甲状腺癌根治术联合淋巴清扫对甲状腺癌患者骨密度及生活质量的影响

目的：探讨甲状腺癌根治术联合淋巴清扫对甲状腺癌患者骨密度及生活质量的影响。方法收集行甲状腺癌根治术与淋巴清扫患者76例,并按手术范围分为A、B、C 3组;检测患者血钙、血PTH,比较术前与术后变化;术后6个月随访,检测患者骨密度。结果术后3天A组与B组或C组比较,血钙和血PTH均下降,差异显著（P＜0．05）;B组与C组比较,血钙和血PTH差异不显著（P＞0．05）。术后6个月,3组患者血钙检测结果无显著差异（P＞0．05）;A组与B组、C组或者B组与C组比较,血PTH均存在显著差异（P＜0．05）。3组骨密度检测结果差异不显著（P＞0．05）。结论甲状腺癌根治术联合淋巴清扫可影响患者血PTH水平,对血钙及骨密度无显著影响。     

经尿道膀胱肿瘤电切术联合吡柔比星膀胱灌注治疗对浅表性膀胱癌患者预后及血清相关因子的影响

目的：探究经尿道膀胱肿瘤电切术（ TURBt）联合吡柔比星灌注治疗对浅表性膀胱癌患者的预后及对血清相关因子的影响。方法对120例浅表性膀胱癌患者按照入院时间顺序随机分为对照组与观察组,对照组接受单纯TURBt治疗,观察组接受TURBt联合吡柔比星灌注治疗。比较2组患者术后复发率、血清肿瘤相关因子、并发症。结果观察组术后1年复发率为5．0％,明显低于对照组,P＜0．05。观察组平均复发时间明显低于对照组,P＜0．05。观察组血清中VEGF、FGF、MMP-s水平均明显低于对照组,P＜0．05。2组患者术后并发症发生率无明显统计学差异,P＞0．05。结论 TRUBt联合吡柔比星灌注治疗浅表性膀胱癌可以降低术后复发率,同时改善恶性肿瘤相关血清因子水平,且无明显不良反应,值得临床推广。     

肺癌患者外周血细胞CD25、CD4表达和Apo水平的检测

目的：研究肺癌患者外周血细胞CD25、CD4表达规律和Apo水平。方法：采用流式细胞术对101例肺癌患者外周血细胞CD25^ 、CD3^ /CD4^ 表达率和Apo水平进行了检测。并分析了肿瘤转移状况和化疗对上述3项指标的影响。结果：肺癌患者外周血细胞CD25^ 和CD3^ /CD4^ 率均显著低于正常对照组（P＜0．01和P＜0．05）,Apo显著高于正常对照组（P＜0．01）。化疗者的3项指标均显著高于未化疗者（P＜0．01,P＜0．05和P＜0．05）;在未化疗患者中,有转移者和无转移者之间的CD25和CD3／CD4表达率差异均无显著性（P＞0．05）,而转移者的Apo却显著高于无转移者（P＜0．01）;在化疗患者中,转移者的Apo表达率显著高于无转移者（P＜0．01）,CD25^ 表达率低于无转移者（P＜0．05）,而D3^ /CD4^ 二者差异却无显著性（P＞0．05）。结论：肺癌能抑制患者外周血细胞CD25^ 和CD3^ /CD4^ 细胞进一步降低,但却引起Apo明显升高。化疗可以提高肿瘤患者CD25^ 、CD3^ /CD4^ 和Apo的检出率,使机体免疫功能能有所恢复。     

