Identification of patients at risk for biochemical recurrence after radical prostatectomy with intra-operative frozen section.

OBJECTIVE: To identify patients at risk for biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) with intra-operative whole-mount frozen section (FS) of the prostate. MATERIAL AND METHODS: We examined differences in BCR between patients with initial negative surgical margins at FS, patients with final negative surgical margins with initial positive margins at FS without residual PCa after secondary tumour resection, and patients with final negative surgical margins with initially positive margins at FS with residual PCa in the secondary tumour resection specimen. Institutional data of 883 consecutive patients undergoing RP were collected. Intra-operative whole-mount FS was routinely used to check for margin status and, if necessary, to resect more periprostatic tissue in order to achieve negative margins. Patients with lymph node-positive disease or final positive surgical margins were excluded from the analysis. Kaplan-Meier curves and multivariable Cox proportional hazards regression analyses adjusting for clinical covariates were employed to examine differences in biochemical recurrence-free survival (BRFS) according to the resection status mentioned above. RESULTS: The median follow-up was 22.4 months. The 1- and 2-year BRFS rates in patients with (81.0% and 72.9%, respectively; P = 0.001) and without residual PCa (90.3% and 82.3%, respectively; P = 0.033) after secondary tumour resection were significantly lower compared to patients with initial R0 status (93.4% and 90.9%, respectively). On multivariable Cox regression only residual PCa in the secondary tumour resection was associated with a higher risk of BCR compared to initial R0 status (hazard ratio 1.99, 95% confidence interval 1.01-3.92; P = 0.046). CONCLUSION: Despite being classified as having a negative surgical margin, patients with residual PCa in the secondary tumour resection specimen face a high risk of BCR. These findings warrant closer post-RP surveillance of this particular subgroup. Further research of this high-risk subset of patients should focus on examining whether these patients benefit from early salvage therapy and how resection status impacts oncological outcomes in the changing landscape of PCa treatment.

PSA-Targeted Alpha-, Beta-, and Positron-Emitting Immunotheranostics in Murine Prostate Cancer Models and Nonhuman Primates.

PURPOSE: Most patients with prostate cancer treated with androgen receptor (AR) signaling inhibitors develop therapeutic resistance due to restoration of AR functionality. Thus, there is a critical need for novel treatment approaches. Here we investigate the theranostic potential of hu5A10, a humanized mAb specifically targeting free PSA (KLK3). EXPERIMENTAL DESIGN: LNCaP-AR (LNCaP with overexpression of wildtype AR) xenografts (NSG mice) and KLK3_Hi-Myc transgenic mice were imaged with 89Zr- or treated with 90Y- or 225Ac-labeled hu5A10; biodistribution and subcellular localization were analyzed by gamma counting, PET, autoradiography, and microscopy. Therapeutic efficacy of [225Ac]hu5A10 and [90Y]hu5A10 in LNCaP-AR tumors was assessed by tumor volume measurements, time to nadir (TTN), time to progression (TTP), and survival. Pharmacokinetics of [89Zr]hu5A10 in nonhuman primates (NHP) were determined using PET. RESULTS: Biodistribution of radiolabeled hu5A10 constructs was comparable in different mouse models. Specific tumor uptake increased over time and correlated with PSA expression. Treatment with [90Y]/[225Ac]hu5A10 effectively reduced tumor burden and prolonged survival (P ≤ 0.0054). Effects of [90Y]hu5A10 were more immediate than [225Ac]hu5A10 (TTN, P < 0.0001) but less sustained (TTP, P < 0.0001). Complete responses were observed in 7 of 18 [225Ac]hu5A10 and 1 of 9 mice [90Y]hu5A10. Pharmacokinetics of [89Zr]hu5A10 were consistent between NHPs and comparable with those in mice. [89Zr]hu5A10-PET visualized the NHP-prostate over the 2-week observation period. CONCLUSIONS: We present a complete preclinical evaluation of radiolabeled hu5A10 in mouse prostate cancer models and NHPs, and establish hu5A10 as a new theranostic agent that allows highly specific and effective downstream targeting of AR in PSA-expressing tissue. Our data support the clinical translation of radiolabeled hu5A10 for treating prostate cancer.

Transient stent placement versus tubeless procedure after ureteroscopy retrograde surgery stone extraction (Fast Track Stent study 2): A randomized prospective evaluation.

