The prognostic value of KI-67 proliferation index in transitional cell carcinoma of renal pelvis and ureter

The investigation deals with Ki-67 immunoreactivity assay in upper urinary tract transitional cell carcinoma (TCC) with respect to grade, stage and survival after radical surgery. In a retrospective study (5yrs) of 37 patients with TCC of the renal pelvis and ureter, who had undergone radical nephroureterectomy and bladder resection, pT1-pT4 lesions and G1-G3 tumors were identified. Ki-67 expression was evaluated by immunohistological staining (1:100; MIB-1; Immunotech. Inc., Westbrook, USA). By using fifteen x600 visual fields, Ki-67 labeling index (number of positive cells per 100 tumor cells) was found (mean +SD--29.7 +/- 9.22). There was a correlation between the index and tumor stage (p < 0.001) and grade (p = 0.002). The Ki-67 values in excess of 27 corresponded to high risk of bladder recurrence (p < 0.001) and short duration of recurrence development (p = 0.067) whereas, for the index of under 22, five-year progression-free survival was more frequent (p < 0.001). Having been tested in that study, discriminative modeling yielded the following parameters: sensitivity and specificity for bladder recurrence was 93% and 79% while for 5-year progression-free survival- 89% and 100%.     

Adjuvant radiotherapy in high stage transitional cell carcinoma of the renal pelvis and ureter.

This review was undertaken to assess the influence of adjuvant radiation therapy on failure patterns and survival in high stage transitional cell carcinoma of the renal pelvis or ureter. Ninety-four patients with transitional cell carcinoma of the renal pelvis or ureter were retrospectively reviewed. Twenty-six had American Joint Commission stage T3 or T4 N0/+, M0 disease and underwent curative resections (median follow-up 13.5 months, range 3-311). Local failure was defined as recurrence in the tumor bed, regional nodes, or ureteral stump. Time to recurrence and survival were calculated from the time of pathologic diagnosis. Variables associated with local failure, distant metastasis, and survival were analyzed using univariate and multivariate analysis. Seventeen received surgery only, nine received adjuvant radiation therapy (median dose 50 Gy). Local failure occurred in 9 of 17 without and 1 of 9 with adjuvant radiation therapy (p = 0.07). Actuarial 5-year local control was 34% without and 88% with adjuvant radiation therapy. Cox step-wise regression confirmed adjuvant radiation therapy (p = 0.006) and grade (p = 0.006) as significantly associated with local failure. No patients with low grade lesions suffered local failure either with or without adjuvant radiation therapy. High grade lesions had an local failure rate of 15% with and 71% without adjuvant radiation therapy. Metastatic disease occurred in 4 of 9 and 8 of 17 with and without radiation therapy. No significant factors influencing distant failure were identified. Five-year actuarial survival was 44% with and 24% without adjuvant radiation therapy. The survival differences were not statistically significant on univariate or multivariate analysis. High staged transitional cell carcinoma of the renal pelvis or ureter has a substantial local failure risk after surgery alone. Adjuvant radiation therapy markedly reduces this risk but has no impact on distant disease which occurs in approximately 50%. Effective adjuvant therapy will require effective systemic therapy in addition to adjuvant radiation therapy.     

组织蛋白酶D在肾盂输尿管移行细胞癌中表达的意义

目的：探讨组织蛋白酶D在上尿路移行细胞癌中表达的临床意义。方法：应用免疫组织化学ABC法，对组织蛋白酶D在43例肾盂、输尿管移行细胞癌中的表达进行检测。结果：肿瘤细胞阳性表达19例（44．2％）；间质细胞阳性表达14例（32．6％）。两表达与肿瘤分级、分期无显差异（P＞0．05）。间质细胞组织蛋白酶D阳性表达的患术后肿瘤复发明显高于阴性表达（P＜0．05），且5年生存期明显低于阴性表达（P＜0．05）。结论：上尿路移行细胞癌间质细胞组织蛋白酶D的检测，对术后肿瘤复发、生存期的判断具有一定的临床价值，可能用作判断预后的指标之一。     