尿液中循环肿瘤DNA水平预测非肌层浸润性膀胱癌术后复发及进展的临床价值

目的:探讨尿液中循环肿瘤DNA（circulating tumour DNA,ctDNA）水平在非肌层浸润性膀胱癌（non-muscle-invasive bladder cancer,NMIBC）术后预测复发及进展中的临床价值。方法:选取2017年06月至2019年06月在我院收治的膀胱癌患者96例,均接受经尿道膀胱肿瘤电切术（transurethral resection of bladder tumor,TURBT）,且术后病检均证实为非肌层浸润性膀胱尿路上皮癌。根据术后病检结果分为两组:A组:高级别NMIBC患者46例,B组:低级别NMIBC患者50例。术后每个月测定患者尿液中ctDNA的水平,每3个月复查泌尿系彩超、膀胱镜及尿脱落细胞学检查,每6个月复查膀胱CT;所有患者术后均进行随访,随访期18个月,影像学或膀胱镜检查证实肿瘤临床复发或进展为肌层浸润性膀胱癌（muscle-invasive bladder cancer,MIBC）时即停止随访。结果:在随访期内共有62例患者通过膀胱镜检查或影像学手段证实肿瘤出现了复发或进展,其中A组有36例,B组有26例,两组间差异具有统计学意义（P＜0.05）;在肿瘤复发或进展的62例患者中,A组尿液ctDNA阳性患者27例,B组尿液ctDNA阳性患者21例,差异无统计学意义（P＞0.05）;两组共有63例患者在影像学及膀胱镜检查有异常之前首先从尿液中检测到了ctDNA,其中48例患者在之后的随诊复查中证实肿瘤出现了复发或进展;肿瘤进展组患者尿液中ctDNA水平显著高于复发组,差异具有统计学意义（P＜0.05）。结论:通过液态活检技术动态检测NMIBC术后患者尿液中ctDNA的水平,能更早地发现肿瘤的复发及进展,具有较高的特异性,而且与肿瘤进展存在一定的相关性,可能成为NMIBC术后辅助监测肿瘤早期复发或进展的新手段。     

应用定量PCR方法动态检测膀胱癌患者尿脱落细胞中survivin mRNA的表达及其临床意义

背景与目的：膀胱癌是泌尿系统最常见的恶性肿瘤,目前临床上缺乏理想的早期诊断方法。本研究通过检测膀胱移行细胞癌（bladder transitional cell carcinoma,BTCC）患者手术前后尿脱落细胞中survivinm RNA的表达,探讨其在BTCC患者早期诊断和术后监测肿瘤复发中的意义。方法：采用实时荧光定量PCR（real-time PCR）法检测10例健康志愿者、15例膀胱炎患者和30例初发BTCC患者术前及术后1周、1个月、6个月定期随访至15个月尿脱落细胞中survivin mRNA的表达情况。结果：30例BTCC患者术前尿脱落细胞中survivin mRNA的相对拷贝数为96．01±42．33。明显高于正常对照组及膀胱炎组（P〈0．05）。术后1周（25．30±1．51）较术前显著下降（P〈0．05）;术后1个月（13．20±1．49）、术后6个月（13．90±1．36）与正常对照组比较差异均无统计学意义（P〉0．05）;随访至15个月,3例复发患者复发时的相对拷贝数为97．83±27．47,与术后6个月相比差异有统计学意义（P〈0．05）。结论：尿脱落细胞中survivin mRNA的表达作为诊断膀胱移行细胞癌的指标敏感性高,术后动态随访survivin mRNA表达变化可监测复发。     

癌症患者尿激酶型纤溶酶原激活物及其受体检测的临床意义

目的：探讨癌症患者血浆中尿激酶型纤溶酶原激活物（u-PA)及其受体（u-PAR)检测的临床意义。方法：采用ELISA法测定85例癌症患者血浆中u-PA和u-PAP水平，并与正常人进行比较。结果：肝癌、肺癌、大肠癌、胰腺癌和胃癌患者的血浆u-PA和u-PAR水平均同步升高，与对照组比较有显著性差异（P＜0．05或P＜0．01）；胃癌和肺癌患者u-PA和u-PAR水平在术后出现明显回落（P＜0．05或P＜0．01）,复发时又升高；胰腺癌有转移者明显高于无转移者（P＜0．05）；鼻咽癌仅有u-PAR水平高于对照组（P＜0．01）。结论：癌症患者血浆u-PA和u-PAR水平显著异常，可作为评估浸润转移和复发的参考指标。     

