膀胱癌患者尿NMP22与尿脱落细胞学检测的临床价值

目的研究核基质蛋白22（NMP22）与尿脱落细胞学在膀胱癌早期诊断、监测复发及判断预后中的临床价值。方法收集96份尿液标本,其中包括45例膀胱癌术前患者（经术后病理证实）,20例膀胱癌术后复测患者及3l例良性泌尿系疾病患者。均通过酶联免疫吸附法（ELISA）检测NMP22值,将其结果与尿脱落细胞学通过,检验的形式进行对比。结果45例膀胱癌术前患者NMP22的含量为9．3—112．5U／mL,中位数为48．7U／mL;31例良性泌尿系患者NMP22的含量为2．1～14．7U／mL,中位数为7．9U／mL;20例膀胱癌术后患者NMP22的含量为4．3～18．7U／mL,中位数为8．9U／mL,膀胱癌术前患者NMP22中位数明显高于良性泌尿系患者NMP22中位数,差异有显著统计学意义（P〈0．05）。以NMP22≥10U／mL为临界值,NMP22诊断膀胱癌的敏感性为82．2％,特异性为70．9％;尿细胞学的敏感性为31．1％。特异性为100％。20例膀胱癌术后患者经膀胱镜证实复发有9例。结论NMP22可以作为膀胱癌的早期筛查和术后随访的有效标志物。     

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.     

Patients with clinically unconfirmed positive urinary cytology --retrospective analysis of clinical courses

We retrospectively analyzed the clinical courses of 7 patients with clinically unconfirmed positive urine cytology characterized by persistent positive urine cytology but without any evidence of tumor by endoscopy or image diagnosis during the time from January 1999 to June 2004. A past history of urothelial cancer was found in 5 patients. In 2 of these 5 patients, transurethral resection of the bladder mucosa and ureteroscopy done as the initial examination identified bladder cancer and ureteral cancer, respectively. Urothelial cancer was found in the remaining 3 patients by subsequent endoscopy, image diagnosis and surgical resection that were done in the follow-up period of 8 months. Two patients who did not have a history of urothelial cancer were diagnosed as having bladder cancer and ureteral cancer in the initial or subsequent examination. Patients with clinically unconfirmed positive urine cytology should be carefully followed up with endoscopy and image diagnosis since the subsequent examinations tend to identify urothelial cancer in the upper urinary tract or bladder.     

Sensitivity of human complement factor H related protein (BTA stat) test and voided urine cytology in the diagnosis of bladder cancer

PURPOSE: We compared the sensitivity of the BTA statdagger test, a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine, to that of voided urine cytology in patients with primary bladder cancer. We also assessed the effect of tumor size, number, histological grade and stage on test sensitivity. MATERIALS AND METHODS: We evaluated 151 patients with newly diagnosed bladder cancer in a prospective multicenter study. A voided urine sample obtained before transurethral bladder tumor resection was divided for culture, cytology and BTA stat testing. RESULTS: Overall sensitivity of the BTA stat test and urine cytology for detecting primary bladder cancer was 81.5% and 30.3%, respectively (p <0.0001). The sensitivity of each test increased as tumor size, number, histological grade and stage increased. CONCLUSIONS: Sensitivity of the BTA stat test was superior to that of voided urine cytology in all tumor categories. This noninvasive, easy to perform, point of care test may have the potential to replace cytology for diagnosing bladder cancer.     

The efficacy of urinary cytology in the detection of recurrent bladder tumours

In a prospective study, 71 patients with superficial transitional cell carcinoma of the bladder were given topical immunotherapy with bacillus Calmette-Guerin after transurethral resection and the impact of cystoscopy and bladder wash-out cytology in assessment of recurrent tumours was investigated. Sixteen recurrences were noted histopathologically during the follow-up and 15 of them were also diagnosed properly by wash-out cytology (sensitivity 93.8%). During the follow-up, 10 patients had positive cytology results without evidence of recurrent tumour and 6 of them had recurred cystoscopically in 3 months' time. However, the remaining 4 patients were still tumour-free cystoscopically after a follow-up of 6 months (specificity 92.7%, positive predictive value 78.9%). Although, some false-positive results may be obtained by urine cytology after topical immunotherapy, urine cytology seems to be a reasonable alternative to more invasive and expensive methods during the follow-up of bladder tumours.     

