Performance of Urinary Markers for Detection of Upper Tract Urothelial Carcinoma: Is Upper Tract Urine More Accurate than Urine from the Bladder?

OBJECTIVES: To assess the performance of urine markers determined in urine samples from the bladder compared to samples collected from the upper urinary tract (UUT) for diagnosis of UUT urothelial carcinoma (UC). PATIENTS AND METHODS: The study comprised 758 urine samples either collected from the bladder (n = 373) or UUT (n = 385). All patients underwent urethrocystoscopy and UUT imaging or ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and nuclear matrix protein 22 (NMP22) were performed. RESULTS: UUT UC was diagnosed in 59 patients (19.1%) (UUT urine) and 27 patients (7.2%) (bladder-derived urine). For UUT-derived samples, sensitivities for cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder cancer led to increased false-positive rates of cytology and FISH. CONCLUSIONS: Urine markers determined in urine collected from the UUT exhibit better sensitivity but lower specificity compared to markers determined in bladder-derived urine. Concomitant or recent diagnosis of UC of the bladder can further influence markers determined in UUT urine.

Value of computed tomography texture analysis for prediction of perioperative complications during laparoscopic partial nephrectomy in patients with renal cell carcinoma.

PURPOSE: Tumorous texture is a marker for tumor tissue inhomogeneity. Based on this assumption, this study aims to evaluate the value of computed tomography texture analysis for imaging-based prediction of perioperative complications during laparoscopic partial tumor nephrectomy. METHODS: A total of 106 patients with histologically confirmed renal cell carcinoma and pre-operative CT were included and volumetric texture analysis of the tumors was performed by two readers. Texture analysis parameter ratios and differences were calculated using the kidney parenchyma as reference ("reference-corrected"). Regression analysis was performed, regarding the value of the texture analysis parameters, for assessment of the tumor nuclear grade and the prediction of peri- and postoperative complications and approximated blood loss. Moreover, the inter-rater agreement in terms of the intra-class correlation coefficient (ICC) was calculated. RESULTS: Regarding the reference-corrected values, the predictive value of texture analysis parameters for severe perioperative complications was highest for the standard deviation of the mean attenuation (Area under curve/AUC, .615; sensitivity, 93.8%, specificity, 30.0%), followed by the uniformity (AUC, .599; sensitivity, 62.5%, specificity, 60.0%), and the uniformity of distribution of positive pixels (AUC, .597; sensitivity, 62.5%; specificity, 61.1%). Regarding the blood loss, the uniformity of positive pixel values (UPP; AUC, 0.638), uniformity (AUC, 0.635), and entropy (AUC, 0.633) yielded the best predictive values, whilst the tumor grade was a weaker predictor (AUC, 0.574). The applied texture analysis parameters did not correlate with the time of surgery or the warm ischemic time. All measured parameters were better predictors for complications than the tumor diameter alone. The inter-rater agreement was almost perfect (ICC, .982). CONCLUSION: CT and CT texture analysis parameters are valuable for prediction of perioperative outcome before laparoscopic partial nephrectomy in patients with renal cell carcinoma.

Expression of tumour progression-associated genes in circulating tumour cells of patients at different stages of prostate cancer.

OBJECTIVE: To evaluate the presence of circulating tumour cells (CTCs) at different stages of prostate cancer using the AdnaTest® ProstateCancerDetect kit (Qiagen). Moreover, we aimed to assess the expression of transcripts that are specific for cancer stem cells (AdnaTest StemCell) and epithelial-mesenchymal transition (EMT) in CTCs (AdnaTest EMT), as well as additional genes that are known to promote prostate cancer progression. PATIENTS AND METHODS: In this prospective study, we included 81 patients who underwent treatment for prostate cancer between 07/2014 and 02/2015, including: Group A, 18 patients (22.2%) with low-risk clinically localised prostate cancer; Group B, 25 patients (30.9%) with high-risk clinically localised prostate cancer; Group C, 11 patients (13.6%) with metastatic castration-sensitive prostate cancer (mCSPC); and Group D, 27 patients (33.3%) with metastatic castration-resistant prostate cancer (mCRPC). AdnaTest ProstateCancer and AdnaTest StemCell/EMT were performed in all cases. In addition, expression of the androgen receptor (AR), c-met, c-kit and thymidylate synthase (TYMS) in CTCs was assessed using specific polymerase chain reaction assays. RESULTS: A positive AdnaTest ProstateCancer was present in three (16.7%), two (8.0%), six (54.5%) and 19 (70.5%) patients in groups A, B, C and D, respectively (P < 0.01, chi-squared test). The AdnaTest EMT and AdnaTest StemCell were positive in zero (0.0%), zero (0.0%), one (9.1%), and two (7.4%); and in five (27.8%), four (16.0%), three (27.3%), and 11 (40.7%) patients in groups A, B, C and D, respectively, with no significant differences noted between groups. CTCs expressing TYMS (44.4% and 50.0% vs 13.9%) or AR (18.2% and 25.9% vs 0.0%) were seen more commonly in patients in groups C and D vs patients with non-metastatic disease (all P < 0.05). Expression of c-kit and c-met were rare events, with only two patients positive for either marker. CONCLUSIONS: AdnaTest ProstateCancerDetect exhibits positive results mainly in patients with metastatic disease. Expression of AR and TYMS are frequent events in CTCs of patients with advanced disease, whereas c-met and c-kit gene expression is seen in only a small proportion of patients. The implications of these results for the use of CTC analysis as a decision factor for personalised treatment strategies in advanced prostate cancer remain to be determined.