OBJECTIVES: To determine whether in pre-stented patients undergoing ureteroscopic stone removal (ureteroscopy retrograde surgery) a tubeless procedure provides a better outcome compared with short-term (6 h) ureteral stenting using an external ureteral catheter. METHODS: In this single academic center study (Fast Track Stent study 2), carried out between May 2016 and April 2018, 121 patients with renal or ureteral calculi were initially treated with double-J insertion. Before secondary ureteroscopy retrograde surgery, patients were prospectively randomized into two groups: tubeless versus ureteral catheter insertion for 6 h after ureteroscopy retrograde surgery. Exclusion criteria were acute urinary tract infection, solitary kidney or stone diameter >25 mm. Study end-points were stent-related symptoms assessed by a validated questionnaire (ureteral stent symptom questionnaire), administered both before and 4 weeks after surgery. Numerical ureteral stent symptom questionnaire scores were compared using the Mann-Whitney-U-test. The level of significance was defined as P < 0.05. RESULTS: Ureteroscopy retrograde surgery procedures carried out by 13 surgeons resulted in >90% stone removal in all patients (n = 121), with a mean operation time of 19.9 versus 18.0 min for ureteral catheter versus tubeless, respectively (P = 0.37). Patient groups did not differ significantly in their ureteral stent symptom questionnaire scores (urinary index P = 0.24; pain index P = 0.35). Patients showed a significant preference for tubeless procedure over ureteral catheter reinsertion (Question GQ P < 0.0001). The reintervention rate was 13.3% for the tubeless procedure (n = 8) and 1.6% for the ureteral catheter group (n = 1), respectively (P = 0.034). CONCLUSIONS: Short-term ureteral catheter and no stent insertion after ureteroscopy retrograde surgery stone extraction in pre-stented patients result in comparable quality of life. However, the reintervention rate is higher for tubeless procedures.

Salvage lymph node dissection in hormone-naïve men: How effective is surgery?

OBJECTIVE: Salvage lymph node dissection (SLND) is still a questionable treatment approach for patients with nodal recurrence of prostate cancer after radical prostatectomy. We assessed the oncological benefit after SLND in hormone-naïve patients as well as the diagnostic accuracy of preoperative prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) scanning. MATERIAL AND METHODS: The study relied on retrospective collected data of 43 hormone-naïve men who received transperitoneal SLND between February 2011 and March 2017 at our institution. The oncological outcome for each patient was observed by serum prostate-specific antigen testing. Postoperative complications within 30 and 90 days were assessed according to the Clavien-Dindo classification. The accuracy of PSMA PET/CT was characterized by calculated sensitivity, specificity, positive, and negative predictive values. RESULTS: Overall 8 patients (18.6%) had a complete biochemical response 40 days after SLND. The median time from SLND to biochemical recurrence was 2 months. Adjuvant treatment encompassing radiotherapy, androgen deprivation therapy, or a combination of both, was administrated in 62.8%. According to the Clavien-Dindo classification, no high-grade complications were observed. Sensitivity and specificity for PSMA PET/CT were respectively 32% (95% confidence interval [CI]: 17.21-51.59) and 91.74% (95% CI: 85.45-95.45). Calculated positive predictive values (PPV) and negative predictive values (NPV) of PSMA PET/CT were 44.44% (95% CI: 25.98-64.58) and 86.72% (95% CI: 83.23-89.57). CONCLUSIONS: For most hormone-naïve men with a nodal recurrence of prostate cancer transperitoneal SLND is neither an appropriate treatment to cure nor an option to delay the need for salvage hormone manipulation. PSMA PET/CT scans in hormone-naïve patients are currently too imprecise to diagnose metastatic sites.

Interdisciplinary Comparison of PADUA and R.E.N.A.L. Scoring Systems for Prediction of Conversion to Nephrectomy in Patients with Renal Mass Scheduled for Nephron Sparing Surgery.

