核基质蛋白22检测与尿脱落细胞学检查在膀胱癌诊断中的价值

目的　探讨尿核基质蛋白 2 2 (NMP 2 2 )检测和尿脱落细胞学检查在膀胱移行细胞癌诊断中的价值。　方法　对 15 5例怀疑膀胱癌者进行尿NMP 2 2与尿细胞学检查 ,其中 95例经组织学证实为膀胱移行细胞癌。比较两者诊断膀胱癌的敏感性和特异性。　结果　尿NMP 2 2的敏感性为6 5 .3%、特异性为 70 .0 % ;尿细胞学的敏感性为 4 3.2 %、特异性为 83.3%。NMP 2 2在膀胱癌不同分级和分期中的敏感性优于尿细胞学 (P <0 .0 5 )。　结论　尿NMP 2 2检测在早期诊断膀胱癌方面优于尿细胞学检查 ,可以作为膀胱癌的早期检测指标。     

Immunocyt and the HA-HAase urine tests for the detection of bladder cancer: a side-by-side comparison

OBJECTIVES: The reliable detection of bladder cancer from urine specimen remains an unsolved problem. Especially superficial bladder cancer can be missed with urine tests. We assessed the sensitivity and specificity of the commercial Immunocyt test in a side-by-side comparison with the HA-HAase urine test and cytology. The Immunocyt test measures the immunocytological expression of sulfated mucin-glycoproteins and glycosylated forms of the carcinoembryonic antigen in urine. With the HA-HAase urine test the level of hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are measured in an ELISA-like test. METHODS: A total of 94 consecutive patients were studied and among these 30 patients had bladder cancer and 64 were controls. Among bladder cancer patients, there were 14 pTa, 9 pT1, 5 pT2 and 2 carcinoma in situ (CIS) transitional cell carcinoma of the bladder, respectively. The controls consisted of 55 patients with a history of bladder cancer but no evidence of tumor at the follow-up cystoscopy and 9 benign prostatic hyperplasia (BPH) patients. The 30 transitional cell cancer specimens had 4 (13%) grade 1 tumors, 15 (50%) grade 2 tumors and 11 (37%) grade 3 tumors. Sensitivity and specificity as well as the positive and negative predictive values of each test were evaluated. RESULTS: The sensitivity of the HA-HAase urine test (83.3%; 25/30) was significantly higher than the Immunocyt at 63.3% (19/30) (p = 0.038, McNemar test) and cytology (73%; p < 0.05). The specificity of the HA-HAase test (78.1%; 50/64), Immunocyt (75%; 48/64) and cytology (79.7%; 51/64) were comparable. The prevalence of bladder cancer in our study was 31%. The positive predictive value (PPV) of the HA-HAase test (64.1%) was significantly higher than the Immunocyt test (54.3%). The negative predictive value (NPV) of the HA-HAase test (90.9%) was also higher than the Immunocyt test (81.3%). The PPV and NPV values for cytology were 62.9% and 86.4%, respectively. False negative patients in the HA-HAase urine test were 5 pTa tumors (2 G1, 2 G2 and 1 G3). False negative patients in the Immunocyt test were 7 pTa tumors (1 G1 and 6 G2), 3 pT1 (2 G2, 1 G3) and 1 pT2 G3, respectively. CONCLUSIONS: The sensitivity of the HA-HAase urine test is significantly higher than that of the Immunocyt test to detect bladder cancer. Specificity, as well as the PPV and NPV of the HA-HAase test were higher than that of the Immunocyt test. With a prevalence of 31% bladder cancer patients in all hematuria patients studied, a typical distribution of patients in a urological clinic is presented. Longer follow up of the study patients will give more information on the value of these tests in the detection of bladder cancer.     

