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中华妇幼临床医学杂志(电子版) ›› 2022, Vol. 18 ›› Issue (02) : 150 -157. doi: 10.3877/cma.j.issn.1673-5250.2022.02.005

论著

卵巢透明细胞癌患者并发静脉血栓栓塞症的影响因素
邓洁1,2, 王一然1, 王平1,†()   
  1. 1四川大学华西第二医院妇产科、出生缺陷与相关妇儿疾病教育部重点实验室，成都　610041
    2成都医学院第一附属医院妇科　610500
  • 收稿日期:2021-11-19 修回日期:2022-03-01 出版日期:2022-04-01
  • 通信作者: 王平

Influencing factors of venous thromboembolism in women with ovarian clear cell carcinoma

Jie Deng1,2, Yiran Wang1, Ping Wang1,†()   

  1. 1Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    2Department of Gynecology, First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
  • Received:2021-11-19 Revised:2022-03-01 Published:2022-04-01
  • Corresponding author: Ping Wang
  • Supported by:
    Key Research and Development Project of Science and Technology Department of Sichuan Province(2021YFS0015)
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引用本文：

邓洁, 王一然, 王平. 卵巢透明细胞癌患者并发静脉血栓栓塞症的影响因素[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(02): 150-157.

Jie Deng, Yiran Wang, Ping Wang. Influencing factors of venous thromboembolism in women with ovarian clear cell carcinoma[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(02): 150-157.

目的

探讨卵巢透明细胞癌(OCCC)患者发生静脉血栓栓塞症(VTE)的影响因素。

方法

选择2012年2月至2021年2月，四川大学华西第二医院收治的221例OCCC患者为研究对象。采用回顾性分析方法，根据是否发生VTE，将其分别纳入VTE组(n＝39)和无VTE组(n＝182)。对2组患者相关临床资料、术中情况，以及VTE组患者临床特点进行统计学分析，并采用未校正的Kaplan-Meier曲线模型及log-rank检验，对2组患者的中位总体生存(OS)期和中位无进展生存(PFS)期进行统计学分析。对影响OCCC患者并发VTE因素进行多因素非条件logistic回归分析。2组患者年龄、人体质量指数(BMI)、绝经率、妊娠次数、肿瘤最大直径、原发性高血压和2型糖尿病发生率比较，差异均无统计学意义(P>0.05)。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求。

结果

①本组221例OCCC患者的VTE发生率为17.6%(39/221)。术前，2组OCCC患者糖类抗原(CA)125水平与国际妇产科联盟(FIGO)不同临床分期占比比较，差异均有统计学意义(P<0.05)。② VTE组患者的开腹手术占比、G-Caprini评分、淋巴结阳性率、腹水或腹腔冲洗液细胞学检查阳性率，以及切除淋巴结≥20个及化疗次数>6次占比与铂耐药率，均高于无VTE组，并且差异均有统计学意义(P<0.05)。③VTE组39例患者中，26例(66.7%)被诊断为VTE时无自觉症状；术前发生VTE为7例(17.9%)，术后为18例(46.1%)，化疗期为9例(23.1%)，复发期为5例(12.8%)。VTE发生部位位于下肢、上肢、上肢+下肢、肺部分别为24例(61.5%)、6例(15.4%)、4例(10.3%)、5例(12.8%)。④无VTE组患者中位OS期及中位PFS期，均明显长于VTE组，并且差异均有统计学意义(P<0.05)。⑤影响OCCC患者并发VTE因素的多因素非条件logistic回归分析结果显示，OCCC患者FIGO临床分期为晚期(Ⅲ~Ⅳ期)(OR＝1.012，95%CI：0.110~1.900，P＝0.026)，术前CA125水平≥200 U/mL(OR＝1.472，95%CI：0.476~2.433，P＝0.036)，是导致OCCC患者发生VTE的独立影响因素。

结论

VTE是影响OCCC患者预后的重要因素之一，对于FIGO临床分期为晚期(Ⅲ~Ⅳ期)及术前CA125水平≥200 U/mL的OCCC患者，应重点预防和监测VTE发生可能。

关键词: 卵巢肿瘤, 卵巢透明细胞癌, 静脉血栓栓塞, 肿瘤分期, 抗药性，肿瘤, 影响因素分析, 预后, 随访研究, 女(雌)性
Objective

To explore influencing factors of venous thromboembolism (VTE) in patients with ovarian clear cell carcinoma (OCCC).

