Urinzytologie beim Harnblasenkarzinom

ImmunoCyt is a new immunocytologic fluorescence test promising a higher diagnostic sensitivity, esp. for TaG1 carcinomas. The aim of the study was to evaluate the sensitivity of the test in diagnosis of bladder cancer as compared to both urinary cytology and histopathology. A total of 121 spontaneous urine samples of 92 patients (age range 28 to 86, mean 62.5 years) was examined. 41 of the samples were of patients suspicious of transitional cell carcinoma, 46 of patients in whom symptoms were suggestive of tumor recurrence, and 34 of patients who were part of a follow-up protocol. Cystoscopy was performed in all patients. The ImmunoCyt-test was carried out according to the manufacturers protocol using 3 fluorescent monoclonal antibodies. A total of 113 specimens could be evaluated. In 87 cystoscopy and/or histology was negative (control group). There was histologic evidence of 7 pTaG1, 4 pTaG2, 8 pT1G2/G3, and 7 pT2G2/G3 bladder cancers. As for ImmunoCyt and cytology specificity was 83.9% and 91.9%, resp. The combined specificity was 81.6%. Sensitivity amounted to 38.5% and 34.6%, resp., the combined sensitivity to 53.8%. Sensitivity for TaG1 carcinomas was 14.3% each, for TaG2 carcinomas 25% and 50%, for T1G2/G3 carcinomas 37.5% each, and for T2G2/G3 carcinomas 71.4% and 42.9%, resp. In our study the ImmunoCyt test did not show the expected increase in the detection of TaG1 bladder cancers. Because of false-positive results the test should only be used in combination with urinary cytology which reveals a higher specificity. In conclusion the ImmunoCyt test can not replace cystoscopy (with biopsy) in diagnosis and monitoring of bladder cancer.     

几种新瘤标对膀胱癌早期诊断价值的比较

目的：比较几种新瘤标对膀胱移行细胞癌早期诊断的价值。方法：对322例肉眼或镜检血尿、膀胱刺激症状或发现膀胱占位者，在作膀胱镜检查前行尿液中细胞角蛋白20(CK20)、核基质蛋白(NMP22)、ImmunoCyt、膀胱肿瘤抗原(BTA stat)检测和常规尿细胞学检查，比较它们的敏感性和特异性。结果：经膀胱镜和病理检查诊断膀胱移行细胞癌149例，其中浅表性肿瘤110例，浸润性39例；G181例，G246例．G322例。CK20、NMP22、ImmunoCyt、BTA stat、尿细胞学和膀胱镜检的敏感性分别为90．6％、85．2％、82．6％、65．8％、30．2％和94．6％，特异性分别为83．6％、84．0％、78．1％、64％、100％和100％。结论：新瘤标CK20、NMP22、ImmunoCyt具有较高的敏感性，与BTA stat和尿细胞学比较，差异有统计学意义，可用于膀胱肿瘤的早期诊断。     

ImmunoCyt在膀胱移行细胞癌早期诊断中的应用

目的评价ImmunoCyt检测在膀胱癌早期诊断和随访中的作用. 方法膀胱癌患者86例,其中38例为膀胱肿瘤行经尿道膀胱肿瘤电切术后至少3个月的随访患者,48例有肉眼(镜下)血尿,分别进行标准尿脱落细胞学和ImmunoCyt检测.86例均行膀胱镜检查,对可疑组织进行活检. 结果膀胱镜检和病理证实28例为膀胱移行细胞癌.ImmunoCyt敏感性为82%,与尿脱落细胞学检查(39%)相比差异有显著性意义(P<0.05).两种检查方法相结合的敏感性为89%.ImmunoCyt和细胞学的特异性分别为78%和94%. 结论 ImmunoCyt较细胞学对膀胱肿瘤更敏感,二者联合使用可在保持高特异性的前提下提高诊断的敏感性,早期检测膀胱肿瘤.     

