The association between preoperative Mini-Cog© score and postoperative delirium (POD): a retrospective cohort study.

BACKGROUND: The onset of delirium after major surgery is associated with worse in-hospital outcomes for major surgical patients. Best practice recommends assessing surgical patients for delirium risk factors and this includes screening for cognitive impairment. The Mini-Cog© is a short instrument which has been shown to predict postoperative delirium (POD) and other complications in elderly patients undergoing major elective surgery. The primary aim of this study was to ascertain whether a positive preoperative Mini-Cog© is associated with postoperative delirium in elective colorectal surgery patients at high-risk of mortality due to age or comorbidity. Secondary outcomes were 90-day mortality and length of stay. METHODS: This is a retrospective analysis of data gathered prospectively between October 2015 and December 2017. Baseline data were collected at a preoperative screening clinic, and postoperative data during daily ward rounds by the Perioperative Medicine team at The York Hospital. RESULTS: Three hundred nineteen patients were included in the final analysis, of which 52 (16%) were found to be cognitively impaired on the Mini-Cog©. Older patients (median difference 10 years, p < 0.001) and patients with cognitive impairment (OR 3.04, 95%CI 1.15 to 8.03, p = 0.019) were more likely to develop postoperative delirium in univariate analysis; however, cognitive impairment (OR 0.492, 95%CI 0.177 to 1.368, p = 0.174) loses its significance when controlled for by confounding factors in a logistic regression model. Cognitive impairment (OR 4.65, 95%CI 1.36 to 15.9, p = 0.02), frailty (OR 7.28, 95%CI 1.92 to 27.58, p = 0.009), American Society of Anesthesiologists (ASA) grade (OR 5.95, 95%CI 1.54 to 22.94, p = 0.006) and age (median difference 10 years, p = 0.002) were significantly associated with 90-day mortality in univariate analysis. Sex was the only factor significantly associated with length of stay in the multiple regression model, with males having a 3-day longer average length of stay than females (OR = 2.94, 95%CI 0.10-5.78). CONCLUSIONS: Mini-Cog© is not independently associated with post-operative delirium in high-risk elective colorectal surgery patients in this cohort. Mini-Cog© shows promise as a possible predictor of 90-day mortality. Larger studies exploring preoperative cognitive status and postoperative confusion and mortality could improve risk-stratification for surgery and allocation of resources to those patients at higher risk.

A randomised trial of non-invasive cardiac output monitoring to guide haemodynamic optimisation in high risk patients undergoing urgent surgical repair of proximal femoral fractures (ClearNOF trial NCT02382185).

BACKGROUND: Hip fracture is a procedure with high mortality and complication rates, and there exists a group especially at risk of these outcomes identified by their Nottingham Hip Fracture Score (NHFS). Meta-analysis suggests a possible benefit to this patient group from intravascular volume optimisation. We investigated whether intraoperative fluid and blood pressure optimisation improved complications in this group. METHODS: Patients with a NHFS ≥ 5 were enrolled into this multicentre observer-blinded randomised control trial. Patients were allocated to either standard care or a combination of fluid optimisation and blood pressure control using a non-invasive system. The primary outcome was the number of patients with one or more complications in each group. Secondary outcomes included hospital length of stay (LOS), incidence of hypotension and fluid and vasopressor usage. RESULTS: Forty-six percent of patients in the intervention group suffered one or more complications compared to the 51% in the control group (OR 0.82 (95% CI 0.49-1.36)). Per-protocol analysis improved the OR to 0.73 (95% CI 0.43-1.24). Median LOS was the same between both groups; however, the mean LOS on a per-protocol analysis was longer in the control group compared to the intervention group (23.2 (18.0) days vs. 18.5 (16.5), p = 0.047). CONCLUSIONS: Haemodynamic optimisation including blood pressure management in high-risk patients undergoing repair of a hip fracture did not result in a statistically significant reduction in complications; however, a potential reduction in length of stay was seen. TRIAL REGISTRATION: A randomised trial of non-invasive cardiac output monitoring to guide haemodynamic optimisation in high risk patients undergoing urgent surgical repair of proximal femoral fractures (ClearNOF trial NCT02382185).

Prognostic Markers of Outcome in Patients Undergoing Infra-inguinal Revascularisation: A Prospective Observational Pilot Study.

