宫颈冷刀锥切术诊治宫颈上皮内瘤变的价值

[目的]探讨宫颈冷刀锥切术对宫颈上皮内瘤变(CIN)的诊断及治疗作用.[方法]对比126例行宫颈冷刀锥切术和阴道镜下多点活检的CIN患者的病理检查结果,分析CIN患者行宫颈冷刀锥切术的临床疗效和并发症.[结果]阴道镜下多点活检和宫颈冷刀锥切术后病理完全符合83例(占65.9％).14例(11.1％)患者锥切边缘受累;发现早期浸润癌5例,其中2例早期浸润癌仅行宫颈锥切,随访无复发.宫颈冷刀锥切术的主要并发症为出血和宫颈管狭窄,发生率分别为6.3％ (8/126)和3.9％ (5/126).[结论]宫颈锥切术比阴道镜下多点活检对宫颈上皮内瘤变的诊断更准确,并具有重要治疗作用.     

Clinical Outcomes of Cases with Cervical Dysplasia Absent in Cold Knife Conization Specimens

Background: Cold knife conization is a surgical procedure that allows both diagnosis and treatment of cervicallesions at the same time. It is mainly performed for indications of high-grade cervical intraepithelial neoplasia(CIN). In this study, we aimed to investigate the clinical outcome of cases without CIN in cold knife conizationspecimen, following a high-grade lesion (CIN2/3) in cervical biopsy. Materials and Methods: We performed aretrospective cohort study at a tertiary referral hospital between January 1st 2008 and August 1st 2012. Cases thatunderwent cold knife conization for CIN2/3 within the study period were included. Cone-negative (Group 1) andcone-positive (Group 2) cases were analyzed for various clinical parameters, and were compared in the 1-yearpost-conization period for histological recurrence and human papillomavirus (HPV) DNA status. Results: A totalof 173 women underwent cold knife conization for CIN2/3 within the study period. Twenty-two cases (12.7%)were included in Group 1 and 151 cases (87.3%) in Group 2. There were no significant differences between thetwo groups in terms of age, gravidity, parity, menopausal status and HPV-DNA status (pre-conization and 1year post-conization) (p>0.05). Recurrence rates were also similar between the groups (9.1% vs 9.9%, p>0.05).Conclusions: Clinical outcomes were similar in terms of histological recurrence and HPV persistence after 1year of follow-up between cone-negative and cone-positive cases. Clinical follow-up of cone-negative cases shouldtherefore be performed similar to cone-positive cases.     

Long Term Outcomes of Laser Conization for High Grade Cervical Intraepithelial Neoplasia in Thai Women

Aim: To report long term outcomes of laser conization for high grade cervical intraepithelial neoplasia (CIN)in Thai women. Materials and Methods: A retrospective cohort study was conducted in patients undergoing laserconization due to abnormal cervical cytology suggesting neoplasia during 1989 to 1994 and having follow-up datauntil December 2010. Conization was performed under colposcopy using a 0.5-mm CO2 laser beam with powerdensity of 18,000-20,000 watts/cm2, and the surgical base was vaporized using a low power defocused beam. Thefollow-up protocol included cervical cytology and colposcopy. Long term outcome measures were failure rate(persistence and recurrence), post-conization status of transformation zone, and obstetric outcomes. Results:Of 104 patients undergoing conization, 71 had therapeutic conization for high grade CIN and were followed upfor a median time of 115 (range 12-260) months. There was one case of persistent and one of recurrent diseasecomprising a failure rate of 2.8%. The post treatment transformation zone was well visualized in 68.3% of 63patients with an intact uterus. Sixteen patients achieved 25 pregnancies; none had second trimester miscarriage.The obstetric outcomes were unremarkable. Conclusions: Laser conization under colposcopic visualization for thetreatment of high grade CIN in Thai women has a low failure rate of 2.8%. The post-conization transformationzone could not be evaluated completely in approximately 30% of cases; therefore the follow-up protocol shouldinclude both cytology and colposcopy. Obstetric outcomes are not adversely affected by this therapeutic procedure.     