TURBT术后联合化疗与根治性膀胱切除术治疗肌层浸润性膀胱癌的疗效对比研究

目的:分析对比经尿道膀胱肿瘤切除术（transurethral bladder tumor,TURBT）术后联合静脉化疗与根治性膀胱切除术治疗肌层浸润性膀胱癌的临床效果以及生活质量。方法:回顾性分析2014年07月至2017年03月我院肌层浸润性膀胱癌患者73例,其中TURBT术后行静脉化疗39例为观察组,行根治性膀胱切除术34例为对照组。观察对比两组围术期指标、术后并发症发生情况、术后随访2年内复发和生存情况以及患者术后生活质量评价。结果:观察组手术时间、术中出血量、住院时间均明显低于对照组,差异有统计学意义（P＜0.05）。观察组术后并发症总发生率为10.3%（4/39）;对照组术后并发症总发生率为32.4%（11/34）,两组比较差异有统计学意义（P＜0.05）。观察组和对照组术后3个月、6个月复发率比较无显著差异（P＞0.05）;12、24个月的复发率比较均有显著差异（P＜0.05）。两组患者术后12、24个月的无复发生存率比较均有显著差异（P＜0.05）;两组患者术后6个月、12个月总体生存率比较无显著差异（P＞0.05）,观察组术后24个月总体生存率显著高于对照组（P＜0.05）。观察组患者术后社会功能评分、心理功能评分、躯体功能评分均显著高于对照组（P＜0.05）。结论:TURBT术后联合静脉化疗治疗肌层浸润性膀胱癌效果显著,术后并发症少,恢复快,可以提高患者术后生活质量,适合临床长期推广应用。     

四君子汤对结肠癌术后患者胃肠恢复及免疫功能作用研究

目的：分析四君子汤对结肠癌术后患者胃肠功能恢复及免疫功能的影响。方法将结肠癌术后患者138例,随机分为对照组和实验组,对照组常规肠内营养,实验组在对照组基础上加用四君子汤,分析2组患者胃肠功能恢复及免疫功能情况。结果实验组患者腹胀发生率为14．5％,显著低于对照组（30．4％）,差异具统计学意义（P＜0．05）;实验组患者肠鸣音恢复时间和肛门排气时间显著低于对照组患者,差异具统计学意义（ P＜0．05）。实验组患者和对照组患者治疗后血清IgA、IgG、IgM水平均较治疗前明显提高,差异具统计学意义（ P＜0．05）;治疗后,实验组患者血清IgA、IgG、IgM水平较对照组提高更显著,差异具统计学意义（P＜0．05）。2组患者治疗后细胞免疫因子（C3＋、C4＋、CD3＋、CD4＋、CD8＋、CD4＋／CD8＋、IL-2、IL-8）值均较治疗前显著提高,差异具统计学意义（P＜0．05）;治疗后实验组患者细胞免疫因子水平较对照组提高明显,差异具统计学意义（P＜0．05）。结论加味四君子汤有利于结肠癌术后患者胃肠功能恢复,且可显著改善患者免疫功能,具积极作用。     

肾癌患者血清 VHL、HIF-1α和 HIF-2α的表达及临床意义

目的：探讨血清VHL,HIF-1α和HIF-2α的表达水平与肾癌临床病理特征的关系。方法收集肾癌患者43例（肾癌组）和同期健康查体者40例（对照组）;检测两组血清VHL,HIF-1α和HIF-2α水平;测定患者癌灶最大直径;对所有患者进行6个月随访。结果与对照组比较,肾癌患者血清VHL水平明显降低,而HIF-1α和HIF-2α水平明显升高（P＜0．01）;肾癌患者血清VHL、HIF-1α和HIF-2α表达与患者年龄、性别无明显相关（P＞0．05）,而与病理分级、临床分期、癌灶大小以及淋巴结转移显著相关（P＜0．01）;所有肾癌患者随访6个月,6例复发,37例未复发,复发组患者术后血清VHL水平明显低于未复发组,而HIF-1α和HIF-2α水平明显高于未复发组,比较差异均有统计学意义（ P＜0．05, P＜0．01）。结论血清VHL,HIF-1α和HIF-2α水平与肾癌病理分级、临床分期、癌灶大小以及淋巴结转移显著相关,提示上述指标可成为判定肾癌发生、发展以及复发的重要指标。     

