5-aminolevulinic-acid-hexyl-ester and Urinary-Bladder-Neoplasms

We systematically reviewed the effectiveness of hexaminolevulinic acid (HAL) after traditional light cystoscopy vs. only white light cystoscopy (WLC) on nonmuscle-invasive bladder cancer (NMIBC) clinical outcomes.. Systematic literature searches of PubMed, Embase, Web of Science, and the Cochrane database and reference lists were performed. A total of 12 randomized controlled trials (RCTs) of HAL fluorescent cystoscopy (FC) and WLC vs. white light cystoscopy alone for the diagnosis of initial or recurrent bladder cancer that reported bladder cancer recurrence, progression, recurrence-free survival (RFS), and other effects were selected for review.. Our results included 2,775 patients identified for analysis and showed that the HAL group had a lower recurrence rate than the white light cystoscopy group with a statistically significant difference (RR=0.77, 95% CI 0.69-0.85. P < 0.05), and this advantage still existed for patients receiving intravesical chemotherapy. There was also a statistically significant difference in favour of fluorescent cystoscopy in recurrence-free survival and progression rate (HR=0.79, 95% CI 0.67-0.92. P < 0.05, RR = 0.63, 95% CI 0.43-0.94. P < 0.05, respectively). The time to first recurrence was not significantly different from that in the WLC group (SMD=0.73, 95% CI, -0.39-1.85. P = 0.2). And the HAL group did not have a significantly reduced residual tumor rate (RR=0.59, 95% CI 0.23-1.51. P = 0.27).. Fluorescent cystoscopy was associated with a reduced risk of bladder cancer recurrence and reduced progression rate; it also has advantages for RFS. However, there was no significant difference in the rate of residual tumor and the time of first recurrence. More studies are needed to better understand the effects of the photosensitizer used on NMIBC patients.

Topics: Aminolevulinic Acid; Cystoscopy; Humans; Neoplasm Recurrence, Local; Neoplasm, Residual; Photochemotherapy; Photosensitizing Agents; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms

It has been firmly established that hexaminolevulinate-assisted blue light cystoscopy (HAL-BLC) reduces cancer recurrence rates. This review explores the impact of HAL-BLC on other meaningful outcomes in patients with bladder cancer, including disease progression, and earlier detection of disease at the time of surveillance cystoscopy.. A randomized clinical trial confirmed earlier implementation of HAL-BLC at the time of surveillance cystoscopy increased identification of cancerous lesions, including those of high grade, when compared with white light cystoscopy. In addition, the evidence is evolving that the use of HAL-BLC at the time of endoscopic treatment of high-risk tumors may lead to lower rates of progression to muscle invasion, and this in part may be due to better risk stratification leading to changes in treatment plan. The clinical contexts for the use of HAL-BLC are broader than prior knowledge. It is also becoming more clear that the positive impact of HAL-BLC is likely more than just reducing cancer recurrence rates, and patients would benefit from the technology at many time points in the management and follow-up of their disease.

Topics: Administration, Intravesical; Aminolevulinic Acid; Cystoscopy; Disease Progression; Humans; Light; Neoplasm Recurrence, Local; Neoplasm Staging; Photosensitizing Agents; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms

Blue light cystoscopy (BLC) with hexaminolevulinate (HAL) during transurethral resection of bladder cancer improves detection of non-muscle-invasive bladder cancer (NMIBC) and reduces recurrence rates. Flexible BLC was approved by the FDA in 2018 for use in the surveillance setting and was demonstrated to improve detection. Results of a phase III prospective multicentre study of blue light flexible cystoscopy (BLFC) in surveillance of intermediate-risk and high-risk NMIBC showed that 20.6% of malignancies were identified only by BLFC. Improved detection rates in the surveillance setting are anticipated to lead to improved clinical outcomes by reducing future recurrences and earlier identification of tumours that are unresponsive to therapy. Thus, BLFC has a role in surveillance cystoscopy, and determining which patients will benefit from BLFC and optimal and cost-effective ways of incorporating this technology into surveillance cystoscopy must be developed.

Topics: Aminolevulinic Acid; Consensus Development Conferences as Topic; Cystectomy; Cystoscopes; Cystoscopy; Equipment Design; Humans; Light; Neoplasm Invasiveness; Practice Guidelines as Topic; Surgery, Computer-Assisted; United States; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Carcinoma in Situ; Cystoscopy; Humans; Neoplasm Invasiveness; Photosensitizing Agents; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Urinary Bladder Neoplasms

Blue light cystoscopy improves the detection of bladder cancer at time of transurethral resection of bladder tumor for nonmuscle-invasive bladder cancer. This has translated to decreased tumor recurrence. Given this improvement in rigid cystoscopy, the question remains whether the use of blue light flexible cystoscopy (BLFC) in the surveillance setting provides the same benefits. This review aims to evaluate the recently reported Phase III prospective multicenter study of BLFC which evaluated the detection of bladder cancer during surveillance, which in its earliest reporting demonstrated improved detection of bladder cancer. This study evaluated 304 patients with findings of 63 confirmed malignancies, with 13 (20.6%) only identified by BLFC (p < 0.0001). The question still remains whether the improved detection rate will translate to improved clinical outcomes. Further, studies will be necessary to determine which patients will benefit from BLFC, optimal ways to incorporate into surveillance strategies and cost-effectiveness.

Topics: Aminolevulinic Acid; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Cystoscopes; Cystoscopy; Early Detection of Cancer; Humans; Light; Multicenter Studies as Topic; Urinary Bladder Neoplasms

White-light cystoscopy (WLC) is the diagnostic standard for the detection of bladder cancer (BC). However, the detection of small papillary and subtle flat carcinoma in situ lesions is not always possible with WLC. Several adjunctive optical imaging technologies have been developed to improve BC detection and resection. Photodynamic diagnosis, which requires the administering of a photoactive substance, has a higher detection rate than WLC for the detection of BC. Narrow-band imaging provides better visualization of tumors by contrast enhancement between normal mucosa and well-vascularized lesions. A technology called confocal laser endomicroscopy can be used to obtain detailed images of tissue structure. Optical coherence tomography is a high-resolution imaging process that enables noninvasive, real-time, and high-quality tissue images. Several other optical imaging technologies are also being developed to assist with the detection of BC. In this review, we provide an overview of the strengths and weaknesses of these imaging technologies for the detection of BC.

Topics: Aminolevulinic Acid; Cystoscopy; Humans; Microscopy, Confocal; Molecular Imaging; Photosensitizing Agents; Sensitivity and Specificity; Tomography, Optical Coherence; Urinary Bladder Neoplasms

This study included a network meta-analysis of evidence from randomized controlled trials (RCTs) to assess the therapeutic outcome of transurethral resection (TUR) in patients with non-muscle-invasive bladder cancer assisted by photodynamic diagnosis (PDD) employing 5-aminolaevulinic acid (5-ALA) or hexylaminolevulinate (HAL) or by narrow band imaging (NBI).. Relevant RCTs were identified from electronic databases. The proceedings of relevant congresses were also searched. Fifteen articles based on RCTs were included in the analysis, and the comparisons were made by qualitative and quantitative syntheses using pairwise and network meta-analyses.. Seven of 15 RCTs were at moderate risk of bias for all quality criteria and two studies were classified as having a high risk of bias. The recurrence rate of cancers resected with 5-ALA-based PDD was lower than of those resected using HAL-based PDD (odds ratio (OR) = 0.48, 95 % confidence interval (CI) [0.26-0.95]) but was not significantly different than those resected with NBI (OR = 0.53, 95 % CI [0.26-1.09]). The recurrence rate of cancers resected using HAL-based PDD versus NBI did not significantly differ (OR = 1.11, 95 % CI [0.55-2.1]). All cancers resected using 5-ALA-based PDD, HAL-based PDD, or NBI recurred at a lower rate than those resected using white light cystoscopy (WLC). No difference in progression rate was observed between cancers resected by all methods investigated.. The recurrence rate of some bladder cancers can be decreased by the implementation of either PDD- and NBI-assisted TUR; in real settings, clinicians should consider replacing WLC as the standard imaging technology to guide TUR.

Topics: Aminolevulinic Acid; Cystoscopy; Humans; Image Interpretation, Computer-Assisted; Narrow Band Imaging; Photosensitizing Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Bladder Neoplasms

Hexaminolevulinate (HAL) is an ester derivative of 5-aminolevulinate, and is used in conjunction with blue light (fluorescence) cystoscopy (BLC) to detect bladder cancer. In various studies, HAL-BLC was generally a better detection method than the gold standard method of white light cystoscopy (WLC), as assessed by endpoints including additional lesions (at both the lesion and patient levels) not detected by WLC, higher detection rates, and more complete treatment decisions as a result of improved detection. HAL-BLC in addition to WLC was associated with reduced tumor recurrence rates compared with WLC alone in randomized trials with up to 2 years' follow-up. HAL-BLC was generally well tolerated, and the most common adverse events (i.e. hematuria, dysuria, and bladder spasm) were also the most common adverse events in the WLC alone group, and were expected as a result of the resection procedure. Although its impact on disease progression and survival rates is not yet known, HAL-BLC is a valuable addition to WLC for the diagnosis of bladder cancer in patients who are suitable candidates for its use.

Topics: Aminolevulinic Acid; Clinical Trials as Topic; Cystoscopy; Humans; Meta-Analysis as Topic; Microscopy, Fluorescence; Neoplasm Recurrence, Local; Photosensitizing Agents; Treatment Outcome; Urinary Bladder Neoplasms

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.. 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.. PubMed and conference searches, supplemented by personal experience.. 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.. 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.. 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.

Topics: Aminolevulinic Acid; Cost-Benefit Analysis; Cystectomy; Cystoscopy; Disease Progression; Disease-Free Survival; Health Care Costs; Humans; Models, Economic; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm, Residual; Predictive Value of Tests; Quality of Life; Quality-Adjusted Life Years; Time Factors; Treatment Outcome; Urinary Bladder Neoplasms

Hexaminolevulinate (HAL) is a tumour photosensitizer that is used in combination with blue-light cystoscopy (BLC) as an adjunct to white-light cystoscopy (WLC) in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC). Since being licensed in Europe in 2005, HAL has been used in >200,000 procedures, with consistent evidence that it improves detection compared with WLC alone. Current data support an additional role in the reduction of recurrence of NMIBC. Since the approval of HAL by the FDA in 2010, experience of HAL-BLC in the USA continues to expand. To define areas of need and to identify the benefits of HAL-BLC in clinical practice, a focus group of expert urologists specializing in the management of patients with bladder cancer convened to review the clinical evidence, share their experiences and reach a consensus regarding the optimal use of HAL-BLC in the USA. The focus group concluded that HAL-BLC should be considered for initial assessment of NMIBC, surveillance for recurrent tumours, diagnosis in patients with positive urine cytology but negative WLC findings, and for tumour staging.

Topics: Aminolevulinic Acid; Carcinoma, Transitional Cell; Consensus; Cystoscopy; Humans; Neoplasm Invasiveness; Photosensitizing Agents; Practice Guidelines as Topic; United States; Urinary Bladder; Urinary Bladder Neoplasms

Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence.. To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence.. This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC).. A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy.. We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection.. BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used.. This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.

Topics: Aminolevulinic Acid; Carcinoma in Situ; Cystoscopy; Humans; Kaplan-Meier Estimate; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Predictive Value of Tests; Risk Factors; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms

Bladder cancer is the most common tumor of the urinary tract, with a worldwide incidence of 8.6 x 100000 in men and 2.6 x 100000 in women (1). The majority of patients (75-85%) present as non-muscle invasive bladder cancer (NMIBC); within this category the most represented stage is Ta (70%), followed by T1 (20%) and, less frequently, carcinoma in situ (CIS) (10%) (2). The diagnosis of NMIBC and, more generally, of bladder cancer, depends on urine cytology and endoscopic examination with histological evaluation of the resected tissue. Clearly, an optimal cystoscopy with accurate transurethral resection (TUR) is of great importance in order to improve the detection rate and to reduce the probability of recurrence and progression. Today the cystoscopy is routinely performed with the white light technique (WLC), the same of about 80 years ago (3). Several studies have demonstrated that an initial TUR with WLC can miss small papillary lesions and, particularly, flat lesions such as CIS. Moreover, recurrence rates of non-muscle invasive bladder cancer (NMIBC) are directly related to the possibility of achieving a complete resection: residual cancer is present in a large percentage of re-TUR, showing a not so good performance of resection with this method. For these reasons new methodologies have been investigated in order to improve the sensitivity and specificity of WLC, such as photodynamic diagnosis (PDD), narrow band imaging (NBI), optical coherence tomography (OCT) and CT virtual cystoscopy. Some of them have been well established and supported by consistent literature while others are still to be viewed as experimental. The purpose of this review is to investigate the state of the art of these new techniques.

Topics: Aminolevulinic Acid; Carcinoma in Situ; Carcinoma, Transitional Cell; Cystoscopy; False Negative Reactions; Female; Forecasting; Humans; Light; Male; Multimodal Imaging; Neoplasm Recurrence, Local; Photosensitizing Agents; Protoporphyrins; Sensitivity and Specificity; Tomography, Optical Coherence; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

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).. To systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment.. 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.. 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.. 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.

Topics: Aminolevulinic Acid; Cost-Benefit Analysis; Cystectomy; Cystoscopy; Disease-Free Survival; Health Care Costs; Humans; Neoplasm Invasiveness; Neoplasm, Residual; Photosensitizing Agents; Predictive Value of Tests; Risk Factors; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms

To describe drugs used in bladder carcinoma.. Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies web sites (HAS and ANSM).. The drugs used in the treatment of bladder cancer are represented by the products referred to diagnosis (hexyl aminolevulinate), the intravesical instillations for the treatment of tumors not infiltrating the muscle and the infiltrating tumor chemotherapy (neo-adjuvant treatment or metastatic tumors). The hexyl aminolevulinate cystoscopy allows to identify a significantly greater number of lesions, including carcinoma in situ, compared to conventional white light cystoscopy. For intravesical instillations, BCG has a superior efficacy to mitomycin C with a lower tolerance. The chemotherapies for invasive tumors are effective in metastatic disease in 15-20% of cases with a mean survival of 12 to 14 months.. Except the use of hexyl aminolevulinate for improving the diagnosis, there was no emergence in recent years of new drugs for the treatment of bladder cancer. Targeted therapies currently available for many neoplasms were ineffective for bladder cancer.

Topics: Aminolevulinic Acid; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Carcinoma; Cisplatin; Cystoscopy; Deoxycytidine; Doxorubicin; Fluorescence; Gemcitabine; Humans; Methotrexate; Mitomycin; Photosensitizing Agents; Urinary Bladder Neoplasms; Vinblastine

The question whether conventional cystoscopy should always be performed together with fluorescent diagnostic procedures remains to be answered. The current article presents the current literature dealing with this topic. Particularly for relevant carcinoma in situ lesions of the bladder there is no obvious advantage for photodynamic diagnostics compared to conventional cystoscopy with consistent use of urine cytology.

Topics: Aminolevulinic Acid; Carcinoma in Situ; Carcinoma, Transitional Cell; Cystoscopy; Fluorescence; Humans; Neoplasm Grading; Photosensitizing Agents; Predictive Value of Tests; Urinary Bladder Neoplasms

The clinical benefit of photodynamic diagnosis (PDD) with 5-aminolevulinic acid or hexaminolevulinate in addition to white-light cystoscopy (WLC) in bladder cancer has been discussed controversially.. To assess in a systematic review the effect of PDD in addition to WLC on (1) the diagnosis and (2) the therapeutic outcome of primary or recurrent non-muscle-invasive bladder cancer investigated by cystoscopy or transurethral resection.. An electronic database search of Medline, Embase, the Cochrane Library, and CancerLit was undertaken, plus hand searching of relevant congress abstracts and urologic journals. Trials were included if they prospectively compared WLC with PDD in bladder cancer. The review process followed the guidelines of the Cochrane Collaboration. Two reviewers evaluated independently both trial eligibility and methodological quality and data extraction.. The primary end point of diagnostic accuracy was additional detection rate. The primary end points of therapeutic outcome were residual tumour at second resection and recurrence-free survival (RFS). Seventeen trials were identified. Twelve diagnostic trials used WLC and PDD with the same patients. Seven reported results for the subgroup of patients with carcinoma in situ (CIS). Five randomised trials studied therapeutic outcome. The results were combined in random effects meta-analyses if end points, designs, and populations were comparable. Twenty percent (95% confidence interval [CI], 8-35) more tumour-positive patients were detected with PDD in all patients with non-muscle-invasive tumours and 39% (CI, 23-57) more when only CIS was analysed. Heterogeneity was present among diagnostic studies even when the subgroup of patients with CIS was investigated. Residual tumour was significantly less often found after PDD (odds ratio: 0.28; 95% CI, 0.15-0.52; p<0.0001). RFS was higher at 12 and 24 mo in the PDD groups than in the WLC-only groups. The combined p value of log-rank tests of RFS was statistically significant (0.00002).. PDD detects more bladder tumour-positive patients, especially more with CIS, than WLC. More patients have a complete resection and a longer RFS when diagnosed with PDD.

Topics: Aminolevulinic Acid; Cystectomy; Cystoscopy; Disease-Free Survival; Evidence-Based Medicine; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm, Residual; Predictive Value of Tests; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Cystoscopy; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Photosensitizing Agents; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms

Compared with standard white-light cystoscopy, photodynamic diagnosis with blue light and the photosensitiser hexaminolevulinate has been shown to improve the visualisation of bladder tumours, reduce residual tumour rates by at least 20%, and improve recurrence-free survival. There is currently no overall European consensus outlining specifically where hexaminolevulinate is or is not indicated.. Our aim was to define specific indications for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC).. A European expert panel was convened to review the evidence for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of NMIBC (identified through a PubMed MESH search) and available guidelines from across Europe. On the basis of this information and drawing on the extensive clinical experience of the panel, specific indications for the technique were then identified through discussion.. The panel recommends that hexaminolevulinate-guided fluorescence cystoscopy be used to aid diagnosis at initial transurethral resection following suspicion of bladder cancer and in patients with positive urine cytology but negative white-light cystoscopy for the assessment of tumour recurrences in patients not previously assessed with hexaminolevulinate, in the initial follow-up of patients with carcinoma in situ (CIS) or multifocal tumours, and as a teaching tool. The panel does not currently recommend the use of hexaminolevulinate-guided fluorescence cystoscopy in patients for whom cystectomy is indicated or for use in the outpatient setting with flexible cystoscopy.. Evidence is available to support the use of hexaminolevulinate-guided fluorescence cystoscopy in a range of indications, as endorsed by an expert panel.

