Uretero-neocystostomy: a retrospective comparison of open, laparoscopic and robotic techniques.

BACKGROUND: Uretero-neocystostomy (UNC) is the gold-standard for distal-ureter repair. Whether the surgery should be conducted minimally invasive (laparoscopic (LAP), robotic RAL)) or open remains unanswered by the literature. METHODS: Retrospective analysis of surgical outcome of patients treated with UNC for distal ureteral stenosis (January 2012 - October 2021). Patient demographics, estimated blood loss (EBL), surgical technique, operative time, complications and length of hospital stay (LOS) were recorded. During the follow-up period, patient underwent renal ultrasound and kidney function tests. Success was defined as relieve of symptoms or no findings of obstruction needing urine drainage. RESULTS: 60 patients were included (9 RAL, 25 LAP, 26 open). The different cohorts were similar of age, gender, American Society of Anesthesiologists (ASA) score, body-mass index and history of prior treatment of the ureter. No intraoperative complications were detected in all groups. There was no conversion to open surgery in the RAL group, whereas one was found in the LAP arm. Six patients had a recurrent stricture, but with no significant difference between the cohorts. EBL was not different between the groups. LOS was significantly lower in the RAL + LAP group compared to open (7 vs. 13 days, p = 0.005) despite significantly longer operating times (186 vs. 125.5 min, p = 0.005). CONCLUSION: Minimal invasive UNC, especially RAL, is a feasible and safe surgical method and provides similar results in terms of success rates in comparison to open approach. A shorter LOS could be detected. Further prospective studies need to be done.

External validation of two mpMRI-risk calculators predicting risk of prostate cancer before biopsy.

PURPOSE: Risk calculators (RC) aim to improve prebiopsy risk stratification. Their latest versions now include multiparametric magnetic resonance imaging (mpMRI) findings. For their implementation into clinical practice, critical external validations are needed. METHODS: We retrospectively analyzed the patient data of 554 men who underwent ultrasound-guided targeted and systematic prostate biopsies at 2 centers. We validated the mpMRI-RCs of Radtke et al. (RC-R) and Alberts et al. (RC-A), previously shown to predict prostate cancer (PCa) and clinically significant PCa (csPCa). We assessed these RCs' prediction accuracy by analyzing the receiver-operating characteristics (ROC) curve and evaluated their clinical utility using Decision Curve Analysis (DCA), including Net-Benefit and Net-Reduction curves. RESULTS: We found that the Area Under the ROC Curve (AUC) for predicting PCa was 0.681 [confidence interval (CI) 95% 0.635-0.727] for RC-A. The AUCs for predicting csPCa were 0.635 (CI 95% 0.583-0.686) for RC-A and 0.676 (CI 95% 0.627-0.725) for RC-R. For example, at a risk threshold of 12%, RC-A needs to assess 334 and RC-R 500 patients to detect one additional true positive PCa or csPCa patient, respectively. At the same risk threshold of 12%, RC-A only needs to assess 6 and RC-R 16 patients to detect one additional true negative PCa or csPCa patient. CONCLUSION: The mpMRI-RCs, RC-R and RC-A, are robust and valuable tools for patient counseling. Although they do not improve PCa and csPCa detection rates by a clinically meaningful margin, they aid in avoiding unnecessary prostate biopsies. Their implementation could reduce overdiagnosis and reduce PCa screening morbidity.

En bloc re-resection of high-risk NMIBC after en bloc resection: results of a multicenter observational study.

PURPOSE: To investigate the role of en bloc re-resection (EBRS) in patients who had undergone previous en bloc resection for high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: An international, multicenter, observational retrospective analysis of prospectively collected data. Patients with a high-risk NMIBC who had previously undergone en bloc resection were scheduled for EBRS of the resected area after 40 days. The primary outcome was the presence of residual tumor or recurrence-free survival. RESULTS: Overall, 78 patients underwent EBRS. Only five (6.41%) residual cancers were found: one patient had a pTa G3 (1.28%) cancer and four (5.13%) had a pTis. The detrusor muscle was preserved in all samples. Only one patient had a positive margin on EBRS. No procedure called for a conversion to traditional re-TURBT. No patient experienced bladder perforation or other intra-operative complications. The recurrence rate at the first follow-up cystoscopy (RRFF-C at 3 months) was 3.85% (three patients). The median follow-up period was 30.8 months (range 6.9-76.0 months). In univariate analysis, the only predictor of recurrence was grade. Overall we observed 11 recurrences. Only one tumor progressed to T2 MIBC. CONCLUSIONS: The low rates of residual tumor, recurrence, and progression seem to raise doubts about the efficacy of EBRS in patients who have previously undergone en bloc resection. EBRS appears to be a feasible and safe procedure with a low rate of complications. However, further data will be needed before EBRS can be used in clinical trials or recommended as a treatment modality.

