Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy

PURPOSE: In this European multicenter study we compared hexaminolevulinate (HAL) fluorescence cystoscopy and standard white light cystoscopy for the detection of carcinoma in situ (CIS) in patients suspected of having high risk bladder cancer. MATERIALS AND METHODS: This study was a prospective controlled, within-patient comparison of standard and HAL fluorescence cystoscopy. Eligible patients received an intravesical instillation of 50 ml HAL 8 mM solution. Cystoscopy was performed using a D light system, which provided white and blue light at 375 to 440 nm. The bladder wall was inspected and mapped, first under white light, followed by blue light. All tumors and suspicious areas identified under white light and by red fluorescence were resected or biopsied. Histological findings were assessed by an independent central pathologist blinded to the identity of the biopsies. RESULTS: Of 211 evaluable patients 83 (39%) had CIS, of whom 18 (22%) were detected by HAL cystoscopy only, 62 (75%) were detected by standard and HAL cystoscopy, 2 (2%) were detected by standard cystoscopy only and 1 (1%) was detected by nonguided biopsy. Therefore, HAL cystoscopy identified 28% more patients with CIS than standard cystoscopy. The side effects of HAL instillation were negligible and no unexpected events were reported. CONCLUSIONS: HAL fluorescence cystoscopy improves the detection of bladder CIS significantly, which has consequences for clinical management and may improve the patient prognosis. The procedure is easily implemented as an adjunct to standard cystoscopy and it adds no significant risk of complications.     

A phase III, multicenter comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of superficial papillary lesions in patients with bladder cancer

PURPOSE: We compared hexaminolevulinate fluorescence cystoscopy with white light cystoscopy for detecting Ta and T1 papillary lesions in patients with bladder cancer. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Hexyl aminolevulinate fluorescence cystoscopy: new diagnostic tool for photodiagnosis of superficial bladder cancer--a multicenter study

PURPOSE: We examined the sensitivity and specificity of Hexvix (PhotoCure ASA, Oslo, Norway) hexyl aminolevulinate (HAL) fluorescence cystoscopy in patients with superficial bladder cancer. MATERIALS AND METHODS: A total of 52 patients (38 men and 14 women) with a mean age of 72 years were investigated. HAL hydrochloride (100 mg dissolved in 50 ml phosphate buffer solution) (8 mM) was instilled into the bladder 1 hour prior to the endoscopic procedure. Cystoscopy was performed with the Storz D-light (Karl Storz, Tuttlingen, Germany) system, allowing inspection of the bladder wall under white and blue light (380 to 450 nm). RESULTS: A total of 422 biopsies obtained in fluorescing (165) and nonfluorescing (257) areas, including 5 random biopsies per patient, were analyzed to provide the best reference for the calculation of sensitivity and specificity. There were a total of 143 histologically verified tumors in 45 patients, including carcinoma in situ (CIS), Ta or T1 lesions. A total of 43 patients were diagnosed by fluorescence cystoscopy compared with 33 diagnosed by white light for 96% and 73% per-patient sensitivity, respectively. HAL cystoscopy was found particularly useful for finding CIS tumors. Of 13 patients with CIS tumors all except 1 were diagnosed or confirmed by HAL cystoscopy. HAL cystoscopy was well tolerated with no definite drug related adverse events reported, including effects on standard blood parameters. CONCLUSIONS: HAL fluorescence cystoscopy is a new, sensitive, promising diagnostic procedure that showed improved detection of bladder tumors, in particular CIS. The procedure is well tolerated and can easily be implemented in current clinical practice.     

Flexible Cystoscopy Assisted by Hexaminolevulinate Induced Fluorescence: A New Approach for Bladder Cancer Detection and Surveillance?

