Distended Seminal Vesicles Are Involved in Specific Cerebral Sexual Arousal: A Pilot Study Using Functional Brain Imaging in Young Healthy Men.

Background: Whether seminal vesicles play a role in sexual activity in men is unknown. No study so far has compared the neural processing of visual sexual stimuli in men depending on the filling state of the seminal vesicles. Objective: To evaluate potential specific cortical activation by visual sexual stimuli with distended and empty seminal vesicles. Design setting and participants: A prospective case-control trial was conducted. Six male individuals underwent two visits on 2 consecutive days for hormone analyses; Derogatis Interview for Sexual Functioning (DISF) questionnaire; functional magnetic resonance imaging (fMRI) with passively viewing sexual, neutral, positive, and negative emotional pictures; and structural pelvic MRI. After the first visit, the participants had to empty seminal vesicles by masturbation. During fMRI, every participant viewed alternating blocks of sexual, neutral, positive, and negative emotional pictures. Outcome measurements and statistical analysis: Comparisons between days 1 and 2 were evaluated using paired t tests. Results and limitations: No significant differences were observed regarding hormone analyses, DISF questionnaire score, and arousal scoring between days 1 and 2. Seminal vesicle volume was significantly lower on day 2 (p = 0.003). Significantly higher activation was observed in the right precentral gyrus, middle frontal gyrus, and right superior temporal sulcus when contrasted for sexual over neutral (p < 0.05). Conclusions: In response to pictures with sexual emotional content, significantly higher activation was detected in brain areas involved in motor preparation (arousal) and coding of desirability of visual sexual stimuli in men with distended seminal vesicles than in the same men with emptied seminal vesicles. This suggests that the filling state of the seminal vesicles may influence sexual desire in men. Patient summary: We compared brain activity of men with filled and emptied seminal vesicles by functional magnetic resonance imaging. We found that men with filled seminal vesicles had higher activation of brain areas involved in arousal and sexual desire.

Intensified and Standardized Digital Communication with Cystectomy Patients as a Potentially Simple and Effective Modality for Early Detection of Postoperative Complications: Results from a Pilot Study.

BACKGROUND: Postoperative readmission rates following radical cystectomy remain significant. Early identification of emerging complications could potentially allow for immediate institution of therapy. OBJECTIVE: To intensify postoperative patient-physician communication via a cellphone-based health care application (CHA) and to evaluate its potential for early detection of complications. DESIGN SETTING AND PARTICIPANTS: This was a pilot study involving 18 radical cystectomy patients. During the first 30 d, patients received a push cellphone notification twice a week requesting data input into the CHA. This was reduced to once a week from day 31 to day 90. De-identified recorded data were reviewed by the surgeon involved. If deemed necessary, patients were contacted by the surgeon via telephone to obtain more detailed clinical information. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics were used. RESULTS AND LIMITATIONS: Of the 18 patients enrolled, all completed the 90-d reporting period. On two occasions, interventions were necessary on the basis of data recorded on the CHA. One neobladder patient was given antibiotic therapy for pyelonephritis. Another patient reported weight loss and nausea with clinical suspicion of metabolic acidosis, and his sodium bicarbonate and fluid intake were increased. Limitations include the small number of cases from a single low-volume center. CONCLUSIONS: CHA-based monitoring of clinical parameters within the crucial 90-d postoperative period following radical cystectomy provides meaningful information. In this pilot study, two potential readmissions were possibly avoided on the basis of recorded basic vital signs and early intervention. PATIENT SUMMARY: Besides regular clinic follow-up visits after radical cystectomy, additional aids such as a cellphone-based health care application can provide treating physicians with relevant clinical information and may help to identify imminent deviations from normal postoperative recovery at an early stage.

Lesion Pattern in Patients With Erectile Dysfunction of Suspected Arterial Origin: An Angiographic Study.

