Long term outcomes in classic bladder exstrophy - The adult picture.

With continued improvements in medical care and surgical reconstruction, more patients with classic bladder exstrophy (CBE) are living into adulthood, than ever before. With improved survival, a greater emphasis on adult issues and improving quality of life (QOL) for these individuals is of increasing importance. This review aims to summarize data on long-term considerations for the adult with exstrophy and to highlight areas of future research and collaboration. Key conclusions are that continence or dryness are achievable alongside the ability to enjoy sexual relationships and a good quality of life.

The Additive Diagnostic Value of Prostate-specific Membrane Antigen Positron Emission Tomography Computed Tomography to Multiparametric Magnetic Resonance Imaging Triage in the Diagnosis of Prostate Cancer (PRIMARY): A Prospective Multicentre Study.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI) is validated for the detection of clinically significant prostate cancer (csPCa), although patients with negative/equivocal MRI undergo biopsy for false negative concerns. In addition, 68Ga-PSMA-11 positron emission tomography/computed tomography (prostate-specific membrane antigen [PSMA]) may also identify csPCa accurately. OBJECTIVE: This trial aimed to determine whether the combination of PSMA + MRI was superior to MRI in diagnostic performance for detecting csPCa. DESIGN, SETTING, AND PARTICIPANTS: A prospective multicentre phase II imaging trial was conducted. A total of 296 men were enrolled with suspected prostate cancer, with no prior biopsy or MRI, recent MRI (6 mo), and planned transperineal biopsy based on clinical risk and MRI. In all, 291 men underwent MRI, pelvic-only PSMA, and systematic ± targeted biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity, specificity, and predictive values (negative predictive value [NPV] and positive predictive value) for csPCa were determined for MRI, PSMA, and PSMA + MRI. PSMA + MRI was defined as negative for PSMA negative Prostate Imaging Reporting and Data System (PI-RADS) 2/3 and positive for either MRI PI-RADS 4/5 or PSMA positive PI-RADS 2/3; csPCa was any International Society of Urological Pathology (ISUP) grade group ≥2 malignancy. RESULTS AND LIMITATIONS: Of the patients, 56% (n = 162) had csPCa; 67% had PI-RADS 3-5, 73% were PSMA positive, and 81% were combined PSMA + MRI positive. Combined PSMA + MRI improved NPV compared with MRI alone (91% vs 72%, test ratio = 1.27 [1.11-1.39], p < 0.001). Sensitivity also improved (97% vs 83%, p < 0.001); however, specificity was reduced (40% vs 53%, p = 0.011). Five csPCa cases were missed with PSMA + MRI (four ISUP 2 and one ISUP 3). Of all men, 19% (56/291) were PSMA + MRI negative (38% of PI-RADS 2/3) and could potentially have avoided biopsy, risking delayed csPCa detection in 3.1% men with csPCa (5/162) or 1.7% (5/291) overall. CONCLUSIONS: PSMA + MRI improved NPV and sensitivity for csPCa in an MRI triaged population. Further randomised studies will determine whether biopsy can safely be omitted in men with a high clinical suspicion of csPCa but negative combined imaging. PATIENT SUMMARY: The combination of magnetic resonance imaging (MRI) + prostate-specific membrane antigen positron emission tomography reduces false negatives for clinically significant prostate cancer (csPCa) compared with MRI, potentially allowing a reduction in the number of prostate biopsies required to diagnose csPCa.

Initial outcomes of local anaesthetic freehand transperineal prostate biopsies in the outpatient setting.

