Technical Outcome, Clinical Success, and Complications of Low-Milliampere Computed Tomography Fluoroscopy-Guided Drainage of Lymphoceles Following Radical Prostatectomy with Pelvic Lymph Node Dissection.

To evaluate the technical outcome, clinical success, and safety of low-milliampere CT fluoroscopy (CTF)-guided percutaneous drain (PD) placement in patients with lymphoceles following radical prostatectomy (RP) with pelvic lymph node dissection (LND). This retrospective analysis comprised 65 patients with PD placement in lymphoceles following RP under low-milliampere CTF guidance. Technical and clinical success were evaluated. Complications within a 30-day time interval associated with CTF-guided PD placement were classified according to SIR. Patient radiation exposure was quantified using dose-length products (DLP) of the pre-interventional planning CT scan (DLPpre), of the sum of intra-interventional CT fluoroscopic acquisitions (DLPintra) and of the post-interventional control CT scan (DLPpost). Eighty-nine lymphoceles were detected. Seventy-seven CT-guided interventions were performed, with a total of 92 inserted drains. CTF-guided lymphocele drainage was technically successful in 100% of cases. For all symptomatic patients, improvement in symptoms was reported within 48 h after intervention. Time course of C-reactive protein and Leucocytes within 30 days revealed a statistically significant (p < 0.0001) decrease. Median DLPpre, DLPintra and DLPpost were 431 mGy*cm, 45 mGy*cm and 303 mGy*cm, respectively. Only one minor complication (self-resolving haematoma over the bladder dome; SIR Grade 2) was observed. Low-milliampere CTF-guided drainage is a safe treatment option in patients with lymphoceles following RP with pelvic LND characterized by high technical and good clinical success rates, which provides rapid symptom relief and serves as definite treatment or as a bridging therapy prior to laparoscopic marsupialisation.

A 27-Year-Old Primigravida with a Right Renal Cell Carcinoma Removed at 30 Weeks of Gestation by Robot-Assisted Retroperitoneoscopic Partial Nephrectomy.

BACKGROUND Large renal tumors during pregnancy are rare findings (0.07-0.1%). Current guidelines recommend surgical removal. This surgery should be carefully planned in an interdisciplinary team and involves special risks for mother and fetus. This report describes a case of a 27-year-old primigravida woman with a right renal cell carcinoma involving the lower pole of the kidney, which was removed at 30 weeks of gestation by robot-assisted retroperitoneoscopic partial nephrectomy (RARPN). CASE REPORT The patient was referred by the treating obstetrician with a newly diagnosed right lower pole renal mass of 6×4 cm in greatest diameter extending deeply into the parenchyma. No metastasis or enlarged lymph nodes were described in subsequent magnetic resonance tomography. Clinical and laboratory examinations documented a healthy mother and fetus. A right-sided RARPN was advised and planned by an interdisciplinary team of treating physicians (gynecologists, oncologists, and urologists). The surgery was conducted under general anesthesia with an obstetrician on stand-by. Surgery was performed without any complications (operation time 95 min, renal-ischemia time 15 min, and negligible blood loss) and histopathology confirmed the diagnosis of a chromophobe renal cell carcinoma. Further follow-up consultations showed regular wound healing and normal progression of pregnancy, and the patient gave birth to a healthy child at term. Follow-up examinations of the patient were uneventful. CONCLUSIONS This case shows that RARPN can be a safe and effective surgical procedure for partial nephrectomy during pregnancy, where surgery is performed in a specialist center and by an interdisciplinary experienced surgical team. It seems to offer advantages and better risk profile over the laparoscopic approach.

Retrospective Evaluation of the Clinical Values of Minimally Invasive Marsupialization of Symptomatic Giant Renal Cysts.

