Clinical significance of macroscopic 5-aminolevulinic acid (ALA)-inducer fluorescence in transurethral resection of non-invasive bladder cancer

Macroscopic fluorescence which is induced with aminolevulinic acid (ALA) allows visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and dysplasias of the bladder. Following ALA instillation, cystoscopy was performed under both standard and blue light illumination. In a prospective randomized multicenter study, 102 patients underwent TUR of bladder tumor(s) either with white light or ALA-fluorescence. Significant reduction in the number of residual tumours was detected in 59% (p = 0.005) after 8 weeks, 3 months--in 58% (p = 0.002) and 6 months in 38% (p = 0.01) respectively.     

Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy : A multicenter randomized, double-blind, placebo-controlled trial

BACKGROUND:

The medical community lacks results from prospective controlled multicenter studies of the diagnostic efficacy of 5‐aminolevulinic acid (5‐ALA) cystoscopy on tumor recurrence in patients with superficial bladder tumors.

METHODS:

A prospective randomized, double‐blind, placebo‐controlled study was conducted in 370 patients with nonmuscle‐invasive urinary bladder carcinoma who received either 5‐ALA (n = 187) or a placebo (n = 183) intravesically before cystoscopy. Each group underwent cystoscopy under visible white light and under fluorescent light followed by transurethral tumor resection. The primary study objective was to evaluate the 12‐month recurrence‐free survival.

RESULTS:

Slightly more patients with tumors were detected by using 5‐ALA than by using the placebo (88.5% vs 84.7%). The mean numbers of tumor specimens per patient were 1.8 (5‐ALA) and 1.6 (placebo). Intrapatient comparison of fluorescent light versus white light cystoscopy in patients randomized to receive 5‐ALA showed a higher tumor detection rate with fluorescent light than with white light cystoscopy. In patients receiving 5‐ALA cystoscopy, the percentage of lesions that would not have been detected in these patients by white light cystoscopy ranged between 10.9% (pT1) and 55.9% (atypia). Progression‐free survival was 89.4% (5‐ALA) and 89.0% (placebo) (P = .9101), and recurrence‐free survival 12 months after tumor resection was 64.0% (5‐ALA) and 72.8% (placebo) (P = .2216).

CONCLUSIONS:

In comparison to the placebo, 5‐ALA cystoscopy did not increase the rates of recurrence‐free or progression‐free survival 12 months after tumor resection. Although more tumors per patient were detected in the 5‐ALA group, the higher detection rate did not translate into differences in long‐term outcome. Cancer 2011. © 2010 American Cancer Society.     

Diagnostic approach for cancer cells in urine sediments by 5‐aminolevulinic acid‐based photodynamic detection in bladder cancer

Bladder urothelial carcinoma is diagnosed and followed up after transurethral resection using a combination of cystoscopy, urine cytology and urine biomarkers at regular intervals. However, cystoscopy can overlook flat lesions like carcinoma in situ, and the sensitivity of urinary tests is poor in low‐grade tumors. There is an emergent need for an objective and easy urinary diagnostic test for the management of bladder cancer. In this study, three different modalities for 5‐aminolevulinic acid (ALA)‐based photodynamic diagnostic tests were used. We developed a compact‐size, desktop‐type device quantifying red fluorescence in cell suspensions, named “Cellular Fluorescence Analysis Unit” (CFAU). Urine samples from 58 patients with bladder cancer were centrifuged, and urine sediments were then treated with ALA. ALA‐treated sediments were subjected to three fluorescence detection assays, including the CFAU assay. The overall sensitivities of conventional cytology, BTA, NMP22, fluorescence cytology, fluorescent spectrophotometric assay and CFAU assay were 48%, 33%, 40%, 86%, 86% and 87%, respectively. Three different ALA‐based assays showed high sensitivity and specificity. The ALA‐based assay detected low‐grade and low‐stage bladder urothelial cells at shigher rate (68–80% sensitivity) than conventional urine cytology, BTA and NMP22 (8–20% sensitivity). Our findings demonstrate that the ALA‐based fluorescence detection assay is promising tool for the management of bladder cancer. Development of a rapid and automated device for ALA‐based photodynamic assay is necessary to avoid the variability induced by troublesome steps and low stability of specimens.     