OBJECTIVES: The aim was to investigate whether cardiopulmonary exercise testing (CPET) variables derived from cycle and arm ergonometry correlate, and whether CPET variables and pre-operative N-terminal pro-brain natriuretic peptide (NT-proBNP) have prognostic significance and if the combination of the two has incremental value. METHODS: A prospective observational pilot study was conducted; 70 patients who underwent infra-inguinal bypass surgery were recruited. Pre-operatively subjects underwent CPET with both arm and leg ergonometry, to measure peak oxygen consumption, anaerobic threshold (AT), and ventilatory equivalents. In addition pre-operative serum samples of NT-proBNP were obtained. The primary endpoint was 1 year all-cause mortality; in addition, data were collected on complications, morbidity, length of stay, and major adverse cardiac events (MACE). RESULTS: The 1 year mortality rate was 6%, the overall complications rate was 23%, and the combined incidence of MACE and 1 year mortality was 10%. Cycle ergonometry peak VO2 14 mL/kg/min (RR 5.5, 95% CI 1.4-22.4, p = .007) and AT < 10mL/kg/min (RR 3.0, 95% CI 1.1-7.0, p = .03) were predictors of post-operative complications. Pre-operative NT-proBNP > 320 ng/L (RR 18, 95% CI 2.5-140 p = .0003) was the sole predictor of 1 year mortality or MACE. CONCLUSION: The measurement of pre-operative NT-proBNP in peripheral vascular disease patients undergoing infra-inguinal bypass can predict 1 year mortality and MACE. CPET variables from cycle ergonometry are predictors of post-operative complications in this patient group.

[Epidemiology and risk factors of upper urinary tract tumors: literature review for the yearly scientific report of the French National Association of Urology]. / Épidémiologie et facteurs de risque des tumeurs de la voie excrétrice urinaire supérieure: revue de la littérature pour le rapport annuel de l'Association française d'urologie.

AIM: To describe the epidemiology, the risk and genetic factors involved in carcinogenesis pathways of upper urinary tumors UTUCs. MATERIAL: A systematic review of the scientific literature was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM using the following keywords: epidemiology; risk factor; tobacco; aristolochic acid; urothelial carcinoma; ureter; renal pelvis. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: The estimated UTUC incidence is 1.2 cases/100,000 inhabitant per year in Europe. The incidence of renal pelvis tumor has been stable for 30years, while the frequency of ureteric locations has increased over time. Locally advanced stage and high grade are more frequent at the time of diagnosis. The median age for diagnosis is 70-years-old. Male-to-female ratio is nearly 2. Main carcinogenic factors are tobacco consumption and occupational exposure. There are specific risk factors for UTUC such acid aristolochic (balkan's nephropathy and Chinese herbs nephropathy). Familial cases are distinct from sporadic cases. UTUCs belong to the HNPCC syndrome and they rank third in its tumor spectrum. CONCLUSION: UTUCs are scarce tumors with specific epidemiologic characteristics. UTUCs share common risk factors with other urothelial carcinomas such as bladder tumors but have also specific risk factors that clinicians should know.

Crystalloid or colloid for goal-directed fluid therapy in colorectal surgery.

BACKGROUND: Goal-directed fluid therapy has been shown to improve outcomes after colorectal surgery, but the optimal type of i.v. fluid to use is yet to be established. Theoretical advantages of using hydroxyethyl starch (HES) for goal-directed therapy include a reduction in the total volume of fluid required, resulting in less tissue oedema. Recent work has demonstrated that new generations of HES have a good safety profile, but their routine use in the perioperative setting has not been demonstrated to confer outcome benefit. METHODS: We randomly assigned 202 medium to high-risk patients undergoing elective colorectal surgery to receive either balanced 6% HES (130/0.4, Volulyte) or balanced crystalloid (Hartmann's solution) as haemodynamic optimization fluid. The primary outcome measure was the incidence of gastrointestinal (GI) morbidity on postoperative day 5. Secondary outcome measures included the incidence of postoperative complications, hospital length of stay, and the effect of trial fluids on coagulation and inflammation. RESULTS: No difference was seen in the number of patients who suffered GI morbidity on postoperative day 5 [30% in the HES group vs 32% in the crystalloid group; adjusted odds ratio=0.96 (0.52-1.77)]. Subjects in the crystalloid group received more fluid [median (inter-quartile ranges) 3175 (2000-3700) vs 1875 (1500-3000) ml, P<0.001] and had a higher 24 h fluid balance [+4226 (3251-5779) vs +3610 (2443-4519) ml, P<0.001]. No difference in the incidence of postoperative complications was seen between the groups. CONCLUSIONS: Goal-directed fluid therapy is possible with either crystalloid or HES. There is no evidence of a benefit in using HES over crystalloid, despite its use resulting in a lower 24 h fluid balance.