Topics: Aminolevulinic Acid; Cystectomy; Cystoscopy; Disease-Free Survival; Evidence-Based Medicine; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm, Residual; Patient Selection; Predictive Value of Tests; Time Factors; Treatment Outcome; Urinary Bladder Neoplasms

Heterogeneous results of single studies with photodynamic diagnosis (PDD) in bladder cancer have been reported. A metaanalysis of prospective studies has now been performed.. The effect of PDD in addition to WLC on a) the diagnosis and b) the therapeutic outcome of primary or recurrent non-muscle invasive bladder cancer (NMIBC) investigated by cystoscopy or transurethral resection was analysed. An electronic database search was performed. Trials were included if they prospectively compared WLC with PDD in bladder cancer. Primary endpoints were additional detection rate, residual tumour at second resection and recurrence-free survival.. Significantly more tumour-positive patients were detected with PDD in all patients with non-muscle invasive tumours (= 20 %) [95 % confidence interval (CI): 8 to 35 %] and in CIS patients (= 39 %) (CI: 23 to 57 %). Residual tumour was significantly less often found after PDD (odds ratio 0.28, CI: 0.15 to 0.52, p < 0.0001). Recurrence-free survival was significantly higher at 12 and 24 months in the PDD groups than in WLC only groups.. More bladder tumour-positive patients are detected by PDD. Best results were found in CIS patients. Diagnosis with PDD results in a more complete resection and a longer recurrence-free survival.

Topics: Aminolevulinic Acid; Cystoscopy; Disease-Free Survival; Fluorescence; Humans; Neoplasm Invasiveness; Photosensitizing Agents; Prospective Studies; Sensitivity and Specificity; Urinary Bladder; Urinary Bladder Neoplasms

Although bladder cancer occurs frequently, early diagnosis and complete removal of malignant lesions usually lead to good clinical outcomes. In the USA, white light cystoscopy (WLC) is commonly used for bladder cancer diagnosis and guidance of the surgical resection. However, with WLC malignant and precancerous lesions may be missed, resulting in a high rate of disease recurrence. Monitoring for and treating these recurrences carry high direct and indirect costs. Because hexyl aminolevulinate (HAL; 5-ALA-hexylester) fluorescence cystoscopy has greater sensitivity than WLC, especially for detecting early stage lesions, and its use provides more complete resection and lower disease recurrence, it has been recommended in European clinical guidelines. This article reports our own HAL experiences and first time recurrence data, describes how HAL was developed, provides key clinical trial results, and discusses how HAL, which has revolutionized fluorescence cystoscopy and bladder cancer care in Europe, may ultimately revolutionize bladder cancer care in the USA.

Topics: Aminolevulinic Acid; Clinical Trials as Topic; Cystoscopy; Fluorescent Dyes; Humans; Neoplasm Recurrence, Local; Practice Guidelines as Topic; Sensitivity and Specificity; Urinary Bladder Neoplasms

Non-muscle invasive bladder cancer is one of the most prevalent and incident neoplastic conditions in the Western world. Its clinical management involves significant costs for health systems. Diagnosis and treatment are based on direct visualization of the disease and on detection of flat forms having no specific morphology and which are sometimes overlooked. Prognosis of NMIBC often depends on quality of transurethral resection and on early detection of undifferentiated flat forms. Cystoscopy using photosensitive substances such as 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinic acid (HAL) achieves overdetection rates of 29 % for bladder neogrowths and 59% for carcinoma in situ. This overdetection ability results in an increased disease-free survival and a longer time to the first relapse. Increased costs resulting from use of these resources are compensated by a lower number of or delayed performance of cystectomies, resections, and instrumentations. It is concluded that PDD should be universally used, rather than in high risk patients only.that has been shown in both animal studies and human tumors.

Topics: Aminolevulinic Acid; Carbon Radioisotopes; Diagnostic Techniques, Urological; Humans; Photosensitizing Agents; Urinary Bladder Neoplasms

Non-muscle invasive bladder cancer is the most expensive cancer to manage on a per patient basis due to the high recurrence rate, low mortality and the need for long term, often lifelong surveillance. Current white-light endoscopic surgery leads to a significant number of patients having "recurrent" cancer at their first follow-up cystoscopy. The introduction of a single dose of intravesical chemotherapy immediately after the initial resection has helped to reduce the recurrence rate but it can be toxic and should not be administered to patients with potential bladder perforations after transurethral resection of bladder tumour (TURBT). Photodynamic diagnosis cystoscopy has been shown to significantly improve the quality of the initial TURBT leading to a 20% reduction in tumour recurrences at 3 months. This benefit is sustained for at least 8 years, leading to a reduction in further invasive procedures and treatment. Despite the initial increased cost related to introducing a photodynamic diagnosis service there is clearly long-term significant cost savings to be made, as well as improving the patient experience and quality of life.

Topics: Aminolevulinic Acid; Carcinoma, Transitional Cell; Fluorescence; Humans; Neoplasm Invasiveness; Photochemotherapy; Urinary Bladder Neoplasms

In flat bladder cancer and carcinoma in situ, and in multifocal papillary cancer, some smaller lesions may be overlooked at cystoscopy. For 10 years fluorescence cystoscopy has been promoted to solve these problems without wider acceptance. New fluorophobes now promise better clinical applicability.. In prospective multicenter studies fluorescence cystoscopy shows significant improvement in the detection of flat bladder cancer and carcinoma in situ. It also permits more reliable identification of all neoplastic lesions with multifocal tumors, hence more precise removal and as a consequence lower recurrence rates.. New agents bring a significant benefit. Hexyl-aminolevulinate offers more rapid urothelial accumulation, better fluorescence contrast and less photobleaching than previously used fluorophobes. It is simple to use in everyday practice and has a favorable toxicity profile.

Topics: Aminolevulinic Acid; Anthracenes; Carcinoma in Situ; Cystoscopy; Fluorescence; Fluorescent Dyes; Humans; Perylene; Practice Guidelines as Topic; Predictive Value of Tests; Sensitivity and Specificity; Urinary Bladder Neoplasms

Non-muscle-invasive bladder cancer is labor intensive and costly to manage. Owing to long-term survival rates and life-long monitoring and treatment, it is the most expensive cancer to manage in per-patient terms. Significant costs are attributable to the treatment of recurrences and complications. Fluorescence-guided cystoscopy, using 5-aminolevulinic acid (ALA) or its hexyl ester, hexaminolevulinate 5-ALA (Hexvix [HAL], Photocure, Oslo, Norway), improves the detection of bladder tumors, particularly carcinoma in situ, compared with standard white-light cystoscopy. The quality of transurethral resection of the bladder tumor is also improved. It has been shown that improved tumor detection leads to better patient management and, in the case of ALA, reduced long-term recurrence rates and costs. Long-term studies in this area with HAL are ongoing. The technique is well tolerated and is a useful adjunct to white-light cystoscopy.

Topics: Aminolevulinic Acid; Carbon Radioisotopes; Cystoscopy; Fluorescent Dyes; Humans; Survival Rate; Urinary Bladder Neoplasms

Bladder cancer is a frequent disease and represents the second most common genitourinary neoplasm. Although many aspects of the management of not-muscle-infiltrating bladder cancer are now well established, significant challenges remain, which influence patient outcome. Early detection and treatment of recurrent disease is required to optimize bladder preservation, reduce patient morbidity and increase quality of life and survival. Fluorescence cystoscopy, often referred to as "photodynamic diagnosis" (PDD) with intravesical application of photosensitizing agents has been developed in order to enhance the early detection of bladder cancer. Since March 2005 the hexyl-ALA ester (Hexvix) has been approved for the diagnosis of bladder cancer in 27 EU/EEA countries through the European Mutual Recognition Procedure. There is growing evidence that PDD enhances the detection of bladder cancer, particularly of high-grade flat lesions. Furthermore, transurethral resection of bladder tumor under fluorescence guidance has been shown to reduce the risk of recurrent tumors. Nevertheless, a resulting relatively decreased number of recurrences have still to be verified in prospective randomized trials.

Topics: Aminolevulinic Acid; Biopsy; Carcinoma in Situ; Carcinoma, Transitional Cell; Cystoscopy; Fluorescence; Humans; Photosensitizing Agents; Predictive Value of Tests; Sensitivity and Specificity; Urinary Bladder; Urinary Bladder Neoplasms

Urology is a preferential domain of endoscopy and as such an important research field for photodynamic procedures. An important milestone in the long-lasting and successful history of "photodynamics" in urology is the European approval of hexaminolevulinate (HAL, Hexvix) for fluorescence cystoscopy. All clinical studies carried out so far have demonstrated a significant increase in sensitivity of fluorescence versus standard cystoscopy for the detection of bladder cancer, especially concerning carcinoma in situ. The majority of the randomised, two-armed studies additionally show significantly reduced rates of residual tumour and recurrences. Tumor-selective fluorescence can also be observed in the kidney and prostate. Intraoperative fluorescence detection might thus simplify the achievement of high rates of R0 resections. Apart from the diagnostic potential of "photodynamics", also some possible therapeutic indications will be mentioned, including photodynamic therapy of bladder cancer and prostate cancer. Whereas initial clinical experience has been obtained for photodynamic therapy of bladder cancer, clinical studies for other indications are currently being designed. By providing an overview over methods and procedures as well as hitherto the available clinical results, we hope to provide reader with a basis for obtaining his/her own judgement.

Topics: Aminolevulinic Acid; Carcinoma in Situ; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cystoscopy; Dermatitis, Phototoxic; Fluorescence; Follow-Up Studies; Humans; Male; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Pilot Projects; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Time Factors; Urinary Bladder Neoplasms

Hexyl aminolevulinate [aminolevulinic acid hexyl ester, hexyl 5-aminolevulinate, 5-ALA hexylester, hexaminolevulinate, Hexvix, Hexvix PD, Hexvix PDT, P 1206] is being developed by PhotoCure, a Norwegian company, for the diagnosis and treatment of bladder cancer. The current standard diagnosis of bladder cancer involves cystoscopic examination of urine and bladder washings and is combined with biopsy for better detection of low-grade malignancies. However, the method largely relies on the experience of the surgeon and often results in false negatives especially for low-grade malignancies and pre-cancerous tissues. Photocure believes that imaging with hexyl aminolevulinate (Hexvix) offers significant advantages over standard diagnostic methods for detection of bladder cancer and also can be used in combination with those to ensure the optimal diagnostic accuracy. PhotoCure's procedure for diagnosis of bladder cancer involves filling of the patient's bladder with hexyl aminolevulinate solution and allowing the active agent to accumulate in the cancerous tissue. Following bladder emptying, blue light illumination is applied to the bladder causing red fluorescence that is clearly visible, thus identifying the cancerous tissue. Imaging with hexyl aminolevulinate improves detection of bladder tumours and also can be used together with transurethral resection to check the completeness of tumour removal. PhotoCure is looking for the opportunity to out-license hexaminolevulinate for all regions except the Nordic regions. PhotoCure has proprietary rights for hexyl aminolevulinate from the Norwegian Radium Hospital. Under the terms of the agreement with the Norwegian Radium Hospital, PhotoCure gains an access to, and an option to acquire, all of the new photodynamic therapy technologies developed by the Norwegian Radium Hospital. For its part, PhotoCure provides research and development funding to the Norwegian Radium Hospital. This 3-year agreement was extended in February 2003 until December 2006. PhotoCure and Karl Storz GmbH of Germany have signed a formal collaboration for the development and marketing of hexyl aminolevulinate (Hexvix) and Karl Storz's D-light system. The two systems will be used in the diagnosis of bladder cancer. PhotoCure and Karl Storz GmbH will jointly apply for a marketing approval of hexyl aminolevulinate (Hexvix) and Karl Storz' D-light system in the US for detection of bladder cancer. The D-light system is already approved in Europe. Ph

Topics: Aminolevulinic Acid; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drugs, Investigational; Fluorescent Dyes; Humans; Urinary Bladder Neoplasms

Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix. Non-inferiority of Hexvix

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Antineoplastic Agents; Carcinoma; Chemotherapy, Adjuvant; Cystectomy; Cystoscopy; Disease-Free Survival; Female; Humans; Male; Middle Aged; Mitomycin; Photochemotherapy; Photosensitizing Agents; Prospective Studies; Urinary Bladder Neoplasms

To examine whether photodynamic diagnosis (PDD) in addition to flexible cystoscopy in the outpatient clinic can reduce risk of tumor recurrence in patients with previous nonmuscle invasive bladder cancer. PDD is an optical technique that enhances the visibility of pathologic tissue and helps guidance tumor resection.. From February 2016 to December 2017, 699 patients from 3 urologic departments in Denmark were enrolled in a randomized controlled trial. Four months after transurethral resection of bladder tumor patients were randomized 1:1 to either an intervention group (hexaminolevulinate was instilled in the bladder before flexible cystoscopy with PDD video cystoscope) or a control group (white light flexible cystoscope), only. Primary endpoint was tumor recurrence within 8 months from the randomization. Secondary outcomes were numbers of procedures in general anesthesia, time to the first recurrence, differences in tumor size, risk of tumor progression, and identification of carcinoma in situ.. A total of 351 patients were allocated to the intervention group (flexible PDD), and 348 to the control group (flexible white light). Throughout the following 8 months after randomization, only 117 patients in the intervention group had at least 1 tumor recurrence compared to 143 patients in the control group (P = .049). Odds ratio of 0.67 (P = .02, 95% CI: 0.48-0.95) correlates with a tumor reduction of 33% in favor of the intervention group.. Use of PDD in a routine surveillance cystoscopy first time after transurethral resection of bladder tumor for nonmuscle invasive bladder cancer reduces subsequent risk of tumor recurrence compared to WL cystoscopy alone.

Topics: Aged; Aminolevulinic Acid; Carcinoma in Situ; Cystoscopy; Female; Humans; Image Enhancement; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Outcome Assessment, Health Care; Patient Selection; Photosensitizing Agents; Reproducibility of Results; Urinary Bladder; Urinary Bladder Neoplasms

To evaluate blue-light flexible cystoscopy (BLFC) with hexaminolevulinate in the office surveillance of patients with non-muscle-invasive bladder cancer with a high risk of recurrence by assessing its impact on pain, anxiety, subjective value of the test and patient willingness to pay.. A prospective, multicentre, phase III study was conducted during which the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, Pain and 'Was It Worth It' questionnaires were administered at baseline, after surveillance with BLFC and after resection for those referred to the operating room. Comparisons of scores were performed between groups.. A total of 304 patients were enrolled, of whom 103 were referred for surgical examination. Of these, 63 were found to have histologically confirmed malignancy. Pain levels were low throughout the study. Anxiety levels decreased after BLFC (∆ = -2.6), with a greater decrease among those with negative pathology results (P = 0.051). No differences in anxiety were noted based on gender, BLFC results, or test performance (true-positive/false-positive). Most patients found BLFC 'worthwhile' (94%), would 'do it again' (94%) and 'would recommend it to others' (91%), with no differences based on BLFC results or test performance. Most patients undergoing BLFC (76%) were willing to pay out of pocket.. Anxiety decreased after BLFC in patients with negative pathology, including patients with false-positive results. Most of the patients undergoing BLFC were willing to pay out of pocket, found the procedure worthwhile and would recommend it to others, irrespective of whether they had a positive BLFC result or whether this was false-positive after surgery.

Topics: Aged; Aminolevulinic Acid; Anxiety; Color; Cystoscopy; False Positive Reactions; Female; Fluorescent Dyes; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Pain, Procedural; Patient Acceptance of Health Care; Patient Reported Outcome Measures; Population Surveillance; Prospective Studies; Quality of Life; Urinary Bladder Neoplasms

We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance.. Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false-positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy.. Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5-32.7) recurrence was seen only with blue light flexible cystoscopy (p <0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2-55.7, p <0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false-positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious.. Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Photosensitizing Agents; Prospective Studies; Urinary Bladder Neoplasms

Bladder cancer (BC) currently accounts for 5% of all malignancies and the most common tumor of the urinary tract. Diagnosis of bladder cancer is based on urine cytology and white-light cystoscopy (WLC) performed for patients with suspected bladder mass and÷or hematuria. Recent studies suggest that using the fluorescence photodynamic diagnosis (PDD) significantly improves diagnostic sensitivity with a positive influence upon the recurrence rate of bladder cancer.. To evaluate the diagnostic efficiency and long-term influence upon the tumor recurrence rate for patients with non-muscle-invasive bladder cancer (NMIBC) undergoing hexaminolevulinate PDD compared to standard WLC.. Between 2009 and 2011, 113 primary NMIBC patients were enrolled in our prospective study and randomized in two parallel groups: 57 patients in the study group (PDD) and 56 patients in the control group (WLC). All patients had primary Ta÷T1 NMIBC with good life expectancy and no significant bladder outlet obstruction [postvoid residual urine volume (PVR) <100 mL].. Fluorescence cystoscopy examination identified 26.3% more tumors than the conventional examination (p=0.034) in the PDD group. Tumor recurrence rate analysis proved a significant reduction by up to 20% after five years of follow-up by using PDD [hazard ratio (HR) 0.566, 95% confidence interval (CI) 0.343-0.936; p=0.0267].. The use of PDD for patients with NMIBC results in a significant 26% diagnostic sensitivity improvement as well as superior patient prognosis and quality of life following conservative treatment by reducing the tumor recurrence rate with up to 20% after five years of follow-up.