The thermoexpandable nitinol stent: a long-term alternative in patients without nephropathy or malignancy.

OBJECTIVE: The aim of this study was to investigate the long-term outcome of a thermoexpandable nickel-titanium nitinol ureteral stent (Memokath 051™) and to identify individual risk factors for failure. MATERIALS AND METHODS: This retrospective single-centre study included 125 patients who underwent implantation of the self-expandable Memokath 051 stent. Complications, indwelling time and reason for explantation were recorded. Analyses were stratified by gender, age, body mass index, American Society of Anesthesiologists score, estimated glomerular filtration rate (eGFR), side, localization and cause of the stricture. RESULTS: In total, 91 out of 125 patients (73%) were available for analysis. Median indwelling time was 355 days (range 7-2125 days). Most stents were removed because of dislocation (42%) or occlusion (40%). Stent removal was rarely performed because of infection (3%). Patients with sufficient renal function (eGFR ≥60 ml/min/1.73 m²) showed increased indwelling times compared with those with nephropathy (386 vs 317 days; p < 0.01). Patients with active malignant disease showed reduced patency time compared with strictures of benign origin (455 vs 190 days; p < 0.01). CONCLUSIONS: This thermoexpandable nitinol stent offers safe mid-term treatment of ureteric strictures, especially in patients without active malignancy and with good renal function.

Prediction of Postoperative Risks in Laparoscopic Partial Nephrectomy Using RENAL, Mayo Adhesive Probability and Renal Pelvic Score.

AIM: To evaluate the Mayo Adhesive Probability (MAP) score, renal pelvis score, and RENAL nephrometry score for the prediction of surgical outcome in patients with renal masses undergoing laparoscopic partial nephrectomy at a single center. PATIENTS AND METHODS: A total of 280 patients who underwent laparoscopic partial nephrectomy were identified retrospectively. Thirty-eight patients were excluded because of a lack of preoperative imaging. The outcome measures included surgical technique, patient characteristics, MAP score, renal-pelvis-score, RENAL nephrometry score, and complication rates according to the Clavien-Dindo classification. Regression analysis was performed for assessment of the predictive value of the given scores. RESULTS: Complications occurred after 32 (13%) operations. There was a significant positive association between the development of complications and RENAL nephrometry score (p=0.003). Prediction of complications was improved by the RENAL nephrometry score [area under the curve (AUC) =0.675] and the MAP score (AUC=0.655): With an increasing MAP score, there was a significantly increased operative time (p=0.033). The renal pelvis score had a minor predicitive role (AUC=0.516) and no correlation was found with postoperative urine leakage. CONCLUSION: The MAP score and RENAL nephrometry score seem to be able to predict a complex or complicated intra- and postoperative course, while the renal pelvis score is not suitable for predicting postoperative complications, especially urine leakage.

Oncologic Impact of Renal Tissue Adjacent to Renal Cell Carcinoma.