OBJECTIVE: The aim of this study was the assessment of flexible cystoscopy assisted by hexaminolevulinate (HAL) fluorescence. METHODS: This study was a prospective controlled, within-patient comparison of flexible HAL cystoscopy with standard flexible cystoscopy, HAL rigid and standard white light rigid cystoscopy. Eligible patients received an intravesical instillation of 50 ml hexylaminolevulinate 8 mM solution. First flexible than rigid cystoscopy was performed in each patient using a Combilight PDD system (Richard Wolf, Germany), which provided standard white light and blue light at 375 to 440 nm, with mapping of all lesions detected. All tumors and suspicious areas identified under white light and by red fluorescence with flexible or rigid cystoscopy were then resected by TUR or biopsied. The specimen was assessed by an independent blinded pathologist. RESULTS: In the 45 patients studied 41 (91%) patients had exophytic tumors, of which 39 (95.1%) were detected by HAL flexible cystoscopy and 40 (97.5%) by HAL rigid cystoscopy. 17 (37.8%) patients had concomitant or carcinoma in situ only, which was identified by HAL flexible cystoscopy in 14 (82.3%), by HAL rigid cystoscopy in 15 (88.2%), by flexible standard in 11 (64.7%) and by standard white light rigid cystoscopy in 13 (76.7%) patients. CONCLUSION: HAL fluorescence flexible cystoscopy compared to HAL rigid cystoscopy showed almost equivalent results in detecting papillary and flat lesions in bladder cancer patients. Both procedures were superior to standard white light flexible cystoscopy.     

Treatment changes and long‐term recurrence rates after hexaminolevulinate (HAL) fluorescence cystoscopy: does it really make a difference in patients with non‐muscle‐invasive bladder cancer (NMIBC)?

Study Type – Therapy (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? HAL fluorescence cystoscopy is known to improve tumour detection in NMIBC cases and to have a potentially favourable impact concerning the recurrence rates. The present trial assessed the advantages of HAL cystoscopy with regard to postoperative treatment changes and 2 years' recurrence rates, subjects that are poorly evaluated in the literature.

OBJECTIVES

• ? 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.

PATIENTS AND METHODS

• ? 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.

RESULTS

• ? 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).

CONCLUSIONS

• ? 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.

     

5-ALA荧光膀胱镜的应用对非肌层浸润性膀胱癌早期复发率的影响

目的：探讨5-氨基乙酰丙酸（5-ALA）荧光膀胱镜的应用对非肌层浸润性膀胱癌术后早期复发率的影响。方法：将90例非肌层浸润性膀胱癌患者随机分为两组,每组45例,分别在白光膀胱镜和5-ALA荧光膀胱镜下行TURBt,术后6周所有患者均行5-ALA荧光膀胱镜检查以观察肿瘤复发情况,并对复发肿瘤行二次TURBt。结果：行二次TURBt后,90例患者中,25例（27．7％）发现有肿瘤发生,其中自光膀胱镜组18例（40％）,荧光膀胱镜组7例（15．5％）,两组间比较差异有统计学意义（P=0．05）。结论：5=ALA荧光膀胱镜对膀胱肿瘤的诊断和治疗具有较高价值,可以显著降低非肌层浸润性膀胱癌术后早期复发率。     

A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study

PURPOSE: We compared hexaminolevulinate (Hexvix) fluorescence cystoscopy with white light cystoscopy for detecting carcinoma in situ. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Fluorescence Cystoscopy in Bladder Cancer: The Case Pro

IntroductionNon–muscle-invasive bladder cancer is labour intensive and costly. Due to lifelong monitoring and treatment in many of these patients, it is the most expensive cancer in per-patient terms. A significant part of the costs is due to the high recurrence rate, its treatment, and follow-up.MethodsStudies on fluorescence cystoscopy were reviewed.ResultsFluorescence-guided cystoscopy, using 5-aminolevulinic acid (5-ALA) or its hexyl ester, hexaminolevulinate 5-ALA (HAL), improves the detection of bladder tumours, particularly carcinoma in situ, compared to standard white light cystoscopy. The quality of transurethral resection of the bladder tumour is also improved, as is further patient management. Finally, fluorescence cystoscopy leads to reduced long-term recurrence rates and lower overall costs. The technique is well tolerated and easy.ConclusionFluorescence cystoscopy is safe, better for the patient, and cheaper for community.     

The role of hexaminolevulinate fluorescence cystoscopy in bladder cancer

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.     

