Urine colour after radical prostatectomy predicts urinary leakage at the vesicourethral anastomosis.

OBJECTIVE: The aim of this investigation was to determine whether postoperative urine colour could be used as a predictor for the presence or absence of a urinary leakage at the vesicourethral anastomosis after open radical prostatectomy. MATERIAL AND METHODS: In this prospective study, the urine colour of 223 patients who underwent open radical prostatectomy due to histologically proven localized prostate cancer was assessed macroscopically and microscopically on postoperative day (POD) 6, 7 and 8. All patients underwent evaluation of perianastomotic extravasation by retrograde cystography on POD 8. Baseline characteristics included age; prostate-specific antigen; prostate volume; tumour, node, metastasis classification; and Gleason score. RESULTS: The urine colour was a highly significant predictor for perianastomotic extravasation in cystography when it was red on POD 6, 7 and 8. The sensitivity and specificity of urine colour as a predictor for extravasation were 71.4% and 83.2% on POD 6, 71.4% and 85.8% on POD 7, and 81.8% and 90.9% on POD 8, respectively, with a clear or slightly ensanguined urine colour. The negative and positive predictive values were 98.6% and 81.8%, respectively. CONCLUSION: A cystography can be omitted if the patient demonstrates a clear urine colour on POD 8, without an increased risk of missing a perianastomotic extravasation.

Detection of urinary leakage after radical retropubic prostatectomy by contrast enhanced ultrasound - do we still need conventional retrograde cystography?

INTRODUCTION: To prospectively evaluate the accuracy of transvesical contrast-enhanced ultrasound (CEUS) as an alternative method for the detection of anastomotic leakage after radical retropubic prostatectomy (RRP) in comparison with the current standard method of conventional retrograde cystography (CG). PATIENTS AND METHODS: Forty-three patients underwent RRP for histologically proven localized prostate cancer. The vesico-urethral anastomosis was evaluated 8 days after RRP by CG and CEUS. Any peri-anastomotic leakage was assessed and determined in CG and CEUS as follows: no extravasation (EV), small leakage (≤0.5 cm), moderate leakage (>0.5 cm to ≤2 cm), large leakage (>2 cm diameter of EV seen). RESULTS: In total, 21 (49%) patients showed a watertight anastomosis. Ten (23%), two (4.7%) and ten (23%) patients showed a small, intermediate and large EV, respectively. In 31 cases (72%) there was 100% agreement of CG and CEUS for detection of no, moderate and large EV, respectively. In nine cases a small and in two cases a moderate EV was categorized as watertight anastomosis by CEUS. Only in one case did CG detect a small EV where a large EV was detected in CEUS. The agreement between both methods was 95% for detecting absence or large leakages. CONCLUSION: CEUS is a promising imaging modality that seems to be equivalent to CG for detecting the presence of a large anastomotic leakage that is clinically relevant for postoperative persistence of the indwelling catheter. CEUS could be a cheap and time-saving alternative to the CG without exposure of the patient to radiation.

Influence of clinical information on the interpretation of urinary cytology in bladder cancer: how suggestible is a cytologist?

OBJECTIVE: to determine the influence of the knowledge of the endoscopic findings and the influence of the patient's history on the cytologist's judgement, as urinary cytology is known to be subjective and has several limitations, in particular a high inter- and intra-observer variability. PATIENTS AND METHODS: we analysed the cytological and histological findings of patients who underwent transurethral resection of a bladder tumour, and determined whether the cytologist was aware of the endoscopic findings or not. The sensitivity and specificity of cytology were calculated with or without this knowledge, and that of the patients' bladder cancer history. RESULTS: the findings of 1705 patients were reviewed; in 641 the histological examination confirmed a malignant tumour and 1046 were classified as benign. The sensitivity of cytology was 66.0% and the specificity was 78.4%. The cytologist was aware of the endoscopic finding and patient history in 742 cases, and unaware of the endoscopic findings in 963. The specificity was higher in the latter group (80.2% vs 73.0%; P= 0.006). The specificity in patients with the endoscopic findings described as 'negative', 'inflammation', 'scar tissue', 'flat lesion', 'suspicious for tumour', and 'exophytic tumour' was 89.8%, 89.9%, 85.0%, 77.1%, 63.2% and 48.6%, respectively (P < 0.001). In 898 patients the history was negative for bladder tumours. Among these patients the sensitivity and specificity of cytology was 67.3% and 79.7%; the sensitivity and specificity was 65.4% and 74.8% for the 807 patients with a positive history of bladder cancer (P= 0.054). CONCLUSION: both being aware of the endoscopic findings and a positive patient history for bladder cancer lowers the specificity of cytology. Consequently, the cytologist should be unaware of the endoscopic findings.