核基质蛋白22在膀胱移行上皮癌诊断中的价值(附48例报告)

目的:评价患者尿中核基质蛋白22(NMP 22)在泌尿系上皮肿瘤诊断中的意义。方法:采用ELISA法测定48例膀胱移行上皮肿瘤患者尿中NMP 22的值,并与尿脱落细胞学检查进行比较。结果:48例膀胱移行上皮肿瘤患者尿NMP 22的中位值为19.53 IU/L。以10 IU/L为临界值,NMP 22诊断膀胱移行上皮肿瘤的敏感性为86.96％,特异性为50％;尿脱落细胞学检查的敏感性为17.39％,特异性为100％。尿NMP 22在肿瘤的分期、分级间的差别无显著性意义(P>0.05)。结论:尿NMP 22检测比尿脱落细胞学检查更敏感,可以作为血尿患者和既往膀胱肿瘤患者的首选筛选方法。     

Urinary level of nuclear matrix protein 22 in the diagnosis of bladder cancer: experience with 130 patients with biopsy confirmed tumor

PURPOSE: We prospectively evaluated the value of nuclear matrix protein 22 (NMP22dagger) and cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: We analyzed NMP22 in voided urine from 235 patients before cystoscopy. Of the patients 130 had transitional cell carcinoma of the bladder and subsequently underwent surgery. In a subset of 200 patients bladder washout samples for cytology were collected during cystoscopy. The cutoff for NMP22 was 10.0 units per ml. For cytology only high grade atypia was considered positive. RESULTS: Histology showed 77 superficial (pTa, pTis) and 53 invasive (pT1 or greater) tumors. Sensitivity of NMP22 was 51% and specificity was 83%. NMP22 sensitivity was 36% for superficial tumors and 73% for invasive transitional cell carcinoma. Overall sensitivity of cytology was 52% and specificity was 89%. Cytology sensitivity was 38% for superficial tumors and 83% for invasive transitional cell carcinoma. NMP22 sensitivity for grades 1, 2 and 3 tumors was 30%, 56% and 68%, respectively. Cytology sensitivity for grades 1, 2 and 3 tumors was 30%, 50% and 91%, respectively. Combined NMP22 and cytology had a sensitivity of 70%. CONCLUSIONS: NMP22 has sensitivity and specificity similar to those of cytology from bladder washout samples. Particularly in low stage and low grade tumors both tests show the same disappointing sensitivity. Because of a false-negative rate of 49%, NMP22 cannot replace cystoscopy in clinical practice, as the danger of missing NMP22 negative tumors is too high to rely on its results in an individual patient.     

survivin与nmp22对诊断尿路上皮肿瘤价值的比较

目的 :评价尿脱落细胞中survivin的表达和尿nmp2 2的表达对诊断尿路上皮肿瘤的价值。 方法 :对4 8例尿路上皮肿瘤患者 ,在行膀胱镜检查或手术前留新鲜尿液分别行尿脱落细胞survivin、尿nmp2 2和尿脱落细胞检查 ,并分别比较各方法的敏感性、特异性。结果 :尿路上皮肿瘤患者尿脱落细胞涂片中survivin表达 4 8例中4 6例阳性 ,尿NMP2 2有 38例阳性 ,而尿脱落细胞学仅 15例阳性 ,survivin的敏感性高于nmp2 2及脱落细胞学 (P <0 .0 5及P <0 .0 1)。三者的特异性分别为 10 0 %、90 %和 10 0 % ,差异无统计学意义。结论 :检测尿脱落细胞中survivin的表达方法简单无创敏感性、特异性高对诊断尿路上皮肿瘤的价值优于尿nmp2 2。     

Urine cytology in bladder tumors

A review of experience with urine cytology in the diagnosis and follow up of bladder cancer at Roswell Park Memorial Institute from 1971 to 1981 is reported. All patients had biopsy-proven transitional cell carcinoma of the bladder. A total of 677 patients underwent 2,877 cytological evaluations. Of these, 317 patients had concomitant cystoscopy, cytologic evaluations and bladder biopsies. A total of 1,091 evaluations were performed in this group. The overall incidence of positive cytology in the presence of biopsy-proven bladder tumor (all grades included) was 74.4%. A linear correlation is present with grade, stage and positive cytology; high-grade tumors and carcinoma-insitu showed 89.9% and 96.9% incidence of positive cytology, respectively. Grade II tumors showed a 64% incidence of positive cytologies. Regarding correlation with the pathological stage, submucosal involvement of the urothelium was associated with a 62% incidence of positive exfoliative urine cytology, while 80% of tumors invading the bladder muscle were found to have a positive cytology.     

Current bladder tumor tests: does their projected utility fulfill clinical necessity?