LithoVue™ for renal stone therapy - a perfect fit for high volume academic centers; a retrospective evaluation of 108 cases.

BACKGROUND: Over the last few years the number of flexible ureterorenoscopies, used for renal stone treatment, has risen steadily. This was associated with an increase in costs for maintenance and repair of the fragile ureterorenoscopes used. To overcome this problem single-use devices have been introduced to the market. The aim of this study was to assess surgical outcome and workability for LithoVue™, a single-use flexible ureterorenoscope. METHODS: We retrospectively analyzed all flexible ureterorenoscopies performed at our department between January and October 2017. We included a total of 108 interventions for renal stone therapy, all performed using the single-use device LithoVue™. We assessed patients' characteristics including stone size, count and location. We evaluated the surgical outcome, analyzing stone-free rates, reintervention rates, complication rates, as well as surgery time. Learning curve for single-use ureterorenoscopes was evaluated by comparing the surgical outcome between residents and consultants. RESULTS: The average time needed per intervention was 52,31 min ± 28,11. In 77 out of 108 (71,30%) patients we were able to remove all stones by a single intervention. In 8 patients (7,41%) intra- or postoperative complications occurred, none of which was graded higher than Clavien-Dindo III B. We did not find any statistical differences comparing the surgical outcome between residents and consultants. No technical difficulties occurred during surgery. CONCLUSION: Single-use flexible ureterorenoscopes provide decent working properties resulting in good surgical outcome. Furthermore, they are proven to be easy to handle even for unexperienced surgeons, making them a feasible choice for high volume academic centers.

Can a Simple Geriatric Assessment Predict the Outcome of TURP?

PURPOSE: To determine the impact of a simple preoperative geriatric assessment on the outcome in older patients with recurrent urinary retention who underwent desobstructive surgery. PATIENTS AND METHODS: Patients aged 75 years or older with recurrent urinary retention referred for TURP entered this prospective, multicentre study. Several demographic, intra- and postoperative parameters were assessed. Preoperative geriatric assessment was performed by the 7-item Canadian Study of Health and Ageing (CSHA) frailty scale (1: very fit, 7: severely frail; completion takes less than a minute). The main outcome parameters were successful voiding rates at discharge and 3 months postoperatively. RESULTS: A total of 54 patients were recruited; 42 (77.8%) patients had a CSHA index of 1-3 and were considered as "fit", the remaining 12 (22.2%) formed the "frail" group (CSHA index 4-7). Age was identical in both cohorts (79.5 ± 3.7 vs. 79.7 ± 3.3 years); differences were demonstrable for the American Society of Anesthesiologists (ASA) score (p = 0.001), the number of daily medications (>4: 32 vs. 75%, p = 0.02), falls within the past 6 months (12 vs. 33%), and the necessity of home/nursing care (5 vs. 42%, p = 0.004). Intra- and perioperative complications, duration of postoperative catheterization, and length of hospitalization were identical in both cohorts. The success rate at discharge was 80.6% in fit and 75.0% in frail patients; the respective values at 3 months were 95.2 and 83.3%. CONCLUSIONS: A simple 1-min geriatric assessment tool can predict - to a certain extent - the outcome of desobstructive surgery in older patients with recurrent urinary retention. Fit patients achieve an excellent outcome while frail patients might benefit from a more in-depth urodynamic/geriatric evaluation.

The Feasibility, Technique, and Medium-Term Follow-Up of Laparoscopic Transvesical Diverticulectomy.