Background: To evaluate the indication and benefit of minimally invasive laparoscopic marsupialization (MIS) of symptomatic giant renal cysts. Materials and Methods: Sixty-four consecutive patients who underwent MIS for large renal cysts (Bosniak I; 4 × 5-16 × 12 cm) by one surgeon were included in the study. Presenting symptoms were renal pain (100%), associated with hypertension (28%), renal dysfunction (4.7%), hematuria (4.7%), ureteropelvic junction obstruction (UPJO) (7.8%), ipsilateral urolithiasis (4.7%), polycystic kidney (6.3%), adrenal cyst (1.6%), and retroperitoneal cysts (1.6%). Seven patients with peripelvic cysts and previous retroperitoneal operations were treated by a laparoscopic approach; all other patients underwent retroperitoneoscopic marsupialization. Single-port retroperitoneoscopy was performed in 4 patients. Follow-up included clinical examination, abdominal ultrasound, and computed tomography scan. Postoperative radiologic success was defined as a minimum of 50% in size reduction and no recurrence. Results: Mean patients' age was 46 (21-65) years. All procedures were successfully completed without conversion or revision. Mean operative time was 55 (40-85) minutes with a mean hospital stay of 3 days. All patients underwent uneventful postoperative recovery. Observed minor complications (transitory fever/pain) were found in 4 patients during the first postoperative month. Median follow-up was 12 months (10 months-2 years). About 98.5% of patients reported of no relevant postoperative pain. A relief from UPJO and hematuria was achieved in 100% of patients. Ten patients with known hypertensive disease (55.6%) had a significant reduction of mean blood pressure resulting in a reduction of antihypertensive medication. Ureterorenoscopic stone extractions were performed successfully afterward. No cyst recurrences were detected during the follow-up period. Conclusion: Treatment indications for symptomatic renal cysts could include not only symptoms but also associated diseases like UPJO and hypertension. Retroperitoneoscopic MIS may be curative for these cyst-associated pathologies. The feasibility, safety and efficacy of these techniques could be demonstrated.

Evaluation of Testicular Self Examination and Testicular Partner Examination in Medical versus Non-Medical Students.

OBJECTIVES: Although testicular cancer (TC) is the most common tumor in young men in Western countries, there is no official cancer detection/screening program for young men in Germany. The most important TC detection tool is self-examination of the testis. Hypothetically medical students may have a diagnosis lead time and detection superiority. This study was designed to analyze whether medical students have a possible knowledge advantage over students of other faculties concerning TC and to compare male and female cancer screening demeanor and mentality. METHODS: Male and female students of various faculties at the Goethe University Frankfurt/Main, Germany were invited to participate in this internet-based anonymous questionnaire with questions about TC awareness/knowledge, testicular (self) examination, and cancer screening behavior. RESULTS: In total 1,049 students (329 medical and 716 non-medical students) completed the questionnaire. In general, medical students had a significantly higher TC knowledge, especially in the more advanced stages of their medical studies (year 3-6). About 50% of medical students had knowledge of TC whereas only 21.3% of non-medical students knew about the disease (p < 0.01). In addition, medical students conducted scrotal examinations more frequently (34.7%) than non-medical students (18.8%). CONCLUSION: The knowledge about TC is low among students. In general, medical students are more aware of TC and perform more frequent testicular examinations compared to non-medical students. Female TC knowledge rises in the clinical part of studies to the same level as their male counterparts, with the result of more testicular partner examinations.

Patient Selection in Surgical Centers of Expertise in the Treatment of Patients with Moderate to Severe Male Urinary Stress Incontinence.

OBJECTIVE: To analyze decision-making in patients with male urinary incontinence (SUI) in centers of expertise. The artificial urinary sphincter (AUS) remains the gold standard for male patients with moderate to severe SUI but adjustable male slings are a minimally invasive treatment option with good results, hence without a high level of evidence regarding the optimal patient selection. MATERIALS AND METHODS: In total, 220 patients (88 AUS; 132 adjustable slings) were investigated from the DOMINO database that underwent surgery between 2010 and 2012 in 5 urological departments that offer adjustable sling systems as well as AUS systems for patients with moderate to severe urinary incontinence. For statistical analysis, the Mann-Whitney U test was used to identify differences between both groups. RESULTS: Patients selected for an adjustable male sling were less likely to have a neurological disease (5.3 vs. 9.1%; p = 0.030), a prior urethral stricture (22.7 vs. 50.0%; p = 0.001), a prior incontinence surgery (24.4 vs. 45.5%; p = 0.01), or a prior radiation therapy (26.5 vs. 40.1%; p = 0.001). The severity of preoperative incontinence was higher in patients selected for an AUS with a mean pad usage per day of 7.60 versus 5.80 (p < 0.001). Mean postoperative pad usage and patients' subjective perception were comparable in both groups. CONCLUSION: In centers offering both options, the decision-making is mainly based upon presence of radiation therapy and previous failed incontinence surgery. Despite the more complex patient cohort selected for an AUS implantation with a possible impact on the postoperative outcome, the functional results seem to be comparable indicating a proper preoperative patient assessment and selection in this cohort.

