MicroSegNet: A deep learning approach for prostate segmentation on micro-ultrasound images.

Micro-ultrasound (micro-US) is a novel 29-MHz ultrasound technique that provides 3-4 times higher resolution than traditional ultrasound, potentially enabling low-cost, accurate diagnosis of prostate cancer. Accurate prostate segmentation is crucial for prostate volume measurement, cancer diagnosis, prostate biopsy, and treatment planning. However, prostate segmentation on micro-US is challenging due to artifacts and indistinct borders between the prostate, bladder, and urethra in the midline. This paper presents MicroSegNet, a multi-scale annotation-guided transformer UNet model designed specifically to tackle these challenges. During the training process, MicroSegNet focuses more on regions that are hard to segment (hard regions), characterized by discrepancies between expert and non-expert annotations. We achieve this by proposing an annotation-guided binary cross entropy (AG-BCE) loss that assigns a larger weight to prediction errors in hard regions and a lower weight to prediction errors in easy regions. The AG-BCE loss was seamlessly integrated into the training process through the utilization of multi-scale deep supervision, enabling MicroSegNet to capture global contextual dependencies and local information at various scales. We trained our model using micro-US images from 55 patients, followed by evaluation on 20 patients. Our MicroSegNet model achieved a Dice coefficient of 0.939 and a Hausdorff distance of 2.02 mm, outperforming several state-of-the-art segmentation methods, as well as three human annotators with different experience levels. Our code is publicly available at https://github.com/mirthAI/MicroSegNet and our dataset is publicly available at https://zenodo.org/records/10475293.

Robotic Puboprostatic Fistula Repair with Holmium Laser Pubic Debridement.

INTRODUCTION AND OBJECTIVE: Urosymphyseal fistula (UF) with osteomyelitis most commonly occurs as a result of prostate cancer and benign prostate hyperplasia therapy. UF presentation typically includes debilitating pelvic pain exacerbated with ambulation. Traditional management required open surgical genitourinary (GU) reconstruction with pubectomy leading to significant morbidity. However, progressive utilization of robotic approaches and advances in holmium laser technology has led to a less invasive alternative. Herein, we present our series of robotic-assisted holmium laser debridement of pubic osteomyelitis in the setting of UF. METHODS: After physical exam, all patients presenting with concerns for GU fistula and osteomyelitis are evaluated with BMP, CBC, serum albumin, urine culture, and cystoscopy. Patients often present with previously obtained CT abdomen/pelvis. However, all patients presenting with concerns of pubic osteomyelitis should undergo a MRI of the pelvis to characterize the pubis. Specific indications for holmium laser debridement of the pubic bone include: 1) history of sacral insufficiency fractures which eliminate management with partial pubectomy due to risk of pelvic ring instability and 2) mild osteomyelitis which can be managed with debridement. The patient is placed in dorsal lithotomy position. After the robot is docked, the space of retzius is developed and the fistula is resected down to the pubic bone. The symphysis is debrided using the Cobra grasper followed by holmium laser debridement at 2J and 50Hz settings. Appropriate GU reconstruction versus urinary diversion is then performed per clinical judgement. Antibiotic beads are then placed in the symphyseal defect. If available, an interposition flap may be advanced between the urethra/bladder and symphysis. RESULTS: In our series of four patients, all patients underwent successful robotic pubic symphyseal debridement and were discharged without experiencing a major complication. At follow up (7-16 months) there have been no fistula recurrence or recurrent episodes of osteomyelitis. CONCLUSION: Robotic assisted pubic symphyseal debridement with a holmium laser is feasible, safe, and efficacious in this small series with short follow up. This approach represents a minimally invasive alternative to open pubectomy while minimizing incisions and overall morbidity. Additional long-term data is necessary before wide spread adoption of this approach.

Robot-Assisted Radical Nephroureterectomy.

