The HELENA study: Hexvix®-TURB vs. white-light TURB followed by intravesical adjuvant chemotherapy-a prospective randomized controlled open-label multicenter non-inferiority study.

PURPOSE: Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT. METHODS: Between 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113) RESULTS: Median follow-up was 1.81 years. Hexvix® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; pnon-inferiority = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], pnon-inferiority = 0.493). There was no significant difference in overall survival between both groups (p = 0.257). CONCLUSION: Non-inferiority of Hexvix® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix®-improved TURB only, confirming its important role in patient treatment.

Expression patterns of the immune checkpoint ligand CD276 in urothelial carcinoma.

BACKGROUND: CD276 is an immune checkpoint molecule. Elevated CD276 expression by urothelial carcinoma is associated with poor prognosis, but little is known about its expression across different tumor stages. We therefore investigated CD276 expression in bladder cancer (BC) cells and in tissue samples of BC stages from pT2 to pT4. METHODS: CD276 expression was explored in 4 urothelial cancer cell lines and 4 primary normal urothelial cell populations by quantitative RT-PCR, Western blot and flow cytometry. CD276 was investigated in bladder tumors from 98 patients by immunohistochemistry using a score (0-300) incorporating both, staining intensity and area of CD276 staining. Normal appearing urothelium in the bladder of the same patients served as controls. RESULTS: The urothelial carcinoma cell lines expressed significantly higher levels of CD276 on transcript (p < 0.006), total protein levels (p < 0.005), and on the cell surface (p < 0.02) when compared to normal urothelial cells. In pT2-T4 tumor tissue samples, CD276 was overexpressed (median score 185) when compared to corresponding healthy tissues from the same patients (median score 50; p < 0.001). No significant differences in CD276 expression were recorded in late, locally advanced ≥ pT3a tumors (median score 185) versus organ-confined < pT3a tumors (median score 190), but it was significantly lower in the normal urothelial tissue associated with ≥ pT3a tumors (median score 40) versus < pT3a tumors (median score 80; p < 0.05). CONCLUSION: CD276 expression is significantly elevated in urothelial carcinoma cells in all stages but varies between individuals considerably. Reduced CD276 expression in normal urothelial cells may imply that these cells would be protected from CD276-mediated immuno therapies.

Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

68Ga-PSMA-PET/CT-directed IGRT/SBRT for oligometastases of recurrent prostate cancer after initial surgery.

Background: We evaluated efficacy and toxicity of 68Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (SBRT/IGRT) for oligometastases of prostate cancer recurrences after previous surgery.Methods: Nineteen patients were analyzed within a prospective PET-registry study (064/2013BO1) and retrospectively analyzed (807/2017BO2) fulfilling the following inclusion criteria: biochemical recurrence after radical prostatectomy, ≤five 68Ga-PSMA-PET/CT positive lesions. Biochemical control was evaluated with EORTC (European Organization for Research and Treatment of Cancer)- and Phenix-definitions. Toxicity was scored according to CTCAE-criteria v. 4.03.Results: A total of 38 oligometastases (19 patients, 2 with re-treatment) were treated with SBRT/IGRT from October 2014 to July 2017. 68Ga-PSMA-PET/CT-positive lesions were detected on average 39 months (5-139) after prostatectomy (pT2b-3b pN0-1 cM0). Mean PSA (Prostate-specific antigen)-level at time of imaging reached 2.2 ng/mL (range 0.2-10.1). PET/CT-positive lesions were treated with different fractionation schedules reaching biological equivalent doses (BED) of 116.7-230.0 Gy. Concomitant androgen deprivation therapy (ADT) was given in seven patients. After a median follow-up of 17 months (4-42) all patients were alive. Estimated 1-year PSA- control (n = 19) reached 80.8% (Phenix) and 67.5% (EORTC). A PSA-decline (≥50%) was detected in 16/19 patients after radiotherapy. Higher graded G3+-acute toxicity did not occur. Temporary late G3-proctitis was detected in one patient.Conclusions: Reaching of nadir ≤0.1 or 0.2 ng/mL was associated by improved DMFS (distant metastases free survival) and could serve as a surrogate endpoint for RT of oligometastases after initial prostatectomy. Short term effects of 68Ga-PSMA-PET/CT-based ablative radiotherapy for oligometastases demonstrated an acceptable toxicity profile and favorable biochemical response.

Rare and changeable as a chameleon: paraneoplastic syndromes in renal cell carcinoma.