Predicting individual outcomes after radical cystectomy: an external validation of current nomograms.

OBJECTIVE: To determine whether published nomograms, i.e. The International Bladder Cancer Nomogram Consortium (IBCNC) and the Bladder Cancer Research Consortium (BCRC) statistical models for predicting disease recurrence and survival of patients after radical cystectomy, are feasible for routine use in intermediate-volume institutions in Europe, as although these nomograms had high accuracy by internal validation tests, they stem from high-volume centres and have not been validated elsewhere and thus their general applicability remains unproven. PATIENTS AND METHODS: We externally validated the published nomograms. Information about treatments, pathological details, and recurrence and survival status was retrospectively collected from 246 patients. The expected survival according to the nomograms was calculated. The predictive accuracy of the proposed models was calculated by Harrell's concordance indices. To assess the independent prognostic value of the variables proposed by IBCNC and BCRC, stepwise multivariable Cox regressions based on Akaike's Information Criterion (AIC) for the different endpoints were used. A best model for prediction was created on the basis of our data. RESULTS: The IBCNC and the BCRC nomograms showed an improvement in the predictive accuracy of recurrence, all-cause and bladder-cancer-specific survival after radical cystectomy of up to 4% compared to Tumour-Node-Metastasis stage-based predictions. According to the calculated AIC values for the different models, all nomograms performed better than the TNM classification. CONCLUSIONS: The BCRC and IBCNC nomograms provided accurate predictions when they were applied to an external cohort of patients from low- to intermediate-volume centres. The prediction of recurrence and survival based on the addressed nomograms is better than TNM stage-based prediction. The application of such nomograms can be supported on a sound basis, but further amendments are warranted.

Photodynamic diagnosis in patients with T1G3 bladder cancer: influence on recurrence rate.

INTRODUCTION: Therapeutic strategies on treatment of T1G3 urothelial cancer of the urinary bladder are controversial. The objective of this study was to investigate the impact of photodynamic diagnosis (PDD) on the recurrence-free survival rate of patients with the initial diagnosis of T1G3 bladder cancer. PATIENTS AND METHODS: Between 1995 and 2007, 153 patients were treated for T1G3 bladder cancer at our institution. In 77 patients, initial TUR-BT was performed under PDD condition at our hospital, and 76 patients underwent TUR-BT in a standard white light setting at other institutions. PDD was performed either using 5-aminolevulinate or hexaminolevulinate for induction of fluorescence. Average follow-up was 53.9 months. Fisher's exact test and Kaplan-Meier method were used to test data for significance. RESULTS: Of the 77 patients who were treated using PDD at initial TUR-BT, recurrence was observed in 23 (29.9%) cases, whereas 43 of 76 (56.6%) patients treated without PDD showed recurrence (P < 0.001). The detection rate of additional carcinoma in situ was 35.4% in the PDD group versus 21.8% in the white light group (P = 0.077). A limitation of the present study is the retrospective, monocentre setting, which is more likely to be biased. CONCLUSION: PDD during initial TUR-BT in T1G3 bladder cancer seems to reduce significantly the rate of recurrence in our study population. Therefore, PDD seems to be associated with superior initial tumour control and more effective tumour treatment even in patients with highly aggressive tumours like T1G3 bladder cancer.

Radical cystectomy in the elderly patient: a contemporary comparison of perioperative complications in a single institution series.