OBJECTIVES: To evaluate the histopathological outcomes, morbidity and tolerability of freehand transperineal (TP) prostate biopsies using the PrecisionPoint™ access system (Perineologic, Cumberland, MD, USA) under local anaesthetic (LA) in the day surgery and outpatient environments, as systematic and targeted biopsies can be taken with the potential for reduced morbidity, particularly sepsis. PATIENTS AND METHODS: In all, 176 patients underwent freehand TP prostate biopsies from May 2016 to November 2017. The procedure was carried out either under LA alone or with the addition of sedation. Magnetic resonance imaging (MRI) scans were reported using the Prostate Imaging-Reporting and Data System (PI-RADS), version 2. Tolerability was assessed using a visual analogue scale pain score for each procedural stage. Histopathological outcomes and complications were recorded. RESULTS: The mean (range) age was 65 (36-83) years, median (range) prostate-specific antigen level was 7.9 (0.7-1374) ng/mL, and the mean (range) prostate volume 45 (15-157) mL. Biopsies were taken under LA alone (160 patients, 90%) or under LA with sedation (16, 9%). The main indication for biopsy was primary diagnosis (88.6%). In all, 91 (52%) patients underwent systematic TP biopsies (mean 24.2 cores). Cognitive MRI-targeted biopsies alone were performed in 45 patients (26%; mean 6.8 cores), and 40 (23%) had both systematic and target biopsies (mean 27.9 cores). Of the 75 patients who had primary systematic biopsies alone, 46 (61%) were positive, and 28/46 (60.9%) were diagnosed with clinically significant disease (Gleason ≥3+4). VAS pain scores were greatest during LA administration. There were five complications (2.8%, Clavien-Dindo Grade I/II). No patients developed urosepsis. CONCLUSIONS: Freehand TP biopsies using the PrecisionPoint access system is a safe, tolerable and effective method for systematic and targeted biopsies under LA in the outpatient setting. It has replaced transrectal biopsies in our centre and has potential to transform practice.

Extended-spectrum ß-lactamase in the rectal flora of patients undergoing transrectal prostate biopsy: a study of the prevalence in a major metropolitan hospital.

OBJECTIVES: To determine the prevalence of extended-spectrum ß-lactamase (ESBL) in patients undergoing transrectal prostate biopsy, to assess the incidence of postoperative sepsis, to correlate the development of sepsis with the presence of preoperative ESBL on rectal swabs, and to assess the adequacy of prophylactic antibiotic guidelines in the context of local ESBL prevalence. METHODS: Patients undergoing transrectal ultrasonography (TRUS)-guided biopsy at the Royal Melbourne Hospital between January 2012 and July 2016 had rectal swabs taken immediately prior to TRUS with specific cultures to identify the presence of ESBL. Patients were given a prophylactic antibiotic, 500 mg oral ciprofloxacin, 1 h before the TRUS procedure. Data were collected prospectively, with retrospective review of all readmitted patient files and audit data to ensure complete capture of events. RESULTS: A total of 387 TRUS-guided biopsy procedures were performed. Rectal swabs were correctly collected in 352 patients (91%). The median patient age was 65 years. In all, 25 (7%) ESBL-positive swabs were identified. Most ESBL were Escherichia coli. Half (50%) of ESBL were resistant to ciprofloxacin and all were sensitive to meropenem. A small increase in ESBL prevalence over time was not significant (R2 = 0.35). Four patients (1.1%) were readmitted with sepsis; ESBL Pseudomonas had previously grown in one patient, but sepsis was attributable to non-ESBL E. coli. In one of the readmitted patients ESBL E. coli was present, but this patient did not have ESBL preoperatively. There were no deaths or high-dependency/intensive care unit admissions. CONCLUSIONS: This study represents the largest Australian series to investigate ESBL prevalence, and reveals a rate lower than that of many other nations. Our sepsis rate is lower than many international series, perhaps because of our low ESBL rate and strict antibiotic prophylaxis. Preoperative swab results did not predict postoperative sepsis, and the process was therefore not useful for guiding antibiotic therapy. In this patient population, TRUS biopsy, with ciprofloxacin prophylaxis, remains a safe option for diagnostic prostate biopsy.

Introducing new technology safely into urological practice.