Comparison of the ImmunoCyt test and urinary cytology with other urine tests in the detection and surveillance of bladder cancer

Despite several new urine markers urinary cytology remains the gold standard for the non-invasive detection of bladder carcinoma. The use of monoclonal antibodies against tumor associated antigens offers a promising approach to improve urinary cytology. The aim of this study was to compare fluorescence immunocytology (ImmunoCyt/Ucyt+ test), alone and in combination with the conventional cytology, with other urine markers. Urine samples from 126 patients undergoing cystoscopy were included in the study. Among them, 42 patients had urothelial carcinoma, two dysplasia, two other malignancies, and 78 had no evidence of bladder cancer. Urine samples were taken before any manipulation. We used the ImmunoCyt test and Papanicolaou staining for conventional cytology. The ImmunoCyt slides were examined under a fluorescence microscope. Evaluations of the tests were blinded to clinical and pathological data and were carried out by three independent observers. The results of cytology and ImmunoCyt were compared with the BTAstat, NMP22, Lewis X, 486p3/12, and Urovision tests. The sensitivity for the ImmunoCyt test was 78.3% and for conventional cytology 84.6%. The combination of ImmunoCyt and cytology showed a sensitivity of 89.1%. The specificity was 73.8% for the ImmunoCyt alone, 80.0% for the cytology, and 72.5% for the combination of ImmunoCyt and cytology. Sensitivities for the other tests were 68.8% for (FISH), 66.6% (BTA-Stat), 68.8% (486p3/12), 95.5% (Lewis X), and 71.1% for (NMP22). Specificity was 89.1% for (FISH), 78.2% (BTA-Stat), 76.4% (486p3/12), 32.8% (Lewis X), and 65.5% for (NMP22). Urinary cytology can be improved by immunostaining with monoclonal antibodies against tumor-associated antibodies. The combination of ImmunoCyt with conventional cytology offers a superior sensitivity to other commercial tests. The ImmunoCyt test provides a useful supplement to urinary cytology in the diagnosis of bladder cancer.M.I. Toma, M.G. Friedrich contributed equally to this study     

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.     

尿端粒酶、NMP22和ImmunoCyt联合检测在膀胱癌诊断中的应用

目的评价尿端粒酶、核基质蛋白22（NMP22）和ImmunoCyt测定在膀胱癌（BTCC）早期诊断中的应用价值,寻找早期诊断膀胱癌的有效方法。方法选择60例经病理诊断明确为早期膀胱移行细胞癌和60例非膀胱肿瘤患者,分别进行尿端粒酶、ImmunoCyt、NMP22和标准尿脱落细胞学检测。结果尿端粒酶、NMP22和ImmunoCyt和尿脱落细胞学的敏感度分别为58.3%、60.0%、61.6%、26.6%;准确度分别为75.8%,78.3%,78.3%和63.3%;特异度分别为93.3%,96.6%,95.0%和100%。三者联合检测与尿端粒酶、NMP22和ImmunoCyt单独检测相比,敏感度（分别为χ2=6.53,P〈0.05;χ2=5.17,P〈0.05;χ2=4.54,P〈0.05）和准确度（分别为χ2=4.01,P〈0.05,χ2=4.38,P〈0.05,χ2=4.91,P〈0.05）都有所提高;尿端粒酶、NMP22和ImmunoCyt联合检测的敏感度（χ2=28.06,P〈0.01）和准确度（χ2=16.2,P〈0.01）均高于尿脱落细胞学,差异有统计学意义。结论尿端粒酶、NMP22和ImmunoCyt是早期诊断膀胱移行细胞癌的一种高特异性指标,三者联合检测能提高膀胱癌的早期诊断率。     

ImmunoCyt a useful method in the follow-up protocol for patients with urinary bladder carcinoma.