高级别宫颈上皮内瘤变临床特点与诊治分析

[目的]分析高级别宫颈上皮内瘤变（CIN）患者的临床及诊治特点,评估彩超、术中冰冻（FSE）的诊断价值。[方法]回顾性分析经手术治疗的CIN2／3患者的临床病理资料,分析术前、术中、术后病理分级转化及手术治疗情况。[结果]①CIN2／3患者的流产率（73．91％）、恶性肿瘤家族史比例（32．02％）均高于正常对照组,与CIN的发生呈正相关。②58．89％（149／253）的CIN2／3病例彩超表现为宫颈回声异常。③FSE漏诊宫颈癌77.33％,未提高高级别CIN的诊断符合率,与PSE一致性较差（Kappa=0．217,P〈0．001）。[结论]高流产率、恶性肿瘤家族史可能与CIN发生有关。彩超对高级别CIN有辅助诊断价值。FSE对术中决策有一定价值,但依据FSE指导手术存在风险。高级别CIN的治疗应避免治疗过度／不足。     

高危型HPV负荷量和p16INK4A蛋白监测评估宫颈锥切术治疗CIN

[目的]评价高危型人乳头状瘤病毒HPV负荷量的检测和p16INK4A蛋白的表达在预测宫颈上皮内瘤变(CIN)宫颈锥切术后残存病变或复发中的意义.[方法]回顾性分析142例2008年10月至2010年12月因CIN行宫颈锥形切除术治疗患者的临床资料.所有患者均于宫颈锥形切除术前6个月以内和术后6～12个月进行HPV负荷量检测,并采用免疫组化方法检测HPV DNA阳性患者宫颈细胞中p16INK4A蛋白表达.[结果]宫颈锥切术前,随着CIN级别的上升,HPV负荷量以及p16INK4A蛋白表达均明显增强(P＜0.05).但在宫颈锥切术后,HPV负荷量和p16INK4A蛋白表达明显降低,宫颈锥切术前和术后两者之间差异有统计学意义(P＜0.05).[结论] HPV负荷量持续增高和p16INK4A蛋白持续呈强阳性是宫颈锥切术后发生残存病变或复发的高危因素,在监测HPV负荷量的同时检测p16INK4A蛋白的表达,对判断宫颈锥切术后发生残存病变或复发有重要意义.     

HR-HPV对CIN冷刀锥切后的随访价值

探讨HR-HPV监测CIN冷刀锥切后病变残余或复发的价值。方法：118例冷刀锥切后患者第3、6、12、18、24个月均检测HR-HPV和细胞学及阴道镜,病理证实存在CIN视为残留或复发。结果：术后病理切缘阳性10例（8.5%）;术后24个月残留或复发18例（15.3%）。术后第6个月HR-HPV转阴率较术后第3个月升高,差异有统计学意义,较6个月后的转阴率无统计学意义。术后第6个月HR-HPV阳性者28例（23.7%）,阳性者发病18例（64.3%）,阴性患者无发病。术后第6个月HR-HPV诊断病变残留或复发的敏感度和特异度分别为100.0%和90.0%,阳性预测价值和阴性预测价值分别为64.3%和100.0%。HR-HPV与TCT正确诊断率为91.5%和81.4%,Youden's指数为0.900和0.598,HR-HPV优于TCT。切缘阳性者残留或复发率（40.0%）较阴性患者（13.0%）高（P=0.045）,切缘阳性者发病风险是阴性者4.5倍（95% CI=1.121～17.866）。结论：术后第6个月HR-HPV检测是监测冷刀锥切后病变残留或复发的早期敏感指标,阳性者密切监测,阴性者常规监测不增加发病风险。此外,切缘阳性是病变残留或复发的一个重要危险因素。     

宫颈锥切诊治CIN Ⅲ和宫颈癌ⅠA1期临床观察

[目的]探讨宫颈锥切对宫颈上皮内瘤变(CIN)Ⅲ及宫颈癌ⅠA1期的诊治作用。[方法]回顾性分析2002年1月至2004年12月行宫颈锥切术的114例患者的临床资料。[结果]宫颈锥切前多点活检准确率为87.7%(100/114)。宫颈粘连狭窄率为3.2%。21例患者补充全子宫切除术,切缘阳性者标本残留率为28.6%(2/7)、阴性者则为14.3%(2/14)。中位随诊16个月,仅行锥切术的93例患者(切缘阳性者2例、切缘阴性者91例),1例切缘阴性者复发(占1.1%)。11例患者有生育要求,已妊娠9例(81.8%),其中早产率为12.5%(1/8)。[结论]宫颈锥切是一种并发症少的手术方法,可提高CINⅢ、宫颈癌ⅠA1期的诊断准确性并有治疗作用。锥切治疗后复发率低,切缘阳性者易有残留,术后应适当处理及密切随诊。     