Robot-assisted laparoscopic nephron sparing surgery for tumors over 4 cm: operative results and preliminary oncologic outcomes from a multicentre French study.

OBJECTIVE: To assess operative and pathological results obtained after robot-assisted partial nephrectomy (RAPN) in renal masses over 4 cm. PATIENTS AND METHODS: Between 2007 and 2011, 220 robotic nephron-sparing surgeries (NSS) were performed at six French urology departments. Data were prospectively collected: age, BMI, pre and post-operative eGFR (MDRD), operative time (OT), warm ischemia time (WIT), estimated blood loss (EBL), length of hospital stay (LOS), Clavien complications, pathological results and oncologic outcome. Tumor complexity was assessed according to the RENAL nephrometry score. RESULTS: Overall, 54 tumors were included. Median follow up was 26 months. Median age at surgery was 62 years. Median RENAL nephrometry score was 7 (4-10). Median WIT was 23 min (10-59). Median OT and EBL were 180 min (110-425) and 100 cc (0-2500). Blood transfusion occurred in 7 cases (13%). Median tumor size was 45 mm (40-70). Three patients had positive surgical margins. Median LOS was 5 days (2-28). Nine patients presented post-operative complications of which 1/3 were considered as major (Clavien IIIb). Median pre-operative and post-operative eGFR was 88 (36-136) and 75 ml/min (33-122) (p = 0.01), respectively. Two patients developed subsequent metastasis. The 2-year progression free survival (PFS) rate was 90.5%. CONCLUSION: Our results confirm that RAPN is a useful and acceptable approach for renal masses greater than 4 cm in size. When technically possible, NSS provides promising short-term cancer-specific survival rates with acceptable morbidity. Tumor size is not sufficiently discriminant enough and RENAL nephrometry score should increasingly used to describe tumor complexity.

Influence of preoperative hydronephrosis on the outcome of urothelial carcinoma of the upper urinary tract after nephroureterectomy: the results from a multi-institutional French cohort.

OBJECTIVES: Recent publications have assessed the prognostic significance of hydronephrosis in the outcome of upper tract urothelial carcinoma (UUT-UC). Our study sought to determine the prognostic impact of hydronephrosis on UUT-UC survival and its relationship to the clinicopathological features. MATERIALS AND METHODS: A retrospective, multi-institutional French study was conducted on 401 patients who underwent radical nephroureterectomy for non-metastatic UUT-UC. Hydronephrotic status was determined using preoperative imaging reports. Univariate and multivariate analyses were conducted to identify factors associated with survival. RESULTS: Preoperative hydronephrosis was present in 74 patients. Median follow-up was 26 months. Hydronephrosis was associated only with ureteral localisation (p < 0.001). No difference was observed in 5-year cancer-specific survival (CSS) between the hydronephrosis group (80.1 %) and the no hydronephrosis group (83.6 %) (p > 0.05). Only age (p = 0.02) and pT stage (p = 0.01) were independent predictors of CSS. Hydronephrosis was not a significant predictor of CSS in the univariate and multivariate analyses (p = 0.87 and p = 0.66). No significant difference was observed for 5-year metastasis-free survival (MFS) between the hydronephrosis group (69.8 % ± 6.6 %) and the no hydronephrosis group (80.5 % ± 3 %) (p = 0.052). Hydronephrosis was not a significant predictor of MFS in the univariate and multivariate analyses (p = 0.16 and p = 0.36). Multifocality (p = 0.02), pT stage (p < 0.001) and positive surgical margins (p = 0.02) were independent predictors of MFS. For the pelvic tumours subgroup, hydronephrosis was an independent predictor of MFS (p = 0.01) but not CSS (p = 0.86). CONCLUSION: Preoperative hydronephrosis was not associated with survival. However, among tumours presenting with hydronephrosis, pelvicalyceal tumours appear to have a worse prognosis than ureteral tumours.