Urinary cytology studied during 10 days after transurethral resection of bladder tumour and its relation to tumour recurrence

Whether or not recurrence is related to the results of urinary cytology examined within 10 days after transurethral resection of bladder tumour was studied retrospectively in 47 patients with superficial bladder tumour. Of 7 cases with positive cytology during the postoperative 10 day period, 4 cases had a later recurrence of tumour and 2 cases had a residual tumour due to incomplete resection of original tumour. By microscopic chromocystoscopy, in 11 patients concurrent urothelial atypia (carcinoma in situ or dysplasia) was found in the apparently normal mucosa. Nine of the 11 cases had a later recurrence of tumour or a residual tumour. Of in total 15 patients combined with abnormal cytology and concurrent urothelial atypia, 12 (80%) were found with recurrence of tumor cystoscopically 4 approximately 64 months (mean; 20.6 months) after TUR. This recurrence rate was significantly (p less than 0.05) higher than that (42.4%) in patients without positive cytology and concurrent urothelial atypia. These results suggest that positive urinary cytology during 10 days subsequent to TUR and/or association with concurrent urothelial atypia are indicative of later tumour recurrence, incomplete resection of tumour or presence of additional occult tumour foci.     

Various staining procedures in exfoliative urine cytology. Use in routine urology

Exfoliative urinary cytology should be included in the diagnostics and follow up of bladder carcinomas. Staining according to Papanicolaou is time consuming and expensive. Therefore the accuracy of cytology after methylene blue staining, use of prestained slides and Papanicolaou staining was investigated. Urine and bladder washouts were taken from 77 patients with histologically proven bladder tumors, 152 patients after resection of the tumor and 100 patients without tumor of the urinary tract. The results show comparable accuracy of the different staining techniques. Methylene-blue stained and prestained slides cannot be used for documentation; therefore all specimens, which show tumor or are suspicious should also be stained according to Papanicolaou.     

Monitoring endoscopic treatment of superficial bladder carcinoma by postoperative urinary cytology

Transurethral resection was the only modality of treatment in 39 patients with long-standing, recurrent, superficial bladder carcinoma. Postoperative urinary cytology was performed within 3 days of each endoscopy. Tumor recurrence was defined by the presence of a positive biopsy or visible papillary tumors on followup cystoscopic examination. Tumor recurred in 38 patients (97.4 per cent) and 1 patient (2.6 per cent) has remained free of disease 74 months following transient positive postoperative cytology. Among the 38 recurrences 15 (39.5 per cent) were positive, 3 (7.9 per cent) suspicious and 20 (52.6 per cent) negative at the postoperative cytological examination. The interval to recurrence did not differ significantly among the 3 groups. The failure of a negative postoperative cytology study to predict a durable response to treatment by transurethral resection reflects the polychronotopic nature of superficial bladder tumors in this select patient population and suggests the need for adjuvant therapy.     

UroVysion compared with cytology and quantitative cytology in the surveillance of non-muscle-invasive bladder cancer

OBJECTIVES: The multitarget fluorescence in situ hybridization probe set Vysis UroVysion, consisting of probes for chromosomes 3, 7, and 17 and for the 9p21 band, was studied to evaluate its value in the follow-up of patients with bladder cancer. The results were compared with conventional cytology and quantitative cytology (Quanticyt). The aim of this study was to evaluate whether UroVysion is a better adjunct to urethrocystoscopy than cytology and quantitative cytology. METHODS: UroVysion, cytology, and quantitative cytology were performed on 113 voided urinary samples of 105 patients under surveillance for non-muscle-invasive bladder cancer. Before urethrocystoscopy or transurethral resection of the bladder, a voided urinary sample was obtained. Results of all tests were compared to evaluate the value of UroVysion. RESULTS: Sixty-four patients had biopsy-proven urothelial cell carcinoma. Sensitivity and specificity were, respectively, 39.1% and 89.7% for UroVysion, 40.6% and 89.7% for cytology, and 42.1% and 67.9% for quantitative cytology. When the UroVysion test and cytology were combined, sensitivity increased to 53.1%, but specificity decreased to 79.5%. Detection of Ta tumours was equal for cytology and UroVysion (26.7%), detection of T1 and T2-T4 samples by UroVysion was 60% and 50%, respectively. Detection of grade 1, 2, and 3 tumours by UroVysion was 21.4%, 36.8%, and 66.7%, respectively. In four cases the UroVysion test was positive, but no abnormalities were seen at cystoscopy. CONCLUSIONS: Our data suggest that the use of UroVysion provides no improvement over cytology or quantitative cytology in the diagnosis of recurrent non-muscle-invasive bladder tumours.     