The use of digitized endoscopic imaging of 5-ALA-induced PPIX fluorescence to detect and diagnose oral premalignant and malignant lesions in vivo

5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) fluorescence has shown an outstanding sensitivity for the assessment of oral lesions, but its application was hampered by low specificity due to the high false-positive rates. The purpose of our study was to explore the feasibility of quantifying PPIX fluorescence images to improve the diagnostic specificity for detecting early oral lesions in vivo. A digitized 5-ALA-mediated endoscopic imaging system was utilized to acquire PPIX fluorescence images from in vivo oral tissues. Forty-nine patients (118 biopsies) with known or suspected premalignant or malignant oral lesions were recruited for ALA-PPIX fluorescence endoscopic imaging. The red and blue channels of PPIX fluorescence images were digitized and stored for fluorescence quantification. The red-to-blue intensity ratios were calculated from the fluorescence images to correlate with histologic findings of the biopsies. The results showed that normal oral mucosa exhibited blue color of the back-scattered excitation light in the fluorescence images, whereas the suspicious lesions displayed bright reddish fluorescence. Applying the red-to-blue intensity ratio (I(R)/I(B)) as a diagnostic algorithm yielded a sensitivity of 92% and 98%, and specificity of 96% and 96%, for separating benign tissue from dysplasia, and cancer tissue, respectively, and a sensitivity and specificity of 98% and 92%, respectively, for differentiating cancer tissue from dysplasia in the oral cavity. Our study demonstrates that quantifying ALA-PPIX fluorescence endoscopic images associated with the red-to-blue intensity ratio as a diagnostic algorithm can provide good differentiation between the different stages of oral premalignancy and malignancy (p<0.0001, unpaired 2-sided Student's t-test), and thus has a potential to significantly improve the noninvasive diagnosis and evaluation of early oral neoplasia in vivo.     

盐酸吡柔比星荧光膀胱镜对非肌层浸润性膀胱癌的诊断价值

目的:评估以盐酸吡柔比星作为荧光剂的荧光膀胱镜检查对非肌层浸润性膀胱癌的诊断价值。方法:本次研究共63例患者,膀胱灌注盐酸吡柔比星溶液40 mg,保留30 min后排空置入膀胱镜,分别在普通白光及荧光下观察,对白光和/或荧光下显示阳性或可疑区域进行活检,同时行电切术。结果:63例患者中,18例患者普通白光膀胱镜及荧光膀胱镜检查均阴性;其余45例患者共取活检92处,平均每例患者取活检2.04处。其中53处病理报告为尿路上皮癌,荧光膀胱镜敏感性为90.57%（48/53）,特异性为64.10%（25/39）;普通白光膀胱镜敏感性为71.70%（38/53）,特异性为56.41%（22/39）。结论:吡柔比星荧光膀胱镜诊断非肌层浸润性膀胱癌的敏感性和特异性均显著高于普通白光膀胱镜,具有较高的临床应用价值。     

荧光膀胱镜在尿路上皮膀胱癌中的诊断价值

目的:评估以5-氨基乙酰丙酸(5-aminolevulinic acid, 5-ALA)作为荧光剂的荧光膀胱镜检查对非肌层浸润性膀胱癌的诊断价值。方法:按照筛除纳入标准,纳入97名研究对象,膀胱灌注50 mL浓度为3%的5-ALA溶液,保留1小时后,排空膀胱后置入膀胱镜,分别在普通白光和荧光下观察,对白光和/或荧光下显示阳性或可疑区域取组织做病理活检,同时行电切术。结果:97例患者中,19例患者普通白光膀胱镜及荧光膀胱镜下检查均为阴性,剩余78例患者取156处组织进行活检,平均每例患者取2块组织。结果显示97处病理报告为尿路上皮癌。经计算得出荧光膀胱镜的敏感性为91.75%(89/97),特异性为64.41%(38/59);普通白光膀胱镜的敏感性为71.13%(69/97),特异性55.93%(33/59);P<0.05,差异具有统计学意义。结论:荧光膀胱镜在诊断尿路上皮膀胱癌上的敏感性和特异性均显著高于普通白光膀胱镜,具有较高的临床应用价值。     