宫颈上皮内瘤变管理的进展

宫颈上皮内瘤变（CIN）是一组宫颈癌的癌前病变,它能反应宫颈癌发生发展的连续过程。宫颈癌早诊早治工作的广泛开展,使其预防和治疗关口明显前移。因此,如何规范CIN的管理已成为宫颈癌防治工作的关键。该文针对CIN各级的特性及其管理的新进展进行综述。     

bcl-2蛋白在宫颈上皮内瘤样变及宫颈癌中的表达和意义

目的　探讨bcl-2在宫颈上皮内瘤样变及宫颈浸润癌中过度表达的意义。方法　采用免疫组织化学SP法检测了 10例宫颈上皮内瘤样变 (CIN)及 5 7例宫颈癌中bcl-2蛋白的表达 ,并以 11例正常宫颈组织作对照。结果　bcl-2蛋白在CIN中的表达强度明显高于正常对照 (P <0 0 5 ) ;bcl-2蛋白在宫颈癌中的表达 ,不仅表达阳性率 ( 94 7% )明显高于正常对照 ( 5 4 5 % ) (P <0 0 1) ,而且表达强度亦明显高于正常对照 (P <0 0 1) ;bcl -2蛋白在宫颈癌临床Ⅲ期中的过表达 ( 6 4 3 % )明显高于临床Ⅱ期 ( 2 2 2 % ) (P <0 0 5 )。结论　bcl-2蛋白的过度表达不仅与宫颈癌的发生有关 ,而且与宫颈癌的发展有关。     

Comparison of Cervical Levels of Interleukins-6 and -8 in Patients with and without Cervical Intraepithelial Neoplasia

Introduction: Interleukins-6 and -8 are two pro-inflammatory cytokines increasing in serum and local levels under malignant conditions. There are limited evidences on the association between cervical level of these two factors and cervical intraepithelial neoplasia (CIN). So, this study aimed to explore the association between cervical levels of IL-6 and IL-8 with cervical premalignant lesions. Methods: The present case-control study was conducted on married women undergone Pap smear for routine screening in two groups as the group with CIN (n=100) and the healthy control group (n=100). Cervical secretions were collected using sterile swab and the levels of IL-8 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). The obtained data were analyzed by SPSS software. Results: The mean cervical IL-6 level was 568.66±594.62 pg/ml in the patients with CIN and 212.7±213.9 pg/ml in the controls (P <0.001). The cervical IL-8 levels in the case and control groups were measured to be 1320.43±876.5 pg/ml and 1053.59±747.64 pg/ml, respectively (p=0.02). By modifying the confounding size effect of the age and marital duration, it was determined that cervical levels of IL-6 and IL-8 were both associated with CIN. Conclusion: Our results showed that the cervical levels of IL-6 and IL-8 are associated with CIN independent of age and marital dura     

子宫颈锥形切除术病理结果分析

目的:对照子宫颈锥形切除术与活检的病理结果,探讨重度子宫颈上皮内瘤变(CIN-Ⅲ)的临床处理方法.方法:分析在阴道镜下活检,病理诊断为CIN-Ⅲ,行子宫颈锥形切除术的患者153例,采用自身对照的方法,对比子宫颈锥形切除术后的病理结果.结果:子宫颈锥形切除术与阴道镜下活检病理诊断相符者95例,占62.09%:不相符者58例,占37.91%:其中诊断升高为子宫颈浸润癌16例,占10.46%;诊断降低者42例,占27.45%,最终诊断以病理诊断级别高者为准.结论:子宫颈锥形切除术与阴道镜下活检病理诊断仍有一定的差异,重度子宫颈上皮内瘤变(CIN-Ⅲ)的病例,建议行子宫颈锥形切除术进行最终诊断与治疗.     

宫颈上皮内瘤变150例临床分析

目的：探讨宫颈上皮内瘤变（CIN）的诊断及治疗方法。方法：回顾分析1984年1月至1998年12月住院治疗的150例CIN的临床资料。结果宫颈细胞学检查诊断的阳性率为76．65,与宫颈管细胞学检查联合应用诊断的阳性率为78．8％,两者比较无显著性差异。细胞检查结合阴道镜下活检诊断CIN阳性率为95．3％,与单一细胞学诊断相比较,有显著性差异。阴道镜下活检与病理诊断的符合率为91．6％,镜下活检与宫颈管刮术结合诊断的阳性率明显高于单纯阴道镜下活检。141例采用手术治疗,无1例切缘阳性;9例原位癌采用腔内放疗,全组无1例复发或死亡。结论宫颈细胞学检查结合阴道镜检是诊断CIN的有效方法,对绝经后妇女应同时行宫颈管刮术,对不宜手术的原位癌患者可行单纯腔内放疗。     