Can we define reliable risk factors for anastomotic strictures following radical prostatectomy?

BACKGROUND: To identify risk factors for anastomotic strictures in patients after radical prostatectomy. METHODS: In all, 140 prostate cancer patients with one or more postoperative anastomotic strictures after radical prostatectomy were included. All patients underwent transurethral anastomotic resection at the University Hospital of Munich between January 2009 and May 2016. Clinical data and follow-up information were retrieved from patients' records. Statistical analysis was done using Kaplan-Meier curves and log rank-test with time to first transurethral anastomotic resection as endpoint, Chi-square-test, and Mann-Whitney-U test. RESULTS: In all, 140 patients with a median age of 67 years (IQR: 61-71 years) underwent radical prostatectomy. Median age at time of transurethral anastomotic resection was 68 years (IQR: 62-72). Patients needed 2 surgical interventions in median (range: 1-15). Median time from radical prostatectomy to transurethral anastomotic resection was 6 months (IQR: 3.9-17.4). Median duration of catheterization after radical prostatectomy was 10 days (IQR: 8-13). In all, 26% (36/140) received additional radiotherapy. Regarding time to first transurethral anastomotic resection, age and longer duration of catheterization after radical prostatectomy with a cutoff of 7 days showed no statistically significant differences (p = 0.392 and p = 0.141, respectively). Tumor stage was no predictor for development of anastomotic strictures (p = 0.892), and neither was prior adjuvant radiation (p = 0.162). Potential risk factors were compared between patients with up to 2 strictures (low-risk) and patients developing > 2 strictures (high-risk): high-risk patients had more often injection of cortisone during surgery (14% vs 0%, p < 0.001) and more frequently advanced tumor stage pT > 2 (54% vs 38%, p = 0.055), respectively. Other risk factors did not show any significant difference compared to number of prior transurethral anastomotic strictures. CONCLUSIONS: We could not identify a reliable risk factor to predict development of anastomotic strictures following radical prostatectomy.

Secondary Sling Implantation after Failure of Primary Surgical Treatment for Male Stress Urinary Incontinence: A Retrospective Study.

OBJECTIVE: The artificial urinary sphincter (AUS) is the surgical gold standard after previously failed surgical treatment for male urinary stress incontinence. The evidence for a male sling as salvage treatment is poor, but there is a proportion of patients that refuse implantation of an AUS or have a relative contraindication. The goal of our retrospective study was an analysis of outcome and complications of patients with a secondary sling after previously failed surgery for stress urinary incontinence (SUI). MATERIALS AND METHODS: Data on 186 patients who had a prior incontinence surgery were extracted from the DOMINO database. 139 patients (74.7%) received an AUS and 41 patients (22.0%) who had received a secondary sling system between 2010 and 2012 after previously failed surgery for male urinary incontinence could be identified and were further analyzed. RESULTS: Eight patients (19.5%) received a secondary repositioning sling and 33 patients (80.5%) received a secondary adjustable sling system. A prior surgery for urethral stricture was performed in 4 patients (9.8%). No major intraoperative complications were reported. A simultaneous explantation was performed in 12 patients (29.3%). The mean number of pad reductions was 4.93 (p = 0.026). No intraoperative complications and no postoperative surgical revisions were reported. The mean follow-up of the patient cohort with a secondary sling was 16 months. CONCLUSION: We provide the largest cohort of male patients up to date with a secondary sling after primary failure of surgery for male SUI. Although the procedure is a rarely performed surgery and without a high level of evidence, a secondary adjustable male sling system might be a feasible option in selected patients with acceptable complication rates, whereas a valuable outcome regarding continence rates cannot be sufficiently supplied by our data.

Quality of Patient Information by Urologists Is Associated with Mental Distress in Bladder Cancer Patients.

