膀胱移行细胞癌组织中p16、p53和PCNA的表达及其意义

目的:探讨p16、p53蛋白及PCNA在膀胱移行细胞癌的表达及其与病理分级和临床分期关系.方法:采用免疫组化SABC法并结合图像分析方法检测40例膀胱移行细胞癌中p16、p53蛋白及PCNA的表达.结果:3种蛋白在膀胱肿瘤中的表达与正常膀胱组织均有显著差异.p16与病理分级及临床分期呈负相关,p53、PCNA与病理分级呈正相关.结论:p16与p53可作为膀胱移行细胞癌分化程度和预后判断的参考指标,而PC-NA可作为预后判断辅助指标.     

胰岛素样生长因子I受体在膀胱移行细胞癌中的表达

目的研究胰岛素样生长因子Ⅰ受体(IGF-1R)在膀胱移行细胞癌中的表达及其与临床的关系。方法78例膀胱癌标本来自2000年~2002年间在我院手术治疗的膀胱移行上皮肿瘤患者,采用免疫组织化学法检测不同临床分期,病理分级患者以及初发及复发患者膀胱移行细胞癌组织的IGF-1R水平。结果在膀胱移行细胞癌中IGF-1R的表达阳性率明显升高,IGF-1R的表达与肿瘤的临床分期和病理分级以及肿瘤复发呈正相关(P<0.05)。结论IGF-1R在膀胱移行细胞癌的生长中起重要的作用,可以作为临床判断患者预后的辅助指标。     

动脉化疗栓塞对膀胱癌组织中Ki-67和PCNA表达的影响

目的：探讨术前动脉化疗栓塞对膀胱癌组织Ki-67和增殖细胞核抗原（PCNA）表达的影响及其临床意义。方法：对30例膀胱癌患者化疗栓塞前后的肿瘤组织,应用免疫组织化学法测定Ki-67和PCNA的表达,并分析Ki-67和PCNA与膀胱癌病理分级和临床分期的关系。结果：对30例膀胱癌患者化疗栓塞前后的肿瘤组织,应用免疫组织化学法测定Ki-67和PCNA的表达,并分析Ki-67和PCNA与膀胱癌病理分级和临床分期的关系。结论：化疗栓塞前后Ki67中高度阳性表达率为70％、26.67％,PCNA为73.33％、20％,差异均有非常显著性意义（P〈0.01）,经随访24.6个月,复发率为16.67％。Ki-67和PCNA阳性表达及下降幅度与膀朊癌的病理分级、临床分期和患者术后复发率关系密切,两者阳性表达及表达强度呈正相关（P〈0.001）。结论：术前化疗栓塞能降低膀胱癌组织Ki-67和PCNA的表达,调节膀胱癌的分化程度,使肿瘤降级降期,减少术后转移,降低复发率,提高生存率。Ki-67和PCNA的表达可作为膀胱癌预后估计的指标。     

PCNA在膀胱移行细胞癌的应用意义

为了了解增殖细胞核抗原（ＰＣＮＡ）与膀胱肿瘤的病理分级、临床分期和复发的关系，选择５５例有随访结果的膀胱移行细胞癌石蜡病理切片进行ＰＣＮＡ检测，与临床随访结果进行对比。结果显示：ＰＣＮＡ表达与病理分级关系显著（Ｐ＜０．０５），与临床分期关系不明显。ＰＣＮＡ高表达、ＰＣＮＡ阳性细胞在组织层次中的分布均与肿瘤复发、恶化有明显关系。认为瘤旁组织的ＰＣＮＡ指数增高和复发肿瘤中ＰＣＮＡ高表达均为肿瘤恶化的一个客观指标；ＰＣＮＡ表达对肿瘤演变、术后随访及治疗有一定的指导意义，是监测膀胱移行细胞癌恶性程度和预后的一个重要标记。     