Cancer-specific survival after radical nephroureterectomy for upper urinary tract urothelial carcinoma: proposal and multi-institutional validation of a post-operative nomogram.

BACKGROUND: Owing to the scarcity of upper urinary tract urothelial carcinoma (UUT-UC) it is often necessary for investigators to pool data. A patient-specific survival nomogram based on such data is needed to predict cancer-specific survival (CSS) post nephroureterectomy (NU). Herein, we propose and validate a nomogram to predict CSS post NU. PATIENTS AND METHODS: Twenty-one French institutions contributed data on 1120 patients treated with NU for UUT-UC. A total of 667 had full data for nomogram development. Study population was divided into the nomogram development cohort (397) and external validation cohort (270). Cox proportional hazards regression models were used for univariate and multivariate analyses and to build a nomogram. A reduced model selection was performed using a backward step-down selection process, and Harrell's concordance index (c-index) was used for quantifying the nomogram accuracy. Internal validation was performed by bootstrapping and the reduced nomogram model was calibrated. RESULTS: Of the 397 patients in the nomogram development cohort, 91 (22.9%) died during follow-up, of which 66 (72.5%) died as a consequence of UUT-UC. The actuarial CSS probability at 5 years was 0.76 (95% CI, 71.62-80.94). On multivariate analysis, T stage (P<0.0001), N status (P=0.014), grade (P=0.026), age (P=0.005) and location (P=0.022) were associated with CSS. The reduced nomogram model had an accuracy of 0.78. We propose a nomogram to predict 3 and 5-year CSS post NU for UUT-UC. CONCLUSION: We have devised and validated an accurate nomogram (78%), superior to any single clinical variable or current model, for predicting 5-year CSS post NU for UUT-UC.

[Results obtained after robotic-assisted laparoscopic sacral colpopexy for the management of urogenital prolapse: a review]. / Résultats de la promontofixation par voie laparoscopique robot-assistée pour la prise en charge des prolapsus urogénitaux : analyse de la littérature.

INTRODUCTION: Laparoscopic sacral colpopexy (LSCP) is one of the gold standard surgical treatment for the management of urogenital prolapse. Robot-assisted laparoscopic sacrocolpopexy (RALSCP) is an alternative surgical access which has been recently proposed. The aim of the current study was to report the functional results obtained after RALSCP. MATERIAL AND METHODS: [corrected] A systematic review of the scientific literature was achieved in the Pubmed database, using the following keywords: robotic; robot; sacrocolpopexy; sacralcolpopexy. Clinical cases and series of less than five cases were spontaneously not selected herein. RESULTS: Overall, 12 series in published between September 2004 and September 2011 which included 350 female patients were selected. The mean age was 63 years old with a pelvic organ prolapse of stage 3 to 4 in the Baden Walker classification. The mean operative time of the RALSCP was 207 minutes with a conversion rate of 3,4% and an intraoperative complication rate of 4,6%. The mean length of hospital stay was 3 days and the perioperative complication rate of 7,1%. The success rate of the RALSCP was 97% and the vaginal erosion rate was 2,5% with a median follow-up of 13,5 months. CONCLUSION: The mid-term functional results obtained after RALSCP were equivalent to those obtained with the LSCP approach. However, there is no prospective randomized comparison available between the two access so far. In addition, the experience with RALSCP remains limited due to the important cost that the robotic access generates.

[Prevention of complications of general anesthesia linked with laparoscopic access and with robot-assisted radical prostatectomy]. / Complications de l'anesthésie générale inhérentes à la voie laparoscopique et à la prostatectomie totale robot-assistée.