INTRODUCTION: Paraneoplastic syndromes (PNS) in renal cell carcinoma (RCC) are important to be recognized by the treating physician, because they may lead to diagnosis of underlying malignant disease. On the other hand, PNS may dominate the clinical picture and can hide the true disorder like a chameleon. When realized, a PNS can be used as a 'neoplastic tumour marker', especially in case of recurrence. Their occurrence can even be linked to prognosis of disease. METHODS: A PubMed search combining the MeSH terms renal cell carcinoma and paraneoplastic syndrome was executed in April 2015. All hits concerning these MeSH terms have been taken into account when writing this review. RESULTS: There is a big gap between reporting and incidence of paraneoplastic syndromes in renal cell carcinoma. Most of the articles in Medline are case reports and reviews of research done in the 1950s-1990s. One problem is that a clear definition of a paraneoplastic syndrome is still lacking. The most important PNS in RCC are hypercalcemia. It is important that PNS are not only arising in advanced stages of renal cell carcinoma; in contrast, a PNS can often be the first symptom of RCC. CONCLUSION: Paraneoplastic syndromes are often unrecognized but are important biomarkers in RCC. Further research into the underlying pathomechanisms of PNS may improve our understanding of the RCC tumour biology and is urgently needed.

First report of robot-assisted transperineal fusion versus off-target biopsy in patients undergoing repeat prostate biopsy.

PURPOSE: To clarify the value of targeted versus off-target biopsies in men with a suspicion of prostate cancer (PC) and a visible lesion in multi-parametric magnetic resonance imaging (mpMRI) using transperineal robot-assisted biopsy. METHODS: Fifty-five consecutive men with one non-palpable suspicious lesion in mpMRI after negative 12-core transrectal ultrasound-guided biopsy were enrolled in 2014-2015. Lesions were scored using the Prostate Imaging Reporting and Data System. A robot-assisted system was utilized to collect four robot-assisted targeted transperineal biopsy cores (RA-TB) within the lesion using mpMRI-TRUS elastic fusion. Untargeted transperineal 14-core biopsy was performed only outside the lesion (RA-UB). Histological grade was compared in biopsies and available prostatectomy specimens. RESULTS: Overall, 34 of 55 patients (62%) were diagnosed with PC based on biopsy. 85% of cancers were clinically significant PC (csPC) defined as GS ≥ 7. 85% of biopsy-proven cancers were detected with RA-TB alone. RA-UB identified only one additional patient with csPC and lead to upgrading in five biopsy cases (14.7%). Pathological evaluation of 14 prostatectomy specimens showed upgrading in 2 patients (14.3%), while all other patients were correctly classified by RA-TB without need of additional RA-UB. Mean procedure duration was 43 (±6) min, and only minor complications according to Clavien-Dindo were recorded during 30-day follow-up. CONCLUSIONS: This is the first report of transperineal robot-assisted elastic mpMRI-TRUS fusion biopsy. RA-TB of positive MR lesions enabled reliable detection of csPC, while RA-UB in MRI-negative regions is of minor importance.

Prostate cancer gene 3 (PCA3) is of additional predictive value in patients with PI-RADS grade III (intermediate) lesions in the MR-guided re-biopsy setting for prostate cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) improves diagnostic accuracy in re-biopsies of men with prostate cancer (PC) suspicion, but predictive value is limited despite the use of the new Prostate Imaging Reporting and Data System (PI-RADS). Prognostic value of the PC-specific biomarker prostate cancer gene 3 (PCA3) added to the PI-RADS score was evaluated. METHODS: The study was a retrospective analysis of the institutional database for men with MR-guided biopsy (MR-GB) for suspicious lesion in mpMRI and who had an additional pre-MR-GB PCA3 testing for ongoing PC suspicion. All men had ≥ 1 negative ultrasound GB. Lesions were retrospectively scored by PI-RADS in three MRI sequences (T2w, DCE, and DWI). PCA3 was analyzed with cutoffs of 25 and 35. The prognostic value of mpMRI and PCA3 and the additional value of both were explored. RESULTS: Tumor detection rate (49 men, mean PSA 10 ng/ml, lesion size 40 mm(2)) was 45 % (22/49 patients). In the subgroup of PI-RADS IV°, 17/17 patients had PC; in PI-RADS III° (intermediate) 5/15 had PC, and all 5 had a PCA3 > 35. PCA3 > 35 had no additional prognostic value in the whole cohort. Out of the 10/15 PC negative patients (PI-RADS III°), PCA3 was < 35 in 6. The inclusion of PCA3 value in PI-RADS III° patients improved predictive accuracy to 91.8 %. CONCLUSION: MpMRI and subsequent grading to PI-RADS significantly improves PC detection in the re-biopsy setting. The diagnostic uncertainty in the PI-RADS intermediate group can be ameliorated by the addition of PCA3 cutoff of 35 to avoid potential unnecessary biopsies.