AIM: The aim of the study was to investigate the clinical impact of the surgical margin width after nephron-sparing surgery (NSS) on the oncological course of renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised of 126 RCC patients with NSS between 2002 and 2009. Inclusion criteria were negative resection margins and a tumor diameter of ≤100 mm with the possibility of a complete circumferential histopathological reevaluation. The minimal benign margin width was correlated to the patients' clinical course. RESULTS: Median safety margin width was revealed to be 1 mm. Nine of 126 patients (7.1%) developed recurrent disease (five local, four distant). All patients with local recurrence had safety margins ≤1 mm, whereas out of 49 patients with a margin >1 mm no one developed local recurrence (p=0.0245). Safety margin ≤1 mm showed associations with increased risk for overall recurrence in univariate and multivariate analysis (p=0.0531 and 0.0539, respectively). CONCLUSION: Tumor adjacent renal parenchyma may have oncological relevance, corroborating the need for further molecular investigation of tumor-adjacent tissue in RCC.

Transcripts of circulating tumor cells detected by a breast cancer-specific platform correlate with clinical stage in bladder cancer patients.

PURPOSE: There is increasing interest in circulating tumor cells (CTCs) as a biomarker in bladder cancer (BC). In the present pilot study, we used a platform originally developed for detection of breast cancer CTCs to assess breast cancer-associated transcripts in CTCs of patients with different stages of BC. Moreover, transcripts specific for cancer stem cells and epithelial mesenchymal transition (EMT) were assessed. METHODS: We prospectively enrolled 83 BC patients and 29 controls. The AdnaTest® system was used to enrich epithelial cells in peripheral blood and to detect breast cancer-associated, stem cell-specific or EMT-specific transcripts. Test results were correlated with clinical and pathological stage. RESULTS: A positive AdnaTest® BreastCancerDetect was present in 6.9 % of controls (group A), 6.7, 15.0 and 18.7 % of patients with non-muscle-invasive BC (B), cM0 muscle-invasive BC (C) and metastatic BC (D) (p = 0.13). Stem cell-specific transcripts in group A, B, C and D were detected in 10.3, 10.0, 22.5 and 31.3 % (p = 0.03). EMT-associated transcripts were present in 3.5, 3.3, 15.0 and 18.7 % (p = 0.03). In group C, epithelial and stem-like transcripts correlated with tumor stage (p = 0.01 and 0.04). CONCLUSIONS: CTCs with expression of breast cancer-associated transcripts are present in a considerable proportion of patients with BC. EMT and stem cell-specific transcripts of CTCs correlate with clinical stage and can be detected in patients negative for epithelial transcripts. The prognostic relevance of AdnaTest® results in BC patients and potential implications for therapy decisions remain to be determined in prospective studies.

Return to Work and Normal Daily Life Activity after Open and Robot-Assisted Radical Prostatectomy--A Single Surgeon Analysis.

PURPOSE: To evaluate differences in health related quality of life and time to return to normal activities between patients treated with open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Three hundred and two patients treated with RARP or ORP were prospectively enrolled. One year after surgery, patients received a questionnaire to evaluate social life, duration of being limited in daily and sexual life as well as satisfaction with the treatment. RESULTS: Both cohorts showed no differences in age, prostate specific-antigen-levels, Gleason score, prostate volume or T-stage (p > 0.05). Median blood loss was significant lower and the surgical time was significant higher in the RARP group. There were no significant differences regarding the duration of being limited in social or daily life or regarding the satisfaction with the treatment. The median time patients felt affected in their work was 2 months. There were no significant differences in terms of subjective global health status and HrQoL 3 months (p = 0.60 and p = 0.40) and 6 months (p = 0.30 and p = 0.20) after surgery. CONCLUSION: The present study confirms significant perioperative benefits for patients undergoing RARP compared to ORP. However, there is no difference in HrQoL as well as in the time to return to normal activities between patients treated with RARP and ORP.

Prostate tumor overexpressed 1 expression in invasive urothelial carcinoma.

PURPOSE: To determine the expression patterns of the proliferation marker prostate tumor overexpressed 1 (PTOV1) in invasive urothelial cancer (UC). METHODS: Corresponding UC and benign samples from paraffin-embedded tissue of 102 patients treated with cystectomy for invasive UC were immunohistochemically (IHC) assessed for PTOV1. Expression was evaluated gradually separated for cytoplasmic and nuclear staining. Results were correlated to histological and clinical data. To correlate PTOV1 expression with molecular subtypes of UC, analysis of PTOV1 RNA expression data of the Cancer Genome Atlas UC cohort was performed. RESULTS: PTOV1 expression was present in UC and benign urothelium, whereby nuclear staining was significantly more frequent in UC tissue (p = 0.0004). Lower cytoplasmic expression was significantly associated with pathological stage >pT2 (p = 0.0014) and grade ≥G3 (p = 0.0041), respectively. IHC expression patterns did not show correlation to survival data. PTOV1 RNA expression correlated with features of the luminal UC subtype. CONCLUSIONS: Subcellular distribution seems to be the most important feature of PTOV1 expression in UC. Nuclear localization of PTOV1 along with cytoplasmic decrease in PTOV1 expression was identified as putative surrogate for PTOV1-associated cellular proliferation and dedifferentiation in UC. The functional relevance as well as the potential role of PTOV1 as a biomarker in UC remains to be specified in future studies.