局部晚期肾盂输尿管癌单纯手术与术后辅助放疗疗效比较

目的 比较肾盂输尿管癌单纯手术与术后辅助放疗的疗效。方法 回顾分析2005—2008年间 103例肾盂输尿管移行细胞癌患者的临床资料,37例行术后辅助三维适形放疗,66例单纯手术。局部控制率、生存率用Kaplan-Meier法计算并Logrank法检验及单因素分析,多因素分析采用Cox回归模型。结果 单纯手术组、术后放疗组随访率分别为89%、92%,其中随访满 5年者分别为33、17例。单纯手术组1、3、5年局部控制率分别为89%、74%、72%,术后放疗组分别为94%、90%、90%(χ²=3.90,P=0.048)。单纯手术组1、3、5年无膀胱癌发生率分别为87%、60%、57%,术后放疗组分别为94%、79%、79%(χ²=4.50,P=0.037)。单纯手术组1、3、5年总生存率为90%、71%、65%,术后放疗组分别为84%、65%、62%(χ²=0.32,P=0.573)。单因素和多因素分析均显示分期、淋巴结转移、手术断端阳性与总生存率相关(χ²=7.91、64.69、40.20和5.08、17.23、8.22,P=0.005、0.000、0.000和0.024、0.000、0.004)。结论 术后辅助三维适形放疗能提高肿瘤控制率,降低膀胱癌发生率,但在改善患者生存方面尚未现优势。     

不能手术肾癌及肾盂输尿管癌放疗效果分析

目的 回顾性分析不能手术治疗的肾癌及肾盂输尿管癌放疗结果。方法 2006—2015年间 29例无法行肾癌及肾盂输尿管癌手术患者实行了放疗,其中男 18例、女 11例,年龄 41~95岁(中位数 76岁);肾癌 17例,肾盂输尿管癌 12例;临床血尿 14例,腰背痛 7例。采用剂量递增放疗模式,其中伽马刀治疗 17例、HT治疗 12例。伽马刀50%等剂量线为处方剂量线,3~5 Gy/次,PTV边缘 40~50 Gy,GTV边缘 60~70 Gy。HT 50、60、70 Gy分 15~20次。结果 原发灶CR率为17%(5/29)、PR率为69%(20/29),总有效率(CR+PR)为86%。血尿消失93%,腰背痛消失100%。3、5年样本量分别为15、11例,肾癌和肾盂输尿管癌3、5年生存率分别为81%、81%和69%、69%。治疗期间1、2级消化系统反应 25例,1、2级骨髓抑制 20例,给予药物对症治疗后好转。结论 肾癌和肾盂输尿管癌伽马刀和HT安全有效切可提高LC和OS率,为不能手术肾癌和肾盂输尿管癌患者提供了有效治疗手段。     

肾盂移行上皮细胞癌CT诊断

目的探讨肾盂移行上皮细胞癌CT特点, 评价CT在肾盂移行上皮细胞癌诊断中的价值。方法 报告经手术病理证实的肾盂移行上皮细胞癌32例, 回顾性分析CT表现。结果 32例中15例见肾盂、肾盏内1.5cm-4.0cm大的结节状软组织肿块影, 肾窦脂肪受压、变薄, 但间隙存在;8例见肾盂、肾盏内直径4.1cm-9.0cm肿块, 累及肾门, 肾窦脂肪间隙消失;4例沿肾盂壁浸润性生长, 肾盂壁不规则增厚, 经肾门蔓延至输尿管上端, 肾盂、肾盏轻度扩张积水;5例肿块浸润肾实质, 并侵犯邻近组织, 形成密度不均的团块, 分不清肾盂、肾盏和肾实质, 肾门和腹膜后淋巴结增大。平扫:32例CT值33Hu-50Hu, 其中25例等密度, 4例略高密度, 3例略低密度;密度均匀21例, 密度不均匀11例;瘤内伴有小斑片状高密度出血灶5例, 小点状钙化5例, 坏死囊变3例。增强:CT增强扫描21例中13例于皮质期见肿块呈轻度均匀强化, 轻度不均匀强化8例;21例于实质期及肾盂期病灶强化程度均无明显增加, 与邻近增强肾实质相比, 肿瘤略呈低密度。32例中CT直接诊断肾盂癌21例, 提示肾盂癌可能7例, 误诊2例, 漏诊2例。结论 肾盂移行上皮细胞癌在CT平扫以等密度, 增强以轻度强化为主要征象, 在病灶的发现及定性, 螺旋CT具有较高价值。     

