Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology

PURPOSE: The multitarget fluorescence in situ hybridization (FISH) probe set UroVysion (Vysis, Downers Grove, Illinois), containing probes to chromosomes 3, 7 and 17, and to the 9p21 band, has been recently shown to have high sensitivity and specificity for detecting transitional cell carcinoma. In this study we retrospectively tested 120 urine samples from patients with atypical, suspicious and negative cytology for whom concurrent and followup bladder biopsy data were available. We evaluated the ability of FISH to identify malignant cells in cytologically equivocal or negative cases. MATERIALS AND METHODS: Archived slides from 120 voided (47) or instrumented (73) urine cytology specimens from patients with concurrent bladder biopsy and a minimum of 12 months of biopsy followup were subjected to hybridization with UroVysion. The cohort included patients with biopsy proven transitional cell carcinoma, which was grades 1 to 3 in 23, 35 and 24, respectively, and stages pTis in 3, pTa in 64, pT1 in 6, pT2 in 6 and pT4 in 3, while it showed negative histology in 38. Cytology findings were suspicious, atypical and negative for transitional cell carcinoma in 31, 49 and 40 cases, respectively. A positive FISH result was defined as 5 transitional cells or greater with a gain of 2 or more of chromosomes 3, 7 or 17, 12 cells or greater with 9p21 deletion, or 10% or greater of cells with isolated trisomy of 1 of chromosomes 3, 7 and 17. RESULTS: All except 12 of the 82 biopsy proven transitional cell carcinoma cases (11 pTa and 1 pT1 tumors) were positive by FISH (85% sensitivity). Sensitivity in patients with suspicious, atypical and negative cytology was 100%, 89% and 60%, respectively. Nine patients with atypical cytology had positive FISH in the setting of a negative concurrent bladder biopsy. However, 8 of these 9 patients (89%) had biopsy proven transitional cell carcinoma within 12 months following the date when the sample tested by FISH was obtained. The last of these patients with false-positive results had previously documented pTis disease, which was also present in the next bladder biopsy 15 months following the positive FISH result. The remaining 29 specimens from patients with negative biopsy and a negative 12-month followup tested negative by FISH (97% overall specificity). CONCLUSIONS: The UroVysion FISH assay provides high sensitivity and specificity to detect transitional cell carcinoma in cytologically equivocal and negative urine samples. These results emphasize the important role of this assay in the management of bladder cancer.     

Prognostic study of cell proliferative markers ki67, PCNA and p53 oncoprotein in bladder tumors

We report a study of cell proliferative factors Ki67, PCNA and p53 oncoprotein in 55 patients with bladder tumors. Fifty-three of the patients were male and two were female, with a mean age of 56.6 and 68.5 years, respectively. These tumors were of transitional cell type in 97.9% of the cases. Staging was, respectively, pTis (4.76%), pTa (30.9%), pT1 (19.04%), pT2 (23.8%) and Pt3 (21.4%). Our study of proliferative nuclear markers Ki67 showed that cell proliferation increased in bladder tumors according to grade in the same stage. This variation was highlighted by our results for PCNA but was not verified for Ki67. However, these results revealed an increase of cell proliferation for a same grade (grade I and II) in different stages (pTa, pT1, pT2) for PCNA; this was not ascertained for Ki67. The study of p53 oncoprotein showed that detection of mutated p53 protein increased according to grade only for grades II and III and to stage only when moving from pTis to superficial tumors (pTa, pT1) and to deep tumors (pT2, pT3), thus individualizing two groups without significant variation within these groups. A variation according to grade in the same stage was noted only for stages pT1 and pT2. A variation for a same grade (grades II and III) was reported between stages pTa, pT1 and pT2. The combined study of Ki67, PCNA and p53 oncoprotein showed a prognostic correlation between these three markers in general.     