OBJECTIVE: To evaluate the ImmunoCyt test--a urine-bound test for the detection of malignant transitional cells. PATIENTS AND METHODS: ImmunoCyt was compared with the standard investigation at our hospital for bladder cancer--cystoscopy, cytological examination of bladder wash material and, if necessary, a histological examination. A voided urine sample was collected before cystoscopy. We investigated 121 patients; seven specimens could not be evaluated. RESULTS: Thirty-one of the 114 patients had a histologically proven urinary bladder carcinoma. All 31 cases were positive in the ImmunoCyt test. Twenty-six of the 83 negative cases were ImmunoCyt positive. The sensitivity was 100% and the specificity was 68.7%. CONCLUSION: ImmunoCyt is easily applicable in a small laboratory and has high sensitivity and acceptable specificity.     

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.     

Cyclophosphamide-induced bladder cancer in a patient with Wegener granuromatosis

Cyclophosphamide (CPM) has been considered to be a factor of bladder carcinogen. A 60-years old woman had been received a total dose of 370 g of CPM for the treatment of Wegener's granulomatosis since August, 1977. She was consulted to our department with chief complaint of macrohematuria in August, 1986. Hemorrhage cystitis was diagnosed and cystoscopy and urine cytology were performed as follow-up schedule in every year. In 1996, urine cytology showed class IV and cystoscopy revealed multiple nonpapillary tumors. Abdominal computerized tomography demonstrated a low density mass on the posterior wall of the bladder. A transurethral cold cup biopsy showed G3 transitional cell carcinoma (TCC). Radical cystectomy and tubeless cutaneous ureterostomy was performed on December 6, 1996 and histopathological diagnosis was TCC, G 3, pT3 bNXM0. She died of liver failure due to metastatic bladder cancer after seven months postoperatively.     

¿Cuál es el valor de la biopsia aleatoria en el seguimiento del carcinoma uroterial superficial de vejiga?

IntroductionTransitional cell carcinoma of the bladder represents a disease of entire urothelial tract. The follow up is very important to detect any lesion that might represent a progression or a local recurrence. Some authors recommend randomized biopsies as a routine workup, others recommend cystoscopies and urinary cytology as the main part of superficial bladder cancer follow up.Patients and MethodsForty nine patients with superficial bladder cancer were followed up during a ten-year period. Randomized biopsies and urinary cytology were harvested according to the international cancer protocol on bladder cancer.Results15 (1%) out of 1.489 randomized biopsies found to be positive to transitional cell carcinoma. Four out (10.5%) of 35 biopsies targeted to suspicious areas were positive to transitional cell carcinoma. 50 (17.4%) out of 288 cystoscopies with urinary cytology found to be positive to transitional cell carcinoma. Sensitivity and Specificity of biopsies (including randomized and targeted) were 31% and 85.2% respectively. Sensitivity and specificity of cystoscopies with urinary cytology were 48% and 86.5% respectively.ConclusionRandomized biopsies did not show to detect more local recurrence or progression when compared to the urinary cytology. Cystoscopies with urinary cytology have good sensitivity and specificity for detection of tumor recurrence during follow up of transitional cell carcinoma.     

Can transabdominal ultrasonography of the bladder replace cystoscopy in the followup of superficial bladder tumors?

Transabdominal ultrasonography of the bladder was performed on 100 patients 3 to 9 months after endoscopic resection of stage Pa or Pl transitional cell carcinoma of the bladder. In 81 patients there was a close correlation between the results of suprapubic ultrasonography and cystoscopy. In 19 patients the ultrasonography results were incorrect: 4 had false positive and 15 had false negative findings. Specificity for the diagnosis of recurrence was 90 per cent and sensitivity was 74 per cent. Transabdominal ultrasonography combined with cytology studies should be part of the diagnostic approach for recurrent superficial bladder tumors. When performed before cystoscopy these studies should reduce greatly without eliminating the frequency of this investigation.     

Urinary cytology for the detection of urothelial carcinoma of the bladder—a flawed adjunct to cystoscopy?