PURPOSE: We reviewed currently available bladder cancer tests in the context of the clinical expectations of a noninvasive bladder cancer test. MATERIALS AND METHODS: We reviewed the literature on bladder cancer tests that are commercially available or have shown clinical usefulness and examined how each test compares with standard methods of bladder cancer diagnosis. RESULTS: The clinical necessity for a noninvasive test for bladder cancer is 2-fold, including the early detection of high grade bladder tumors before muscle invasion and monitoring tumor recurrence or new onset. An ideal noninvasive test should be sensitive, specific, rapid, technically simple and have low intra-assay and interassay variability. Urine cytology has high specificity but limited applicability due to its relatively low sensitivity and subjective nature. Hematuria detection by Hemastix dipstick is sensitive but not specific for detecting bladder cancer. Molecules associated with bladder tumor growth and progression may serve as a basis for designing noninvasive diagnostic tests. The Food and Drug Administration approved BTA Stat and BTA TRAK tests, which detect human complement factor H and a related protein in urine, have 60% to 80% sensitivity and 50% to 70% specificity (lower in symptomatic patients) for bladder cancer. The Food and Drug Administration approved NMP22 test, which measures the level of nuclear mitotic apparatus protein in urine, has 50% to 100% sensitivity and 60% to 90% specificity. Accu-Dx detects fibrin degradation products, fibrin and fibrinogen in urine, although this test is no longer commercially available. The Immunocyt test combines cytology with an immunofluorescence technique to improve the sensitivity of cytology for detecting low grade tumors. The telomeric repeat amplification protocol assay for telomerase in exfoliated cells has 70% to 86% sensitivity and 60% to 90% specificity for bladder cancer. However, the low stability of telomerase in urine affects its sensitivity. The hyaluronic acid and hyaluronidase (HA-HAase) test, which measures the urinary level of hyaluronic acid and hyaluronidase, has 90% to 92% sensitivity and 80% to 84% specificity for bladder cancer. Quanticyt karyometry evaluates nuclear shape and DNA content of exfoliated cells to detect bladder cancer. The list of bladder tumor markers is growing rapidly and large multicenter trials are essential to assess their usefulness. CONCLUSIONS: Although currently noninvasive bladder cancer tests cannot replace cystoscopy, some have shown a promise of being clinically useful. One or a combination of these tests-markers may prove to be a prostate specific antigen for bladder cancer provided that patients and, more importantly, clinicians accept it.     

Immunocyt test improves the diagnostic accuracy of urinary cytology: results of a French multicenter study

PURPOSE: The limitations of urinary cytology and the invasiveness of cystoscopy generate an increasing interest in noninvasive diagnostic tools for the management of transitional cell carcinoma. We assess the clinical performance of ImmunoCyt (DiagnoCure, Inc., Saint-Foy, Canada) in the detection of bladder cancer in a 10-center French trial. MATERIALS AND METHODS: From October 2000 to April 2001, 694 patients undergoing cystoscopy were prospectively included in the study. Of the patients 458 (66%) had been previously treated for superficial transitional cell carcinoma and 236 (34%) were referred for symptoms suggestive of bladder cancer. All patients underwent ImmunoCyt test and standard urinary cytology from voided urine as well as a complete evaluation including cystoscopy and transurethral resection or biopsy of suspicious lesions. Sensitivity and specificity values of urinary cytology and ImmunoCyt whether or not combined were calculated using cystoscopy as the gold standard and histopathology when available. RESULTS: A total of 85 recurrent and 58 newly diagnosed bladder tumors were diagnosed by cystoscopy and histologicaly confirmed. Overall sensitivity of urinary cytology was 17.9%, 46.3% and 63.8% respectively, for G1, G2 and G3 transitional cell carcinoma, whereas that of ImmunoCyt was 60.7%, 75.6% and 76.8%. Sensitivity of the combined tests was 66.7%, 78% and 87%, respectively. Moreover, 10 of 55 (18.2%) new pT1 and pT2 or greater tumors were diagnosed by ImmunoCyt alone. Specificity of urinary cytology was 94.5%, whereas that of ImmunoCyt was 84.2%. Specificity of the combined tests was 80.7%. Marked variations in urinary cytology sensitivity were observed among the different centers (27.3% to 66.7%), whereas combined assays (urinary cytology and ImmunoCyt) enhanced the overall sensitivity in the 80% range at most centers. CONCLUSIONS: This prospective multicenter series confirmed a marked increase in sensitivity without significant loss in specificity when including ImmunoCyt in standard urinary cytology protocol. This increased sensitivity was observed in high grade lesions (with 100% sensitivity for carcinoma in situ) as well in low grade, low stage tumors.     