Laparoscopic radical nephrectomy with inferior vena cava thrombectomy: highlight of key surgical steps.

OBJECTIVE: Vascular involvement in the form of renal vein (RV) or inferior vena cava (IVC) thrombus can be seen in 4-10% of patients presented with RCC. In patients without presence of metastasis, surgical treatment in the form of radical nephrectomy remains the treatment of choice with 5-year survival rates of 45-70%. Open surgery is still the first treatment option of choice at the moment for RCC patients with IVC thrombus. MATERIALS AND METHODS: In our study, we are reporting a case of patient with RCC and level I IVC thrombus treated with laparoscopy. Our patient is a 72 years old man with underlying co-morbidity of hypertension and chronic kidney disease (CKD) presented with right-sided RCC. The CT scan done showed a large right renal upper pole tumor measuring 8.4x5.2cm with level I IVC thrombus (Figure-1). There were no regional lymphadenopathy and the staging scans were negative. RESULTS: The operative time was 124 minutes and blood loss was minimal. The patient was progressed to diet on POD 1 with bowel movement on POD 2. There was no significant change in the pre and post-operative glomerular filtration rate (GFR). The surgical drain was removed on POD2. The patient was discharged well on POD 5. There were no perioperative complications. The pathology was pT3bN0M0 Fuhrman grade II clear cell RCC. CONCLUSIONS: As a conclusion, laparoscopic radical nephrectomy and IVC thrombectomy is a complex and technically demanding surgery. With advancement of surgical skills as well as technology, more cases of minimally invasive laparoscopic radical nephrectomy and IVC thrombectomy can performed to improve the perioperative outcomes of carefully selected patients in a high volume center.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.

Seminal vesicle invasion: accuracy and analysis of infiltration patterns with high-spatial resolution T2-weighted sequences on endorectal magnetic resonance imaging.

OBJECTIVE: To evaluate the accuracy of high-spatial resolution T2-weighted endorectal magnetic resonance imaging (eMRI) for detection and pattern depiction of seminal vesicle invasion (SVI) in patients with prostate cancer (PCa). METHODS: 376 patients were included who underwent eMRI for staging before radical open prostatectomy at 1.5 T with an endorectal coil. Statistical accuracy for detection of SVI was calculated. MR images of patients with SVI were further evaluated by two radiologists according to the classification by Wheeler and Ohori. RESULTS: In the cohort, 35 patients had SVI after histopathological evaluation of the prostatectomy specimen (stage pT3b). Sensitivity and specificity for detection of SVI were 48.6 and 97.7%, respectively. Negative and positive predictive values and overall accuracy were 94.9, 68.0, and 93.1%, respectively. Infiltration pattern analysis showed that type I invasion was most common with 48.6 followed by type IIa (31.4%) and IIb (20%). Type III was not present. There was no statistical significant difference between the three groups regarding Gleason score, age, and prostate-specific antigen level. CONCLUSIONS: eMRI with high-spatial resolution T2-weighted imaging is accurate for assessment of SVI. Depiction of different infiltration types of SVI is feasible. By adding information about the extent of SVI, diagnostic reporting and risk stratification could be improved.

Hsa-mir-124-3 CpG island methylation is associated with advanced tumours and disease recurrence of patients with clear cell renal cell carcinoma.

BACKGROUND: Whether methylation of the microRNA (mir)-124-3 CpG island is of relevance for the clinical course of a solid cancer and whether it shows association with clinicopathology or survival of patients with renal cell cancer (RCC) is not known as yet. METHODS: In a cross-sectional study, relative methylation of mir-124-3 was measured in 111 RCC samples and 77 paired normal appearing tissues using quantitative methyl-specific PCR. Results were statistically compared with tumour histology, clinicopathological parameters and disease recurrence. RESULTS: We found tumour-specific hypermethylation of mir-124-3 in samples of RCCs with clear cell histology (ccRCC) compared with paired normal appearing tissues (P<0.0001). Methylation was significantly increased in tumours with state of advanced disease (P<0.0001). Higher relative methylation was associated with worse recurrence-free survival in both univariate (hazard ratio=9.37; P=0.0005) as well as bivariate Cox regression analyses considering age, sex, diameter of tumours and state of advanced disease, metastasis and lymph node metastases as covariates (hazard ratios=5.9-18.2; P-values of 0.0003-0.008). CONCLUSION: We identified mir-124-3 CpG islands (CGI) methylation as a relevant epigenetic mark for ccRCC thus underlining the need for functional studies of potentially affected signalling pathways in kidney tumour models. Methylation of mir-124-3 is suggested as an independent prognosticator for ccRCC.

