HE4在上皮性卵巢癌中的表达情况及其与临床特征及预后的关系分析

目的 探讨HE4在上皮性卵巢癌中的表达情况及其与临床特征及预后的关系.方法 选取150例上皮性卵巢癌患者和72例良性卵巢疾病患者,采用酶联免疫吸附法(ELISA)检测并比较150例上皮性卵巢癌患者和72例良性卵巢疾病患者的血清HE4水平;采用免疫组织化学法(IHC)检测150例上皮性卵巢癌患者癌组织和相应癌旁正常组织中HE4的表达情况,分析其与上皮性卵巢癌临床特征的关系;随访36个月,记录并分析HE4表达与上皮性卵巢癌患者生存情况的关系.结果 上皮性卵巢癌患者的血清HE4水平明显高于良性卵巢疾病患者,上皮性卵巢癌组织中HE4蛋白的阳性表达率明显高于癌旁正常组织,差异均有统计学意义(P﹤0.01);肿瘤直径﹥3 cm、低分化、Ⅲ～Ⅳ期、有淋巴结转移的上皮性卵巢癌组织的HE4蛋白的阳性表达率分别高于肿瘤直径≤3 cm、中高分化、Ⅰ～Ⅱ期、无淋巴结转移的癌组织,差异均有统计学意义(P﹤0.05);随访36个月,HE4蛋白阳性表达的上皮性卵巢癌患者的生存率低于阴性表达的患者,差异有统计学意义(P﹤0.05).结论 HE4是上皮性卵巢癌的良好肿瘤标志物,与肿瘤的良、恶性鉴别及临床特征有密切的关系,对上皮性卵巢癌患者的早期诊断及预后有一定的价值.     

上皮性卵巢癌预后因素的研究进展

卵巢癌是女性生殖系统中最常见的肿瘤之一,其中上皮性卵巢癌是卵巢癌最常见的病理类型。约70%的上皮性卵巢癌患者被诊断时已经是晚期,因此早发现、早诊断、早治疗是提高上皮性卵巢癌患者生存率的重要方法之一。上皮性卵巢癌的标准治疗方式为细胞瘤减灭术及铂类为主的化疗,但是随着肿瘤细胞对化疗产生耐药性大多数患者在医治后容易复发,患者存活率一般都很低并且疾病很难控制。近年来,对上皮性卵巢癌发病的分子机制的研究不断进展,发现了更多影响上皮性卵巢癌预后的因素,并且可作为潜在的治疗靶点提高患者生存率。     

Twist在上皮性卵巢癌组织中的表达及与临床预后的关系

目的:观察Twist在上皮性卵巢癌组织中的表达情况，分析Twist 阳性表达与上皮性卵巢癌患者铂类耐药、无病生存期的关系。方法:回顾性分析 2011年至2016年西京医院妇科121例手术患者，对其术后石蜡组织标本进行免疫组化染色，分析Twist在正常卵巢组织、肿瘤组织中的表达，在耐药、敏感组中的表达和相关性分析及其与预后的关系。结果:Twist阳性表达率在正常卵巢组织与肿瘤组织中分别为40.00%、60.40%， 其差异有统计学意义(P<0.05)。耐药及敏感组中的上皮性卵巢癌患者中Twist阳性表达率分别为80.00%、52.11%，差异有统计学意义（P<0.05)。上皮性卵巢癌患者中，Twist表达水平越高，患者生存率越低。单因素分析显示:肿瘤复发、FIGO分期、淋巴结转移、铂反应及Twist高表达为影响上皮性卵巢癌患者预后的危险因素；多因素分析显示:复发为上皮性卵巢癌患者的独立预后因素。结论:Twist在上皮性卵巢癌组织中的表达明显高于正常组织，在耐药组的表达明显高于敏感组，但与患者平均无病生存期及总生存期的长短是否也存在统计学差异有待进一步研究。     

影响上皮性卵巢癌术后复发的相关危险因素

目的:探讨影响上皮性卵巢癌术后复发的危险因素。方法:对近年来我院收治的上皮性卵巢癌患者171例进行回顾性分析,其中随访资料完整者91例为研究对象。91例患者中,术后复发33例为复发组,随访未复发的58例为对照组,比较两组患者临床特征、手术情况、病理类型及术后治疗方案有无差别,并采用Logistic回归方法对影响术后复发的独立危险因素进行分析。结果:单因素分析显示:临床分期(P=0.00)、病理类型(P=0.03)、腹水肿瘤细胞阳性(P=0.02)和术后化疗大于4个周期(P=0.03)与上皮性卵巢癌患者术后复发有关。Logistic回归分析显示晚期 (Ⅲ/Ⅳ)(OR=4.22,P=0.01)和腹水肿瘤细胞阳性(OR=2.81,P=0.03)是影响上皮性卵巢癌术后复发的独立危险因素。结论:腹水中肿瘤细胞阳性的晚期上皮性卵巢癌患者是术后复发的高危人群,应加强术后辅助治疗,降低复发风险。     

