上尿路移行上皮细胞癌根治术后复发膀胱肿瘤的高危因素分析

目的 探讨肿瘤部位与上尿路移行上皮细胞癌根治术后复发膀胱肿瘤风险的关系.方法 对行根治手术并获随访的168例上尿路移行上皮细胞癌患者的临床资料进行回顾性总结,比较不同部位上尿路移行上皮细胞癌根治术后复发膀胱肿瘤的风险,采用Cox回归分析术后复发膀胱肿瘤风险的独立影响因素.结果 168例患者术后1、3、5年的无复发膀胱肿瘤的生存率分别为88%、76%和63%.观察期内,共有49例术后发生膀胱肿瘤复发,中位首次复发时间为20个月.肾盂癌术后复发率为30.8%(28/91);输尿管中段癌术后复发率为8.3%(2/24),输尿管下段癌术后复发率为48.7%(19/39).肾盂癌与输尿管癌患者术后无复发膀胱肿瘤生存率比较差异无统计学意义(P>0.05).多因素分析结果显示输尿管下段癌为影响上尿路移行上皮细胞癌根治术后复发膀胱肿瘤风险的独立变量(P<0.01).结论 输尿管下段癌患者术后复发膀胱肿瘤的风险高于其他部位上尿路移行上皮细胞癌.

Abstract：

Objective To investigate the relationship between tumor location and the risk of developing bladder cancer in pafients treated by nephroureterectomy(NU)for upper urinary tract transitional cell carcinoma(UUT-TCC).Methods The clinical data of 168 UUT-TCC patients who underwent NU were reviewed.Univariate and multivariate analysis were carried out to determine the risk factors for intravesical recurrence after NU.Results The recurrence-free survival rate at 1,3 and 5 years after NU were 88%, 76%and 63%.All patients were followed up for a median period of 45(12-107)months During this period, a total of 49 patients developed bladder tamors after surgery,of which 28 cases were renal pelvic carcinoma, 2 cases were rniddle ureter carcinoma and 19 cases were distal ureter carcinoma.The recurrence-free survival of renal pelvic carcinoma and ureter carcinoma had no significant difference by Log-Rank test(P>0.05).On multivariate analysis,only locating in distal ureter carcinoma was the independent risk predictor for intravesical recurrence after NU (P<0.01).Conclusion Pafients with UUT-TCC at distal ureter carry a higher risk for intraeesieal recunerrce after NU than those with TCC at other location of upper urinary tract.     

胸苷酸合酶启动基因与膀胱移行细胞癌侵袭性关系的实验研究

目的研究胸苷酸合酶(TS)启动基因在膀胱移行细胞癌生长与进展中的作用。方法采用多聚酶链式反应(PCR)技术检测87例原发性膀胱移行细胞癌TS启动基因,用链霉菌抗生素蛋白-过氧化酶(SP)免疫组化检测TS蛋白表达,并计算其免疫反应评分(IRS)。结果膀胱移行细胞癌的TS IRS为(3.38±2.15)分。浸润性膀胱移行细胞癌的TS IRS明显高于表浅性膀胱移行细胞癌,且随膀胱移行细胞癌病理级别的增高而升高(P均<0.01)。膀胱移行细胞癌的TS启动基因表现为2R/2R、2R/3R和3R/3R 3种亚型,87例中三者分别为3,23和61例。浸润性和低分化(G3)膀胱移行细胞癌的TS启动基因多为3R/3R,分别高于表浅性及中高等分化的膀胱移行细胞癌(P均<0.05)。结论TS启动基因的串联重复序列数目与膀胱移行细胞癌的浸润深度及分级呈正相关,癌组织的TS启动基因可作为判断其预后的分子生物学指标之一。     

