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.     

Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study

PURPOSE: We determined if improved tumor detection using hexaminolevulinate (HAL) fluorescence cystoscopy could lead to improved treatment in patients with bladder cancer. MATERIALS AND METHODS: A total of 146 patients with known or suspected bladder cancer were assessed in this open, comparative, within patient, controlled phase III study. Patients received intravesical HAL for 1 hour and were assessed with standard white light cystoscopy and blue light fluorescence cystoscopy. All lesions were mapped onto a bladder chart and biopsies were taken from suspicious areas for assessment by an independent pathologist. An independent urologist blinded to the detection method used recommended treatment plans based on biopsy results and medical history according to European Association of Urology bladder cancer guidelines. Any differences in recommended treatment plans arising from the 2 cystoscopy methods were recorded. RESULTS: HAL imaging improved overall tumor detection. Of all tumors 96% were detected with HAL imaging compared with 77% using standard cystoscopy. This difference was particularly noticeable for dysplasia (93% vs 48%), carcinoma in situ (95% vs 68%) and superficial papillary tumors (96% vs 85%). As a result of improved detection, additional postoperative procedures were recommended in 15 patients (10%) and more extensive treatment was done intraoperatively in a further 10. Overall 17% of patients received more appropriate treatment at the time of the study following blue light fluorescence cystoscopy, that is 22% or 1 of 5 if patients without tumors were excluded. CONCLUSIONS: HAL imaging is more effective than standard white light cystoscopy for detecting bladder tumors and lesions. This leads to improved treatment in a significant number of patients (p <0.0001).     

Diagnostic efficacy of fluorescence cystoscopy for detection of urothelial neoplasms.

BACKGROUND AND PURPOSE: A major problem diagnosing bladder cancer using conventional white-light cystoscopy is that flat and tiny papillary neoplasms can be overlooked. Fluorescence cystoscopy is based on the detection of protoporphyrin IX (PpIX)-induced fluorescence in urothelial neoplasms through the topical administration of 5-aminolevulinic acid (ALA). The diagnostic efficacy of fluorescence cystoscopy in urothelial neoplasms was evaluated in this study. The focus of this investigation was to ascertain whether fluorescence cystoscopy could make a major contribution to staging and improving the choice of adjuvant therapy after transurethral resection. PATIENTS AND METHODS: A series of 62 patients with suspected bladder cancer were investigated by fluorescence cystoscopy. An intravesical instillation of ALA was conducted 2 hours prior to fluorescence. A total of 274 tissue samples were obtained from the fluorescing and nonfluorescing areas of the bladder. RESULTS: The sensitivity and negative predictive value of fluorescence cystoscopy were 98.0% and 94.7%, respectively, but the specificity was low (42.9%). Among a total of 148 lesions of urothelial neoplasm, 58 foci (dysplasia in 5, carcinoma in situ in 19, stage Ta in 15, T1 in 15, above T2 in 4) that were invisible under white-light cystoscopy were detected by fluorescence cystoscopy. The final histopathologic status was changed in 45% of patients (28/62) according to this technique. Among these patients, eight (13%) needed additional therapy, including a radical cystectomy in one patient and intravesical therapy in 10. CONCLUSIONS: The ALA-based fluorescence cystoscopy technique is a safe and simple procedure that enhances the detection of flat and papillary urothelial neoplasms. Moreover, it will be able to provide useful information that will enable proper staging and appropriate further treatment.     

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.     

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: 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.     

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.     

膀胱内灌注ALA光动力学技术早期诊断和治疗膀胱乳头状癌的初步体会

为了研究以5-氨基果糖酸(ALA)作为荧光物质的光动力学诊断系统(PDD)对膀胱微小乳头状癌、上皮的不典型增生和原位癌诊断的敏感性和特异性,对12例临床诊断为膀胱癌的患者,于术前用ALA 1．5克 8．4％NaHCO3 50ml行膀胱内灌注,2～4小时后进行常规膀胱镜检和荧光膀胱镜检(光源为λ=375～440nm蓝光),然后在有荧光部位行活检送病理检查。12例共69个活检标本,病理结果显示PDD对膀胱癌及不典型增生的诊断敏感性为100％,特异性为86．7％,假阳性率为13．3％,无假阴性。荧光膀胱镜检可以发现常规膀胱镜检难以发现的微小癌灶及不典型增生,指导电切,对减少肿瘤的遗漏和降低复发率有较大的临床意义。     

Three-dimensional ultrasonography of the urinary bladder: preliminary experience of assessment in patients with haematuria