PURPOSE: To report on our recent experience with peri- and postoperative morbidity of radical cystectomy in patients 75 years and older compared to younger patients. PATIENTS AND METHODS: Medical records of 326 consecutive patients undergoing radical cystectomy from May 2004 through April 2008 were reviewed. RESULTS: Eighty-five of 326 patients (26%) were > or =75 years (75-95) old. ASA score was equal 3 or greater in 51% of patients > or =75 years and 32% of patients <75 years. Ileal conduit was performed in 83% of patients > or =75, 16% received an ileal neobladder compared to 46 and 51%, respectively, in patients <75. A total of 33 patients (39%) in the older patient group received blood transfusions intraoperatively compared to 76 patients (32%) in the younger age group. In 6 patients > or =75 years (7.1%) and 17 patients <75 (7.1%) open surgical revision was necessary, perioperative complication rate was 22 and 21%, respectively. The most common complications were wound dehiscence (5.9 vs. 7.5%), infections (4.7 vs. 4.6%), and pulmonary embolism (3.5 vs. 2.1%). Perioperative mortality was 1.2% (1 patient) in the elderly versus 0.4% (1 patient) in the younger age group. CONCLUSION: Our data show that radical cystectomy can be offered to the elderly patient with acceptable morbidity. Because of higher comorbidity rate in the elderly, therapeutic decision for radical cystectomy in elderly patients should be made carefully and individually. Nevertheless our results demonstrate that age itself is not a main criterion which has to be considered strongly in decision making for radical cystectomy.

Positive urine cytology but negative white-light cystoscopy: an indication for fluorescence cystoscopy?

OBJECTIVE: To evaluate the possible benefit of fluorescence cystoscopy (FC) in detecting cytologically 'confirmed' lesions when assessing urothelial carcinoma of the bladder, as negative white-light cystoscopy in cases of a positive cytological finding represents a diagnostic dilemma. PATIENTS AND METHODS: From January 1996 to December 2006, 348 patients, who had cystoscopy for surveillance or due to suspicion of urothelial carcinoma, presented with an entirely negative white-light cystoscopy at our hospital. However, 77 of the 348 patients (22.2%) were diagnosed with a positive cytological finding. All patients had white-light cystoscopy first and a bladder-wash cytological specimen was obtained, then FC, followed by cold-cup biopsies and/or transurethral resection of the bladder tumour. RESULTS: In the 77 patients with a positive cytological specimen FC enabled the detection of the precise site of malignancy within the bladder in 63 (82%). As malignant or premalignant lesions, there were 18 moderate dysplasias, 27 carcinoma in situ (CIS), and 18 pTa-1/G1-3 tumours. Moreover using FC, malignant or premalignant lesions were detected in 43 of 271 patients (15.9%) who had a negative cytological specimen (15 moderate dysplasias, six CIS, 22 pTa-1/G1-3). CONCLUSION: This study shows that FC is beneficial in the detection of malignant and premalignant lesions, if there is negative white-light cystoscopy but positive urine cytology. The immediate identification of the exact site of a malignant lesion during FC enables the physician to diagnose and treat these patients more accurately and with no delay.

Does the current World Health Organization classification predict the outcome better in patients with noninvasive bladder cancer of early or regular onset?

OBJECTIVE: To compare the clinical outcome and prognostic power of the former and current World Health Organization (WHO) grading system in patients with early vs regular onset of noninvasive urothelial bladder cancer (UBC), as little is known of the natural history of early onset UBC and in how far it is reflected by histopathological grading and staging in guiding clinical decisions. PATIENTS AND METHODS: The medical records of 69 consecutive patients presenting with initial UBC of early onset (>or=45 years old, EO) and of 100 randomly chosen patients with regular onset (RO) were reviewed. There were no significant differences in gender distribution, risk factors or tumour stage. All histopathological specimens were re-staged and re-graded according to the former and current WHO grading. RESULTS: In all, 51 EO and 63 RO patients with tumours staged pTa and complete follow-up information were analysed. Recurrence-free survival (RFS) was prolonged in patients with EO. In EO neither the former nor the current WHO grading system was significantly related to RFS or to progression to muscle-invasive disease. In RO, while both WHO grading systems were significantly related to RFS, only the current WHO grading system was related to progression. CONCLUSION: While larger studies are needed, UBC in patients with EO and RO do not seem to differ in risk factors and oncological outcome. The current WHO classification reflects the outcome more accurately than the former classification in patients with RO. However, for EO no grading system has sufficient prognostic power and novel methods, i.e. molecular markers, need to be evaluated for clinical use.

Non-muscle-invasive bladder cancer: a vision for the future.