Comparison of hexaminolevulinate based flexible and rigid fluorescence cystoscopy with rigid white light cystoscopy in bladder cancer: results of a prospective Phase II study

INTRODUCTION AND OBJECTIVE: Several studies have shown that rigid fluorescence cystoscopy (RFC) with hexaminolevulinate (HAL) is superior to standard rigid white light (RWLC) cystoscopy in diagnosing bladder tumours, with a clinically relevant impact on the patient's management. These studies, however, have been done with rigid cystoscopes. We carried out a study to evaluate whether the technique of fluorescence cystoscopy with HAL was also feasible with a specially designed flexible fluorescence cystoscope (FFC). METHODS: 20 patients with known or suspected bladder cancer were included in a comparative within patient controlled Phase II study. All patients signed informed consent. All patients received 50 ml of HAL (Hexvix) 8 mM 1h prior to transurethral resection. Using a D-light-C system (Storz, Germany), FFC and RFC were performed followed by RWLC. All lesions visible during these three cystoscopies were mapped, taped and resected. RESULTS: In these 20 patients (mean age 71 years (49-89), 3 females) mean HAL instillation time was 81 min. Overall 27 histologically confirmed lesions were found in 19 patients. Detection rates in these 19 patients were 14 with FFC, 17 with RFC and 15 with RWLC. Of the 27 lesions 19 were detected with FFC, 23 with RFC and 20 with RWLC. Overall fluorescence intensity using the flexible system was 76% (30-147%) as compared to RFC using a visual analogue score. No side effects were noted which were attributable to HAL. CONCLUSION: The use of FFC is feasible and seems to be comparable to RWLC and slightly inferior to RFC. Larger studies should determine the role of flexible fluorescence cystoscopy.     

Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5-aminolaevulinic acid

OBJECTIVE: To report the results of a clinical study investigating the diagnosis of malignant and dysplastic bladder lesions by protoporphyrin IX (PPIX) fluorescence and to compare them with those from earlier studies. PATIENTS AND METHODS: The study included 55 patients with suspected bladder carcinoma (at initial diagnosis or at tumour follow-up visits); 130 bladder biopsies from 49 patients were classified by pathological analysis. All patients received an intravesical instillation of 50 mL of a 3% 5-aminolaevulinic acid (ALA) solution a mean of 135 min before cystoscopy, which was then performed under white and blue light. Malignant/dysplastic lesions showing red fluorescence under blue-light excitation were noted and the increase in detection rate calculated. RESULTS: There were 63 benign and 67 malignant/dysplastic areas biopsied; 10 malignant/dysplastic lesions (four transitional cell carcinoma, two carcinoma in situ, four dysplasia) were not detected during routine white-light cystoscopy but were identified under blue light. Fluorescence cystoscopy improved the overall diagnosis of malignant/dysplastic bladder lesions by 18% over standard white-light cystoscopy. The improvement was greater for dysplastic lesions and carcinoma in situ (50%). However, the improvement over standard cystoscopy was less than that found by other groups. CONCLUSION: The ALA-based fluorescence detection system significantly enhanced the diagnosis of malignant/dysplastic bladder lesions. However, determining the optimum drug exposure time requires further investigation using well-characterized instrumentation and study protocols, which would then allow comparison of the results from different groups.     

5-氨基乙酰丙酸诱导荧光膀胱镜在膀胱肿瘤诊断中的应用（附31例报告）

目的：研究5-氨基乙酰丙酸（5-ALA）诱导荧光光动力学对膀胱肿瘤的早期诊断价值。方法：对血尿患者行5-ALA诱导荧光膀胱镜检查及活组织检查,以5-ALA膀胱灌注,2h后采用D-light光源系统进行膀胱镜检,对荧光阳性区域及白光下肉眼可见异常但荧光阴性区域进行活检,活检后行经尿道膀胱肿瘤电切术。结果：31例患者中有4例荧光阴性且普通光肉眼观阴性者未活检。余27例患者共取活检96处,其中荧光阳性区域取活检89处（包括普通光肉眼观阴性区域35处）,切缘取活检7处。病理检查结果显示：尿路上皮癌65处,阳性率为73．03％（65／89）,非肿瘤性病变24例,假阳性率为27％（24／89）,切缘活检7处为阴性。荧光下阳性而白光下阴性的肿瘤位点11处,切缘活检7处均为阴性。结论：5-ALA诱导荧光光动力学诊断对膀胱肿瘤有较高价值,能发现早期肿瘤,同时进行电切将更彻底。     

Fluorescence cystoscopy: is it ready for use in routine clinical practice?