Fluorescent cystoscopy and transurethral electroresection in diagnosis and treatment of patients with invasive cancer of the urinary bladder

From 1996 to 2002 we examined and treated 224 patients with invasive cancer of the urinary bladder (ICUB). The examination complex included clinical, laboratory, radiation tests, endoscopic and morphological investigations of the surgical material. The patients received four types of treatment: transurethral resection (TUR) of the bladder wall (n = 102) alone; TUR+MVAC chemotherapy (n = 56); open resection of the urinary bladder only (n = 38); open resection+MVAC chemotherapy (n = 28). In diagnosis of papillary lesions sensitivity of cystoscopy (CS) was 66.6%, fluorescent CS (FCS)--95.2%. Sensitivity in diagnosis of squamous tumors was 33.3 and 91.6%, respectively. The best results were achieved in patients with pT2A tumor invasion depth, G1 differentiation of tumor cells after TUR with adjuvant polychemotherapy (PCT) recurrences in these patients arose by 41.2% less frequently than in patients after TUR only, 5-year survival in patients after TUR+PCT was 83.3%. Thus, FCS improves diagnosis of urinary bladder tumors (sensitivity of CS was 70.0% vs that of FCS--95.0%). In cancer of the urinary bladder the organ can be saved only at stage pT2G1. A method of choice is TUR of the bladder wall with adjuvant PCT.     

Role of 5-aminolevulinic acid in the detection of urothelial premalignant lesions

BACKGROUND: The authors evaluated the role of 5-aminolevulinic acid (5-ALA)-induced fluorescence endoscopy (AFE) in the detection of flat urothelial lesions in light of the suggestions made for flat neoplastic lesions within the 1999 World Health Organization (WHO) classification of urinary bladder tumors. METHODS: From 1995 to 2000, 713 patients underwent 1414 AFE procedures for the detection of transitional cell carcinoma of the bladder (TCCB). Fluorescence imaging was performed with an incoherent light source (D-light; 380-440 nm) that was filtered for efficient protoporphyrin IX excitation and with cystoscopes partially blocking reflected excitation light to enable fluorescence evaluation by a red/blue color contrast 2-3 hours after 50 mL of a 3% solution of 5-ALA was instilled into the bladder. In total, 3834 biopsy specimens (mean, 2.7 specimens per AFE procedure) were taken. RESULTS: Malignant disease was found in 1250 (32.6%) of all biopsies, with 304 biopsies (24.3%) showing carcinoma in situ (cis) and dysplasia II degrees (dys II) according to the previous diagnostic criteria of the WHO. Under prior conventional white-light endoscopy, 30.3% of specimens with dys II and 52.8% of specimens with cis had been missed. CONCLUSIONS: The current results suggest that 5-ALA may be more effective in the detection of flat urothelial lesions than the current diagnostic devices.     

Molecular genetic evaluation of fluorescence diagnosis in bladder cancer

Fluorescence diagnosis of superficial bladder cancer using 5-aminolevulinic acid (ALA) is a highly sensitive technique (95%). However, the specificity is only 60-70% due to false-positive results after histopathological examination. We hypothesized that the biopsies in fluorescence endoscopy could represent early preneoplastic lesions not detectable by histopathology. In order to evaluate the specificity of fluorescence endoscopy at the molecular genetic level we performed comparative genomic hybridization (CGH) and investigated telomerase activity of ALA-positive tissue samples. For CGH, DNA was isolated from 5-10 frozen sections. Tumor and normal (control) DNAs were amplified by DOP-PCR and labeled with biotin-dUTP and digoxigenin-dUTP, respectively. Hybridization and detection were carried out according to standard protocols. Telomerase activity was analyzed using a non-radioactive system (TRAP-assay). In 33 out of 118 bladder cancer cases (28%) detected by conventional cystoscopy, additional suspicious areas were found using ALA. CGH revealed genetic changes in 27% of samples with non-malignant histological diagnoses. Telomerase activity was found in 59% of these samples. Tumor samples showed genetic alterations in 84% and in 69% telomerase activity occurred. The type of genetic alterations in the normal biopsies was identical to the tumors. Based on these molecular data, the portion of false-positive results obtained by fluorescence diagnosis is lower than defined by histopathology alone. Genetic alterations and activation of telomerase activity are early events of tumor development in bladder cancer occurring earlier than histological features of neoplasia. The clinical importance of fluorescence diagnosis and the possible reduction of the recurrence rate have to be shown in ongoing clinical studies.     