PURPOSE: To determine the specific lesion pattern of supplying arteries in patients with cardiovascular risk factors suffering from treatment-refractory erectile dysfunction (ED). METHODS: From May 2012 to August 2013, 26 men (median age 55 years) poorly responsive to phosphodiesterase-5 inhibitor therapy were evaluated for a possible vascular cause for their ED. The men were examined with penile duplex sonography and digital subtraction angiography (DSA). Arterial lesions in the common and internal iliac arteries and the internal pudendal arteries considered amenable to endovascular therapy were treated with angioplasty ± stents. Retrospectively, 2 blinded investigators independently evaluated the DSA images and categorized the vascular patterns of the erection-related arteries as normal, macroangiopathy (occlusive lesions of the internal pudendal arteries), or microangiopathy (smaller caliber arteries distal to the internal pudendal circulation with no distal arterial reconstitution). RESULTS: Seventeen macroangiopathic lesions were successfully treated by angioplasty in 11 patients. The treated arterial lesions were mainly located in the internal (n=10) and common iliac arteries (n=2), whereas the internal pudendal artery were involved in 5 cases. Microangiopathic lesions lacking distal reconstitution were present in 7 patients, and the remaining 8 patients had normal vessels supplying the penis. Patients with macroangiopathy undergoing angioplasty had a higher prevalence of peripheral artery disease (63.6% vs 6.7%, p=0.003). CONCLUSION: In this preliminary series of ED patients with cardiovascular risk factors and pathologic duplex sonographic flow parameters, roughly 40% exhibited arterial lesions amenable to endovascular revascularization. In the patients with macroangiopathy, vessels upstream of the internal pudendal artery were most commonly affected. More studies are warranted to define the role of endovascular procedures in this ED subpopulation.

[Acute urinary retention: a few simple rules for a successful catheterization]. / Die akute Harnverhaltung in der Praxis.

Acute urinary retention is a common emergency condition in elderly men. Transurethral and suprapubic catheterization are easy and safe procedures provided that a few simple rules are followed. Primarily, a transurethral catheter is placed if there is no urethral injury or stricture. Local anaesthesia of the urethra up to the sphincter region and a well-stretched penis warrant an atraumatic insertion of the catheter into the bladder. The use of a thick catheter with a round tip or of a catheter with a bended tip under rectal guidance facilitate the insertion of the catheter in difficult conditions. Alternatively, a suprapubic catheterization can be performed provided that no contraindication such as history or suspicion of transitional cell carcinoma is present. Optimal interventional conditions using ultrasound-guidance are mandatory in patients after abdominal surgery and with hemorrhagic diathesis in view of a safe and straight-forward placement of the suprapubic catheterization. In case of persistent bleeding after insertion of a suprapubic catheter, the suprapubic catheter should be replaced by one with a balloon blocked and kept under tension for several minutes.

Bacillus Calmette-Guérin strain differences have an impact on clinical outcome in bladder cancer immunotherapy.

BACKGROUND: Whether the commonly used bacillus Calmette-Guérin (BCG) strains Connaught and Tice confer different treatment responses in non-muscle-invasive bladder cancer (NMIBC) is unknown. OBJECTIVES: To compare clinical efficacy, immunogenicity, and genetics of BCG Connaught and Tice. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized single-institution trial with treatment of 142 high-risk NMIBC patients with BCG Connaught or Tice. INTERVENTION: Patients were randomized to receive six instillations of BCG Connaught or Tice. For experimental studies, BCG strains were compared in C57Bl/6 mice. Bladders and lymphoid tissues were analyzed by cytometry and the latter cultivated to detect live BCG. BCG genomic DNA was sequenced and compared with reference genomes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Recurrence-free survival was the primary end point of the clinical study. The Kaplan-Meier estimator was used for estimating survival and time-to-event end points. Nonparametric tests served for the analysis of the in vivo results. RESULTS AND LIMITATIONS: Treatment with BCG Connaught conferred significantly greater 5-yr recurrence-free survival compared with treatment with BCG Tice (p=0.0108). Comparable numbers of patients experienced BCG therapy-related side effects in each treatment group (p=0.09). In mice, BCG Connaught induced stronger T-helper cell 1-biased responses, greater priming of BCG-specific CD8(+) T cells, and more robust T-cell recruitment to the bladder than BCG Tice. Genome sequencing of the BCG strains revealed candidate genes potentially involved in the differential clinical responses. CONCLUSIONS: BCG strain may have an impact on treatment outcome in NMIBC immunotherapy. PATIENT SUMMARY: We compared the efficacy of two commonly used bacillus Calmette-Guérin (BCG) strains for the treatment of NMIBC and found that treatment with BCG Connaught prevented recurrences more efficiently than BCG Tice. Comparison of the immunogenicity of the two strains in mice indicated superior immunogenicity of BCG Connaught. We also identified genetic differences that may explain the differential efficacy of the Connaught and Tice BCG strains. TRIAL REGISTRATION: NCT00003779.