TNM-oriented therapy planning in bladder cancer

The standard diagnostic procedures for bladder carcinoma include transurethral resection, bimanual palpation of the bladder under general anaesthesia, ultrasound examination and CT scan of the abdominal and pelvic regions. An IVP is additionally carried out for the detection of concomitant upper urinary tract tumours. Preoperative urinary cytology is also performed, as in 10% of all patients the degree of malignancy of bladder cancer according to the TNM system is revealed more exactly by cytology than by histology. New computerized examination techniques have been designed in attempts to improve the accuracy of the diagnostic process. Therapeutic modalities according to the classification of bladder carcinoma in the TNM system have to be based on the different efficacies of the diagnostic procedure: In superficial low-grade tumours the diagnostic efficacy is quite high, so that transurethral resection remains the treatment of choice. Superficial high-grade tumours are attended by reduced 5-year survival rates, and patients with such tumours must therefore be regarded as a high-risk group. In muscle-invasive bladder carcinoma reduced diagnostic efficacy and unsatisfactory treatment results are seen, so that in this condition cystectomy at an early stage is indicated.     

Comparison of the nuclear matrix protein 22 with voided urine cytology in the diagnosis of transitional cell carcinoma of the bladder

Several urinary markers for transitional cell carcinoma have been investigated, including urine cytology, bladder tumor antigen, autocrine motility factor receptor and fibrin degradation products. Unfortunately, they have poor overall sensitivity. The United States Food and Drug Administration have recently approved nuclear matrix protein (NMP 22) for the detection of occult or rapidly recurring disease after transurethral resection of bladder tumor. The objective of the current study was to assess the sensitivity of NMP 22 for the detection of bladder carcinoma, as well as to correlate the NMP 22 values with multiplicity of tumor, tumor size, configuration, stage and grade respectively. A total of 78 patients (38 with bladder cancer) provided a urine sample which was divided into appropriate aliquots for each of urine cytology and NMP 22. Comparative results demonstrate a clear superiority of NMP 22 in bladder cancer detection (52.6% vs 31.6% sensitivity), while specificity was in favor of urine cytology (100% vs 82.5%). For superficial tumors, sensitivity was 78.5% for NMP 22 and 41.6% for cytology and for invasive cancers, sensitivity was 90% for NMP 22 and 60% for cytology. Urinary NMP 22 levels were significantly correlated with tumor grade and were significantly higher in large tumors than small tumors. NMP 22 test results showed sufficient sensitivity in comparison with urine cytology for the detection of transitional cell carcinoma. However, we do not think that it is a useful tool as a substitute for endoscopic examination for the detection and surveillance in bladder cancer.     

Significance of atypical urinary cytology in the evaluation of patients with end‐stage renal disease for kidney transplantation – a retrospective study

To determine what percentage of renal transplant candidates have atypical urinary cytology, what proportion have urothelial carcinoma and whether cystoscopy is necessary with atypical cytology. All end‐stage renal disease (ESRD) patients (703) presenting for renal transplantation at our institution were retrospectively reviewed. Individuals producing sufficient urine were screened with urine cytology and those with atypical cytology or risk factors for bladder cancer underwent cystoscopy. Four hundred and thirty patients had available urinary cytology and, of these, 151 (35%) had atypical cytology. Of patients with atypical cytology, three were identified to have urothelial carcinoma. However, three additional patients with urothelial carcinoma did not present with atypical cytology. In total, 6 of 703 (0.85%) patients had bladder cancer. All were treated with transurethral resection and eventually underwent renal transplant. One patient has had disease progression post‐transplant to distant metastases. This is the largest study to date evaluating the incidence of urothelial carcinoma in ESRD patients presenting for transplant workup. We found the incidence of bladder cancer to be higher than in the general Canadian population, however, most lesions were low grade. We found atypical cytology in transplant candidates to be a poor predictor for these low‐grade lesions and do not recommend routine cystoscopy for atypical cytology.     

Bladder cancer

Urothelial carcinoma of the bladder is the most common malignancy affecting the urinary tract. This review examines the current standards in the diagnosis and management of this disease. Cystoscopy and urine cytology remain important tools in the diagnosis and follow-up of bladder cancer. Alternatives include photodynamic diagnosis, narrow band imaging and professional image enhancement which may improve detection of tumours. En-bloc resection using either laser or electrocautery shows promise in improving the quality of transurethral resection. For patients with muscle-invasive bladder cancer, robot-assisted radical cystectomy has been shown to be oncologically equivalent to open radical cystectomy; however, cost effectiveness remains to be determined. The mainstay of bladder preservation treatment in muscle-invasive cancer is trimodal therapy utilizing transurethral resection and chemoradiotherapy with equivalent outcomes to radical cystectomy in selected patients. Management of locally advanced and metastatic disease has rapidly advanced through the use of systemic immunotherapy agents targeting the PD-L1/PD-1 axis.     