E-CD在膀胱移行细胞癌中表达的意义

为了解钙依赖性上皮细胞粘附分子（ＥＣＤ）与膀胱肿瘤的病理分级、临床分期以及预后的关系，采用免疫组化方法检测５５例膀胱移行细胞癌石蜡病理切片中ＥＣＤ的表达情况，并与其病理分级、临床分期及随访结果相比较。结果显示：ＥＣＤ的低表达或无表达与膀胱肿瘤的病理分级及临床分期有显著关系（Ｐ＜００５，Ｐ＜００１），同时与肿瘤复发及患者的生存情况有显著关系（Ｐ＜００１，Ｐ＜００１）。ＥＣＤ低表达或无表达是肿瘤恶性程度的重要标志之一，ＥＣＤ表达情况可以作为监测膀胱移行细胞癌恶性程度、复发及预后的重要指标。     

MCM5和PCNA在膀胱移行细胞癌中的表达及临床意义

目的：研究微型染色体维持蛋A5（MCM5）和增殖细胞核抗原（PCNA）在膀胱移行细胞癌中的表达及临床意义。方法：采用免疫组化S—P法检测56例膀胱移行细胞癌和10例正常膀胱黏膜中MCM5及PCNA的表达，分析它们的相关性及与膀胱移行细胞癌分化、分期和预后的关系。结果：①MCM5和PCNA在膀胱移行细胞癌与正常组织中皆有表达，两者在膀胱移行细胞癌组的表达明显高于正常组（P〈0．01）。②MCM5和PCNA的表达均与膀胱移行细胞癌的组织分级、临床分期、术后复发有关（P〈0．05）。③MCM5表达和PCNA表达呈正相关（相关系数r=0．854，P〈0．05）。结论：MCM5蛋白是膀胱移行细胞癌的一种可靠标志物，MCM5的表达可以预示膀胱移行细胞癌的恶性程度高低和复发倾向，并有助于临床判断患者的预后以及选择合适的治疗方法。     

上尿路移行细胞癌术后发生膀胱癌的危险因素分析

目的探讨上尿路移行细胞癌临床与病理特点及对术后膀胱癌发生及预后的影响.方法对133例肾盂和(或)输尿管癌病例的临床特点与术后发生膀胱癌以及预后情况分别应用Cox比例风险模型分析,作Kaplan-Meier曲线并行LogRank检验.结果133例患者接受根治手术后发生膀胱癌者40例,占30.1%.原发上尿路肿瘤数目、分期和有无同发膀胱癌对术后发生膀胱癌有显著影响,风险度>1,回归系数>0,二者间相关系数小.应用LogRank检验显示原发肿瘤为单发者术后无膀胱癌发生的机率低于多发者(P=0),随着病理分期的升高,膀胱癌发生率随之增加(P＝0.0039).首次发生膀胱癌者有92.5%在2年之内.原发肿瘤数目、分期、有无同发膀胱癌以及术后膀胱癌发生间隔时间对存活率有显著影响,四种因素的相关系数小.结论原发上尿路肿瘤的数目、分期和有无同发膀胱癌为术后发生膀胱癌的危险因素;原发肿瘤数目、分期、有无同发膀胱癌以及术后膀胱癌发生间隔时间对存活率有显著影响.     

膀胱癌中缺氧诱导因子-1α的表达和肿瘤血管生成的关系

目的：探讨缺氧诱导因子-1α（HIF-1α）在膀胱移行细胞癌中的表达和肿瘤血管生成的关系。方法：采用免疫组化SABc法观察42例膀胱移行细胞癌石蜡标本中HIF-1α、VEGF、PCNA的表达情况及微血管密度。并结合临床资料进行分析。结果：HIF一1n在膀胱移行细胞癌中的表达显著增强（P〈0．05）并与VEGF、MVD、PCNA和肿瘤复发呈正相关（依次为：P〈0．01，P〈0．05，P〈0．01，P〈0．05），但与膀胱癌的病理分级、临床分期和患者年龄无关；且VEGF与MVD在膀胱癌组织中表达增高。与其病理分级相关（P〈0．05）。在logistic回归模型中，HIF—1α和PCNA均呈现为膀胱癌复发的危险因素。结论：HIF-1α在膀胱移行细胞癌肿瘤血管生成中起重要作用，并可能成为膀胱癌诊断和复发预测的生物学标记，以及抗血管生成治疗新的靶点。     