PURPOSE: Surgical innovation is necessary to ensure continued improvement in patient care. However, several challenges unique to the surgical craft are encountered during the development and validation of such new technology. This article highlights some of these challenges and gives an overview of existing solutions. METHODS: A Pubmed review was performed about the "introduction of new technology" to identify challenges. Cross-referencing was used to explore the possible solutions per challenge. RESULTS: Several characteristics of the surgical craft itself limit our ability to establish randomised controlled trials and hence provide clear categorical evidence. Existing certification bodies for new technology often use unstructured regulations and allow fast-track bypassing systems. Consequently the IDEAL framework (innovation, development, exploration, assessment, long-term follow-up) proposes an objective scientific approach whilst defining stakeholder responsibilities. The selection of which new modality to implement is heavily influenced by third parties unrelated to the best patient outcomes and thus professional organisations can aid in this decision-making. Appropriate training of surgeons and their teams until proficiency is achieved is essential prior to credentialling. Finally long-term surveillance of outcomes in the form of registries is an increasing responsibility of the urological community to maintain our role in directing the adoption or rejection of these innovations. CONCLUSION: Urological innovation is a dynamic and challenging process. Increasing efforts are identified within the urological community to render the process more reliable and transparent.

What robot for tomorrow and what improvement can we expect?

PURPOSE OF REVIEW: The purpose of this review is to summarize the status of robotic surgery currently, contextualizing the advances and improvements we can expect in the immediate future. Robotics continues to demonstrate increased utility and expansion in medicine, particularly surgery. When coupled with the imminent expiry of Intuitive patents in the next few years, it is timely to consider what we can expect to see from new platforms; what new features might we anticipate and what technology will be available to enhance and improve patient care. RECENT FINDINGS: There really are no limits with the anticipated developments in the field of medical robotics. Multiple large companies and academic institutions continue to invest in design and production with the release of a number of platforms already having occurred, whereas others are to come in the near future. The main anticipated advances will be haptic feedback, decreased cost, improved theatre assimilation with open consoles permitting free communication and lower theatre footprint. The robot patient interface is to be enhanced with single port platforms in production with a better interface including haptic feedback. The addition of NOTES and smarter flexible robotics is the next key area of interest, whereas the introduction of technology with image guidance and networking where large data sets or connectivity permit increased clinical acumen to enhance decision making. SUMMARY: We are at the cusp of a tipping point as the intellectual property for the first major robotic system in surgery comes to an end. It is likely to be a period of great opportunity with enhanced surgery and patient outcomes through significant innovation, multiple platforms nearing dissemination, with various technological advances. We anticipate this will yield a great period of innovation and diversity. Will we see a truly automated robot soon; the Smart Tissue Autonomous Robots are the limit.

Extraprostatic extension into periprostatic fat is a more important determinant of prostate cancer recurrence than an invasive phenotype.

PURPOSE: Although micrometastasis development correlates closely with the depth of invasion of many tumor types, it is unclear whether invasion into but not through the prostatic pseudocapsule has a negative impact on prognosis, similar to extraprostatic extension. We defined the impact of pseudocapsular invasion on the risk of post-prostatectomy biochemical recurrence. MATERIALS AND METHODS: Patients with pT2-3a prostate cancer were identified from a prospectively recorded database. Those with pT2 disease were categorized according to pseudocapsular invasion presence or absence. The impact of pseudocapsular invasion on biochemical recurrence was determined by univariable and multivariable Cox regression analysis. RESULTS: In a cohort of 1,338 patients we identified 595 with organ confined cancer positive for pseudocapsular invasion. Compared to tumors without evidence of invasion, pseudocapsular invasion was positively associated with higher Gleason grade and tumor volume (1.2 vs 1.9 cc, each p<0.001). On univariable analysis there was no difference in biochemical recurrence-free survival between patients with vs without pseudocapsular invasion, although those with extraprostatic extension had significantly lower biochemical recurrence-free survival (p<0.001). This was confirmed on multivariable analysis, which revealed that extraprostatic extension was a significant independent predictor of biochemical recurrence (HR 1.53, p=0.018). The presence of pseudocapsular invasion had no effect (HR 0.81, p=0.33). CONCLUSIONS: Pseudocapsular invasion is not a pathological feature associated with an adverse outcome after prostatectomy. Thus, the depth of tumor invasion is not a continuum of risk and access to periprostatic adipose tissue is a more important determinant of disease behavior than an invasive phenotype.