NMP22与BTA stat检测在膀胱肿瘤诊断中的应用

目的评价NMP22和BTAstat诊断膀胱肿瘤的价值.方法对82例临床怀疑膀胱肿瘤的患者,在膀胱镜检查前将尿样分为3份,分别进行NMP22、BTAstat和脱落细胞学检测,分析比较3种方法的敏感性、特异性和阳性预测价值.结果82例中病理证实膀胱肿瘤32例,其他疾病50例.NMP22诊断膀胱肿瘤敏感性为87.5%,与BTAstat(65.6%)、细胞学(21.9%)比较,差别有显著性意义(P<0.05).3种方法诊断特异性分别为84.0%、64.0%和100.0%.阳性预测值分别为77.8%、53.9%和100.0%.结论NMP22是一种简单、敏感、非侵袭性的早期诊断膀胱肿瘤的肿瘤标记物.     

IMMUNOSTAINING OF LEWIS X IN CELLS FROM VOIDED URINE, CYTOPATHOLOGY AND ULTRASOUND FOR NONINVASIVE DETECTION OF BLADDER TUMORS

Purpose

We examined the use of immunostaining of the Lewis X antigen in exfoliated cells from voided urine samples, cytopathology and bladder ultrasound for noninvasive detection of bladder tumors as a potential substitute for cystoscopy.

Materials and Methods

A total of 260 patients were included, of whom 80 were evaluated because of irritative symptoms or hematuria and 180 were examined during followup visits after resection of bladder tumors. Voided urine samples were obtained from each patient for immunocytology and cytopathology. Bladder ultrasound and cystoscopy were performed. Biopsies were obtained whenever a bladder tumor was seen or if carcinoma in situ was suspected. Indirect immunoperoxidase staining was done on cytocentrifuge slides, using the P12 monoclonal antibody against the Lewis X antigen.

Results

Cystoscopy and biopsies revealed bladder tumors in 84 patients. Immunocytology of 1 urine sample resulted in a sensitivity of 79.8% and a specificity of 86.4%. The diagnosis of primary carcinoma in situ by immunocytology was correct in 100% of the cases. The examination of 2 consecutive urine samples detected 95.1% of the tumors. False-negative results occurred in a few cases with small, superficial, low grade tumors. Cytopathology and bladder ultrasound resulted in a sensitivity of 47.6 and 66.7%, and a specificity of 97.7 and 97.2%, respectively. The results of immunocytology of 2 urine samples were equivalent to the combination of immunocytology of a single urine sample, cytology and ultrasound.

Conclusions

Immunostaining of the Lewis X antigen is significantly more sensitive than cytopathology for the detection of low grade as well as high grade tumor cells in voided urine. Immunocytological evaluation of 2 consecutive voided urine specimens for the Lewis X antigen is the most sensitive method currently available for noninvasive detection of transitional cell tumors. This assay may replace cystoscopy for detection of bladder cancer.     

联合检测尿膀胱癌抗原和survivin诊断膀胱癌的临床应用

目的 临床评价联合检测尿液中尿膀胱癌抗原(urinary bladder cancer antigen,UBC)和survivin基因诊断膀胱癌的临床应用价值.方法 对64例膀胱癌患者、20例泌尿系其他良性疾病患者,在膀胱镜检查之前留尿将尿样分为3份,分别进行UBC、survivin和脱落细胞检测,分析比较三种方法诊断膀胱癌的临床应用价值.结果 UBC和survivin诊断膀胱癌的敏感度分别为85.9%(55/64)和93.8%(60/64),与脱落细胞学(40.6% )比较,差异有统计学意义(P＜0.01〉,三种方法诊断膀胱癌的特异度分别为85.0%(17/20)、95%(19/20) 和95%(19/20).各分级和分期UBC和survivin诊断膀胱癌的敏感度均高于尿脱落细胞学检查;UBC值和survivin检测的敏感度在各分级和分期中差异无统计学意义(P＞0.05);而尿脱落细胞学检查,肿瘤的分级越高,其敏感度越高(P＜0.01),各分期之间差异无统计学意义(P＞0.05).联合运用UBC和survivin,敏感度和特异度均达到100%.结论 尿液中的UBC和survivin是早期诊断膀胱癌较好的肿瘤标志物,联合检测能提高诊断的敏感度和特异度.     