The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden on healthcare resources and on patients' quality of life. Deeper understanding of the molecular basis of the disease and developments in optics, lasers and computer science are already offering opportunities to revolutionize care and improve long-term prognosis. This article discusses developments likely to cause a paradigm shift towards the delivery of personalized care and reduced burden of disease in NMIBC.

Gene expression profiling of progressive papillary noninvasive carcinomas of the urinary bladder.

PURPOSE: The aim of the present study was to define gene expression profiles of noninvasive and invasive bladder cancer, to identify potential therapeutic or screening targets in bladder cancer, and to define genetic changes relevant for tumor progression of recurrent papillary bladder cancer (pTa). EXPERIMENTAL DESIGN: Overall, 67 bladder neoplasms (46 pTa, 3 pTis, 10 pT1, and 8 pT2) and eight normal bladder specimens were investigated by a combination of laser microdissection and gene expression profiling. Eight of 16 patients with recurrent noninvasive papillary bladder tumors developed carcinoma in situ (pTis) or invasive bladder cancer (> or = pT1G2) in the course of time. RNA expression results of the putative progression marker cathepsin E (CTSE) were confirmed by immunohistochemistry using high-throughput tissue microarray analysis (n = 776). Univariate analysis of factors regarding overall survival, progression-free survival, and recurrence-free survival in patients with urothelial bladder cancer was done. RESULTS: Hierarchical cluster analyses revealed no differences between pTaG1 and pTaG2 tumors. However, distinct groups of invasive cancers with different gene expression profiles in papillary and solid tumors were found. Progression-associated gene profiles could be defined (e.g., FABP4 and CTSE) and were already present in the preceding noninvasive papillary tumors. CTSE expression (P = 0.003) and a high Ki-67 labeling index of at least 5% (P = 0.01) were the only factors that correlated significantly with progression-free survival of pTa tumors in our gene expression approach. CONCLUSIONS: Gene expression profiling revealed novel genes with potential clinical utility to select patients that are more likely to develop aggressive disease.

Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder.

To define the genetic changes of flat urothelial lesions, carcinoma in situ (CIS) and moderate dysplasias (DII) were investigated for alterations in the two chromosomal regions most frequently involved in bladder cancer. Overall, 33 CIS and 16 DII from 21 patients were used to microdissect urothelium. Dual color fluorescence in situ hybridization (FISH) using gene locus probes of 9q22 (FACC), 9p21 (CDK), 17p13 (p53), and related centromeric probes was applied on interphase nuclei. In parallel, preamplified DNA of these samples was used for loss of heterozygosity (LOH) analyses with eight microsatellite markers on chromosomes 9p, 9q and 17p, and for sequencing of exons 5-9 of p53. Data indicated nearly identical deletion frequencies for chromosomes 9 and 17 for CIS (chromosome 9, 86%; p53, 84%). DII showed a lower deletion rate in comparison with CIS (chromosome 9, 75%; p53, 53%). A very high correlation between the results of FISH and LOH analyses was found. p53 mutations were detected in 12 of 15 patients (CIS, 72%; DII, 67%). In three of 16 patients with multifocal tumors, oligoclonal lesions were identified by LOH analyses, a finding further supported by sequencing of p53, by which two different p53 deletions were detected in two cases. In conclusion, data from microdissected flat urothelial lesions indicate that chromosome 9 deletions cannot be regarded as indicators of papillary growth, because they are found frequently in both types of flat lesions of the urothelium: those associated with papillary tumors and those that are not. The similar distribution and lower amount of genetic changes in DII render DII a possible precursor lesion of CIS.

No evidence for involvement of beta-catenin and APC in urothelial carcinomas.