PURPOSE OF REVIEW: To review the recent literature on the use of fluorescence cystoscopy in the diagnosis and management of bladder cancer. RECENT FINDINGS: Recent advances have been made in fluorescence cystoscopy with the use of newer fluorescence agents (hexylester aminolevulinate and hypericin) and their application to flexible cystoscopy. Within several hours of intravesical administration of these agents, bladder tumors can be detected using fluorescence cystoscopy resulting in improved cancer detection and lower short-term recurrence rates than white light cystoscopy. Preliminary results with flexible fluorescence cystoscopy suggest that this technique can be used for office-based cystoscopy. SUMMARY: Significant advances have been made in the field of fluorescence cystoscopy. The currently available fluorescence agents in recent phase II and III trials outperform white light cystoscopy in terms of cancer detection and recurrence-free survival. Fluorescence cystoscopy should be considered as an adjunctive tool for the diagnosis and management of superficial bladder cancer.     

荧光膀胱镜下膀胱肿瘤电切术治疗非肌层浸润性膀胱癌的效果观察

目的 观察荧光膀胱镜下膀胱肿瘤电切术(transurethral resection of bladder tumor,TURBT)治疗非肌层浸润性膀胱癌的临床效果.方法 57例非肌层浸润性膀胱癌患者根据所使用的膀胱镜的不同分为两组:白光膀胱镜组(n=30),采用白光膀胱镜下TURBT治疗;荧光膀胱镜组(n=27),采用荧光膀胱镜下TURBT治疗.比较两组的临床一般资料、手术相关指标及术后3、6、12及18个月不同时间点的复发率.结果 两组患者在性别、年龄、肿瘤数目、病理分期及病理分级等方面比较,差异无统计学意义(P>0.05);两组患者的手术时间、术中出血量、留置导管时间及术后住院时间等手术相关指标比较,差异亦无统计学意义(P>0.05);荧光膀胱镜组术后3、6、12及18个月不同时间点的复发率均明显低于白光膀胱镜组(P<0.05). 结论 荧光膀胱镜下TURBT治疗非肌层浸润性膀胱癌可明显降低术后早期复发率.     

Fluorescence detection of bladder tumors with 5-amino-levulinic acid

BACKGROUND: Preliminary data suggest that photodiagnosis by fluorescence detection of protoporphyrin IX, a biosynthetic product of the photosensitizer 5-amino-levulinic acid (ALA), is superior to conventional cystoscopy in bladder tumor detection. PATIENTS AND METHODS: We instilled 1.5 g of ALA into the bladders of 52 patients with suspect bladder lesions 1 to 4 hours prior to transurethral resection or biopsy. Red fluorescence was induced by violet-blue light (wavelength 380-450 nm). RESULTS: In 13 patients (25%), significant tumors were detected by fluorescence that were missed on conventional cystoscopy. In the present series, ALA photodetection had a sensitivity of 94.6% (compared with 76% for cystoscopy) and a specificity of 43%. CONCLUSION: Fluorescence diagnosis with ALA may become a standard procedure for bladder tumor detection and resection, especially in endoscopically difficult situations (carcinoma in situ, multifocal tumors, multiple prior resections, or previous drug instillation therapy).     

Hexylaminolaevulinate fluorescence cystoscopy in patients previously treated with intravesical bacille Calmette‐Guérin

Study Type – Diagnosis (case series) Level of Evidence 4

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^TM, 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.     