Loss of APKC expression independently predicts tumor recurrence in superficial bladder cancers.

OBJECTIVES: Epithelial-mesenchymal transition (EMT) is known to play an important role in the development of tumor invasion and progression in tumors of epithelial origin. Our aim was to investigate the role of tight junction proteins, Par3/Par6/atypical protein kinase C (APKC), Discs large (Dlg), and Scribble in human bladder pathogenesis. METHODS: We evaluated levels of APKC, Dlg, and Scribble in 92 superficial bladder tumors using tissue microarrays and immunohistochemistry, and correlated expression with pathologic variables and clinical outcomes. RESULTS: There was a slight apparent enrichment in strong vs. weak staining for APKC (54.9% vs. 45.1%), Dlg (65.7% vs. 34.3%), and a marked enrichment for Scribble (75% vs. 25%) in the superficial bladder tumors. Univariate analysis determined that both tumor focality and APKC expression were significantly associated with tumor recurrence (P < 0.05). Multivariate analysis using the Cox's proportional hazards model revealed that only APKC (P = 0.025) as well as tumor focality (P = 0.018) were independent and significant prognostic factors for tumor recurrence in all patients. We found that no immunohistochemical staining of any of the cell polarity proteins significantly predicted for tumor progression on either univariate or multivariate analysis. CONCLUSIONS: Loss of APKC expression in superficial bladder tumors is a strong predictor of tumor recurrence.

Prostate weight is the preferred measure of prostate size in radical prostatectomy cohorts.

OBJECTIVE: To evaluate the accuracy of calculated prostate volume variables in a radical prostatectomy (RP) cohort, as many recent studies use these measures of prostate size instead of prostate weight. To determine whether this accuracy could be improved by modifying the mathematical model used in the volume estimation. PATIENTS AND METHODS: Patients who underwent RP for prostate cancer at our associated institutions had calculated specimen volumes and weights from RP specimens determined at one pathology institution and transrectal ultrasonography (TRUS) volumes were recorded preoperatively (n= 236). Correlation analysis was performed and errors were determined for calculated volume variables when compared with prostate weight. Bland-Altman plots were drawn and concordance coefficients calculated. Analysis was repeated with smaller prostates mathematically modelled as bullet-shaped rather than ellipsoid (n= 165). RESULTS: Although correlation was good for both TRUS and specimen volumes, they equally underestimated prostate weight with a large range of errors and poor concordance coefficients. Only 22% of TRUS volumes and 11% of calculated specimen volumes were within 10% of weight measurements. Application of a bullet-shaped mathematical model for prostates <55 g did not correct the large individual variation seen within these values. CONCLUSION: Calculated prostate volume variables are prone to a large range of individual error regardless of the mathematical model used and should be avoided in statistical studies involving RP cohorts, and the more accurate prostate weight variable should instead be used as a size variable or correction factor.

Do routinely repeated computed tomography scans in traumatic brain injury influence management? A prospective observational study in a level 1 trauma center.