Topics: Aminolevulinic Acid; Female; Fluorescence; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Prospective Studies; Urinary Bladder Neoplasms

Photodynamic diagnosis (PDD) of non-muscle-invasive bladder cancer (NMIBC) following transurethral administration of a hexalated form of 5-aminolevulinic acid (5-ALA), 5-ALA hexyl ester, is widely performed in Western countries. In this study, effectiveness and safety of the oral administration of 5-ALA is assessed in a phase II/III study of PDD for NMIBC in comparison to those of conventional white-light endoscopic diagnosis.. Patients with NMIBC were allocated to two groups that were orally administered 10 and 20 mg/kg of 5-ALA under the double-blind condition. Effectiveness was evaluated by setting the primary endpoint to sensitivity. Safety was also analyzed. Moreover, clinically recommended doses of 5-ALA was also investigated as an investigator-initiated multicenter cooperative clinical trial in which five medical institutions participated.. All 62 enrolled patients completed the clinical trial. The sensitivities of PDD were higher (84.4 and 75.8% in the 10 and 20 m g/kg-groups, respectively) than those of conventional endoscopic diagnosis (67.5 and 47.6%, respectively) (p = 0.014 and p < 0.001, respectively). Five episodes of serious adverse events developed in four patients; whereas a causal relationship with the investigational agent was ruled out in all episodes.. This investigator-initiated clinical trial confirmed the effectiveness and safety of PDD for NMIBC following oral administration of 5-ALA. Both doses of 5-ALA may be clinically applicable; however, the rate of detecting tumors only by PDD was higher in the 20 mg/kg-group suggesting that this dose would be more useful.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluorescence; Humans; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Sensitivity and Specificity; Urinary Bladder Neoplasms

To assess the impact of hexaminolevulinate (HAL) on the long-term recurrence rate of NMIBC.. A total of 130 patients with bladder tumour were randomized into two groups. The patients in one group had a HAL instillation before surgery, and they first had a white-light and after that a blue-light cystoscopy (BL group) and resection. The second group had only white-light cystoscopy (WL group) and resection. They have been followed up with cystoscopy every 3 months for a period of up to 40 months.. The recurrence-free period was not significantly different between the two groups (BL and WL groups) (long-rank test p = 0.202). The use of HAL helped detect four flat lesions and 28 papillary lesions with cancer that would have been missed under WL only, on 16 out of the 54 patients (29.6 % CI 95 % 11.1-33.3). The use of HAL changed the proposed postoperative treatment and follow-up for one out of the five patients.. Although the use of HAL cystoscopy identified at least one cancer lesion more than WL cystoscopy on one out of the three patients, the recurrence-free period was not significantly different.

Topics: Aged; Aminolevulinic Acid; Color; Contrast Media; Cystoscopy; Disease-Free Survival; False Positive Reactions; Female; Follow-Up Studies; Humans; Image-Guided Biopsy; Male; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Optical Imaging; Prospective Studies; Urinary Bladder; Urinary Bladder Neoplasms

In accordance with the European Association of Urology guidelines, a second transurethral resection of the bladder (TURB) is recommended for high-grade or T1-category tumors. This practice brings into question the benefit of photodynamic diagnosis (PDD) in reducing the residual disease after TURB in patients with positive results on urine cytology showing high-grade cancer cells.. A prospective, bicentric, randomized study comparing white light cystoscopy (WLC)+PDD with hexaminolevulinate arm with WLC alone (control arm) during the first TURB in patients with primary non-muscle-invasive bladder cancer and with positive results on urine cytology showing high-grade cancer cells. Patients underwent a first TURB with WLC and PDD or WLC alone, and then a second TURB with WLC and PDD, after 4 to 6 weeks. The number of tumors visualized in WLC and PDD and histology of the TURB specimen was recorded to perform a statistical analysis comparing both the 2 arms.. A total of 151 patients were enrolled (hexaminolevulinate, n = 72; control, n = 79). The number of visualized tumors did not increase with PDD in the first or second TURB. During the second TURB, the residual tumor rate was not reduced in patients who had PDD during the first TURB. No significant difference was observed regarding the pattern of category and grade, the size, and the recurrence and progression risks during either the first or the second TURB.. In the setting of primary non-muscle-invasive bladder cancer with positive results on urine cytology, performing a second TURB allows to diagnose residual tumor in approximately half of the cases. This rate was not significantly reduced by the use of the PDD during the first TURB.

Topics: Aged; Aminolevulinic Acid; Cystoscopy; Female; Humans; Male; Photochemotherapy; Photosensitizing Agents; Prospective Studies; Urinary Bladder Neoplasms; Urologic Surgical Procedures

To determine if photodynamic 'blue-light'-assisted resection leads to lower recurrence rates in newly presenting non-muscle-invasive bladder cancer (NMIBC).. We conducted a prospective randomized trial of hexylaminolevulinate (HAL) photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumour (TURBT) plus single-shot intravesical mitomycin C vs standard white-light-assisted TURBT plus single-shot intravesical mitomycin C. A total of 249 patients with newly presenting suspected NMIBC enrolled at Guy's Hospital between March 2005 and April 2010. Patients with a history of bladder cancer were excluded. The surgery was performed by specialist bladder cancer surgical teams. Of the eligible patients, 90% agreed to be randomized.. Of the 249 patients, 209 (84%) had cancer and in 185 patients (89%) the cancer was diagnosed as NMIBC. There were no adverse events related to HAL in any of the patients randomized to the intravesical HAL-PDD arm. Single-shot intravesical mitomycin C was administered to 61/97 patients (63%) in the HAL-PDD arm compared with 68/88 patients (77%) in the white-light arm (P = 0.04) Intravesical HAL was an effective diagnostic tool for occult carcinoma in situ (CIS). Secondary CIS was identified in 25/97 patients (26%) in the HAL-PDD arm compared with 12/88 patients (14%) in the white-light arm ((P = 0.04) There was no significant difference in recurrence between the two arms at 3 or 12 months: in the HAL-PDD and the white-light arms recurrence was found in 17/86 and 14/82 patients (20 vs 17%), respectively ((P = 0.7) at 3 months, and in 10/63 and 15/67 patients (16 vs 22%), respectively ((P = 0.4) at 12 months.. Despite HAL-PDD offering a more accurate diagnostic assessment of a bladder tumour, in this trial we did not show that this led to lower recurrence rates of newly presenting NMIBC compared with the best current standard of care.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Antibiotics, Antineoplastic; Cystoscopy; Female; Fluorescence; Humans; Light; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Predictive Value of Tests; Prospective Studies; Treatment Outcome; Urinary Bladder Neoplasms

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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Time Factors; Treatment Outcome; Urinary Bladder Neoplasms; Urinary Tract Infections; Urologic Diseases

•  To evaluate in a prospective, randomized study the impact of hexaminolevulinate blue-light cystoscopy (HAL-BLC) on the diagnostic accuracy and treatment changes in cases of non-muscle invasive bladder cancer (NMIBC) compared with standard white-light cystoscopy (WLC). •  To compare the long-term recurrence rates in the two study arms.. •  In all, 362 patients suspected of NMIBC were included in the trial based on positive urinary cytology and/or ultrasonographic suspicion of bladder tumours and underwent transurethral resection of bladder tumours. •  A single postoperative mytomicin-C instillation was performed in all cases, intravesical chemotherapy for intermediate-risk patients and BCG instillations for high-risk cases. •  The follow-up protocol consisted of urinary cytology and WLC every 3 months for 2 years. •  Only first-time recurrences after the initial diagnosis were considered.. •  In the 142 patients with NMIBC in the HAL-BLC series, tumour detection rates significantly improved for carcinoma in situ, pTa andoverall cases. •  In 35.2% of the cases, additional malignant lesions were found by HAL-BLC and consequently, the recurrence- and progression-risk categories of patients and subsequent treatment improved in 19% of the cases due to fluorescence cystoscopy. •  In all, 125 patients in the HAL-BLC group and 114 of the WLC group completed the follow-up. •  The recurrence rate at 3 months was lower in the HAL-BLC series (7.2% vs 15.8%) due to fewer 'other site' recurrences when compared with the WLC series (0.8% vs 6.1%). •  The 1 and 2 years recurrence rates were significantly decreased in the HAL-BLC group compared with the WLC group (21.6% vs 32.5% and 31.2% vs 45.6%, respectively).. •  HAL-BLC was better than WLC for detecting NMIBC cases and improved tumour detection rates. •  HAL-BLC significantly modified the postoperative treatment of cases. •  The 3 months, 1 and 2 years recurrence rates were significantly improved in the HAL-BLC arm.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Contrast Media; Cystoscopy; Disease Progression; Female; Follow-Up Studies; Humans; Incidental Findings; Male; Microscopy, Fluorescence; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Sensitivity and Specificity; Urinary Bladder Neoplasms

We assessed the impact of hexaminolevulinate fluorescence cystoscopic detection of papillary, nonmuscle invasive bladder cancer on the long-term recurrence rate.. Long-term followup was assessed in 551 participants enrolled in a prospective, randomized study of fluorescence cystoscopy for Ta or T1 urothelial bladder cancer. In the original study 280 patients in the white light cystoscopy group and 271 in the fluorescence cystoscopy group were followed with cystoscopy for 3, 6 and 9 months after initial resection or until recurrence. A study extension protocol was done for long-term followup of these patients.. Followup information was obtained for 261 of the 280 patients (93%) in the white light group and 255 of the 271 (94%) in the fluorescence group. Median followup in the white light and fluorescence groups was 53.0 and 55.1 months, and 83 (31.8%) and 97 patients (38%) remained tumor free, respectively. Median time to recurrence was 9.4 months in the white light group and 16.4 months in the fluorescence group (p = 0.04). The intravesical therapy rate was similar in the 2 groups (46% and 45%, respectively). Cystectomy was done in 22 of 280 cases (7.9%) in the white light group and in 13 of the 271 (4.8%) in the fluorescence group (p = 0.16).. Hexaminolevulinate fluorescence cystoscopy significantly improves long-term bladder cancer time to recurrence with a trend toward improved bladder preservation.

Topics: Aged; Aminolevulinic Acid; Canada; Carbon Radioisotopes; Cystoscopy; Diagnosis, Differential; Europe; Female; Fluorescence; Follow-Up Studies; Humans; Male; Morbidity; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Photosensitizing Agents; Prospective Studies; Reproducibility of Results; Time Factors; United States; Urinary Bladder Neoplasms

To date, no study has presented results of photodynamic diagnosis (PDD) cystoscopy compared with white-light cystoscopy (WLC) in daily practice. The aim of the present study is to evaluate the diagnostic accuracy of hexylaminolevulinate hydrochloride (Hexvix(®)) PDD cystoscopy compared with standard WLC used in daily practice.. An observational, open-label, comparative, controlled (within patient), multicenter study was carried out on 96 consecutive patients with suspected or confirmed bladder cancer. All patients had standard WLC followed by blue-light cystoscopy (BLC). Positive lesions detected using WLC and BLC were recorded. Biopsies/resection of each positive lesion were taken after the bladder was inspected. Sensitivity, specificity, positive predictive value, and negative predictive value with each method were calculated.. Overall, 234 suspicious lesions were detected; 108 (46.2%) were histologically confirmed to be bladder tumors/carcinoma in situ (CIS). The sensitivity of BLC biopsies was significantly higher than for WLC technique (99.1 vs 76.8%; p < 0.00001). The relative sensitivity of BLC versus WLC was 1.289, showing superiority of BLC of 28.9%. The specificity of BLC biopsies was not significantly different compared with WLC (36.5 vs 30.2%). Positive predictive value for BLC- and WLC-guided biopsies was 54.9 and 50.9%, respectively. Negative predictive value per biopsy for BLC- and WLC-guided biopsies was 97.4 and 64.8%, respectively. BLC and WLC reached the correct diagnosis in 97.9 and 88.5% of patients, respectively. This difference was statistically significant (p = 0.0265). The lack of a random biopsy protocol was the major limitation of the study.. Hexvix(®) PDD cystoscopy used in daily practice enhances the diagnostic accuracy of standard cystoscopy with higher negative predictive value, potentially permitting an improvement in patient prognosis.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; Female; Fluorescence; Humans; Light; Male; Middle Aged; Prospective Studies; Urinary Bladder Neoplasms

To evaluate the effect of hexaminolevulinate (HAL)-induced fluorescence during resection of noninvasive bladder cancer on tumor recurrence compared with resection under white light.. Between 2008 and 2010, 102 consecutive patients with suspected bladder cancer were randomized to undergo transurethral resection with either conventional white light or combination of white light and HAL-induced fluorescence. Difference in tumor recurrence rate and recurrence-free survival between the 2 groups was evaluated. Subgroup analysis on recurrence-free survival was performed for different tumor parameters.. Cystoscopy at 3 months revealed tumor recurrence in 6 of 45 (13.3%) patients of the white light group compared with only 1 of 41 patients of the HAL group (2.4%) (P < .001). The recurrence-free rates in white light patients at 12 and 18 months were 56.3% and 50.6%, respectively, compared with 91% and 82.5% in HAL patients (P = .0006). In subgroup analyses, recurrence-free survival was similar between the 2 groups when solitary tumors were treated (P = .3525). However, the HAL group had a favorable recurrence-free survival compared with the white light group when multifocal tumors (P < .001), primary tumors (P = .0237), recurrent tumors (P = .0189), nonaggressive (papillary urothelial neoplasm of low malignant potential and low grade) tumors (P = .0204), or aggressive (high grade and carcinoma in situ) tumors (P = .0134) were treated.. HAL significantly aids resection of non-muscle-invasive bladder cancer with the result of reduction in tumor recurrence rates.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystectomy; Female; Fluorescence; Humans; Light; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Radionuclide Imaging; Urethra; Urinary Bladder Neoplasms

Bladder cancer (BC) is the most common tumor of the urinary tract. White light cystoscopy (WLC) is currently considered the standard investigation for diagnosis of bladder tumors. Recent studies suggest that using exogenous fluorescence (photodynamic diagnosis, PDD) can improve its diagnostic sensitivity and specificity.. Our study aims to analyze the value of using fluorescent cystoscopy (PDD) in the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC).. The study designed as a prospective randomized clinical trial was conducted over a 12 months period and included 44 patients with primitive NMIBC diagnosed and treated in our department in 2009. Twenty-two patients were included in the study group (PDD), while 22 patients were diagnosed and treated by conventional methods (WLC).. There were no statistically significant differences between the two groups regarding age, sex, place of origin, smoking history, clinical symptoms or presence of urological history as well as tumor size, location or number. Fluorescence cystoscopy examination identified 25.8% more tumors than the conventional examination (p=0.004). We demonstrated a significant reduction of tumor recurrence rates at 3, 6, 9 and 12 months by using PDD (HR=0.3271, 95% CI 0.1091-0.9809; p=0.0461).. The use of PDD in patients with NMIBC results in significant improvement of the efficiency of their initial diagnosis cystoscopy (by over 25%). We demonstrated improved patient prognosis and quality of life following conservative TUR treatment of these tumors by significantly reducing the tumor recurrence rate (by 9-27%) in the first year of follow-up.

Topics: Aminolevulinic Acid; Cystoscopy; Female; Humans; Kaplan-Meier Estimate; Light; Male; Middle Aged; Muscles; Neoplasm Invasiveness; Recurrence; Single-Blind Method; Urinary Bladder Neoplasms

To evaluate the impact of hexaminolevulinate blue-light cystoscopy and transurethral resection of bladder tumors (TURBT) upon the short-term recurrence rate in high-risk nonmuscle-invasive bladder cancer (NMIBC) compared with conventional cystoscopy and resection.. Between December 2007 and November 2009, 446 patients were randomized for blue-light cystoscopy/resection and for standard cystoscopy/resection, respectively. The inclusion criteria consisted of positive urinary cytology and ultrasonographic suspicion of bladder tumors. High-risk NMIBC patients (carcinoma in situ [CIS], pTaG3, and pT1) from both series underwent standard Re-TURBT 6 weeks after the initial procedure.. The proportions of CIS, pTaG3, and pT1 cases in the initial series were 13.1%, 5.7%, and 22.2% in the blue light series and 11.3%, 5.7%, and 23.3% in the white light series. In total, 72 and 64 high-risk cases, respectively, were diagnosed in the blue- and white-light series. The overall short-term recurrence rate at Re-TURBT was 11.1% for the blue-light group and 31.2% for the white-light group. The recurrence rates were 4.3% versus 27.8% for CIS, 10% versus 22.2% for pTaG3, and 15.4% versus 35.1% for pT1 cases, in favor of the blue-light arm. The recurrence rate in patients presenting with high-grade tumors was 17.2% in the blue-light group and 37% in the white-light group.. Blue-light cystoscopy and resection significantly reduced the short-term recurrence rates determined during the standard Re-TURBT in all categories of high-risk patients compared with the standard cystoscopy and resection.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Carbon Radioisotopes; Cystoscopy; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Radionuclide Imaging; Risk Factors; Urinary Bladder Neoplasms

We assessed the impact that improved detection of nonmuscle invasive bladder cancer with hexaminolevulinate fluorescence cystoscopy may have on early recurrence rates.. This prospective, randomized study enrolled 814 patients suspected of having bladder cancer at increased risk for recurrence. All patients underwent white light cystoscopy and mapping of lesions, followed by transurethral resection of the bladder when indicated. Patients in the fluorescence group also received intravesical hexaminolevulinate solution at least 1 hour before cystoscopy to induce fluorescence of cancerous lesions, and underwent additional inspection with blue light before and after transurethral resection of the bladder. Adjuvant intravesical therapy was based on risk. Followup cystoscopy at 3, 6 and 9 months was conducted with white light.. Detection was performed as a within patient comparison in the fluorescence group. In this group 286 patients had at least 1 Ta or T1 tumor (intent to treat). In 47 patients (16%) at least 1 of the tumors was seen only with fluorescence (p = 0.001). During the 9-month followup (intent to treat) there was tumor recurrence in 128 of 271 patients (47%) in the fluorescence group and 157 of 280 (56%) in the white light group (p = 0.026). The relative reduction in recurrence rate was 16%.. Hexaminolevulinate fluorescence cystoscopy significantly improves the detection of Ta and T1 lesions and significantly reduces the rate of tumor recurrence at 9 months.