早期上皮性卵巢癌术后辅助化疗及疗程对其预后的影响

早期上皮性卵巢癌经规范化治疗后5年生存率能达90%左右，但当肿瘤复发时预后很差。因此，早期上皮性卵巢癌患者初次是否行规范化治疗与其预后密切相关。目前，对于早期上皮性卵巢癌术后是否化疗以及化疗多少周期等问题，尚存很大争议，本文将对相关问题的研究进展进行综述。     

肿瘤负荷在上皮性卵巢癌中的研究进展

摘 要：肿瘤负荷泛指肿瘤细胞的数量、肿瘤大小或体内病灶的数量，其评估形式多样，在预测药物疗效及疾病预后方面有重要意义。在上皮性卵巢癌的发生、发展过程中，监测肿瘤负荷对评估其疗效及预后有重要意义。关于肿瘤负荷的评估在上皮性卵巢癌患者治疗选择方面已有大量研究，同时也为上皮性卵巢癌患者的预后预测带来了希望。全文就肿瘤负荷应用于预测上皮性卵巢癌疗效及预后的研究进展进行综述。     

前列腺癌根治术后复发的诊断和治疗

临床局限型前列腺癌患者在接受根治术后有一部分会发生生化复发，生化复发是肿瘤继续进展并发生临床复发或转移的前兆。术后随访中检出生化复发患者，进行恰当的评估，可以筛选出高危患者接受进一步治疗。挽救性放疗和内分泌治疗对前列腺癌根治术后复发或转移的患者有一定的疗效。本文综述了前列腺癌根治术后复发和转移的诊断方法和治疗选择的进展。     

肿瘤细胞减灭术联合洛铂腹腔灌注化疗治疗ⅢC期上皮性卵巢癌的疗效及对患者血清肿瘤标志物的影响

目的 探讨肿瘤细胞减灭术联合洛铂腹腔灌注化疗治疗ⅢC期上皮性卵巢癌的疗效及对患者血清肿瘤标志物的影响.方法 依据治疗方法的不同将80例上皮性卵巢癌患者分为观察组(n=46)和对照组(n=34),对照组患者给予肿瘤细胞减灭术治疗,观察组患者给予肿瘤细胞减灭术联合洛铂腹腔灌注化疗.比较两组患者的近期疗效、肿瘤标志物[血管内皮生长因子(VEGF)、人附睾上皮分泌蛋白4(HE4)]水平、不良反应发生情况和随访1～3年生存率.结果 观察组患者的治疗总有效率为80.43％,高于对照组的55.88％(P﹤0.05).治疗后,两组患者血清VEGF、HE4水平均低于本组治疗前(P﹤0.05),且观察组患者血清VEGF、HE4水平均低于对照组(P﹤0.05).两组患者1年生存率无明显差异(P﹥0.05);随访2、3年,观察组患者的生存率均高于对照组(P﹤0.05).两组患者肝脏损伤、骨髓抑制、心脏毒性及恶心呕吐发生率均无明显差异(P﹥0.05).结论 肿瘤细胞减灭术联合洛铂腹腔灌注化疗治疗ⅢC期上皮性卵巢癌患者的疗效显著,可有效提高生存率,且不增加术中不良反应.     

多肿瘤标志物联合检测在妇科恶性肿瘤临床治疗中的应用研究

目的探讨多肿瘤标志物联合检测在妇科恶性肿瘤治疗过程中的应用价值。方法采用多肿瘤标志物蛋白质芯片系统（C-12），检测了35例卵巢癌、38例宫颈癌和26例绒癌患者治疗前及治疗1个月后的血清肿瘤标志物含量，以肿瘤标志物含量的变化来评估治疗措施。结果治疗1个月后多数患者体内肿瘤标志物含量降至正常范围，但仍有40．1％的卵巢癌、34．2％的宫颈癌、23．1％的绒癌患者治疗后呈阳性，说明部分患者临床疗效不明显，建议改善治疗措施。结论肿瘤标志物联合检测对妇科恶性肿瘤卵巢癌、宫颈癌、绒癌具有高度敏感性，监测治疗前后患者体内的肿瘤标志物含量，对指导临床治疗妇科恶性肿瘤有很大的应用价值。     