First proposed by Kimball and Ferris in 1933 for the treatment of papillary tumors in the upper urinary tract, radical nephroureterectomy (RNU) with bladder cuff excision remains the gold standard for management of high-risk upper tract urothelial carcinoma involving the proximal ureter and/or pelvicaliceal system. Over three decades since the first description of laparoscopic RNU, minimally invasive approaches to RNU have continued to evolve and become increasingly utilized. More recently, robot-assisted RNU (RARNU) has increasingly become a viable approach. Specifically, RARNU affords a reduction in perioperative morbidity and improved convalescence as a minimally invasive approach, all while adhering to traditional open surgical principles and providing surgeons with improved technical ergonomics and streamlined operating room logistics, particularly with the advent of the da Vinci Xi platform. In this study, we describe our approach to transperitoneal RARNU, including indications, operating room setup, step-by-step surgical technique, and perioperative care.

Outcomes in Patients with Known Contrast Allergy Undergoing Contrast-Enhanced Endourologic Procedures: A Retrospective Cohort Study.

Background: Intravenous (IV) administration of iodinated contrast agents carries the risk of allergic reaction, yet this risk is unclear with administration into the urinary tract. We sought to evaluate patients with known contrast, iodine, or shellfish allergies for allergic response when undergoing urologic imaging requiring intraluminal urinary tract contrast administration. Materials and Methods: We retrospectively reviewed consecutive patients undergoing endourologic procedures from 2010 to 2015 at our institution. Clinical records were reviewed for demographics, medical history, allergies, procedure details, fluids administered, anesthetic and pharmacologic agents administered, and continuous monitoring parameters. Patients with known allergies to iodine, shellfish, and/or contrast were identified and evaluated for clinical or hemodynamic signs of allergy. A convenience sample of 50 patients without allergy history was used as a comparison group. Results: We identified 1405 procedures involving 1000 consecutive patients. Procedures included retrograde pyelograms and antegrade nephrostograms. Eighty-six cases involving 58 patients with contrast, iodine, or shellfish allergies were identified. Of those with contrast allergy history, 18 (20.1%) cases involved patients with a history of anaphylactic reaction. Of these, 11 (61%) received steroid prophylaxis. No patients in either group (Allergy, No Allergy) were identified as having an allergic reaction during the procedure. There were no statistically significant differences in intraoperative IV fluids (p = 0.931), procedure duration (p = 0.747), or vasopressor use (p = 0.973) between groups. Owing to the zero event rate of contrast allergy, we used the Hanley and Lippman-Hand method, which places true population risk (95% confidence interval) of a significant event at <3.5%. Conclusions: In 86 cases involving patients with a history of contrast allergy, we found no evidence of clinically significant allergic reaction to intraluminal endourologic contrast administration under continuous anesthesia monitoring. The risk of significant reactions to contrast administered within the urinary tract appears to be low in these patients, regardless of prophylaxis.

Intraureteral indocyanine green augments ureteral identification and avoidance during complex robotic-assisted colorectal surgery.

AIM: Up to 10% of patients who undergo nonurological abdominopelvic operations suffer a ureteral injury. While preoperative ureteral stenting to facilitate identification of the ureter is common, it does not reduce the incidence of intraoperative ureteral injury and is not without risk. As we continue to broaden the application of minimally invasive surgical techniques, a new form of ureteral identification and avoidance that does not rely on tactile feedback is needed. We report our initial experience with intraureteral indocyanine green (ICG) for ureteral identification and avoidance during complex robotic-assisted colorectal surgery. METHOD: Patients undergoing adjunctive ureteral identification during robotic-assisted colorectal surgery were prospectively identified. Each patient underwent intraureteral ICG administration using rigid cystoscopy (22 Fr). A 5-Fr open-ended ureteral catheter was inserted up to 20 cm and used to inject 5 ml of 2.5 mg/ml ICG as the catheter was withdrawn to the ureteral orifice. Intraureteral ICG was then detected using near-infrared laser fluorescence technology (Firefly®). RESULTS: Successful ICG-enhanced ureteral identification and avoidance was performed in 15 of 16 (94%) patients undergoing robotic-assisted colorectal surgery. The median ICG instillation time was 11.5 min (range 4-21 min) and the median operative time with ICG visualization was 489 min (8 h 9 min) [range 268-738 min (4 h 28 min-12 h 18 min)]. No patient experienced intraoperative ureteral injury and there were no adverse sequelae or complications associated with intraureteral ICG administration. CONCLUSION: Intraureteral ICG is a safe and effective method of intraoperative ureteral identification and avoidance during complex robotic-assisted colorectal surgery. Precise and prolonged ureteral visualization was achieved, allowing for long operative times compatible with complex robotic-assisted operations.