Comparative study between cystoscopy, urinary cytology, NMP-22 and a new method, bladder chek, in the follow-up of superficial bladder cell carcinoma

Objective: The goal of this work tries to evaluate the utility of the qualitative determination of NMP-22 in the evaluation of the superficial bladder carcinoma in asymptomatic patients, comparing it with its quantitative determination, the cytology and the cystoscopyMaterial and methodsA simple of urine just voided was taken in 88 asymptomatic patient follow-up for superficial bladder cell carcinoma. This dose was distributed in 3 parts, for performed cytology, for determination of NMP-22, and 4 drops of the third part are added to device bladder chek. Later, we performered cystoscopy and transurethral resection in patients with a suspicion of bladder cancerResults26 patients had tumor relapse and 62 patients were free of disease. The sensitivity for the bladder chek was of 28%, 34.62% for nmp-22, 34.62% for cytology and 100% for cystoscopy. The specificity was of 93.55%, 80.33%, 87.10% and 87.10% respectively. The sensitivity by degree was 25 in g1, 28.57 in g2 and 50 in g3 for Bladder chek; 29.41, 42.86and 50 for NMP-22; 23.53, 71.43 and 0 for cytology. The sensitivity by stages was 27.7 in Ta-1 and 50 in t2 for Bladder chek; 34.78 and 50 for NMP-22; 39.13 and 0 for the cytologyConclusionsThe low sensitivity of bladder chek invalidates it like alternative method to the cystoscopy in the follow-up of the superficial asymptomatic bladder cell carcinoma     

Surveillance of upper urinary tract transitional cell carcinoma: the role of ureteroscopy, retrograde pyelography, cytology and urinalysis

PURPOSE: A select group of patients with upper tract transitional cell carcinoma are treated with ureteroscopic resection. We determine the validity and accuracy of urinalysis, bladder cytology, upper tract biopsy/cytology and retrograde pyelography for the detection of recurrent upper tract transitional cell carcinoma compared to endoscopic findings. MATERIALS AND METHODS: Patients with ureteroscopically treated upper tract transitional cell carcinoma were followed with surveillance every 3 to 6 months. Surveillance included urinalysis with dipstick and microscopic examination, bladder cytology, retrograde pyelography read by a urologist and radiologist, and ureteropyeloscopy with cytology and biopsy of suspicious areas. Not all results were available for all surveillance procedures. Measures of sensitivity and specificity for the aforementioned surveillance procedures were determined relative to endoscopic findings that were defined as the standard. Confidence intervals were also estimated. Initially, a generalized estimation equation approach was used to take into account the clustering of repeated testing within patients. The accuracy of each procedure was also calculated. RESULTS: There were 23 patients with previously resected low grade upper tract transitional cell carcinoma who underwent a total of 88 surveillances in 30 months. A total of 56 of 88 (64%) recurrences were detected ureteroscopically, including 11 (12%) associated bladder recurrences. In patients who did not have bladder recurrences urinalysis had a sensitivity of 37.5% but specificity was 85%, while bladder cytology had a sensitivity of 50% and specificity was 100%, and retrograde pyelography read in the endoscopy room revealed a sensitivity of 71.7% and specificity of 84.7%. Ureteroscopic biopsy/cytology had a sensitivity and specificity of 93.4% and 65.2%, respectively. CONCLUSIONS: Our findings indicate that compared to ureteroscopy, urinalysis, bladder cytology, retrograde pyelography and ureteroscopic cytology/biopsy are less valid and accurate in detecting upper tract transitional cell carcinoma recurrences. Based on our data we recommend ureteroscopic evaluation as an essential procedure for the surveillance of patients treated endoscopically for upper tract transitional cell carcinoma.     

Intraoperative upper urinary tract cytology examination is a risk factor of upper urinary tract recurrence in patients with non-muscle-invasive bladder cancer