BACKGROUND: To present our experience and results with the transvesical laparoscopic diverticulectomy, developed by Pansadoro et al. [BJU Int. 2009;103(3):412-24], as treatment of symptomatic bladder diverticula, with a medium-term follow-up. METHODS: Between June 2010 and July 2018, we successfully operated 15 patients (13 male/2 female), aged 32-85 years (mean age 61 years) in 2 centers in Austria, using the aforementioned technique. RESULTS: The median operative time was 297 min (range 83-488 min), and the blood loss was minimal. The median diameter of the diverticula was 94 mm (range 40-110 mm). The transurethral catheter was removed in most patients on day 7 (range 1-26 days), and cystography was performed before catheter removal. Patients were discharged on the ninth postoperative day (range 4-18 days). One case had a Clavien-Dindo grade IIIb complication (ureter injury), and 2 cases had a grade IIIa complication (nephrostomy drainage). After a median follow-up of 19 months, no recurrences were observed. CONCLUSION: The laparoscopic, transvesical diverticulectomy is a feasible and valuable procedure with good outcomes. To avoid complications, the ureter needs to be spared meticulously.

Risk-adapted moderate hypofractionation of prostate cancer : A prospective analysis of acute toxicity, QOL and outcome in 221 patients.

PURPOSE: Prostate cancer (PCA) is highly heterogeneous in terms of its oncologic outcome. We therefore aimed to tailor radiation treatment to the risk status by using three different hypofractionated radiation regimen differing in applied dose, use of rectum spacer, inclusion of pelvic lymph nodes (pLN) and use of androgen deprivation therapy (ADT). Here we report on acute toxicity, quality of life (QOL) and oncologic outcome at a median follow-up of 12 months. METHODS: A total of 221 consecutive PCA patients received hypofractionated intensity-modulated radiotherapy (IMRT). Low-risk (LR) patients were planned to receive 60 Gy in 20 fractions (EQD2α/ß1.5 = 77.1 Gy), intermediate-risk (IR) patients 63 Gy in 21 fractions (EQD2α/ß1.5 = 81 Gy), and high-risk (HR) patients 67.5 Gy in 25 fractions (EQD2α/ß1.5 = 81 Gy) to the prostate and 50 Gy in 25 fractions to the pLN. Acute rectal toxicity was assessed by endoscopy. In addition, toxicity was scored using CTC-AE 4.0 and IPSS score, while QOL was assessed using QLQ-PR25 questionnaires. RESULTS: Acute CTC reactions were slightly higher in the HR regimen but reverted to baseline at 3 months. GI G2 toxicity was 4%, 0% and 12% for the LR, IR and HR regimen. Compared to IR patients, the increase in toxicity in HR patients was statistically significant (p = 0.002) and mainly caused by a higher incidence of diarrhea presumably due to pelvic EBRT. QOL scores of all domains were worse for the HR regimen (not significant). CONCLUSION: Risk-adapted moderate hypofractionation is associated with low GI/GU toxicity. Given the higher rate of pelvic metastases in HR patients, slightly higher transient acute reactions should be outweighed by possible oncological benefits.

Combined prostatic urethral lift and remodeling of the prostate and bladder neck: a modified transurethral approach in the treatment of symptomatic lower urinary tract obstruction.

PURPOSE: The aim of the study was to evaluate the feasibility and safety of combining prostatic urethral lift (PUL) and a limited resection of the prostatic middle lobe or bladder neck incision in the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: Twenty-eight patients were treated at two tertiary centers and followed prospectively. Patient evaluations included patient characteristics, relief of LUTS symptoms, erectile and ejaculatory function, continence, operative time and adverse events. Patients were followed for a mean of 10.9 months. RESULTS: Patient characteristics were as follows: age 66 years (46-85), prostate volume 39.6 cc (22-66), preoperative IPSS/AUASI 20 (6-35)/QoL 3.9 (1-6)/peak flow 10.5 mL/s (4.0-19)/post-void residual volume (PVR) 123 mL (0-500). Mean operating time was 31 min (9-55). Postoperative complications were minor except for the surgical retreatment of one patient for blood clot retention (Clavien 3b). One patient required catheterization due to urinary retention. Reduction of symptoms (IPSS - 59.6%), increase in QoL (+ 49.0%), increase in flow (+ 111.5%), and reduction of PVR (- 66.8%) were significant. Antegrade ejaculation was always maintained. CONCLUSION: Our data suggest that a combination of PUL and transurethral surgical techniques is feasible, safe, and effective. This approach may be offered to patients with moderate size prostates including those with unfavorable anatomic conditions for PUL. This procedure is still 'minimally invasive' and preserves sexual function. In addition, it may add to a higher functional efficacy compared to PUL alone. STUDY REGISTER NUMBER: DRKS00008970.