Outcomes of RestoreX Penile Traction Therapy in Men With Peyronie's Disease: Results From Open Label and Follow-up Phases.

BACKGROUND: A randomized, controlled clinical trial evaluating the efficacy of RestoreX traction therapy in men with Peyronie's disease (PD) has been completed, with the 3-month results previously reported. The present study presents outcomes from the open-label and follow-up phases of the original trial. AIM: To report 6-month (open-label phase) and 9-month (follow-up phase) outcomes from a randomized, controlled trial (NCT03389854). METHODS: A randomized controlled trial was performed from 2017 to 2019 in 110 all-comer men with PD. Men were randomized 3:1 to RestoreX (PTT) or no therapy (control) for 3 months, followed by 3-month open-label and follow-up phases. Key outcomes included adverse events (AEs), changes in penile curvature and length, erectile function, and standardized and nonstandardized assessments of PD. OUTCOMES: The primary outcomes are safety, penile length, penile curvature, Peyronie's Disease Questionnaire, International Index of Erectile Function, and satisfaction. RESULTS: 6-month (n = 64) and 9-month (n = 63) outcomes were reported, with a mean duration of PTT use of 31.1 minutes. No significant AEs were reported, with temporary erythema and discomfort being most common and resolving within minutes. On intent-to-treat analysis, control-to-PTT men experienced significant length (1.7-2.0 cm) and curvature improvements (18-20%). PTT-to-PTT men also achieved additional length (0.6-0.8 cm) without further curvature improvements. An as-treated analysis of PTT use ≥15 minute/day demonstrated 2.0- to 2.3-cm length gains (largest of any PTT to date) and 18-21% curve improvement. All sexual function domains of the International Index of Erectile Function and Peyronie's Disease Questionnaire were significantly improved (except orgasmic domain). 95% of men treated for 6 months experienced length gains (mean 2.0-2.2 cm), and 61% had curve improvements (16.8-21.4° [32.8-35.8%]). RestoreX was preferred 3-4:1 over all other PD treatments, and 100% preferred it over other PTT devices. CLINICAL IMPLICATIONS: Use of RestoreX 30 minutes daily results in significant length and curve improvements in PD men without significant AEs. STRENGTHS & LIMITATIONS: Strengths include largest randomized study of PTT, blinded assessments, and inclusion of all-comers with few restrictions; limitations include sample size that precludes comparisons between treatment cohorts and lack of long-duration (>3-9 hours) treatment arm. CONCLUSION: PTT with RestoreX results in significant improvements in length, curve, and subjective and objective measures of sexual function without significant AEs. RestoreX PTT represents a safe, conservative, low-cost option for managing men with PD. Joseph J, Ziegelmann M, Alom M, et al. Outcomes of RestoreX Penile Traction Therapy in Men With Peyronie's Disease: Results From Open Label and Follow-up Phases. J Sex Med 2020;17:2462-2471.

Enhanced ambulatory male urethral surgery: a pathway to successful outpatient urethroplasty.

