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

doi:10.3877/cma.j.issn.1673-5250.2022.02.005

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(%)]
组别	例数	年龄(岁，±s)	<24.0 kg/m²	≥24.0 kg/m²	≥2次	<2次	绝经[例数(%)]
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(%)]
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	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<0.001^a	W＝2 548.000	χ²＝18.442
P值		0.285	0.738	>0.999	<0.001	<0.010

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(%)]
组别	例数	年龄(岁，±s)	<24.0 kg/m²	≥24.0 kg/m²	≥2次	<2次	绝经[例数(%)]
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(%)]
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	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<0.001^a	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
组别	例数	开腹	腹腔镜	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)	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(%)]
组别	例数	阳性	阴性	未送检	<20个	≥20个	>6次	≤6次	未化疗	铂耐药[例数(%)]^{b, c}	缩瘤满意[例数(%)]
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
组别	例数	开腹	腹腔镜	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)	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(%)]
组别	例数	阳性	阴性	未送检	<20个	≥20个	>6次	≤6次	未化疗	铂耐药[例数(%)]^{b, c}	缩瘤满意[例数(%)]
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
诊断时间	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	合计
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
诊断时间	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	合计
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)
组别	例数	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

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)
组别	例数	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	—

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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