OBJECTIVE: To prospectively examine the clinical role of routine repeat computed tomographic scans of the brain (CTB) in patients with traumatic head injury. SUMMARY BACKGROUND DATA: The use of routine serial CTB after traumatic head injury is recommended by some authors, but remains controversial. METHODS: From March 2007 to October 2008, all patients with traumatic head injury admitted to the Royal Melbourne Hospital, a metropolitan, Level I trauma center, were prospectively studied. After the initial computed tomography brain scans, any subsequent CTBs were assessed and were recorded as being either "clinically indicated" or "routine" and ensuing medical and surgical management. Inpatient information was recorded and comparisons made according to indication for CTB, Glasgow Coma Scale, and management changes. RESULTS: A total of 651 patients were admitted with traumatic head injury over the 20-month study period. Of those, 39 underwent immediate craniotomy/craniectomy and were excluded from analysis. Another 25 were excluded due to incomplete data, leaving 591 patients for analysis. Of the 591 assessed, 401 were discharged with no further computed tomography investigation. One hundred and ninety patients underwent a total of 305 repeat brain scans, of which 149 were clinically indicated, whereas 156 were obtained as a "routine" investigation with no deterioration in patients' neurological status. Of the repeated scans, 71 were improved, 169 were unchanged, and 64 were worse. None of the 156 patients who received a "routine" CTB required a change in management. The 149 CTB performed for clinical deterioration resulted in a change in management in 28 patients (19%). The patients who underwent "indicated" computed tomographic scans and subsequently required a change in management were on average younger (P < 0.001) and more severely head injured (P = 0.001) than the patients not requiring a change in management. CONCLUSIONS: No patients from our cohort with a "routine" repeat CTB required a change in management. Given the costs and potential risks of routine repeat CTB, and lack of demonstrable benefit, the practice should be reconsidered. Repeat CTB is clearly indicated in patients with deteriorating neurological status, especially younger and more severely head-injured patients.

Cadaveric analysis of periprostatic nerve distribution: an anatomical basis for high anterior release during radical prostatectomy?

PURPOSE: An accurate, complete understanding of the prostate neuroanatomy is required to optimize nerve sparing techniques during radical prostatectomy. However, the precise topography and function of the periprostatic nerves remain contentious and there is uncertainty about which nerve sparing technique is most optimal. We accurately quantified the distribution, precise localization and cross-sectional area of periprostatic neural tissue using cadaveric specimens. MATERIALS AND METHODS: We analyzed 13 cadaveric hemipelves using hematoxylin and eosin stained sections from the base, mid zone and apex of each prostate. Each section was digitized and divided into 6 sectors numbered clockwise. Analysis was performed using National Institutes of Health ImageJ software to calculate the total periprostatic neural cross-sectional area per sector. RESULTS: Calculating the total neural cross-sectional area highlighted a decrease from prostate base to mid zone to apex of 24.7, 19.7 and 13.7 mm(2), respectively. Most neural tissue was located in the posterolateral region. However, the proportion surrounding the anterior part of the prostate increased toward the apex with a median of 6.0% and 7.6% at the base and mid zone regions, respectively, increasing to 11.2% at the apex. CONCLUSIONS: Simple numerical nerve quantification may be insufficient to accurately describe the periprostatic neural distribution. Calculating nerve bundle cross-sectional area confirmed that most neural tissue is in the posterolateral region, although the proportion located anterior increases from base to apex. Thus, higher release of the periprostatic fascia may be indicated toward the apex.

Prostate tumour volume is an independent predictor of early biochemical recurrence in a high risk radical prostatectomy subgroup.

AIMS: To assess if accurately determined tumour volume variables could serve as independent predictors of early biochemical recurrence in high risk prostate cancer patients who underwent radical prostatectomy. METHODS: Tumour volume variables were calculated by digital planimetry in 269 prostatectomy specimens of patients with high risk prostate cancer. The associations to biochemical progression of tumour volume and clinicopathological variables, including age, pre-operative prostate specific antigen (PSA) levels, final Gleason score, pathological T stage, and surgical margins, were examined using univariate and multivariate Cox proportional hazards analyses. RESULTS: Median tumour volume was 3.7 ml [interquartile range (IQR) 2.1-6.1 mL] and median follow-up time was 12 months (IQR 6-24 months). Biochemical recurrence occurred in 64 men (24%) during this period, with a median time to recurrence of 7.5 months (IQR 3.0-15.5 months). On univariate analysis all of the tumour volume variables were strongly correlated with the clinicopathological variables, as well as biochemical recurrence (p < 0.001). On multivariate analysis, we found that tumour volume variables served as independent predictors of PSA progression whilst other routinely reported pathological variables did not. CONCLUSION: Accurately assessing tumour volume in the high risk setting may aid in identifying patients at greatest risk of developing early biochemical recurrence and most in need of adjuvant therapy.