Photodynamic Diagnosis in Non-Muscle-Invasive Bladder Cancer

ObjectiveThis paper reviews the development and clinical validation of photodynamic diagnosis (PDD) of bladder cancer.MethodsThe authors reviewed the literature on the development of PDD, in particular the evidence for the clinical efficacy of hexaminolevulinate PDD in the diagnosis of bladder cancer.ResultsAfter initial work on ultraviolet cystoscopy following oral tetracycline, the focus of PDD research shifted to the use of synthetic porphyrins. First, the prodrug delta-aminolevulinic acid (ALA) was shown to cause a transient but significant accumulation of protoporphyrin IX (PpIX) in malignant or premalignant bladder tissue. Excitation by blue light leads to PpIX fluorescence (red), which distinguishes tumour from normal tissue (blue). Hexaminolevulinate (HAL, Hexvix), an ester of ALA, was then developed and has greater bioavailability and stability than the parent compound. It has been approved for clinical use in the diagnosis of bladder cancer. Clinical studies have shown that HAL PDD detects tumours, including carcinoma in situ (CIS), that are missed by conventional white-light cystoscopy.ConclusionsHAL PDD is a valuable aid to the detection of bladder tumours, including CIS.     

Is photodynamic diagnosis using hypericin better than white‐light cystoscopy for detecting superficial bladder carcinoma?

OBJECTIVE: To review the initial clinical results of photodynamic diagnosis (PDD) using hypericin (a new photosensitizer for PDD that helps to label flat urothelial tumours to facilitate biopsy) for the early detection of superficial bladder carcinoma, as flat noninvasive tumours of the bladder may be missed during conventional white-light cystoscopy (WLC) if there is bladder overdistension or ongoing cystitis. PATIENT AND METHODS: Between 1 January 2001 and 30 October 2004, 41 consecutive patients (mean age 66.1 years, sd 9.1, range 46-81) had transurethral resection for bladder cancer. Hypericin was introduced intravesically for 2 h before cystoscopy. Immediately after WLC, fluorescence cystoscopy (FC) was used at the same location and the same bladder site inspected using violet light. FC findings, e.g. positive or negative red fluorescence, were documented for each specific bladder site examined, and the exact location sampled for biopsy. RESULTS: The mean (sd, range) bladder capacity of the patients was 431 (86, 300-650) mL. In all, 179 biopsies were taken from the 41 patients; urothelial cancers were found in 41% (74) and 80% (33) had macroscopically visible bladder tumours; 40% (71) of the biopsies were positive under FC and 86% (61) of the 71 FC-positive biopsies showed cancer on histology. Twenty-five biopsies (14%) were positive on FC but not WLC. PDD testing with hypericin had a sensitivity of 82% (61/74) and specificity of 91% (95/105), vs WLC, at 62% (46/74) and 98% (103/105), respectively. The PDD test had a positive predictive value of 86% (61/71) and a negative predictive value of 88% (95/108), vs 96% (46/48) and 79% (103/131), respectively for WLC. There were no reports of significant complications after the procedure. CONCLUSION: PDD using hypericin shows promise, as it has a higher sensitivity but equivalent specificity than WLC. It can be used to detect flat lesions not seen on WLC. PDD testing is also well tolerated with minimal side-effects.     

A comparison of white-light cystoscopy and narrow-band imaging cystoscopy to detect bladder tumour recurrences

OBJECTIVE

To determine whether narrow‐band imaging (NBI) cystoscopy enhances the detection of non‐muscle‐invasive bladder tumours over standard white‐light imaging (WLI) cystoscopy, as surveillance WLI is the standard method used to diagnose patients with recurrent bladder tumours, but they can be missed by WLI cystoscopy, possibly accounting for early recurrences.

PATIENTS AND METHODS

We evaluated 427 patients for recurrent bladder tumours by WLI cystoscopy, followed by NBI cystoscopy as a further procedure, using the same video‐cystoscope. Recurrent tumours visualized by WLI or NBI cystoscopy were mapped, imaged, biopsied and subsequently treated by transurethral resection (TUR) or fulguration. Biopsies or TUR specimens obtained by WLI and NBI were examined separately for presence of tumour.

RESULTS

In all, 103 patients (24%) had tumour recurrences; 90 (87%) were detected by both WLI and NBI and another 13 (100%) only by NBI cystoscopy. NBI detected extra papillary tumours or more extensive carcinoma in situ in 58 (56%) patients found to have recurrences. The mean number of recurrent tumours visualized on WLI cystoscopy was 2.3, vs to 3.4 seen on NBI cystoscopy (P = 0.01).

CONCLUSION

NBI cystoscopy improved the detection of recurrent non‐muscle‐invasive bladder tumours over standard WLI cystoscopy.