OBJECTIVE: To assess the value of three-dimensional (3D) vs two-dimensional (2D) ultrasonography (US) in the diagnostic evaluation of the urinary bladder in patients with haematuria. PATIENTS AND METHODS: In all, 42 patients with painless haematuria and/or irritative voiding symptoms were examined with 2D- and 3D-US. US was done with an Acuson Sequoia unit (Siemens Medical Sol. Mountain View, CA, USA) and the Perspective(R) 3D technique, to assess the presence of bladder lesions, including bladder cancer, bladder wall hypertrophy with trabeculation and diverticula, mucosal bladder folds or re-growth of the prostate mimicking a bladder tumour. The imaging findings were compared with cystoscopy and/or bladder biopsy. RESULTS: In 21 of the 42 patients (50%) cystoscopy with bladder biopsy revealed bladder cancer. Overall, 3D-US gave a correct diagnosis for 36 of 42 patients (86%). All 21 bladder cancers were correctly diagnosed, and 15 (71%) of the 21 benign bladder lesions were correctly identified. By contrast, 2D-US findings gave suspected bladder cancer in all patients. CONCLUSIONS: 3D-US is significantly more accurate than standard 2D-US in the diagnostic evaluation of patients with haematuria. Thus, this diagnostic technique might be useful for routine evaluation of the urinary bladder.     

Clinically relevant improvement of recurrence-free survival with 5-aminolevulinic acid induced fluorescence diagnosis in patients with superficial bladder tumors

PURPOSES: Fluorescence diagnosis induced by 5-aminolevulinic acid enables more thorough transurethral resection of superficial bladder carcinoma compared with conventional white light. We performed a prospective, single institution, randomized trial to investigate whether the residual tumor rate and long-term tumor recurrence can be decreased by fluorescence diagnosis. MATERIALS AND METHODS: A total of 301 patients underwent transurethral resection of bladder tumors with white light or fluorescence diagnosis. Transurethral resection was repeated 5 to 6 weeks later to evaluate the residual tumor rate. To determine recurrence-free survival patient followup was performed every 3 months by white light cystoscopy and urine cytology. Recurrence-free survival was analyzed via Kaplan-Meier methods and multivariable Cox regression analysis. RESULTS: A total of 191 patients with superficial bladder carcinoma were available for efficacy analysis. The residual tumor rate was 25.2% in the white light arm versus 4.5% in the fluorescence diagnosis arm (p <0.0001). Median followup in the white light arm in 103 cases was 21.2 months (range 4 to 40) compared with 20.5 (range 3 to 40) in the 88 in the fluorescence diagnosis arm. Recurrence-free survival in the fluorescence diagnosis group was 89.6% after 12 and 24 months compared with 73.8% and 65.9%, respectively, in the white light group (p = 0.004). This superiority proved to be independent of risk group. The adjusted hazard ratio of fluorescence diagnosis versus white light transurethral resection was 0.33 (95% confidence interval 0.16 to 0.67). CONCLUSIONS: Fluorescence diagnosis is significantly superior to conventional white light transurethral resection with respect to the residual tumor rate and recurrence-free survival. The differences in recurrence-free survival imply that fluorescence diagnosis is a clinically relevant procedure for decreasing the number of tumor recurrences.     

AUTOFLUORESCENCE GUIDED BIOPSY FOR THE EARLY DIAGNOSIS OF BLADDER CARCINOMA

Purpose

We validate the usefulness of laser-induced autofluorescence for the detection of bladder carcinoma.

Materials and Methods

We obtained and analyzed fluorescence spectra from 75 patients in whom bladder cancer was suspected. Tissue fluorescence was excited by a nitrogen laser using a quartz optical fiber placed in gentle contact with the area of interest. The laser-induced autofluorescence spectrum was recorded using an intensified optical multichannel analyzer system. Spectra were corrected for the spectral response of the optical system, and the ratios of laser-induced autofluorescence intensities (I) at 385 and 455 nm. (I₃₈₅/I₄₅₅) were determined. We had previously established this ratio as a diagnostic algorithm. We included only suspicious bladder lesions (erythematous, edematous, raised and so forth) that were difficult to diagnose by cystoscopy as well as areas from which random biopsies were obtained. The fluorescence ratio algorithm was applied to 130 bladder areas.

Results

Of the 130 biopsies obtained during routine cystoscopy 107 (82%) were nonmalignant by histological classification. In contrast, because laser-induced autofluorescence effectively guides biopsies towards malignant lesions, only 30 biopsies (72% fewer) would have been obtained from nonmalignant tissue if the fluorescence ratio that identifies 95% of malignant lesions (95th percentile) had been selected as the decision criterion during standard cystoscopy.

Conclusions

By guiding the surgeon to suspicious lesions that are most likely to be malignant, laser-induced autofluorescence substantially decreases the number of biopsies obtained from nonmalignant tissue during cystoscopy to diagnose bladder carcinoma.     

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

OBJECTIVE

To evaluate the possible benefit of fluorescence cystoscopy (FC) in detecting cytologically ‘confirmed’ lesions when assessing urothelial carcinoma of the bladder, as negative white‐light cystoscopy in cases of a positive cytological finding represents a diagnostic dilemma.