Immunohistochemical study of the cavernous nerves in the periprostatic region.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The anatomy of the periprostatic tissues, in particular the fascial layers and neurovascular structures, remain a somewhat enigmatic and controversial area. Despite the considerable advances made in this area since the original dissections of Walsh and Donker almost thirty years ago, the precise location and function of these structures remains uncertain. The topic is of tremendous importance as we continue to refine surgical techniques to allow men the maximum opportunity to recover erectile function following radical prostatectomy. Yet many of these surgical refinements are not based on definitive knowledge of the relevant anatomy and clearly more knowledge is required. For the first time, we have not just characterized the quantitative nature of the periprostatic nerves, but we also offer some insight into the likely functional nature of these nerves by selectively staining the sympathetic and parasympathetic nerves using immunohistochemical methods. OBJECTIVE: • To characterize the immunohistochemical nature of sympathetic and parasympathetic nerves surrounding the prostate. MATERIALS AND METHODS: • Using serial sectioning, four male cadavers were investigated using a combination of haematoxylin and eosin staining and immunohistochemistry. Both the sympathetic and parasympathetic contributions to the autonomic nervous system in the periprostatic region were assessed by staining analysis, the number of nerves fibres was quantified, their position relative to the prostate recorded and their function inferred. • The fascial architecture of the neurovascular bundle (NVB) was also quantified. RESULTS: • Approximately 27.8% of all nerve fibres identified were found on the anterior half of the prostate, above the 3 to 9 o'clock level. At the base, mid, and apex of prostate, parasympathetic fibres accounted for 4%, 5% and 6.8% of the nerves located on the anterolateral aspect of the prostate, respectively. • Sympathetic nerves found above the 3 to 9 o'clock level represented ≈15% of the total number of nerves. • When staining the periprostatic fascia, the classical NVB exhibited a distinct fascial architecture with three separate compartments. CONCLUSIONS: • A tiny minority of nerves in the anterior periprostatic region are functionally significant parasympathetic nerves. • There is little anatomical evidence to support higher incisions in the lateral prostatic fascia to spare cavernous nerve fibres, although such approaches may reduce the risk of traction injury on the more posterolaterally located NVB. • The presence of distinct fascial compartments in the NVB is also confirmed.

Potential use of circulating endothelial cells as a biomarker of renal cell carcinoma.

Each year, renal cell carcinoma (RCC) accounts for significant mortality in the population. Whilst the disease is now being diagnosed earlier, determining patient prognosis remains a challenge. Current prognostic indicators, such as TNM stage, Fuhrman grade, and RCC subtype, are inadequate. Unlike several other malignancies, RCC lacks a biomarker that can stratify patients into high, intermediate, or low risk for developing metastases. Additionally, antiangiogenic therapy is currently offered to patients with metastatic disease, however, a biomarker to monitor treatment efficacy is lacking. Recent attention has focused on surrogate markers of tumor vascularization as a source of prognostic biomarkers, as tumor growth is ultimately dependent on neovascularization. Two cell populations of interest, circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs), have been demonstrated across several studies to contribute to tumor vascularization. Given these findings, studies have examined their utility as biomarkers of prognosis by correlating their levels with progression-free survival and prognostic determinants such as tumor volume and weight. However, their role in predicting prognosis in RCC, as well as their potential to act as markers of treatment efficacy in metastatic RCC, remains to be established. Previous studies on CECs and CEPs in the context of cancer will be outlined in this review.

Paraneoplastic syndromes in prostate cancer.