The wnt pathway plays an important role in embryonal patterning and cell fate determination, involving stabilization of nuclear and cytoplasmic beta-catenin (CTNNB1) mediated by APC, axin, and other proteins. Uncomplexed beta-catenin binds to TCF/LEF transcription factors and activates the expression of growth regulatory target genes such as c-myc or cyclin D1. In colorectal and other cancers, constitutive wnt signaling results frequently from mutations in one or more pathway components, e.g. APC and beta-catenin, resulting in nuclear and/or cytoplasmic accumulation of beta-catenin. In the present study, the most frequent alterations in the CTNNB1 and APC genes were investigated in primary urothelial bladder tumors and cell lines. Snap-frozen bladder tumors (n=99) of different stages and grades and 4 cell lines (RT4, RT112, J82, UROtsa) were investigated for APC allelic deletions by loss of heterozygosity (LOH) analysis. The most frequent mutated regions of CTNNB1 (degradation box in the third exon) and APC (mutation cluster region) were directly sequenced. Beta-catenin expression was analyzed by immunofluorescence in the cell lines. LOH at the APC gene locus on chromosome 5q21 was found in 7 of 72 (10%) of the informative cases. No mutations were found in either CTNNB1 or APC. A previously described polymorphism at codon 1493 of the APC gene was detected in 8 tumors and 3 cell lines. All cell lines showed normal membranous beta-catenin staining without evidence for nuclear or cytoplasmic accumulation. Alteration of APC and beta-catenin, which are the most frequent wnt pathway alterations in many tumor types, are rare events in urothelial carcinomas. Other wnt pathway members, such as axin, may play an important role in urothelial carcinogenesis.

Fluorescence in situ hybridization detects frequent chromosome 9 deletions and aneuploidy in histologically normal urothelium of bladder cancer patients.

Investigation of early urothelial lesions is essential to gain insight into the development of bladder cancer. In order to evaluate if deletions of chromosome arms 9p and 9q are preceding histomorphological changes in the urothelium, histologically normal urothelial samples of patients with previous and/or simultaneous (pre)malignant urothelial lesions were investigated. Dual colour fluorescence in situ hybridization (FISH) was performed on 96 histologically inconspicuous urothelial biopsies from 41 patients. Centromeric probes for chromosomes 9 and 17 were combined with gene locus specific probes for 9p21 (p16/CDKI2), 9q22 (FACC) and 17p (p53). Deletions of chromosome 9 (defined as presence of only one copy of centromere 9 or fewer gene-specific than centromeric signals in at least 40% of evaluated cells) were found in 21% of the samples (18/87). Deletions of chromosome 9p were present in 16% of cases (14/89), whereas deletions of chromosome 9q were encountered in 10% of specimens (9/93). A hemizygous deletion of p53 was found only once. Polysomy in more than 10% of cells was encountered in 16% of cases for both chromosome 9 and chromosome 17. Non-diploidy (defined as polysomy of both chromosomes) was found in 6% of samples (5/80). In summary, chromosome 9 deletions are frequently found in histologically normal urothelium of patients with bladder cancer, although less frequently than in hyperplasias and dysplasias. These findings support the hypothesis of multi-focal development of bladder cancer from histologically inconspicuous but already genetically altered urothelium. FISH analysis of chromosome 9 regions could provide a useful tool to detect potentially premalignant lesions in the follow-up care of patients with bladder cancer.

Interstitial laser coagulation combined with minimal transurethral resection of the prostate for the treatment of benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) represents the gold standard in the surgical treatment of benign prostatic hyperplasia (BPH). However, this method still has significant morbidity mainly associated with irrigation fluid absorption and blood loss. PATIENTS AND METHODS: A combination of interstitial laser coagulation (ILC) with limited TURP was established to reduce specific risks of transurethral resection and was applied in 41 patients with bladder outlet obstruction caused by BPH. In these patients, a subtotal resection of the prostate was not possible because of anesthesiologic risk factors. After insertion of a suprapubic catheter, ILC was performed under visual control using an Nd:YAG laser followed by resection of the bladder neck or the median lobe. Isotonic carbohydrate solution with 1% ethanol was used for irrigation, and irrigation fluid uptake was quantified by measurements of the ethanol concentration in the patients' exhaled breath. Additional measures such as blood loss, need for blood transfusions, and operative time were evaluated. RESULTS: The operations were performed without major complications with a mean operative time of 35 +/- 11 minutes for the entire procedure. An irrigation fluid uptake of 9 +/- 32 mL and no TUR syndrome were observed. The mean blood loss was minimal with a change in the hemoglobin of -1.3 +/- 1.1 g/dL and no need for blood transfusions. CONCLUSION: These results demonstrate that ILC with subsequent minimal TURP is an applicable method in the surgical treatment of BPH with reduction of blood loss and of the risk of TUR syndrome. This procedure may help to reduce the morbidity of TURP, especially in high-risk patients.

