes with 13 ± 6 bursts. On average, 3 bursts moved a stone more than 4 mm and collectively accounted for the majority of relocation. Stones (3 mm) were detected and repositioned in the 200-kg stone-forming model. No injury was detected in the acute or survival studies. CONCLUSION: Ultrasonic propulsion is safe and effective in the porcine model. Stones were expelled from the kidney. De novo stones formed in a large porcine model were repositioned. No adverse effects were identified with the acute studies directly targeting kidney or pancreatic tissue or during the survival studies indicating no evidence of delayed tissue injury.

Role of maximal endoscopic resection before cystectomy for invasive urothelial bladder cancer.

INTRODUCTION/BACKGROUND: The aim of this study was to examine whether TUR of all visible endophytic tumors performed before RC, with or without NC, affects final pathologic staging. PATIENTS AND METHODS: We retrospectively reviewed data from patients with clinical T2-T4N0-1 urothelial carcinoma of the bladder who underwent RC at our institution between July 2005 and November 2011. Degree of TUR was derived from review of operative reports. We used multivariate logistic regression to assess the association of maximal TUR on pT0 status at time of RC. RESULTS: Of 165 eligible RC patients, 81 received NC. Reported TUR of all visible tumors was performed in 38% of patients who did not receive NC and 48% of NC patients (P = .19). Nine percent of patients who underwent maximal TUR and did not receive NC were pT0, whereas among NC patients, pT0 was seen in 39% and 19% of those with and without maximal TUR, respectively (P = .05). On multivariate analysis in all patients, maximal TUR was associated with a nonsignificant increased likelihood of pT0 status (odds ratio [OR], 2.03; 95% confidence interval [CI], 0.84-4.94), which was significant when we restricted the analysis to NC patients (OR, 3.17; 95% CI, 1.02-9.83). CONCLUSION: Maximal TUR of all endophytic tumors before NC is associated with complete pathologic tumor response at RC. Candidates for NC before RC should undergo resection of all endophytic tumors when feasible. Larger series are warranted to see if maximal TUR leads to improved overall and disease-specific survival.

Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer.

Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC) versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0) and any response (≤pT1). Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45-6.64), P = 0.03) and any response (52% versus 25%, OR 3.23 (95% CI: 1.21-8.64), P = 0.01). Seventy-two patients received GC (n = 41) or MVAC (n = 31). CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10-1.58). Any response (≤pT1) was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12-1.71). Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC). Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

Comparison of lymph node yield in robot-assisted laparoscopic prostatectomy with that in open radical retropubic prostatectomy.

OBJECTIVE: • To investigate both the feasibility and the adequacy of pelvic lymph node dissection (PLND) during robot-assisted laparoscopic prostatectomy (RALP) by comparing lymph node yields obtained during RALP with those obtained during traditional open retropubic radical prostatectomy (RRP). PATIENTS AND METHODS: • We retrospectively reviewed 1047 patients who underwent radical prostatectomy between 2001 and 2009. • In all, 626 patients underwent RALP while 421 patients had traditional open RRP. All patients undergoing bilateral PLND were included in our analysis. • Lymph node yields and lymph node involvement for each surgical approach were calculated and examined. • PLND-related complications were analysed. RESULTS: • Of the 1047 patients, 816 patients underwent bilateral PLND of whom 473 underwent RALP, while 343 underwent RRP. The mean lymph node yields for the RALP cohort (7.1, interquartile range 4-10) was significantly higher (P < 0.001) than for the RRP cohort (6.0, interquartile range 3-8). • The percentage of patients with nodal involvement was 1.1 for RALP and 2.3 for RRP (P= 0.167). • Mean age, preoperative PSA values, and pre- and postoperative Gleason scores were similar between the two cohorts. • PLND-related complications were similar between both cohorts. CONCLUSIONS: • In patients undergoing RALP, PLND is feasible and provides lymph node yields comparable with those of the standard open approach. • PLND should be strongly considered in all radical prostatectomy patients when clinically indicated, regardless of surgical technique.

High-resolution ultrasonography in the diagnosis and intraoperative management of peripheral nerve lesions.

OBJECT: The diagnosis of peripheral nerve lesions relies on clinical history, physical examination, electrodiagnostic studies, and radiography. Magnetic resonance neurography offers high-resolution visualization of structural peripheral nerve lesions. The availability of MR neurography may be limited, and the costs can be significant. By comparison, ultrasonography is a portable, dynamic, and economic technology. The authors explored the clinical applicability of high-resolution ultrasonography in the preoperative and intraoperative management of peripheral nerve lesions. METHODS: The authors completed a retrospective analysis of 13 patients undergoing ultrasonographic evaluation and surgical treatment of nerve lesions at their institution (nerve entrapment [5], trauma [6], and tumor [2]). Ultrasonography was used for diagnostic (12 of 13 cases) and intraoperative management (6 of 13 cases). The authors examine the initial impact of ultrasonography on clinical management. RESULTS: Ultrasonography was an effective imaging modality that augmented electrophysiological and other neuroimaging studies. The modality provided immediate visualization of a sutured peroneal nerve after a basal cell excision, prompting urgent surgical exploration. Ultrasonography was used intraoperatively in 2 cases to identify postoperative neuromas after mastectomy, facilitating focused excision. Ultrasonography correctly diagnosed an inflamed lymph node in a patient in whom MR imaging studies had detected a schwannoma, and the modality correctly diagnosed a tendinopathy in another patient referred for ulnar neuropathy. Ultrasonography was used in 6 patients to guide the surgical approach and to aid in intraoperative localization; it was invaluable in localizing the proximal segment of a radial nerve sectioned by a humerus fracture. In all cases, ultrasonography demonstrated the correct lesion diagnosis and location (100%); in 7 (58%) of 12 cases, ultrasonography provided the correct diagnosis when other imaging and electrophysiological studies were inconclusive or inadequate. CONCLUSIONS: High-resolution ultrasonography may provide an economical and accurate imaging modality with utility in diagnosis and management of peripheral nerve lesions. Further research is required to assess the role of ultrasonography in evaluation of peripheral nerve pathology.

2-(N-Fmoc)-3-(N-Boc-N-methoxy)-diaminopropanoic acid, an amino acid for the synthesis of mimics of O-linked glycopeptides.

Amino acids with N-alkylaminooxy side chains have proven effective for the rapid synthesis of neoglycopeptides. Chemoselective reaction of reducing sugars with peptides containing these amino acids provides glycoconjugates that are structurally similar to their natural counterparts. 2-(N-Fmoc)-3-(N-Boc-N-methoxy)-diaminopropanoic acid (Fmoc: 9-fluorenylmethoxycarbonyl; Boc: t-butyloxycarbonyl) was synthesized from Boc-Ser-OH in >40% overall yield and incorporated into peptides by standard Fmoc chemistry based solid phase peptide synthesis. The resulting peptides are efficiently glycosylated and serve as mimics of O-linked glycopeptides. The synthesis of this derivative greatly expands the availability of the N-alkylaminooxy strategy for neoglycopeptides.