Non-ischemic laparoscopic partial nephrectomy using 1318-nm diode laser for small exophytic renal tumors.

PURPOSE: Warm ischemia (WI) and bleeding constitute the main challenges for surgeons during laparoscopic partial nephrectomy (LPN). Current literature on the use of lasers for cutting and coagulation remains scarce and with small cohorts. We present the largest case series to date of non-ischemic LPN using a diode laser for small exophytic renal tumors. METHODS: We retrospectively evaluated 29 patients with clinically localized exophytic renal tumors who underwent non-ischemic laser-assisted LPN with a 1318-nm wavelength diode laser. We started applying the laser 5 mm beyond the visible tumor margin, 5 mm away from the tissue in a non-contact fashion for coagulation and in direct contact with the parenchymal tissue for cutting. RESULTS: The renal vessels were not clamped, resulting in a WIT (warm ischaemic time) of 0 min, except for one case that required warm ischemia for 12 min and parenchymal sutures. No transfusion was needed, with a mean Hemoglobin drop of 1,4 mg/dl and no postoperative complications. The eGFR did not significantly change by 6 months. Histologically, the majority of lesions (n = 22/29) were renal-cell carcinoma stage pT1a. The majority of malignant lesions (n = 13/22) had a negative margin. However, margin interpretation was difficult in 9 cases due to charring of the tumor base. A mean follow-up of 1.8 years revealed no tumor recurrence. The mean tumor diameter was 19.4 mm. CONCLUSION: The 1318-nm diode laser has the advantages of excellent cutting and sealing properties when applied to small vessels in the renal parenchyma, reducing the need for parenchymal sutures. However, excessive smoke, charring of the surgical margin, and inability to seal large blood vessels are encountered with this technique.

Neoadjuvant Chemotherapy with Gemcitabine plus Cisplatin in Patients with Locally Advanced Bladder Cancer.

BACKGROUND: Neoadjuvant chemotherapy with methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) is the standard of care for muscle-invasive urothelial bladder cancer. Gemcitabine plus cisplatin (GC) shows similar efficacy with less toxicity in the metastatic setting and has therefore often been used interchangeably with MVAC. We report on the efficacy and safety of neoadjuvant GC in patients with locally advanced urothelial cancer. MATERIALS AND METHODS: We prospectively evaluated 87 patients in 2 centers. Their median age was 68 years. Treatment consisted of 3× GC prior to radical cystectomy. The primary endpoint was pathologic response. The secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). RESULTS: In all, 83 patients finished chemotherapy; 80 patients were evaluable for the primary endpoint. Pathologic complete response (pCR) was achieved in 22.5% and near pCR was seen in 33.7% of the patients. The 1-year PFS rate was 79.5% among those patients achieving ≤pT2 versus 100% among those patients achieving pCR or near pCR (p = 0.041). Five-year OS was 61.8% (95% CI 67.6 to NA). GC was well tolerated. Grade 3/4 toxicities occurred in 38% of the patients. There was no grade 3/4 renal toxicity, febrile neutropenia, or death. CONCLUSION: Neoadjuvant GC is a well-tolerated regimen. Although the pathologic response is lower than that reported with MVAC, our data support GC as a feasible option in the absence of a prospective randomized comparison, particularly for older patients, since its toxicity is lower than that of MVAC.

Emerging techniques in 'truly' minimal-invasive treatment options of benign prostatic obstruction.