BACKGROUND: Length of stay following anterior urethroplasty (AU) surgery has progressively shortened over the past two decades with most patients discharging the day of surgery or following overnight observation. We sought to assess overall analgesia and patient satisfaction with same-day discharge after AU surgery. METHODS: Our prospectively maintained anterior urethroplasty database was reviewed. Men were identified who underwent anterior urethroplasty surgery by a single surgeon (B.R.V.) with the Enhanced Ambulatory Male Urethral Surgery (EAMUS) protocol followed by same-day discharge. Patients were contacted within 3 weeks of surgery and completed validated assessment tools to characterize satisfaction with the outpatient experience and with analgesia management. A statistical analysis was performed to assess predictors of overall satisfaction with same-day discharge following AU surgery. RESULTS: Fifty-seven patients with median age 52.2 years underwent same-day AU surgery between August 2017 and October 2018. In total, 46 patients (80.7%) responded to post-discharge surveys assessing overall outpatient satisfaction and satisfaction with analgesia. Median satisfaction with outpatient experience (scale 1-5) was 5 (IQR 4, 5) with 93.4% of patients indicating they were satisfied to very satisfied (4 or 5). Median patient satisfaction with analgesia (scale 1-6) was 6 (IQR 5, 6) with 93.4% of patients indicating a satisfaction with analgesia score of ≥5 (satisfied to very satisfied). Median number of 5 mg oxycodone tablets used following discharge was 3 (IQR 0.75, 5). Postoperative complications occurred in 14 patients (25%) with 12 (86%) being low grade complications (Clavien-Dindo Classification ≤ II). CONCLUSIONS: With appropriate preoperative education and peri-operative analgesia, anterior urethroplasty surgery can be performed with same-day discharge with comparable postoperative complication rates while maintaining excellent patient satisfaction. Additional high volume, prospectively collected studies are necessary to verify short-term satisfaction rates while confirming long-term urethroplasty success rates remain comparable to AU surgery performed with next day discharge.

Screening Postoperative Hemoglobin after Robot-Assisted Radical Prostatectomy-Frequently Used, but Is It Necessary?

INTRODUCTION: Robot-assisted radical prostatectomy is associated with low rates of postoperative transfusion and hemorrhage. At our institution the decision to obtain screening hemoglobin testing after uncomplicated robot-assisted radical prostatectomy is left to surgeon discretion. It is unknown whether this testing represents high value care. We assessed the prevalence and clinical utility of hemoglobin testing after uncomplicated robot-assisted radical prostatectomy. METHODS: We retrospectively reviewed patients undergoing robot-assisted radical prostatectomy between 2002 and 2016. Patients transfused intraoperatively were excluded. Demographic and perioperative data were reviewed. In patients requiring blood transfusion and/or with hemorrhage clinical signs/symptoms of anemia were reviewed. The primary endpoint was rate of routine postoperative hemoglobin testing. Secondary endpoints included rates of postoperative transfusion and hemorrhage, rates of signs/symptoms of anemia in patients transfused postoperatively and/or with hemorrhage. RESULTS: A total of 3,405 patients were identified of whom 73.8% (2,514) underwent postoperative hemoglobin testing. Mean change relative to preoperative hemoglobin was -2.7±1.0 gm/dl with 10.2% (256) and 3.5% (87) experiencing a decrease in hemoglobin 4 gm/dl or greater and postoperative hemoglobin 10 gm/dl or less, respectively. Of patients undergoing at least 1 postoperative hemoglobin test subsequent testing was prompted for 13.4% (337). Of patients transfused (1.7%, 58) and/or with postoperative hemorrhage (1.5%, 48) with records available for review (46), 95.7% (44) had clinical signs/symptoms of anemia. CONCLUSIONS: Our results suggest that routine hemoglobin testing after uncomplicated prostatectomy should be performed when clinically indicated rather than as routine practice.

Comparison of prescribing patterns before and after implementation of evidence-based opioid prescribing guidelines for the postoperative urologic surgery patient.