Laparoscopic fluorescence detection of ovarian carcinoma metastases using 5-aminolevulinic acid-induced protoporphyrin IX

BACKGROUND: The aim of the current clinical study was to evaluate the in vivo fluorescence detection of ovarian carcinoma metastases in a second-look laparoscopic procedure after intraperitoneally applied 5-aminolevulinic acid (ALA). METHODS: Five hours before laparoscopic surgery, ALA was applied intraperitoneally via short infusion in a concentration of 30 mg/kg bodyweight in a sterile, 1% solution. Application of ALA resulted in the endogenous production of the fluorescent photosensitizer, protoporphyrin IX (PP IX). The Combilight PDD 5133 system served as a light source, permitting the switch from white light mode to blue light mode to excite the PP IX accumulated in the ovarian tissue specimens. By means of blue light illumination, intraperitoneally located red fluorescent lesions, which were suspected to be metastases, underwent a biopsy. In addition, several biopsy specimens were taken from nonfluorescent areas of the peritoneal cavity. RESULTS: In 13 of 29 patients, ovarian carcinoma was confirmed histologically or cytologically. In 12 of these patients, metastases were visible by red fluorescence. In total, 123 biopsies were performed. Comparison of histologic assessment of the biopsy specimens with the fluorescence detection showed that strong red fluorescence had a sensitivity of 92% for detecting tumor tissue on specimens. In only 2% of all biopsy specimens was endometriosis observed in benign tissue specimens using fluorescence. In four of 13 patients with ovarian carcinoma, lesions were detected under fluorescence, which were not observed under white light illumination. CONCLUSIONS: Laparoscopic fluorescence detection of endogenous PP IX after intraperitoneal application of ALA may provide a higher sensitivity of finding peritoneal metastases of epithelian ovarian carcinoma compared with conventional laparoscopy. Direct visualization of in vivo fluorescence after ALA application may improve the early detection of intraperitoneal ovarian carcinoma micrometastases. The high tissue selectivity of PP IX accumulation in tumor tissue specimens also offers the opportunity for therapeutic approaches using photodynamic therapy in the future.     

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin for prophylaxis of recurrence of superficial bladder cancer: a preliminary report

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of 40 mg epirubicin immediately after transurethral resection (TUR) of the bladder cancer. At 1 week after TUR, 80 mg Tokyo-strain BCG was instilled into the bladder once a week for 6 weeks. Thereafter, the patients were followed by cystoscopy and urinary cytology at 3-month intervals until recurrence was detected. Of the 29 patients, 28 had no evidence of disease over a mean follow-up period of 20 months. The 1 case of recurrence occurred at 3 months after TUR and that patient died of cancer progression. The simple recurrence rate was 3.5% after therapy. According to the person-years method, the number of recurrent tumors per 100 patient-months was 0.17. The cumulative nonrecurrence rate determined for all cases was 96.5% at 30 months. Adverse reactions, including urinary frequency, urgency, and miction pain, among others, were observed in 27 patients (93%). Only 1 patient was withdrawn from the treatment because of severe bladder-irritation symptoms due to the BCG instillation. The intravesical chemoimmunotherapy with epirubicin and BCG seemed to be effective for prophylaxis of recurrence of superficial bladder cancer.Paper presented at the 5th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 24–25 September 1993, Hakone, Japan     

Interferon alfa 2a in superficial bladder cancer prophylaxis: toleration and long-term follow-up. A phase I-II study.