Topics: Aged; Aminolevulinic Acid; Carbon Radioisotopes; Cystoscopy; Female; Fluorescence; Humans; Male; Neoplasm Recurrence, Local; Prospective Studies; Urinary Bladder Neoplasms

To determine the potential for hexylaminolevulinate (HAL) photodynamic diagnosis (PDD) to improve the management of multifocal recurrent nonmuscle-invasive bladder cancer (NMIBC).. Patients with a history of NMIBC and with at least two suspected papillary recurrences were enrolled in this prospective study between April 2005 and October 2006. The photosensitizer was hexylaminolevulinate (HAL) (PhotoCure, Norway), and the Storz D-light system was used to detect fluorescence. The bladder was mapped initially under white light and then using HAL-photodynamic diagnosis (PDD). The number and types of additional lesions detected by HAL-PDD over white light cystoscopy were measured.. Eighteen patients (11 men), median age 74 years (range 35-84 yrs), underwent HAL-PDD. The median HAL instillation time was 109 minutes (range 60-250 min). Recurrent bladder cancer was confirmed histologically in 14/18 (78%) patients. Additional pathology was detected in 8/14 (57%) patients with confirmed recurrence and confirmed histologically in 6 of these. Additional pathology was papillary in 5/6 (83%) patients, and flat pathology was found in all six patients with additional foci. Carcinoma in situ (CIS) was detected in 4/6 (67%) patients with additional foci, three of whom were subsequently treated with intravesical bacille Calmette-Guérin (BCG). The sensitivity of HAL-PDD for the detection of tumor was 97.8%, compared with 69.6% for white light cystoscopy. The false-positive fluorescence-guided biopsy rate was 18/63 (29%).. HAL-PDD allows more complete management of bladder tumor in patients with multifocal recurrence. The high frequency of additional lesions detected and the rate of detection of CIS suggest that HAL-PDD should be the standard of care.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Biopsy; Carcinoma in Situ; Cystoscopy; Demography; Female; Humans; Male; Middle Aged; Muscles; Photosensitizing Agents; Recurrence; Urethra; Urinary Bladder; Urinary Bladder Neoplasms

We compared hexaminolevulinate (HAL) blue light cystoscopy (BLC) with standard white light cystoscopy (WLC) in the diagnosis of noninvasive bladder tumors (NIBT) and analyzed the efficiency of blue light transurethral resection of the bladder (BL-TURB).. WLC and BLC were performed in 64 cases. BL-TURB was applied for lesions that were detected only by BLC. Patients who received a diagnosis of NIBT were followed up after 18 weeks by WLC and BLC. The control group included the same number of consecutive patients with NIBT, diagnosed only by WLC and treated by WL-TURB.. WLC correctly diagnosed 66.4%, with a 9.7% rate of false-positive results, while BLC diagnosed 95.7%, but had a 13.5% rate of false-positive results. The study group had a recurrence rate of 5.3% vs 23.2% in the control group.. HAL fluorescence cystoscopy is a valuable diagnostic method, with considerably improved accuracy. BL-TURB represents a superior treatment modality, with significant impact on the recurrence rate.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; False Positive Reactions; Female; Fluorescence; Humans; Male; Middle Aged; Urethra; Urinary Bladder; Urinary Bladder Neoplasms

The advantage of photodynamic diagnosis in detecting urothelial cell carcinoma (UCC) of the bladder has been demonstrated clearly, but it comes at the price of a higher false-positive rate. Optical coherence tomography (OCT) is a noninvasive, real-time, microstructural imaging modality that uses near-infrared light for a point analysis of the bladder-wall microstructure.. To evaluate whether adding targeted OCT analysis of lesions that are suspicious at white-light (WL) and hexaminolevulinate (HAL) fluorescence cystoscopy improves diagnostic accuracy in the detection of UCC.. In this prospective single-center study with same-patient comparison, patients with suspected UCC first received an intravesical instillation of HAL. Cystoscopy was performed in WL, followed by blue-light inspection and OCT scanning.. Suspicious lesions identified by WL or HAL were evaluated by OCT and were subsequently resected or biopsied.. We measured changes in sensitivity and specificity in detecting UCC using WL, HAL, and targeted OCT.. In 66 patients studied, 232 lesions were detected, were scanned by OCT, and were subsequently resected or biopsied. Additionally, 132 areas of normal-appearing urothelium were investigated by all three methods and biopsied. On a per-lesion basis, sensitivity and specificity were respectively 69.3% and 83.7% for WL, 97.5% and 78.6% for HAL, and 97.5% and 97.9% for HAL combined with OCT. Overall, UCC was diagnosed in 58 patients (87.9%), with a per-patient sensitivity of 89.7% for WL and 100% for both HAL alone and HAL with targeted OCT. Per-patient specificity for HAL alone and targeted HAL was 62.5% and 87.5%, respectively. The limitation of OCT results from poor visualization of flat lesions in WL, making scanning a time-consuming procedure.. Combining fluorescence cystoscopy with targeted OCT increases the specificity of fluorescence cystoscopy significantly, with no added morbidity, and reduces the need for unnecessary (false-positive) biopsies.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; False Positive Reactions; Female; Fluorescence; Humans; Male; Middle Aged; Mucous Membrane; Prospective Studies; Sensitivity and Specificity; Tomography, Optical Coherence; Urinary Bladder Neoplasms; Urothelium

We compared hexaminolevulinate fluorescence cystoscopy with white light cystoscopy for detecting Ta and T1 papillary lesions in patients with bladder cancer.. A total of 311 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM HAL for 1 hour. The bladder was inspected using white light cystoscopy, followed by blue light (fluorescence) cystoscopy. Papillary lesions were mapped and resected for histological examination.. Noninvasive pTa tumors were found in 108 of 196 evaluable patients (55.1%). In 31 patients (29%) at least 1 more tumor was detected by HAL than by white light cystoscopy (p<0.05). Six of these patients had no lesions detected by white light, 12 had 1 lesion detected by white light and more than 1 by HAL, and 13 had multiple Ta lesions detected by the 2 methods. Conversely at least 1 more tumor was detected by white light cystoscopy than by HAL cystoscopy in 10 patients (9%, 95% CI 5-16). Tumors invading the lamina propria (T1) were found in 20 patients (10.2%). At least 1 additional T1 tumor was detected by HAL but not by white light cystoscopy in 3 of these patients (15%), while at least 1 more T1 tumor was detected by white light cystoscopy than by HAL cystoscopy in 1 patient (5%, 95% CI 0-25). Detection rates for Ta tumors were 95% for HAL cystoscopy and 83% for white light cystoscopy (p=0.0001). Detection rates were 95% and 86%, respectively, for T1 tumors (p=0.3). HAL instillation was well tolerated with few local or systemic side effects.. HAL fluorescence cystoscopy detected at least 1 more Ta and T1 papillary tumor than white light cystoscopy in approximately a third of the patients with such tumors. Whether this would translate to improved patient outcomes has yet to be determined.

Topics: Aged; Aminolevulinic Acid; Carbon Radioisotopes; Carcinoma in Situ; Carcinoma, Transitional Cell; Cystoscopy; Female; Humans; Male; Middle Aged; Urinary Bladder Neoplasms

We compared hexaminolevulinate (Hexvix) fluorescence cystoscopy with white light cystoscopy for detecting carcinoma in situ.. In this multicenter study 298 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM hexaminolevulinate for 1 hour. Cystoscopy was then performed, first using standard white light and then hexaminolevulinate fluorescence cystoscopy. Lesions or suspicious areas identified under the 2 illumination conditions were mapped and biopsied for histological examination. In addition, 1 directed biopsy was obtained from an area appearing to be normal.. Of 196 evaluable patients 29.6% (58 of 196) had carcinoma in situ, including 18 with carcinoma in situ alone, and 35 with carcinoma in situ and concomitant papillary disease, which was only detected on random biopsy in 5. Of the 18 patients with no concomitant papillary disease carcinoma in situ was detected only by hexaminolevulinate fluorescence in 4 and only by white light in 4. In the group with concomitant papillary disease carcinoma in situ was found only by hexaminolevulinate fluorescence in 5 patients and only by white light in 3. The proportion of patients in whom 1 or more carcinoma in situ lesions were found only by hexaminolevulinate cystoscopy was greater than the hypothesized 5% (p=0.0022). Overall more carcinoma in situ lesions were found by hexaminolevulinate than by white light cystoscopy in 22 of 58 patients (41.5%), while the converse occurred in 8 of 58 (15.1%). Biopsy results confirmed cystoscopy findings. Of a total of 113 carcinoma in situ lesions in 58 patients 104 (92%) were detected by hexaminolevulinate cystoscopy and 77 (68%) were detected by white light cystoscopy, while 5 were detected only on directed visually normal mucosal biopsy. Hexaminolevulinate instillation was well tolerated with no local or systemic side effects.. In patients with bladder cancer hexaminolevulinate fluorescence cystoscopy with blue light can diagnose carcinoma in situ that may be missed with white light cystoscopy. Hexaminolevulinate fluorescence cystoscopy can be used in conjunction with white light cystoscopy to aid in the diagnosis of this form of bladder cancer.

Topics: Aged; Aminolevulinic Acid; Carbon Radioisotopes; Carcinoma in Situ; Cystoscopy; Female; Humans; Male; Middle Aged; Urinary Bladder Neoplasms

Successful photodynamic therapy of epithelial cancer requires a specific photosensitization of malignant tissue. We evaluate the intensity and localization of protoporphyrin IX (PpIX) in superficial transitional cell carcinoma and nonmalignant cells of the human bladder following topical administration of its precursor, either aminolevulinic acid (ALA) or hexylester aminolevulinate (HAL).. Solutions of ALA or HAL were instilled into the bladder of 18 patients presenting with recurrent transitional cell carcinoma. The distribution of PpIX through the bladder wall was studied on frozen biopsies using fluorescence microscopy and correlated with pathological findings.. Topical bladder instillation with 180 mmol (3%) ALA administered for 6 hours or 8 mmol (0.2%) HAL administered for 4 hours gave similar results regarding intensity and tissue distribution of PpIX fluorescence, whereas 8 mmol HAL administered for 2 hours followed by 2 hours of resting time (2+2 hours concept) induced a PpIX fluorescence twice as high. The fluorescence remained limited to cancer cells. Only a trace of PpIX fluorescence was observed in suburothelial connective tissue, that is chorion, but none in the bladder smooth muscle regardless of experiment conditions.. HAL is an excellent precursor for PpIX synthesis in bladder cancer. With the 2+2 hour topical administration condition it yielded the highest PpIX fluorescence intensity and fluorescence contrast between normal and malignant urothelial cells. This approach allows us to optimize PpIX tissue distribution for photodynamic therapy in superficial bladder cancer.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Aminolevulinic Acid; Carcinoma, Transitional Cell; Female; Humans; Male; Microscopy, Fluorescence; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Protoporphyrins; Spectrometry, Fluorescence; Urinary Bladder; Urinary Bladder Neoplasms

To compare the recurrence of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection employing cystoscopy with hexaminolevulinate-based photodynamic diagnosis (PDD) or with standard white light.. We included patients with newly suspected NMIBC in this retrospective cohort study and compared those undergoing transurethral resection by white light cystoscopy (WLC) (2008-2010) and PDD (2010-2012). All patients were treated following established criteria for good quality resection. The primary outcome was the difference in the recurrence rate after 60 months' follow-up, but we also stratified recurrence by risk groups, as set by the European Organization for Research and Treatment of Cancer. The mean recurrence-free survival was compared between the cohorts. Odds ratios or hazard ratios are reported with their 95% confidence intervals.. The WLC and PDD cohorts comprised 124 and 91 subjects, respectively. There were no significant differences in recurrence rates between the cohorts at 6 months (recurrence rate 9/123; 7.3%), 12 months (17/118; 14.4%) or 60 months (39/102; 38.2%), with odds ratios of 1.23 (CI 0.48-3.25), 1.32 (CI 0.67-2.62) and 1.12 (CI 0.70-1.79), in favour of WLC, respectively. Further analysis showed no significant effect of PDD on either recurrence by risk group or on mean recurrence-free survival (hazard ratio, 1.12 [CI 0.70-1.79]).. We found no relevant differences in the recurrence of NMIBC after the introduction of PDD with hexaminolevulinate compared to standard WLC when used for transurethral resection in our single institution.

Topics: Aminolevulinic Acid; Carcinoma; Cystoscopy; Humans; Neoplasm Recurrence, Local; Retrospective Studies; Urinary Bladder; Urinary Bladder Neoplasms

The therapeutic benefit of intravesical instillation of hexaminolevulinate (HAL) at the time of transurethral resection of bladder tumor (TURBT) has been demonstrated in multiple studies. The purpose of this study was to prospectively assess the safety of repeated administration of HAL from a phase III pre-trial planned analysis.. All patients evaluated in the study received at least 1 dose of HAL at the time of office cystoscopy, and a subset of these patients (n = 103, 33.2%) received a second dose a few weeks later at the time of TURBT. Adverse events (AEs) were recorded, and the safety of repeat use of HAL was determined by comparing the proportion of patients with AEs considered causally related to HAL in the surveillance examination compared to the OR examination. Association between categorical variables was tested using Fisher's Exact Test, and a P < 0.05 was considered statistically significant.. HAL-related AEs were experienced by 6 patients (2.2%) during surveillance cystoscopy and 3 patients (3.4%) following TURBT (P = 0.76); 181 patients (59.5%) had prior exposure to HAL before enrolling in the study with no difference in the number of AEs when comparing prior exposure to HAL to no prior exposure (P = 0.76). Of the patients who previously received intravesical therapy, 8 (2.9%) had at least 1 AE during surveillance compared to 3 (9.7%) who had no prior intravesical therapy (P = 0.09).. Repeat use of HAL is safe even when administered within a few weeks of receiving a dose of intravesical therapy.

Topics: Aminolevulinic Acid; Cystectomy; Cystoscopy; Humans; Urinary Bladder Neoplasms

Seven different inhibitors of the heme metabolic pathway were applied in combination with HAL to study the formation of PpIX in bladder cancer HT1197 and normal fibroblast HFFF2 cells ex vivo, specifically with the aim to increase the fluorescence contrast between cancer and non-cancer cells. The mRNA expression of enzymes involved in the heme biosynthesis pathway were measured via PCR following incubation with the drugs in order to link the fluorescence levels and metabolic activity. The exogenous administration of HAL does lead to cancer-specific PpIX accumulation. However, the contrast between cancer and normal cells in suspension was not enhanced by the enzyme inhibitors and iron-chelating agents tested, nor did the mRNA expression necessarily correlate with the fluorescence intensity. The results indicate that a difference in the metabolic activity of cells in suspension may limit the applicability of exogenous enzyme inhibitor administration as a mean to improve the fluorescence-based detection of cancer cells shed in body fluids.

Topics: Aminolevulinic Acid; Cell Line, Tumor; Fluorescence; Heme; Humans; Pharmaceutical Preparations; Photochemotherapy; Photosensitizing Agents; Protoporphyrins; RNA, Messenger; Urinary Bladder Neoplasms

Bladder cancer (BC) is considered one of the malignancies with moderate-high incidence, high rate of recurrence and costly management. Diagnosis and staging are thus important for therapeutic purposes. Considering the risk of residual tumour and understaging, in specific cases, international guidelines recommend performing a second transurethral resection of the bladder (reTURB). Our study aimed to evaluate the impact of hexaminolevulinate Photodynamic Diagnostics (PDD) at first TURB on the rate of residual tumour.. We retrospectively analysed patients undergoing TURB in our centre between 2012 and 2020. Eightytwo patients had a re-TURB after a first complete TURB with a delay < 3 months. Patients who had an incomplete first resection were excluded. We compared patients who underwent standard white light cystoscopy/TURB and then hexaminolevulinate PDDguided reTURB (group A, n = 49) and patients with PDD-cystoscopy/ TURB at the first procedure then white light cystoscopy/reTURB (group B, n = 33). The residual tumour rate at reTURB as well as median recurrence-free survival (RFS) were compared between the two groups.. Residual tumour at reTURB was detected in 48.8% of cases in our cohort, with a significant difference between the two groups (71.4% in group A versus 12.5% in group B, p < 0.001). After a median follow-up of 22 months, the median RFS was 15 months in Group A and 32 months in Group B, but this difference was not significant (p = 0.7).. Using PDD at the time of the initial TURB had a statistically significant impact on the rate of residual tumour at the reTURB. Nevertheless, the percentage of residual tumour even with the use of PDD does not allow for safely omitting second resection. Performing a reTURB with PDD for patients who did not have it initially, provides the same benefit in terms of recurrence-free survival.

Topics: Cystoscopy; Humans; Neoplasm Recurrence, Local; Neoplasm, Residual; Retrospective Studies; Urinary Bladder; Urinary Bladder Neoplasms

To determine the estimated budget impact to practices that incorporate blue light cystoscopy (BLC) with hexaminolevulinate HCl (HAL) for the surveillance of non-muscle-invasive bladder cancer (NMIBC) in the clinic setting. With the introduction of advanced technologies in the clinic setting such as HAL, further cost comparative research is needed to justify HAL as a high value option.. A budget impact model was developed from the facility perspective assessing projected costs at 2 years for a simulated facility with 50 newly diagnosed bladder cancer patients. Treatment and surveillance cystoscopy intervals were based on clinical guidelines. Clinical inputs, including tumor stage and grade at diagnosis, rates of recurrence and relative risk reduction when using BLC with HAL, were derived from published studies. Cost inputs were based on Medicare reimbursement rates and facility costs.. Use of BLC identified 9 additional recurrences over two years compared to white light cystoscopy alone. Use of flexible BLC for surveillance marginally increased costs to the practice, with a net difference of $0.76 per cystoscopy over 2 years.. From the office/clinic perspective, the model suggests that the use of flexible BLC for the surveillance of NMIBC may not impact cost per cystoscopy and identifies 9 recurrences over 2 years that would be missed using white light cystoscopy alone. These findings could have important implications in the management of NIMBC and help guide clinical practice guidelines that promote cost-effective care and improved patient outcomes.