BACKGROUND: We developed evidence-based guidelines for postoperative opioid prescribing after urologic surgery and assessed changes in prescribing after implementation. METHODS: Prescribing data for adults who underwent 21 urologic procedures were used to derive a four-tiered guideline for postoperative opioid prescribing. This was implemented on January 1, 2018, and prescribing patterns including quantity of opioids prescribed (oral morphine equivalents; OME) and refill rates were compared between patients undergoing surgery prior to (January-April, 2017; n equals 1732) and after (January-April, 2018; n equals1376) implementation. RESULTS: The median OME (IQR) prescribed was significantly lower for 2018 compared with 2017 [100 (0; 175) versus 150 (60; 225); p < .0001]. The median prescribed OME decreased in 14/21 procedures (67%). The refill rates did not significantly change. Guideline adherence rates after implementation, based on individual procedures, ranged from 33 to 95%. CONCLUSIONS: Fewer opioids were prescribed after implementing a prescribing guideline. Additional study is required to assess patient opioid utilization.

Percutaneous Image-guided Core Needle Biopsy for Upper Tract Urothelial Carcinoma.

OBJECTIVE: To better understand the safety and diagnostic yield of percutaneous core-needle biopsy (PCNB) for upper tract urothelial carcinoma (UTUC). METHODS: Of 444 patients undergoing radical nephroureterectomy (RNU) for UTUC between 2009 and 2017 at our institution, 42 who had PCNB prior to RNU were identified for analysis. Endpoints included safety, diagnostic yield, and concordance with RNU pathology. PCNB specimens were deemed histologically concordant with RNU specimens for cases when cytologic evaluation of biopsy specimen and corresponding pathologic evaluation of RNU specimen both made a histologic diagnosis of urothelial carcinoma. RESULTS: Median tumor size was 3.8 cm (1.2-10.2 cm). All lesions arose from the pelvicalyceal system. CT-guidance was utilized in 52% (n = 22), and ultrasound-guidance in 48% (n = 20). Relative to RNU pathology, 95% of PCNBs demonstrated histologic concordance. Histologic grade was provided in 69% (n = 29) of PCNBs, with a 90% (n = 26) concordance with surgical pathology. Grades 1-2 and 3 complications occurred in 14.3% (n = 6) and 2.4% (n = 1), respectively. At a median follow-up of 28.2 months (range, 1.2-97.1 months) after biopsy, no cases of radiographic tract seeding were identified. CONCLUSION: In our cohort of 42 patients undergoing RNU for UTUC, PCNB appeared a safe diagnostic tool with high histologic yield and grade concordance. With greater than 2 years of follow-up, no cases of tract seeding were identified.

Evaluating the impact of radiation therapy on patient quality of life following primary artificial urinary sphincter placement.

BACKGROUND: The impact of prior radiation therapy on patient satisfaction following primary artificial urinary sphincter (AUS) placement is not well described, therefore our aim was to evaluate the effect of radiation on patient satisfaction among men undergoing primary AUS with and without a history of prior radiation. METHODS: From 1983-2011, 1,082 men underwent primary AUS placement at our institution. Of these, 467 were alive, with an intact primary AUS and invited to participate in a mailed survey assessing AUS status, patient satisfaction, and urinary control. Clinical subjective outcomes were assessed via reported change in urinary control from pre-operative to post-AUS placement. RESULTS: In total, 229/467 (49%) of men with an intact primary AUS completed the survey, with a median follow-up of 8.4 years [interquartile range (IQR) 5.8-11.4]. Of these, 64 men (28%) had a prior history of radiation therapy. Both men with and without history of radiation, reported a high likelihood of electing to have AUS surgery again, 87% vs. 91% respectively (P=0.87), and of recommending AUS surgery to a family member, 86% vs. 93% respectively (P=0.18). There were no significant differences between those with and without prior radiation with regard to rates of reported: substantial improvement in urinary control following surgery (72% vs. 78%, P=0.30), minimal bothersome leakage (57.1% vs. 66%, P=0.31), and pad use ≤1 pad/day (49% vs. 59%, P=0.06). CONCLUSIONS: In a large cohort of primary AUS implants with and without prior radiation therapy we noted a high-level of satisfaction and though many patients still utilized 1 or more pads/day with long-term follow-up. Importantly, there was no significant difference in quality of life (QoL) outcomes compared between those with and without prior radiation therapy.