上皮性卵巢癌多药耐药相关信号传导通路及其靶向药物研究进展*

卵巢癌是严重威胁女性生殖健康的肿瘤之一,死亡率居各类妇科肿瘤的首位。上皮性癌是卵巢癌中最常见的病理类型,近年来虽然手术及放化疗技术不断提高,但75% ～80% 晚期患者在治疗后仍出现复发或进展。多药耐药是导致上皮性卵巢癌治疗后复发、转移和死亡的重要原因,严重制约上皮性卵巢癌患者生存率的提高。信号传导通路是多药耐药的重要调控机制之一,目前对其作用机制的研究取得了一定进展,其靶向药物亦在临床各期试验获得了良好效果。本文拟对信号传导通路在上皮性卵巢癌多药耐药机制及目前相关靶向药物在临床研究进展进行综述,为其进一步在临床应用提供指导价值。      

Tests for detecting recurrent disease in the follow-up of patients with breast cancer

In 141 postmenopausal node-positive patients with primary breast cancer, routine biochemical markers (alkaline phosphatase, gamma-glutamyl transpeptidase, carcinoembryonic antigen), and chest x-ray, in combination with history and clinical examination, have been performed at 3 monthly intervals for at least 2 years. Sixty one patients relapsed at a median time of 14 months. The recurrence was detected at routine follow-up in 40 (66%) patients. Of these 40 patients, 26 (65%) presented with symptoms, 11 (28%) were asymptomatic but were found to have relapsed on clinical examination, and only 3 (8%) had their relapse diagnosed on the basis of an abnormal chest x-ray. The remaining 21 patients presented early with symptoms. Therefore symptoms and clinical examination accounted for the detection of relapse in 58 of the 61 (95%) patients. Of the patients who had relapsed, 49% (30 of 61) had one or more abnormal markers/chest x-rays prior to relapse, rising to 79% (48 of 61) at the time of relapse. Of 80 patients with no evidence of recurrence, 36% (29) had no marker abnormality recorded, whereas in 64% (51) one or more abnormalities were found. These results suggest that history and examination are the important procedures in follow-up, and that abnormal markers are not always due to metastatic disease and may be misleading.     

影响复发上皮卵巢癌手术疗效的临床病理因素分析

  目的  分析影响复发卵巢上皮癌手术疗效的相关临床病理因素。   方法  采用Logistic回归方法进行分析, 并通过多因素Logistic逐步回归分析对接受手术治疗60例复发卵巢上皮性癌患者进行影响手术疗效的临床病理因素相关分析。   结果   1) 60例复发卵巢上皮癌术后平均中位生存时间为26个月(95%CI: 1 8.302~33.698), 其中肿瘤细胞减灭术满意者(残留灶≤2 cm)中位生存时间为28个月(95%CI: 25.043~30.957), 不满意者为16个月(95%CI: 13.184~18.816, P=0.002)。2)Logistic回归单因素分析显示复发数目、复发时伴有腹水、复发部位是影响手术满意效果的因素(P < 0.05);而年龄、初次手术情况、病理类型、细胞学分级、手术病理分期、初次化疗方案、复发距离末次化疗时间、复发CA125水平、最大复发病灶直径大小、术前先期化疗对手术效果无明显影响(P > 0.05)。3)Logistic逐步回归分析显示复发病灶个数、复发部位、复发后伴有腹水、年龄是影响手术满意度的主要因素。   结论  多个临床病理因素影响复发卵巢上皮癌手术疗效, 其中复发病灶个数、复发部位、复发后伴有腹水、年龄是影响手术满意度的主要因素。      

Routine chest X-rays have no additional value in the detection of relapse during routine follow-up of patients treated with chemotherapy for disseminated non-seminomatous testicular cancer.