P_(53)蛋白和增殖细胞核抗原在膀胱癌中的表达及意义

采用免疫组化法对69例膀胱移行细胞癌中P_(53)蛋白及增殖细胞核抗原(PCNA)进行检测。发现膀胱癌中P_(53)蛋白的过度表达与病理分级无关,而与临床分期及预后有关。PCNA-LI与病理分极、临床分期及预后均相关,随着肿瘤分级、分期的增高,PCNA-LI呈明显上升趋势;P_(53)蛋白过度表达或PCNA高表达组术后5年生存率明显低于P_(53)蛋白非过度表达或PCNA低表达组。结果表明:P_(53)蛋白的过度表达在膀胱癌发生、发展中起着一定作用,PCNA是判定膀胱癌恶性程度及预后的重要指标,同时发现膀胱癌中P_(53)蛋白的过度表达与PCNA-LI相关。     

肾细胞癌数据库三年临床资料COX模型分析

目的通过对同济医院肾细胞癌数据库三年临床数据的研究，探讨肾细胞癌的特征及影响其预后相关因素。方法采用Kapplan-Meier法计算生存概率及应用COX模型对肾细胞癌数据库中回访数据齐全的145例性别、年龄、是否偶发、临床分期、病理分类、病理分级、手术方式、有无免疫治疗等因素作为分析因子，计算生存率，分析预后影响因素。结果145例肾细胞癌患者存活满1年、3年分别为126例、105例，生存概率分别为86．3％、72．4％。COX回归模型提示影响肾细胞癌患者预后的主要因素依次为是否行肾癌根治手术、病理分级、有无淋巴结转移、肿瘤分期；建立肾细胞癌术后生存预测方程：h（t，x）-ho（t）exp（O．850Xs＋0．997X。＋1．497X9—1．974X10）。结论肾细胞癌的预后与是否行肾癌根治手术、肿瘤细胞的病理分级、有无淋巴结转移、肿瘤T分期等因素有关。     

The outcome of patients on dialysis with upper urinary tract transitional cell carcinoma

PURPOSE: Transitional cell carcinoma is the most common upper urinary tract cancer in Taiwanese patients on dialysis. It is a unique finding compared with Western countries. Unfortunately, the long-term outcomes of patients with upper urinary tract transitional cell carcinoma on dialysis are largely unknown. This study presents clinical outcome of patients on dialysis with upper urinary tract transitional cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients with upper urinary tract transitional cell carcinoma who had end stage renal disease and underwent dialysis. Traditional prognostic factors including age, sex, tumor grade, stage and tumor location were analyzed with respect to disease recurrence and survival. RESULTS: A total of 73 patients were included in this study. The major complaints were painless gross hematuria and urethral bloody discharge. Disease relapsed in 40 (54.8%) patients at average time of 15 months (2 to 92). Univariate analysis failed to identify significant prognostic factors for recurrence. The average duration between primary and contralateral metachronous upper urinary tract transitional cell carcinoma recurrence was 36 months (range 5 to 96). Patients on dialysis with upper urinary tract transitional cell carcinoma who had previous or concurrent bladder tumor, or who had a history of recurrent bladder tumor, had high contralateral upper urinary tract transitional cell carcinoma recurrence. (p = 0.038) The statistically significant prognostic factor for disease-free survival was pT stage (p = 0.041). CONCLUSIONS: Patients on dialysis with painless gross hematuria or bloody urethral discharge must undergo detail urinary system evaluation. Since patients with upper urinary tract transitional cell carcinoma on dialysis have a high recurrence rate and metachronous or even multiple, early synchronous tumor characteristics that may be missed by imaging, total urinary tract exenteration is a recommended therapeutic option.     