Technical Considerations of Single Port Ureteroneocystostomy Utilizing da Vinci SP Platform.

OBJECTIVE: To demonstrate technical considerations of a true single port robotic assisted ureteroneocystostomy using the da Vinci SP platform (Intuitive Surgical, Sunnyvale, CA). METHODS: We present a 34 year-old female with an obliterative right distal ureteral stricture after undergoing a total abdominal hysterectomy for benign indications. After a period of ureteral rest, the patient elected to undergo a robotic assisted ureteroneocystostomy using the da Vinci SP platform. RESULTS: A refluxing ureteroneocystostomy was performed in 127 minutes, estimated blood loss was 20cc, and there were no complications. The infra-umbilical incision length was 25 mm. Intraoperative suction was achieved using flexible nasotracheal suction tubing passed alongside the 25 mm cannula. This was manipulated by the console surgeon with coordinated suction by the bedside assistant. A JJ stent was placed percutaneously with the assistance of a 14 gauge angiocatheter prior to completion of the anastomosis. CONCLUSION: To our knowledge, this represents the first case of a robotic assisted ureteroneocystostomy using the da Vinci SP platform without the use of an assistant port. This approach is safe and was completed in a similar operative time to other da Vinci systems. Single port specific considerations include novel suction device placement type, percutaneous stent advancement, and needle introduction without the use of an assistant port. Potential advantages of this technique include improved cosmesis as well as enhanced visualization and dexterity of the fully jointed instruments. Future studies are needed to assess for differences in perioperative outcomes.

Wide Variation in Opioid Prescribing After Urological Surgery in Tertiary Care Centers.

OBJECTIVE: To describe postoperative opioid prescribing practices in a large cohort of patients undergoing urological surgery. PATIENTS AND METHODS: We identified 11,829 patients who underwent 21 urological surgical procedures at 3 associated facilities from January 1, 2015, through December 31, 2016. After converting opioids to oral morphine equivalents (OMEs), prescribing patterns were compared within and across procedures. Subgroup analysis for opioid-naive patients (those without a history of long-term opioid use) was performed. Statistical analysis was utilized to evaluate variations based on demographic and perioperative/postoperative variables. RESULTS: Of the 11,829 patients, 9229 (78.0%) were prescribed an opioid at discharge, and the median (interquartile range [IQR]) OME prescribed was 188 (150-225). The remaining 9253 patients (78.2%) were considered opioid naive. Striking variation in prescribing patterns was observed within and across surgical procedures. For instance, IQR ranges of 150 or greater were observed for open cystectomy (median, 300; IQR, 210-375], open radical nephrectomy (median, 300; IQR, 225-375), retroperitoneal node dissection (median, 300; IQR, 225-375), hand-assisted laparoscopic nephrectomy (median, 225; IQR, 150-300), and penile prosthesis (median, 225; IQR, 150-315). On multivariate analysis, younger age, cancer diagnosis, and inpatient hospitalization were associated with higher likelihood of receiving a highest-quartile OME prescription for opioid naive patients. Thirty-day refill rates varied from 1.6% to 25.9%. Interestingly, refill rates were higher in patients receiving more opioids at discharge. CONCLUSION: The United States is facing an opioid epidemic, and physicians must take action. In this study, we found considerable variation in opioid prescribing patterns within and across surgical procedures. These data provide support for the development of standardized opioid prescribing guidelines for postoperative analgesia.

Postoperative rhabdomyolysis following robotic renal and adrenal surgery: a cautionary tale of compounding risk factors.