中药方剂（乳癌术后方）治疗术后HE R－2阳性型乳腺癌90例临床观察

目的：探讨中药方剂（乳癌术后方）抗HER2阳性乳腺癌复发转移的临床疗效。方法：纳入HER2阳性乳腺癌术后患者90例,根据术后治疗方案的不同分为研究组与对照组。对照组给予常规西药治疗,研究组则在对照组治疗的基础上加入中药方剂口服。所有患者进行为期1年的临床随访,观察两组患者淋巴结转移情况。另外,采用中医症状疗效评定方法评价乳癌术后方抗HER2阳性乳腺癌复发转移的疗效。结果：两组患者在淋巴结转移率差异均无显著性（P＞0．05）。治疗前及治疗3个月,两组患者中医症候量化表评分差异无显著性（P＞0．05）。治疗后6个月、9个月、12个月,研究组中医症候量化表评分均明显低于对照组,差异有显著性（P＜0．05）。具体症状评分方面,两组患者治疗前神疲乏力、腰膝酸软、对侧乳房结块疼痛、质地、数目等差异均无显著性（P＞0．05）。研究组治疗后上述症状评分均明显低于对照组,差异具有显著性（P＜0．05）。结论：乳癌术后方不但可以有效改善HER2阳性乳腺癌患者术后神疲乏力、腰膝酸软等临床症状,同时还对对侧乳腺增生有着较好的治疗作用,有助于预防术后复发。     

The inverse relationship between bladder and liver in 4-aminobiphenyl-induced DNA damage

Bladder cancer risk is significantly higher in men than in women. 4-Aminobiphenyl (ABP) is a major human bladder carcinogen from tobacco smoke and other sources. In mice, male bladder is more susceptible to ABP-induced carcinogenesis than female bladder, but ABP is more carcinogenic in the livers of female mice than of male mice. Here, we show that castration causes male mice to acquire female phenotype regarding susceptibility of bladder and liver to ABP. However, spaying has little impact on organ susceptibility to ABP. Liver UDP-glucuronosyltransferases (UGTs) are believed to protect liver against but sensitize bladder to ABP, as glucuronidation of ABP and its metabolites generally reduces their toxicity and promotes their elimination via urine, but the metabolites are labile in urine, delivering carcinogenic species to the bladder. Indeed, liver expression of ABP-metabolizing human UGT1A3 transgene in mice increases bladder susceptibility to ABP. However, ABP-specific liver UGT activity is significantly higher in wild-type female mice than in their male counterparts, and castration also significantly increases ABP-specific UGT activity in the liver. Taken together, our data suggest that androgen increases bladder susceptibility to ABP via liver, likely by modulating an ABP-metabolizing liver enzyme, but exclude UGT as an important mediator.     

Infrequent Somatic Mutation of the MTS1 Gene in Primary Bladder Carcinomas

We examined a candidate tumor suppressor gene on chromosome 9p21, MTS1/CDK4I (multiple tumor suppressor 1/cyclin-dependent kinase 4 inhibitor), which has been found to be mutated frequently in cell lines derived from bladder carcinomas, for somatic mutations in 39 primary bladder cancers by means of SSCP (single-stranded conformational polymorphism) and DNA sequencing. Mutations were detected in two of these carcinomas; one was a 61-base deletion and the other a 1-base deletion. In both cases the homologous allele was missing, indicating that "two-hit"mutation of the MTS1 gene had taken place in these tumors. The results indicated that inactivation of the MTS1 gene is likely to be a contributing factor in some, but not the majority of, bladder cancers.     