PURPOSE OF REVIEW: Benign prostatic enlargement is a common age-related condition, affecting over 50% of men aged more than 60 years. Side effects of medical therapy and significant morbidity of transurethral resection of the prostate and open surgery led to the development of so-called minimally invasive procedures, with the aim to be efficient but with less morbidity and shorter or no hospitalization. For this review, a systematic literature was performed. We report recent results in different treatment options for benign prostate hypoplasia (BPH) and recommend the best minimal-invasive treatment for BPH. RECENT FINDINGS: Within recent years, BPH surgical interventions underwent a shift. Although standard techniques have further improved because of new products and increased business competition, there has been a request from healthcare administration to reduce costs and inpatient treatment. As important, the patients understanding of outcome, fast relief, and recovery might change the common urological outcome measurement. The two main aspects are quality of life and sexuality. SUMMARY: Some of the presented treatments are already established in EAU guidelines, others may be recognized in clinical practice as a suitable alternative treatment to transurethral resection of the prostate and medical therapy. Patients now wish to be more involved in the treatment option decision-making and seem very concerned about side effects and their return to normal life. However, variations in reimbursements allowed in different countries can affect the treatment option.

Fluorescence Guided Targeted Pelvic Lymph Node Dissection for Intermediate and High Risk Prostate Cancer.

PURPOSE: We investigated whether visualization of the drainage system of the prostate by free indocyanine green would lead to identification of all or even more lymph node metastases detected by super-extended pelvic lymph node dissection in an intermediate and high risk patient population with prostate cancer. MATERIALS AND METHODS: A total of 38 consecutive men with intermediate or high risk prostate cancer according to the D'Amico criteria underwent fluorescence targeted pelvic lymph node dissection during laparoscopic radical prostatectomy. Super-extended pelvic lymph node dissection was added as the control. Patients with neoadjuvant hormonal therapy, macroscopic lymph node involvement or prior transurethral prostate resection were excluded from study. Statistical descriptive methods, and the chi-square test and independent t-test were used to analyze data. RESULTS: Mean patient age was 64.9 years (range 46 to 74) and mean preoperative prostate specific antigen was 13.8 ng/ml (range 0.3 to 44). A total of 23 (60.5%) and 15 cases (39.5%) were classified as intermediate and high risk, respectively. Fluorescence stained nodes were found on each side in all except 1 patient. A total of 700 lymph nodes (mean ± SD 18.4 ± 8.2 per patient) were removed, of which 531 (75% of all nodes) were fluorescence stained (mean 14 ± 8.07 per patient). Lymph node metastases were found in 15 patients (39.5%). Two patients (5.3%) had a solitary micrometastasis and 3 (7.9%) had nodes containing isolated tumor cells. Metastases were found outside the extended pelvic lymph node dissection template in 5 of 15 patients (33.3%). Three of those 5 patients attained a prostate specific antigen nadir of less than 0.1 ng/ml 6 weeks postoperatively. Fluorescence targeted pelvic lymph node dissection showed superior sensitivity and negative predictive value compared to extended and super-extended pelvic lymph node dissection to detect lymph node metastasis. CONCLUSIONS: Fluorescence targeted pelvic lymph node dissection allows for the lymphatic drainage of the prostate to be identified with great reliability. Since only the nodes draining the prostate are removed, the absolute number of removed nodes is decreased while diagnostic accuracy is increased.

Update on the use of diode laser in the management of benign prostate obstruction in 2014.

AIM: To determine the status quo in respect of various diode lasers and present the techniques in use, their results and complications. We assess how these compare with transurethral resection of the prostate and other types of laser in randomized controlled trials (RCTs). When adequate RCTs were not available, case studies and reports were evaluated. MATERIALS AND METHODS: Laser for the treatment of benign prostatic hyperplasia (BPH) has aroused the interest and curiosity of urologists as well as patients. The patient associates the term laser with a successful and modern procedure. The journey that started with coagulative necrosis of prostatic adenoma based on neodymium: yttrium-aluminum-garnet (Nd:YAG) laser has culminated in endoscopic "enucleation" with holmium laser. Diode laser is being used in urology for about 10 years now. Various techniques have been employed to relieve bladder outlet obstruction due to BPH. RESULTS: The diode laser scenario is marked by a diversity of surgical techniques and wavelengths. We summarize the current published literature in respect of functional results and complications. CONCLUSION: More randomized controlled studies are needed to determine the position and the ideal technique of diode laser treatment for BPH.