This study aimed at reviewing a contemporary series of patients who underwent robotic renal and adrenal surgery by a single surgeon at a tertiary referral academic medical center over a 6-year period, specifically focusing on the unique and serious complication of post-operative rhabdomyolysis of the dependent lower extremity. The cases of 315 consecutive patients who underwent robotic upper tract surgery over a 6-year period from August 2008 to June 2014 using a standardized patient positioning were reviewed and analyzed for patient characteristics and surgical variables that may be associated with the development of post-operative rhabdomyolysis. The incidence of post-operative rhabdomyolysis in our series was 3/315 (0.95%). All three affected patients had undergone robotic nephroureterectomy. Those patients who developed rhabdomyolysis had significantly higher mean Body Mass Index, Charlson Comorbidity Index, and median length of stay than those who did not. The mean OR time in the rhabdomyolysis group was noted to be 52 min longer than the non-rhabdomyolysis group, though this value did not reach statistical significance. Given the trends of increasing obesity in the United States and abroad as well as the continued rise in robotic upper tract urologic surgeries, urologists need to be increasingly vigilant for recognizing the risk factors and early treatment of the unique complication of post-operative rhabdomyolysis.

Cytotoxic and targeted therapy for treatment of pseudomyogenic hemangioendothelioma.

Pseudomyogenic hemangioendothelioma (PMH) is a recently described, indolent vascular tumor that usually presents in the distal extremities. PMH typically has a multi-focal presentation and can involve several tissue planes including the dermis, subcutis, muscle, and bone. This soft tissue tumor predominantly affects men between 20 and 50 years of age. PMH tumors typically are resected but frequently recur locally; thus, more efficacious treatment options are needed. Herein, we report two cases of patients with PMH who were treated with systemic therapy. To the best of our knowledge, our report is the first to describe a response of PMH either to gemcitabine/taxane cytotoxic chemotherapy or to a mammalian target of rapamycin inhibitor. In the first case, a 45-year-old man with PMH of the right ilium was treated with gemcitabine plus docetaxel. Although chemotherapy was ultimately halted owing to gemcitabine-induced pulmonary toxicity, positron emission tomography-computer tomography scans taken after three cycles of gemcitabine plus docetaxel illustrated a noticeable response to the regimen. In the second case, a 22-year-old man with PMH of the right distal femur and metastases in the left ilium showed no response to gemcitabine plus docetaxel therapy, but underwent surgical resection after cisplatin and doxorubicin resulted in stable disease. DNA sequencing of his tumor revealed the presence of a tuberous sclerosis 1 (TSC1) mutation, so daily everolimus, which inhibits mammalian target of rapamycin, was started. Two months after beginning everolimus, the patient underwent magnetic resonance imaging of the pelvis, which revealed mild shrinkage of PMH metastases in the left iliac bone. Despite the apparent heterogeneity of response to gemcitabine/taxane chemotherapy in our two patients, these two cases indicate that gemcitabine/taxane and mammalian target of rapamycin inhibitor may serve as systemic treatment options for PMH and warrant further investigation.

Robot-assisted anterior wall extravesical ureteral reimplantation.

INTRODUCTION: Here we describe our technique for robot-assisted, extravesical, anterior wall ureteral reimplantation for select patients with obstructive megaureter or high grade VUR with paraureteral diverticulum. We performed anterior wall reimplantation, extrapolating our experience with anterior wall appendicovesicostomy [Famakinwa et al., Eur Urol 2013;64(5):831-6] METHODS: We applied this technique at our institution for a total of 6 patients: 4 pediatric, 2 adult. Amongst our pediatric patients, 3 underwent surgery for obstructive megaureter, and 1 for a paraureteral bladder diverticulum with high grade VUR. Our 2 adult patients opted for surgery in the setting of distal ureteral strictures. To avoid ureteral kinking, we perform detrusorotomy in alignment with the ureter, and take care to avoid ureteral laxity during reimplantation. RESULTS: Following surgery, each of our 6 patients continues to remain without evidence of obstruction, including ureteral kinking, with follow-up ranging from 3 months to 5 years. No procedural-related complications have been noted to date. CONCLUSION: We have found this approach to be technically straightforward, avoiding intravesical dissection and associated morbidity of bladder spasm, while achieving functional outcomes.

Angiotensin type 2 receptor (AT2R) and receptor Mas: a complex liaison.