AIMS: The study aimed to evaluate the prevalence of mental distress in patients with newly diagnosed bladder cancer, the cancer-information search behavior, and the influence of information seeking on distress. METHODS: One hundred and one bladder cancer patients answered 2 established questionnaires ("Hospital Anxiety and Depression Scale" [HADS] and the "Fragebogen zur Belastung von Krebskranken" [FBK-R23]) for evaluation of mental distress and a self-developed questionnaire with questions concerning information seeking and socioeconomic facts. RESULTS: Regarding risk group stratification, 57.4% were classified as high-risk and 42.6% as low-risk tumor-bearing patients. Analysis of mental distress showed that 23.2% had a score above the HADS-A cutoff, 25.3% above the HADS-D cutoff, and 21.4% showed a pathologic FBK-R23 score. Overall, 75% felt well informed about their illness. Risk group stratification did not correlate with HADS-A, HADS-D, or FBK-R23 score. Furthermore, active search for information or the use of the Internet did not correlate with the HADS-A, HADS-D, or FBK-R23 score. However, the quality of the urologist's information and the feeling of being informed correlated with the grade of mental distress. CONCLUSION: Besides the treatment of bladder cancer, informing the patient about the disease in a psychologically wholesome manner and working together with psycho-oncologically trained psychologists are essential tasks for the treating urologist.

Comprehensive analysis of Twitter activity on #Incontinence.

AIM: The aim of this study is comprehensive analysis of the Twitter activity on #Incontinence. MATERIAL AND METHODS: The following six functional-urology hashtags on Twitter were analyzed from 2015 to 2018 to gain a comprehensive insight into the topic: #Incontinence, #InterstitialCystitis, #OAB, #FPMRS, #BPH, and #UroBPH. For the Twitter analysis, Symplur Signals was used, which is a health care social media analytics tool. RESULTS: In total 191 383 tweets by 54 094 users in 2015 through 2018 were analyzed. A rise in the number of tweets could be identified for all six analyzed hashtags on functional urology, in summary, the numbers raised from 25 629 tweets in 2015 to 66 551 tweets in 2018. For the hashtag incontinence (#Incontinence), the number of tweets raised from 13 823 in 2015 to 19 996 in 2018 (+44.7%). Main influencers on functional urology topics identified by the Symplur algorithm were individuals from the health care sector in 44.6% of the cases and health care organizations in 36.5% of the cases, whereas for #Incontinence, only 7% of influencers were patients in 2018. The ten most common words connected to #Incontinence were Incontinence, Urinary, Women, Help, New, Bladder, Stress, Treatment, Pelvic, and Sex. Of the tweets, 66% were categorized as positive statements and 34% were categorized as negative. CONCLUSION: Social media is an emerging tool of communication in urology, whereas discussions on #Incontinence are underrepresented compared to the high prevalence of urinary incontinence. In addition, patients' activity is low.

Comparative evaluation of tissue damage induced by ultrasound and impact dual-mode endoscopic lithotripsy versus conventional single-mode ultrasound lithotripsy.

OBJECTIVE: The aim of our study was to perform comparative investigation of the tissue safety of three different endoscopic lithotripter devices including a new single-probe/dual-energy lithotripter in an in vivo animal model. The Swiss LithoClast Trilogy was compared to the Storz Calcuson and the Swiss LithoClast Vario. The safety test simulated the accidental direct contact between lithotripter probes and the urothelium, which can occur when sliding off a stone or drilling through a calculus during lithotripsy. The safety test included a smallest (1.5 mm) and largest (3.3/3.4 mm) probe diameter per device. METHODS: Testing was performed in nine pigs (three animals per device). The bladder tissue was exposed to direct lithotripter probe contact at maximum power for 10 s to produce visible tissue lesions. Acute tissue trauma was evaluated using a simplified scoring model describing the expected bladder wall injuries for histological examination. After 7 days, all animals were killed, necropsied and examined post mortem. For between-group comparisons regarding microscopic histopathologic features, a Chi-square test was used. A p value < 0.05 was considered to be statistically significant. RESULTS: Irrespective of the lithotripter used, no systemic signs of toxicity were observed. Histologically, signs of normal ongoing healing were observed on the bladder mucosa. There were no significant differences in histological findings taking changes of the epithelium (p = 0.360), the leucocyte infiltration (p = 0.123), the vascular congestion (p = 0.929) and the edema (p = 1.0) between the groups into account. CONCLUSIONS: The results of this study demonstrated a comparable safety between all lithotripsy devices.