Fluorescence In Situ Hybridisation in the Diagnosis of Upper Urinary Tract Tumours

Background

Upper urinary tract (UUT) tumours are often a diagnostic challenge. Because of delayed diagnosis at an advanced stage, prognosis is less qualitative when compared to bladder tumours. There is, therefore, a need for reliable markers to improve diagnosis.

Objective

Because of the difficulty in interpreting washing cytologies of the UUT, we evaluated the reliability of fluorescence in situ hybridisation (FISH) in the detection of upper tract urothelial cancer.

Design, setting, and participants

A prospective, multicentre cohort study was carried out on 55 consecutive patients with a suspected UUT tumour.

Measurements

Between May 2007 and May 2009, 55 consecutive patients (mean age 71.7 yr; range: 52–93) with a suspected urinary tract tumour were studied with intravenous pyelography, cytology, washing cytology, ureterorenoscopy, and endoscopic biopsies. The patients were followed for a mean observation time of 12.21 mo (range: 0.5–20; standard deviation: 6.12). A multicolour-FISH approach was performed on a liquid-based washing urinary cytology in all cases.

Results and limitations

Twenty-one out of 55 patients had a histologically proven urothelial carcinoma, of which 10 had stage pTa disease, 6 had pT1 disease, 2 had pT2 disease, 2 had pTis disease, and 1 had pTx disease (6 G1, 6 G2, and 9 G3). Three patients had a papilloma, 2 had renal cell carcinoma, 27 had a negative histologic report, and 2 had a nondiagnostic histology. In total, 68 analyses were performed. The cytology was negative or doubtful in 60 out of a total 68 specimens (88.2%) and was suspicious or positive for malignancy in 7 (10.3%) specimens. One specimen was not diagnostic. FISH was negative in 37 of 68 analyses (54.4%) and positive in the other 30 analyses (44.1%). One FISH analysis was not diagnostic as a result of insufficient cellular material. The overall sensitivity of the cytology was 20.8% and of FISH 100%. The specificity was 97.4% for cytology and 89.5% for FISH. Even though this is the largest UUT cohort studied with FISH, the sample size is relatively small.

Conclusions

The UroVysion FISH test is a reliable method in the diagnosis of UUT tumours in cases with clinical suspicion but negative or doubtful cytology and no diagnostic histology.     

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.     

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.     

Grading the invasive component of urothelial carcinoma of the bladder and its relationship with progression-free survival

Although grading is valuable prognostically in pTa and pT1 papillary urothelial carcinoma, it is unclear whether it provides any prognostic information when applied to the invasive component in muscle-invasive carcinoma. The authors analyzed 93 cases of muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy for which follow-up information was available. Each case was graded using the Malmstr?m grading system for urothelial carcinoma, applied to the invasive component. Pathologic stage, lymph node status, and histologic invasion pattern were also recorded and correlated with progression-free survival. Thirty-four cases (37%) were pT2, 40 (43%) were pT3, and 19 (20%) were pT4. Of the 77 patients who had a lymph node dissection at the time of cystectomy, 34 (44%) had metastatic carcinoma to one or more lymph nodes. The median survival for pT2, pT3, and pT4 stages was 85, 24, and 29 months, respectively (p = 0.0001). Lymph node-negative and lymph node-positive patients had a median survival of 63 and 23 months, respectively (p = 0.0001). Fifteen patients (16%) were graded as 2b and 78 patients (84%) were graded as 3. Median survival of patients graded as 2b was 34 months compared with 31 months for patients graded as 3 (p value not significant). Three invasive patterns were recognized: nodular (n = 13, 14%), trabecular (n = 39, 42%), and infiltrative (n = 41, 44%). The presence of any infiltrative pattern in the tumor was associated with a median survival of 29 months, compared with 85 months in tumors without an infiltrative pattern (p = 0.06). Pathologic T stage and lymph node status remain the most powerful predictors of progression in muscle-invasive urothelial carcinoma. In this group of patients histologic grade, as defined by the Malmstr?m system and as applied to the invasive component, provided no additional prognostic information. An infiltrative growth pattern may be associated with a more dismal prognosis.     