PURPOSE: We examined interdisciplinary variability using 2 established preoperative nephrometry scores to predict conversion to nephrectomy in patients with a renal mass who were scheduled for partial nephrectomy. MATERIALS AND METHODS: A total of 229 consecutive candidates for partial nephrectomy were included in this study at a single institution between January 2013 and May 2017. Patient, tumor and treatment characteristics were assessed. The PADUA (preoperative aspects and dimensions used for an anatomical) score and the R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) score were independently calculated by board certified radiologists and urological residents using computerized tomography or magnetic resonance imaging. Statistical analyses were done with the κ statistic, ROC curves, and univariable and multivariable binary logistic regression analyses. RESULTS: Partial nephrectomy was performed in 198 of the 229 cases (86.5%) while 31 (13.5%) were converted to nephrectomy. The prevalent tumor stage was pT1a, noted in 94 of the 229 cases (41.1%), and the predominant histological entity was clear cell carcinoma, found in 128 (55.9%). Radiologist and urologist interdisciplinary comparison of the PADUA and R.E.N.A.L. scores revealed a κ of 0.40 and 0.56, respectively. ROC curve analyses demonstrated a higher AUC predicting conversion to nephrectomy using the PADUA score by the urologist and the radiologist (0.79 and 0.782) compared to that of the R.E.N.A.L. score (0.731 and 0.766, respectively). Using a cutoff of 10 or greater the PADUA score determined by the urologist had 81% sensitivity and 71% specificity, and it was independently associated with conversion to nephrectomy (OR 10.98, p<0.001). CONCLUSIONS: Our results indicate higher prediction of conversion to nephrectomy when using the PADUA score compared to the R.E.N.A.L. score. Calculation of the PADUA and the R.E.N.A.L. score by physicians without specialized radiological training is feasible and might achieve comparable results to predict conversion to nephrectomy compared to the gold standard provided by board certified radiologists. This information is helpful if nephrometry scores are not regularly included in the radiology report.

Parastomal Hernia Repair With 3-D Mesh Implants After Radical Cystectomy and Ileal Conduit Urinary Diversion - A Single-center Experience Using a Purpose Made Alloplastic Mesh Implant.

OBJECTIVE: To report and evaluate our open surgical technique for the treatment of parastomal hernias (PSH) after ileal conduit urinary diversion and results using a specifically designed, three-dimensional intraperitoneal onlay mesh aiming to minimize PSH recurrence and perioperative complications. METHODS: We retrospectively evaluated all patients who developed a PSH after ileal conduit urinary diversion and were treated with the 3-dimensional alloplastic IPST mesh at the Marien Hospital Herne, Ruhr-University Bochum, Germany between 01/2009 and 12/2015. As a surgical approach, we used a small, open incision in order to reduce the hernia sac and place the mesh. Subsequently, we performed a voluntary follow-up of the surviving patients to evaluate long-term recurrence and complication rates. In addition, we conducted a reassessment of the cross-sectional imaging available. RESULTS: Between January 2009 and December 2015, 40 patients underwent hernia repair due to a clinically significant hernia. Out of those patients, 1 suffered from a postoperative wound infection. In total 27 patients participated in a voluntary follow-up with a median follow-up period of 29 months (IQR 16, 63 months). Follow-up examination revealed 2 cases of recurrent PSH (7, .4%), 2 patients who developed stoma stenosis (7.4%) and 5 patients who suffered from minor complications (18.5%). CONCLUSION: Our localized open surgical approach using a 3-dimensional mesh implant presents an effective method of treating a PSH with a low complication and recurrence rate.

Transurethral resection of bladder tumours: established and new methods of tumour visualisation.

Transurethral resection (TUR) of bladder tumours does not only serve diagnostic purposes by securing histological proof of the disease but might also resemble the final therapy. During recent years, technical innovations improved the intraoperative detection and visibility of tumourous lesions during TUR. The most important techniques, which have individually found their way into international guidelines, are photodynamic imaging (PDI) and narrowband imaging (NBI). Furthermore, there are more or less experimental approaches such as optical coherence tomography (OCT), confocal laser endomicroscopy (CLE), red/green/blue analysis (RGB) of WLC. Moreover, the combination of two or more techniques in a multiparametric setting is another development in improving intraoperative imaging. The aim of this review is to describe today's knowledge of the more established methods and to depict the most recent developments in intraoperative imaging.

Short-term external ureter stenting shows significant benefit in comparison to routine double-J stent placement after ureterorenoscopic stone extraction: A prospective randomized trial - the Fast track stent study (FaST).