Prostate cancer is the second most common urological malignancy to be associated with paraneoplastic syndromes after renal cell carcinoma. These syndromes tend to occur in the setting of late stage and aggressive tumors with poor overall outcomes. Recognition of these syndromes is clinically important as it might lead to the detection of underlying malignancy and impact on the treatment options available. The literature features around 100 cases of paraneoplastic syndromes associated with prostate cancer and these include endocrine manifestations, neurological entities, dermatological conditions, and other syndromes. Over 70% of cases document the syndrome as the initial clinical manifestation of prostate cancer, while in just under 20% the syndrome was an initial sign of disease progression to the castrate-resistant state. The vast majority of cases involved advanced metastatic malignancy. The syndromes generally resolve upon institution of treatment for the underlying prostate cancer, but some syndromes require specific therapies. Some syndromes are associated with serum markers that are readily detectable and demonstration of these putative markers within prostate cancer tissue at an individual level would firmly link the paraneoplastic syndrome with its underlying prostatic malignancy. The causes of paraneoplastic syndromes in prostate cancer are incompletely understood, and further research into their biology might shed more light on the complex molecular mechanisms that underpin prostate cancer and its lethal potential.

Circulating endothelial cells and progenitors: potential biomarkers of renal cell carcinoma.

OBJECTIVE: To compare the levels of circulating endothelial cells (CECs) and progenitors (CEPs) between tumour-bearing mice and healthy controls, in human renal cell carcinoma (RCC) xenograft models. The secondary objective was to correlate CEC and CEP levels with tumour variables such as tumour volume, weight and vascularity, indicators of disease severity. MATERIALS AND METHODS: Two human RCC xenograft models were used. Tumour cells were inoculated either subcutaneously or beneath the renal subcapsule (orthotopic). Tumour dimensions were recorded and blood samples were taken throughout the experiment, as well as at the end of the experiment, upon which tumours were excised and prepared for histological examination. All blood samples were analysed by flow cytometry. RESULTS: CEC and CEP levels were significantly elevated in tumour-bearing mice compared with healthy controls. In particular, there was a divergence in CEC levels between RCC-bearing mice and controls during early phases in disease, whereas CEP levels were only elevated towards the end. Additionally, CEC levels correlated with tumour variables such as tumour volume, when tumour volume was <200 mm³ and with tumour vascularity in certain models. CEP levels did not correlate significantly with most tumour variables examined. CONCLUSION: In human RCC xenograft models, CEC levels showed promise as an adjuvant biomarker in evaluating disease burden. RESULTS from correlating CEC levels with tumour variables such as tumour volume, weight and vascularity suggested that CEC levels were a better prognostic indicator during early phases of tumour growth. CEP levels were elevated in tumour-bearing mice compared with controls; however, enumerated numbers were small and require further validation in future studies.

Snail expression is an independent predictor of tumor recurrence in superficial bladder cancers.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is known to play an important role in the development of tumor invasion and progression in tumors of epithelial origin. OBJECTIVES: Our aim was to investigate the role of Snail transcription repressor family members in human bladder pathogenesis. MATERIAL AND METHODS: We evaluated levels of Snail and Slug in 87 patients who received transurethral resection of a transitional cell carcinoma at our institution during the period from June 1999 until November 2003. Immunohistochemistry was performed on tissue microarrays, and expression correlated with pathological variables and clinical outcomes. Degree and intensity of Snail and Slug staining was quantified by immunohistochemistry. RESULTS: There was no apparent enrichment in strong vs. weak staining for either Snail (43.7% vs. 56.3%) or Slug (46% vs. 54%) in the superficial bladder tumors. Univariate analysis determined that tumor focality and Snail expression were significantly associated with tumor recurrence (P < 0.05). Only for tumor focality did such a relationship exist when assessing tumor progression. Multivariate analysis using the Cox's proportional hazards model revealed similar results to that of the univariate analysis. Snail expression (P = 0.038) and tumor focality (P = 0.011) were independent and significant prognostic factors for tumor recurrence in all patients. However, only tumor focality was an independent predictor of tumor progression (P = 0.034). CONCLUSIONS: High expression of Snail in superficial bladder tumors is a strong predictor of tumor recurrence enhancing risk stratification and prognostication.