The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striking similarities. Moreover, in some instances, antagonists for one receptor are able to inhibit the action of agonists for the respective other receptor. These observations suggest that there may be a functional or even physical interaction of both receptors. This article discusses potential mechanisms underlying the phenomenon of blockade of angiotensin-(1-7) [Ang-(1-7)] actions by AT2R antagonists and vice versa. Such mechanisms may comprise dimerization of the receptors or dimerization-independent mechanisms such as lack of specificity of the receptor ligands used in the experiments or involvement of the Ang-(1-7) metabolite alamandine and its receptor MrgD in the observed effects. We conclude that evidence for a functional interaction of both receptors is strong, but that such an interaction may be species- and/or tissue-specific and that elucidation of the precise nature of the interaction is only at the very beginning.

The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke.

Evidence indicates that angiotensin II type 2 receptors (AT2R) exert cerebroprotective actions during stroke. A selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exert beneficial effects in models of cardiac and renal disease, as well as hemorrhagic stroke. Here, we hypothesize that C21 may exert beneficial effects against cerebral damage and neurological deficits produced by ischemic stroke. We determined the effects of central and peripheral administration of C21 on the cerebral damage and neurological deficits in rats elicited by endothelin-1 induced middle cerebral artery occlusion (MCAO), a model of cerebral ischemia. Rats infused centrally (intracerebroventricular) with C21 before endothelin-1 induced MCAO exhibited significant reductions in cerebral infarct size and the neurological deficits produced by cerebral ischemia. Similar cerebroprotection was obtained in rats injected systemically (intraperitoneal) with C21 either before or after endothelin-1 induced MCAO. The protective effects of C21 were reversed by central administration of an AT2R inhibitor, PD123319. While C21 did not alter cerebral blood flow at the doses used here, peripheral post-stroke administration of this agent significantly attenuated the MCAO-induced increases in inducible nitric oxide synthase, chemokine (C-C) motif ligand 2 and C-C chemokine receptor type 2 mRNAs in the cerebral cortex, indicating that the cerebroprotective action is associated with an anti-inflammatory effect. These results strengthen the view that AT2R agonists may have potential therapeutic value in ischemic stroke, and provide the first evidence of cerebroprotection induced by systemic post stroke administration of a selective AT2R agonist.

Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke.

Activation of angiotensin-converting enzyme 2 (ACE2), production of angiotensin-(1-7) [Ang-(1-7)] and stimulation of the Ang-(1-7) receptor Mas exert beneficial actions in various peripheral cardiovascular diseases, largely through opposition of the deleterious effects of angiotensin II via its type 1 receptor. Here we considered the possibility that Ang-(1-7) may exert beneficial effects against CNS damage and neurological deficits produced by cerebral ischaemic stroke. We determined the effects of central administration of Ang-(1-7) or pharmacological activation of ACE2 on the cerebral damage and behavioural deficits elicited by endothelin-1 (ET-1)-induced middle cerebral artery occlusion (MCAO), a model of cerebral ischaemia. The results of the present study demonstrated that intracerebroventricular infusion of either Ang-(1-7) or an ACE2 activator, diminazine aceturate (DIZE), prior to and following ET-1-induced MCAO significantly attenuated the cerebral infarct size and neurological deficits measured 72 h after the insult. These beneficial actions of Ang-(1-7) and DIZE were reversed by co-intracerebroventricular administration of the Mas receptor inhibitor, A-779. Neither the Ang-(1-7) nor the DIZE treatments altered the reduction in cerebral blood flow elicited by ET-1. Lastly, intracerebroventricular administration of Ang-(1-7) significantly reduced the increase in inducible nitric oxide synthase mRNA expression within the cerebral infarct that occurs following ET-1-induced MCAO. This is the first demonstration of cerebroprotective properties of the ACE2-Ang-(1-7)-Mas axis during ischaemic stroke, and suggests that the mechanism of the Ang-(1-7) protective action includes blunting of inducible nitric oxide synthase expression.