Diagnosis, risk factors, and outcome of urethral recurrences following radical cystectomy for bladder cancer in 729 male patients

OBJECTIVES: We evaluated incidence, diagnosis, risk factors, and outcome of urethral recurrences (URs) following radical cystectomy in men with bladder urothelial carcinoma (UC). METHODS: Between 1978 and 2003, a total of 729 male patients underwent radical cystectomy for UC. We determined UR presentation mode and diagnosis. UR was analysed by multivariate analyses according to clinical and pathological risk factors. We evaluated the relative influence of bladder versus urethral pathology on overall survival. RESULTS: A total of 34 URs (4.6%) were identified. Previous history of non-muscle-invasive bladder cancer (NMIBC) (p=0.005), NMIBC pathological subgroup (pTis, pTa, pT1) (p=0.038) and prostate tumor involvement (p=0.0001) in cystectomy specimens were independent predictors of UR. URs developed in 5 (2.2%) of 219 cases with orthotopic diversion and in 29 (5.6%) of 510 with cutaneous diversion (p=0.073). The difference could be explained by patient selection. Cutaneous diversion group had more patients at risk of UR: more cases with prostate tumor involvement (p=0.026) and with a history of NMIBC (p=0.009). Neither bladder nor urethral pathology showed any superiority as a predictor of overall survival. CONCLUSIONS: Previous history of NMIBC, and also NMIBC and prostate tumor involvement in cystectomy specimen were predictors of UR. The lower incidence of UR in patients with orthotopic diversion could be a result of patient selection. Bladder tumor, UR, and even an upper urinary tract tumor could have been the cause of death in these patients.     

荧光原位杂交法和全自动图像细胞仪在膀胱尿路上皮癌诊断中的应用

目的 探讨荧光原位杂交法(FISH)和全自动图像细胞仪(ICM)在膀胱尿路上皮癌诊断中的应用.方法 在2008年8月至2009年3月共选取60例患者,包括20例非尿路上皮癌和40例膀胱尿路上皮癌的患者,取患者的尿液作常规尿细胞学检查、FISH和ICM检测.结果 FISH的敏感性显著高于ICM的敏感性(82.5%比62.5%,P＜0.05)和常规尿细胞学的敏感性(82.5%比25.0%,P＜0.05),同时ICM敏感性也高于常规尿细胞学的敏感性(62.5%比25.0%,P＜0.05);FISH、ICM和常规尿细胞学检查的特异性都为100%,三者在特异性方面差异无统计学意义(P＞0.05).FISH、ICM和常规尿脱落细胞学检测的敏感性与病理分期无相关性(P＞0.05),但与分级有相关性(P＜0.05).结论 FISH和ICM在膀胱尿路上皮癌诊断中,其特异性和常规尿细胞学检查一致,但敏感性显著高于常规尿细胞学检查;同时FISH在膀胱尿路上皮癌诊断中的敏感性高于ICM,所以FISH技术更有望成为膀胱尿路上皮癌无创性的诊断和检测手段.     