Robotic-assisted Excision of Giant Prostatic Utricular Cysts: Technique, Outcomes and Follow-up.

BACKGROUND: Utricular cysts are usually the result of incomplete involution of the Müllerian ducts and may have no urethral connection. Treatment options for symptomatic utricular cysts include an open abdominal approach, trans-vesical excision, vasoligation without excision and laparoscopic/robotic-assisted excision. PATIENTS AND METHODS: Two patients (14 and 45 years old) with recurrent urinary tract infections associated with recurrent lower urinary tract irritative symptoms and recurrent perineal pains presented to our department. Clinical, radiological and MRI examinations showed 6x3 and 5x4cm utricular cysts, respectively. Both patients underwent robotic-assisted complete dissection of the cyst, including its neck. Separation of the cysts from surrounding tissues as well as the seminal vesicles while avoiding injury to the neurovascular bundles was followed by incision of the prostate base to dissect the cyst neck from the prostatic parenchyma up to its connection to the urethra. The cyst neck was secured with either one clip or 4/0 vicryl sutures. The field was reconstructed with 4/0 sutures. The patients were followed-up at 3, 6 and 12 months postoperatively. RESULTS: There were no intraoperative complications or injuries to the neighboring structures (seminal vesicles, vas deferens and urethra). The operative time was 95 and 80 minutes, respectively, with negligible blood loss. Both patients underwent an uneventful recovery from surgery, and were discharged on the 5th postoperative day. Both patients were asymptomatic throughout the entire follow-up period (15 months). MRI at 3 months showed no abnormalities. The postoperative IIEF score in the older patient showed no difference compared to his baseline findings. The life quality score showed high patient acceptance and both patients indicated that they would recommend the procedure. CONCLUSIONS: Symptomatic presentation of utricular cysts may be associated with recurrent urinary tract infections, orchitis-epididymitis and potential for malignancy. The present cases demonstrate that robotic-assisted surgical excision of symptomatic utricular cysts is a feasible and safe procedure. It seems to provide excellent visualization and access to these lesions. This procedure provides patients the advantages of minimally invasive surgery with outcomes comparable to those with other management techniques.

Acquired resistance to temsirolimus is associated with integrin α7 driven chemotactic activity of renal cell carcinoma in vitro.

The mechanistic target of the rapamycin (mTOR) inhibitor, temsirolimus, has significantly improved the outcome of patients with renal cell carcinoma (RCC). However, development of temsirolimus-resistance limits its effect and metastatic progression subsequently recurs. Since integrin α7 (ITGA7) is speculated to promote metastasis, this investigation was designed to investigate whether temsirolimus-resistance is associated with altered ITGA7 expression in RCC cell lines and modified tumor cell adhesion and invasion. Caki-1, KTCTL-26, and A498 RCC cell lines were driven to temsirolimus-resistance by exposing them to temsirolimus over a period of 12 months. Subsequently, adhesion to human umbilical vein endothelial cells, to immobilized fibronectin, or collagen was investigated. Chemotaxis was evaluated with a modified Boyden chamber assay and ITGA7 expression by flow cytometry and western blotting. Chemotaxis significantly decreased in temsirolimus-sensitive cell lines upon exposure to low-dosed temsirolimus, but increased in temsirolimus-resistant tumor cells upon reexposure to the same temsirolimus dose. The increase in chemotaxis was accompanied by elevated ITGA7 at the cell surface membrane with simultaneous reduction of intracellular ITGA7. ITGA7 knock-down significantly diminished motility of temsirolimous-sensitive cells but elevated chemotactic activity of temsirolimus-resistant Caki-1 and KTCTL-26 cells. Therefore, ITGA7 appears closely linked to adhesion and migration regulation in RCC cells. It is postulated that temsirolimus-resistance is associated with translocation of ITGA7 from inside the cell to the outer surface. This switch forces RCC migration forward. Whether ITGA7 can serve as an important target in combatting RCC requires further investigation.

A prospective randomised comparison between the transperitoneal and retroperitoneoscopic approaches for robotic-assisted pyeloplasty in a single surgeon, single centre study.