INTRODUCTION: The aim of our work was to present a review of technical features and complications of general anesthesia during robot-assisted laparoscopic radical prostatectomy (RALRP). MATERIALS AND METHODS: Data on RALRP and general anesthesia were explored on Medline using the following MeSH terms: radical prostatectomy; morbidity; anesthesia complications; laparoscopy; robotics; Trendeleburg. Publications were considered on the following criteria: methodology, relevance and date of publication. RESULTS: There was no data of level of evidence 1 available. The first RALRP was reported in 2000. Technological innovation brought by the robot with its 3-D vision, the acquisition of degrees of mobility and a more ergonomic position for the surgeon, have led to a growing interest from new teams in the western world. However, the RALRP generates constraints for the anesthesia team who need to incorporate the rules of laparoscopy and the patient's specific installation to guarantee maximum safety. There are inherent complications with the installation of the patient himself in the Trendelenburg position (ocular, neurological, hemodynamic, respiratory) and respiratory complications related to the specific procedure in gaseous atmosphere due to pneumoperitoneum. One of the criteria of the quality of publications in the field of surgery is related to the objective evaluation of complications by appropriate scale systems and the complications of general anesthesia must also be absolutely recorded. CONCLUSION: RALRP had deeply modified the anatomical landmarks of the surgical removal of prostate cancer. However, the perioperative environment has also been completely altered and the installation of RALRP in the daily routine of a service requires from the anesthesia team to adapt their behavior to this sophisticated surgical access.

Contemporary management of patients with high-risk non-muscle-invasive bladder cancer who fail intravesical BCG therapy.

It is advocated that patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG, either early with persistent (refractory) disease or recur late after a long disease-free interval (relapsing). Guideline recommendation in the 'refractory' setting is radical cystectomy, but there are situations when extirpative surgery is not feasible due to competing co-morbidity, a patient's desire for bladder preservation or reluctance to undergo surgery. In this review, we discuss the contemporary management of NMIBC in patients who have failed prior BCG and are not suitable for radical surgery and highlight the potential options available. These options can be categorised as immunotherapy, chemotherapy, device-assisted therapy and combination therapy. However, the current data are still inadequate to formulate definitive recommendations, and data from ongoing trials and maturing studies will give us an insight into whether there is a realistic efficacious second-line treatment for patients who fail intravesical BCG but are not candidates for definitive surgery.

[Asynchronous implantation of a penile prosthesis (AMS 700) in patients with an artificial urinary sphincter (AMS 800): what functional outcomes can we expect from the AMS 1500?]. / Implantation asynchrone d'une prothèse pénienne (AMS 700) chez des patients avec un sphincter urinaire artificiel (AMS 800) : quels sont les résultats fonctionnels de l'AMS 1500 ?

OBJECTIVE: To report the functional results and morbidity after metachronous implantation of an AMS 800 artificial urinary sphincter (AUS) and an AMS 700 inflatable penile prosthesis (IPP). PATIENTS AND METHODS: From the 250 patients treated in our department between 2000 and 2011 for the insertion of an AUS, we retrospectively selected patients who also underwent implantation of an IPP. The following data were recorded: age, aetiology of urinary incontinence (UI) and erectile dysfunction (ED), treatment history of UI/ED, date of insertion of the AUS and the IPP and time gap between the two implants. We evaluated both the pad-test and the number of protective pads used per day, before and after AUS insertion. We also analysed the IIEF5 score before and after IPP. Patients were reviewed at 3, 6 and 12 months and annually thereafter. RESULTS: In total, five patients were included. The median age was 69 years. The median follow-up after IPP was 22.6 months and the time gap between the two implants was 50 months. The aetiology of UI and ED was prostate surgery in four cases. Complete continence without leakage was observed in three patients and the IIEF5 score increased from 6.6 preoperatively to 22.2 for four patients. One patient developed a urethral erosion of the AUS cuff 6 months after implantation of the IPP. The AUS cuff has been explanted but the patient remains continent with the IPP cylinders semi-inflated. CONCLUSION: From our small study, it appears that the combined use of an AMS 800 AUS and an AMS 700 IPP was a feasible and efficacious option in patients with concomitant refractory UI and ED.