Rolle der Immunzytologie in der Abklärung von Patienten mit schmerzloser Makrohämaturie

Objective

Gross hematuria is a highly worrisome episode in a patient’s history mainly due to the fact that the prevalence of bladder cancer is significant in this group of patients. In this prospective study the role of immunocytology in the evaluation of patients with gross hematuria was investigated.

Materials and methods

Ucyt® is an immunocytological assay based on microscopic detection of tumor-associated antigens on urothelial cells. The study included 103 consecutive patients with a first episode of painless gross hematuria without prior transitional cell carcinoma. Urine samples were obtained from all patients and examined cytologically and immunocytologically.

Results

Clinical assessment by physical examination, laboratory tests, endoscopy, and imaging modalities yielded urothelial cancer in 22 cases (21%). Further diagnoses were BPH (30%), inflammation (10%), urolithiasis (7%), and“further conditions” (16%). In 17 patients the reasons for hematuria were not determined. For cystoscopy, immunocytology, and conventional urine cytology a sensitivity of 89 (excluding UUT), 86, and 45% was observed. Specificity was 94, 82, and 89%, respectively. Two and three bladder tumors were not detected by cystoscopy and immunocytology, respectively.

Conclusions

The combination of cystoscopy and immunocytology yielded 100% sensitivity, while combining cystoscopy and cytology only marginally improved the sensitivity of cystoscopy alone. Since sensitivity appears to be of key relevance in the assessment of patients with gross hematuria, the authors suggest the addition of a sensitive noninvasive test to the diagnostic armamentarium in this situation.     

Bladder cancer. II. Molecular aspects and diagnosis.

The current system used to classify bladder carcinoma by stage and histological grade is very useful, yet still has limited ability to predict the natural history, or treated natural history, of a bladder tumor. Cystoscopy and urine cytology are currently the gold standard in the diagnosis and follow-up of bladder cancer. Classical urine cytology, however, at least in the diagnosis of G1 tumors, is definitely characterized by a relative low sensitivity. The low sensitivity and subjective interpretation of cytology led to the development of several tests to detect bladder cancer in urine. We provide a current, comprehensive review of the literature on bladder tumor markers and summarize their diagnostic potential. In conclusion, under the premise that cystoscopy has never been subjected to evaluation, no diagnostic marker with a sensitivity and specificity comparable to cystoscopy currently exists. The combined analysis of several tumor markers, as in the Immunocyt test, seems to be the most promising approach. In the future, rather highly sensitive tests may be able to replace cystoscopy or prolong the intervals of cystoscopies in the follow-up of selected patients.     

Initial evaluation of the diagnostic performance of the new urinary bladder cancer antigen test as a tumor marker for transitional cell carcinoma of the bladder

PURPOSE: We evaluated the diagnostic performance of the new noninvasive bladder cancer test on voided urine samples from patients with transitional cell carcinoma compared to symptomatic and asymptomatic controls. MATERIALS AND METHODS: Urinary bladder cancer antigen was measured in urine from 86 patients with active transitional cell carcinoma of the bladder (group 1), 76 patients free of transitional cell carcinoma as confirmed by cystoscopy at followup (group 2), 25 patients with other benign urological diseases (group 3), 25 patients with other malignant pathological conditions (group 4) and 30 healthy subjects free of urological diseases (group 5). RESULTS: Mean urinary bladder cancer antigen concentrations were 104.84, 4.57, 11.79, 48.87 and 1.38 microg/l, for groups 1 to 5, respectively, which was statistically different (p = 0.00005) except for groups 1 and 4 (p = 0.187). Sensitivity was 87.0% (95% confidence interval 79.2 to 92.7) and specificity was 86.8% (77.1 to 93.5%), and both were optimized by receiver operating characteristics plot analysis at a threshold value of 9.74 microg/l using asymptomatic (group 2) compared to known cancer (group 1) cases. CONCLUSIONS: Urinary bladder cancer antigen might have a role as a potential tumor marker for diagnosing transitional cell carcinoma of the bladder.     