Muscle-invasive bladder cancer is characterized by overexpression of thymidine kinase 1.

OBJECTIVE: Thymidine kinases have an important role in the synthesis of DNA and exhibit high activity in rapidly proliferating cells. Thymidine kinase 1 (TK1) activity has been shown to be increased in various cancer types and proposed as a prognostic parameter. Aim of the present study was to investigate TK1 in muscle-invasive urothelial carcinoma (UC). METHODS: Corresponding UC and benign samples from paraffin embedded tissue of 111 patients treated with cystectomy for invasive UC from 1996 to 2006 were immunohistochemically (IHC) assessed for TK1. IHC expression patterns were evaluated in a semiquantitative fashion by 2 independent reviewers. Localization of staining was categorized into pure nuclear and additional cytoplasmic localization. Uni- and multivariate analyses were performed to assess differential expression in normal and UC tissue and to evaluate the diagnostic and predictive capability of TK1 by correlation to clinical data. To correlate TK1 expression with molecular subtypes of UC, analysis of TK1 RNA expression levels of the Cancer Genome Atlas UC cohort was performed. RESULTS: TK1 was significantly overexpressed in invasive UC, compared to benign urothelium (P<0.0001), and cytoplasmic expression was more often found in cancer tissue than in benign tissue (P = 0.0001). No correlations of TK1 protein expression patterns to standard histopathological determinants were detected. In univariate analysis, TK1 nuclear and cytoplasmic expression was associated with improved cancer-specific survival (P = 0.0119). However, only metastasis status and histologic grade were identified as independent predictors of cancer-specific survival in multivariate analysis. TK1 expression was merely found in the basal layers of benign urothelium. RNA overexpression of TK1 could be correlated to the biologically more aggressive basal UC subtype. CONCLUSIONS: TK1 expression is significantly different in invasive UC and benign urothelium, which underlines its potential as a diagnostic marker. Although TK1 is considered to be a marker of proliferation, and TK1 RNA overexpression is associated with an aggressive UC subtype, its capability as a predictive IHC biomarker for invasive UC remains limited.

Robot-assisted radical cystectomy and intracorporeal urinary diversion - safe and reproducible?

INTRODUCTION: Robot-assisted radical cystectomy (RARC) plus intracorporeal urinary diversion is feasible. Few centers worldwide demonstrated comparable functional and oncologic outcomes. We reported a large series of RARC and intracorporeal diversion to assess its feasibility and reproducibility. MATERIAL AND METHODS: We identified 101 RARCs in 82 men and 19 women (mean age 68.3 years) from October 2009 to October 2014. The patients underwent RARC and pelvic lymphadenectomy followed by intracorporeal urinary diversion (ileal conduit/ neobladder). Out of the 101 patients, 28 (27.7%) received intracorporeal ileal conduits and 73 (72.3%) intracorporeal neobladders. Studer pouch was performed in all the patients who underwent intracorporeal neobladder formation. Perioperative, functional and oncologic results including CSS and OS are reported. RESULTS: Mean operative time was 402.3 minutes (205-690) and blood loss was 345.3 ml (50-1000). The mean hospital stay was 17.1 days (5-62). All the surgeries were completed with no open conversion. Minor complications (Grade I and II) were reported in 27.7% of patients while major complications (grade III and above) were reported in 36.6% of patients. The mean nodal yield was 20.6 (0-46). Positive ureteric margins were found in 8.9% of patients. The average follow-up was 27.5 months (1-52). Daytime continence could be achieved in 89.2% of patients who underwent intracorporeal neobladder. The 3-year cancer specific survival (CSS) and overall survival (OS) was 80.2% and 69.8% respectively. CONCLUSIONS: RARC with intracorporeal diversion is safe and reproducible in 'non-pioneer' tertiary centers with robotic expertise having acceptable operative time and complications as well as comparable functional and oncologic outcomes.