Topics: Aminolevulinic Acid; Cystoscopy; Humans; Neoplasm Invasiveness; Population Surveillance; Urinary Bladder Neoplasms

To evaluate the utility of blue-light flexible cystoscopy (BLFC) for surveillance of non-muscle-invasive bladder cancer (NMIBC).. Prospective cohort of consecutive patients who underwent office-based BLFC for NMIBC. Clinical information was collected including cystoscopic findings and pathological data.. A total of 322 cases were performed on 190 patients. The mean age was 71 years and 83% were men. The highest stage prior to BLFC was Ta, carcinoma in situ (CIS), T1, and T2 in 45.3%, 18.4%, 30% and 2%, respectively. Prior to BLFC, 16.8%, 60.5%, and 16.8% were low grade (LG), high grade (HG), and CIS, respectively. Intravesical bacille Calmette-Guérin and intravesical chemotherapy were used in 54.2% and 18.4%, respectively. White-light cystoscopy (WLC) and BLFC were both normal in 173 (53.7%) of cases. WLC was normal and BLFC was abnormal in 26 (8%) cases. Of these, 15 had office-based biopsy and cancer was detected in 13 (87%; six CIS, four HG Ta, three LG Ta). Both WLC and BLFC were positive in 83 (25.8%) cases and 33% had additional tumours found. Cancer was found in 27 (75%) of WLC+/BLFC+ who underwent office-based biopsy including 19 LG Ta, six HG Ta, and two CIS.. Incorporation of BLFC in clinical practice has potential advantages of finding cancer in cases with normal WLC. BLFC detected additional cancers in 33% of patients with positive WLC and BLFC, which can improve surveillance and performance of office-based biopsy. Further research is needed to determine cost-effectiveness and impact on recurrence rates.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Biopsy; Color; Cystoscopy; Disease Progression; Female; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Photosensitizing Agents; Prospective Studies; Urinary Bladder; Urinary Bladder Neoplasms; Watchful Waiting

Photodynamic diagnosis using hexaminolevulinate (HAL)-guided BL-TURB may reduce the recurrence risk in non-muscle invasive BCa compared to standard WL-TURB due to more sensitive tumor detection. The impact of the initial use of WL- vs. BL-TURB on follow-up costs was evaluated in this real-world data analysis.. Anonymous claims data of German statutory health insurances (GKV) from 2011 to 2016 were analyzed in a primary and adjusted study population. Selection criteria included five quarters before enrolment, one index quarter (InQ) of initial TURB and BCa diagnosis, either within two years for the primary analysis or within four years for the adjusted analysis, and a follow-up period (FU) of either eleven or three quarters, respectively.. In the primary analysis (n = 2331), cystectomy was identified as an important cost driver masking potential differences between cohorts. Therefore, patients undergoing cystectomy (InQ + FU) were excluded from the adjusted study population of n = 4541 patients (WL: 79%; BL: 21%). Mean total costs of BL-TURB were initially comparable to WL-TURB (WL: EUR 4534 vs. BL: EUR 4543) and tended to be lower compared to WL-TURB in the first two quarters of FU. After one year (3rd FU quarter), costs equalized. Considering total FU, mean costs of BL-TURB were significantly lower compared to WL-TURB (WL: EUR 7073 vs BL: EUR 6431; p = 0.045).. This retrospective analysis of healthcare claims data highlights the comparability of costs between BL-TURB and WL-TURB.

Topics: Aged; Aminolevulinic Acid; Carcinoma; Cystectomy; Cystoscopy; Female; Germany; Health Care Costs; Health Services Research; Humans; Insurance Claim Review; Male; Neoplasm Recurrence, Local; Photosensitizing Agents; Retrospective Studies; Urinary Bladder Neoplasms

To evaluate the diagnostic performance of fluorescent voided urine cytology (FVUC) using a novel automated detection technology to screen for primary bladder cancer and for surveillance of recurrent bladder tumour.. We created a rapid, objective, automated, and high-throughput detection device for hexylaminolevulinate-mediated FVUC, named the cellular fluorescence analysis unit-II (CFAU-II). Two different cohorts were used in this study: (i) screening test for primary bladder cancer (165 patients with bladder cancer and 52 controls), and (ii) surveillance test for detecting intravesical recurrent tumour (192 patients with treated non-muscle-invasive bladder cancer and 15 with post-nephroureterectomy upper urinary tract cancer). Voided urine samples were subjected to urine analysis, conventional VUC (cVUC), and FVUC. Diagnostic performance was compared between cVUC, FVUC, and a combination of the two.. A total of 614 urine samples were successfully collected, processed, and analysed. Comparative analysis of the screening test cohort demonstrated that the overall sensitivity of FVUC (63%, P < 0.001) and combination testing (72%, P < 0.001) was significantly higher than that of cVUC (29%). FVUC was found to be superior in most of the subgroups, especially in low-grade, Ta, and small tumours. Analysis of the surveillance test cohort showed that combination testing achieved a sensitivity of 82% and a negative predictive value of 98%, whereas those of cVUC were 39% and 96%, respectively. According to the pathological finding of recurrent tumours presenting false-negative result in the FVUC, the majority of the overlooked recurrent diseases were Ta low-grade tumours. Logistic regression analysis suggested an association between the risk of false-positive results and high density of urine white blood cells and alkaluria.. The present findings clearly demonstrate that FVUC using the newly developed automation technology has superior sensitivity to cVUC for both screening for primary bladder cancer and recurrent tumour detection. It is essential to confirm the clinical usefulness of this method via further large-scale studies, in addition to ensuring its affordability and availability.

Topics: Aminolevulinic Acid; Cytodiagnosis; Early Detection of Cancer; Humans; Optical Imaging; Population Surveillance; Prospective Studies; Urinary Bladder Neoplasms

Hexaminolevulinate (HAL) induced Protoporphyrin IX (PpIX) fluorescence is commonly used to differentiate cancer cells from normal cells in vivo, as for instance in blue light cystoscopy for bladder cancer diagnosis. A detailed approach is here provided to use this diagnostic principle ex vivo in an immunosensor device, towards enabling non-invasive cancer diagnostic from body fluids, such as urine. Several factors susceptible to affect the applicability of HAL-assisted diagnosis in body fluids were tested. These included the cell viability and its impact on PpIX fluorescence, the storage condition and shelf life of HAL premix reagent, light exposure (360-450 nm wavelengths) and its corresponding effect on both intensity and bleaching of the PpIX fluorescence as a function of the microscopy imaging conditions. There was no significant decrease in the viability of bladder cancer cells after 6 h at 4 °C (student's t-test: p > 0.05). The cellular PpIX fluorescence decreased in a time-dependent manner when cancer cells were kept at 4 °C for extended period of time, though this didn't significantly reduce the fluorescence intensity contrast between cancer and non-cancer cells kept in the same condition for 6 h. HAL premix reagent kept in long term storage at 4 °C induced stronger PpIX fluorescence than reagent kept in the - 20 °C freezer. The PpIX fluorescence was negatively affected by repeated light exposure but increased with illumination intensity and exposure time. Though this applied to both healthy and cancer cell lines, and therefore did not statistically improved the differentiation between cell types. This study revealed important experimental settings that need to be carefully considered to benefit from the analytical potential of HAL induced fluorescence when used in technologies for the diagnosis of cancer from body fluids.

Topics: Aminolevulinic Acid; Biosensing Techniques; Cell Line, Tumor; Cells, Cultured; Humans; Immunologic Tests; Liquid Biopsy; Microfluidics; Photosensitizing Agents; Protoporphyrins; Sensitivity and Specificity; Urinary Bladder Neoplasms; Urothelium

Bladder cancer is the eleventh most commonly diagnosed cancer worldwide. The recurrence rate of this cancer can be very high, up to 45%. Photodynamic diagnosis (PDD) is more sensitive than standard procedures for the detection of malignant tumours. The aim of the study was to evaluate oncological outcomes in white light TURB (WL-TURB) and hexaminolevuninate blue light TURB (Hal-TURB).. This was a retrospective longitudinal single-center study. In the period between January 2016 and October 2016 WL-TURB was the only therapeutic option available. From November 2016 until April 2017 all TURBs were fluorescence-guided (Hal-TURB). Kaplan-Meier curves have been used to estimate recurrence free survival rates.. One hundred and eleven patients underwent Hal- TURB and 137 underwent WL-TURB. Recurrence rate after 12 months was 19.8% (22 out of 111 patients) and 37.2% (51 out of 137 patients) in HAL-group and WL-group respectively (p < 0.01). The recurrence-free period was longer in HAL-group rather than WL-group (8.9 months vs 7.3 months, p < 0.05). Moreover, the recurrence rate during the first 6 months was 3.7% in patients who underwent HAL-TURB and 16% in those who received WL-TURB (p < 0.01).. The results of the study show that recurrence-free survival was longer in patients undergoing HAL-TURB compared to the patients who received standard WL-TURB.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; Disease-Free Survival; Female; Fluorescence; Humans; Kaplan-Meier Estimate; Light; Male; Middle Aged; Neoplasm Recurrence, Local; Photosensitizing Agents; Retrospective Studies; Time Factors; Urinary Bladder Neoplasms

To investigate whether hexaminolevulinate-based (HAL) bladder tumor resection (TURBT) impacts on outcomes of patients with primary non-muscle-invasive bladder cancer (NMIBC) who were eventually treated with radical cystectomy (RC).. A total of 131 consecutive patients exhibiting NMIBC at primary diagnosis were retrospectively investigated whether they had undergone any HAL-guided TURBT prior to RC. Uni- and multivariable analyses were used to evaluate the impact of HAL-TURBT on cancer-specific (CSS) and overall survival (OS). The median follow-up was 38 months (IQR 13-56).. Of the 131 patients, 69 (52.7%) were managed with HAL- and 62 (47.3%) with white light (WL)-TURBT only prior to RC. HAL-TURBT was associated with a higher number of TURBTs prior to RC (p = 0.002) and administration of intravesical chemotherapy (p = 0.043). A trend towards a higher rate of tumor-associated immune cell infiltrates in RC specimens (p = 0.07) and a lower utilization rate of post-operative systemic chemotherapy (p = 0.10) was noted for patients who were treated with HAL-TURBT. The 5-year CSS/OS was 90.9%/74.5% for the HAL-group and 73.8%/55.8% for the WL-group (p = 0.042/0.038). In multivariable analysis, lymph node tumor involvement (p = 0.007), positive surgical margins (p = 0.001) and performance of WL-TURBT only (p = 0.040) were independent predictors for cancer-specific death.. The present data suggest that the resection of NMIBC under HAL exerts a beneficial impact on outcomes of patients who will need to undergo RC during their course of disease. This finding may be due to improved risk stratification as the resection under HAL may allow more patients to be treated timely and adequately.

Topics: Administration, Intravesical; Aged; Aminolevulinic Acid; Antineoplastic Agents; Cystectomy; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Photochemotherapy; Photosensitizing Agents; Prognosis; Retrospective Studies; Risk Assessment; Urinary Bladder; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Cystoscopy; Humans; Urinary Bladder Neoplasms

While photodynamic diagnosis during transurethral resection of bladder tumor seems warranted only in seemingly high-risk cases, early intravesical instillation of chemotherapy is warranted in all low-risk cases. According to the latest randomized controlled trial, data may make sense also in intermediate- and high-risk cases.

Topics: Administration, Intravesical; Aminolevulinic Acid; Antineoplastic Agents; Carbon Radioisotopes; Cystectomy; Cystoscopy; Dissent and Disputes; Early Detection of Cancer; Early Medical Intervention; Humans; Image Enhancement; Image-Guided Biopsy; Surgery, Computer-Assisted; Urinary Bladder; Urinary Bladder Neoplasms

Confocal laser endomicroscopy (CLE) uses a low-energy laser light source to obtain microscopic histology images of bladder tissue exposed to a fluorescent dye. To evaluate the feasibility of using CLE with two fluorophores: fluorescein (FLUO) and hexylaminolevulinate (HAL) to determine histologic and cytologic bladder cancer criteria.. Patients eligible for HAL-photodynamic diagnosis-assisted transurethral resection of bladder tumor were included. The procedures were performed with the patient under regional or general anesthesia (60-90 minutes) after bladder instillation of HAL (50 mL, 8 mmol/L; Hexvix. Twenty-one patients were included, 12 examined by CVI and 9 by CVII. Sample examination on CVI after HAL-CLE-only histologic analysis was not possible because HAL is mostly cytoplasmic and gives poor details on cellular architecture. On the contrary, FLUO-CLE gives good extracellular architecture and not clear information of nucleocytoplasmic abnormality. Samples on CVII for seven out of nine patients clearly showed cytoplasm of suspect cells and nuclei. In real time, fluorescence observed on bandwidth (673-800 nm) with HAL and FLUO was associated with the presence of cancer, with a sensibility and specificity of 80% and 100%, respectively.. Real-time cytodetection was feasible using two fluorophores (FLUO and HAL) and the new system of CVII. This technology was useful to observe cytoplasm, nuclei, and nucleocytoplasmic abnormality, but an improved system is necessary (to overcome the overlapping of fluorescence) to increase the specificity.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Aminolevulinic Acid; Cell Nucleus; Cross-Sectional Studies; Cytoplasm; Diagnosis, Computer-Assisted; Female; Fluorescein; Fluorescence; Fluorescent Dyes; France; Humans; Lasers; Male; Microscopy, Confocal; Middle Aged; Photochemotherapy; Prospective Studies; Urinary Bladder Neoplasms

The objective of the present study is to evaluate the diagnostic accuracy of hexylaminolevulinate (HAL) blue light cystoscopy compared with standard white light cystoscopy (WLC) in daily practice.. An observational, comparative, controlled (within patient) study was carried out at our Center. 61 consecutive patients with suspected or confirmed bladder cancer were recruited for the study from January 2008 until January 2015. Patients with suspected bladder cancer (positive cytology with negative WLC) or history of previous high-grade NMIBC or CIS were included in the study. Biopsies/resection of each positive lesion/suspicious areas were always taken after the bladder was inspected under WLC and BLC. Diagnoses of bladder tumor or CIS were considered as positive results, and the presence of normal urothelium in the biopsy specimen as negative result.. 61 BLC were performed. 15/61 (24.5%) with suspected initial diagnosis of NMIBC and 46/61 (75.5%) with a history of high-risk non-muscle invasive bladder cancer (NMIBC). We performed a total of 173 biopsies/TURBT of suspicious areas: 129 positive only to the BLC and 44 both positive to WLC and BLC. 84/173 biopsies/TURBT were positive for cancer. All 84 NMIBC were positive to the BLC, while 35/84 were positive to the WLC with a sensitivity of BLC and WLC respectively of 100% and 41.7%. Sensitivity of WLC for highgrade NMIBC and CIS was 34.1% and 39% respectively while sensitivity of BLC for high-grade NMIBC and CIS was 100%. The specificity of the WLC was 79.9% compared to 48.5% of the BLC. The positive predictive value of BLC and WLC were respectively 48% (95% CI: 0.447-0.523) and 79% (95% CI: 0.856-0.734).. Our data confirm those reported in the literature: BLC increases the detection rate of NMIBC particularly in high risk patients (history of CIS or high grade). BLC is a powerful diagnostic tool in the diagnosis of bladder cancer if malignancy is suspected (positive urine cytology) and if conventional WLC is negative.

Topics: Aged; Aminolevulinic Acid; Biopsy; Cystoscopy; Female; Humans; Light; Male; Predictive Value of Tests; Sensitivity and Specificity; Urinary Bladder Neoplasms

The Hexvix® Observational Patients Evaluation (HOPE) study was designed to determine the extent of distribution of the use of hexaminolevulinate in the diagnosis of non-muscle invasive bladder cancer (NMIBC) and assess patient and treatment characteristics associated with different endoscopic modalities and to address the French authorities' request for information on routine practices for NMIBC diagnosis and surveillance.. A prospective, observational study in 30 centres in France with fluorescence endoscopy equipment available. All candidates for endoscopy with transurethral resection who gave their consent were eligible. The primary endpoint was the proportion of patients with an NMIBC diagnosis performed with hexaminolevulinate.. 506 patients were included: 252 (49.8%) diagnosed with hexaminolevulinate and 254 (50.2%) with white-light endoscopy alone. There were more patients with tumour recurrence, multiple lesions, lesions with a diameter <3 cm, stage Ta disease, and grade 1 lesions in the hexaminolevulinate group. The first quartile median recurrence-free survival time was 310 days in the hexaminolevulinate group and 144 days in the standard-endoscopy group (p = 0.0015).. Hexaminolevulinate was in frequent use in France with specific patient and disease characteristics associated with its use. HOPE illustrates the type of data that can be gained in post-authorisation studies to address requests from European health authorities.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystectomy; Cystoscopy; Disease Progression; Disease-Free Survival; Evidence-Based Medicine; Female; France; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Photosensitizing Agents; Practice Patterns, Physicians'; Predictive Value of Tests; Prospective Studies; Time Factors; Treatment Outcome; Urinary Bladder Neoplasms; Urology; Young Adult

To compare the recurrence rate at 3 years (RR-3y) for non-muscle invasive bladder cancer (NMIBC) between good quality (GQ) PDD-TURBT and GQWL-TURBT where PDD is used in routine practice for all new tumours.. All new, consecutive, NMIBC that received "good quality" criteria first TURBT across a university hospital service were prospectively recruited to this study over a 4-year period. Data were prospectively collected on all WL-TURBTs performed in 2007/8 and compared with PDD-TURBT from 2009/10. Only resection meeting strict "good quality criteria" were included from each cohort to control for resection quality, then cases were further matched 1:1 based on demographic and pathological criteria. The primary outcome was overall and risk group-specific recurrence rate at 3 years.. Of 808 patients recruited, 345 had GQ-TURBT for NMIBC and were included. RR-3y was significantly less for GQ-PDD overall [RR-3y: GQ-PDD: 57/146 (39.0%), GQ-WL: 72/135 (53.3%) OR = 0.56 (0.35-0.90) p = 0.02] and on a 1:1 matched pair basis [RR GQ-PDD: 29/118 (24.6) vs. 59/118 (50.0) OR 0.33 (0.19-0.57) p < 0.001)]. Benefit was most marked in high-risk patients: RR-3y in high-risk patients treated with GQ-PDD was 25/48 (52.1%) vs. 28/35 (80%) for GQ-WL [OR 0.27 (0.10-0.74) p = 0.01].. When adopted for all new bladder tumour resections in routine practice, PDD appears to be associated with significantly reduced recurrence rates at 3 years in our "real life" experience, particularly in high-risk patients.