ObjectivesTo test the sensitivity of urinary cytology at a tertiary academic institution and to assess the impact of pathologist' experience on detection of urothelial carcinoma of the bladder (UCB).Materials and methodsBetween April 1999 and September 2008, 8,574 cytology specimens were evaluated. There were 882 consecutive patients (612 males, 270 females) who underwent bladder biopsy or transurethral resection of bladder tumor for UCB. Sensitivity rates of prior urinary cytology were determined. We tested the influence of experience of pathologist on sensitivity.ResultsUrinary cytology detected 237 out of 503 UCB (overall sensitivity 47.1%). Cytology after bladder washing resulted in higher sensitivity than in voided urine (50.4% vs. 36.2%; P = 0.008). Sensitivity rates significantly increased by UCB stage; 30.6% in pTa (n = 245), 60.5% in patients with any form of CIS (n = 119), 62.9% in pT1 (n = 89), and 69.6% in ≥pT2 (n = 46; P < 0.001). Similarly, higher sensitivity was observed with increasing grade, ranging from 16.7% in low (n = 108) to 62.2% in high grade tumors (n = 283; P < 0.001). No statistically significant difference between more and less experienced investigators was observed.ConclusionsSensitivity rates of urinary cytology at our institution are not superior to those reported in the literature. Cytology missed many high grade cancers, pointing to inherent methodological limitations of urinary cytology. A higher experience level of the pathologist was not significantly associated with higher sensitivity rates. Urinary cytology represents a flawed adjunct to cystoscopy with limited potential of improvement even in the hands of experienced pathologists.     

膀胱肿瘤抗原联合尿脱落细胞学检查在膀胱肿瘤诊断中的价值

目的 探讨膀胱肿瘤抗原(BTA)联合尿脱落细胞学检查在膀胱肿瘤诊断中的应用价值.方法 收集2018年9月至2019年9月本院经膀胱镜检查或手术后病检确诊的膀胱肿瘤(37例)及非膀胱肿瘤(32例)患者的尿液标本,分别行尿脱落细胞学及BTA检测并进行相关分析.结果 ①尿BTA诊断前列腺肿瘤的灵敏度(81.08％)高于尿脱落...     

Evaluation of the clinical value of urinary NMP22 as a marker in the screening and surveillance of transitional cell carcinoma of the urinary bladder.

PURPOSE: To prospectively evaluate the clinical role of urinary NMP22 as a marker for transitional cell carcinoma of the urinary bladder in screening and surveillance settings. PATIENTS AND METHODS: Single voided specimens were obtained from 211 consecutive patients who presented for flexible cystoscopy. Of these, 96 patients presented with haematuria or irritative symptoms (screening), the remaining 115 were patients with known transitional cell carcinoma on follow-up (surveillance). The urine sample was used for urine microscopy, cytology and for measuring NMP22 levels. RESULTS: Bladder tumours were found in 16 of 96 (16.6%) patients in the screening group and 17 of 115 (15.6%) patients on surveillance. The NMP22 levels were significantly lower in patients with lower stage (Ta vs. T1-3), low grade (G1, G2 vs. G3, CIS) and papillary morphology. The optimum threshold for NMP22 obtained from the ROC curve was 4.75 U/ml, providing a sensitivity, specificity, positive predictive value and negative predictive value of 42.4, 85, 38.5 and 88.6%, respectively. Sensitivity and specificity were better in patients being screened than in those on surveillance. In both groups, urinary NMP22 had similar diagnostic characteristics as urinary cytology. CONCLUSIONS: Urinary NMP22 levels are significantly higher in patients with bladder tumour than in those negative for tumours, and test predictability improves with increasing stage and grade. The overall sensitivity for urinary NMP22 is similar to, but not superior to urine cytology. Our study suggests that the clinical role of urinary NMP22 as a diagnostic marker can be at best supportive only.     