Twenty patients (17 M., 3F., -mean age 61.5 yrs) affected by superficial bladder tumors (TINOMO) were included in the study. All patients had cold mucosa biopsy to exclude the presence of dysplasia or CIS; the histopathological grade was G1 in 19 cases and G2 in 1. The treatment was started between 3 to 7 days after radical TUR with intravesical instillations of recombinant Interferon alfa 2a, at the daily dose of 54 million/Units for 5 days for 2 consecutive weeks. No systemic adverse effects were observed. Local toleration and efficacy were assessed by cystoscopy, performed at the end of treatment after 6 weeks and then at three month intervals. At the first control 15% of patients showed an early local reaction with bollous oedema surrounding the resected area (with spontaneously disappeared after few days). No other abnormal findings were observed at the 6-week control. After a median follow-up of 98 weeks, 15 of the 19 evaluable patients (79%, C.I. 60-91) were disease-free. The median relapse time was 39.9 weeks, while clinical and local tolerance were optimal. These preliminary data confirm the complete absence of toxicity of Interferon alfa 2a administered at relatively high doses intravesically and indicate that this compound has some effect on superficial bladder cancer.     

Feasibility of Photodynamic Diagnosis for Challenging TURBt Cases Including Muscle Invasive Bladder Cancer,BCG Failure or 2nd-TUR

Background: Despite widely adopted standard methods for follow-up including cystoscopy plus cytology,recurrence rates of non muscle-invasive bladder cancer (NMIBC) have not improved over the past decades, stillranging from 60% through 70%. Hence, widely acceptable surveillance strategies with excellent sensitivity areneeded. Early recurrence has led to the development of a novel cystoscopy technique utilizing photodynamicdiagnosis (PDD). Although, no studies have evaluated the efficacy of PDD for patients of MIBC, BCG failure or2nd-transurethelial resection (TUR). Materials and Methods: The present study was performed from October2012 through May 2013. IRB approved 25 patients initially underwent a cystoscopy examination of white lightand blue light followed by the resection of tumors identified. Resections were performed from bladder mucosaareas considered suspicious at PDD, along with PDD negative normal bladder mucosa area resected by randombiopsy. Specimens were divided into two groups, PDD positive and negative. Primary endpoints were sensitivityand specificity. Results: A total of 147 specimens extracted from 25 patients were included in the analysis. Some45 out of 92 PDD-positive specimens were confirmed to have bladder cancer, and 51 out of PDD-negative 55specimens were confirmed to be cancer negative. The sensitivity of PDD was 91.8% (45/49) and specificity was52.0% (51/98). The sensitivity:specificity was 89.5% (17/19) : 47.6% (30/63) in 12 2nd-TUR patients, 90.5%(19/21) : 61.1% (11/18) in seven MIBC patients, and 95.0% (19/20) : 48.5% (16/33) in eight failed BCG cases.Conclusions: PDD-TURBT has high sensitivity to diagnose BC even for 2nd-TUR, MIBC or BCG failure cases.     

Clinical study of G3 superficial bladder cancer without concomitant CIS treated with conservative therapy

OBJECTIVE: The treatment for superficial G3 transitional cell carcinoma (TCC) of the urinary bladder remains controversial. It is important to reveal the clinical features of superficial G3 bladder cancer that can be treated conservatively. PATIENTS AND METHODS: A total of 39 patients with primary superficial bladder cancer (Ta, T1) with G3 components but without concomitant carcinoma in situ (CIS), who had been treated initially with transurethral resection (TUR), were retrospectively analyzed for factors related to tumor recurrence, progression and survival. The patients were 34 males and five females whose age ranged from 49 to 85 years (average, 68 years). Initial tumor stages were Ta in one patient and T1 in 38. Initial treatments were TUR alone in 18 patients and TUR with adjuvant therapy (intravesical chemotherapy or BCG therapy) in 21. Factors examined included age, gender, morphology, size and number of tumors and adjuvant therapies. RESULTS: Follow-up periods were 3-138 months (median, 37 months). Tumor recurrence, progression and cancer death were observed in 23, seven and four cases, respectively. The 5-year progression-free rate (75%) and survival rate (83%) in 39 patients with G3 did not show a statistically significant difference from those of the 109 patients with G1 or the 187 patients with G2 superficial bladder cancer who were treated with TUR initially. Only the rate of recurrence of patients with G3 was significantly higher than that of patients with G2 or G1. Adjuvant therapies reduced the recurrence rate of the patients with G3. Only tumor morphology, papillary or non-papillary, affected both the progression-free rate and the survival rate of patients with G3. There were no statistically significant differences associated with other factors. CONCLUSION: The results suggest that superficial G3 bladder cancer could be treated with TUR initially, especially for papillary tumors.     