Topics: Administration, Intravesical; Aged; Aminolevulinic Acid; Cystectomy; Cystoscopy; Female; Humans; Kaplan-Meier Estimate; Light; Male; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Photosensitizing Agents; Prospective Studies; Risk Assessment; Surgery, Computer-Assisted; Urinary Bladder Neoplasms

White light cystoscopy (WLC) is the standard procedure for visualising non-muscle invasive bladder cancer (NMIBC). However, WLC can fail to detect all cancerous lesions, and outcomes with transurethral resection of the bladder differ between institutions, controlled trials, and possibly between trials and routine application. This noninterventional study assessed the benefit of hexaminolevulinate blue light cystoscopy (HALC; Hexvix. From May 2013 to April 2014, 403 patients with suspected NMIBC were screened from 30 German centres to perform an unprecedented detailed assessment of the additional detection of cancer lesions with HALC versus WLC alone.. Among the histological results for 929 biopsy samples, 94.3 % were obtained from suspected cancerous lesions under either WLC or HALC: 59.5 % were carcinoma tissue and 40.5 % were non-cancerous tissue. Of all cancer lesions, 62.2 % were staged as Ta, 20.1 % as T1, 9.3 % as T2, 7.3 % as carcinoma in situ (CIS), and 1.2 % were unknown. Additional cancer lesions (+6.8 %) and CIS lesions (+25 %, p < 0.0001) were detected by HALC plus WLC versus WLC alone. In 10.0 % of patients, ≥1 additional positive lesion was detected with HALC, and 2.2 % of NMIBC patients would have been missed with WLC alone. No adverse events were observed.. The results of this study demonstrate that HALC significantly improves the detection of NMIBC versus WLC alone in routine clinical practice in Germany. While this benefit is statistically significant across all types of NMIBC, it seems most relevant in CIS.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Carcinoma in Situ; Carcinoma, Transitional Cell; Cystoscopy; Female; Germany; Humans; Male; Middle Aged; Muscle, Smooth; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Photosensitizing Agents; Urinary Bladder; Urinary Bladder Neoplasms

Hexaminolevulinate hydrochloride with blue light cystoscopy is approved by the U.S. Food and Drug Administration as an adjunct to white light cystoscopy for the detection of urothelial cell carcinoma. In this study we examined the tolerability of the repeat use of white light cystoscopy with blue light cystoscopy.. We retrospectively reviewed the records of all patients who underwent white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride during a 34-month period at 2 institutions. We compared the incidence of adverse events after initial and subsequent procedures. We grouped, graded and assigned the degree of attribution for all adverse events.. A total of 180 patients underwent 269 white light cystoscopy with blue light cystoscopy procedures. Of those 180 patients 118 (65%) underwent white light cystoscopy with blue light cystoscopy only 1 time. The other 62 (35%) patients underwent white light cystoscopy with blue light cystoscopy 2 or more times, including 43 (24%) 2 times and 19 (10%) 3 or more times. We noted 89 adverse events out of 269 procedures (33%), of which 66 (74%) occurred after the first white light cystoscopy with blue light cystoscopy; 14 (16%) after the second time and 9 (10%) after the third time or more. We found no statistically significant difference in adverse events between those patients undergoing 1 vs 2 or more white light cystoscopy with blue light cystoscopy procedures (p=0.134). We observed 1 grade 3 adverse event and no grade 4 or 5 adverse events. None of the adverse events were classified as probably or definitely related to hexaminolevulinate hydrochloride.. In this retrospective study we found no statistically significant difference in the frequency or the grade of adverse events between first and repeat use of white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Carcinoma; Cystoscopy; Female; Humans; Male; Middle Aged; Photosensitizing Agents; Retrospective Studies; Urinary Bladder Neoplasms; Urothelium

Topics: Aminolevulinic Acid; Carcinoma, Transitional Cell; Cystoscopy; Humans; Urinary Bladder Neoplasms

To compare the accuracy of white light cystoscopy (WLC) and blue light cystoscopy (BLC) in a cohort of patients undergoing radical cystectomy (RC) for previously resected urothelial bladder cancer.. A cohort of patients undergoing RC received WLC and BLC prior radical surgery. To evaluate the residual tumor rate, the bladder was inspected after its removal and normal appearing mucosa sampled for histologic analysis. Lesions detected under WLC, BLC, or both, and biopsy samples from normal appearing mucosa, were all recorded separately.. Starting 2011, 64 patients underwent WLC and BLC prior cystectomy. Overall, 540 tissue samples were collected during cystoscopy and from normal appearing mucosa. Residual disease was found in 31/64 (48.4%) patients, including 27 (42.1%) cases of carcinoma in situ (CIS). The accuracy of BLC was much higher than WLC, both in the diagnosis of any residual disease (87.1% vs 32.3%, and 87.9% vs 51.5%, for sensitivity and specificity, respectively), as of CIS only (92.6% vs 29.6% and 83.8% vs 51.4%). We further evaluated the diagnostic accuracy as a result of the analysis on all specimens collected during the study. A total of 535 specimens were analyzed, and 58 specimens with residual disease were found, including 48 CIS foci. Again, detection rates and measures of accuracy were much better for BLC vs WLC, both overall (86.2% vs 31%, and 98.3% vs 93.3%, for sensitivity and specificity, respectively), and when CIS only was considered (89.6% vs 31.2% and 96.9% vs 92.8%).. Although BLC missed 12.9% of positive patients, and 7.4% of those with CIS, the agreement between BLC diagnostic accuracy and the definitive pathology was very robust.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Carcinoma in Situ; Carcinoma, Transitional Cell; Cystectomy; Cystoscopy; Female; Humans; Light; Male; Middle Aged; Neoplasm, Residual; Photosensitizing Agents; Sensitivity and Specificity; Urinary Bladder Neoplasms

To explore the cost impact on Swedish healthcare of incorporating one instillation of hexaminolevulinate hydrochloride (HAL) blue-light cystoscopy into transurethral resection of bladder tumour (TURBT) in patients with suspected new or recurrent non-muscle-invasive bladder cancer (NMIBC).. A decision tree model was built based on European Association of Urology guidelines for the treatment and management of NMIBC. Input data were compiled from two recent studies comparing recurrence rates of bladder cancer in patients undergoing TURBT with either the current standard of care (SOC) of white-light cystoscopy, or with the SOC and HAL blue-light cystoscopy. Using these published data with clinical cost data for surgical and outpatient procedures and pharmaceutical costs, the model reported on the clinical and economic differences associated with the two treatment options.. This model demonstrates the significant clinical benefits likely to be observed through the incorporation of HAL blue-light cystoscopy for TURBT in terms of reductions in recurrences of bladder cancer. Analysis of economic outputs of the model found that the use of one instillation of HAL for TURBT in all Swedish patients with NMIBC is likely to be cost-neutral or cost-saving over 5 years relative to the current SOC of white-light cystoscopy.. The results of this analysis provide additional health economic rationale for the incorporation of a single instillation of HAL blue-light cystoscopy for TURBT in the treatment of patients with NMIBC in Sweden.

Topics: Aminolevulinic Acid; Budgets; Costs and Cost Analysis; Cystoscopy; Disease Progression; Humans; Neoplasm Recurrence, Local; Photosensitizing Agents; Sweden; Urinary Bladder Neoplasms

This study explored the cost consequences of introducing hexaminolevulinate hydrochloride-guided blue-light flexible cystoscopy (HAL BLFC) as an adjunct to white-light flexible cystoscopy compared with white-light flexible cystoscopy alone, for the detection and management of nonmuscle invasive bladder cancer in Sweden.. The model evaluated 231 patients in the outpatient setting after successful initial transurethral resection of the bladder tumor.. HAL BLFC introduction across all risk groups resulted in minimal budget impact (+1.6% total cost/5 years, or 189 Swedish Krona [SEK] per patient/year), and translated to cost savings in intermediate- and high-risk groups from year 2.. HAL BLFC allowed more outpatient treatment with improved recurrence detection and reduced transurethral resection of the bladder tumors, cystectomies, bed days and operating room time, with minimal cost impact across all risk groups, demonstrating the economic benefits of introducing HAL.

Topics: Aminolevulinic Acid; Costs and Cost Analysis; Cystectomy; Cystoscopy; Disease Progression; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Light; Markov Chains; Neoplasm Staging; Outpatients; Population Surveillance; Recurrence; Sweden; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Cystectomy; Cystoscopy; Fluorescence; Humans; Neoplasm Recurrence, Local; Urinary Bladder; Urinary Bladder Neoplasms

The authors evaluated the role of photodynamic cystoscopy in the detection of additional urothelial lesions, mainly carcinoma in situ, that would not be detected solely with white light cystoscopy, leading to disease understaging.. From 2009 to 2011, 70 patients underwent white light cystoscopy, followed by photodynamic cystoscopy (blue light system, Karl Storz, Tuttlingen, Germany). Preoperatively they were instilled intravesically with 50ml of Hexvix (Hexaminolevulinate hexylester). We recorded all lesions found with white light cystoscopy and the additional lesions revealed by blue light cystoscopy. Afterward all lesions were removed and sent for pathologic evaluation.. Seventeen patients (24.3%) had primary tumors while 53 patients (75.7%) had recurrent disease. In 53 out of 70 patients (75.7%) white light cystoscopy revealed urothelial lesions. In the rest 17 patients who had no findings with white light cystoscopy, blue light cystoscopy revealed 7 cases of Cis (41.2%) and 8 cases of dysplasia (47%). In the group of patients with visible lesions in white light cystoscopy photodynamic cystoscopy revealed additional carcinoma in situ in 22 patients. Altogether additional carcinoma in situ cases found with the aid of photodynamic cystoscopy were 29 out of 70 cases (41.4%).. Photodynamic cystoscopy is the most efficient diagnostic procedure for flat urothelial lesions and especially for carcinoma in situ. It is significantly more sensitive than conventional white light cystoscopy in Cis diagnosis, thus reducing understaging of the disease and consequently improving recurrence and progression rates.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Carcinoma in Situ; Cystoscopy; Female; Fluorescence; Humans; Male; Middle Aged; Neoplasm Staging; Photosensitizing Agents; Retrospective Studies; Urinary Bladder Neoplasms

To assess the sensitivity and specificity of blue-light cystoscopy (BLC) with hexaminolevulinate as an adjunct to white-light cystoscopy (WLC) vs WLC alone for the detection of non-muscle-invasive bladder cancer (NMIBC), in routine clinical practice in Spain.. An intra-patient comparative, multicentre, prospective, observational study. Adults with suspected or documented primary or recurrent NMIBC at eight Spanish centres were included in the study. All patients were examined with WLC followed by BLC with hexaminolevulinate. We evaluated the detection rate of bladder cancer lesions by WLC and BLC with hexaminolevulinate, overall and by tumour stage and compared with histological examination of the biopsied lesions. Sensitivity and specificity was calculated.. In all, 1,569 lesions were identified from 283 patients: 621 were tumour lesions according to histology and 948 were false-positives. Of the 621 tumour lesions, 475 were detected by WLC (sensitivity 76.5%, 95% confidence interval [CI] 73.2-79.8) and 579 were detected by BLC (sensitivity 93.2%, 95% CI 91.0-95.1; P < 0.001). There was a significant improvement in the sensitivity in the detection of all types of NMIBC lesions with BLC compared with WLC. Of 219 patients with tumours, 188 had NMIBC [highest grade: carcinoma in situ (CIS), n = 36; Ta, n = 87; T1, n = 65). CIS lesions were identified more with BLC (n = 27) than with WLC [n = 19; sensitivity: BLC 75.0% (95% CI 57.8-87.9) vs WLC 52.8% (95% CI 35.5-69.6); P = 0.021]. Results varied across centres.. This study shows that improvement in diagnosis of NMIBC, mainly CIS and Ta tumours, obtained with BLC with hexaminolevulinate as an adjunct to WLC vs WLC alone can be shown in routine clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; Female; Humans; Male; Middle Aged; Sensitivity and Specificity; Spain; Urinary Bladder Neoplasms

Photodynamic diagnosis after instillation of hexylaminolevulinate (Hexvix(®)) during transurethral resection of the bladder (TURB) helps in the detection of tumors and results in a reduction of recurrence. The medical and economic impact of fluorescence compared to conventional white light TURB needed to be analyzed in the French healthcare system. The aim of this study was to evaluate the medical and economic impact of the blue light TURB in the treatment of NMIBC.. A cost-utility model, based on data from the literature and expert opinions, combining a decision tree and a Markov model was used to simulate the initial management after a first TURB of all new patients diagnosed with symptoms consistent with NMIBC and outcomes at short and long terms. In this model, the initial TURB could be achieved either with fluorescence in addition to white light, or with white light only. The main criteria of the model was based on the quality adjusted life years (QALY). The economic evaluation focused on the direct costs. The test's results and costs were determined from diagnosis until death of patients.. The use of photodynamic diagnosis during TURB resulted in an improvement in QALYs (0.075) and a reduction of € 670 of the costs compared to the conventional treatment with white light. Thus, the blue light resection was defined as a strategy called "dominant" over the TURB in white light.. In the context of the French health system, the model of the study showed that the blue light cystoscopy during TURB was associated with increased QALYs and reduced health spending. This kind of result is rare in oncology. This health economic analysis confirms the interest of hexylaminolevulinate acid in initial management of NMIBC, according to studies conducted in United Kingdom, Italy and Poland.

Topics: Administration, Intravesical; Aged; Aminolevulinic Acid; Carcinoma, Transitional Cell; Cost Savings; Cost-Benefit Analysis; Cystectomy; Cystoscopy; Female; Fluorescence; France; Humans; Light; Male; Neoplasm Invasiveness; Neoplasm Staging; Observational Studies as Topic; Photosensitizing Agents; Predictive Value of Tests; Prevalence; Quality of Life; Sensitivity and Specificity; Treatment Outcome; Urinary Bladder Neoplasms

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.. 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.. 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.. 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.

Topics: Aged; Aminolevulinic Acid; Controlled Clinical Trials as Topic; Cystoscopy; Drug Approval; Female; Humans; Light; Male; Product Surveillance, Postmarketing; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Cystectomy; Cystoscopy; Health Care Costs; Humans; Urinary Bladder Neoplasms

Hexaminolevulinate HCl is a diagnostic imaging agent used with blue light during cystoscopy to help detect non-muscle-invasive bladder cancer. Blue light cystoscopy performed using hexaminolevulinate HCl has been found to detect more papillary non-muscle-invasive bladder tumors than cystoscopy performed using standard white light. Because bladder instillation and retention requirements of hexaminolevulinate during cystoscopy can affect patient flow in the perioperative setting, this technique necessitates changes in nursing practice and care of patients with known or suspected non-muscle-invasive bladder cancer. Nursing personnel at one facility followed the AORN guidelines for preoperative patient care in the ambulatory setting to address staffing, preoperative nursing assessment, anesthesia evaluation, and preoperative teaching related to implementing blue light cystoscopy.

Topics: Aminolevulinic Acid; Cystoscopy; Education, Nursing, Continuing; Humans; Urinary Bladder Neoplasms

Prospective evaluation of bladder tumor targeting by Hexvix(®) fluorescence.. From September 2008 to April 2012, 107 patients have been evaluated using Hexvix(®) technique (blue light) for typically papillary bladder tumor or suspected bladder tumor. Clinical and pathological data have been collected prospectively and patients have been classified using EORTC score.. From the 107 patients, 67 have been identified with bladder cancer and 328 samples have shown positive fluorescence in blue light. Compared to white light, 13 additional tumors have been diagnosed by Hexvix(®) for 11 patients: Cis (n=6), LMP (n=3), pTa low grade (n=3), pT1 low grade (n=1) (P=0.003). The false positive rate for Hexvix(®) was 53.4% versus 52% for white light. Previous TCC history, multifocality and EORTC score for recurrence and progression have been associated with better bladder cancer targeting by Hexvix(®) (P=0.007; P=0.01; P=0.03; P=0.04).. In our experience, Hexvix(®) targeting was associated with better diagnosis for bladder cancer with 9% (13/144) of new positive samples (P=0.003). In our study, false positive rate is a critical point (53.4%). Multifocality, previous TCC, and EORTC score for recurrence and progression might allow selecting patients to be targeted by Hexvix(®).