Superficial transitional cell carcinoma of the ureteral orifice: Higher risk of developing subsequent upper urinary tract tumors

AIM: Reports specifically addressing transitional cell carcinoma (TCC) of the ureteral orifice are scarce. This paper presents our experiences of such tumors, including the characteristics of the disease and the incidence of subsequent upper urinary tract recurrence. METHODS: This study included 572 new cases of TCC of the urinary bladder diagnosed in our institute during a period of 5 years. Thirty-one (5.4%) patients had superficial tumors involving ureteral orifices. All 31 patients underwent transurethral resection of the bladder tumors, including the involved ureteral orifices. After the surgery, patients received regular follow up with cystourethroscopy, urine cytology and periodic intravenous pyelography (IVP). Ureterorenoscopy was performed in cases of suspicious IVP or urine cytology findings. RESULTS: Thirty-one patients with superficial tumors involving the ureteral orifice were followed up for 5-8 years or until death. The pathological stage was Ta in 16 cases and T1 in 15 cases. Bladder tumor recurrence was noted in three (18.8%) of the pTa patients and in seven (46.7%) of the pT1 patients. Subsequent upper urinary tract tumors developed in four (12.9%) patients between 33 and 67 months (mean: 33.5) after the first transurethral resection. All four cases of upper tract recurrence had pT1 primary bladder tumor, which recurred for 1-3 times (mean 1.8) before upper tract recurrence. None of these patients had ureteral stenting after bladder tumor resection. Three of four patients with upper tract recurrence had single lower ureteral tumor, while the remaining one patient had multiple tumors. Patients with subsequent upper urinary tract tumors underwent nephroureterectomy and bladder cuff excision. One died of the disease; the other three cases were free of the disease after the therapy. CONCLUSIONS: Patients with primary superficial bladder transitional cell carcinoma involving the ureteral orifice have a higher risk of developing subsequent upper urinary tract tumors, particularly for pT1 primary bladder tumors. Frequent and close follow up is recommended.     

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.     

Urinary CYFRA 21.1 is not a useful marker for the detection of recurrences in the follow-up of superficial bladder cancer

OBJECTIVES: The objective of this prospective study is to establish an appropriate cutoff value of urinary CYFRA 21.1 assay and to assess its utility combined with voided cytology and/or haemoglobin dipstick in the follow-up of patients with superficial bladder cancer. METHODS: From December 2000 to November 2003, 446 patients in follow-up for superficial bladder cancer (Ta-T1) after transurethral resection of the bladder (TURB) were included in a prospective study. Voided urine specimens were collected 7-14 d before cystoscopy and/or TURB for CYFRA 21.1 (one sample), haemoglobin dipstick (one sample), and cytology (three samples). All samples were processed for CYFRA 21.1 and haemoglobin dipstick according to manufacturer instructions. A control group (n=185) was obtained from patients in follow-up after transurethral resection of superficial disease (without recurrences within the following 6 mo). There were 125 recurrent transitional tumours detected by cystoscopy (34 TaG1; 53 TaG2/T1G1-2; 23 Ta-1G3/Tis, and 15 T2-4). Receiver operator characteristic (ROC) curves were constructed and cutoff values were chosen. Sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and their 95% confidence intervals were calculated. RESULTS: ROC curve analysis based on the previously reported cutoff value of 4ng/ml for CYFRA 21.1 demonstrated a sensitivity and specificity of 43% and 68%, respectively. At a cutoff value of 1.5ng/ml, sensitivity was 73.8% with a low specificity (41%). Further lowering of the cutoff point below 1.5ng/ml did not demonstrate a significant increase in sensitivity. Therefore, this value was chosen as the most sensitive CYFRA 21.1 cutoff point during the rest of the study. Specificity increased when all the patients treated with pelvic radiotherapy or with UTI, urethral catheterisation, and intravesical instillations within 3 previous months were not included in our analysis. CYFRA 21.1 plus cytology and the combination of CYFRA 21.1, cytology, and haemoglobin dipstick demonstrated the highest overall sensitivities, and detected 91.3% of Ta-1G3 tumours and 93.3% of T2-4 tumours. However, there were one muscle-invasive tumour, two T1G3/Tis, three T1G2, and nine T1G1 neoplasms with negative combination of cytology and CYFRA 21.1 (1,5ng/ml). All these tumours were smaller than 2cm in size; most were single tumours. Nevertheless, there were 16 tumours larger than 0.5cm (0.5-2cm), and multiple neoplasms were endoscopically detected in 14 patients. Similar results were obtained through the combination of CYFRA 21.1 (cutoff: 1.5ng/ml), cytology, and haemoglobin dipstick. CONCLUSIONS: In our experience the low sensitivity of urinary CYFRA 21.1, even using lower cutoff values and/or a combination with cytology and/or haemoglobin dipstick, makes its application not very useful as a surveillance tool for superficial bladder carcinoma.     