Bacillus Calmette-Guérin failure in patients with non-muscle-invasive urothelial carcinoma of the bladder may be due to the urologist's failure to detect urothelial carcinoma of the upper urinary tract and urethra.

BACKGROUND: Various reasons exist for so-called bacillus Calmette-Guérin (BCG) failure in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC). OBJECTIVE: To explore whether urothelial carcinoma of the upper urinary tract (UUT) and/or prostatic urethra may be a cause for BCG failure. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 110 patients with high-risk NMIBC repeatedly treated with intravesical BCG, diagnosed with disease recurrence, and followed for a median time of 9.1 yr. INTERVENTION: Two or more intravesical BCG induction courses without maintenance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was pattern of disease recurrence (BCG failure) within the urinary tract categorised into UUT and/or urethral carcinoma (with or without intravesical recurrence), and intravesical recurrence alone. Secondary outcome was survival. Predictors of UUT and/or urethral carcinoma and the effect of pattern of disease recurrence on cancer-specific survival were assessed with multivariable Cox regression analysis adjusting for multiple clinical and tumour characteristics. RESULTS AND LIMITATIONS: Of the 110 patients, 57 (52%) had UUT and/or urethral carcinoma (with or without intravesical recurrence), and 53 (48%) had intravesical recurrence alone. In patients with UUT and/or urethral carcinoma, bladder carcinoma in situ (Tis) before the first and second BCG course was present in 42 of 57 (74%) and 47 of 57 (82%) patients, respectively. On multivariable analysis, bladder Tis before the first and/or second BCG course was the only independent predictor of UUT and/or urethral carcinoma. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) had died due to metastatic urothelial carcinoma, and 23 (21%) had died of other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. Main study limitations were retrospective design and limited power for survival analysis. CONCLUSIONS: In our patients with high-risk NMIBC failing after two or more courses of intravesical BCG, UUT and/or urethral carcinoma was detected in >50% of the cases during follow-up. The vast majority of these patients had bladder Tis before the first and/or second BCG course. In patients experiencing the so-called BCG failure, a diagnostic work-up of UUT and prostatic urethra should always be performed to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy is considered.

Outcomes of radical cystectomy with extended lymphadenectomy alone in patients with lymph node-positive bladder cancer who are unfit for or who decline adjuvant chemotherapy.

OBJECTIVE: To analyse the long-term outcomes of patients with lymph node (LN)-positive bladder cancer, who did not receive any adjuvant therapy after radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND). PATIENTS AND METHODS: We conducted a retrospective, combined cohort analysis based on two prospectively maintained cystectomy databases from the University of Southern California and the University of Bern. Eligible patients underwent RC with ePLND for cN0M0 disease but were found to have LN-positive disease. No patient had neoadjuvant therapy, and all had negative surgical margins. Kaplan-Meier plots were used to estimate recurrence-free survival (RFS) and overall survival (OS). Subgroup comparisons were performed using log-rank tests, and multivariable analysis was based on Cox proportional hazard models. RESULTS: Of 521 patients with LN-positive disease, 251 (48%) never received adjuvant therapy. Although the pathological stage distribution was similar, the 251 patients who did not receive adjuvant therapy were older and had both fewer total and positive LNs than those who underwent adjuvant therapy. The median RFS for patients treated with RC alone was 1.6 years. Recurrences mainly occurred <2 years after RC, resulting in 5- and 10-year RFS rates of 32 and 26%, respectively. Pathological T stage, the total number of LNs and the number of positive LNs detected were independent predictors of RFS and OS. CONCLUSIONS: In this study, 25% of patients with documented LN metastases who did not receive adjuvant therapy were cured with RC and ePLND; however, a few relapses may occur later than 3 years. Predictors of survival were pathological T stage, the number of total LNs and the number of positive LNs identified.

Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging facilitates detection of metastases in normal-sized pelvic lymph nodes of patients with bladder and prostate cancer.