宫颈上皮内瘤变与宫颈鳞癌组织的差异蛋白质组学研究

[目的]比较宫颈上皮内瘤变(CIN)与宫颈鳞癌(SCC)组织之间蛋白质组的差异,寻找与宫颈癌相关的特异性蛋白质,为研究CIN发展为宫颈癌的分子机制及临床诊治工作提供新的线索。[方法]收集正常宫颈组织9例、CIN组织23例(其中CINⅠ7例、CINⅡ8例、CINⅢ8例)及SCC组织7例。应用二维荧光差异凝胶电泳(2-DDIGE)寻找差异表达蛋白质点,基质辅助激光解析飞行时间串联质谱(MALDI-TOF/TOFMS)分析差异蛋白质点。进一步对3个重要差异蛋白S100A9、eEF1A1及PKM2应用免疫组织化学定性及WesternBlot定量检测其在宫颈组织中的表达。[结果]建立了分辨率高、重复性好的CIN与SCC的双向凝胶电泳图谱。两组差异蛋白质点共860个,标记蛋白质点46个(27个上调,19个下调),成功鉴定25个蛋白质。免疫组化及免疫印迹结果显示S100A9在SCC中表达水平高于CIN,而PKM2、eEF1A1在SCC中表达水平显著低于CIN。[结论]CIN与SCC间存在蛋白质表达的差异,这些差异表达的蛋白质可能成为宫颈癌早期诊断的标志物及治疗的新靶点。     

Integration Sites and Genotype Distributions of Human Papillomavirus in Cervical Intraepithelial Neoplasia

Objectives: To analyse HPV integration prevalence and genotype distributions in cervical intraepithelialneoplasia (CIN) in east part of China, furthermore to assess preferential sites for common HPV integrations andprovide baseline information for cervical abnormality screening and prevention. Methods: Integration of HPV in113 paraffin-embedded cervical intraepithelial neoplasia samples was assessed using Gencap technology in KeyLaboratory of Biotechnologies in BGI-Shenzhen. Results: 64 samples were HPV-integrated and as the cervicallesions increased, the integration rate became higher significantly (P=0.002). Fifteen different HPV genotypeswere detected, 14 high-risk (16, 18, 31, 33, 51, 52, 56, 58, 66, 68) and 1 low-risk (11). The most common genotypeswere HPV-16, 58, 33, 52, 66, and 56. Thirteen patients had co-integration involving mainly HPV-16 and 58. Thefrequency of HPV gene disruption was higher in L1 and E1 genes than in other regions of the viral genomes.Conclusion: Some 56.6% of CIN lesions in Qingdao had HPV integrations, and 67.2% of HPV-integrated patientswere HPV-16 and 58, more prone to be integrated in younger patients below 45 years old. There exist preferentialsites for HPV-16 and HPV-58 integration, and they are more likely to be disrupted in the L1 and E1 loci.     

轻度宫颈上皮内瘤变自然转归的前瞻性研究

[目的]研究轻度宫颈上皮内瘤变（CINⅠ）的自然转归、人乳头瘤病毒（HPV）的自然清除率及两者之间的关系。[方法]对2003年5月到2006年4月期间,在北京大学深圳医院经阴道镜下活检病理诊断为CINⅠ的548名患者,定期随访4～6年。以宫颈液基细胞学检查（LCT）联合高危型HPV（HR-HPV）DNA检测（HC-Ⅱ）作为随访的监测方法,每6～12月随访一次。对于随访中细胞学为未明确诊断意义的不典型鳞状上皮细胞（ASCUS）及以上病变,及/或HR-HPV阳性者行阴道镜下多点活检,病理诊断。[结果]随访48个月时共失访27人,剔除34人,继续随访487人,累积未完全随访率为11.13%。随访6个月、12个月、24个月、36个月、48个月时进展为高度宫颈上皮内瘤变的百分率分别为0.55%、1.65%、3.10%、4.05%、4.11%;病变持续存在的百分率分别为70.25%、45.77%、23.79%、11.54%、7.19%;病变逆转为正常的百分率分别为29.20%、52.57%、73.11%、84.41%、88.71%。随访48个月时,35岁以上组和35岁以下组的病变进展率和逆转率均无显著性差异。随访开始时HR-HPV阳性的患者462例,随访6个月、12个月、24个月、36个月、48个月时病毒自然清除率分别为24.26%、48.69%、70.05%、81.54%、86.36%,HPV清除与CINⅠ病变逆转趋势一致。24个月内HPV持续阳性的患者,在48个月内进展为高度宫颈上皮内瘤变的比率为18.9%,显著高于HPV阴转组和HPV持续阴性组。[结论]2年内超过2/3的CINⅠ病变会自然逆转,HPV也会自然清除,但对于HPV持续阳性的患者应警惕其进展为高度宫颈上皮内瘤变。     