膀胱移行上皮癌患者尿及癌组织中Survivin表达的临床意义

目的：探讨Survivin对膀胱癌早期发现、常规筛选且无损伤的方法,研究其与肿瘤病理分级（期）的相关性。方法：留取53例膀胱移行上皮癌、20例泌尿系其他疾病、10例健康志愿者新鲜中段晨尿,同上53例术后癌组织。利用巢式RT—PCR、实时定量PCR技术检测Survivin的表达,同时行尿脱落细胞学及膀胱镜病检。结果：53例膀胱癌患者尿及癌组织中Survivin均有表达,敏感性为100％,特异性为90％。与尿脱落细胞学敏感性比较两者差异有统计学意义（P〈0．05）,与膀胱镜检比较差异无统计学意义。三种方法特异性比较差异无统计学意义（P〉0．05）。癌组织中Survivin的量与肿瘤病理分级（期）正相关（P〈0．01）。结论：检测尿脱落细胞中Survivin的表达有望成为临床诊断、筛检膀胱癌的较可靠方法。Survivin在膀胱的演进过程中可能起重要作用,可望作为检测膀胱癌恶化进展的指标。     

The role of urine cytology in the assessment of lower urinary tract symptoms.

OBJECTIVE: To evaluate the role of urine cytology in the investigation of men with lower urinary tract symptoms (LUTS) in the absence of haematuria. PATIENTS AND METHODS: The study comprised 336 men attending a LUTS assessment clinic, who had neither macroscopic nor microscopic haematuria. One sample of urine was collected for cytology. Those with suspicious urine cytology were investigated with intravenous urography and cystoscopy. RESULTS: Five men had abnormal urine cytology results; on further investigation one of them was found to have carcinoma in situ (CIS) and one to have a transitional cell carcinoma. Three had false-positive urine cytology results. CONCLUSION: A bladder tumour or CIS was detected in 0.6% of the population tested. The cost per cancer diagnosed was GB pound 2020. Urine cytology is a simple noninvasive way of assisting accurate diagnosis of men who have LUTS in the absence of haematuria.     

Combined assay of CYFRA21-1, telomerase and vascular endothelial growth factor in the detection of bladder transitional cell carcinoma

BACKGROUND: CYFRA21-1, telomerase and vascular endothelial growth factor (VEGF) are regarded as useful tumor markers in the detection of bladder transitional cell carcinoma. However, the sensitivity of each single marker seemed to be unsatisfactory. In the current study, we assessed the sensitivity of the combined assay of these three markers in the detection of human bladder transitional cell carcinoma. METHODS: Voided urine samples of 100 patients with bladder transitional cell carcinoma were obtained and each sample was aliquoted for the various assay. Urinary CYFRA21-1 and VEGF were detected by enzyme-linked immunosorbent assay and telomerase detected by the telomeric repeat amplification protocol. The sensitivity of combined assay was compared to that of each single marker and urinary cytology, respectively. RESULTS: In the 100 patients, the sensitivity was 74% for urinary CYFRA21-1, 71% for telomerase, 69% for VEGF, and 38% for cytology. CYFRA21-1, telomerase and VEGF proved significantly more sensitive than cytology, respectively (P = 0.000). The sensitivity of the combined assay in the current study was 94% and it was significantly higher than that of cytology, urinary telomerase, CYFRA21-1 or VEGF (P = 0.000). In 50 patients with hematuria but without bladder cancer, the overall specificity of the assays was 78% for CYFRA21-1, 84% for telomerase, 88% for VEGF, and 92% for cytology. CONCLUSIONS: Combined assay of the markers which show different characteristics of the tumor behaviors seemed to be of interest in the detection of bladder transitional cell carcinoma.     

Urothelkarzinom der Harnblase

Background

Transurethral resection of transitional cell carcinoma of the bladder provides a definitive surgical treatment and supplies tissue for histological evaluation. Superficial low-grade carcinomas with a small risk of progression are treated properly with fulguration alone. To justify fulguration as a definitive treatment of papillary bladder tumours, one must be able to safely distinguish low-grade, noninvasive tumours from those that are high grade and potentially invasive.

Material and methods

A total of 160 patients with a transitional cell carcinoma at cystoscopy underwent transurethral resection of the tumour. The macroscopic appearance of the tumour, the aspect with bimanual palpation and the perioperative urine cytology were compared with the histological report.