BACKGROUND: Conventional cross-sectional imaging with computed tomography and magnetic resonance imaging (MRI) has limited accuracy for lymph node (LN) staging in bladder and prostate cancer patients. OBJECTIVE: To prospectively assess the diagnostic accuracy of combined ultrasmall superparamagnetic particles of iron oxide (USPIO) MRI and diffusion-weighted (DW) MRI in staging of normal-sized pelvic LNs in bladder and/or prostate cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Examinations with 3-Tesla MRI 24-36 h after administration of USPIO using conventional MRI sequences combined with DW-MRI (USPIO-DW-MRI) were performed in 75 patients with clinically localised bladder and/or prostate cancer staged previously as N0 by conventional cross-sectional imaging. Combined USPIO-DW-MRI findings were analysed by three independent readers and correlated with histopathologic LN findings after extended pelvic LN dissection (PLND) and resection of primary tumours. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity and specificity for LN status of combined USPIO-DW-MRI versus histopathologic findings were evaluated per patient (primary end point) and per pelvic side (secondary end point). Time required for combined USPIO-DW-MRI reading was assessed. RESULTS AND LIMITATIONS: At histopathologic analysis, 2993 LNs (median: 39 LNs; range: 17-68 LNs per patient) with 54 LN metastases (1.8%) were found in 20 of 75 (27%) patients. Per-patient sensitivity and specificity for detection of LN metastases by the three readers ranged from 65% to 75% and 93% to 96%, respectively; sensitivity and specificity per pelvic side ranged from 58% to 67% and 94% to 97%, respectively. Median reading time for the combined USPIO-DW-MRI images was 9 min (range: 3-26 min). A potential limitation is the absence of a node-to-node correlation of combined USPIO-DW-MRI and histopathologic analysis. CONCLUSIONS: Combined USPIO-DW-MRI improves detection of metastases in normal-sized pelvic LNs of bladder and/or prostate cancer patients in a short reading time.

Unaltered oncological outcomes of radical cystectomy with extended lymphadenectomy over three decades.

OBJECTIVE: To evaluate oncological outcome trends over the last three decades in patients after radical cystectomy (RC) and extended pelvic lymph node (LN) dissection. PATIENTS AND METHODS: Retrospective analysis of the University of Southern California (USC) RC cohort of patients (1488 patients) operated with intent to cure from 1980 to 2005 for biopsy confirmed muscle-invasive urothelial bladder cancer. To focus on outcomes of unexpected (cN0M0) LN-positive patients, the USC subset was extended with unexpected LN-positive patients from the University of Berne (UB) (combined subgroup 521 patients). Patients were grouped and compared according to decade of surgery (1980-1989/1990-1999/≥2000). Survival probabilities were calculated with Kaplan-Meier plots, log-rank tests compared outcomes according to decade of surgery, followed by multivariable verification. RESULTS: The 10-year recurrence-free survival was 78-80% in patients with organ-confined, LN-negative disease, 53-60% in patients with extravesical, yet LN-negative disease and ≈30% in LN-positive patients. Although the number of patients receiving systemic chemotherapy increased, no survival improvement was noted in either the entire USC cohort, or in the combined LN-positive USC-UB cohort. In contrast, patient age at surgery increased progressively, suggesting a relative survival benefit. CONCLUSIONS: Radical surgery remains the mainstay of therapy for muscle-invasive bladder cancer. Yet, our study reveals predictable outcomes but no survival improvement in patients undergoing RC over the last three decades. Any future survival improvements are likely to result from more effective systemic treatments and/or earlier detection of the disease.

Salvage-targeted kidney cancer therapy in patients progressing on high-dose interleukin-2 immunotherapy: the UCLA experience.

PURPOSE: To analyze the outcomes of patients with metastatic renal cell carcinoma treated with salvage-targeted therapy after progressing on high-dose interleukin (IL)-2 immunotherapy in a tertiary referral center. MATERIALS AND METHODS: A retrospective nonrandomized cohort consisting of 286 patients with metastatic renal cell carcinoma treated from 2003 to 2010 was analyzed from the University of California, Los Angeles (UCLA) Kidney Cancer database. All patients underwent cytoreductive nephrectomy, and 21 patients received salvage-targeted therapy after progression on high-dose IL-2, whereas 111 patients received targeted therapy alone. The remaining 154 patients had other treatment combinations or experimental targeted therapy agents only. Since 2003, selection of patients for high-dose IL-2 was increasingly based on clinical, pathologic, and molecular criteria (UCLA CPM criteria). Disease-specific survival was calculated from diagnosis of metastatic renal cell carcinoma. RESULTS: Patients selected according to UCLA CPM criteria and treated with salvage-targeted therapy after progressing on high-dose IL-2 experienced a significantly greater disease-specific survival (median not reached) than those treated with targeted therapy alone (30 months; P = 0.004). Since 2006, all high-dose IL-2 patients met the UCLA CPM criteria and were able to receive salvage-targeted therapy upon progression. Disease-specific survival calculated from initiation of targeted therapy was comparable for patients treated with salvage-targeted therapy after progression on high-dose IL-2 (34 months) versus first-line targeted therapy (26 months; P = 0.175). DISCUSSION: Patients selected for high-dose IL-2 based on UCLA CPM criteria and treated with salvage-targeted therapy upon progression have achieved outstanding disease-specific survival. Our data suggest a new algorithm for carefully selected patients with metastatic renal cell carcinoma based on UCLA CPM criteria to receive first-line high-dose IL-2 while reserving their option for salvage-targeted therapy with uncompromised efficacy upon progression.