OBJECTIVES: To determine whether short-term stenting using an external ureter catheter following ureterorenoscopic stone extraction provides a better outcome in comparison to double-J stent ureteral stenting. METHODS: Between August 2014 and August 2015, 141 patients initially managed with a double-J stent insertion were prospectively randomized to ureter catheter for 6 h vs double-J stent insertion for 5 days after stone extraction via ureteroscopy retrograde surgery (including flexible ureteroscopy retrograde surgery) in a single academic center. Endoscopic procedures were performed by nine surgeons. Exclusion criteria were acute urinary tract infection, a solitary kidney, or a stone mass more than 25 mm. Study endpoints were ureter-stent related symptoms and pain assessed by a validated questionnaire (ureteral stent symptom questionnaire) and visual analogue scale before and 4 weeks after surgery. RESULTS: Overall stone-free rate was more than 90%. Mean operative time was 24 min (range 5-63). Groups did not differ in terms of age, body mass index, and stone size. Patients who received short-term ureter catheter showed a significantly higher quality of life. In the ureter catheter group, the urinary index score (16.8 vs 27.8; P < 0.0001), the pain score (9.7 ± 1.3 vs 20.2 ± 1.5; P < 0.0001), and general health index (15.3 ± 0.7 vs 8.5 ± 0.6; P < 0.0001) were significantly lower. Consultation of a physician and antibiotic treatment were rarely needed (1.3 ± 0.1 vs 1.6 ± 0.1; P = 0.017). CONCLUSION: A short-term ureter catheter insertion for 6 h following ureteroscopy retrograde surgery stone removal is a safe procedure and superior to double-J stent insertion with regard to urinary symptoms, pain, quality of life, and stent related symptoms. Patients treated with a short-term ureter catheter recover more quickly, return to work earlier, and need less doctor visits. Most patients would recommend a ureter catheter, and would prefer this strategy in case of future stone treatments.

De novo neurogenic bladder dysfunction after salvage lymph node dissection in patients with nodal recurrence of prostate cancer.

AIMS: To examine the impact of Salvage lymph node dissection (SLND) on bladder function and oncological outcome in hormone naïve patients with nodal recurrence of prostate cancer (PCa) after radical prostatectomy (RP). METHODS: In a prospective study between October 2015 and November 2016, 20 patients underwent transperitoneal SLND for nodal recurrence of PCa after RP at our institution. Standardized urodynamics were performed pre- and postoperatively after 6 weeks, 3, and 6 to 12 months. Prostate-specific antigen (PSA) levels were used to monitor the oncological outcome. Perioperative outcomes encompassed, among others, type of complications after surgery classified to Clavien-Dindo. RESULTS: The proportion of patients with neurogenic bladder dysfunction was postoperative at 6 weeks, 3, and 6 to 12 months 78.5%, 70%, and 45.5%, respectively. Compared to preoperative urodynamics, follow-ups revealed a statistical significant cleavage of bladder wall compliance until six to twelve months after SLND (34.5 vs 22 mL/cmH2 O, P = 0.044). Referring to the oncological outcome all patients experienced a PSA progression, 10 patients (50%) within 11 weeks after surgery. Overall, four patients (20%) suffered from a postoperative complication after SLND, which comprises Clavien grade I-IIIa. CONCLUSIONS: Transperitoneal SLND, as a treatment option for patients with nodal recurrence of PCa after RP reveals additional potential pitfalls than previously reported. Urodynamics reveal a significant impact of SLND on postoperative functional bladder dysfunctions. Therefore, informed consent prior to SLND should include the risk of persistent low compliance bladder.

Detection of Acute Tubular Necrosis Using Blood Oxygenation Level-Dependent (BOLD) MRI.