The role of volume weighted mean nuclear volume in predicting the prognosis of patients with primary transitional cell carcinoma of the upper urinary tract: a report of 102 new cases

PURPOSE: We compare estimates of volume weighted mean nuclear volume (MNV) with histological grading to determine the prognosis of primary transitional cell carcinoma of the upper urinary tract using a Cox proportional hazards model. MATERIALS AND METHODS: We retrospectively reviewed 102 patients who underwent nephroureterectomy for primary transitional cell carcinoma of the upper urinary tract at our hospital between April 1981 and March 1997. Traditional prognostic factors, such as patient age, sex, stage and grade, multiplicity and unbiased estimates of MNV were analyzed with respect to disease recurrence and survival. RESULTS: Estimates of mean nuclear volume were significantly larger for patients with than without lymph node metastasis (p = 0.0031). No prognostic factor significantly correlated with recurrence of transitional cell carcinoma of the bladder. For pTxN0M0 cases univariate analysis revealed that histological grade (p = 0.0018), pathological T stage (p = 0.0030) and estimates of MNV (p = 0.0001) correlated significantly with disease specific survival, and multivariate stepwise regression analysis revealed that estimate of MNV was the only powerful predictor of prognosis (p = 0.0007). CONCLUSIONS: Our results indicate that estimate of MNV is an important predictor of prognosis for transitional cell carcinoma of the upper urinary tract. We recommend MNV estimate as a supportive method for subjective histological grading.     

Tumor necrosis as prognostic indicator in transitional cell carcinoma of the upper urinary tract

PURPOSE: The clinicopathological features predictive of outcome in patients with upper urinary tract transitional cell carcinoma are not clearly established. We analyzed the prognostic impact of tumor necrosis with respect to metastasis-free survival. MATERIALS AND METHODS: The presence of focal (10% or less of the tumor area) and extensive (greater than 10% of the tumor area) coagulative tumor necrosis was retrospectively reevaluated in 268 cases of consecutive upper urinary tract transitional cell carcinoma and correlated with outcome. RESULTS: Overall tumor necrosis was noted in 113 of 268 (42.2%) cases of transitional cell carcinoma with 63 (23.5%) showing focal and 50 (18.7%) showing extensive necrosis, respectively. Tumor necrosis was associated with high tumor stage (p <0.001) and high tumor grade (p <0.001). In addition, tumor necrosis was more common in pelvic tumors compared with ureteral tumors (p <0.001). Actuarial 5-year metastasis-free survival rates for patients with transitional cell carcinoma with extensive, focal and lacking necrosis were 24%, 45% and 78%, respectively (log rank test p <0.001). Multivariate analysis proved pT stage greater than 1 (p <0.001, RR 6.04, 95% CI 2.82-12.93), high tumor grade (p <0.001, RR 3.37, 95% CI 1.65-6.89) and extensive tumor necrosis as independent predictors of poor patient outcome (p = 0.02, RR 1.82, 95% CI 1.09-3.05). CONCLUSIONS: The presence of extensive tumor necrosis proved to be an additional histological variable with an independent influence on metastasis-free survival in patients with upper urinary tract transitional cell carcinoma. Its assessment is readily applicable in routine sections and should thus be commented upon separately in the pathology report.     

Prognostic significance of bladder tumor history and tumor location in upper tract transitional cell carcinoma

PURPOSE: We studied prognostic factors for 5-year disease specific and recurrence-free survival in patients treated for upper urinary tract transitional cell carcinoma. MATERIALS AND METHODS: Since July 1987, 72 patients with a mean age of 58.9 years have undergone nephroureterectomy with bladder cuff excision. Median followup was 62.2 months (range 6 to 192). Patient age, sex, detection duration and mode, bladder tumor history, smoking habit, stone disease history, and tumor stage, grade and location were evaluated as prognostic factors. RESULTS: Overall 5-year disease specific and recurrence-free survival rates were 74.9% and 67.8%, respectively. Univariate analysis revealed anemia, positive bladder tumor history, T stage, grade and tumor location in the upper tract as significant prognostic factors. On multivariate analysis T stage, grade and tumor location in the urothelium were the only significant variables for the 5-year disease specific and recurrence-free survival rates. CONCLUSIONS: High tumor stage and grade, and ureteral location were significantly associated with worse disease specific and recurrence-free survival in patients with upper urinary tract transitional cell carcinoma. Our results may help define the patient groups that need adjuvant therapy and they may form a basis for further controlled studies.     