The immunomodulating effect of interferon-gamma intravesical instillations in preventing bladder cancer recurrence.

PURPOSE: The purpose is to investigate the prophylactic effect of intravesically instillated recombinant IFN-gamma against recurrence of superficial transitional cell carcinoma of the bladder and to evaluate its effect in local immune response, presumably mediating its therapeutic efficacy. EXPERIMENTAL DESIGN: We prospectively randomized in two groups 123 patients with initially diagnosed superficial transitional cell carcinoma and stage Ta, T1, grade 2 tumors, who underwent transurethral tumor resection (TUR). In group A, 60 patients received IFN-gamma (1.5 x 10(7) IU/instillation), whereas 63 patients, consisting of the control group B, received mitomycin C (40 mg/instillation). The annual administration schedule consisted of eight weekly followed by four biweekly and then by eight monthly instillations for both regimens. We also analyzed the immunophenotype of the intratumoral and intramural leukocytes by immunohistochemical and flow-cytometric techniques. To this purpose, tumor samples were obtained at TUR and random biopsies at TUR and during cystoscopy at 6 and 12 months, and bladder washings were collected before TUR and at preselected time points. RESULTS: In group A, 44 of 60 (73.4%) patients, and in group B, 36 of 63 (57.2%) patients, were tumor free during the median follow-up period of 26.5 months (range, 3-49 months). IFN-gamma was well tolerated. Six months after starting treatment, follicular cystitis was detected in patients responding to IFN-gamma. After IFN-gamma instillations, statistically significant increases in T cells, T-helper cells, T-cytotoxic cells, natural killer cells, and total leukocytes, as well as in the number of B cells expressing intercellular adhesion molecule-1 and total leukocytes expressing HLA-DR, were observed by flow cytometry in tissue specimens and bladder washings. CONCLUSIONS: Recombinant IFN-gamma appears to be effective against stage Ta, T1, grade 2 bladder tumors' recurrence. Recruitment and activation of intramural leukocytes seem to be involved in the mechanism of IFN-gamma action.     

Role of fluorescent control in raising radicality of surgical treatment for superficial bladder cancer

Solution of 5-aminolevulinic acid (5-ALA) and D-Light unit (Karl Storz GmbH & Co) were used for fluorescent control over radicality of transurethral resection (TUR) of the urinary bladder. TUR with the fluorescent control was performed in 85 patients. The new procedure allowed to remove tumors undetectable at standard TUR in 46(54.1%) patients. Sensitivity and specificity of the method was 98.7 and 76.3%, respectively. 5-ALA-induced fluorescence used to control radicality of bladder TUR reduced the number of recurrences within 12 postoperative months 2-fold.     

Non-invasive molecular detection of bladder cancer recurrence

Transitional cell carcinoma (TCC) is the most common bladder tumor and approximately 90% of bladder TCC are superficial at initial diagnosis. High recurrence rate and possible progression to muscle invasive disease that is eventually indicated for radical cystectomy are established features of these tumors. Therefore, reliable predictors of tumor recurrence are of critical importance for management of superficial bladder TCC. Successful molecular diagnosis of bladder cancer by detecting genetic lesions: loss of heterozygosity (LOH) or microsatellite instability (MSI) in cells exfoliated in urine has been reported by several groups including ours. The aim of our study was to evaluate the predictive potential of microsatellite analysis of cells exfoliated in urine in the detection of superficial bladder TCC recurrence. We studied 47 Caucasian patients with confirmed superficial bladder TCC (37 pTa, 10 pT1) at initial diagnosis. Blood samples were obtained once from every patient whereas urine samples were collected before each cystoscopy (initial and follow-up). Matched DNAs from blood and urine were subjected to microsatellite analysis in a blinded fashion. The follow-up period ranged 12-48 months after tumor resection. Microsatellite analysis correctly identified 94% (44/47) of primary tumors and 92% (12/13) of tumor recurrences. Interestingly enough, 75% (9/12) of tumor recurrences were molecularly detected 1-9 months before cystoscopic evidence of recurrent disease. This study demonstrated clearly that not only urine microsatellite analysis reliably detected superficial bladder tumors, but also was a reliable test for detecting and predicting tumor recurrence in Caucasian patients. These results warrant multicenter randomized trials.     