BACKGROUND/AIMS: To date, there is no imaging technique to assess tubular function in vivo. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) measures tissue oxygenation based on the transverse relaxation rate (R2*). The present study investigates whether BOLD MRI can assess tubular function using a tubule-specific pharmacological maneuver. METHODS: Cross sectional study with 28 participants including 9 subjects with ATN-induced acute kidney injury (AKI), 9 healthy controls, and 10 subjects with nephron sparing tumor resection (NSS) with clamping of the renal artery serving as a model of ischemia/reperfusion (I/R)-induced subclinical ATN (median clamping time 15 min, no significant decrease of eGFR, p=0.14). BOLD MRI was performed before and 5, 7, and 10 min after intravenous administration of 40 mg furosemide. RESULTS: Urinary neutrophil gelatinase-associated lipocalin was significantly higher in ATN-induced AKI and NSS subjects than in healthy controls (p=0.03 and p=0.01, respectively). Before administration of furosemide, absolute medullary R2*, cortical R2*, and medullary/cortical R2* ratio did not significantly differ between ATN-induced AKI vs. healthy controls and between NSS-I/R vs. contralateral healthy kidneys (p>0.05 each). Furosemide led to a significant decrease in the medullary and cortical R2* of healthy subjects and NSS contralateral kidneys (p<0.05 each), whereas there was no significant change of R2* in ATN-induced AKI and the NSS-I/R kidneys (p>0.05 each). CONCLUSION: BOLD-MRI is able to detect even mild tubular injury but necessitates a tubule-specific pharmacological maneuver, e.g. blocking the Na+-K+-2Cl- transporter by furosemide.

Detecting Prostate Cancer.

BACKGROUND: When prostate cancer is suspected, the prostate gland is biopsied with the aid of transrectal ultrasound (TRUS). The sensitivity of prostatic biopsy is about 50%. The fusion of magnetic resonance imaging (MRI) data with TRUS enables the targeted biopsy of suspicious areas. We studied whether this improves the detection of prostate cancer. METHODS: 168 men with suspected prostate cancer underwent prostate MRI after a previous negative biopsy. Suspicious lesions were assessed with the classification of the Prostate Imaging Reporting and Data System and biopsied in targeted fashion with the aid of fused MRI and TRUS. At the same sitting, a systematic biopsy with at least 12 biopsy cores was performed. RESULTS: Prostate cancer was detected in 71 patients (42.3%; 95% CI, 35.05-49.82). The detection rate of fusion-assisted targeted biopsy was 19% (95% CI, 13.83-25.65), compared to 37.5% (95% CI, 30.54-45.02) with systematic biopsy. Clinically significant cancer was more commonly revealed by targeted biopsy (84.4%; 95% CI, 68.25-93.14) than by systematic biopsy (65.1%; 95% CI, 52.75-75.67). In 7 patients with normal MRI findings, cancer was detected by systematic biopsy alone. Compared to systematic biopsy, targeted biopsy had a higher overall detection rate (16.5% vs. 6.3%), a higher rate of infiltration per core (30% vs. 10%), and a higher rate of detection of poorly differentiated carcinoma (18.5% vs. 3%). Patients with negative biopsies did not undergo any further observation. CONCLUSION: MRI/TRUS fusion-assisted targeted biopsy improves the detection rate of prostate cancer after a previous negative biopsy. Targeted biopsy is more likely to reveal clinically significant cancer than systematic biopsy; nevertheless, systematic biopsy should still be performed, even if the MRI findings are negative.

Preoperative predictive model of recovery of urinary continence after radical prostatectomy.

OBJECTIVE: To build a predictive model of urinary continence recovery after radical prostatectomy (RP) that incorporates magnetic resonance imaging (MRI) parameters and clinical data. PATIENTS AND METHODS: We conducted a retrospective review of data from 2,849 patients who underwent pelvic staging MRI before RP from November 2001 to June 2010. We used logistic regression to evaluate the association between each MRI variable and continence at 6 or 12 months, adjusting for age, body mass index (BMI) and American Society of Anesthesiologists (ASA) score, and then used multivariable logistic regression to create our model. A nomogram was constructed using the multivariable logistic regression models. RESULTS: In all, 68% (1,742/2,559) and 82% (2,205/2,689) regained function at 6 and 12 months, respectively. In the base model, age, BMI and ASA score were significant predictors of continence at 6 or 12 months on univariate analysis (P < 0.005). Among the preoperative MRI measurements, membranous urethral length, which showed great significance, was incorporated into the base model to create the full model. For continence recovery at 6 months, the addition of membranous urethral length increased the area under the curve (AUC) to 0.664 for the validation set, an increase of 0.064 over the base model. For continence recovery at 12 months, the AUC was 0.674, an increase of 0.085 over the base model. CONCLUSION: Using our model, the likelihood of continence recovery increases with membranous urethral length and decreases with age, BMI and ASA score. This model could be used for patient counselling and for the identification of patients at high risk for urinary incontinence in whom to study changes in operative technique that improve urinary function after RP.

Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.

PURPOSE: The fusion of multiparametric resonance imaging and ultrasound has been proven capable of detecting prostate cancer in different biopsy settings. The addition of real-time elastography promises to increase the precision of the outcome of targeted biopsies. We investigated whether real-time elastography improves magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy in patients after previous negative biopsies. MATERIALS AND METHODS: Prospectively 121 men underwent 3T magnetic resonance imaging. Using magnetic resonance imaging/real-time elastography fusion every suspicious lesion was characterized according to its tissue density and sampled by 2 fusion guided targeted biopsies. Additionally, all patients underwent 12-core systematic biopsy. The detection rate of clinically significant and insignificant cancers was compared between targeted und systematic biopsies. The accuracy to predict high grade prostate cancer was evaluated for with the PI-RADS scoring system and compared to the magnetic resonance imaging/real-time elastography fusion score. RESULTS: Overall prostate cancer was detected in 52 patients (43%). Targeted fusion guided biopsy revealed prostate cancer in 32 men (26.4%) and systematic biopsy in 46 (38%). The proportion of clinically significant cancers was higher for targeted biopsy (90.6%) compared to systematic biopsy (73.9%). The detection rate per core was higher for targeted biopsies (14.7%) compared to systematic biopsies (6.5%, p <0.001). The prediction of biopsy result according to magnetic resonance imaging/real-time elastography fusion was better (AUC 0.86) than magnetic resonance imaging alone (AUC 0.79). Sensitivity and specificity for magnetic resonance imaging/real-time elastography fusion was 77.8% and 77.3% vs 74.1% and 62.9% for magnetic resonance imaging. CONCLUSIONS: Magnetic resonance imaging/transrectal ultrasound fusion enhances the likelihood of detecting clinically significant cancers in a repeat biopsy setting. Adding real-time elastography to magnetic resonance imaging supports the characterization of cancer suspicious lesions.

Predictors of short-term recovery of urinary continence after radical prostatectomy.

PURPOSE: To evaluate treatment variables for early urinary continence status 6 weeks following radical prostatectomy. METHODS: In this retrospective analysis, 4,028 consecutive patients underwent open radical retropubic (RRP) or robot-assisted transperitoneal prostatectomy (RARP) at a single academic institution (07/2003-07/2013). After discharge, patients were offered 3-week treatment in a rehabilitation facility. Patients who opted for rehabilitation (n = 2,998, 74.4%) represent our study cohort. Exclusion criteria were acute urinary retention after catheter removal (n = 55, 1.4%), incomplete datasets (n = 50, 1.2%) or refusal of rehabilitation (n = 925, 23.0%). Results of urinary continence were evaluated from final rehabilitation reports. Twenty-two clinical and oncological variables were statistically analysed in uni- and multivariable analyses to determine whether they were associated with early urinary continence status six weeks after radical prostatectomy. Odds ratios and 95% CI as well as p values were calculated. A p level of 0.05 was considered as significant. RESULTS: Six weeks after surgery, 1,962 (65.4%) patients were continent (≤1 pad/day) and 1,036 (34.6%) patients were considered incontinent. Age, clinical stage, PSA, ASA score, prior TURP, seminal vesicle invasion, Gleason score, nerve-sparing status, intraoperative blood loss, catheterisation time, OR time, surgical caseload >1,000 and the surgeon were associated with continence status on univariable analysis (p < 0.05). On multivariable analysis, nerve-sparing procedure (NS), clinical stage, individual surgeon, patient age, surgical procedure (RARP vs. RRP) and duration of catheterisation were independent predictors (p < 0.05) of incontinence status. CONCLUSIONS: Strategies that can ensure NS procedures and early catheter removal should be applied to enable early recovery of urinary continence.

Effect of perioperative complications and functional outcomes on health-related quality of life after radical prostatectomy.