Novel prototype sewing device, EndoSew®, for minimally invasive surgery: an extracorporeal ileal conduit construction pilot study in 10 patients.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The EndoSew(®) prototype was first tested in a porcine model several years ago. The investigators found it both simple to master and reliable, its greatest advantage being a 2.4-fold time saving compared with straight laparoscopic suturing. In addition to that publication, there is a single case report describing the performance of an open EndoSew(®) suture to close parts (16 cm) of an ileal neobladder. The time for suturing the 16 cm ileum was 25 min, which is in line with our experience. The knowledge on this subject is limited to these two publications. We report on the first consecutive series of ileal conduits performed in humans using the novel prototype sewing device EndoSew(®). The study shows that the beginning and the end of the suture process represent the critical procedural steps. It also shows that, overall, the prototype sewing machine has the potential to facilitate the intracorporeal suturing required in reconstructive urology for construction of urinary diversions. OBJECTIVE: To evaluate the feasibility and safety of the novel prototype sewing device EndoSew(®) in placing an extracorporeal resorbable running suture for ileal conduits. PATIENTS AND METHODS: We conducted a prospective single-centre pilot study of 10 consecutive patients undergoing ileal conduit, in whom the proximal end of the ileal conduit was closed extracorporeally using an EndoSew(®) running suture. The primary endpoint was the safety of the device and the feasibility of the sewing procedure which was defined as a complete watertight running suture line accomplished by EndoSew(®) only. Watertightness was assessed using methylene blue intraoperatively and by loopography on postoperative days 7 and 14. Secondary endpoints were the time requirements and complications ≤30 days after surgery. RESULTS: A complete EndoSew(®) running suture was feasible in nine patients; the suture had to be abandoned in one patient because of mechanical failure. In three patients, two additional single freehand stitches were needed to anchor the thread and to seal tiny leaks. Consequently, all suture lines in 6/10 patients were watertight with EndoSew(®) suturing alone and in 10/10 patients after additional freehand stitches. The median (range) sewing time was 5.5 (3-10) min and the median (range) suture length was 4.5 (2-5.5) cm. There were no suture-related complications. CONCLUSIONS: The EndoSew(®) procedure is both feasible and safe. After additional freehand stitches in four patients all sutures were watertight. With further technical refinements, EndoSew(®) has the potential to facilitate the intracorporeal construction of urinary diversions.

Dendritic cell-based immunotherapy in prevention and treatment of renal cell carcinoma: efficacy, safety, and activity of Ad-GM·CAIX in immunocompetent mouse models.

The dendritic cell vaccine DC-Ad-GM·CAIX is an active, specific immunotherapy with the potential of providing a safe and effective therapy against renal cell carcinoma (RCC). Using immunocompetent Balb/c mouse models we tested the efficacy and mechanism of the vaccine to prevent and treat the growth of a syngeneic RCC (RENCA) engineered to overexpress the human TAA carbonic anhydrase IX (NPR-IX). In a prevention model, NPR-IX tumor development was specifically and significantly delayed by 13 days in DC-Ad-GM·CAIX-treated mice (P < 0.001), tumor volumes were 79% smaller (day 24, P < 0.007), and body weight was maintained at study termination compared with the controls. Six of these mice remained tumor-free for > 1 year. In a treatment model, NPR-IX tumors remained smaller in DC-Ad-GM·CAIX-treated mice for 8 days (P < 0.002), achieving a 60% growth inhibition at termination. No vaccine-related organ toxicity was observed in either model. The critical mechanistic parameter separating responsive from nonresponsive tumors was hCAIX protein expression, demonstrated by aggressive growth of tumors that did not express hCAIX protein and in sham-treated mice (DC-Ad-Null). No murine serum anti-hCAIX antibodies were detected. Moreover, altered mechanisms of immunoediting as a means for immune evasion were suggested by differential gene expression (Ccl1, Hmgb1, Fgl2, Cd209a, and Klra2) and therapy evasion miRNAs (miR-1186, miR-98, miR-5097, miR-1942, and miR-708) in tumors that evaded DC-Ad-GM·CAIX immunotherapy. This is the first study in immunocompetent mice that provides a proof of concept for the specificity, efficacy, safety, and activity of the DC-Ad-GM·CAIX immunotherapy, forming the basis for a first-in-human phase I trial in RCC patients.

Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma.

BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau (VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1α (HIF-1α) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1α gene) in clear cell renal cell carcinoma (ccRCC). METHODS: In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL +3p/+14q (VHL wild type [VHL-WT]), VHL +3p/-14q (VHL-WT plus HIF2α [WT/H2]), -3p/+14q (HIF1α and HIF2α [H1H2]), and -3p/-14q (HIF2α [H2]). RESULTS: Among patients who had loss of 3p, tumors with -3p/-14q (H2) alterations were larger (P = .002), had higher grade (P = .002) and stage (P = .001), and more often were metastatic (P = .029) than tumors that retained 14q (H1H2). All patients who had tumors with -3p/-14q (H2) had worse cancer-specific survival (P = .014), and patients who had localized disease (P = .012) and primary T1 (pT1) tumors (P = .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses. CONCLUSIONS: Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1α gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1α functions as an important tumor suppressor gene in ccRCC.

Ultrasmall superparamagnetic particles of iron oxide allow for the detection of metastases in normal sized pelvic lymph nodes of patients with bladder and/or prostate cancer.

AIM: Lymph node metastases influence prognosis and outcome in patients with bladder and prostate cancer. Cross sectional imaging criteria are limited in detecting metastases in normal sized lymph nodes. This prospective study assessed the diagnostic accuracy of ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) for the detection of metastases in normal sized lymph nodes using extended pelvic lymph node dissection (ePLND) and histopathology as the reference standard. METHODS: Seventy-five patients (bladder cancer, n=19, prostate cancer n=48, both, n=8) were examined using 3T MR before and after USPIO-administration. A preoperative reading with two readers in consensus and a second postoperative reading with three independent blinded readers were performed. Results were correlated with histopathology and diagnostic accuracies were calculated for all readings. RESULTS: A total of 2993 lymph nodes were examined histopathologically. Fifty-four metastatic nodes were found in 20/75 patients (26.7%). The first reading had a sensitivity of 55.0%, specificity of 85.5%, positive predictive value (PPV) of 57.9%, negative predictive value (NPV) of 83.9%, and diagnostic accuracy (DA) of 77.3% on a per patient level. The second reading had a mean sensitivity of 58.3%, specificity of 83.0%, PPV of 58.0%, NPV of 84.4% and DA of 76.4% on a per patient level. The majority of missed metastases were smaller than 5mm in short axis diameter. CONCLUSIONS: USPIO-enhanced MRI in bladder and prostate cancer patients allows detection of metastases in normal sized lymph nodes and might guide the surgeon to remove suspicious lymph nodes not included in standard PLND.

Parenteral nutrition does not improve postoperative recovery from radical cystectomy: results of a prospective randomised trial.

BACKGROUND: After radical cystectomy, patients are in a catabolic state because of postoperative stress response, extensive wound healing, and ileus. OBJECTIVE: To evaluate whether recovery can be improved with total parenteral nutrition (TPN) in patients following extended pelvic lymph node dissection (ePLND), cystectomy, and urinary diversion (UD). DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective, randomised, single-centre study of 157 consecutive cystectomy patients. INTERVENTION: Seventy-four patients (group A) received TPN during the first 5 postoperative days, with additional oral intake ad libitum. Eighty-three patients (group B) received oral nutrition alone. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the occurrence of postoperative complications. Secondary outcomes were time to recovery of bowel function, biochemical nutritional (serum albumin, serum prealbumin, serum total protein) and inflammatory (C-reactive protein) parameters, length of hospital stay, and costs attributed to the TPN. The Pearson χ(2) test was used for dichotomous variables; the Wilcoxon rank sum test was used for continuous variables. RESULTS AND LIMITATIONS: Postoperative complications occurred in 51 patients (69%) in group A and in 41 patients (49%) in group B (p=0.013), a difference resulting from group A having more infectious complications than group B (32% vs 11%; p=0.001). Serum prealbumin and serum total protein were significantly lower in group B on postoperative day 7 but not on postoperative day 12. Time to gastrointestinal recovery and length of hospital stay did not differ between the two groups. The costs for TPN were €614 per patient. A potential limitation is the use of a glucose-based parenteral nutrition without lipids. CONCLUSIONS: Postoperative TPN is associated with a higher incidence of complications, mainly infections, and higher costs following ePLND, cystectomy, and UD versus oral nutrition alone.