Prognostic relevance of positive urine markers in patients with negative cystoscopy during surveillance of bladder cancer.

BACKGROUND: The role of urine markers in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC) is discussed extensively. In case of negative cystoscopy the additional prognostic value of these markers has not been clearly defined yet. The present study is the first systematic approach to directly compare the ability of a urine marker panel to predict the risk of recurrence and progression in bladder cancer (BC) patients with no evidence of relapse during surveillance for NMIBC. METHODS: One hundred fourteen patients who underwent urine marker testing during surveillance for NMIBC and who had no evidence of BC recurrence were included. For all patients cytology, Fluorescence-in-situ-hybridization (FISH), immunocytology (uCyt+) and Nuclear matrix protein 22 enzyme-linked immunosorbent assay (NMP22) were performed. All patients completed at least 24 months of endoscopic and clinical follow-up of after inclusion. RESULTS: Within 24 months of follow-up, 38 (33.0%) patients experienced disease recurrence and 11 (9.8%) progression. Recurrence rates in patients with positive vs. negative cytology, FISH, uCyt+ and NMP22 were 52.6% vs. 21.9% (HR = 3.9; 95% CI 1.75-9.2; p < 0.001), 47.6% vs. 25.0% (HR 2.7; 1.2-6.2; p = 0.01), 43.8% vs. 22.4% (HR 3.3; 1.5-7.6; p = 0.003) and 43.8% vs. 16.7% (HR 4.2; 1.7-10.8; p = 0.001). In patients with negative cytology, a positive NMP22 test was associated with a shorter time to recurrence (p = 0.01), whereas FISH or uCyt+ were not predictive of recurrence in these patients. In the group of patients with negative cytology and negative NMP22, only 13.5% and 5.4% developed recurrence and progression after 24 months. CONCLUSIONS: Patients with positive urine markers at time of negative cystoscopy are at increased risk of recurrence and progression. In patients with negative cytology, only NMP22 is predictive for recurrence. Patients with negative marker combinations including NMP22 harbour a low risk of recurrence. Therefore, the endoscopic follow-up regimen may be attenuated in this group of patients.

Significance of apoptotic and non-apoptotic disseminated tumor cells in the bone marrow of patients with clinically localized prostate cancer.

BACKGROUND: Disseminated tumor cells (DTC) can be detected in a high proportion of patients with localized solid malignancies. In prostate cancer (PC), determination of DTCs is critically discussed as there are conflicting results on their prognostic value. The aim of the present study was to evaluate the presence and prognostic role of DTCs in PC patients with a high risk of disease recurrence. METHODS: 248 patients with clinically localized PC undergoing radical prostatectomy with features of increased risk of recurrence (PSA ≥10 ng/ml or Gleason score ≥ 4 + 3 = 7 or pT ≥3) were included. All patients underwent intraoperative bone marrow (BM) aspiration biopsy. BM cells were evaluated by immunocytochemistry for cytokeratines and the apoptosis marker caspase-cleaved cytokeratin 18 (M30). Results of immunocytochemistry were correlated with clinical and pathological parameters and clinical outcome of the patients. RESULTS: Of 248 patients, 47 (19.0%) had evidence of DTCs at time of radical prostatectomy. In 17 of these 47 patients (36.2%), DTCs expressed the apoptosis marker M30. We observed no correlation between the presence of DTCs and tumor stage, nodal stage, prostate-specific antigen, or Gleason score. After a median-follow-up of 58 months (23-76), no differences in rates of biochemical recurrence, development of metastases and cancer-specific death were observed between patients with and without DTCs while apoptosis markers had no role. CONCLUSIONS: In a single-centre cohort of patients with increased risk for disease recurrence, the presence of DTCs at the time of prostatectomy does not influence clinical outcome. For the first time in patients with PC, DTCs were evaluated for immunocytological features indicating apoptosis. Due to conflicting results of studies on DTCs, BM biopsies at time of radical prostatectomy cannot be recommended as a standard procedure in patients with clinically localized PC.

Robot-assisted radical cystectomy and intracorporeal neobladder formation: on the way to a standardized procedure.