Results

In our study we were able to safely distinguish low-grade tumours from high-grade tumours. All noninvasive tumours could be identified visually as such.

Conclusion

Urologists skilled in the evaluation of urine cytology can distinguish low-grade noninvasive tumours of the bladder from high-grade and potentially invasive tumours by means of appearance at cystoscopy and perioperative urine cytology.     

CAN URINE BOUND DIAGNOSTIC TESTS REPLACE CYSTOSCOPY IN THE MANAGEMENT OF BLADDER CANCER?

Purpose

We compare the diagnostic value of NMP22 [dagger] and BTA stat [double dagger] testing, and QUANTICYT [section] computer assisted dual parameter image analysis to cytology and cystoscopy in patients who had symptoms suggestive of transitional cell cancer or were being followed after treatment for that disease.[dagger] Matritech, Inc., Newton, Massachusetts.[double dagger] Bard Diagnostics, Redmond, Washington.[section] Gentian Scientific Software, Niawier, The Netherlands.

Materials and Methods

We prospectively evaluated voided urine and/or barbotage specimens from 291 patients a mean of 65.2 years old. All voided urine samples were evaluated by quick staining and standard cytology, the BTA stat 1-step qualitative assay (which detects a bladder tumor associated antigen) and the NMP22 test (which detects a nuclear mitotic apparatus protein). In addition, barbotage specimens were evaluated by QUANTICYT computer assisted dual parameter image analysis. All patients underwent subsequent cystoscopy and biopsy evaluation of any suspicious lesion. Sensitivity, specificity, and the predictive value of positive and negative results were determined in correlation with endoscopic and histological findings.

Results

In 91 patients with histologically proved transitional cell carcinoma overall sensitivity was 48, 57, 58, 59 and 59% for the NMP22 test, the BTA stat test, rapid staining cytology of barbotage samples, rapid staining cytology of voided urine specimens and image analysis, respectively. For histological grades 1 to 3 underlying transitional cell carcinoma sensitivity was 17, 61 and 90% for urinary cytology, 48, 58 and 63% for the BTA stat test, and 52, 45 and 50% for the NMP22 test, respectively. Specificity was 100% for cytology, 93% for image analysis, 70% for the NMP22 test and 68% for the BTA stat test.

Conclusions

Immunological markers are superior to cytological evaluation and image analysis for detecting low grade transitional cell carcinoma but they have low specificity and sensitivity in grade 3 transitional cell carcinoma. Urine bound diagnostic tools cannot replace cystoscopy.     

Assessment of fibrin-fibrinogen degradation products (Accu-Dx) test in bladder cancer patients

OBJECTIVES: Measurement of urine fibrin-fibrinogen degradation products has been reported to be a useful marker for bladder malignancies. This is a simple, noninvasive and rapid method in the diagnosis and follow-up of bladder cancer. We performed a prospective study to evaluate the reliability of the Accu-Dx test which detects urinary fibrin and fibrinogen products associated with bladder cancer. MATERIAL AND METHODS: 97 patients were included in this study. 55 patients with bladder cancer were under surveillance, and 35 were evaluated as primary cases. The Accu-Dx test was performed in 7 additional patients presenting with hematuria due to benign disorders. Urine cytology specimens were collected in all, whereas bladder pathology specimens were obtained in 93. The Accu-Dx test was evaluated with regard to the results of urine cytology and pathological assessment, which constituted the gold standard. RESULTS: According to pathology, 69 patients had carcinoma of the bladder. In 48 (69.6%), the Accu-Dx test was positive whereas urine cytology was positive in only 31 (44.9%; p<0.001). Specificity rates were 67.9 and 96.4%, respectively. With higher stages and higher tumor grades, the Accu-Dx test yielded higher positive rates (50% in Ta versus 100% in T2 or higher and 42.9% in G1 versus 94.1% in G3). On the other hand, the test was positive in 6 patients with cystitis of various etiologies. The overall accuracy rate for Accu-Dx was 69%. CONCLUSIONS: The Accu-Dx test is a simple, rapid, reproducible and more importantly a noninvasive method in the detection of bladder malignancies. But it seems inadequate to replace conventional cystoscopy plus pathologic assessment due to its relatively low accuracy and specificity rates. It may be helpful in selecting patients who should be evaluated with rigid endoscopes together with bladder biopsies.