Rationale and design of an implant procedure and pivotal study to evaluate safety and effectiveness of Medtronic's tibial neuromodulation device.

Percutaneous tibial neuromodulation is a medical guideline recommended therapy for treating symptoms of overactive bladder. Stimulation is delivered to the tibial nerve via a thin needle placed percutaneously for 30 min once a week for 12-weeks, and monthly thereafter. Studies have shown that this therapy can effectively relieve symptoms of overactive bladder; however, the frequent office visits present a barrier to patients and can impact therapy effectiveness. To mitigate the burden of frequent clinic visits, small implantable devices are being developed to deliver tibial neuromodulation. These devices are implanted during a single minimally invasive procedure and deliver stimulation intermittently, similar to percutaneous tibial neuromodulation. Here, we describe the implant procedure and design of a pivotal study evaluating the safety and effectiveness for an implantable tibial neuromodulation device. The Evaluation of Implantable Tibial Neuromodulation (TITAN 2) pivotal study is a prospective, multicenter, investigational device exemption study being conducted at up to 30 sites in the United States and enrolling subjects with symptoms of overactive bladder.

Evaluation of clinical performance and safety for the rechargeable InterStim Micro device in overactive bladder subjects: 6-month results from the global postmarket ELITE study.

AIMS: Sacral neuromodulation (SNM) is an advanced therapy option for the treatment of overactive bladder (OAB), nonobstructive urinary retention, and fecal incontinence. The aim of this ongoing prospective, multicenter, global, postmarket study is to confirm safety and clinical performance of the InterStimTM Micro system for SNM in all indications. Reported here are the results for the OAB cohort through 6-month follow-up. METHODS: Eligible OAB subjects that had a successful therapy evaluation were enrolled after implant of an InterStim Micro implantable pulse generator (IPG). Subjects completed voiding diaries and the Overactive Bladder Quality of Life questionnaire (OAB-q) at baseline and follow-up visits occurring at 3 months and 6 months postimplant. Safety was evaluated as device-, procedure-, or therapy-related adverse events. The primary objective for the OAB cohort was to demonstrate an improvement in OAB-q Health Related Quality of Life (HRQL) total score at 3 months postimplant compared to baseline. RESULTS: Sixty-eight OAB subjects were enrolled and implanted with an InterStim Micro IPG. Of those, 67 and 66 subjects completed the 3- and 6-month follow-up visits, respectively. The OAB-q HRQL demonstrated a statistically significant improvement from baseline to 3-month follow-up with an average increase of 33 ± 24 points (n = 67, p < 0.001). The change was also observed at 6-months with an average increase of 31 ± 23 points (n = 65) compared to baseline. Eighty-two percent of subjects achieved the minimally important difference in HRQL score at 3- and 6-month, respectively, with a change of 10 points or greater. The majority of subjects reported that their bladder condition was better at 3-month (92.5%, 62/67) and 6-month (89%, 59/66) compared to before they were treated with SNM therapy delivered by the InterStim Micro system. For subjects with urgency urinary incontinence (UUI), the average change from baseline to follow-up in UUI episodes/day was -3.6 (95% CI: -4.7, -2.6; n = 62) at 3-month and -3.7 (95% CI: -4.7, -2.7; n = 61) at 6-month. Among subjects with urgency-frequency (UF), the average change from baseline to follow up in voids/day was -4.5 (95% CI: -6.3, -2.7; n = 52) at 3-months and -4.4 (95% CI: -6.0, -2.7; n = 52) at 6-month. The cumulative incidence of device-, procedure-, or therapy- related adverse events was 7.4% (5/68). Out of these five related adverse events, there was one serious adverse event (1.5%, implant site pain) at the time of database snapshot. CONCLUSIONS: These data confirm the safety and clinical performance of the InterStim Micro device for subjects with OAB by demonstrating a significant improvement in OAB-q HRQL score at 3-month. Similar improvements were observed at 6 months in addition to an incidence of adverse events that is comparable to previously reported rates for SNM.

Prospective, multicenter study to evaluate performance and safety of a re-engineered temporary lead for InterStim™ therapy evaluation.