CD10 expression in urothelial bladder carcinomas: a pilot study

OBJECTIVES: The aims of this study were to investigate the expression of CD10 in normal bladder tissue and urothelial bladder carcinomas and to clarify its association with histopathological variables. MATERIALS AND METHODS: A total of 79 urothelial bladder carcinomas were selected from routine archival material. All cases were reevaluated histopathologically and graded according to the World Health Organization (WHO) 1973, WHO/ISUP 1998, and WHO 1999 systems. The TNM system was used for their pathological staging. CD10 immunohistochemical staining was performed in selected slides. RESULTS: Tumoral cases consisted of 74 men (93.7%) and 5 women (6.3%). According to the pathological stage, 25 (31.6%), 33 (41.8%), and 21 (26.6%) cases had pTa, pT1, and pT2-3 carcinomas, respectively. 34 of 79 (43%) urothelial carcinomas and only 1 of 11 (9.1%) nontumoral cases showed positive CD10 immunostaining. It was a cytoplasmic diffuse or granular immunostaining pattern both in nontumoral and tumoral urothelia. There was no statistically significant difference between tumoral and nontumoral cases with respect to CD10 reactivity (p = 0.051), but there was a trend toward significance. In urothelial tumors, there was a significant inverse correlation between pathological stages and CD10 immunoreactivity (p = 0.036, r = -0,237). There was also a statistically significant difference between pTa and pT2-3 urothelial tumors in relation to the CD10 expression (p = 0.034). No association was detected between CD10 expression and grades according to all systems used (p > 0.05). CONCLUSIONS: According to our findings, the CD10 expression in noninvasive carcinomas showed a higher level than that in invasive carcinomas, and it is inversely correlated with the pathological stage. CD10 may play an important role in the progression of urothelial bladder carcinomas, and downregulation probably facilitates invasion, especially muscle invasion.     

荧光原位杂交法在膀胱尿路上皮癌诊断中的应用

目的：探讨荧光原位杂交法（FISH）在膀胱尿路上皮癌诊断中的应用。方法：选取20例非尿路上皮癌和40例膀胱尿路上皮癌的人群尿液作常规尿脱落细胞学检查和FISH检测。结果：FISH技术的敏感性为82．5％,显著高于常规尿脱落细胞学的敏感性25．0％（P〈0．05）;FISH技术和常规脱落尿细胞学检查的特异性均为100％,两者在特异性方面差异无统计学意义（P〉0．05）。结论：荧光原位杂交法在膀胱尿路上皮癌诊断中的特异性与常规尿脱落细胞学检查一致,但其敏感性显著高于常规尿脱落细胞学检查,所以,FISH技术更有望成为膀胱尿路上皮癌无创性的诊断和检测手段。     

Value of urethral wash cytology in the retained male urethra after radical cystoprostatectomy

PURPOSE: We determined the outcome in patients who underwent urethrectomy after cystectomy followed by routine urethral wash cytology versus those not followed by urethral wash cytology who presented with bleeding or urethral discharge. We retrospectively evaluated the outcome in post-cystectomy urethrectomy cases at our institution from 1994 to 2000. MATERIALS AND METHODS: A total of 24 patients with a median age of 70.5 years underwent urethrectomy after cystectomy, including 17 due to asymptomatic, positive urethral wash cytology (group 1) and 7 who were not followed by urethral wash and presented with bleeding/urethral discharge (group 2). Median time from cystectomy to urethrectomy was 11.4 months (range 6.7 to 67.1). Median followup after cystectomy and urethrectomy was 37 and 27.7 months, respectively. RESULTS: Urethrectomy pathological evaluation showed pTis disease in cases 12 (50%), pT0 in 9 (37.5%) and pT1 in 3 (12.5%). Cystectomy pathology was organ confined (pT0, pTis and pT1-pT2b disease) in 12 cases (50%), nonorgan confined (pT3a-pT4) in 6 (25%) and pT any N1 in 5 (21%). Cystectomy pathology was unknown in 1 case. At the most recent followup there was no evidence of disease in 14 patients (58%), 5 (21%) were alive with disease, 3 (12.5%) were dead of disease, 1 (4%) was dead of other causes and disease status was unknown in 1 (4%). There was no statistical difference in survival in groups 1 and 2 when controlling for original bladder tumor stage. Cox regression analysis revealed that cystectomy pathology was the only statistically significant parameter of disease-free survival (p = 0.011), while urethrectomy pathology and followup method (urethral washing versus no washing) were not significant. There were no perioperative or postoperative complications and no patients died. CONCLUSIONS: There was no significant survival difference in patients followed and not followed with urethral washing. Longer followup and increased patient numbers are needed to determine the significance of these findings.     