Peri-interventional antibiotic prophylaxis only vs continuous low-dose antibiotic treatment in patients with JJ stents: a prospective randomised trial analysing the effect on urinary tract infections and stent-related symptoms.

OBJECTIVE: To evaluate the antibiotic treatment regime in patients with indwelling JJ stents, the benefits and disadvantages of a peri-interventional antibiotic prophylaxis were compared with those of a continuous low-dose antibiotic treatment in a prospective randomised trial. PATIENTS AND METHODS: In all, 95 patients were randomised to either receive peri-interventional antibiotic prophylaxis during stent insertion only (group A, 44 patients) or to additionally receive a continuous low-dose antibiotic treatment until stent removal (group B, 51). Evaluations for urinary tract infections (UTI), stent-related symptoms (SRSs) and drug side-effects were performed before stent insertion and consecutively after 1, 2 and 4 weeks and/or at stent withdrawal. All patients received a peri-interventional antibiotic prophylaxis with 1.2 g amoxicillin/clavulanic acid. Amoxicillin/clavulanic acid (625 mg) once daily was administered for continuous low-dose treatment (group B). Primary endpoints were the overall rates of UTIs and SRSs. Secondary endpoints were the rates and severity of drug side-effects. RESULTS: Neither the overall UTI rates (group A: 9% vs group B: 10%), nor the rates of febrile UTIs (group A: 7% vs group B: 6%) were different between the groups. Similarly, SRS rates did not differ (group A: 98% vs group B: 96%). Antibiotic side-effect symptoms were to be increased in patients treated with low-dose antibiotics. CONCLUSION: A continuous antibiotic low-dose treatment during the entire JJ stent-indwelling time does not reduce the quantity or severity of UTIs and has no effect on SRSs either compared with a peri-interventional antibiotic prophylaxis only.

Preexisting BCG-specific T cells improve intravesical immunotherapy for bladder cancer.

Therapeutic intravesical instillation of bacillus Calmette-Guérin (BCG) is effective at triggering inflammation and eliciting successful tumor immunity in patients with non-muscle invasive bladder cancer, with 50 to 70% clinical response. Therapeutic success relies on repeated instillations of live BCG administered as adjuvant therapy shortly after tumor resection; however, the precise mechanisms remain unclear. Using an experimental model, we demonstrate that after a single instillation, BCG could disseminate to bladder draining lymph nodes and prime interferon-γ-producing T cells. Nonetheless, repeated instillations with live BCG were necessary for a robust T cell infiltration into the bladder. Parenteral exposure to BCG before instillation overcame this requirement; after the first intravesical instillation, BCG triggered a more robust acute inflammatory process and accelerated T cell entry into the bladder, as compared to the standard protocol. Moreover, parenteral exposure to BCG before intravesical treatment of an orthotopic tumor markedly improved response to therapy. Indeed, patients with sustained preexisting immunity to BCG showed a significant improvement in recurrence-free survival. Together, these data suggest that monitoring patients' response to purified protein derivative, and, in their absence, boosting BCG responses by parenteral exposure before intravesical treatment initiation, may be a safe and effective means of improving intravesical BCG-induced clinical responses.

Gain of chromosome 8q is associated with metastases and poor survival of patients with clear cell renal cell carcinoma.

BACKGROUND: The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease-specific survival (DSS). METHODS: The tumor karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated with classical cytogenetic analysis. Chromosome 8q status was correlated with clinicopathological variables, and its impact on DSS was evaluated. RESULTS: Gain of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs 24.4%, P = .006), and greater tumor sizes (P = .030). Patients with gain of 8q had a 3.22-fold increased risk of death from CCRCC (P < .001). In multivariable analysis, gain of 8q was identified as an independent prognostic factor (hazard ratio, 2.37; P = .006). The concordance index of a multivariable base model increased significantly following inclusion of 8q gain (P = .0015). CONCLUSIONS: Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. Because the proto-oncogene c-MYC is among the list of candidate genes located on 8q, our data suggest that these tumors may have unique pathways activated, which are associated with an aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may assist in identifying patients who would benefit for specific c-MYC inhibitors or agents that target the MAPK/ERK (mitogen-activated protein kinase) pathway.