A randomized, double-blind, multicenter, phase 2 study of a human monoclonal antibody to human αν integrins (intetumumab) in combination with docetaxel and prednisone for the first-line treatment of patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Intetumumab is a fully human mAb with antiangiogenic, antitumor properties which has shown potential therapeutic effect in castration-resistant prostate cancer (CRPC) patients. PATIENTS AND METHODS: In a phase 2, randomized, double-blind, multicenter study, men with metastatic CRPC without prior systemic nonhormonal therapy were randomly assigned to 75-mg/m(2) docetaxel (Taxotere) and 5-mg prednisone plus placebo (N = 65) or 10-mg/kg intetumumab (N = 66) q3w. Placebo patients with progressive disease (PD) could cross over to 10-mg/kg intetumumab alone or with docetaxel. The primary end-point was progression-free survival (PFS). The secondary end-points included tumor response (complete response + partial response, CR + PR), prostate-specific antigen (PSA) response, and overall survival (OS). RESULTS: All efficacy end-points favored placebo over intetumumab, including PFS (median 11.0 versus 7.6 months, P = 0.014), tumor response (20% versus 16%, P = 0.795), PSA response (68% versus 47%, P = 0.018), OS (median 20.6 versus 17.2 months, P = 0.163). Common all-grade adverse events (AEs) with placebo and intetumumab were alopecia (43% versus 26%); diarrhea, leukopenia (both 34% versus 27%); neutropenia (35% versus 23%). Grade ≥ 3 leukopenia (28% versus 17%) and neutropenia (26% versus 18%) occurred more often with placebo than with intetumumab. Intetumumab serum concentrations increased with repeated dosing and did not reach steady-state. Greater decreases in N-telopeptide of type I collagen (NTx), C-telopeptide (CTx) and CTCs occurred with intetumumab than with placebo. CONCLUSION: The addition of intetumumab to docetaxel resulted in shorter PFS without additional toxicity among CRPC patients.

Influence of age on false positive rates of urine-based tumor markers.

INTRODUCTION: Several influencing factors on false positive rates (FPRs) of urine-based tumor markers in the detection of urothelial cancer (UC) have been identified. We evaluated age as a possible influencing factor. METHODS: Urinary cytology (Cyt), UroVysion (FISH), ImmunoCyt (uCyt+) and NMP22 were determined in 1,554 patients suspicious for UC of the bladder before cystoscopy and in case of cancer detection before TURB. Additionally, upper urinary tract imaging was performed. Maker sensitivity, specificity and FPRs were evaluated in the entire cohort and in subgroups divided by age into <50, ≥ 50-70 and ≥ 70 years. Contingency tables and the Cochrane Armitage tests were used for statistical comparisons. RESULTS: UC was found in 377 and no UC in 1,177 (75 %) patients. A total of 336 patients were diagnosed with UC of the bladder and 41 with UC of the upper urinary tract. Overall sensitivity and specificity for Cyt were 82 and 82 %: for FISH, 73 and 79 % and for uCyt+, 79 and 75 %, respectively. For NMP22, regardless of the exclusion criteria they were 72 and 34 % and after exclusion of urinary tract infection (UTI) or prior to manipulation 46 and 86 %, respectively. Significantly higher FPRs were found with increasing age for Cyt (p = 0.001), a trend to higher FPRs for uCyt+ (p = 0.11) and almost no difference for FISH (p = 0.63). For NMP22, differences became significant after exclusion of patients with UTI or prior manipulation (p = 0.02). CONCLUSIONS: The results of the present study give evidence that false positive rates of Cyt and NMP22 increase with age indicating that age should be respected for their correct interpretation.

Prostatic peripheral nerve distribution may impact the functional outcome of nerve-sparing prostatectomy.