Clinical experience with BCG immune prevention in superficial bladder cancer]

Previous randomized studies have shown that in cases of superficial urothelial carcinoma or carcinoma in situ of the urinary bladder, complete and long-lasting remission can be obtained by immunotherapy with bacillus Calmette-Guérin (BCG). Such studies have shown that BCG reduces the recurrence rate significantly compared with transurethral resection alone. Our 6-year experience with BCG Pasteur strain (and Connaught strain, respectively) in tumour stages pTis, pTa and pT1 (G I-II) shows lasting remission in 88.5% (73%) of 78 (26) patients after transurethral resection of the tumour. A complete remission was found in 92% of patients with carcinoma in situ (12 patients). The local and the rare systemic side effects were all of limited duration, tolerable, easily treated and fully reversible.     

Downstaging to non-invasive urothelial carcinoma is associated with improved outcome following radical cystectomy for patients with cT2 disease

Introduction

Pathologic stage is a critically important prognostic factor after radical cystectomy (RC) that is used to guide the use of secondary therapies. However, the risk of disease recurrence, for patients clinically diagnosed with muscle-invasive tumors who are found not to have muscle-invasive disease at RC are poorly defined. Therefore, we reviewed the long-term outcomes in patients who were downstaged to non-invasive urothelial carcinoma at time of RC.

Methods

We identified 1,177 consecutive patients with muscle-invasive urothelial carcinoma of the bladder who underwent radical cystectomy at our institution between 1980 and 1999 without neoadjuvant therapy. Postoperative disease recurrence and survival were estimated using the Kaplan?CMeier method and compared using the log rank test. Cox proportional hazard regression models were used to analyze the impact of pathologic stage on survival.

Results

Pathologic downstaging to non-muscle invasive disease was identified in 538 (45.7?%) patients. The 10-year cancer-specific survival was 84.1, 77.4, 71.1 and 58.5?% for those with pT0, pTis, pT1 and pT2 tumors, respectively. On multivariate analysis, the risk of cancer-specific mortality was significantly decreased for patients with non-muscle invasive disease than those with organ-confined muscle invasion (RR?0.39; p?=?0.002). There was no difference in disease-specific mortality among patients who had non-invasive (pT0, pTa, or pTis) disease (p?=?0.19).

Conclusions

Downstaging from clinical muscle-invasive bladder cancer to non-muscle invasive disease at RC is associated with a significant reduction in cancer-specific mortality. However, even patients with residual non-muscle invasive disease may suffer disease recurrence and require continued surveillance after surgery.     

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.     

Superficial bladder cancer treated by total cystectomy: Tumour characteristics and patient survival

Of 113 patients with bladder cancer who underwent total cystectomy from January 1980 to December 1990, 30 (27%) had superficial tumours (pTa, pTis, and pT1). Nineteen of these 30 patients (63%) were primarily treated by total cystectomy and the remaining 11 (37%) had a past history of treatment for bladder cancer. Major reasons for choice of total cystectomy were multifocal tumours, frequent recurrence, and diffuse carcinoma in situ. Histologically stage pT1, grade 3 tumours were frequently accompanied by carcinoma in situ and often by lymphatic invasion. None of the 24 patients undergoing pelvic lymphadenectomy had lymph node metastasis. Of 25 male patients 15 (60%) underwent simultaneous prophylactic urethrectomy. Two of the remaining 10 males (20%) not undergoing this additional operation died of subsequent urethral recurrence. The 5-year actuarial survival rate was 80% for the 30 patients when all causes of death were considered. It was concluded that patients with superficial bladder cancer who undergo total cystectomy without prophylactic urethrectomy require close follow-up with urethral washings for cytology to detect early urethral recurrence, an important determinant for survival.     