Comparison of NMP22 BladderChek test and urine cytology for the detection of recurrent bladder cancer

OBJECTIVE: To assess the clinical performance of the NMP22 BladderChek test, which is a qualitative test, and to compare it with voided urine cytology for the detection of recurrent bladder cancer. We also evaluated whether cystoscopy can be omitted from the surveillance protocol by combining the two tests. METHODS: A total of 131 patients with a history of superficial transitional cell carcinoma of the bladder provided urine samples before a cystoscopic examination. Urine samples were assayed for the presence of NMP22 using the NMP22 BladderChek test and cytology was performed by a cytopathologist. Selected patients underwent a biopsy, with appropriate additional therapy. Results of the two tests were compared with that the results of cystoscopy, which was retained as the gold standard. For positive biopsies, the results of the NMP22 test and cytology were also correlated with the tumor stage and grade. RESULTS: Of the 46 recurrences detected by cystoscopy, the NMP22 test was positive in 39 cases and cytology in 19 cases. The sensitivity of the NMP22 test was 85%, which was significantly greater than that of cytology (41%). In particular, for low-risk tumors it was eight times more sensitive than cytology. The specificities of the NMP22 test and cytology were 77 and 96%, respectively. Combining the two tests increased overall sensitivity to 91%. However, 9% of the tumors were still not detected. CONCLUSION: The NMP22 BladderChek test is an in vitro qualitative test that is easily available and cheap; it can be performed by a urologist in the office and results can be interpreted within 30 min. The NMP22 test is superior to cytology for all grades and stages in the detection of recurrence in patients with a history of superficial bladder cancer. Our study indicates that the NMP22 test can be used as a substitute for urine cytology. The NMP22 test cannot replace cystoscopy, but it can be used as an adjunct to cystoscopy in the surveillance protocol for patients with superficial bladder cancer.     

Three-dimentional echography in diagnosis and staging of urinary bladder cancer

The role of USI and three-dimentional volumetric reconstruction was studied in diagnosis of urinary bladder cancer diagnosis. 69 UBC patients were examined. Examination included renal USI of the kidneys, urinary bladder, prostate, echoureterography, cystoscopy, CT, MRT. The number of the tumors, volume, area, invasion were studied in 3D mode. US angiography assessed resistance index and tumor vascularization by degrees 0-3. USI findings were compared with those of MRT, cystoscopy, histomorphology of the biopsies. 2D USI technique proved effective in detection of urinary bladder cancer at stage T1 in 66%, 3D in 100. At stage T2a-b informative value of both techniques reached 87%. Overall informative value of 2D in detection of urinary bladder cancer was 81%, three-dimentional echography--96%. USI proved effective in diagnosis and staging of urinary bladder cancer. Use of 3D ultrasonic angiography facilitates the choice of more effective surgical policy in the treatment of urinary bladder cancer patients.     

经尿道钬激光与电切治疗表浅性膀胱肿瘤的临床疗效比较

目的:总结比较经尿道行钬激光治疗(holmium laser resection)与电切治疗(transurethral resection)表浅性膀胱肿瘤的临床疗效.方法:共收治64例膀胱肿瘤患者,其中26例行经尿道钬激光切除手术,38例行经尿道电切手术;分析2组患者手术时间、膀胱穿孔例数、术后膀胱冲洗例数、导尿管留置时间、尿道狭窄发生率、肿瘤复发等指标,并比较其临床疗效.结果:随访6.28个月,2组患者平均手术时间、导尿管留置时间、术后尿道狭窄发生率、肿瘤复发率均经比对差异均无统计学意义(P＞0.05),但钬激光治疗组的膀胱穿孔及术后膀胱冲洗例数明显少于电切治疗组(P＜0.05).结论:钬激光治疗表浅性膀胱肿瘤疗效确切,并发症少,在减少膀胱穿孔等方面比电切治疗更有优势.