The UroVysion fluorescence in situ hybridization assay is an effective tool for monitoring recurrence of bladder cancer

The newly developed UroVysion fluorescence in situ hybridization (FISH) probe was applied to urine specimens from 19 patients being monitored for recurrence of bladder cancer. The results for the multi-target DNA FISH assay were compared with independent analyses of urine cytology and flexible cystoscopy. Patients with tumors identified through the cystoscopy exam were biopsied and/or underwent surgery. In 12 patients with normal cytoscopy, cytology and FISH were also normal. Therefore, the specificity of these two tests was 100%. In 7 patients, a tumor was diagnosed by cystoscopy, and 3 of them had abnormal urine cytology while 6 of them had an abnormal result in the FISH assay. Accordingly, the sensitivity was 43% for the cytology and 87% for the FISH test. Interestingly, a pT1G3 tumor in a bladder diverticulum was not detected by cytology or the FISH test. These results agreed with a large series previously published using similar FISH probes and support the proposal for a multicenter trial to confirm the usefulness of the UroVysion probe as a screening tool to select patients for cystoscopy.     

Immunocyt: a new tool for detecting transitional cell cancer of the urinary tract

PURPOSE: The limitations of cytology and the invasiveness of cystoscopy for detecting bladder cancer generate increasing interest in noninvasive, urine bound diagnostic tools. We assessed the diagnostic value of the newly developed immunocytochemical test, Immunocyt, which detects cellular markers specific for transitional cell cancer in the voided urine of patients with bladder cancer. MATERIALS AND METHODS: Participating in our prospective study were 264 consecutive patients with a mean age of 65.9 years, including 114 in whom symptoms were suggestive of bladder cancer and 150 who were being followed after complete transurethral resection of superficial transitional cell carcinoma. Voided urine specimens were evaluated by standard cytology and the Immunocyt test, which traces the monoclonal antibodies M344, LDQ10 and 19A211 against transitional cell carcinoma in exfoliated urothelial cells. In all cases cystoscopy was subsequently performed and any suspicious lesion was evaluated by biopsy. RESULTS: Histologically proved transitional cell carcinoma was found in 79 patients. Immunocyt with cytology had 89.9% sensitivity overall (84, 88 and 96.5% in grades 1 to 3 disease, respectively). A total of 34 (43%), 3 (3.8%) and 34 (43%) cases were positive on Immunocyt only, cytology only and both evaluations, respectively. In 8 cases (10.1%) both tests were negative. Overall Immunocyt only was 86.1% sensitive (84, 84 and 89.6% in grades 1 to 3 disease, respectively) and 79.4% specific. Overall cytology only was 46.8% sensitive (4, 52 and 79.3% in grades 1 to 3 disease, respectively) and 98.2% specific. CONCLUSIONS: Immunocyt is a noninvasive, highly sensitive test for detecting transitional cell carcinoma of all grades and stages. When combined with conventional urinary cytology, it may replace cystoscopy in select patients, especially in followup protocols of low grade transitional cell carcinoma.     

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.