'Nephrostomy-free' percutaneous nephrolithotomy: experience in a UK district general hospital.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the first-line treatment for large and complex renal calculi. Accepted UK practice is to insert a nephrostomy tube at the end of the procedure to drain the kidney and reduce potential complications. 'Tubeless' or 'nephrostomy-free' PCNL has been advocated in selected patients as it is thought to reduce length of hospital stay, analgesia requirements and pain experienced. We present our outcomes of a consecutive series (n = 101) of 'nephrostomy-free' PCNLs compared to standard PCNL over a 4-year period. PATIENTS AND METHODS: Between January 2004 and October 2006, we performed 55 standard (with nephrostomy tube) PCNLs (Group 1). From October 2006 onwards, we changed our technique and have performed 46 consecutive 'nephrostomy-free' PCNLs (JJ stent inserted), independent of patient and stone factors (Group 2). We have compared the two groups in terms of length of hospital stay (LOS), analgesia requirements, transfusion rates, haemoglobin (Hb) decrease and immediate, early and late complications. RESULTS: 'Nephrostomy-free' PCNL significantly reduced the length of hospital stay (2.8 vs 5.1 days; P < 0.001), morphine-based analgesia requirements (23% no morphine required vs 2.8%; P < 0.001), transfusion rate (2.5% vs 7%; P < 0.01) and mean Hb decrease (1.89 g/dl vs 2.25 g/dl; P > 0.05). Overall, no patient experienced a serious complication. All attempted 'nephrostomy-free' PCNLs were completed (stone clearance 95%) and no patient needed an unplanned nephrostomy. Only 5% in Group 2 needed their ureteric JJ stent removing earlier than planned secondary to pain. Both groups were comparable in terms of immediate, early and late complications, though three patients in Group 1 developed chronic loin pain and one patient in the 'nephrostomy-free' group developed a delayed perirenal haematoma. CONCLUSIONS: 'Nephrostomy-free' percutaneous nephrolithotomy is a safe, effective and feasible procedure independent of patient and stone factors. It decreases the length of hospital stay, the pain experienced and the need for morphine-based analgesia; we feel it should be the standard of care for patients undergoing a PCNL.

Behavior of urothelial carcinoma with respect to anatomical location.

PURPOSE: Urothelial carcinoma is a disease of the entire urothelium. Recent molecular insights suggest that the biology of some upper urinary tract and bladder urothelial carcinoma differ. These differences may affect tumor phenotype. Observational studies conflict as to the significance of anatomical location on the behavior of urothelial carcinoma. We compared the biological outcome in a large series of urothelial carcinoma with respect to anatomical location. MATERIALS AND METHODS: We analyzed urothelial carcinoma in 425 patients treated at 4 centers according to stage and anatomical location, including the bladder in 275, the ureter in 67 and the renal pelvis in 79. Relapse surveillance was performed for a median of 46 months (range 2 to 216). A separate invasive bladder urothelial carcinoma population was also included to pathologically balance upper and lower tract urothelial carcinoma cases to allow behavioral comparisons. RESULTS: As a whole, upper urinary tract urothelial carcinoma is more invasive and worse differentiated than bladder cancer (chi-square test p<0.0001 and 0.015, respectively). In pathologically matched cohorts recurrence to less aggressive disease, progression to more advanced disease and death occurred in 37%, 40% and 44% of patients with bladder urothelial carcinoma, and in 41%, 44% and 43% of those with upper urinary tract urothelial carcinoma, respectively. Multivariate analysis revealed that tumor stage and grade (Cox p=0.0001 and 0.012, respectively) but not location were associated with behavior. CONCLUSIONS: Urothelial carcinoma behaves identically in the upper and lower urinary tracts when stage and grade are considered. The majority of tumors relapse within 5 years of excision. The current move to minimally invasive/nephron sparing techniques for urothelial carcinoma of the upper urinary tract appears safe. Care could be analogous to that for bladder urothelial carcinoma.

Methylational urinalysis: a prospective study of bladder cancer patients and age stratified benign controls.

Tumour suppressor gene (TSG) methylation has been proposed as a diagnostic marker for urothelial cancer (UC). Here, we compare the frequency of urinary TSG methylation in young and elderly patients, with and without UC. Urine samples were obtained prospectively from 35 UC patients, 35 benign controls over the age of 70 years and 34 healthy volunteers under the age of 40 years. Methylation analysis was performed for eight gene promoters using quantitative methylation-specific PCR. Methylation was detected in urine DNA from all three patient groups. The highest frequencies were seen in UC patients. Significantly less methylation was present in control samples than UC cases for RASSF1a and APC (P < 0.034). The 'methylation index' and level of methylation was highest in the UC group and lowest in the young control group. A marker panel of RASSF1a, E-cad and APC generated a sensitivity of 69%, a specificity of 60% and a diagnostic accuracy of 86%. TSG methylation is detectable in urine DNA from patients with and without bladder cancer. The frequency and extent of methylation appears to increase with age and malignancy. The lack of tumour specificity suggests that further investigation is required before this test is introduced into clinical practice.