Methods

From February 2012 to February 2021, 221 women with OCCC who underwent gynecological surgery and confirmed by pathology in the West China Second University Hospital, Sichuan University were enrolled. According to whether the occurrence of VTE or not, they were divided into VTE group (n=39) and non-VTE group (n=182) by retrospective analysis mothod. The clinical data, intraoperative situation and VTE characteristics in two groups were retrospectively analyzed. The uncorrected Kaplan-Meier curve model and log-rank test were used to statistically analyze the median overall survival (OS) time and median progression-free survival (PFS) time between two groups. Multivariate unconditional logistic regression analysis was used to analyze the effect factors of OCCC patients complicated with VTE. There were no significant differences between two groups in age and body mass index (BMI), etc. (P>0.05). The procedure followed in this study was in accordance with the World Medical Association Declaration of Helsinki revised in 2013.

Results

①Among 221 OCCC patients, the incidence of VTE was 17.6%(39/221). There were statistically significant differences in preoperative carbohydrate antigen (CA)125 level and proportion of different International Federation of Gynecology and Obstetrics (FIGO) stages (P<0.05). ②In VTE group, the proportion of open surgery, G-Caprini score, positive rate of lymph nodes, positive rate of cytological examination of ascites or peritoneal lavage fluid, the number of lymph node dissection ≥20, proportion of chemotherapy >6 times, and platinum drug resistance rate were all higher than those in non-VTE group, and the differences between two groups were statistically significant (P<0.05). ③Twenty-six patients (66.7%) had no self-conscious symptoms when they were diagnosed with VTE. VTE occurred in 7 cases (17.9%) before operation, 18 cases (46.1%) after operation, 9 cases (23.1%) during chemotherapy, and 5 cases (12.8%) during OCCC recurrence. VTE occurred in lower limbs, upper limbs, upper limbs+ lower limbs and lungs in 24 cases (61.5%), 6 cases (15.4%), 4 cases (10.3%) and 5 cases (12.8%), respectively. ④Survival analysis showed that the OS time and PFS time in non-VTE group were significantly longer than those in VTE group, and the differences were statistically significant (P<0.05). ⑤The results of multivariate unconditional logistic regression analysis showed that advanced-stage (FIGO staging Ⅲ-Ⅳ) (OR=1.012, 95%CI: 0.110-1.900, P=0.026), and preoperative CA125 level ≥200 U/mL (OR=1.472, 95%CI: 0.476-2.433, P=0.036) were independent influencing factors of OCCC patients complicated with VTE.

Conclusions

VTE is one of the important factors affecting prognosis of patients with OCCC. The prevention and early diagnosis of VTE should be strengthened in FIGO staging Ⅲ-Ⅳ and preoperative CA125 level ≥200 U/mL.