Inhibition of smooth muscle force generation by focal adhesion kinase inhibitors in the hyperplastic human prostate.

Smooth muscle contraction may be critical for lower urinary tract symptoms (LUTS) in patients with benign prostate hyperplasia and requires stable anchorage of the cytoskeleton to the cell membrane. These connections are regulated by focal adhesion kinase (FAK). Here, we addressed the involvement of FAK in the regulation of smooth muscle contraction in hyperplastic human prostate tissues. Prostate tissues were obtained from radical prostatectomy. Expression of FAK and focal adhesion proteins was assessed by Western blot analysis and immunohistochemical stainings. Effects of the FAK inhibitors PF-573228 and Y-11 on contraction of prostate strips were examined in the organ bath. Expression of FAK and focal adhesion proteins (integrin-5α, paxilin, and c-Src) was detected by Western blot analysis in prostate samples. By double immunofluorescence staining with calponin and pan-cytokeratin, expression of FAK was observed in stromal and epithelial cells. Immunoreactivity for FAK colocalized with integrin-5α, paxilin, talin, and c-Src. Stimulation of prostate tissues with the α1-adrenergic agonist phenylephrine increased the phosphorylation state of FAK at Tyr³97 and Tyr9²5 with different kinetics, which was blocked by the α1-adrenoceptor antagonist tamsulosin. Norepinephrine and phenylephrine induced concentration-dependent contractions of prostate strips. Both FAK inhibitors PF-573228 and Y-11 significantly inhibited norepinephrine- and phenylephrine-induced contractions. Finally, PF-573228 and Y-11 inhibited contractions induced by electric field stimulation, which was significant at the highest frequency. In conclusion, α1-adrenergic smooth muscle contraction or its regulation involves FAK in the human prostate. Consequently, FAK may be involved in the pathophysiology of LUTS and in current or future LUTS therapies.

Laparoscopic and robotic postchemotherapy retroperitoneal lymph node dissection.

PURPOSE OF REVIEW: Open surgical postchemotherapy retroperitoneal lymph node dissection remains the standard of care. On the contrary, laparoscopy is an emerging technique and reports of laparoscopic lymph node dissection postchemotherapy are increasing. Our purpose is to present indications, technique and outcomes of laparoscopic postchemo retroperitoneal lymph node dissection. RECENT FINDINGS: With growing expertise and knowledge the morbidity of the laparoscopic approach is much reduced compared with open surgery with the same oncological outcome. Robotic surgery is a more recent approach with growing usage in urology. However, no reports of robotic postchemotherapy lymph node dissection are available. SUMMARY: In expert hands laparoscopic lymph node dissection is a feasible technique, offering less morbidity to patients with good oncological results.

The receptor antagonist picotamide inhibits adrenergic and thromboxane-induced contraction of hyperplastic human prostate smooth muscle.

Inhibition of prostate smooth muscle contraction is an important strategy for medical treatment of lower urinary tract symptoms (LUTS). Besides α1-adrenoceptors, prostate smooth muscle contraction is induced by activation of thromboxane (TXA2) receptors (TXA2-R). Here, we examined the effects of the TXA2-R antagonist picotamide on contraction of human prostate tissue. Prostate tissues were obtained from radical prostatectomy. The effects of picotamide (300 µM), L-665,240 (3 µM), and seratrodast (3 µM) on U46619-, electric field stimulation- (EFS-), phenylephrine-, and norepinephrine-induced contractions were studied in organ baths. Expression of TXA2-R and TXA2 synthase (TXS) was examined by fluorescence stainings. Picotamide, seratrodast, and L-655,240 inhibited concentration-dependent contractions induced by the TXA2 analog U46619. Picotamide, but not seratrodast or L-655,240, inhibited frequency-dependent contractions induced by EFS. Picotamide inhibited concentration-dependent contractions induced by norepinephrine or by the selective α1-adrenoceptor agonist phenylephrine. In prostate strips, where only submaximal contraction by a low dose of phenylephrine was induced, application of U46619 raised tone to maximum phenylephrine-induced tension. Immunoreactivity for TXA2-R and TXS was observed in the stroma and in epithelial cells of glands. Colocalization of both immunoreactivites was observed with the smooth muscle markers calponin and α-smooth muscle actin, with the epithelial marker pan-cytokeratin, and with prostate-specific antigen in the stroma and glands. The receptor antagonist picotamide inhibits α1-adrenergic, TXA2-mediated, and EFS-induced contractions in the human prostate. To the best of our knowledge, this is the first antagonist able to inhibit two different contraction systems in the prostate.