Cyclin-dependent kinase inhibitor p27(Kip1) expression in transitional cell carcinoma of renal pelvis and ureter

We examined the expression and significance of p27^Kip1 protein in 79 patients with transitional cell carcinoma of the renal pelvis and ureter. Immunohistochemical staining of archival tissue specimens was done using a labeled streptavidin–biotin–peroxidase method. There was no significant association between p27^Kip1 labeling index and histologic grade or pathologic stage. Patients with p27^Kip1 labeling indices of 27 or greater had more favorable prognoses in comparison to those with p27^kip1 labeling indices less than 27 (P<0.01). Multivariate analysis indicated that p27^Kip1 had an independent predictive prognostic value (P<0.05). The p27^Kip1 may be a novel prognostic marker for transitional cell carcinoma of the renal pelvis and ureter.     

Recurrent transitional cell carcinoma of the renal pelvis presenting as diabetes insipidus

We present the case of a 61-year old man with intracranial recurrence of transitional cell carcinoma of the renal pelvis presenting as diabetes insipidus. Metastatic infiltration of the pituitary stalk was demonstrated by magnetic resonance imaging when cerebral computerized tomography scanning was unhelpful. Successful treatment followed, comprising radiotherapy and intranasal desmopressin.     

Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma

BACKGROUND: To identify organ-specific, metastasis-related factors that can be used to predict the development and location of metastasis of clear cell renal cell carcinoma (CRCC), the authors assessed the angiogenesis and the expression of angiogenesis-related genes in primary and metastatic tumors. METHODS: They evaluated intratumoral microvessel density (MVD) by immunohistochemical staining, assessed the expression of angiogenesis-related genes by mRNA in situ hybridization, and determined the clinicopathologic characteristics of 92 archival specimens of primary and metastatic CRCCs from 54 patients. All 38 metastatic tumor specimens were resected from 24 patients. RESULTS: The pathologic stage (P=0.026) of the primary tumor specimen was an important predictor for metastasis, as were MVD (P=0.000025) and the ratio of matrix metalloproteinases (MMPs) to E-cadherin (M/E ratio; P=0.000041). In addition, primary tumor specimens resected from patients with metastatic CRCCs had high MVD, high levels of MMP-2 expression, and a high M/E ratio (P <0.05). Relative to the primary tumors, the metastatic tumors also had high MVD, overexpression of basic fibroblast growth factor, vascular endothelial growth factor, interleukin-8, MMPs, and a high M/E ratio (P <0.05). Multivariate analysis revealed that MVD and the M/E ratio in the primary tumor were independent prognostic factors for metastasis (P=0.049 and P=0.001, respectively). Furthermore, the M/E ratio in metastatic tumor specimens resected from the lung and lymph node was an independent prognostic factor for metastasis (P=0.01823 and P=0.03950, respectively). CONCLUSIONS: The current study indicated that angiogenesis and M/E ratio were specific predictors for metastases of RCC, especially to the lung or lymph node. Therefore, MMPs and E-cadherin could be relevant targets for novel therapeutic strategies to control or prevent the metastasis of RCC.     

原发性输尿管癌预后的临床病理因素回顾性分析

为了探讨输尿管癌临床病理因素对预后的影响,回顾性分析1995-01-2008-12接受手术治疗的原发输尿管癌51例患者的临床资料.在51例输尿管癌患者中,年龄(P=0.000)、临床分期(P=0.004)、组织学分级(P=0.000)及手术方式(P=0.048)与输尿管癌手术预后显著相关;性别(P=0.655)、肿瘤部位(P=0.245)及病理分级(P=0.092)与输尿管癌手术预后无关.临床分期中,浅表性输尿管癌(Ta～T1) 10例(19.6％),浸润性输尿管癌(T2～T4)41例(80.4％),Kaplan-Meier法分析显示,浸润性输尿管癌生存率明显低于表浅输尿管癌,P=0.002.多因素Cox回归模型生存分析结果表明,临床分期(P=0.021),组织学分级(P=0.001)、病理分级(P=0.048)及手术方式(P=0.039)是影响手术预后最显著的独立因素.初步研究结果提示,输尿管癌临床病理分级及手术方式与患者的生存相关,可作为患者的独立预后因素.     

