基于切缘状态的子宫颈原位腺癌分层管理的探讨

Risk stratified management of cervical adenocarcinoma in situ based on cone margin state

目的探讨子宫颈原位腺癌(AIS)基于切缘状态的分层管理方案。方法收集2010年1月至2015年12月在复旦大学附属妇产科医院行子宫颈环形电切(LEEP)术,术后病理诊断为AIS的患者249例,回顾性分析其临床病理资料,探讨LEEP术后切缘状态与病灶残留的关系,并采用多因素logistic回归法分析影响子宫颈AIS患者LEEP术后病灶残留的相关因素。结果(1)249例子宫颈AIS患者的诊断年龄为(40±8)岁(范围:23~71岁)。249例子宫颈AIS患者中,19例有病灶残留,病灶残留率为7.6%(19/249)。其中,LEEP术后病理诊断为单纯AIS者69例,其病灶残留率为13.0%(9/69),LEEP术后病理诊断为AIS+高级别鳞状上皮内病变者180例,其病灶残留率为5.6%(10/180),两者比较,差异有统计学意义(χ^(2)=3.968,P=0.046);多灶性病变者33例,其病灶残留率为21.2%(7/33),单灶性病变者216例,其病灶残留率为5.6%(12/216),两者比较,差异有统计学意义(χ^(2)=7.858,P=0.005)。181例术前行子宫颈管搔刮术(ECC)患者中,ECC阳性患者的病灶残留率为14.0%(14/100),显著高于ECC阴性者[4.9%(4/81);χ^(2)=4.103,P=0.043]。(2)249例子宫颈AIS患者中,LEEP术后切缘阳性者88例,切缘阳性率为35.3%(88/249);切缘阳性患者的病灶残留率(14.8%,13/88)显著高于切缘阴性者[3.8%(6/156);χ^(2)=9.355,P=0.002]。249例子宫颈AIS患者中,LEEP术后152例行子宫全切除术、97例未行子宫切除术;LEEP术后行子宫全切除术患者的年龄为(43±7)岁,显著高于97例未行子宫切除术者[(37±8)岁;t=6.518,P<0.01];LEEP术后行子宫全切除术患者中有生育要求者3例,占2.0%(3/152),显著低于未行子宫全切除术者[38例,占39.2%(38/97);χ^(2)=59.579,P<0.01]。152例LEEP术后行子宫全切除术的患者中,18例有病灶残留,病灶残留率为11.8%(18/152),其中切缘阳性患者的病灶残留率显著高于切缘阴性者[分别为18.8%(12/64)、7.0%(6/86);χ^(2)=4.861,P=0.028]。97例LEEP术后未行子宫全切除术患者的中位随访时间为32个月(范围:4~70个月),随访期内子宫颈AIS复发3例(3.1%,3/97),进一步行子宫全切除术,未发现浸润性腺癌。(3)多因素logistic回归法分析显示,切缘阳性(OR=4.098,95%CI为1.235~13.595,P=0.021)、多灶性病变(OR=5.464,95%CI为1.494~19.981,P=0.010)为影响子宫颈AIS患者LEEP术后病灶残留的独立危险因素。结论子宫颈AIS患者LEEP术后的管理,建议以切缘状态作为一级分层管理指标,以年龄、生育需求作为二级分层管理指标,结合病灶残留的高危因素综合评估,制定个体化的治疗方案。

Objective To investigate the hierarchical management scheme of cervical adenocarcinoma in situ(AIS)based on cervical conization margin state.Methods All medical records of 249 patients diagnosed as AIS by loop electrosurgical excision procedure(LEEP)conization from Jan.2010 to Dec.2015 in Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed,to explore the relationship between the status of the resection margin and the residual lesion after LEEP,and the multivariate logistic regression method was used to analyze the related factors that affect the residual lesion after LEEP in cervical AIS patients.Results(1)The age of 249 cervical AIS patients was(40±8)years old(range:23-71 years old).Of the 249 patients,19(7.6%,19/249)had residual lesions;69 cases were pathologically diagnosed as AIS after LEEP,and the residual lesion rate was 13.0%(9/69),which was significantly higher than that of AIS+high-grade squamous intraepithelial lesion[5.6%(10/180);χ^(2)=3.968,P=0.046];33 cases were multifocal lesions,the residual rate of lesions was 21.2%(7/33),which was significantly higher than that of single focal lesions patients[5.6%(12/216);χ^(2)=7.858,P=0.005];181 patients underwent endocervical curettage(ECC)before surgery,the residual rate of lesions in ECC-positive patients was 14.0%(14/100),significantly higher than that of ECC-negative patients[4.9%(4/81);χ^(2)=4.103,P=0.043].(2)Among 249 cases of AIS patients,the positive rate of resection margins after LEEP was 35.3%(88/249);the residual rate of lesions in patients with positive resection margins(14.8%,13/88)was significantly higher than those with negative margins[3.8%(6/156);χ^(2)=9.355,P=0.002].The age of patients underwent total hysterectomy after LEEP was(43±7)years old,which was significantly higher than that of patients who did not undergo total hysterectomy[(37±8)years old;t=6.518,P<0.01].Among the patients underwent total hysterectomy after LEEP,3 cases(2.0%,3/152)had fertility requirements,while 38 cases(39.2%,38/97)did not underwent total hysterectomy,the difference between the two groups was statistically significant(χ^(2)=59.579,P<0.01).Among the 152 patients who underwent total hysterectomy after LEEP,the residual rate of lesions was 11.8%(18/152);the residual rate of lesions in patients with positive resection margins was significantly higher than that of patients with negative resection margins[18.8%(12/64)vs 7.0%(6/86);χ^(2)=4.861,P=0.028].The median follow-up time of 97 patients who did not undergo total hysterectomy after LEEP was 32 months(range:4-70 months).During the follow-up period,3 cases of cervical AIS recurrence(3.1%,3/97)and were followed by hysterectomy,no invasive adenocarcinoma were seen.(3)Multivariate logistic regression analysis showed that the positive resection margin(OR=4.098,95%CI:1.235-13.595,P=0.021),multifocal lesions(OR=5.464,95%CI:1.494-19.981,P=0.010)were independent risk factors that affected the residual lesions in patients with cervical AIS after LEEP.Conclusions The cervical AIS patients after LEEP conization suggested be stratified by cone margin state as the first-line stratified index,age and fertility needs as the second-line stratified management index.The individualized management plan should be developed based on comprehensive assessment of high-risk factors of residual lesions.