Incremental Impact of [68 Ga]Ga-PSMA-11 PET/CT in Primary N and M Staging of Prostate Cancer Prior to Curative-Intent Surgery: a Prospective Clinical Trial in Comparison with mpMRI.

PURPOSE: The main objective of this prospective study was to assess the value of gallium-68 prostate-specific membrane antigen ([68 Ga]Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) in primary N and M staging of intermediate- and high-risk prostate cancer (PCa) patients before planned curative-intent radical prostatectomy (RPE) and extended pelvic lymph node dissection (ePLND). The second objective was to compare the [68 Ga]Ga-PSMA-11 PET/CT findings with standard of care pelvic multi-parametric magnetic resonance imaging (mpMRI) in the detection of locoregional lymph node metastases and intraprostatic prostate cancer. PROCEDURES: A total of 81 patients (mean age: 64.5 years, baseline mean trigger PSA (tPSA) 15.4 ng/ml, ± 15.9) with biopsy proven PCa (24 intermediate- and 57 high risk) scheduled for RPE and ePLND were enrolled in this prospective study. In 52 patients [68 Ga]Ga-PSMA-11 PET/CT, pelvic mpMRI, and RPE with ePLND have been performed. Clinical risk stratification and related biomarkers as well as Gleason score (GS) were recorded. The location of the index lesion (IL) was documented systematically for each modality using a standardized segmentation of the prostate in six segments. Distant bone and lymph node metastasis detected by [68 Ga]Ga-PSMA-11 PET/CT were documented. [68 Ga]Ga-PSMA-11 PET/CT findings were correlated with results of mpMRI and histopathology. A consensus of imaging, clinical and/or follow-up findings were used for determining the distant metastases, which were not verified by histopathology. RESULTS: In the patient cohort who underwent RPE, [68 Ga]Ga-PSMA-11 PET/CT and mpMRI detected the IL in 86.5% and 98.1% of the patients, respectively. The median of the maximum standardized uptake value (SUVmax) in the intraprostatic IL was 12 (range, 4.7-67.8). Intraprostatic IL of the high-risk patients showed significantly higher SUVmax than those in patients with intermediate risk for distant metastases (n = 48; median: 17.84 vs. 8.77; p = 0.02). In total 729 LN were removed by ePLND in 48 patients. The histopathology verified 26 pelvic lymph node metastases (pLNM) in 20.8% (10/48) of the patients, which have been correctly identified in 60% of the patients on [68 Ga]Ga-PSMA-11 PET/CT, and in 50% on mpMRI. All but one pLNM had a maximum diameter below 10 mm. Bone metastases (BM) and distant LNM (dLNM) were found in 17.3% of the patients on [68 Ga]Ga-PSMA-11 PET/CT imaging. 39.0% of the [68 Ga]Ga-PSMA-11 PET-positive BM showed no suspicious morphological correlation on CT. CONCLUSION: [68 Ga]Ga-PSMA-11 PET/CT shows high diagnostic performance for N and M staging of patients with intermediate- and high-risk prostate cancer and seems to be superior to pelvic mpMRI in the detection of locoregional lymph node metastases. A significant correlation was found between SUVmax of the intraprostatic index lesion and risk stratification based on tPSA level and GS. The results of this study emphasize again on the role of metabolic molecular imaging using specific tracers in selected patients, leading to tailored therapy approach.

Effect of Simulation-based Training on Surgical Proficiency and Patient Outcomes: A Randomised Controlled Clinical and Educational Trial.