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; Female; Fluorescence; France; Humans; Light; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Photosensitizing Agents; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Survival Analysis; Urinary Bladder Neoplasms

Several studies, including the recently published phase III study by Stenzl and colleagues have demonstrated that hexaminolevulinate hydrochloride, when used with blue light fluorescence cystoscopy, improves detection of non-muscle invasive bladder tumors compared to white light cystoscopy and transurethral resection of bladder tumors (TURB) alone.. The objective of this study was to conduct a detailed assessment of the cost-effectiveness of using hexaminolevulinate hydrochloride with blue light cystoscopy as an adjunct to white light versus white light cystoscopy alone at time of initial TURB in the United States. A probabilistic decision tree model, using TreeAge Pro 2011 software, was developed using base case scenario cost and utility estimates.. Incorporation of hexaminolevulinate hydrochloride into diagnostic cystoscopy results in lower costs over 5 years ($25,921) as compared to those patients who initially receive white light cystoscopy ($30,581). Those patients who initially receive hexaminolevulinate hydrochloride blue light TURB also experience a lower overall cancer burden.. Hexaminolevulinate hydrochloride may be cost effective when used at first TURB for patients with suspected new or recurrent non-muscle invasive bladder cancer.

Topics: Aged; Aminolevulinic Acid; Cost-Benefit Analysis; Cystoscopy; Female; Follow-Up Studies; Humans; Male; Retrospective Studies; Software; United States; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Antibiotics, Antineoplastic; Cystoscopy; Female; Humans; Male; Mitomycin; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Urinary Bladder Neoplasms

Photodynamic Diagnosis (PDD), an adjunct to white light cystoscopy, has been shown to improve detection and thoroughness of resection of bladder cancer by enhancing visualisation of malign lesions during transurethral resection of bladder tumours (TURBT) compared to the sole use of standard white light cystoscopy. The PDD also has been shown to improve recurrence of free survival in non-muscle invasive bladder cancer. Little data on its impact on outcome in non-muscle invasive bladder cancer of high risk of progression is available however. The few trials and studies available demonstrate improved accuracy of diagnosis especially of flat malign lesions. In addition, improved recurrence rates have been suggested without an impact on progression rates in early invasive bladder cancer indicating little influence of thoroughness of resection on the tumour biology in those tumour stages. While no specific and larger data on impact of PDD on cancer specific survival exist to date and the few long-term data suggest little impact, improved accuracy of diagnosis is suggested to be beneficial for clinical decision making and thus a value of PDD is postulated in the management of high-risk non-muscle invasive bladder cancer.

Topics: Aminolevulinic Acid; Carcinoma, Transitional Cell; Cystoscopy; Humans; Optical Imaging; Photosensitizing Agents; Urinary Bladder Neoplasms

We studied how to avoid irritative bladder symptoms after bladder photodynamic therapy, such as urgency, frequency and pain, which are associated with the inflammation and destruction of normal urothelium.. Rats bearing orthotopic bladder tumors were instilled with hexyl-aminolevulinate and illuminated with red light at a high vs low (100 vs 15 mW/cm(2)) fluence rate. Cystectomy specimens 48 hours after treatment were subjected to anatomopathological examination. Inflammatory reaction and apoptosis were evaluated. In vivo photobleaching was assessed during illumination at each fluence rate.. All superficial tumors were eradicated irrespective of light dose and fluence rate. High fluence rates induced necrosis with inflammatory reaction and absent normal urothelium. Low fluence rates did not provoke inflammation and resulted in apoptotic cell death with preserved urothelial integrity. This could be attributable to faster photobleaching of the photosensitizer in normal urothelium at low fluence rates.. Bladder photodynamic therapy at a low fluence rate minimizes side effects without hampering therapeutic efficacy.

Topics: Aminolevulinic Acid; Animals; Apoptosis; Cystectomy; Female; Immunoenzyme Techniques; Photochemotherapy; Photosensitizing Agents; Rats; Rats, Inbred F344; Spectrometry, Fluorescence; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL-FC has a role in improving detection of NMIBC and provide recommendations on situations for its use. Since the publication of the EAU guidelines and the European consensus statement, new evidence on the efficacy of HAL-FC in reducing recurrence of NMIBC, compared with white light cystoscopy (WLC), have been published.. To consider whether these new trials have an impact on the expert guidelines and on clinical practice (e.g. supporting existing recommendations or providing evidence for a change or expansion of practice), a group of bladder cancer experts from Denmark, Finland, Norway and Sweden met to address the following questions: What is the relevance of the new data on HAL-FC for clinical practice in managing NMIBC? What impact do the new data have on European guidelines? How could HAL-FC be used in clinical practice? and What further information on HAL-FC is required to optimize the management of NMIBC?. This article reports the outcomes of the discussion at the Nordic expert panel meeting, concluding that, in line with European guidance, HAL-FC has an important role in the initial detection of NMIBC and for follow-up of patients to assess tumour recurrence after WLC. It provides practical advice, with an algorithm on the use of this diagnostic procedure for urologists managing NMIBC.

Topics: Aminolevulinic Acid; Consensus; Cystoscopy; Europe; Fluorescence; Humans; Photosensitizing Agents; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms

Estimate the feasibility and the results of the realization in consultation of a flexible videocystoscopy in blue light preceded by an instillation of Hexvix(®) (GE Healthcare) for the initial diagnosis or the surveillance of vesicals tumors (VT). The objective of this study was to compare the number of hurts seen in white light and in blue light, and to estimate in which percentage of case the use of the Hexvix(®) in consultation modified the care.. Thirty consecutive patients (26 men and four women) were estimated prospectively by vesical videofibroscopy in blue light (Wolf's PD videofibroscope) realized 1 hour after an endovesical instillation of Hexvix(®). All the examinations were realized in external consultation under local anesthetic by xylocaine gel: 23 (76.6%) patients within the framework of a surveillance of VT and seven (23.4%) for the diagnosis of a hematuria with normal echography. When a suspect hurt or a VT was discovered, the patients benefited from an endoscopic resection under anesthesia with new cystoscopy in blue light.. Suspect hurts were revealed in 10 out of 30 patients, five in white and blue light, five in blue light only. Among the five only visible hurts in blue light, three were urothelial tumors (any pTa of bottom-rank, less of 5 mm) and two non-specific hurts. No CIS's hurt was revealed during this study. The fibroscopy in blue light allowed to diagnose invisible hurts in white light in three patients (10%) and has modified the care of five patients (16.7%). The duration of the cystoscopy was on average of 9.5 minutes. The tolerance of the examination was good and no complication arose.. The use of the flexible videocystoscopy in blue light +Hexvix(®) has allowed to improve the rate of detection of VT. Except CIS's hurts, this improvement was bound to the diagnosis of little aggressive small-sized VT. The indications must be specified by studies of bigger scale and a medical economic evaluation.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; Feasibility Studies; Female; Humans; Male; Middle Aged; Prospective Studies; Urinary Bladder Neoplasms; Video Recording

In patients with non-muscle invasive bladder cancer, fluorescence cystoscopy can improve the detection and ablation of bladder tumors. In this paper we describe the technique and practical aspects of hexaminolevulinate (HAL) fluorescence cystoscopy, also known as "blue light cystoscopy".

Topics: Aminolevulinic Acid; Carcinoma in Situ; Cystoscopy; Fluorescence; Humans; Patient Selection; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Cystoscopy; Female; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Carcinoma in Situ; Diagnostic Techniques, Urological; False Positive Reactions; Humans; Male; Middle Aged; Photosensitizing Agents; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Carbon Radioisotopes; Carcinoma, Papillary; Cost-Benefit Analysis; Cystoscopy; Humans; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms

To assess the learning curve for fluorescence cystoscopy using hexaminolevulinate hydrochloride (HAL) in patients with bladder cancer.. Fifty patients underwent bladder instillation with HAL. Two senior residents inspected separately the bladder using white light cystoscopy, followed by fluorescence cystoscopy and mapped the lesions. An experienced with photodynamic diagnosis (PDD) urologist also performed both cystoscopies, mapped, resected or cold biopsied suspect lesions under the supervision of another experienced urologist. To evaluate the learning curve, patients were divided into five subgroups, including group 1 (patients 1-10), group 2 (11-20), group 3 (21-30), group 4 (31-40) and group 5 (41-50). The kappa statistics was calculated to assess interobserver agreement between the physicians and the false positive rates of urologists and residents were also compared.. Histologically verified tumors were diagnosed in 103 of 142 lesions identified by PDD. The interobserver agreement between urologists and residents was moderate, moderate, good, excellent, and excellent for group 1, 2, 3, 4, and 5, respectively. Both residents had increased false positive rates compared to urologists in all subgroups of patients but this difference did not reach statistical significance. In addition, false positive rate of residents was declining as the number of procedures was increasing.. Our data suggest that 20 cases of HAL PDD are required to achieve a good interobserver agreement between inexperienced and experienced operator, and excellent agreement is achieved after 30 cases. The false positive rate of inexperienced operators was comparable to the experts and showed a gradual decrease.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Carcinoma; Clinical Competence; Cystoscopy; False Positive Reactions; Female; Fluorescence; Humans; Learning Curve; Light; Male; Middle Aged; Observer Variation; Photosensitizing Agents; Prospective Studies; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Cystectomy; Female; Humans; Light; Male; Neoplasm Recurrence, Local; Radionuclide Imaging; Urinary Bladder Neoplasms

What's known on the subject? and What does the study add? Fluorescence cystoscopy with hexylaminolevulinate (h-ALA, Hexvix®) is known to improve tumour detection in non-muscle-invasive bladder cancer. However, specificity is relatively low and the intensity of the observed fluorescence signal decreases over time due to protoporphyrin IX (PpIX) efflux. This study evaluates in an in vivo model the use of a dendritic 5-aminolevulinic acid compound for fluorescence diagnosis. Fluorescence ratios between tumour and urothelium as well as muscle were significantly better as compared with h-ALA. Sustained synthesis of PpIX accounts for preservation of fluorescence for >24 h.. • To overcome the relative lack of tumour selectivity of fluorescence-guided cystoscopy using 5-aminolevulinic acid (ALA) or its ester derivative (e.g. hexylaminolevulinate, h-ALA; Hexvix®), we evaluated the use of dendrimers bearing different ALA loads in rats bearing orthotopic bladder tumours.. • Rat bladders were instilled with h-ALA or ALA dendrimers and fluorescence ratio between tumour and normal urothelium, as well as tumour and muscle and depth of fluorescence were determined with Image J software. • Quantification of ALA and/or esters systemic reabsorption was evaluated by high-performance liquid chromatography.. • Slow hydrolysis of ALA from dendrimers as observed in vitro implies a higher initial ALA load and longer resting times in vivo. Sustained synthesis of protoporphyrin IX (PpIX) explains persistence of fluorescence for >24 h. • There were significantly better fluorescence ratios with dendrimers, as well as higher penetration depths and absence of systemic reabsorption.. • The prolonged and sustained PpIX synthesis, the improved tumour selectivity with a deeper penetration and the absence of systemic reabsorption are primary indicators that ALA dendrimers could be an alternative to h-ALA in fluorescence-guided cystoscopy.

Topics: Administration, Intravesical; Aminolevulinic Acid; Animals; Dendrimers; Female; Microscopy, Fluorescence; Neoplasms, Experimental; Photosensitizing Agents; Rats; Rats, Inbred F344; Reproducibility of Results; Urinary Bladder Neoplasms

In this preclinical study, we examined the biodistribution of hypericin formulated as its water-soluble PVP-hypericin complex in the different layers (urothelium, submucosa, muscle) of a normal rat bladder and a rat bladder bearing a malignant urothelium composed of syngeneic AY-27 tumor cells. The results were compared with the biodistribution of hexaminolevulinate (HAL)-induced protoporphyrin IX (PpIX).. Freshly prepared PVP-hypericin and HAL solutions were instilled in both normal as well as tumor-bearing rat bladders. Following instillation, bladders were removed and snap frozen in liquid nitrogen. Fluorescence of PVP-hypericin or PpIX-induced HAL was measured in the bladder layers and quantified using image analysis software.. The results of these experiments show that PVP-hypericin (30 μM) accumulated about 3.5-fold more in malignant urothelial tissue when compared to normal urothelium, whereas PpIX accumulated to the same extent in malignant and normal urothelium, both after intrabladder instillation of 8 or 16 mM HAL. Besides, PVP-hypericin and PpIX accumulated selectively in the urothelium with a tumor-to-muscle ratio of 30.6 for PVP-hypericin and 3.7-8.3 for 16 and 8 mM HAL, respectively.. This study shows that PVP-hypericin appears to have great potential as a photodynamic agent against non-muscle-invasive bladder cancers after intravesical administration, with a limited risk of affecting the deeper layers of the bladder.

Topics: Aminolevulinic Acid; Animals; Anthracenes; Antineoplastic Agents; Female; Fluorescence; Perylene; Photochemotherapy; Povidone; Protoporphyrins; Rats; Rats, Inbred F344; Solubility; Tissue Distribution; Urinary Bladder Neoplasms

Photodynamic therapy (PDT) is of increasing interest as a relevant treatment for human urinary bladder cancer. In the present experiments, the rat bladder transitional carcinoma cell line AY-27 was used as a model to study cell destruction mechanisms induced by PDT. Red LED light (630 nm) PDT with hexylaminolevulinate (HAL) as precursor for the photosensitizer protoporphyrin IX (PpIX) was used in treatment of the cells. Flow cytometry with fluorescent markers annexin V, propidium iodide and YO-PRO-1, as well as MTT assay and confocal microscopy, were used to map cell inactivation after PDT. Dark toxicity of HAL alone was low in these procedures and LD(50) (24 h, MTT assay) was approximately 1.6 J cm(-2) for standard red light (LED) irradiation (36 mW cm(-2)). Measurements done 1 h after HAL-PDT showed a maximum apoptotic level of about 10% at 6 J cm(-2), however the dominating mode of cell death was necrosis. Forward light scattering indicated an increase in cell size at low doses, possibly due to necrosis. Survival curves had a dual-slope shape, a fit to single hit, multi-target approximation gave a parameter estimate of n = 10 and D(0) about 2.6 J cm(-2). Replacing continuous light with fractionated light delivery (45 s light/60 s darkness) did not affect the treatment outcome.

Topics: Aminolevulinic Acid; Animals; Apoptosis; Carcinoma, Transitional Cell; Cell Line, Tumor; Flow Cytometry; Light; Photochemotherapy; Photosensitizing Agents; Rats; Urinary Bladder Neoplasms

Photodynamic therapy (PDT) using blue light and the potent precursor for protoporphyrin IX, hexyl aminolevulinate (HAL), has been shown to induce apoptosis and necrosis in cancer cells, but the mechanism remains obscure. In the present study, we examined protein carbonylation, expression levels and post-translational modifications in rat bladder cells (AY-27) after PDT with HAL. Altered levels of expression and/or post-translational modifications induced by PDT were observed for numerous proteins, including proteins required for cell mobility, energy supply, cell survival and cell death pathways, by using two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry (MS). Moreover, 10 carbonylated proteins associated with cytoskeleton, transport, oxidative stress response, protein biosynthesis and stability, and DNA repair were identified using immunoprecipitation, two-dimensional gel electrophoresis and MS. Overall, the results indicate that HAL-mediated PDT triggers a complex cellular response involving several biological pathways. Our findings may account for the elucidation of mechanisms modulated by PDT, paving the way to improve clinic PDT-efficacy.

Topics: Aminolevulinic Acid; Animals; Apoptosis; Cell Line, Tumor; Cell Survival; DNA Repair; Electrophoresis, Gel, Two-Dimensional; Photochemotherapy; Photosensitizing Agents; Protein Carbonylation; Protein Processing, Post-Translational; Proteome; Rats; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Urinary Bladder Neoplasms

Photodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area.. Fluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients.. A total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL.. Hexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Cystoscopy; Female; Humans; Male; Middle Aged; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Cystoscopy; Female; Humans; Male; Urinary Bladder Neoplasms

This study was carried out to learn whether cytological specimens from urinary bladder lavages express the tumor suppressor gene p16INK4a, whether an abnormally increased expression indicates a cancerous state and whether cytological measurements are comparable regarding sensitivity and specificity with measurements made in histological sections of biopsies.. A total of 82 urine specimens of patients suspected of having a bladder tumor were examined for the presence of p16INK4a.. Out of 46 patients with urothelial carcinoma 29 expressed p16INK4a in the cells in the urine specimens. Out of 36 patients free of cancer 30 expressed no p16INK4a in cytological specimens. The sensitivity of the expression proved to be 63% and the specificity 83%. Well-differentiated carcinomas seldomly expressed an increased p16INK4a (sensitivity 27%), whereas moderately differentiated carcinomas showed a sensitivity of 69% and poorly differentiated carcinomas a sensitivity of 77%.. Compared to other minimally invasive tumor markers, such as NMP22, the expression of p16INK4a in cytology specimens of urine appears to be a sensitive marker for urothelial carcinoma, especially for the detection of poorly differentiated carcinomas. Its high specificity makes it ideal for use in tumor screening.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Biomarkers, Tumor; Biopsy; Carcinoma, Transitional Cell; Cyclin-Dependent Kinase Inhibitor p16; Cystoscopy; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Male; Mass Screening; Middle Aged; Predictive Value of Tests; Reagent Kits, Diagnostic; Urinary Bladder; Urinary Bladder Neoplasms

OBJECTIVE To determine if hexylaminolaevulinate fluorescence cystoscopy (HAL-FC) has the potential to improve the diagnosis of bladder cancer in patients who have been treated with bacille Calmette-Guérin (BCG). PATIENTS AND METHODS Patients scheduled for rigid cystoscopy after BCG therapy were recruited prospectively between April 2005 and February 2006. Patients received HAL (Hexvix, PhotoCure ASA, Oslo, Norway) and the D-light system (Storz, Tuttlingen, Germany) was used to detect fluorescence. The bladder was mapped and biopsies taken under white light and then using HAL-FC. The main outcome was the frequency and nature of additional pathology detected by HAL-FC. Twenty-seven patients (21 men and six women; median age 70 years, range 49-82) underwent 32 HAL-FC. RESULTS Recurrent bladder cancer was detected in 11 of the 32 (34%) examinations. HAL-FC detected additional pathology in five of the 27 (19%) patients. In two of these cases the additional pathology was clinically significant (one pT4G3 intraprostatic transitional cell carcinoma and one intravesical pT1G2 + carcinoma in situ), whereas in three cases the pathology was hyperplasia/dysplasia. Overall, the false-positive biopsy rate with HAL-FC was 63%. In the presence of positive voided urine cytology six of eight patients had recurrent bladder tumour and the false-positive biopsy rate was only 34%. Urine cytology was positive in four of five of the patients in whom additional pathology was detected by HAL-FC. CONCLUSIONS Clinically significant occult pathology can be detected using HAL-FC after BCG therapy, but in <10% of cases. The rate of false-positive biopsies is high but in our hands appears to be lower than with white-light guided biopsies after BCG. Our pragmatic approach is to use HAL-FC after BCG when clinical suspicion is high, and when the preoperative voided urine cytology is positive.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Aminolevulinic Acid; Antineoplastic Agents; BCG Vaccine; Cystoscopy; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Photosensitizing Agents; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Humans; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms

Fluorescence cystoscopy improves the detection of non-muscle-invasive bladder cancer, particularly carcinoma in situ, and reduces recurrence. The technique is well tolerated with few side effects. Guidelines recommend fluorescence cystoscopy in multifocal tumors, tumors >3cm, early recurrence, High grade cytology, follow-up of high-risk bladder cancer (T1G3 and CIS).