PATIENTS AND METHODS

From January 1996 to December 2006, 348 patients, who had cystoscopy for surveillance or due to suspicion of urothelial carcinoma, presented with an entirely negative white‐light cystoscopy at our hospital. However, 77 of the 348 patients (22.2%) were diagnosed with a positive cytological finding. All patients had white‐light cystoscopy first and a bladder‐wash cytological specimen was obtained, then FC, followed by cold‐cup biopsies and/or transurethral resection of the bladder tumour.

RESULTS

In the 77 patients with a positive cytological specimen FC enabled the detection of the precise site of malignancy within the bladder in 63 (82%). As malignant or premalignant lesions, there were 18 moderate dysplasias, 27 carcinoma in situ (CIS), and 18 pTa‐1/G1‐3 tumours. Moreover using FC, malignant or premalignant lesions were detected in 43 of 271 patients (15.9%) who had a negative cytological specimen (15 moderate dysplasias, six CIS, 22 pTa‐1/G1‐3).

CONCLUSION

This study shows that FC is beneficial in the detection of malignant and premalignant lesions, if there is negative white‐light cystoscopy but positive urine cytology. The immediate identification of the exact site of a malignant lesion during FC enables the physician to diagnose and treat these patients more accurately and with no delay.     

Fluorescence cystoscopy in the management of bladder cancer: a help for the urologist!

As a disease characterized by a nature polymorphic and fluctuant in its evolution, superficial transitional cell carcinoma of the bladder remains a perpetual therapeutic challenge, and raises a great interest in the development of new diagnostic and surveillance techniques. This paper reviews 10 years of experience of fluorescence cystoscopy, a simple technique perfectly adapted to the current endoscopic equipment. Its principle is to enhance the visual contrast between benign and malignant cells. Three photosensitizing agents are available, two prodrugs: delta-aminolevulinic acid or hexaminolevulinate, and a natural substance: hypericin. With a detection rate of over 90% for carcinoma in situ and a real potential for detecting small tumors overlooked by standard cystoscopy, fluorescence cystoscopy may be clearly recommended in clinical practice. This technique favors a standardization of superficial bladder cancer endoscopic management and is susceptible to have a real impact on the disease recurrence and progression rate.     

Comparison of cytology and nuclear matrix protein 22 for the detection and follow-up of bladder cancer

OBJECTIVES: This study was designed to determine the clinical usefulness of the nuclear matrix METHODS: 84 patients suffering from bladder cancer or suspected bladder cancer, 25 patients with benign urological lesions and 60 healthy controls participated in a prospective study. Freshly voided spot urine samples were taken for cytological examination and determination of NMP 22 levels by enzyme-linked immunoassay. RESULTS: The sensitivity of the NMP 22 test according to the tumor grading was (results of cytology in brackets): G1 25.0% (20.0%); G2 68.2% (59.1%), and G3 100.0% (66.7); overall sensitivity was 62.5% (45.0%). The sensitivity for superficial bladder cancer was 46.7% (36.7%) and for invasive bladder cancer 90.0% (70.0%). The specificity was 65.9% (88.9%). CONCLUSIONS: NMP 22 is a reliable tool for detecting invasive bladder cancer. Results for the frequently occurring low grade superficial bladder cancer are as poor as those obtained with cytology. In addition benign lesions such as urolithiasis or urinary tract infection lead to false-positive results. Therefore cystoscopy has to be performed when trying to detect and follow-up bladder cancer.     

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.     

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.     

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.     

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。     

Photodynamic diagnosis of bladder cancer: Initial experience of a single UK centre

ObjectivesTo describe the introduction and evaluate efficacy of photodynamic diagnosis with Hexvix for detecting tumours and abnormal mucosal lesions during transurethral resection of bladder tumour (TURBT).Subjects and methodsProspective study of consecutive eligible patients who underwent TURBT with aid of Hexvix-guided cystoscopy in a single District General Hospital (NHS Trust in England).The participants selected were patients suspected to have bladder cancer or enlisted to undergo TURBT.The main outcome measures were the number of tumours or abnormal mucosal lesions that were missed by white light cystoscopy (WLC) but detected by Hexvix, blue light cystoscopy (BLC).ResultsA total of 63 patients (39 males and 24 females; mean age 74 years; age range, 35–88 years) met study criteria. 15 were excluded: in 6 intra-vesical Hexvix was retained for <1 h, and in 4, TURBT was delayed by >1 h; of the remaining 53 patients, 5 were excluded for technical reason, failure of fluorescence. Seventy five lesions were detected in the remaining 48 patients. Of these, 51 (68%) were detected by WLC and BLC both. BLC detected additional 24 (32%) lesions that were missed by WLC. Of these lesions, 15 (20%) were cancer and 9 (12%) were inflammation or dysplasia.ConclusionBLC with Hexvix was easily introduced into a Bladder cancer management protocol and well tolerated by most patients. BLC increased diagnostic accuracy of cystoscopy during TURBT, although some of the lesions it detected were false positive.     

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).