BACKGROUND: It is hypothesised that simulation enhances progression along the initial phase of the surgical learning curve. OBJECTIVE: To evaluate whether residents undergoing additional simulation, compared to conventional training, are able to achieve proficiency sooner with better patient outcomes. DESIGN, SETTING, AND PARTICIPANTS: This international, multicentre, randomised controlled trial recruited 94 urology residents with experience of zero to ten procedures and no prior exposure to simulation in ureterorenoscopy, selected as an index procedure. INTERVENTION: Participants were randomised to simulation or conventional operating room training, as is the current standard globally, and followed for 25 procedures or over 18 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number of procedures required to achieve proficiency, defined as achieving a score of ≥28 on the Objective Structured Assessment of Technical Skill (OSATS) scale over three consecutive operations, was measured. Surgical complications were evaluated as a key secondary outcome. This trial is registered at www.isrctn.com as ISCRTN 12260261. RESULTS AND LIMITATIONS: A total of 1140 cases were performed by 65 participants, with proficiency achieved by 21 simulation and 18 conventional participants over a median of eight and nine procedures, respectively (hazard ratio [HR] 1.41, 95% confidence interval [CI] 0.72-2.75). More participants reached proficiency in the simulation arm in flexible ureterorenoscopy, requiring a lower number of procedures (HR 0.89, 95% CI 0.39-2.02). Significant differences were observed in overall comparison of OSATS scores between the groups (mean difference 1.42, 95% CI 0.91-1.92; p < 0.001), with fewer total complications (15 vs 37; p = 0.003) and ureteric injuries (3 vs 9; p < 0.001) in the simulation group. CONCLUSIONS: Although the number of procedures required to reach proficiency was similar, simulation-based training led to higher overall proficiency scores than for conventional training. Fewer procedures were required to achieve proficiency in the complex form of the index procedure, with fewer serious complications overall. PATIENT SUMMARY: This study investigated the effect of simulation training in junior surgeons and found that it may improve performance in real operating settings and reduce surgical complications for complex procedures.

Lower ureteral compression through external vascular elongation in a cyclist: A case report.

INTRODUCTION AND IMPORTANCE: There is sparse literature about lower ureteric obstruction due to aberrant blood vessels. We report a case of a patient who was referred to our hospital due to left sided flank pain caused by external compression of the distal ureter. CASE PRESENTATION: A 47-year-old male patient presented with left sided flank pain. A computed tomography scan revealed external compression of the lower ureter. Hypertrophy of the psoas muscle due to extensive cycling for 20 years lead to concomitant kinking and elongation of the iliacal vessels which caused the distal ureteric obstruction. Robotic-assisted laparoscopic ureterocystoneostomy with psoas hitch technique was performed. CLINICAL DISCUSSION: Lower ureteric obstruction, mostly seen in children, is mostly caused by vascular anomalies such as a persistent umbilical artery. After literature review, we presume it to be the first reported case of distal ureteric obstruction caused by external vascular elongation. CONCLUSION: The external elongation of pelvic vessels due to excessive cycling and the concomitant extrinsic compression of the distal ureter should be considered as rare but possible cause of lower uretic obstructions.

The phytostilbene resveratrol induces apoptosis in INS-1E rat insulinoma cells.

We investigated the effect of resveratrol on proliferation and induction of apoptosis of INS-1E rat insulinoma cells by cell counting, crystal violet staining, flow cytometry and immunoblotting. Resveratrol treatment of INS-1E cells at concentrations > or =50 microM resulted in a dose-dependent inhibition of cell proliferation, accumulation of the cells in the S and G0/G1 phase and a significant increase of the percentage of apoptotic cells. This was paralleled by an increase of cell granularity, apoptotic volume decrease (AVD), exposure of phosphatidylserine at the outer leaflet of the plasma membrane, an increase of the 7-AAD signal and caspase activation. The AMP-kinase (AMPK) inhibitor compound C (10 microM) significantly inhibited cell proliferation and induced caspase activation within 48 hours but this effect was not modified by resveratrol suggesting that AMPK is not a major target involved in mediating the proapoptotic effect of resveratrol in INS-1E cells. Immunoblotting revealed a significant inhibition of Akt (PKB) phosphorylation by 100 muM resveratrol within 1 hour. Addition of insulin (10 microM) to the culture medium strongly enhanced basal Akt phosphorylation. This enhancement was significantly attenuated by 50 and 100 microM resveratrol. We conclude that the antiproliferative/proapoptotic effect of resveratrol on INS-1E cells is due to negative interference with Akt signaling and most likely disruption of auto/paracrine insulin signaling.