BACKGROUND: Robot-assisted radical cystectomy (RARC) with intracorporeal diversion has been shown to be feasible in a few centers of excellence worldwide, with promising functional and oncologic outcomes. However, it remains unknown whether the complexity of the procedure allows its duplication in other non-pioneer centers. We attempt to address this issue by presenting our cumulative experience with RARC and intracorporeal neobladder formation. METHODS: We retrospectively identified 62 RARCs in 50 men and 12 women (mean age 63.6 years) in two tertiary centers. Intracorporeal Studer neobladders were created, duplicating the steps of standard open surgery. Perioperative and postoperative variables and complications were analyzed using standardized tools. Functional and oncological results were assessed. RESULTS: The mean operative time was 476.9 min (range, 310 to 690) and blood loss was 385 ml (200 to 800). The mean hospital stay was 16.7 (12 to 62) days with no open conversion. Perioperative complications were grade II in 15, grade III in 11, and grade IV in 5 patients. The mean nodal yield was 22.9 (8 to 46). Positive margins were found in in 6.4%. The 90- and 180-day mortality rates were 0% and 3.3%. The average follow-up was 37.3 months (3 to 52). Continence was achieved in 88% of patients. The cancer-specific survival rate and overall survival rate were 84% and 71%, respectively. CONCLUSIONS: A RARC with intracorporeal neobladder creation is safe and reproducible in 'non-pioneer' tertiary centers with robotic expertise with acceptable operative time and complications. Further standardization of RARC with intracorporeal diversion is a prerequisite for its widespread use.

Y pouch neobladder-a simplified method of intracorporeal neobladder after robotic cystectomy.

In recent years, robot-assisted radical cystectomy (RARC) has shown similar oncologic outcomes compared with the gold standard open radical cystectomy with the added benefit of less blood loss and shorter hospital stay. Robot-assisted cystectomy with intracorporeal ileal neobladder is a complex surgical procedure and is usually performed in centers with experienced surgeons. We propose robot-assisted cystectomy with intracorporeal neobladder using the Y pouch previously described in open radical cystectomy. We think that the Y pouch is easier to perform than conventional spherical pouches without compromising functional outcomes. It may therefore be a good alternative for patients undergoing RARC with intracorporeal diversion.

Intracorporeal ileal ureter replacement using laparoscopy and robotics.

INTRODUCTION: Ileal ureter is a suitable treatment option for patients with long ureteric strictures. Minimally invasive techniques have been shown to be as safe as open techniques but superior in terms of post-operative recovery. We report our experience using minimally invasive techniques for total intracorporeal ureteral replacement. MATERIAL AND METHODS: A chart review revealed five patients who underwent intracorporeal ileal ureter using minimally invasive techniques in the preceding 5 years. 4 patients underwent conventional laparoscopic surgery and 1 patient underwent robotic-assisted surgery. Patient's characteristics, perioperative data and functional outcomes as well as a detailed description of surgical technique are reported. In all 5 of these patients, the ileal ureter was performed completely intracorporeally. RESULTS: The median age of our patients is 61 (range 42-73). The median operative time was 250 minutes (range 150-320) and median blood loss was 100 ml (range 50-200). The median hospital stay was 8 days (range 6-10) and there were no major perioperative complications reported. At median follow up of 22 months (range 4-38), there were no recurrences of strictures or any other complications. CONCLUSIONS: We have demonstrated the safety and feasibility of minimally invasive intracorporeal ileal ureter. Numbers are still small but its application is likely to grow further.

Stepwise application of urine markers to detect tumor recurrence in patients undergoing surveillance for non-muscle-invasive bladder cancer.

BACKGROUND: The optimal use of urine markers in the surveillance of non-muscle-invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to investigate the combined and stepwise use of the four most broadly available urine markers to detect tumor recurrence in patients undergoing surveillance of NMIBC. PATIENTS AND METHODS: 483 patients with history of NMIBC were included. Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy. Characteristics of single tests and combinations were assessed by contingency analysis. RESULTS: 128 (26.5%) patients had evidence of tumor recurrence. Sensitivities and negative predictive values (NPVs) of the single tests ranged between 66.4-74.3 and 82.3-88.2%. Two-marker combinations showed sensitivities and NPVs of 80.5-89.8 and 89.5-91.2%. A stepwise application of the two-test combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+ and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and 99.1%, respectively. CONCLUSIONS: Combinations of cytology, FISH, immunocytology, and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test combinations of cytology, FISH, and immunocytology have a low probability of missing a high-risk tumor. The high sensitivities may justify the use of these combinations in prospective studies assessing the use of urine markers to individualize intervals between cystoscopies during follow-up.