Topics: Aminolevulinic Acid; Carbon Radioisotopes; Cystoscopy; Fluorescence; Humans; Practice Guidelines as Topic; Radionuclide Imaging; Urinary Bladder Neoplasms

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.. 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.. 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.. 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.

Topics: Aged; Aminolevulinic Acid; Carcinoma in Situ; Cystoscopy; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Photosensitizing Agents; Prognosis; Retrospective Studies; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Cystoscopy; Humans; Urinary Bladder Neoplasms

To investigate the value of photodynamic diagnosis (PDD) using hexylaminolaevulinate (Hexvix, PhotoCure, Oslo, Norway) in the investigation of patients with positive urine cytology who have no evidence of disease after standard initial investigations.. Twenty-three patients referred with positive urine cytology but no current histological evidence of cancer were investigated between April 2005 and January 2007 with PDD, using Hexvix and the D-light system (Karl Storz, Tuttlingen, Germany) to detect fluorescence. The bladder was mapped initially under white light and then under 'blue-light'. Biopsies were taken from abnormal urothelium detected by white light, fluorescence, or both. All cytological specimens were reviewed by a reference cytopathologist unaware of the result of the PDD.. Twenty-five PDD-assisted cystoscopies were carried out on 23 patients (20 men/3 women; median age 64 years, range 24-80 years). Of the 23 patients, 17 (74%) were previously untreated for transitional cell carcinoma (TCC), whilst six were under surveillance for previous TCC. Nineteen of the 23 (83%) cytology specimens were confirmed as suspicious or positive by the reference pathologist. TCC of the bladder or preneoplastic lesions were diagnosed in six patients, i.e. six (26%) of those investigated and six of 19 (32%) with confirmed positive cytology. Four of the six were under surveillance for previous bladder tumour. Additional pathology was detected by fluorescence in five of the six patients, including two carcinoma in situ (CIS), one CIS + G3pT1 tumour, and two dysplasia. Diagnoses in PDD-negative cases included one upper tract TCC and four patients with stones. In addition, one patient had CIS diagnosed on both white light and PDD 6 months later.. Additional pathology was detected by HAL fluorescence cystoscopy in 32% of patients with confirmed positive urinary cytology. PDD is a key step in the management of patients with positive urinary cytology and no evidence of disease on conventional tests.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Carcinoma in Situ; Carcinoma, Transitional Cell; Cohort Studies; Cystoscopy; Female; Humans; Male; Microscopy, Fluorescence; Middle Aged; Photosensitizing Agents; Predictive Value of Tests; Sensitivity and Specificity; Urinary Bladder Neoplasms; Young Adult

Topics: Aminolevulinic Acid; Carbon Radioisotopes; Carcinoma in Situ; Diagnostic Techniques, Urological; Forecasting; Humans; Reproducibility of Results; Urinary Bladder Neoplasms

A decision analytic model was established to estimate the budget impact on the Swedish health service of using hexaminolevulinate (HAL) in conjunction with white light cystoscopy (WLC) in the management of bladder cancer for 1 year following initial diagnosis.. Flowcharts were developed to represent the diagnostic and treatment pathways for each of four risk groups for non-muscle-invasive bladder cancer (NMIBC), as defined by risk of tumour recurrence and progression. Flowcharts were based on European Association of Urology Guidelines and adjusted to current Swedish clinical practice. The model covers the use of HAL cystoscopy in the operating room to guide transurethral resection of the bladder (TURB) in all patients. HAL cystoscopy as an adjunct to WLC allows for more accurate and complete resection of tumours compared with WLC alone, and the model assumed a consequent reduction in recurrence of 40%.. The model projects that compared with WLC alone, use of HAL cystoscopy in the first TURB of all patients and for all TURBs due to recurrence in the first year after diagnosis, leads to a reduction of 23 cystectomies and 180 TURBs in a population of 2032 newly diagnosed bladder cancer patients. Avoidance of these procedures would result in a saving of SEK1 321 716 to the Swedish health service.. HAL cystoscopy, used as an adjunct to white light in guiding TURB in NMIBC patients, may result in reduction of invasive, time-intensive and high-cost procedures such as cystectomy and TURB, compared with WLC alone.

Topics: Adult; Aminolevulinic Acid; Carbon Radioisotopes; Computer Simulation; Cost Savings; Cystectomy; Cystoscopy; Decision Trees; Fluorescence; Health Care Costs; Humans; Male; Models, Economic; State Medicine; Sweden; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Carcinoma in Situ; Clinical Trials, Phase III as Topic; Cystoscopy; Humans; Microscopy, Fluorescence; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Photosensitizing Agents; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Cystoscopy; Humans; Microscopy, Fluorescence; Neoplasm Recurrence, Local; Photosensitizing Agents; Randomized Controlled Trials as Topic; Reoperation; Sensitivity and Specificity; Treatment Outcome; Urinary Bladder Neoplasms

To compare the outcomes of 5-aminolaevulinic acid (ALA) vs hexaminolaevulinate (HEX) vs white light (WL) transurethral resection of bladder tumors (TURB) to assess transferability of ALA findings to HEX. Extending WL-TURB with photodynamic diagnostic improves outcome. Two fluorescent agents have been commonly used for this. Although numerous and specific data exist on the older substance ALA, considerably less are available on hex, the only agent approved however. To date no such report has been published.. By random generator, each 200 patients with non-muscle-invasive bladder cancer having undergone TURB with WL, ALA or HEX were selected from our institutional data bank. Residual tumor in control TURB (RT) and recurrence-free survival (RFS) were assessed.. Complete follow-up data were available on 142 WL, 139 ALA, and 135 HEX patients. Median duration of follow-up was 24 months. RT was 33% in WL, 15% in ALA, and 9% in hex, respectively. RFS at 3 years was 67% in WL, 80% in ALA, and 82% in hex, respectively. RT was significantly reduced in ALA and HEX vs WL (P < .001) and RFS prolonged (P < .01). There were no significant differences between ALA and HEX in RT and RFS, respectively (RT: P = .37; RFS: P = .72).. In the present retrospective series, ALA and HEX were found to be significantly superior to WL. No differences between ALA and HEX were demonstrated. Even from a careful perspective both fluorescent agents seem to be comparable. Thus, ALA-based findings seem to be transferable on the approved agent HEX.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Carbon Radioisotopes; Cystectomy; Cystoscopy; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm, Residual; Photosensitizing Agents; Retrospective Studies; Urethra; Urinary Bladder Neoplasms

Topics: Aminolevulinic Acid; Carbon Radioisotopes; Cystectomy; Cystoscopy; Humans; Neoplasm Recurrence, Local; Neoplasm, Residual; Photosensitizing Agents; Urethra; Urinary Bladder Neoplasms

White light cystoscopy is the current standard for the diagnosis of bladder cancer and monitorization for recurrence. Recent studies suggest that porphyrin based fluorescence cystoscopy may improve endoscopic detection of bladder tumors. We aimed to evaluate the improvement that hexaminolevulinate fluorescence cystoscopy could lead in bladder cancer detection and treatment at one single centre.. Between September 2006 and September 2007 a total of 39 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM hexaminolevulinate (HAL) for 1 hour. The bladder was inspected using white light cystoscopy (WLC), followed by blue light (fluorescence) cystoscopy (BLC). Papillary and suspicious lesions were resected for histological examination. Mean age was 70.1 years (50-86). Thirty patients were male (76.9%) and 9 female (23.1%). The tumor characteristics were: 18% primary tumors, 51% recurrences and 30% control cystoscopies. 24 patients had previously received some treatment (9 MMC and 15 BCG). Only 7 patients had previous positive urine cytology.. All papillary lesions visualized with WLC were confirmed by BLC (18 patients). From these, 17 have positive biopsies (6 pTaG1, 9 pT1G1-3, 1 pT2, 1 CIS). In 15 patients (38.4%) we found at least 1 lesion more with BLC. In this group 8 cases (20.5%) had positive histological diagnosis (3 pTaG1, 2 pT1G3, 3 CIS). In five patients (13%) post-TUR therapeutic management has changed by using BLC (BCG vs MMC). All four patients with CIS were diagnosed by BLC. There was no evidence of local or systemic side effects due to HAL in the postoperative time.. Our results suggest there is an improvement in the diagnosis of papillary and flat lesions in bladder cancer by using HAL fluorescence cystoscopy. This has changed the management in the postoperative period (MMC vs BCG) in 13% of the patients. Obviously, we need more patients to assess our data and long-term follow-up to analyze the impact in terms of tumor recurrence and progression.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Carbon Radioisotopes; Cystoscopy; Female; Fluorescence; Humans; Male; Middle Aged; Urinary Bladder Neoplasms

New diagnostic or therapeutic options (NDTOs) are remunerated separately in the German DRG system. The Institute for Remuneration in Hospitals decides which proposed NDTOs are accepted for separate remuneration for 1 year. With this acceptance, hospitals can enter negotiations with insurance companies for an individual price of the NDTO. Because there are no general recommendations for these negotiations, we present a scheme for how to calculate an NDTO, based on the example of the NDTO for transurethral resection of bladder tumors using photodynamic diagnostic with hexaminolevulinic acid.

Topics: Aminolevulinic Acid; Biopsy; Budgets; Carcinoma, Transitional Cell; Cost-Benefit Analysis; Cystoscopy; Diagnosis-Related Groups; Germany; Hospital Costs; Humans; Laser Therapy; Lasers, Solid-State; National Health Programs; Negotiating; Neoplasm Staging; Reimbursement Mechanisms; Technology, High-Cost; Time and Motion Studies; Urinary Bladder Neoplasms

The hexylester of 5-aminolevulinic acid (HAL) is a very efficient precursor of the photosensitizer protoporphyrin IX (PpIX) for photodynamic therapy (PDT). Our previous study, performed in rat orthotopic bladder tumors, indicated an opposite effect of HAL/PpIX-PDT according to HAL concentration. The present study investigated possible reasons for this differential effect considering the impact of extracted amounts of PpIX in normal and tumor bearing bladders along with PpIX distribution in distinctive histopathological layers. High performance liquid chromatography (HPLC) analysis of tumor and normal bladder tissues after 8 mM and 16 mM HAL instillation showed that PpIX was the main porphyrin species. The PpIX production in tumor bladders instilled with 8 mM HAL was significantly higher than after 16 mM HAL. Fluorescence confocal microscopy demonstrated a punctuate bright fluorescence pattern in tumor zones of bladders instilled with 8 mM HAL, whereas a more diffuse cytoplasmatic fluorescence distribution was observed after 16 mM HAL instillation. Immunofluorescence staining together with transmission electron microscopy showed severe mitochondrial damage in tumor zones of bladders treated with 8 mM HAL/PpIX PDT, with intact mitochondria in tumor zones of bladders treated with 16 mM HAL/PpIX PDT. We conclude that the differential response to HAL/PpIX PDT in function of HAL concentrations could be attributed to diminished PpIX synthesis and differential intracellular localisation of PpIX. Mitochondria were shown to be the critical photodamaged sites of HAL/PpIX PDT and as such tissue sensitivity to treatment can be estimated through investigation of intracellular PpIX distribution.

Topics: Aminolevulinic Acid; Animals; Cell Line, Tumor; Chromatography, High Pressure Liquid; Disease Models, Animal; Female; Microscopy, Electron, Transmission; Photochemotherapy; Photosensitizing Agents; Protoporphyrins; Rats; Rats, Inbred F344; Urinary Bladder Neoplasms

Photodynamic therapy (PDT) of superficial bladder cancer may cause damages to the normal surrounding bladder wall. Prevention of these is important for bladder healing. We studied the influence of photosensitizer concentration, irradiation parameters, and production of reactive oxygen species (ROS) on the photodynamically induced damage in the porcine urothelium invitro. The aim was to determine the threshold conditions for the cell survival.. Living porcine bladder mucosae were incubated with solution of hexylester of 5-aminolevulinic acid (HAL). The mucosae were irradiated with increasing doses and cell alterations were evaluated by scanning electron microscopy and by Sytox green fluorescence. The urothelial survival score was correlated with Protoporphyrin IX (PpIX) photobleaching and intracellular fluorescence of Rhodamine 123 reflecting the ROS production.. The mortality ratio was dependent on PpIX concentration. After 3 hours of incubation, the threshold radiant exposures for blue light were 0.15 and 0.75 J/cm(2) (irradiance 30 and 75 mW/cm(2), respectively) and for white light 0.55 J/cm(2) (irradiance 30 mW/cm(2)). Photobleaching rate increased with decreasing irradiance. Interestingly, the DHR123/R123 reporter system correlated well with the threshold exposures under all conditions used.. We have determined radiant exposures sparing half of normal urothelial cells. We propose that the use of low irradiance combined with systems reporting the ROS production in the irradiated tissue could improve the in vivo dosimetry and optimize the PDT.

Topics: Aminolevulinic Acid; Animals; Cell Survival; In Vitro Techniques; Microscopy, Electron, Scanning; Mucous Membrane; Photobleaching; Photochemotherapy; Photosensitizing Agents; Protoporphyrins; Reactive Oxygen Species; Soft Tissue Injuries; Spectrometry, Fluorescence; Swine; Urinary Bladder Neoplasms; Urothelium

Urinary bladder urothelial carcinoma is diagnosed by a combination of cystoscopy and biopsy, with cytology as a valuable additional technique. The accuracy of cytological diagnosis depends on the experience of the cytologist and can inevitably vary from one cytologist to another. There is a need for an easy, reliable and objective diagnostic method. In the present study a new method was designed for the detection of bladder cancer cells in urine.. Flow cytometry was utilized to detect protoporphyrin IX in an artificial model consisting of normal urinary bladder transitional epithelial cells (NBECs) from healthy volunteers' urine and an established human urinary bladder carcinoma cell line, TCCSUP, after incubation with hexaminolevulinate (HAL). In addition, urine samples from 19 patients with histopathologically confirmed superficial bladder cancer were examined.. Incubation of NBECs or TCCSUP cells with HAL for 1 hour resulted in production of protoporphyrin IX only in the TCCSUP cells. Incubation of a mixture of NBECs and TCCSUP cells with HAL gave rise to a separated subpopulation of cells with protoporphyrin IX fluorescence. After cell sorting by flow cytometry the protoporphyrin IX-containing subpopulation of cells was confirmed as TCCSUP cells on cytological examination. It was possible to detect 5% TCCSUP cells in the mixture of NBECs/TCCSUP cells. To test the feasibility of the method in clinica diagnosis, urine samples from patients with bladder cancer were also measured with comparable, although preliminary and limited, results to those of cytological examination.. The preliminary results show that the technique may be feasible for the detection of bladder cancer cells in urine with possible advantages of simplicity, reliability and objectivity.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Biomarkers, Tumor; Carcinoma, Transitional Cell; Cell Line, Tumor; Cytodiagnosis; Feasibility Studies; Female; Flow Cytometry; Humans; Male; Middle Aged; Protoporphyrins; Reproducibility of Results; Sensitivity and Specificity; Urinalysis; Urinary Bladder Neoplasms; Urine; Urothelium

To optimize photodynamic therapy (PDT) we investigated the kinetics and biodistribution of hexylester 5-aminolevulinate (hALA) induced protoporphyrin IX (PpIX) and the therapeutic efficacy of PDT at different drug and light doses in an orthotopic rat bladder tumor model.. Healthy and tumor bearing rats were instilled intravesically with hALA (4, 8 and 16 mM) for 1 hour. Fluorescence was recorded spectroscopically in situ. PpIX fluorescence distribution and quantification across the bladders was visualized with fluorescence microscopy. PDT efficacy at different fluences (15 to 80 J/cm2) was histologically assessed 48 hours and 1 week after treatment.. Spectroscopic analysis in normal or tumor bearing rats showed the highest tumor-to-normal ratios 2 or 3 hours after the end of the 8 or 16 mM hALA instillation (5.4 and 5.7, respectively). Within the same tumor bearing animal the same fluorescence levels were observed in normal epithelium and transitional cell carcinoma, whereas the tumor-to-muscle ratio was 3. Tumor necrosis with an intact normal bladder wall was observed with a fluence of 20 J/cm2 for 8 mM hALA, while 15 J/cm2 was ineffective and 25 J/cm2 induced total wall necrosis. Although it induced comparable PpIX fluorescence, 16 mM hALA did not result in tumor eradication at any fluence.. An optimal PDT effect was obtained with 8 mM hALA and a fluence of 20 J/cm2. While different hALA concentrations ind uce identical PpIX fluorescence intensities, the PDT outcome was considerably different. Thus, fluorescence does not necessarily predict the therapeutic efficacy of PDT.

Topics: Aminolevulinic Acid; Animals; Carcinoma, Transitional Cell; Disease Models, Animal; Photochemotherapy; Rats; Tissue Distribution; Urinary Bladder Neoplasms