Literature data comparing robotic-assisted laparoscopic versus retroperitoneoscopic approaches are still lacking, probably due to difficulties with the retroperitoneoscopic approach. The objective is to compare the results of robotic-assisted pyeloplasty using transperitoneal and retroperitoneal approaches in a prospective randomised single surgeon study. 80 consecutive patients with primary ureteropelvic junction obstruction were prospectively randomised between transperitoneal (40 patients, group 1) and retroperitoneal (40 patients, group 2) robotic-assisted pyeloplasty. All patients underwent preoperative clinical evaluation, retrograde urography, and diuretic isotope renography. All operations were performed by a single-experienced surgeon. Patients were followed up by postoperative clinical examination, sonography, and diuretic renography at 3-6 months. Both approaches were compared with regard to patients' demographic data, radiological and operative findings, and functional outcomes, and correlations were statistically evaluated. Preoperative demographic, clinical, and renal scintigraphy data were comparable for both groups. No open/laparoscopic conversions were necessary. Mean operative times (skin to skin) were 125 (70-305) and 118 (60-345) min for groups 1 and 2, respectively (p = 0.726). Only minor complications were found in three and four patients from groups 1 and 2, respectively. Pyeloplasty technique included a renal pelvis flap in three patients from either group,; otherwise, the Anderson-Hynes technique was employed. None of perioperative patient and operative parameters, including approach, had a significant impact on operative time or functional outcomes. Median follow-up was 3 months for both groups. Success was recorded in 39 and 38 patients from groups 1 and 2, respectively, while equivocal results were obtained in 3 cases. Postoperative 3 month renal scintigraphy showed no significant GFR or split renal function differences between the groups. There was no detectable postoperative deterioration in ipsilateral split renal function or hydronephrosis grade. Robotic-assisted retroperitoneoscopic pyeloplasty exhibits low morbidity and satisfactory operative and functional outcomes comparable to the usually preferred laparoscopic approach. Robotic-assisted pyeloplasty has high success rates regardless of the used approach. Accordingly, every surgeon should use the approach which he/she feels most comfortable with.

mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro.

Mechanistic target of rapamycin (mTOR) signaling is typically increased in hepatocellular carcinoma (HCC). A panel of HCC cell lines (HepG2, Hep3B and HuH6) was exposed to various concentrations of the mTOR inhibitors, everolimus and temsirolimus, in order to investigate their effects on cell growth, clonal formation, cell cycle progression, and adhesion and chemotactic migration using MTT and clonal cell growth assays, fluorometric detection of cell cycle phases and a Boyden chamber assay. In addition, integrin α and ß adhesion receptors were analyzed by flow cytometry and blocking studies using function blocking monoclonal antibodies were conducted to explore functional relevance. The results demonstrated that everolimus and temsirolimus significantly suppressed HCC cell growth and clonal formation, at 0.1 or 1 nM (depending on the cell line). In addition, the number of cells in G0/G1 phase was increased in response to drug treatment, whereas the number of G2/M phase cells was decreased. Drug treatment also considerably suppressed HCC cell adhesion to immobilized collagen. Integrin profiling revealed strong expression of integrin α1, α2, α6 and ß1 subtypes; and integrin α1 was upregulated in response to mTOR inhibition. Suppression of integrin α1 did not affect cell growth; however, it did significantly decrease adhesion and chemotaxis, with the influence on adhesion being greater than that on motility. Due to a positive association between integrin α1 expression and the extent of adhesion, whereby reduced receptor expression was correlated to decreased cell adhesion, it may be hypothesized that the adhesion­blocking effects of mTOR inhibitors are not associated with mechanical contact inhibition of the α1 receptor but with integrin α1­dependent suppression of oncogenic signaling, thus preventing tumor cell­matrix interaction.

Sulforaphane as an adjunctive to everolimus counteracts everolimus resistance in renal cancer cell lines.