PURPOSE: To study microscopic patterns of remaining peripheral nerves (PN) after nerve-sparing (NS) radical prostatectomy (RP) and possible consequences for nerve preparation. METHODS: Specimens from 27 patients (7 = non-NSRP, 20 = unilateral NS) were examined. Sections were investigated for PN content by immunoassaying. 120 whole-mounted slides were divided into four sectors, and extracapsular nerves were counted; the mean posterior/anterior ratio was calculated. Calculated ratios were correlated with the respective volumes of prostatic tissue (PV). After dividing the patient cohort into two subgroups, shared by the median value of the posterior/anterior nerve ratios, the absolute PN contents on the anterior surface of the NS sides were compared. RESULTS: Anatomical posterior nerve percentage in non-NS aspects ranged from 0.0-100.0 to 26.7-94.6% with a mean of 66.60 ± 25.4% and 68.83 ± 16.0% (>/<200 µm, respectively). Individual ratios from two nerve categories showed significant correlation (P < 0.008). Mean posterior ratios were 83.04/79.68 and 39.21/56.00, respectively. After unilateral NS, 3.17-fold (2.25 vs. 0.71 nerves, P = 0.05) and 2.26-fold (21.54 vs. 9.53, P = 0.08) nerve fibers were resected in the anterior area in comparison with type A. After unilateral NS, the variation impact on the anterior nerve content of the NS side could be demonstrated. CONCLUSIONS: The amounts of nerves localized on the anterior prostate after RP vary interindividually. Saving only a minor part of the anterior areas may have an impact on the quantity of excised nerves adjacent to the specimen and impair postoperative functional results. Especially for those patients without a major posterolateral bundle distribution, surgeons should adapt the procedure and start nerve preservation more anteriorly to maximize the probability of satisfactory postoperative functional results.

Influence of body mass index, surgical approach and lymphadenectomy on the development of symptomatic lymphoceles after radical prostatectomy.

PURPOSE: Identification of factors influencing lymphocele formation requiring intervention after radical prostatectomy. METHODS: 302 patients undergoing radical retropubic prostatectomy (RRP, n = 174) or transperitoneal robot-assisted laparoscopic prostatectomy (RALP, n = 128) by the same surgeon were retrospectively reviewed. Incidence of symptomatic lymphoceles (SLC) was compared with clinical and pathological data (contingency analyses, Wilcoxon-Kruskal-Wallis test). RESULTS: Sixteen patients (5.3%) developed SLC. SLC occurred significantly more frequently after RRP compared to RALP (8.0 vs. 0.8%, p = 0.0008). Patients with SLC had more lymph nodes (LN) removed median (17 vs. 13, p = 0.009) and a significantly lower BMI (median 24.4 vs. 26.4, p = 0.0008). Presence of LN metastases (n = 18 patients, 6.0%) showed no statistical impact on SLC. In a multivariate analysis surgical method, the number of resected LN and the BMI remained independent predictors of SLC formation. CONCLUSIONS: The lower incidence of SLC after RALP compared to RRP probably results from peritoneal drainage of lymphatic fluid. The correlation of removed LN and SLC might be explained by increased injury of lymphatic vessels during more extended LN dissection. Why patients with lower BMI are more prone to develop SLC still remains unclear. However, early postoperative mobilization in nonobese patients might be a contributing factor.

Cost effective laparoendoscopic single-site surgery with a reusable platform.

BACKGROUND AND OBJECTIVES: Many disposable platforms have been applied in laparoendoscopic single-site surgery (LESS). Besides technical issues, cost is one of the limiting factors for its widespread acceptance. The current study describes the first completely reusable LESS-platform. METHODS: We performed LESS-procedures in 52 patients including nephrectomy (18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15), and lymphocele ablation (6). All procedures were conducted using a novel reusable single-port device (X-Cone, Karl-Storz) with a simplified set of instruments. We obtained perioperative and demographic data, including a visual analogue pain scale (VAS), and a complication reporting system based on Clavien grading. RESULTS: Mean age was 50.04 y. Conversion to standard laparoscopy was necessary in 3 cases and addition of a needlescopic instrument in 6 cases. There was no open conversion. Intra- and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operative time was 110, 90, and 89 min, and hospital stay was 4.9, 3.1, and 3.6 d for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. Mean VAS was 2.13, 1.07, and 1.5 while blood loss was 81.3 mL, 25.67 mL, and 17.5 mL, respectively. Mean lymph node yield was 15 (range, 8 to 21). CONCLUSIONS: A completely reusable LESS-platform is applicable to various uses in urology, yielding favorable functional and cosmetic results. Reusable materials are useful to reduce the cost of LESS, further increasing its acceptance. LESS with a completely reusable platform is more cost effective than standard laparoscopy.

A high-fidelity prototype of a sterile information system for the perioperative area: OR-Pad.