Safety of hexaminolevulinate for blue light cystoscopy in bladder cancer. A combined analysis of the trials used for registration and postmarketing data.

OBJECTIVE: To detail and put into perspective, safety of hexaminolevulinate blue light cystoscopy (HAL-BLC), including repeated use, based on combined data of controlled trials used for registration of HAL and postmarketing experience. METHODS: Safety data of 2 randomized comparative studies (group 1) and 4 within patient control studies (group 2) were combined. Postmarketing data from >200,000 patients were analyzed. RESULTS: In group 1, 533 patients were examined with HAL-BLC and 499 with white light (WL) cystoscopy. In group 2, 791 patients were examined with both WL and HAL-BLC. Between 73% and 93% of these patients had concomitant diseases. Between 41% and 58% of the patients had at least 1 adverse event (AE), although predominantly mild to moderate. The majority was considered as not related to HAL-BLC and reported in the urinary tract. No serious adverse events (SAEs) were considered definitely related to HAL-BLC, but in 6 patients serious AEs were of an uncertain relationship. Four possibly related hypersensitivity reactions have been reported. Repeated use did not reveal additional toxicity, also supported by data from 3 European centers. CONCLUSION: This combined and detailed analysis of patients from 6 HAL-BLC studies with very comparable criteria shows that HAL-BLC is safe and poses very little additional risks other than expected for WL cystoscopy for bladder tumor resection in this specific patient population. This is supported by 9 years of postmarketing experience. Repeated use also seems safe.

Clinical and cost effectiveness of hexaminolevulinate-guided blue-light cystoscopy: evidence review and updated expert recommendations.

CONTEXT: Non-muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence risk, partly because of the persistence of lesions following transurethral resection of bladder tumour (TURBT) due to the presence of multiple lesions and the difficulty in identifying the exact extent and location of tumours using standard white-light cystoscopy (WLC). Hexaminolevulinate (HAL) is an optical-imaging agent used with blue-light cystoscopy (BLC) in NMIBC diagnosis. Increasing evidence from long-term follow-up confirms the benefits of BLC over WLC in terms of increased detection and reduced recurrence rates. OBJECTIVE: To provide updated expert guidance on the optimal use of HAL-guided cystoscopy in clinical practice to improve management of patients with NMIBC, based on a review of the most recent data on clinical and cost effectiveness and expert input. EVIDENCE ACQUISITION: PubMed and conference searches, supplemented by personal experience. EVIDENCE SYNTHESIS: Based on published data, it is recommended that BLC be used for all patients at initial TURBT to increase lesion detection and improve resection quality, thereby reducing recurrence and improving outcomes for patients. BLC is particularly useful in patients with abnormal urine cytology but no evidence of lesions on WLC, as it can detect carcinoma in situ that is difficult to visualise on WLC. In addition, personal experience of the authors indicates that HAL-guided BLC can be used as part of routine inpatient cystoscopic assessment following initial TURBT to confirm the efficacy of treatment and to identify any previously missed or recurrent tumours. Health economic modelling indicates that the use of HAL to assist primary TURBT is no more expensive than WLC alone and will result in improved quality-adjusted life-years and reduced costs over time. CONCLUSIONS: HAL-guided BLC is a clinically effective and cost-effective tool for improving NMIBC detection and management, thereby reducing the burden of disease for patients and the health care system. PATIENT SUMMARY: Blue-light cystoscopy (BLC) helps the urologist identify bladder tumours that may be difficult to see using standard white-light cystoscopy (WLC). As a result, the amount of tumour that is surgically removed is increased, and the risk of tumour recurrence is reduced. Although use of BLC means that the initial operation costs more than it would if only WLC were used, over time the total costs of managing bladder cancer are reduced because patients do not need as many additional operations for recurrent tumours.

Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature.

