Philip Dorsey

Phosphodiesterase type 5 (PDE5) inhibitors for the treatment of erectile dysfunction

Importance to the field: Since sildenafil was introduced 10 years ago, highly selective phosphodiesterase type 5 inhibitors (PDE5i) have changed the medical management of erectile dysfunction (ED). A significant body of research has been devoted to the use of this class of medication for the treatment of ED and has advanced our understanding of erectile physiology. Recently, investigators have noted the potential benefits of this class of medication in the treatment of various urologic and non-urologic conditions, and novel agents in this class are in late-stage trials. Areas covered in this review: Clinical and basic science articles published between 1990 and 2009 were selected from multiple sources, including PubMed, Lexis-Nexis, EBSCO, and manufacturer websites. Our search focused on clinical outcomes of PDE5i for the treatment of ED and other medical conditions and basic science publications examining pharmacologic effects. What the reader will gain: This review provides a thorough description of the currently available PDE5i and the major clinical trials published for the use of PDE5i for the treatment of ED, as well as notable animal and basic science studies. In addition, we review upcoming drugs in this class, emerging indications and goals for future research. Take-home message: PDE5i will remain the mainstay initial medical treatment for ED and will play a larger role in the treatment of other medical conditions. Novel formulations in this class will allow patients to select agents that best suit their needs.

Optimizing Vesicourethral Anastomosis Healing After Robot-Assisted Laparoscopic Radical Prostatectomy: Lessons Learned from Three Techniques in 1900 Patients

BACKGROUND AND PURPOSE Creation of an optimally apposed, tension-free, well-supported vesicourethral anastomosis remains the cornerstone for anastomotic healing after radical prostatectomy. We report the effect of three techniques of bladder neck reconstruction during robot-assisted radical prostatectomy on anastomotic leak, stricture formation, and continence recovery. PATIENTS AND METHODS Between January 2005 to September 2009, 1900 consecutive patients underwent robotic-assisted laparoscopic prostatectomy (RALP) by a single surgeon. Of these, the first 214 underwent vesicourethral conventional anastomosis (CA); the next 303 men underwent anterior reconstruction (AR) only; and last 1383 men underwent total anatomic restoration (TR). Data elements included patient age, body mass index, preoperative biopsy Gleason score and prostate-specific antigen level, prostate volume, total operative time, console time, time for performing vesicourethral anastomosis, estimated blood loss, tumor stage, and margin status on final pathologic findings. Primary end points were rates of clinically significant anastomotic leaks, bladder neck contractures, and time to return of continence. Chi-square and Fisher exact tests were used for analysis of categoric variables. The Cox proportional hazard model was used for both univariate and multivariate analysis. RESULTS Clinically significant anastomotic leakage and bladder neck strictures were significantly fewer in the reconstructed groups (2.3% vs 1.0% vs 0.3% and 3.7% vs 1.3% vs 0.5% in the CA, AR, and TR groups, P < 0.01). Continence rates at 1, 6, 12, 26, and 52 weeks after RALP were also significantly better at all time points with AR and TR compared with CA alone (P < 0.001). CONCLUSIONS TR of the continence mechanism optimizes vesicourethral anastomosis healing and hastens early continence return after RALP.

Next-generation prostate cancer biobanking: toward a processing protocol amenable for the International Cancer Genome Consortium.

Next-generation DNA and RNA sequencing requires intact nucleic acids from high-quality human tissue samples to better elucidate the molecular basis of cancer. We have developed a prostate biobanking protocol to acquire suitable samples for sequencing without compromising the accuracy of clinical diagnosis. To assess the clinical implications of implementing this protocol, we evaluated 105 consecutive radical prostatectomy specimens from November 2008 to February 2009. Alternating levels of prostate samples were submitted to Surgical Pathology as formalin-fixed, paraffin-embedded blocks and to the institutional biobank as frozen blocks. Differences in reported pathologic characteristics between clinical and procured specimens were compared. Clinical staging and grading were not affected by the biobank protocol. Tumor foci on frozen hematoxylin and eosin slides were identified and high-density tumor foci were scored and processed for DNA and RNA extractions for sequencing. Both DNA and RNA were extracted from 22 cases of 44 with high-density tumor foci. Eighty-two percent (18/22) of the samples passed rigorous quality control steps for DNA and RNA sequencing. To date, DNA extracted from 7 cases has undergone whole-genome sequencing, and RNA from 18 cases has been RNA sequenced. This protocol provides prostate tissue for high-throughput biomedical research and confirms the feasibility of actively integrating prostate cancer into The Cancer Genome Atlas Program, a member of the International Cancer Genome Consortium.