肿瘤微血管密度在膀胱移行细胞癌预后评估中的价值

目的　分析肿瘤微血管密度 (MVD)与膀胱移行细胞癌 (BTCC)预后的关系。方法　收集临床资料齐全的原发的膀胱移行细胞癌组织石蜡标本 6 7例 ,以正常膀胱黏膜上皮 10例作为对照 ,通过免疫组化方法用CD34 显示各级膀胱肿瘤的微血管改变并做计数测得微血管密度 ,并对相应患者的预后情况进行随访。结果　 (1)MVD与BTCC的临床分期、病理分级以及预后呈正相关。膀胱癌术后无瘤存活的 31例平均值为 138.2± 35 .9,发生复发或转移的 36例为 196 .6± 5 0 .2 ,差异显著。 (2 )经多因素分析筛选 ,MVD是BTCC的独立预后参数。 (3)对 6 7例BTCC组织标本另以微血管计数值 12 0、2 0 0为界值将相应 6 7例随访患者分为三组 ,以Kaplan -Meier生存曲线对比 ,三组间无瘤生存率差异显著。结论　MVD与BTCC分期、分级以及预后密切相关 ,可以为BTCC预后评估和临床诊治提供参考。     

Survivin mRNA在膀胱移行细胞癌中的表达及其与血管内皮生长因子相关性的研究

目的研究凋亡抑制基因survivin mRNA在膀胱移行细胞癌(TCC)中的表达和意义,以及与血管内皮生长因子(VEGF)蛋白表达的相关性,探讨survivin在TCC发生、发展和转移中的作用及机制。方法分别对45例TCC组织、34例相应的癌旁组织和10例正常膀胱组织,采用逆转录聚合酶链反应(RT-PCR)检测survivin mRNA的表达,免疫蛋白印迹(W estern B lotting)法检测VEGF蛋白的表达。结果Survivin mRNA和VEGF蛋白在45例TCC组织中的阳性表达率分别为71.11%和66.67%,均显著高于癌旁组织(8.82%和5.88%)(P<0.05),而在正常膀胱组织均无表达。TCC组织中survivin mRNA的表达与肿瘤的淋巴转移密切相关,与病理分级有一定关系(P<0.05);而与患者性别、年龄、临床分期、肿瘤直径和肿瘤发生情况等均无相关性。相关性检验表明survivin与VEGF表达呈正相关(χ2=4.881,r=0.32,P<0.05)。结论Survivin mRNA在TCC组织中的高表达提示其可能参与TCC的发生和发展;survivin和VEGF的表达密切相关,推测survivin可能通过上调VEGF的表达而促进TCC的转移。     

Cancer risk due to occupational exposure to polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) demonstrate carcinogenic activity in animal models. Although some epidemiologic studies have implicated PAHs as risk factors for human cancer, the evidence reported to date has not been consistent. The purpose of this report is to describe the associations between occupational exposure to PAHs in the workplace and each of 14 types of cancer. A population-based, case-control study was carried out in Montreal to investigate associations between a large variety of environmental and occupational exposures on the one hand, and several types of cancer on the other. A detailed job history was obtained from each subject along with information on a number of potential confounders. Each job history was reviewed by a team of experts, who used this information to construct a corresponding history of occupational exposures. Among the PAH exposures considered were benzo(a)pyrene (B(a)P) and five categories of PAHs defined on the basis of the source material, namely, wood, petroleum, coal, other sources, and any source. Altogether, 3,730 cancer patients and 533 population controls were interviewed and their job exposure histories coded. For each of 14 types of cancer analyzed, three control groups were available: other cancer patients, population controls, and the pooled set of cancer and population controls. The associations between 14 cancer types and 6 PAH exposures were analyzed using logistic regression methods. For most types of cancer evaluated, there was no evidence of excess risk due to PAHs at the levels encountered in the occupations in which PAH exposure has been prevalent in the Montreal area. For a few cancer sites–the esophagus, the pancreas, and the prostate gland–there were suggestions of excess risk; these observations are noteworthy hypotheses for further investigation. For lung cancer, there appeared to be an increased risk due to PAHs among nonsmokers and light smokers, but not among heavy smokers.     