原发性输尿管癌的临床特点及诊治要点

目的 探讨原发性输尿管癌的临床特点及诊治要点.方法 回顾性分析2000年2月至2016年2月本院行手术治疗的41例输尿管癌患者的临床资料及诊疗经过.结果 所有患者中有28例行根治性肾输尿管全切除术,13例患者行保肾手术,肿瘤组织分期为:pTis、pTa、pT1共有24例,pT2有11例、pT3有6例;病理分级结果为:低度恶性潜能尿路上皮乳头状瘤3例,低级别尿路上皮癌18例及高级别尿路上皮癌20例.出现肿瘤复发及转移的患者共15例,共有7例患者死于输尿管癌的多发转移.结论 输尿管癌具有恶性程度高,易复发,易远处转移等特点,诊断主要依靠影像学及细胞病理学检查,根治性肾输尿管全切术是治疗的金标准,保肾手术可选择性应用,中晚期输尿管癌的治疗需要采取综合治疗以提高生存率.     

Urinary cytology has a poor performance for predicting invasive or high-grade upper-tract urothelial carcinoma

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Accurate preoperative staging for upper‐tract urothelial carcinoma (UTUC) lesions is presently limited. Urinary cytology has shown promise for characterizing pathological features of bladder cancer. The role of cytology for UTUC is at present poorly defined. In this large multi‐institutional cohort of patients, urinary cytology was limited in its ability to accurately predict the grade and stage of upper‐tract lesions. Selective ureteral sampling improved the diagnostic accuracy of cytology when compared to bladder specimens. Improved preoperative surrogate markers for staging UTUC remain necessary.

OBJECTIVE

? To evaluate the diagnostic accuracy of urine cytology for detecting aggressive disease in a multi‐institutional cohort of patients undergoing extirpative surgery for upper‐tract urothelial carcinoma (UTUC).

METHODS

? We reviewed the records of 326 patients with urinary cytology data who underwent a radical nephroureterectomy or distal ureterectomy without concurrent or previous bladder cancer. ? We assessed the association of cytology (positive, negative and atypical) with final pathology. Sensitivity and positive predictive value (PPV) of a positive (± atypical) cytology for high‐grade and muscle‐invasive UTUC was calculated.

RESULTS

? On final pathology, 53% of patients had non‐muscle invasive disease (pTa, pTis, pT1) and 47% had invasive disease (≥pT2). Low‐grade and high‐grade cancers were present in 33% and 67% of patients, respectively. ? Positive, atypical and negative urine cytology was noted in 40%, 40% and 20% of cases. Positive urinary cytology had sensitivity and PPV of 56% and 54% for high‐grade and 62% and 44% for muscle‐invasive UTUC. ? Inclusion of atypical cytology with positive cytology improved the sensitivity and PPV for high‐grade (74% and 63%) and muscle‐invasive (77% and 45%) UTUC. Restricting analysis to patients with selective ureteral cytologies further improved the diagnostic accuracy when compared with bladder specimens (PPV > 85% for high‐grade and muscle‐invasive UTUC).

CONCLUSIONS

? In this cohort of patients with UTUC treated with radical surgery, urine cytology in isolation lacked performance characteristics to accurately predict muscle‐invasive or high‐grade disease. ? Improved surrogate markers for pathological grade and stage are necessary, particularly when considering endoscopic modalities for UTUC.     

Decreased expression of KAI1 metastasis suppressor gene is a recurrence predictor in primary pTa and pT1 urothelial bladder carcinoma