BACKGROUND: The routine follow-up of patients with disseminated non-seminomatous testicular cancer (DNSTC) treated with the combination of orchidectomy, polychemotherapy, and if needed, resection of the residual mass, consists of regular physical examinations, chest X-rays (CXR) and tumor marker assessments. Most guidelines for this routine follow-up originate from multi-center trials. In order to estimate the value of CXR in the detection of tumor relapse after complete remission, we reviewed all patients with disseminated testicular cancer treated with chemotherapy at the University Hospital Groningen. PATIENTS AND METHODS: Three hundred and fifty-three consecutive patients with DNSTC treated between February 1977 and February 1999 at our institution were reviewed. Two hundred and ninety (82.2%) patients, who were in complete remission after cisplatin-containing chemotherapy followed by, if necessary, resection of the residual mass, entered this analysis. The follow-up schedule consisted of regular physical examinations, tumor marker assessment (lactate dehydrogenase, beta-human chorionic gonadotropin and alpha-FP) and CXR. In all patients the first diagnostic sign of tumor relapse was documented. RESULTS: During a median follow-up of 107 months (range 8-261) a tumor relapse was documented in 33 patients (11.4%). Median time to relapse was 17 months (range 6-179) after the start of chemotherapy. In 27 patients, tumor relapse was first detected by a rise in tumor markers. Two patients presented their relapse with neurological complaints. Both were diagnosed with brain metastasis. In four patients the relapse was detected by both increase in tumor markers and abnormalities in the physical examination. In none of the 33 relapsed patients was routine CXR during follow-up involved in the detection of tumor recurrence. All but one of the relapsed patients had elevated tumor markers before the start of chemotherapy. The total number of CXR made during follow-up in all 290 patients was 10 160; none were diagnostic for the detected relapses. CONCLUSIONS: These data suggest that routine CXR has no additional value in the detection of tumor relapses during follow-up after chemotherapy in the subset of patients who present their DNSTC with increased tumor markers and are in complete remission after treatment. In order to save valuable resources, CXR can be omitted from the follow-up schedule after chemotherapy for marker-positive non-seminomatous testicular cancer in complete remission.     

上皮性卵巢癌患者术前外周血中性粒细胞/淋巴细胞比值在诊断及复发预测中的作用

目的:评价上皮性卵巢癌患者术前外周血中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)在诊断及预测复发中的应用价值.方法:回顾性分析在青岛大学附属医院2003年1月至2011年1月收治的147例良性卵巢肿瘤和134例上皮性卵巢癌(epithelial ovarian cancer,EOC)患者的临床病理资料,通过受试者工作特征曲线确定术前外周血NLR诊断EOC的价值并选取最佳截断值;通过单因素及多因素分析寻找患者5年内复发的高危因素.结果:患者术前NLR对诊断EOC最佳截断值为2.04.术前NLR＜2.04组与NLR≥2.04组患者在年龄、FIGO分期、CA125水平、腹水及淋巴结转移等方面均有明显差异(P＜0.05),而与不同病理类型和分化程度无明显差异(P＞0.05).单或多因素分析结果显示,术前NLR≥2.04为EOC患者术后5年内复发的危险因素(P＜0.05).结论:EOC患者术前NLR升高与癌症的存在及多种临床侵袭性指标相关,是影响EOC患者术后复发的独立危险因素.     

影响上皮性卵巢癌复发患者预后相关临床病理因素分析

目的分析影响上皮性卵巢癌(epithelial ovarian cancer,EOC)复发患者预后的相关临床病理因素。方法采用Kaplan-meier生存率曲线,Log rank检验和Cox模型多因素回归分析法对92例临床病理及随访资料完整的复发癌患者进行影响其预后的相关因素分析。结果(1)92例复发上皮性卵巢癌临床病例的总体中位生存时间是18月(95%CI:16.052~19.948);(2) Kaplan-Meier单因素分析提示,FIGO分期、复发距离末次化疗时间、复发部位、最大复发病灶、复发后伴有腹水、CA125升高、复发后二次肿瘤细胞减灭术、再次治疗化疗方案是影响复发EOC患者的重要预后因素(P<0.1)。而年龄、肿瘤细胞分级、初次治疗方案与预后无关(P>0.1);(3)Cox回归分析结果显独示,复发后再次治疗化疗方案、最大复发病灶大小、复发部位是影响患者预后的独立危险因素。结论 多个临床病理因素影响复发上皮性卵巢癌预后,其中复发后再次治疗化疗方案、最大复发病灶大小、复发部位是影响患者预后的独立危险因素。     

A prognostic regulatory pathway in stage I epithelial ovarian cancer: new hints for the poor prognosis assessment