Bmi-1和p16基因在膀胱移行细胞癌中的表达及临床意义

目的 检测Bmi-1和p16基因在膀胱移行细胞癌组织中的表达,并探讨其临床意义.方法 采用实时荧光反转录定量聚合酶链反应方法检测61例膀胱移行细胞癌组织和12例正常膀胱组织中Bmi-1和p16基因的表达情况.结果 膀胱移行细胞癌组织中Bmi-1表达量显著高于正常膀胱组织（0.242±0.129比0.031±0.011）,而p16表达量显著低于正常膀胱组织（0.059±0.021比0.165±0.029）,差异均有统计学意义（P＜0.05）.Bmi-1和p16基因的表达量与病理分级、临床分期、肿瘤复发有相关性（P＜ 0.05或＜0.01）,而与年龄、性别无相关性（P＞0.05）.在膀胱移行细胞癌组织中p16基因的表达量与Bmi-1基因的表达量呈负相关（rs=-0.714,P＜0.05）.结论 Bmi-1基因的高表达和p16基因的低表达可能参与了膀胱移行细胞癌的发生和发展过程,Bmi-1可能通过某种机制下调p16的表达,从而促进膀胱移行细胞癌的发生和发展.     

Inhalation and dietary exposure to polycyclic aromatic hydrocarbons and urinary 1-hydroxypyrene in non-smoking university students

Objective To examine which exposure pathway, dietary or inhalation, contribute more to the exposure to, and/or internal dose of, polycyclic aromatic hydrocarbons (PAHs) of non-smoking Japanese. Methods Duplicated diet, personal air samples and 24-h urine were collected from14 non-smoking male university students without occupational exposure and the concentrations of PAHs in diet and air and that of 1-hydroxypyrene (1-OHP) in urine were measured with HPLC-fluorescence detector. Results Daily dietary exposure contributed more than 90% of the total (diet + inhalation) daily exposure level for pyrene (diet/inhalation: 757/1.2 ng/day), benzo[k]fluoranthene (25/1.7 ng/day) and benzo[a]pyrene (91/2.1 ng/day). Urinary excretion of 1-OHP (median: 37 ng/day) was statistically significantly correlated only with dietary PAHs exposure level but not with inhalation. Conclusion Countermeasures to lower PAHs levels in atmosphere has been successful in Japan and more attention should be directed to dietary exposure to PAHs for reducing cancer risk in general population.     

职业多环芳烃暴露人群尿中生物标志物浓度水平

多环芳烃类化学物质因为其被熟知的致癌性而一直备受关注, 近来越来越多的学者意识到单一的接触生物标志物并不能完全代表暴露者体内的暴露水平。本研究就1999年以后15年间报道的职业环境中接触多环芳烃类物质的工人尿中接触生物标志物进行综述, 重点对其浓度水平进行描述, 为职业环境中多环芳烃类化学物质暴露的生物学检测提供理论依据。     

膀胱尿路上皮癌中PTEN、MDM2的表达及其相关性研究

目的 初步探讨膀胱尿路上皮癌中PTEN、MDM2的表达及其临床意义.方法 应用SP免疫组织化学染色法对80例膀胱尿路上皮癌及20例正常膀胱黏膜组织中PTEN、MDM2基因的表达进行检测,结合临床病理因素进行分析.结果 PTEN在不同病理分级(G1、G2、G3)和临床分期[浅表型(Tis～ T1)、浸润型(T2～T4)]的膀胱尿路上皮癌中的阳性率(86.20％、74.07％、37.50％;80.00％、46.67％)比较差异均有统计学意义(x2=15.004,P＜0.01;x2 =9.497,P＜0.01);MDM2在不同病理分级(G1、G2、G3)和临床分期[浅表型(Tis～T1)、浸润型(T2～T4)]的膀胱尿路上皮癌中的阳性率(82.75％、55.55％、37.50％;70.00％、43.35％)比较差异均有统计学意义(x2=11.543,P ＜0.01;x2 =5.556,P＜0.05);PTEN和MDM2在膀胱尿路上皮癌中的表达呈负相关(r=-0.611,P＜0.05).结论 PTEN和MDM2的异常表达在膀胱尿路上皮癌的发生发展中起重要作用,联合检测对于判断膀胱尿路上皮癌的恶性程度和预后有重要意义.