Real Time Monitoring of Temperature Changes in Neurovascular Bundles During Robotic Radical Prostatectomy: Thermal Map for Nerve-Sparing Radical Prostatectomy

OBJECTIVE A rise in temperature of more than 55 degrees C in tissues, even for short a duration has been implicated in irreversible tissue damage. This study was aimed at recording real time temperature changes at the neurovascular bundle (NVB) during the use of cautery in robotic radical prostatectomy. METHODS The temperature was monitored with a needle electrode in 15 cases of athermal nerve sparing and 10 cases of non-nerve sparing robotic radical prostatectomy (RRP). The needle was placed in the peritoneal cavity through the camera port and inserted around the NVB. Body temperature was recorded by nasal cannula and compared with the baseline temperature at the neurovascular bundle. The distance of the needle probe from the area of cautery use, changes in temperature at the neurovascular bundle and the duration of cautery use was recorded during the use of monopolar and bipolar current in tissue dissections. RESULTS The mean baseline temperature at the neurovascular bundle was 0.8 degrees C lower than the body temperature. Average duration for cautery use at the anterior bladder neck and NVB with monopolar and bipolar current was 53.6 (45-65) and 79.8 (70-92) and 56.8 (45-60) and 65.7 seconds (59-76) respectively. The mean temperature rise during bladder neck dissection (distance more than 1 cm) was 43.6 degrees C [36.4-47.3 degrees C] with the monopolar and 38.8 degrees C [36.8 degrees-42.6 degrees C] with bipolar. During NVB dissection, the mean temperature rise was 53.6 degrees C (45.1 to 68.1 degrees C) with monopolar and 60.91 degrees C (47.2 to 109.8 degrees C) with bipolar. Though this difference was not significant, the mean time to return to baseline temperature was 3 seconds more with bipolar than monopolar. CONCLUSIONS Bipolar cautery may not be safer than monopolar because of a greater rise in temperature of surrounding tissues within 1 cm of its use. Further investigation is needed to fully establish the pathologic consequences associated with increased temperature due to cautery.

The dangers of sexual enhancement supplements and counterfeit drugs to “treat” erectile dysfunction

Counterfeit phosphodiesterase-5 inhibitors (PDE-5i) are an increasing problem. Already in widespread use, the market for PDE-5i is steadily growing as the population ages. Counterfeiters are taking advantage of this growing market by developing illicit and counterfeit PDE-5i products. Many factors are contributing to the rapid growth of the illicit market, such as the low risk of prosecution, potentially high financial reward, and ease of distribution via Internet pharmacies. Consumers of illicit PDE-5i often do not realize they are using counterfeit products and placing themselves at an unnecessary health risk. Others seek to bypass the legitimate healthcare system due to either embarrassment of the underlying condition or desire for cheaper alternatives. However, taking illicit PDE-5i may harm consumers directly, as many illicit products contain detrimental contaminants and inaccurate amounts of the active ingredient without the appropriate warnings. Bypassing the legitimate healthcare system also endangers consumers indirectly, as erectile dysfunction (ED) is often associated with other medical comorbidities that patients should be screened for. Furthermore, PDE-5i can have potentially dangerous interactions with other pharmaceuticals that are rarely warned against with counterfeit PDE-5i. This communication reviews the literature regarding counterfeit PDE-5i, and summarizes both the scope and dangers of the illicit PDE-5i market.

Double-Pigtail Stenting of the Ureters: Technique for Securing the Ureteral Orifices During Robot-Assisted Radical Prostatectomy for Large Median Lobes

Patients with large median prostate lobes undergoing robot-assisted radical prostatectomy are at potential risk of ureteric orifice injury, during posterior bladder neck transection and vesicourethral anastomosis reconstruction. We describe our technique of in situ robot-assisted ureteral stenting with double-pigtail stents for accurate observation and preservation of the ureteral orifices. We have performed this maneuver in over 30 patients in our cohort of over 1500 patients undergoing robot-assisted radical prostatectomy to date--none of these patients developed urinary leak or bladder neck contracture, and had uneventful cystoscopic removal of stents at 6 weeks after surgery.

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy

Abstract. Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Retrograde Renal Cooling to Minimize Ischemia

OBJECTIVE During partial nephrectomy, renal hypothermia has been shown to decrease ischemia induced renal damage which occurs from renal hilar clamping. In this study we investigate the infusion rate required to safely cool the entire renal unit in a porcine model using retrograde irrigation of iced saline via dual-lumen ureteral catheter. MATERIALS AND METHODS Renal cortical, renal medullary, bowel and rectal temperatures during retrograde cooling in a laparoscopic porcine model were monitored in six renal units. Iced normal saline was infused at 300 cc/hour, 600 cc/hour, 1000 cc/hour and gravity (800 cc/hour) for 600 seconds with and without hilar clamping. RESULTS Retrograde cooling with hilar clamping provided rapid medullary renal cooling and significant hypothermia of the medulla and cortex at infusion rates ≥ 600 cc/hour. With hilar clamping, cortical temperatures decreased at -0.90 C/min. reaching a threshold temperature of 26.90 C, and medullary temperatures decreased at -0.90 C/min. reaching a temperature of 26.10 C over 600 seconds on average for combined data at infusion rates = 600 cc/hour. The lowest renal temperatures were achieved with gravity infusion. Without renal hilum clamping, retrograde cooling was minimal at all infusion rates. CONCLUSIONS Significant renal cooling by gravity infusion of iced cold saline via a duel lumen catheter with a clamped renal hilum was achieved in a porcine model. Continuous retrograde irrigation with iced saline via a two way ureteral catheter may be an effective method to induce renal hypothermia in patients undergoing robotic assisted and/or laparoscopic partial nephrectomy.

Difficulties in Robotic-Assisted Nerve-Sparing Radical Prostatectomy

Serum prostate-specific antigen (PSA) screening, coupled with a rising incidence of needle biopsies in asymptomatic men, have all contributed to prostate cancer becoming the most common cancer in men in the United States1,2 and other parts of the world.3 With increasing evidence of improved long-term survival and progression-free outcomes,4–7 radical prostatectomy has become increasingly popular as the treatment of first choice for organ-confined disease.