Different treatment strategies for end stage renal disease in patients with transitional cell carcinoma

PURPOSE: Transitional cell carcinoma is the most common urinary tract cancer in Taiwanese patients on dialysis. It is a unique finding compared within Western countries. Due to this geographic difference and a higher recurrence rate a more extensive operation and aggressive followup protocols should be refined for these patients on dialysis. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients with transitional cell carcinoma who had end stage renal disease and underwent hemodialysis. Records were reviewed for hemodialysis duration, initial tumor location, tumor grade, stage, operative method, operative complication and final surgical status. Tumor grade and stage was determined by the WHO and proposed Jewett systems. Six patient groups were classified according to final surgical status for comparative analysis. RESULTS: A total of 30 patients were included in this study. Painless gross hematuria and urethral bloody discharge were the most common complaints. Tumor in 25 of the 30 cases was high grade and all were early stage. Of the patients 11 (36.7%) had undergone bilateral nephroureterectomy and radical cystectomy in as a 1 or multiple step procedure. Six patients (20%) had undergone bilateral nephroureterectomy at 1 or 2 sequential operations. Seven of the 13 patients (53.8%) in whom low urinary tract transitional cell carcinoma was initially treated with transurethral resection unfortunately had recurrent transitional cell carcinoma of the upper urinary tract. Ten of the 14 patients (71.4%) with upper urinary tract transitional cell carcinoma who underwent nephroureterectomy and bladder cuff excision had subsequent transitional cell carcinoma within the bladder. CONCLUSIONS: Patients with transitional cell carcinoma on dialysis had a higher recurrence rate in the upper urinary tract than patients not on dialysis. Most cases were at an early stage but with high grade tumor behavior. In 11 patients (36.7%) total exenteration of the urinary tract except the urethra was eventually done. The final bilateral nephroureterectomy rate was 56.7%. Since the rate of total exenteration and bilateral nephrectomy was abnormally high at such a short followup, 1-step bilateral nephroureterectomy and radical cystectomy are a recommended treatment for patients with transitional cell carcinoma on dialysis.     

A comparison of the pathology of transitional cell carcinoma of the bladder and upper urinary tract

OBJECTIVE: To clarify the histopathological patterns of upper and lower urinary tract transitional cell carcinomas (TCCs), as previous reports suggest that upper urinary tract TCCs have a greater tendency towards high-grade disease than bladder TCCs, of which most are low-grade and low-stage tumours. PATIENTS AND METHODS: All patients presenting with TCC of bladder or upper urinary tract between February 1991 and December 2001 at one institution were identified. Further patient information was obtained from the hospital database and case-note review. RESULTS: In all, 164 patients with upper urinary tract TCC and 2197 with bladder TCC were identified. There was a correlation between grade and stage of both upper urinary tract and bladder TCCs. 35% of the upper tract TCCs were classified as grade 2 and 44% as grade 3, while for bladder TCCs, 31% of lesions were classified as grade 2 and 35% as grade 3 (P = 0.003). Of the upper urinary tract lesions 33% were stage pT2-T4, compared with only 20% of bladder TCCs (P = 0.001). CONCLUSIONS: Upper urinary tract TCC is a higher grade and stage disease than bladder cancer, a finding that emphasizes the need for aggressive treatment of upper urinary tract TCC. If endourological management of upper urinary tract TCC is considered, histopathological determination of tumour grade before treatment is essential.     