Occlusion of seminal vesicles increases sexual activity in a mouse model.

BACKGROUND: Little is known about the physiologic role of seminal vesicles beyond their fertility function. It has been suggested repeatedly that seminal vesicles have an impact on sexual activity. Although this has been investigated in various animal models, such a role has never been found. OBJECTIVE: To assess in a novel mouse model whether occlusion of seminal vesicles affects sexual activity. DESIGN, SETTING, AND PARTICIPANTS: Adult male CD1 mice (n=77) were assigned randomly to the experimental groups: (1) seminal vesicle occlusion (SVO) (n=24), (2) seminal vesicle resection (SVR) (n=23), and (3) sham operation (SO) (n=30). Adult females were brought into estrus by the Whitten effect. After recuperation, mouse pairs were observed during sessions of 3h each. Sexual activity was analyzed separately by three observers blinded to the experimental conditions. INTERVENTION: SVO, SVR, and SO. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was percentage of sessions with intromission; secondary end points were number of intromissions and latency until first intromission. A logistic regression model and the Kruskal-Wallis test were used. RESULTS AND LIMITATIONS: A total of 141 sessions for a total of 423h were analyzed. Intromission was scored in 20 of 42 sessions (48%) with SVO mice, a significantly higher rate than the 8 of 39 sessions (21%) with SVR mice (p=0.001) and 18 of 60 sessions (30%) with SO mice (p=0.004). Secondary end points were comparable in all three groups (p=0.303 and 0.450, respectively). CONCLUSIONS: Males with SVO were significantly more often sexually active than males undergoing SVR or SO. This suggests that occluded, and thus engorged, seminal vesicles increase sex drive in male mice. Since the potential clinical benefit might be highly relevant, further studies should confirm these promising results and investigate the potential application in men.

Vasectomy reversal with ultrasonography-guided spermatic cord block.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Vasectomy reversal is often performed in general or neuraxial anaesthesia. Even though the site of vasectomy reversal is easily amenable to regional/local anaesthesia, spermatic cord blocks are rarely applied because of their risk of vascular damage within the spermatic cord. Recently, we described the technique of ultrasonography (US)-guided spermatic cord block for scrotal surgery, which, thanks to the US guidance, at the same time avoids the risk of vascular damage of blindly performed injections and the risks of general and neuraxial anaesthesia. Vasectomy reversal can easily be done in regional anaesthesia with the newly described technique of US-guided spermatic cord block without the risks of vascular damage by a blindly performed injection and the risks of standard general and neuraxial anaesthesia. In addition, this technique grants long-lasting postoperative pain relief and patients recover more quickly. Microsurgical conditions are excellent and patient satisfaction is high. Thanks to these advantages, more patients undergoing vasectomy reversal might avoid general or neuraxial anaesthesia. OBJECTIVE: • To assess the success rate, microsurgical conditions, postoperative recovery, complications and patient satisfaction of ultrasonography (US)-guided spermatic cord block in patients undergoing microscopic vasectomy reversal and to compare them to a control group with general or neuraxial anaesthesia. PATIENTS AND METHODS: • The present study comprised a prospective series of 10 consecutive patients undergoing US-guided spermatic cord block for microscopic vasectomy reversal. • The cohort was compared with 10 patients in a historical control group with general or neuraxial anaesthesia. RESULTS: • Nineteen of 20 (95%) blocks were successful, defined as no pain >3 on the Visual Analogue Scale (VAS), no additional analgesics and/or no conversion to general anaesthesia. Median pain was 0 on the VAS (range 0-5). Additional analgesics were requested in one (5%) block, and there was no conversion to general anaesthesia. • Microsurgical conditions were excellent. • In the spermatic cord block vs general/neuraxial anaesthesia groups, median times (range) between surgery and first postoperative analgesics, alimentation, mobilization and hospital discharge were 12 (2-14) vs 3 (1-6), 1 (0.25-3) vs 4 (3-6), 2 (1-3) vs 6 (3-10), and 4 (3-11) vs 8.5 (6-22) h, respectively. • No complications were reported after the spermatic cord block. • Patient satisfaction was excellent. CONCLUSIONS: • US-guided spermatic cord block for microscopic vasectomy reversal is highly successful and provides long-lasting perioperative analgesia. • Times to alimentation, mobilization and hospital discharge are shorter under US-guided spermatic cord block than under general/neuraxial anaesthesia. • Additional anaesthetic pain management might, however, be required unexpectedly with US-guided spermatic cord block.