Cervical Cytologic Abnormalities of Cervical Intraepithelial Neoplasia 1 Treated with Cryotherapy and Expectant Management during the First Year Follow-Up Period

Aim: To determine the frequency of cervical cytologic abnormalities in patients who were diagnosed ashaving CIN 1 and had undergone either cryotherapy or expectant management. Methods: A retrospective medicalrecord review of 87 patients with colposcopic cervical biopsy-proven CIN 1, was undertaken including age,parity, menstruation status, cervical cytology reports, colposcopic findings, and cervical cytologic follow-upreports. There were 38 patients (43.7%) treated with cryotherapy and the remainder underwent expectantmanagement. Results: Mean (SD) age of patients treated with cryotherapy was less than that of the patients whohad expectant management (36.2 (9.4) vs 41.1 (9.4) years, respectively, p=0.02). There were no differences in thefrequencies of cervical cytologic abnormalities between the groups at 6- and 12-month-follow-up visits(cryotherapy group vs expectant group: 18.4% vs 18.4% at 6-months and 19.2% vs 16.1% at 12-months).Conclusion: Cryotherapy and expectant management with cytologic surveillance had comparable frequenciesof cytologic abnormalities during a 12-month follow-up period. Expectant management requires adherence tofollow up and high quality cytology and colposcopy testing. Therefore, it should be reserved for these settings.Cryotherapy may be more reasonable in women who are likely to be lost to follow up and high quality cytologycannot be guaranteed.     

宫颈上皮内瘤变相关危险因素102例分析

[目的]研究宫颈鳞状上皮内瘤变（CIN）的发病相关危险因素及诊疗方法。[方法]102例CIN患者行阴道镜下活检和高频电波刀宫颈环状电圈切除术（LEEP），并同时行高危型HPV检测（HCU）。[结果]102例患者中CINⅠ54例，CINⅡ29例，CINⅢ19例。LEEP术后治愈率为96．1％（98／102），发现病灶残留4例，复发8例（7．8％）。63例高危型HPV阳性，总感染率为61．76％。CINⅡ、Ⅲ组较CINⅠ感染率显著升高（P〈0．05）。术后HPV持续感染率25％。多因素非条件Logistic回归分析显示，年龄、近5年性传播疾病（STD）感染、无性生活防护和性伴的多性是CIN的独立危险因素。[结论]CIN与性行为和下生殖道感染等因素相关。LEEP是CIN诊断和治疗的有效方法。高危型HPV与重度CIN的发生有关，术后高危型HPV检测对预测残留或复发有指导意义。     

宫颈上皮内瘤变自然史转移概率的研究

[目的]探讨1级宫颈上皮内瘤变(CIN1)进展、退化或保持不变的转移概率,为使用基于转移概率为基本参数的Markov模型进行卫生经济学评价提供参数。[方法]利用前瞻性的宫颈癌自然史随访6年队列(SPOCCS-I)的宫颈癌自然史的数据,使用指数分布模型和微积分方法对CIN1进展和退化的年转移概率进行了估计。[结果]SPOCCS-I人群中CIN1患者的疾病保持不变的、发生进展和退化的年转移概率分别为0.658、0.020和0.322,相应的6年累积转移概率分别为0.081、0.054和0.865。[结论]SPOCCS-I人群中CIN1的患者在1年内发生进展的可能性为2%,该人群中有32.2%的CIN1患者会在1年内发生退化。根据中国宫颈癌自然史队列SPOCCS-I计算出的CIN1的转移概率符合卫生经济学评价中使用的Markov模型需要的参数,可以为之提供参数的参考依据。     

端粒酶在宫颈癌及其癌前病变组织中的表达及意义

目的探讨端粒酶在宫颈癌及癌前病变组织中的表达及其在宫颈癌发生、发展过程中的作用。方法采用免疫组织化学EnVision二步法,检测30例浸润性宫颈癌（ICC）、90例宫颈上皮内瘤变（CIN）和10例正常宫颈组织标本中端粒酶的表达。结果端粒酶在正常宫颈组织、CINⅠ、CINⅡ、CINⅢ及浸润性宫颈癌中的阳性表达率分别为30.0%、40.0%、43.3%、70.0%和93.3%。端粒酶表达率浸润性宫颈癌高于CINⅢ,CINⅢ高于CINⅡ,差异均有统计学意义（P〈0.05）;CINⅡ与CINⅠ,CINⅠ与正常宫颈组织比较,差异均无统计学意义（P〉0.05）。结论端粒酶的表达与宫颈癌的发生、发展密切相关。端粒酶可作为宫颈癌癌前病变转归的预测指标。