CONTEXT: Controversy exists regarding the therapeutic benefit and cost effectiveness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinate (HAL) in addition to white-light cystoscopy (WLC) in the management of non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment. EVIDENCE ACQUISITION: We performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in October 2012 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forty-four publications were selected for inclusion in this analysis. EVIDENCE SYNTHESIS: Included reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies) as photosensitising agents. PDD increased the detection of both papillary tumours (by 7-29%) and flat carcinoma in situ (CIS; by 25-30%) and reduced the rate of residual tumours after transurethral resection of bladder tumour (TURBT; by an average of 20%) compared to WLC alone. Superior recurrence-free survival (RFS) rates and prolonged RFS intervals were reported for PDD, compared to WLC in most studies. PDD did not appear to reduce disease progression. Our findings are limited by tumour heterogeneity and a lack of NMIBC risk stratification in many reports or adjustment for intravesical therapy use in most studies. Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied for HAL. CONCLUSIONS: Moderately strong evidence exists that PDD improves tumour detection and reduces residual disease after TURBT compared with WLC. This has been shown to improve RFS but not progression to more advanced disease. Further work to evaluate cost effectiveness of PDD is required.

Photodynamic therapy of bladder cancer - a phase I study using hexaminolevulinate (HAL).

OBJECTIVES: To assess the safety and feasibility of hexaminolevulinate (HAL) based photodynamic therapy (PDT) as adjuvant treatment after transurethral resection of the bladder (TURB) in patients with intermediate or high-risk urothelial cell carcinoma (UCC) of the bladder. MATERIALS AND METHODS: Seventeen patients received 50 ml of either a 16 mM (4 patients) or 8 mM HAL (13 patients) solution instilled intravesically. Bladder wall irradiation was performed using an incoherent white light source coupled via a quartz fiber assembled into a flexible transurethral irrigation catheter. Each patient received 3 treatments with HAL-PDT 6 weeks apart. After PDT, patients were followed by regular cystoscopy for up to 21 months to assess time to recurrence. Reported adverse events (AEs) were coded according the World Health Organization Adverse Reaction Terminology (WHO-ART). Efficacy was assessed by cystoscopy, cytology, and histology, and was defined as the number of patients who were tumor-free at 6 or 21 months after initial PDT treatment. Transient bladder irritability was reported by 15 of the 17 patients and resolved completely in all patients. No evidence of a cumulative effect of treatment on the incidence of AEs could be detected. PDT treatment was performed without any technical complications. Furthermore preliminary assessment of efficacy showed that of the 17 patients included, 9 (52.9%; 95% CI: 27.8-77.0) were tumor-free at 6 months, 4 (23.5%; 95% CI: 6.8-49.9) were tumor-free at 9 months, and 2 (11.8%, 95% CI: 1.5-36.4) were tumor-free after 21 months. CONCLUSIONS: PDT using hexaminolevulinate and an incoherent white light system with the special flexible irradiation catheter system is technically feasible and safe and may offer an alternative in the treatment of non-muscle-invasive intermediate and high-risk bladder cancer.

The impact of bladder neck mucosal eversion during open radical prostatectomy on bladder neck stricture and urinary extravasation.

PURPOSE: To determine whether the bladder neck mucosal eversion (BNM-eversion) during radical retropubic prostatectomy (RRP) reduces the risk of bladder neck stricture (BNS) and of peri-anastomotic extravasation (PAE) in postoperative cystography. METHODS: Two hundred and eleven patients with clinically localized prostate cancer underwent RRP and were prospectively randomized into patients with BNM-eversion (group I) and without BNM-eversion (group II). All patients underwent an evaluation of PAE by retrograde cystography on postoperative day 8. We assessed BNS after 6 months. RESULTS: Ninety-two patients with and 113 patients without BNM-eversion were included. There was no significant difference in baseline characteristics, including age, TNM-classification, Gleason score, PSA, prostate volume, and blood loss in both groups. A complete follow-up of 6 months for BNS was available for 188 patients (89.1 %). Sixteen BNS out of 188 patients were recorded, 4.7 % (n = 4) in group I and 11.7 % (n = 12) in group II (p = 0.09). Data from 205 out of 211 patients were available for the evaluation of the extravasation by cystography. Peri-anastomotic extravasation was detectable in 11.96 %, (11/205) in group I and in 21.24 % (24/205) in group II (p = 0.08). CONCLUSION: BNM-eversion does not have a positive influence on the prevention of bladder neck strictures. Peri-anastomotic extravasation detected by cystography does not correlate with a formation of bladder neck stricture.