Prognostic variables in patients with transitional cell carcinoma of the renal pelvis and proximal ureter

Recent technological advances in urological endoscopic surgery of the renal pelvis and proximal ureter via ureteroscopy or percutaneous nephroscopy have made it possible to consider parenchymal-sparing procedures in patients with transitional cell carcinoma. To define the role of these procedures in the management of renal pelvic or proximal ureteral transitional cell carcinoma we analyzed retrospectively 31 patients who underwent nephroureterectomy for transitional cell carcinoma of the renal pelvis and/or proximal ureter. High grade upper urinary tract transitional cell carcinoma and a history of metachronous or synchronous bladder transitional cell carcinoma were independent adverse prognostic factors. However, patients with low grade upper urinary tract transitional cell carcinoma and no evidence of a urothelial field change had a 100 per cent 5-year survival rate. It would appear that parenchymal-sparing endoscopic techniques should be regarded with caution in patients with either high grade transitional cell carcinoma of the renal pelvis and proximal ureter or a history of bladder cancer.     

The impact factors on prognosis of patients with pT3 upper urinary tract transitional cell carcinoma

PURPOSE: Stage 3 upper urinary tract transitional cell carcinoma is a heterogeneous disease including different tumor locations (pelvis vs ureter) and invasion patterns (renal parenchyma, peripelvic fat and periureteral fat). Unfortunately the outcomes of patients with pT3 disease with different invasion pattern are largely unknown. This study presents the clinical outcome of patients with pT3 disease with upper urinary tract transitional cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients with pT3 disease with upper urinary tract transitional cell carcinoma. Four patient groups were classified according to tumor location and tumor invasion pattern. Prognostic factors including age, gender, tumor grade, tumor size, tumor number, tumor location and microscopic finding of vascular invasion were analyzed with respect to disease recurrence and survival. RESULTS: A total of 72 patients were included in this study. The most common complaint and tumor relapse pattern were painless gross hematuria and distant metastasis, respectively. Patients with pT3 disease with superficial parenchymal invasion had better disease-free and recurrence-free survival than the other 3 groups. Initial tumor location (p = 0.02) and vascular invasion (p = 0.02) were independent factors for disease-free survival, and vascular invasion (p = 0.001) was the only predictive factor for recurrence-free survival. CONCLUSIONS: The present study demonstrated that patients with pT3 disease with superficial parenchymal invasion should be considered to have lower stage disease, and that vascular involvement is the only independent prognostic factor for patients with pT3 disease for disease-free and recurrence-free survival. Systemic adjuvant therapy should be recommended for patients with pT3 disease with vascular involvement.     

Survival of patients with transitional cell carcinoma of the ureter and renal pelvis in Balkan endemic nephropathy and non-endemic areas of Serbia

OBJECTIVE: To evaluate the characteristics and survival of patients with upper urinary tract (UUT) transitional cell carcinoma (TCC) in Serbia, followed for >/=5 years or until death. PATIENTS AND METHODS: From 1998 to 2005 we analysed 114 cases of pathologically confirmed UUT TCC, divided into two groups according to topographical characteristics, and compared their demographic, clinical and pathological characteristics. The influence of various factors on overall 5-year survival of patients with UUT TCC was also tested. The prognostic value of different variables was assessed by univariate and multivariate Cox proportional-hazard models. RESULTS: The most important change in demographic characteristics of the patients with UUT TCC in Serbia was a similar proportion of patients residing in areas of Balkan endemic nephropathy (BEN) and non-endemic areas. The median (range) follow-up was 67 (46-88) months. The 5-year probability of survival was 51.2 +/- 5.8%. There was a significantly lower probability of 5-year survival for patients with a higher histological grade (P = 0.001), higher T stage (P < 0.001) and tumour size >3 cm (P = 0.001) at diagnosis. In this cohort of patients the independent predictors of a poorer outcome of the disease were being female (hazard ratio, HR, 2.2, P = 0.010), tumour size >3 cm (HR 2.8, P = 0.001) and T3 or T4 stages (HR 3.1, P = 0.001). CONCLUSION: Comparative analysis of the characteristics of UUT TCC between patients from BEN and non-endemic areas of Serbia showed similarities in demographic, clinical and pathological features. Factors that significantly influenced survival of patients with UUT TCC were being female, tumour size and tumour grade and stage.