AIMS: The basic evaluation or percutaneous nerve evaluation (PNE) is a method to assess pre-implantation therapeutic response in patients considering sacral neuromodulation for the treatment of refractory overactive bladder. A new PNE lead with a more robust design and greater distensibility designed to reduce the possibility of lead migration has recently been introduced to the market. The aim of this prospective, multicenter, global, postmarket study was to evaluate the clinical performance and safety of the new InterStim PNE lead with the foramen needle. METHODS: Patients with overactive bladder were enrolled in this study. The primary objective of this study was to determine the proportion of subjects who demonstrated motor or sensory response(s) during lead placement using the InterStim PNE lead. Additional measures included the Patient Global Impression of Improvement (PGI-I), patient satisfaction at the end of therapy evaluation, and change in bladder symptoms from baseline to the end of therapy evaluation (1-week follow-up visit). RESULTS: One-hundred and ten subjects met the inclusion and exclusion criteria and underwent a lead implant procedure. Of those, 108 had a successful procedure and 107 completed the 1-week follow-up visit. Ninety-nine percent of subjects (109/110) had a motor or sensory response during needle placement (95% confidence interval [CI]: 95%-100%) and 97% of subjects (107/110) had a motor or sensory response during lead placement (95% CI: 92%-99%). The majority of subjects (88%, 95/108) reported their bladder condition was better at the follow-up visit compared to before the PNE implant procedure, as reported in PGI-I. Subjects reported being satisfied with how the therapy impacted their voiding symptoms (82%, 88/108) and that they would recommend this therapy (87%, 94/108) to other patients. Symptom improvement was demonstrated with urinary urge incontinence subjects having an average of 4.2 ± 3.4 urinary incontinence episodes/day at baseline and 2.2 ± 2.5 at follow-up, and urinary frequency subjects having an average of 12.5 ± 4.4 voids/day at baseline and 10.5 ± 4.3 voids/day at follow-up. Lead removal was deemed to be easy and safe by the implanting physician, with a total of three adverse device effects in 3/110 subjects. No event was categorized as serious and all were resolved without sequelae. CONCLUSIONS: The updated InterStim PNE lead with a more robust design and greater distensibility designed to reduce migration was shown to have a high rate of motor or sensory response during lead placement. Furthermore, subjects reported high rates of global improvements and amelioration of symptoms, and the lead was easy to remove with minimal morbidity.

Virtue Quadratic Male Sling for stress incontinence-surgical guide for placement and delayed revision.

The algorithm for surgical management of post prostatectomy incontinence classically includes male slings and artificial urinary sphincter (AUS) placement. The Virtue Quadratic Male Sling was designed to provide both urethral elevation and prepubic compression making it a viable option for a wider spectrum of incontinent men whose symptoms range from mild to severe. With a focus on two key steps of the surgery, (I) sling fixation (II) use of intraoperative retrograde leak point pressure (RLPP), this guide is intended to outline a safe and efficacious treatment for post-prostatectomy incontinence. Intriguingly, the sling can be revised in the event of refractory or worsening leakage, and does not preclude the placement of an AUS should it be needed. This paper describes a step by step approach to performing the procedure as well as expert tips to improve outcomes and avoid/manage complications that have been learned over the years.

Prospective randomized evaluation of periureteral botulinum toxin type A injection for ureteral stent pain reduction.

PURPOSE: The use of ureteral stents for ureteral obstruction and after ureteroscopy can result in substantial deterioration in patient quality of life due to pain, frequency and urgency. We postulated that many stent related symptoms may be related to detrusor muscle spasm in and around the intramural ureter, and evaluated the effect of botulinum toxin type A (Botox) in patients with indwelling stents after ureteroscopy. MATERIALS AND METHODS: A total of 51 patients between December 2007 and March 2009 were enrolled in an institutional review board approved, prospective, randomized, single-blind study comparing botulinum toxin type A injection at a concentration of 10 U/ml to 3 locations around the ureteral orifice (30) vs no injection after unilateral ureteral stent insertion (21). Pain and urinary symptoms after stent placement were evaluated through the Ureteral Stent Symptom Questionnaire, which was completed on postoperative day 7. In addition, patients were required to maintain a log of narcotic use after stent placement until removal. The Wilcoxon rank sum and Fisher exact tests were used for nonparametric and categorical data, respectively, with p

Transgastric NOTES: Current experience and potential implications for urologic applications.