OBJECTIVE: To examine the expression of the KAI1 metastasis suppressor gene and to evaluate its relationship with tumor recurrence in primary pTa and pT1 urothelial bladder carcinoma. METHODS: Samples were obtained from 87 patients after transurethral resection (TUR). Tumor stage and grade were reviewed in 33 patients with pTa and in 54 patients with pT1, with a mean follow-up time of 47.4 +/- 30.1 months. The KAI1 protein immunohistochemical assay was performed. Prognosis was analyzed using the Kaplan-Meier method and Cox's proportional hazards model. Correlation between KAI1 expression and recurrence according to each clinicopathological factor was comparatively evaluated using the chi-squared test. RESULTS: Decreased expression of KAI1 protein failed to reach statistical significance for stage (P = 0.25) or morphology of tumor stem (P = 0.19), but it was significantly related to tumor size (P = 0.016). The recurrence-free 5-year survival rates of the group with decreased KAI1 expression was 69.7%, which was significantly higher than the 22.2% for the KAI1-positive group (P < 0.0001). In univariate and multivariate analyses, decreased expression of KAI1 protein, stage pT1, tumor size >3 cm and sessile tumors were independent prognosis factors of recurrence. Despite the lower recurrence rate expected by considering only the clinicopathological factors, decreased KAI1 expression was able to identify the group with a high risk of recurrence. CONCLUSIONS: Downregulated KAI1 expression in bladder tumors tends to relate to stage and morphology of the tumor stem and was significantly correlated to tumor size. Decreased expression of KAI1 was associated with the degree of invasiveness and progression of the cancer and was an independent prognostic factor of recurrence in primary pTa and pT1 urothelial bladder carcinoma.     

Is a second transurethral resection necessary for newly diagnosed pT1 bladder cancer?

PURPOSE: We evaluated the potential benefit of a second transurethral resection in patients with newly diagnosed pT1 transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Between January 2001 and May 2003, 80 patients with stage T1 bladder cancer were included in this protocol in which all patients prospectively received second TUR within 2 to 6 weeks following the initial resection. Patients with incomplete resections were excluded from study. The pathological findings of the second TUR were reviewed. RESULTS: Of the 80 patients who underwent second resection, 18 (22.5%) had macroscopic tumors before resection. However, with the addition of microscopic tumors, overall residual disease was determined in 27 (33.8%) patients. Of the 27 patients 7 had pTa, 14 had pT1, 3 had pT1+pTis and 3 had pT2 disease. Residual cancers were detected in 5.8%, 38.2% and 62.5% in G1, G2 and G3 tumors, respectively. The risk of residual tumor directly correlated with the grade of the initial tumor (p = 0.009). CONCLUSIONS: Although second TUR dramatically changed the treatment strategy in a small percentage of cases, we strongly recommend performing second TUR in all cases of primary pT1 disease, especially in high grade cases.     

Allelic loss of chromosome 17p in urothelial cancer: strong association with invasive phenotype.

Allelic loss of chromosome 17p with a mutated p53 gene on the remaining allele has been observed in various kinds of human cancers. To examine the significance of allelic loss of chromosome 17p in human urothelial cancer with special attention to the clinicopathological features, 49 tumors with various stages and grades from 43 cases (35 bladder cancers and 8 renal pelvic or ureteral cancers) were examined for loss of heterozygosity using 5 polymorphic probes on chromosome 17p. Thirty-seven cases were informative, and allelic loss of chromosome 17p was observed in 15 (41%) of them. In bladder cancers, the loss of 17p was observed with significantly higher frequency (p < 0.01) in cases with invasive (> or = pT2) tumors (7/10, 70%) than in cases with superficial (pTa or pT1) tumors (4/21, 19%). In renal pelvic or ureteral cancers, none of 2 superficial tumors and all of 4 invasive tumors showed the allelic loss. As to tumor grade, the allelic loss was observed in 1/9 (11%) for grade 1 cases, 6/18 (33%) for grade 2 cases, and 8/10 (80%) grade 3 cases (grade 1 versus 3, p < 0.01; grade 2 versus 3, p < 0.05). On the other hand, examination of clinical features, such as primary tumor site, tumor multiplicity or previous history of urothelial cancer did not significantly influence the frequency of the allelic loss. Our results suggest that the allelic loss of chromosome 17p is strongly associated with invasive phenotype in urothelial cancer. The results further indicate that the 17p deletion may represent a new genetic marker of malignant potentials in urothelial cancers.