BACKGROUND: The mechanistic target of rapamycin (mTOR) inhibitors, everolimus and temsirolimus, have widened therapeutic options to treat renal cell carcinoma (RCC). However, chronic treatment with these inhibitors often induces resistance, leading to therapeutic failure. PURPOSE: The natural compound, sulforaphane (SFN), was added to an everolimus based regime in vitro in the hopes of preventing resistance development. METHODS: A panel of RCC cell lines (A498, Caki-1, KTCTL-26) was treated with everolimus or SFN or with an everolimus-SFN-combination, either short- (24h) or long-term (8 weeks), and cell growth, proliferation, apoptosis, and cell cycle phases were measured. The cell cycle regulating proteins cdk1, cdk2, cyclin A, cyclin B, akt and raptor (both total and activated) were also evaluated. RESULTS: Short-term incubation with everolimus (1nM) or SFN (5µM) significantly reduced RCC cell growth. Additive effects on tumor growth and proliferation were evoked by the SFN-everolimus combination. Long-term everolimus-incubation led to resistance development in Caki-1 cells, evidenced by elevated growth and proliferation, associated with an increased percentage of G2/M (non-synchronized cell model) or S-phase (synchronized cell model) cells. Molecular analysis revealed up-regulation of the cdk1-cyclin B and cdk2-cyclin A axis, along with elevated phosphorylation of the mTOR sub-member, raptor. In contrast, resistance development was not observed with the long-term combination of SFN-everolimus. The combination suppressed Caki-1 growth and proliferation, and was associated with an increase in G0/G1-phase cells, diminished cdk1 and akt (both total and activated), cyclin B and raptor expression. CONCLUSION: Adding SFN to an everolimus based RCC treatment regimen in vitro delayed resistance development observed with chronic everolimus monotherapy. Ongoing in vivo studies are necessary to verify the in vitro data.

Sulforaphane inhibits proliferation and invasive activity of everolimus-resistant kidney cancer cells in vitro.

Although the mechanistic target of rapamycin (mTOR) inhibitor, everolimus, has improved the outcome of patients with renal cell carcinoma (RCC), improvement is temporary due to the development of drug resistance. Since many patients encountering resistance turn to alternative/complementary treatment options, an investigation was initiated to evaluate whether the natural compound, sulforaphane (SFN), influences growth and invasive activity of everolimus-resistant (RCCres) compared to everolimus-sensitive (RCCpar) RCC cell lines in vitro. RCC cells were exposed to different concentrations of SFN and cell growth, cell proliferation, apoptosis, cell cycle, cell cycle regulating proteins, the mTOR-akt signaling axis, adhesion to human vascular endothelium and immobilized collagen, chemotactic activity, and influence on surface integrin receptor expression were investigated. SFN caused a significant reduction in both RCCres and RCCpar cell growth and proliferation, which correlated with an elevation in G2/M- and S-phase cells. SFN induced a marked decrease in the cell cycle activating proteins cdk1 and cyclin B and siRNA knock-down of cdk1 and cyclin B resulted in significantly diminished RCC cell growth. SFN also modulated adhesion and chemotaxis, which was associated with reduced expression of the integrin subtypes α5, α6, and ß4. Distinct differences were seen in RCCres adhesion and chemotaxis (diminished by SFN) and RCCpar adhesion (enhanced by SFN) and chemotaxis (not influenced by SFN). Functional blocking of integrin subtypes demonstrated divergent action on RCC binding and invasion, depending on RCC cell sensitivity to everolimus. Therefore, SFN administration could hold potential for treating RCC patients with established resistance towards everolimus.

Long-term Outcome of the Retrourethral Transobturator Male Sling After Transurethral Resection of the Prostate.

PURPOSE: To evaluate long-term outcomes of AdVance and AdVanceXP male slings in patients with persistent stress urinary incontinence (SUI) after transurethral resection of the prostate (TURP). METHODS: A total of 18 consecutive patients received AdVance (n=14) or AdVanceXP (n=4) male sling implantation between 2007 and 2013. Continence was determined by pad use, 24-hour pad testing and validated questionnaires (International Consultation on Incontinence Questionnaire Short Form, ICIQ-SF). Quality of life was evaluated by International Quality of Life (IQoL) score. Patient satisfaction was measured with patient's global impression of improvement score. Cure was defined as 0-5 g in the 24-hour pad test. Statistical analysis included Fisher exact and Wilcoxon test (P<0.05). RESULTS: Follow-up was available for 15 patients who underwent further analysis. After a median follow-up of 70 months (range, 18-83 months), mean daily pad usage was 1.8±2.1 pads (P=0.015 vs. baseline level). Mean IQoL score was 66.4±31.6 (P=0.050 vs. baseline level), and mean ICIQ-SF score was 9.5±6.6 (P=0.077 vs. baseline level). Based on 24-hour pad testing, mean daily urine loss was 31.2±64.5 g (median, 0 g; range, 0-209 g). Cure rate was 46.7%, and cure-and-improved rate was 60.0%. Assessing predictive features for success, better results were found in patients who needed up to 4 pads preoperatively (P=0.041) as well as for patients ≤71 years at the time of implantation (P=0.041). CONCLUSIONS: The findings indicate that AdVance and AdVanceXP implantation can be performed effectively and safely in men suffering from SUI after TURP. However, long-term success rates seem to be lower compared to SUI after radical prostatectomy and patients should be counseled accordingly.