Natural orifice translumenal endoscopic surgery (NOTES) in its current form uses flexible endoscopy technology to perform surgical procedures in the abdomen. NOTES is emerging as a potential alternative to both open and laparoscopic surgery, and the technique eliminates the requirement of abdominal incisions. To date, multiple intraperitoneal procedures have been reported in animal models while only a few reports of NOTES performed in humans exist. Several potential advantages of NOTES include the elimination of visible scars, less postoperative pain, and the reduction of postoperative complications, such as wound infection, abdominal wall pain, hernias, and adhesions. Current clinical applications of NOTES that are being studied heavily include its use in percutaneous endoscopic gastrostomy tube rescue and diaphragmatic pacing in intensive care unit patients. A number of barriers still exist regarding the technical challenges of transgastric NOTES, including access to the peritoneal cavity, the need for endoscope retroflexion for upper abdominal procedures, and endoscopic closure of the gastrotomy. The application of transgastric NOTES in urology has been limited to case reports in the porcine model, and no urologic procedure has been performed solely through a transgastric route. This article discusses the rationale of transgastric NOTES, its potential advantages and disadvantages, past and present work performed, current clinical applications, and its potential use in the future of urology.

Impact of obesity on ureteroscopic laser lithotripsy of urinary tract calculi.

PURPOSE: The treatment of urinary tract stones in obese patients may differ from the treatment of non-obese patients and their success rate varies. Our objective was to compare ureteroscopic treatment outcomes of ureteral and renal stones, stratified for stone size and location, between overweight, obese and non-obese patients. MATERIALS AND METHODS: Charts were reviewed for 500 consecutive patients presenting at our institution for renal and ureteral stones. A total of 107 patients underwent flexible or semi-rigid ureteroscopy with Ho:YAG laser lithotripsy and met criteria for review and analysis. RESULTS: Overall, initial stone-free rates were 91%, 97%, and 94% in normal, overweight and obese individuals respectively. When compared to non-obese patients, there were no significant differences (p value = 0.26; 0.50). For renal and proximal ureteral stones, the stone-free rate in overweight and obese individuals was 94% in both groups; and a stone-free rate of 100% was found for distal stones, also in both groups. CONCLUSIONS: Ureteroscopic treatment of stones in obese and overweight patients is an acceptable treatment modality, with success rates similar to non-obese patients.

Novel use of a ureteroscopic stone entrapment device to prevent antegrade stone migration during percutaneous nephrolithotomy.

The Accordion stone management device is a hydrophilic microcatheter-based tool that blocks stone migration. This instrument has been described for use during ureteroscopy to prevent retropulsion of stone fragments. We used this device during percutaneous nephrolithotomy (PCNL) in 30 patients to prevent antegrade migration of stone fragments (group 1), and find that the device is easily inserted and deployed, preventing antegrade stone fragment migration in all but one patient. When compared with 30 patients who were undergoing PCNL without the Accordion device (group 2), our results suggest that the device prevents antegrade stone fragment migration during PCNL, permits targeting larger stones, reduces the use of ureteral stents, and facilitates tubeless procedures. The Accordion device has proven to be a valuable time and morbidity-saving adjunct to PCNL at our institution.

Outpatient double percutaneous endolaparoscopic extraction of large continent urinary reservoir stones--a new minimally invasive approach.

PURPOSE: We report an efficient new method of managing massive stone burdens in continent urinary reservoirs without urethral access, using the minimally invasive double percutaneous endolaparoscopic technique. PATIENTS AND METHODS: After first obtaining and dilating a percutaneous tract into the reservoir, a second access is established using a laparoscopic trocar under direct vision. Using endoscopic instruments, large stones are placed into a laparoscopic entrapment bag, fragmented (if necessary), and then transferred extracorporeally without any damage to the integrity or mucosa of the reservoir and without leaving behind any stone fragments. RESULTS: This technique was used successfully in 5 of 5 patients with continent reservoirs, achieving stone-free status without short-term or long-term (mean follow-up 32.4 months, range 9-61 months) complications. CONCLUSION: Double percutaneous endolaparoscopic stone extraction is a safe, effective, and minimally invasive method of managing continent urinary reservoir stones.