The Evolving Landscape of Antibody–Drug Conjugates for Urothelial Carcinoma

Metastatic urothelial carcinoma (UC) carries a poor prognosis and a 5-year overall survival of less than 5%, despite standard of care therapy using cisplatin-based chemotherapy and immune checkpoint inhibitors. Thus, novel agents that improve survival and have an acceptable toxicity profile are urgently needed. Antibody–drug conjugates (ADCs) represent a promising new treatment option that utilizes the targeting ability of an antibody to deliver cytotoxic drugs directly to tumors. Many ADCs are currently being investigated for treatment of UC, with enfortumab vedotin being recently approved by the US Food and Drug Administration for treatment of metastatic UC with progressive disease after chemotherapy and/or immune checkpoint inhibitors. Overall, ADCs hold promise as a long-awaited treatment option for UC.     

Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells

Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.     

A population-based study of the use and outcome of radical radiotherapy for invasive bladder cancer

Purpose: The objective of this study is to describe the use and outcome of radical radiotherapy for bladder cancer in the province of Ontario, Canada, between 1982 and 1994.

Methods: Electronic records of invasive bladder cancer (ICD code 188) from the Ontario Cancer Registry were linked to surgical records from all Ontario hospitals and radiotherapy (RT) records from all Ontario cancer centers. We identified cases receiving radical RT by selecting RT records containing “bladder” or “pelvis” anatomic region codes and a radical or curative intent code (or dose > 39.5 Gy if intent missing). We identified cases receiving salvage total cystectomy by selecting total cystectomy procedure codes occurring at any time beyond 4 months from the start of radical RT. We used life table methods to compute the following: the time from diagnosis to radical RT, the time from radical RT to salvage cystectomy, overall and cause-specific survival from radical radiotherapy to death, and overall and cause-specific survival from salvage cystectomy to death. We modeled the factors associated with time to death, time to cystectomy conditional on survival, and time to cystectomy or death, whichever came first, using Cox proportional hazards regression.

Results: From the 20,906 new cases of bladder cancer diagnosed in Ontario from 1982 to 1994, we identified 1,372 cases treated by radical radiotherapy (78% male, 22% female; mean age 69.8 years). The median interval to start of radical RT from diagnosis was 13.4 weeks. Ninety-three percent of patients were treated on high-energy linacs, and the most common dose/fractionation scheme was 60 Gy/30 (31% of cases). Five-year survival rates were as follows: bladder cancer cause-specific, 41%; overall, 28%; cystectomy-free, 25%; bladder cancer cause-specific following salvage cystectomy, 36%; overall following salvage cystectomy, 28%. Factors associated with a higher risk of death and a poorer cystectomy-free survival were histology (squamous or nonpapillary transitional cell carcinoma [TCC]) and advanced age.

Conclusion: This population-based study confirms previous institutional studies and clinical trials and shows that radical RT has a curative role in the management of invasive bladder cancer and allows about one-quarter of patients receiving radiotherapy to survive 5 years while retaining the bladder. Salvage cystectomy following RT provides a chance of cure at the time of bladder relapse.     