An innovative technique of robotic-assisted/laparoscopic re-pyeloplasty in horseshoe kidney in patients with failed previous pyeloplasty for ureteropelvic junction obstruction.

OBJECTIVES: To describe an innovative laparoscopic/robotic-assisted re-pyeloplasty technique in patients with recurrent ureteropelvic junction obstruction (UPJO) in horseshoe kidneys. PATIENTS AND METHODS: Data from five patients (37-65, median 54 years) with symptomatic recurrence of UPJO in horseshoe kidney who underwent laparoscopic/robotic-assisted re-pyeloplasty at our institution since 2004 were evaluated retrospectively. The upper ureter together with wedge resection of the pelvis at the lower calyx was performed. The ureter is spatulated till beyond the isthmus and anastomosed to lower calyx. Rotational renal pelvis flap is used for reconstruction and conisation of the pelvis. RESULTS: Median operative time was 137 min (92-180) with a negligible blood loss. There was no need for conversion or revisions. Perioperative periods were uneventful. The intraoperatively inserted JJ was left for 6-8 weeks. Median postoperative differential function of affected kidney at 3 months (MAG III) was 38 % (26-42 %), unchanged from 35 % (21-41 %), preoperatively. This was stable in three patients and higher in two (5 and 7 %). There were no obstructive elements indicating anatomical ureteric obstruction. After convalescence period, three patients recurred to their work at 5 weeks, while all at 8 weeks. All patients remained asymptomatic and have not required any further interventions during whole follow-up. CONCLUSIONS: Described technique of laparoscopic/robotic-assisted re-pyeloplasty in horseshoe kidneys is technically feasible, safe and effective with high patient satisfaction and early convalescence. Its success rate is comparable with the results after primary pyeloplasty in horseshoe and heterotopic kidneys. Larger series may be required to allow for more accurate comparison.

Impact of pulse duration on Ho:YAG laser lithotripsy: treatment aspects on the single-pulse level.

OBJECTIVES: Holmium-YAG (Ho:YAG) laser lithotripsy is a multi-pulse treatment modality with stochastic effects on the fragmentation. In vitro investigation on the single-pulse-induced effects on fiber, repulsion as well as fragmentation was performed to identify potential impacts of different Ho:YAG laser pulse durations. MATERIALS AND METHODS: A Ho:YAG laser system (Swiss LaserClast, EMS S.A., Nyon, Switzerland) with selectable long- or short-pulse mode was tested with regard to fiber burn back, the repulsion capacity using an underwater pendulum setup and single-pulse-induced fragmentation capacity using artificial (BEGO) stones. The laser parameters were chosen in accordance with clinical application modes (laser fiber: 365 and 200 µm; output power: 4, 6 and 10 W in different combinations of energy per pulse and repetition rate). Evaluation parameters were reduction in fiber length, pendulum deviation and topology of the crater. RESULTS: Using the long-pulse mode, the fiber burn back was nearly negligible, while in short-pulse mode, an increased burn back could be observed. The results of the pendulum test showed that the deviation induced by the momentum of short pulses was by factor 1.5-2 higher compared to longer pulses at identical energy per pulse settings. The ablation volumes induced by single pulses either in short-pulse or long-pulse mode did not differ significantly although different crater shapes appeared. CONCLUSION: Reduced stone repulsion and reduced laser fiber burn back with longer laser pulses may result in a more convenient handling during clinical application and thus in an improved clinical outcome of laser lithotripsy.