ObjectivesTo evaluate the impact of intraoperative upper urinary tract (UUT) cytology examination in patients with non-muscle-invasive bladder cancer (NMIBC) who had undergone transurethral resection of bladder tumor (TURBT).Materials and methodsWe retrospectively evaluated 414 patients with NMIBC who had undergone transurethral resection of bladder tumor between November 1993 and April 2019. Patients with simultaneous UUT urothelial carcinoma (UC) detected via computed tomography were excluded. Patients were divided into 2 groups: those who had undergone intraoperative bilateral UUT cytology examination via retrograde catheterization (study group) and those who had not (control group). We evaluated the utility of intraoperative UUT cytology examination, comparing surgical outcomes and perioperative complications between the 2 groups. In addition, we evaluated the impact of UUT cytology examination on UUT recurrence using background-adjusted multivariate analysis.ResultsWe obtained 292 UUT urine samples from 146 patients with a median age of 72 years. Of 292 UUT urine samples, 11 (3.7%) were positive and 3 were finally diagnosed as UUT UC. Positive predictive value and false positive rate were 18% and 3.1%, respectively. Operative time for the study group was significantly longer than for the control group. Rate of perioperative complications were not significantly different between the 2 groups. However, in background-adjusted multivariate analysis, intraoperative UUT cytology examination was associated with significantly shorter UUT recurrence-free survival.ConclusionIntraoperative UUT cytology examination may not be recommended as a result of low positive predictive value due to contamination and UUT recurrence risk in patients with NMIBC.     

Monitoring intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma by postoperative urinary cytology

We studied 51 patients with superficial bladder carcinoma who had been treated with transurethral resection of all gross tumor followed by intravesical bacillus Calmette-Guerin weekly for 6 weeks. Within 72 hours of either the first or second quarterly cystoscopic surveillance examination after bacillus Calmette-Guerin therapy, a conventional cytology study was obtained. Of these patients 8 (15.7 per cent) had positive, 9 (17.6 per cent) suspicious and 34 (66.7 per cent) negative postoperative cytology studies. Subsequent tumor recurrence was defined as a positive biopsy or visible papillary tumors on cystoscopic examination. All 8 patients with a positive postoperative cytology study had tumor recurrence at a median interval of 4 months. Of the 9 patients with a suspicious study 7 (77.8 per cent) had recurrent tumor at a median interval of 7 months and 2 (22.2 per cent) had no evidence of disease at 16 and 19 months, respectively. Of the 34 patients with a negative postoperative cytology study 13 (38.2 per cent) had tumor recurrence after a median interval of 4 months and 21 (67.8 per cent) had no evidence of disease after a median of 25 months. The tumor recurrence rate in patients with a positive or suspicious postoperative cytology study was significantly greater than that of patients with a negative study (p equals 0.001, Fisher's exact test). Postoperative cytology appears to be a significant prognostic indicator following transurethral resection and intravesical bacillus Calmette-Guerin treatment of superficial bladder 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.     

Two cases of ureteral tumors occurring after operation on bladder tumors

Among 116 patients with bladder tumors treated during a 17-year period, 2 patients were found to have ureteral tumors (1.7%). The first case was found 8 years after transurethral resection (T.U.R.) and the second case was diagnosed as multiple ureteral tumors 3 years after six T.U.R.s. Long term follow-up by urinary cytology should be performed for patients with bladder tumors to find upper urinary tract tumors, especially for the patient with multiple bladder tumors.     

Clinical impact of bladder biopsies with TUR-BT according to cytology results in patients with bladder cancer: a case control study

Background

There seems to be no consensus concerning taking bladder biopsies during transurethral resection of bladder tumor (TUR-BT). We investigate the clinical significance of bladder biopsy with TUR-BT and the relationship between urinary cytology and the biopsy results.

Methods

We reviewed a total of 424 patients with non-muscle invasive bladder cancer treated with TUR-BT between 1998 and 2005. Of the total, 293 patients also underwent a bladder biopsy. Biopsies from suspicious-appearing urothelium (N = 59) and those from normal-appearing urothelium (N = 234) were evaluated separately.

Results

Bladder cancer was observed in 23 cases (39.0%) who underwent a biopsy of suspicious-appearing urothelium. Among these 23 cases, 9 cases with visible tumor resection had carcinoma in situ (CIS) only in the biopsies from suspicious-appearing urothelium. Urinary cytology was negative in 3 of the 9 cases. Bladder cancer was observed in 26 cases (11.1%) who underwent a biopsy of normal-appearing urothelium. Of them, 5 cases with visible tumors had CIS only in the multiple biopsies from normal-appearing urothelium. Urinary cytology was positive in all of the 5 cases. No upstaging or upgrading cases were found in these patients by the addition of these two types of biopsy. Furthermore, therapy was not altered in these patients. With or without bladder biopsy was not a significant factor for tumor recurrence in either the univariate or multivariate analysis.

Conclusions

Based on the results, it is concluded the multiple biopsies from normal-appearing urothelium are not necessary in patients with negative cytology results because of the low detection rate and lack of influence on therapeutic decisions. Meanwhile, biopsy of suspicious-appearing urothelium is needed in patients with negative cytology results in order to detect CIS due to staging properties. This result supports a recent EAU guideline.