PURPOSE: Radical prostatectomy is a commonly performed procedure with perioperative complication rates of 30 % using standardized reporting methodology. We aim to determine whether perioperative complications and functional outcomes impact quality of life 1 year after surgical treatment. PATIENTS AND METHODS: Quality of life, functional and oncological outcomes were assessed in patients who underwent open retropubic radical prostatectomy at a single academic institution between 2003 and 2009, preoperatively and 1 year after surgery using the EORTC QLQ-C30, the IIEF-5 and an institutional questionnaire. Perioperative complications were recorded using the Clavien-Dindo classification. Patients without complications were compared to patients with any, low- or high-grade complications. The global health score domain of the EORTC QLQ-C30 is reported for various oncological and functional outcomes and contrasted to stratified categories of complications and functional outcomes. RESULTS: A full dataset was available for 29.5 % (n = 856) of all patients. The overall complication rate was 27.5 % (235/856). A total of 307 complications were recorded of whom 88.9 % (273/307) were low grade. In this study, population global health perception did not decline after surgery (70.5 ± 21.2 vs. 74.4 ± 19.7; p < 0.0001). Complications showed only statistical but no clinical meaningful influence on global health perception as well as on functional and symptom scales. Patients who met combined outcome criteria experienced the best postoperative global health score (86.0 ± 13.1 and 86.0 ± 14.2). CONCLUSIONS: Perioperative complications and functional outcomes have a measurable impact on quality of life 1 year following surgery. While perioperative complications have a statistical effect, functional outcomes showed a clinically more profound effect on postoperative global health perception.

Standardized assessment of complications in a contemporary series of European patients undergoing radical cystectomy.

OBJECTIVES: To examine postoperative complications in a contemporary series of patients after radical cystectomy using a standardized reporting system, and to identify readily available preoperative risk factors. METHODS: Using the modified Clavien-Dindo classification, we assessed the 90-day postoperative clinical course of 535 bladder cancer patients who underwent radical cystectomy and urinary diversion (ileal conduit n = 349, ileal neobladder n = 186) between June 2003 and February 2012 at a single institution. All Martin criteria for standardized reporting of complications were met. Uni- and multivariable analyses for prediction of complications were carried out; covariates included body mass index, Charlson Comorbidity Index, age, sex, American Society of Anesthesiologists Score, neoadjuvant chemotherapy, prior abdominal or pelvic surgery, localized tumor and urinary diversion type. RESULTS: The 90-day rates for overall (Clavien-Dindo classification I-V) and high-grade complications (Clavien-Dindo classification III-V), as well as mortality (Clavien-Dindo classification V), were 56.4, 18.7 and 3.9%, respectively. Infections (16.4%), bleeding (14.2%) and gastrointestinal complications (10.7%) were the most common adverse outcomes. Independent risk factors for overall complications were body mass index (odds ratio 1.08) and Charlson Comorbidity Index ≥3 (odds ratio 1.93). Risk factors for high-grade complications were Charlson Comorbidity Index ≥3 (odds ratio 1.86), American Society of Anesthesiologists Score ≥3 (odds ratio 1.92) and body mass index (odds ratio 1.07, all P < 0.03). CONCLUSIONS: Radical cystectomy is associated with significant morbidity; nevertheless, the majority of complications are minor. Charlson Comorbidity Index, American Society of Anesthesiologists Score and body mass index might help to identify patients at risk for high-grade complications after radical cystectomy.

Intraoperative frozen section of the prostate decreases positive margin rate while ensuring nerve sparing procedure during radical prostatectomy.

PURPOSE: We evaluated whether intraoperative frozen section analysis of the prostate surface might provide significant information to ensure nerve sparing and minimize the positive margin rate. MATERIALS AND METHODS: In 236 patients treated with radical prostatectomy between June 2011 and September 2012 whole surface frozen section analysis of the removed prostate was done intraoperatively. The apex and base were circumferentially dissected as well as the whole posterolateral tissue corresponding to the neurovascular bundles. Multiple perpendicular sections were cut systematically for frozen section analysis. Pathology results were reported to navigate the procedure. RESULTS: Frozen section analysis identified positive surgical margins in 22% of cases, including the neurovascular bundles in 56.9%, apex in 34.5% and base in 8.6%. Of positive frozen section cases 92.3% could be converted to negative status, while 7.7% remained positive. The final positive margin rate in the total cohort was 3%, including a false-negative frozen section rate of 1.6%. In 14.8% of cases the initial nerve sparing plan was changed intraoperatively due to the positive frozen section and the secondary resected specimen detected cancer in 25%. Final pathology results showed Gleason upgrading or up-staging in 40.7% of cases compared to preoperative variables. When comparing patients with positive vs negative frozen sections, preoperative variables did not significantly differ, while postoperatively pathological stage, tumor volume, operative time and final margin status differed significantly. Of patients with exclusively unilateral positive biopsies 13% had a positive surgical margin intraoperatively on the opposite, biopsy negative side. CONCLUSIONS: The surface frozen section technique is associated with a low false-negative surgical margin rate. It might allow for safer preservation of functional anatomical structures in misclassified patients or even patients at higher preoperative risk.