PURPOSE: Supporting the surgeon during surgery is one of the main goals of intelligent ORs. The OR-Pad project aims to optimize the information flow within the perioperative area. A shared information space should enable appropriate preparation and provision of relevant information at any time before, during, and after surgery. METHODS: Based on previous work on an interaction concept and system architecture for the sterile OR-Pad system, we designed a user interface for mobile and intraoperative (stationary) use, focusing on the most important functionalities like clear information provision to reduce information overload. The concepts were transferred into a high-fidelity prototype for demonstration purposes. The prototype was evaluated from different perspectives, including a usability study. RESULTS: The prototype's central element is a timeline displaying all available case information chronologically, like radiological images, labor findings, or notes. This information space can be adapted for individual purposes (e.g., highlighting a tumor, filtering for own material). With the mobile and intraoperative mode of the system, relevant information can be added, preselected, viewed, and extended during the perioperative process. Overall, the evaluation showed good results and confirmed the vision of the information system. CONCLUSION: The high-fidelity prototype of the information system OR-Pad focuses on supporting the surgeon via a timeline making all available case information accessible before, during, and after surgery. The information space can be personalized to enable targeted support. Further development is reasonable to optimize the approach and address missing or insufficient aspects, like the holding arm and sterility concept or new desired features.

Introducing a large animal model to create urethral stricture similar to human stricture disease: a comparative experimental microscopic study.

PURPOSE: In this tissue engineering study we investigated urethral stricture formation to evaluate different treatment modalities in the large animal model and validate the most current, comparable effect of human stricture development for successful human clinical application. MATERIALS AND METHODS: In 12 male minipigs stricture formation was evaluated by urethrography 1, 8 and 12 weeks after stricture induction by ligation, urethrotomy or thermocoagulation. Normal human urethral and scar tissue of 6 patients was harvested and compared to animal specimens. The effect of urethral damage was investigated for microvessel density and collagen I:III ratio. RESULTS: A week after urethrotomy urothelium covered the spongiosum tissue, showing minimal infiltration of lymphocytes and macrophages, and sporadic eosinophil granulocytes. However, increased connective tissue was observed with time as well as urethral luminal narrowing, vascular network loss (decreased microvessel density) and significantly increased collagen with a favorably revised collagen type I:III ratio. The 3 methods of stricture induction resulted in different stricture severity in the animal model (thermocoagulation >ligation >urethrotomy). Porcine urethral samples after thermocoagulation showed a significantly increased collagen I:III ratio (p <0.001), almost equal to that of human urethral stricture specimens. CONCLUSIONS: We successfully developed a large animal model in which to study urethral stricture formation by defined iatrogenic intervention. The established animal model advances investigation to evaluate new therapy modalities in a preclinical setting to treat urethral stricture and predict clinical outcome.

MRI-guided prostate biopsy detects clinically significant cancer: analysis of a cohort of 100 patients after previous negative TRUS biopsy.

PURPOSE: To investigate the positive biopsy rate of MRI-guided biopsy (MR-GB) in a routine clinical setting, identify factors predictive for positive biopsy findings and to report about the clinical significance of the diagnosed tumors. METHODS: Patients with at least one negative trans-rectal-ultrasound-guided biopsy (TRUS-GB), persistently elevated or rising serum prostate specific antigen (PSA) and at least one lesion suspicious for PCa on diagnostic 1.5 Tesla endorectal coil MRI (eMR) were included. Biopsies were carried out using a 1.5 Tesla MRI and an 18 G biopsy gun. Clinical information and biopsy results were collected; logistic regression analysis was carried out. Definite pathology reports of patients with diagnosis of PCa and subsequent radical prostatectomy (RP) were analyzed for criteria of clinical significance. RESULTS: One hundred patients were included, mean number of previous biopsies was 2 (range 1-9), mean PSA at time of biopsy was 11.7 ng/ml (1.0-65.0), and mean prostate volume was 46.7 ccm (range 13-183). In 52/100 (52.0%) patients, PCa was detected. Out of 52 patients, 27 patients with a positive biopsy underwent RP, 20 patients radiation therapy, and 5 patients active surveillance. In total, 80.8% of the patients revealed a clinically significant PCa. In univariate regression analysis, only serum PSA levels were predictive for a positive biopsy result. Number of preceding negative biopsies was not associated with the likelihood of a positive biopsy result. CONCLUSIONS: MR-GB shows a high detection rate of clinically significant PCa in patients with previous negative TRUS-GB and persisting suspicion for PCa.