基于TCGA数据库探究肾透明细胞癌关键基因的表达及预后作用

目的:探究肾透明细胞癌中关键基因的表达及预后作用,寻找潜在治疗靶点。方法:从TCGA数据库下载肾透明细胞癌mRNA的表达数据,通过Rstudio软件分析肿瘤与正常组织间差异表达基因,对差异表达基因进行富集分析、蛋白-蛋白相互作用网络构建,并分析出关键基因,最后对关键基因进行预后分析。结果:得到1 855个差异表达基因,其中有1 207个是上调的,648个是下调的,富集分析发现差异基因主要与信号转导、物质代谢、免疫反应等信号通路相关。筛选出10个关键基因中有6个存在预后价值。结论:筛选出的差异基因及信号通路可以帮助我们探索肾透明细胞癌发病的分子机制,同时为靶向治疗的研究提供潜在的理论依据。     

Argyrophilic nucleolar organiser regions in transitional cell bladder tumours related to established prognostic factors, progression and independent prognostic value.

Paraffin-embedded archival biopsy specimens from 229 primary transitional cell carcinomas (TCCs) were stained with silver nitrate to demonstrate the nucleolar organiser regions (Ag-NORs). T3-T4 high grade tumours had higher Ag-NOR counts/nucleus than low grade superficial papillary tumours (p less than 0.001). Non-papillary tumours showed more Ag-NORs than papillary ones (p less than 0.001). Aneuploid tumours with high S phase fraction had more Ag-NORs than diploid tumours (p less than 0.001) and mitotic frequency was also related significantly to Ag-NOR count (p less than 0.001). SD of nuclear area and nuclear area as measured by planar morphometry correlated significantly to Ag-NOR count (p less than 0.001). Close to 60% of the total number of Ag-NORs/nucleus can be related to other quantitative variables. Ag-NORs predicted independently survival in Ta-T1 tumours (p = 0.016) whereas in the whole series Ag-NORs had no independent prognostic value.     

Cigarette smoking and cancers of the renal pelvis and ureter.

A population-based case-control study of renal pelvis and ureter cancers (502 cases, 496 controls) conducted in three areas of the United States found cigarette smoking to be associated with a 3.1-fold increase in risk, with long-term (greater than 45 years) smokers having a 7.2-fold increased risk. Statistically significant dose-response associations were observed for both cancer sites and in both sexes regardless of the measure used: cigarettes per day, duration of use, or pack years. A significant decreasing trend in risk with increasing years quit smoking was also demonstrated for these cancers. Attributable risk estimates indicate that approximately 7 of 10 cancers of the renal pelvis and ureter among men and almost 4 of 10 among women are caused by smoking. The results of this study, the largest to date, confirm that cigarette smoking is the major cause of cancers of the renal pelvis and ureter, and that cessation of smoking could eliminate a large proportion of these tumors.     

血清IL-22在肾透明细胞癌患者预后分析中的应用价值

目的:研究IL-22在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）患者血清中的表达情况、临床意义及其在患者预后分析中的应用价值。方法:收集168例ccRCC患者的血清,同时以30例健康志愿者血清作为对照。采用ELISA法检测两组对象血清IL-22的表达水平。生存分析探讨IL-22表达水平与患者预后情况的关系。Cox比例风险模型分析影响患者生存时间的危险因素。结果:ccRCC患者血清中的IL-22水平明显高于健康志愿者。对ccRCC患者随访5~63个月,平均（45±12.4）个月,IL-22高水平组的无进展生存率及总体生存率明显低于低水平组。多因素分析结果表明,血清IL-22表达水平、肿瘤直径、肿瘤分化程度及肿瘤TNM分期是影响ccRCC患者生存期的独立危险因素。结论:ccRCC患者血清IL-22表达水平偏高,且IL-22高水平表达患者预后较差。血清IL-22表达水平在ccRCC患者的预后判断中具有较好的应用价值。