Key words: Ovarian neoplasms, Ovarian clear cell carcinoma, Venous thromboembolism, Neoplasm staging, Drug resistance, neoplasm, Root cause analysis, Prognosis, Follow-up studies, Female
表1 2组OCCC患者临床资料比较
组别 例数 年龄(岁，±s) BMI[例数(%)] 妊娠次数[例数(%)] 绝经[例数(%)]
<24.0 kg/m2 ≥24.0 kg/m2 ≥2次 <2次
VTE组 39 54.0±10.0 24(61.5) 15(38.5) 28(71.8) 11(28.2) 25(64.1)
无VTE组 182 49.1±9.1 116(63.7) 66(36.3) 123(67.6) 59(32.4) 96(52.8)
检验值   t＝1.245 χ2＝0.006 χ2＝0.104 χ2＝1.245
P值   0.060 0.940 0.750 0.260
组别 例数 肿瘤最大直径(cm，±s) 原发性高血压[例数(%)] 2型糖尿病[例数(%)] 术前CA125水平[U/mL，M(P25~P75)]b FIGO临床分期[例数(%)]
Ⅰ~Ⅱ期 Ⅲ~Ⅳ期
VTE组 39 10.7±4.4 7(18.0) 1(2.6) 203.9(67.0~356.4) 19(48.7) 20(51.3)
无VTE组 182 11.4±4.4 25(13.7) 7(3.9) 56.2(17.2~202.9) 150(82.4) 32(17.6)
检验值   t＝1.136 χ2＝0.112 χ2<0.001a W＝2 548.000 χ2＝18.442
P值   0.285 0.738 >0.999 <0.001 <0.010
表2 2组OCCC患者手术情况比较
组别 例数 手术方式[例数(%)] 手术持续时间[min，M(P25~P75)] 术中出血量[mL，M(P25~P75)] G-Caprini评分(分，±s) 淋巴结是否阳性[例数(%)]c
开腹 腹腔镜 是 否 未清扫
VTE组 39 33(84.6) 6(15.4) 276.0(207.5~345.5) 300.0(162.5~700.0) 6.3±1.5 8(20.5) 23(59.9) 8(20.5)
无VTE组 182 121(66.5) 61(33.5) 280.0(215.0-338.8) 300.0(200.0~600.0) 5.9±1.2 12(6.6) 159(87.4) 11(6.0)
检验值   χ2＝4.177 W＝3 550.000 W＝3 310.500 t＝1.971 8.386
P值   0.040 0.999 0.509 0.035 0.004
组别 例数 腹水或腹腔冲洗液细胞学检查[例数(%)] 切除淋巴结数[例数(%)]a 化疗次数[例数(%)]b, c 铂耐药[例数(%)]b, c 缩瘤满意[例数(%)]
阳性 阴性 未送检 <20个 ≥20个 >6次 ≤6次 未化疗
VTE组 39 16(41.0) 14(35.9) 9(23.1) 1(3.2) 30(96.8) 17(43.5) 19(48.7) 3(7.7) 9(25.0) 38(97.4)
无VTE组 182 24(13.2) 106(58.2) 52(28.6) 33(19.3) 138(80.7) 36(19.8) 138(75.8) 8(4.4) 7(4.0) 179(98.3)
检验值   χ2＝14.003 χ2＝3.710 χ2＝9.767 χ2＝15.787 χ2<0.001
P值   <0.001 0.045 0.002 <0.001 >0.999
表3 39例OCCC并发VTE患者的VTE类型及发生部位比较[例数(%)]
诊断时间 VTE类型 VTE发生部位 合计
DVT 肺栓塞+DVT 肺栓塞 上肢 下肢 肺部 上肢+下肢 上肢+肺部 下肢+肺部 上肢+下肢+肺部
术前 6(15.4) 1(2.6) 0(0) 0(0) 6(15.4) 0(0) 0(0) 0(0) 0(0) 1(2.6) 7(18.0)
术后 16(41.0) 1(2.6) 1(2.6) 2(5.1) 11(28.2) 1(2.6) 3(7.7) 0(0) 1(2.6) 0(0) 18(46.2)
化疗期间 8(20.5) 1(2.6) 0(0) 2(5.1) 5(12.8) 0(0) 1(2.6) 1(2.6) 0(0) 0(0) 9(23.1)
复发 4(10.3) 1(2.6) 0(0) 2(5.1) 2(5.1) 0(0) 0(0) 0(0) 1(2.6) 0(0) 5(12.8)
合计 34(87.2) 4(10.3) 1(2.6) 6(15.4) 24(61.5) 1(2.6) 4(10.3) 1(2.6) 2(5.1) 1(2.6) 39(100.0)
表4 2组OCCC患者生存结局比较
组别 例数 生存结局[例数(%)] 中位OS期(月) 中位PFS期(月)
存活 死亡 整体 FIGO Ⅰ~Ⅱ期a FIGO Ⅲ~Ⅳ期a 整体 FIGO Ⅰ~Ⅱ期a FIGO Ⅲ~Ⅳ期a
VTE组 39 24(61.5) 15(38.5) 24.6 26.2 22.9 13.7 13.7 13.8
无VTE组 182 163(89.6) 19(10.4) 54.6 55.0 49.9 23.3 26.7 12.6
χ2值   17.281 37.910 20.812 2.332 4.831 5.743 0.212
P值   <0.001 <0.001 <0.001 0.100 0.030 0.020 0.600
图2 VTE组与无VTE组患者的PFS曲线
表5 OCCC患者发生VTE影响因素的多因素非条件logistic回归分析结果
影响因素 B SE Wald值 P值 OR值 OR值95%CI
G-Caprini评分≥5分(以G-Caprini评分<5分为对照) 1.229 891.819 0.018 0.985 16.324 -23.744~299.408
术前血清CA125水平≥200 U/mL(以术前血清CA125水平<200 U/mL为对照) 1.919 0.457 2.754 0.036 1.472 0.476~2.433
铂耐药(以铂不耐药为对照) 2.699 0.640 1.551 0.121 0.993 -0.250~2.290
FIGO临床分期为晚期(Ⅲ~Ⅳ期)[以FIGO临床分期为早期(Ⅰ~Ⅱ期)为对照] 2.752 0.454 2.230 0.026 1.012 0.110~1.900
常数项 16.325 891.819 -0.021 0.983 -19.127 —
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