Penetration of intravesical doxorubicin in human bladders

 The bladder wall penetration kinetics of intravesical doxorubicin were examined in radical cystectomy patients, to provide insight into drug concentrations at target tumor sites. The dosing solution (40 mg/20 ml) was instilled just prior to the start of surgery and maintained for 60–115 min until just prior to bladder excision. The data showed considerable inter-patient variability in the peak plasma concentration (24-fold), urine concentration (7-fold), and tissue concentration (28-fold). The urine concentration at the time of tissue harvest was about 17% of the concentration in the dosing solution. This was due to the dilution by post-catheterization residual urine and urine produced during treatment. The doxorubicin concentration dropped by 32-fold across the urothelium, and declined semi-logarithmically with respect to depth in the capillary-perfused tissues beneath the urothelium with a 50% decrease over about 500 μm. In three of six patients from whom tumor tissue was obtained, the doxorubicin concentration was higher than the adjacent non-tumor-bearing tissues of comparable tissue depth, whereas the reverse was seen in the remaining three tumors. The plasma concentrations were 0.02, 0.03, 0.05, 0.27, and 0.69% of the concentrations in the tumors, urothelium, lamina propria, superficial and deep muscle layers, respectively. These data indicate: (a) a considerable intra- and inter-patient variability in bladder tissue concentrations, in part due to the variability in the urine concentration; (b) the urothelium is an effective barrier to doxorubicin penetration; and (c) a targeting advantage of intravesical therapy for the treatment of superficial bladder cancer yielding superficial bladder tissue concentrations at least 2000-fold higher than in the systemic circulation. A comparison of the data of doxorubicin with our previously published data on mitomycin C shows similar bladder tissue pharmacokinetics for the two drugs, suggesting that there is no pharmacokinetic preference for either drug. Received: 8 November 1994/Accepted: 22 May 1995     

C-myc蛋白和增殖细胞核抗原在人膀胱癌组织中表达的意义

应用增殖细胞核抗原（PCNA）和C－myc单克隆抗体，以免疫组织化学方法检测正常膀胱组织和膀胱癌组织中Cmyc蛋白和PCNA的表达水平。结果表明：5例正常膀胱组织中未发现C－myc和PCNA阳性表达，阳性表达的C－myc和PCNA均定位于肿瘤的细胞核内。58例膀胱癌中C－myc和PCNA蛋白阳性表达分别为43．1％和62．1％，并且C－myc和PCNA阳性表达率与膀胱癌的病理分级、临床分期和患者术后生存率相关。提示C－myc和PCNA阳性表达与膀胱癌发生发展相关，并有可能成为评价膀胱癌预后的指标之一。     

猪苓多糖对膀胱癌细胞癌基因蛋白表达的影响

目的：分析猪苓多糖对体外培养T24膀胱癌细胞癌基因蛋白表达的影响。方法：应用免疫荧光法、激光共聚焦显徽镜对p53、H—ras基因蛋白表达进行定位、定量观察．结果：猪苓多糖显著增加p53蛋白表达，24小时表达最高，呈弥漫性分布，随后逐渐下降；对照组在24小时表达很弱，48小时表达最强。猪苓多糖对H—ras基因蛋白表达无明显影响。结论：猪苓多糖对T24细胞p53基因蛋白表达有一定的调节作用，对H-ras基因蛋白表达无明显影响。     

Results of bladder-conserving treatment, consisting of brachytherapy combined with limited surgery and external beam radiotherapy, for patients with solitary T1-T3 bladder tumors less than 5 cm in diameter

PURPOSE: To evaluate the long-term, local relapse-free, distant metastasis-free, and overall survival rates in patients with a solitary bladder tumor <5 cm in diameter who were treated with external beam radiotherapy, limited surgery, and brachytherapy. METHODS AND MATERIALS: The results of 122 patients after bladder-saving treatment were analyzed. After EBRT, the patients underwent cystotomy, and catheters were implanted. Of the 122 patients, 99 were treated with a continuous low-dose-rate technique and 23 patients with a pulsed-dose-rate technique. The median follow-up period was 5 years. RESULTS: The 5-year local and distant relapse-free survival rate was 76% and 83%, respectively. The 5 and 10-year relapse-free survival rate was 69% and 66%, respectively. For overall survival, the corresponding rates were 73% and 49%. Toxicity was low. No differences were found between the continuous low-dose-rate and pulsed-dose-rate groups. CONCLUSION: The results of our study have shown that external beam radiotherapy followed by brachytherapy as a bladder-saving treatment for a selected group of patients with bladder cancer yields excellent local tumor control and low toxicity.