Impact of obesity on ureteroscopic laser lithotripsy of urinary tract calculi

Purpose: The treatment of urinary tract stones in obese patients may differ from the treatment of non-obese patients and their success rate varies. Our objective was to compare ureteroscopic treatment outcomes of ureteral and renal stones, stratified for stone size and location, between overweight, obese and non-obese patients. Materials and Methods: Charts were reviewed for 500 consecutive patients presenting at our institution for renal and ureteral stones. A total of 107 patients underwent flexible or semi-rigid ureteroscopy with Ho:YAG laser lithotripsy and met criteria for review and analysis. Results: Overall, initial stone-free rates were 91 percent, 97 percent, and 94 percent in normal, overweight and obese individuals respectively. When compared to non-obese patients, there were no significant differences (p value = 0.26; 0.50). For renal and proximal ureteral stones, the stone-free rate in overweight and obese individuals was 94 percent in both groups; and a stone-free rate of 100 percent was found for distal stones, also in both groups. Conclusions: Ureteroscopic treatment of stones in obese and overweight patients is an acceptable treatment modality, with success rates similar to non-obese patients.

Clinical evaluation of efficacy of novel optically activated digital endoscope protection system against laser energy damage.

OBJECTIVES: To evaluate the clinical reliability and efficacy of a novel endoscope protection system (EPS) against direct laser energy damage during ureteroscopy. METHODS: We performed an in vivo evaluation of a novel EPS prototype that uses optical feedback from the digital sensor of the Invisio Digital Flexible Ureteroscope (DUR-D) to terminate laser energy on retraction of the fiber. We evaluated 20 consecutive patients undergoing flexible ureteroscopy. In each patient, the laser was retracted into the ureteroscope 4 times during active firing using a fast pull (5 cm/s) and a slow pull (2 cm/s) with the ureteroscope straight and flexed. We documented whether the EPS activated, whether the laser shut down properly, and the length of fiber projecting from the ureteroscope at laser shutdown. RESULTS: The EPS was 100% effective in shutting down the laser before entry into the ureteroscope in all trials (80/80). The mean length of fiber showing from the tip of the ureteroscope at shutdown was 1.55 mm (range 0-2.5) when the ureteroscope was straight and 1.28 mm (range 0-2.0) when it was flexed. EPS laser shutoff occurred in 50% (10/20) of the cases when the laser fiber was still outside the ureteroscope. One DUR-D ureteroscope was damaged during the trial from mechanical damage. CONCLUSIONS: In this clinical evaluation, the novel EPS was highly effective and reliable. No energy-based ureteroscope damage was noted with slow and rapid retractions of the activated laser into the ureteroscope. The EPS can be used to complement, rather than replace, the standard safe laser technique.

Stereocontrol in Intermolecular Dirhodium(II)-Catalyzed Carbonyl Ylide Formation and Reactions. Dioxolanes and Dihydrofurans.

Ethyl diazoacetate undergoes dirhodium(II)-catalyzed reactions with aryl aldehydes to form 1,3-dioxolanes as mixtures of diastereoisomers in good yields. Carbonyl ylides are reaction intermediates. Catalyst dependent diastereocontrol is observed for reactions with p-nitrobenzaldehyde, but not for those with p-anisaldehyde or benzaldehyde, so that at least with transformations involving p-nitrobenzaldehyde a metal-stabilized ylide is responsible for product formation. Higher yields are obtained with catalysis by dirhodium(II) carboxamidates than with the carboxylates. Diastereoselectivity in 1,3-dioxolane formation that occurs through the "free" ylide can be effectively controlled so that only one diastereomer is produced through the use of 2,6-di-tert-butyl-4-methylphenyl diazoacetate (BDA) or dicyclohexylmethyl diazoacetate (DCM). The thermodynamically least stable all-cis trisubstituted 1,3-dioxolane is the primary product from p-nitrobenzaldehyde "cycloaddition" to the metal-stabilized ylide. Reactions that take place in the presence of p-anisaldehyde and dimethyl acetylenedicarboxylate (DMAD) result in the formation of one 2,5-dihydrofuran-2-carboxylate stereoisomer in good yield. In contrast, with p-nitrobenzaldehyde and DMAD both dihydrofuran stereoisomers are produced along with, mainly, the dioxolane derived from the metal-stabilized ylide; there is in this case competition between addition reactions of the "free" ylide and the metal-associated ylide.