Multiparametric ultrasound of the prostate: adding contrast enhanced ultrasound to real-time elastography to detect histopathologically confirmed cancer.

PURPOSE: We prospectively assessed whether a combined approach of real-time elastography and contrast enhanced ultrasound would improve prostate cancer visualization. MATERIAL AND METHODS: Between June 2011 and January 2012, 100 patients with biopsy proven prostate cancer underwent preoperative transrectal multiparametric ultrasound combining real-time elastography and contrast enhanced ultrasound. After initial elastographic screening for suspicious lesions, defined as blue areas with decreased tissue strain, each lesion was allocated to the corresponding prostate sector. The target lesion was defined as the largest cancer suspicious area. Perfusion was monitored after intravenous injection of contrast agent. Target lesions were examined for hypoperfusion, normoperfusion or hyperperfusion. Imaging results were correlated with final pathological evaluation on whole mount slides after radical prostatectomy. RESULTS: Of 100 patients 86 were eligible for final analysis. Real-time elastography detected prostate cancer with 49% sensitivity and 73.6% specificity. Histopathology confirmed malignancy in 56 of the 86 target lesions (65.1%). Of these 56 lesions 52 (92.9%) showed suspicious perfusion, including hypoperfusion in 48.2% and hyperperfusion in 48.2%, while only 4 (7.1%) showed normal perfusion patterns (p = 0.001). The multiparametric approach decreased the false-positive value of real-time elastography alone from 34.9% to 10.3% and improved the positive predictive value of cancer detection from 65.1% to 89.7%. CONCLUSIONS: Perfusion patterns of prostate cancer suspicious elastographic lesions are heterogeneous. However, the combined approach of real-time elastography and contrast enhanced ultrasound in this pilot study significantly decreased false-positive results and improved the positive predictive value of correctly identifying histopathological cancer.

The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: a prospective study of 353 patients.

PURPOSE: We evaluated whether real-time elastography guided biopsy improves prostate cancer detection compared to conventional systematic gray scale ultrasound guidance. MATERIALS AND METHODS: A total of 353 consecutive patients suspicious for prostate cancer were prospectively randomized for real-time elastography (178) or gray scale ultrasound (175). Each patient enrolled in the study underwent a 10-core prostate biopsy. Six lateral prostate sectors (base, mid, apex) were scanned for cancer suspicious areas, defined as stiffer blue lesions using real-time elastography and hypoechoic lesions using gray scale ultrasound. Suspicious areas were sampled by a single targeted biopsy and considered representative of a defined prostate sector. If real-time elastography or gray scale ultrasound did not visualize a suspicious area in a sector, the biopsy core was taken systematically. Imaging findings were correlated with histopathological reports. Real-time elastography and gray scale ultrasound cases were compared in terms of cancer detection rate and imaging guidance accuracy. RESULTS: Characteristics of patients undergoing real-time elastography and gray scale ultrasound, including age, prostate specific antigen, prostate volume and digital rectal examination, were not significantly different (p>0.05). Prostate cancer was detected in 160 of 353 patients (45.3%). The prostate cancer detection rate was significantly higher in patients who underwent biopsy with the real-time elastography guided approach compared to the gray scale ultrasound guided biopsy at 51.1% (91 of 178) vs 39.4% (69 of 175) (p=0.027). Overall sensitivity and specificity to detect prostate cancer was 60.8% and 68.4% for real-time elastography vs 15% and 92.3% for gray scale ultrasound, respectively. CONCLUSIONS: Sensitivity to visualize and detect prostate cancer improved using real-time elastography in addition to gray scale ultrasound during prostate biopsy. Overall sensitivity did not reach levels to omit a systematic biopsy approach.