BackgroundClinical and pathological parameters of patients with epithelial ovarian cancer (EOC) do not thoroughly predict patients' outcome. Despite the good outcome of stage I EOC compared with that of stages III and IV, the risk assessment and treatments are almost the same. However, only 20% of stage I EOC cases relapse and die, meaning that only a proportion of patients need intensive treatment and closer follow-up. Thus, the identification of cell mechanisms that could improve outcome prediction and rationalize therapeutic options is an urgent need in the clinical practice.Patients and methodsWe have gathered together 203 patients with stage I EOC diagnosis, from whom snap-frozen tumor biopsies were available at the time of primary surgery before any treatment. Patients, with a median follow-up of 7 years, were stratified into a training set and a validation set.Results and conclusionsIntegrated analysis of miRNA and gene expression profiles allowed to identify a prognostic cell pathway, composed of 16 miRNAs and 10 genes, wiring the cell cycle, ‘Activins/Inhibins’ and ‘Hedgehog’ signaling pathways. Once validated by an independent technique, all the elements of the circuit resulted associated with overall survival (OS) and progression-free survival (PFS), in both univariate and multivariate models. For each patient, the circuit expressions have been translated into an activation state index (integrated signature classifier, ISC), used to stratify patients into classes of risk. This prediction reaches the 89.7% of sensitivity and 96.6% of specificity for the detection of PFS events. The prognostic value was then confirmed in the external independent validation set in which the PFS events are predicted with 75% sensitivity and 94.7% specificity. Moreover, the ISC shows higher classification performance than conventional clinical classifiers. Thus, the identified circuit enhances the understanding of the molecular mechanisms lagging behind stage I EOC and the ISC improves our capabilities to assess, at the time of diagnosis, the patient risk of relapse.     

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。     

上皮性卵巢癌术后复发的相关影响因素分析

目的 分析上皮性卵巢癌(EOC)术后复发的相关影响因素.方法 选择124例EOC患者作为研究对象,入选患者均行手术及化疗治疗,并进行长期随访.根据5年随访结果将患者分为复发组(51例)和未复发组(73例).采用单因素和多因素Logistic回归分析EOC术后复发的相关影响因素.结果 两组年龄、分娩次数、组组织学类型、有...     

Potential biologic markers in Burkitt's lymphoma.

Specific biochemical molecules used as potential biologic markers, including modified nucleosides, polyamines, and pyrimidine catabolic end-products, were quantitatively measured in the urine of seven patients with Burkitt's lymphoma before, during, and after one or more courses of therapy. The results of this preliminary study demonstrated that patients with this disease frequently excrete significantly increased amounts oof modified nuceleosides (considered to be derived primarily from transfer ribonucleic acid), polyamines, and beta-aminoisobutyric acid during the course of their disease. With successful treatment and rapid destruction of tumor cells, a concomitant rise in these molecules occurs. Elevations were observed prior to chemotherapy and changes in levels associated with treatment or tumor progression appeared to correlate with disease status and to aid in assessing antitumor response. Periodic follow-up analysis of these molecules may be helfful in appraising relapse or recurrence of the malignancy prior to overt evidence of tumor by existing clincial means.     

Benefit and costs of follow-up programs in nonseminomatous germ cell tumors of the stages IIb-IV: the Munich experience

Since 1979 we have seen 197 patients with nonseminomatous germ cell tumors (NSGCT) of the stages IIb-IV. 185 of these are evaluable (3 lost to follow-up, 9 still in treatment). The majority of the patients was given platinum-vinblastine-bleomycin treatment (PVB). 138/185 (74.6%) have achieved a first complete remission (CR), and 131/185 (70.8%) are currently found with no evidence of disease (NED). All patients in CR have been followed by physical examinations, blood chemistry including tumor markers, and chest X ray (years 1 and 2: 8 times; year 3: twice; years 4 and 5: twice) and by abdominal computer tomography (CT; years 1 and 2: 6 times; year 3: twice; years 4 and 5: twice). So far this follow-up procedure has been performed for a total of 326 patient years costing approximately $215,000. 18/138 patients (13%) were found in the first relapse. 13/18 could achieve a 2nd CR under salvage therapy. 2 of these patients were found in a 2nd relapse and 1 of these was brought into a third CR. 1 patient died in CR from reasons unrelated to NSGCT. The 20 first and second relapses were detected with clinical symptoms (6 times), chest X ray (6 times), abdominal CT (5 times), and tumor marker elevation (3 times). This represents 14 relapses detected by follow-up examinations without clinical symptoms. Only 1/6 patients complaining of clinical symptoms as a first sign of the 1st recurrence achieved a second CR, and 5/6 died of progressive disease, whereas all 12 patients with first relapses detected without clinical symptoms during follow-up could be brought into second CR. Although this is a retrospective analysis and 3/6 patients with symptomatic relapses had additional brain lesions, these data, with due caution, tend to argue in favor of close follow-up programs with monitoring additional to physical examination for patients with NSGCT in CR. Furthermore, 15/18 first relapses (83%) were found within the first 2 years and 3/18 later. Since all 3 patients detected with a late recurrence achieved a second CR, at least 5 years of follow-up seem justified.