超声造影参数联合甲胎蛋白异质体3及糖类抗原125诊断小肝癌患者分化程度的临床研究

Contrast-enhanced ultrasound parameters combined with serum AFP-L3 and carbohydrate antigen 125 in evaluating the differentiation degree of small hepatocellular carcinoma

目的 观察不同分化程度小肝癌患者增强模式、超声造影参数及血清甲胎蛋白异质体3、糖类抗原125(carbohydrate antigen 125, CA125)水平变化,探讨超声造影消退时间联合血清甲胎蛋白异质体3、CA125对不同分化程度小肝癌的诊断价值。方法 经手术组织病理证实小肝癌患者120例,低分化30例为低分化组,中分化38例为中分化组,高分化52例为高分化组。3组术前均行超声造影检查,记录动脉相、门脉相、延迟相的增强模式,绘制时间-强度曲线记录开始增强时间、达峰时间和消退时间;入院次日采用化学发光法检测血清甲胎蛋白异质体3、CA125水平;绘制ROC曲线,评估超声造影消退时间及血清甲胎蛋白异质体3、CA125对不同分化程度小肝癌的诊断效能。结果 (1)低、中、高分化组动脉相均以高增强为主,门脉相和延迟相均以低增强为主。低、中、高分化组动脉相高增强比率比较差异无统计学意义(P>0.05);低、中分化组门脉相(73.33%、73.68%)、延迟相(100.00%、84.21%)低增强比率均高于高分化组(46.15%,63.46%)(P<0.05),低分化组与中分化组比较差异无统计学意义(P>0.05)。(2)低、中、高分化组开始增强时间[(12.35±1.47)、(11.94±1.62)、(12.03±1.15)s]、达峰时间[(24.36±2.81)、(23.67±2.92)、(24.12±2.37)s]比较差异无统计学意义(P>0.05),消退时间[(42.13±3.52)、(71.45±6.28)、(94.66±8.74)s]比较差异有统计学意义(P<0.05);低、中、高分化组消退时间依次延长(P<0.05)。(3)低、中、高分化组血清甲胎蛋白异质体3[(64.75±6.38)、(50.12±5.26)、(37.41±3.17)μg/L]、CA125[(91.26±8.37)、(82.64±8.29)、(76.33±6.52)u/mL]水平均依次降低(P<0.05)。(4)超声造影消退时间及血清甲胎蛋白异质体3、CA125分别以46.20 s、65.20μg/L、96.50 u/mL为最佳截断值,联合诊断低分化小肝癌的AUC为0.926(95%CI:0.883~0.968,P<0.001),大于三项指标单独检测[0.771(95%CI:0.686~0.856,P<0.001),0.783(95%CI:0.704~0.863,P<0.001),0.811(95%CI:0.720~0.902,P<0.001)](Z=4.254,P=0.005;Z=3.850,P=0.021;Z=4.008,P=0.008);分别以75.62s、56.36μg/L、83.14 u/mL为最佳截断值,联合诊断中分化小肝癌的AUC为0.899(95%CI:0.855~0.900,P<0.001),大于三项指标单独检测[0.685(95%CI:0.602~0.700,P<0.001),0.669(95%CI:0.653~0.690,P<0.001),0.702(95%CI:0.668~0.725,P<0.001)](Z=6.035,P=0.001;Z=4.850,P=0.001;Z=3.968,P=0.017);分别以100.52 s、35.21μg/L、70.22 u/mL为最佳截断值,联合诊断高分化小肝癌的AUC为0.860(95%CI:0.823~0.889,P<0.001),大于三项指标单独检测[0.800(95%CI:0.711~0.820,P<0.001),0.690(95%CI:0.671~0.712,P<0.001),0.715(95%CI:0.700~0.752,P<0.001)](Z=6.960,P<0.001;Z=8.171,P<0.001;Z=5.780,P=0.001)。结论 小肝癌患者血清甲胎蛋白异质体3、CA125水平随分化程度降低而增高;低、中分化患者门脉相、延迟相低增强比率较高;超声造影消退时间联合血清甲胎蛋白异质体3、CA125对不同分化程度小肝癌均具有较高诊断价值。

Objective To observe the changes of contrast-enhanced ultrasound(CEUS)enhancement patterns and parameters,AFP-L3 and carbohydrate antigen 125(CA125)in patients with small hepatocellular carcinoma(HCC)with different differentiation degrees,and to investigate the diagnostic value of CEUS regression time combined with serum AFP-L3and CA125.Methods Totally 120patients with HCC were divided into poor differentiation group(n=30),moderate differentiation group(n=38)and high differentiation group(n=52).CEUS was performed preoperatively in three groups to record the enhancement patterns in the arterial phase,portal phase and delayed phase.Time-intensity curves were drawn to record the beginning enhancement time,peak time and regression time.The levels of AFP-L3and CA125were detected by chemiluminescence method the next day after admission.ROC curve was drawn to evaluate the efficiencies of CEUS regression time,serum AFP-L3 and CA125 on the diagnosis of small HCC with different differentiation degree.Results(1)In three groups,the arterial phase was predominantly characterized by high enhancement,while the portal and delayed phases were predominantly characterized by low enhancement.The high enhancement ratio in the arterial phase showed no significant differences among three groups(P>0.05).The low enhancement ratios in the portal phase(73.33%,73.68%)and delayed phase(100.00%,84.21%)in poor and moderate differentiation groups were higher than those in high differentiation group(46.15%,63.46%)(P<0.05),and showed no significant differences between poor and moderate differentiation groups(P>0.05).(2)There were no significant differences in the beginning time[(12.35±1.47),(11.94±1.62),(12.03±1.15)s]and peak time[(24.36±2.81),(23.67±2.92),(24.12±2.37)s]in poor,moderate and high differentiation groups(P>0.05),while the regression time prolonged successively in three groups in turn[(42.13±3.52),(71.45±6.28),(94.66±8.74)s](P<0.05).(3)The serum levels of AFP-L3[(64.75±6.38),(50.12±5.26),(37.41±3.17)μg/L]and CA125[(91.26±8.37),(82.64±8.29),(76.33±6.52)u/mL]decreased in a descending order in poor,moderate,and high differentiation groups(P<0.05).(4)When the optimal cut-off values of the regression time,serum AFP-L3and CA125were 46.20s,65.20μg/L and 96.50u/mL,the AUCof combined detection of them three for diagnosing poorly differentiated small HCC was 0.926(95%CI:0.883-0.968,P<0.001),which was higher than that of the single detection[0.771(95%CI:0.686-0.856,P<0.001),0.783(95%CI:0.704-0.863,P<0.001),0.811(95%CI:0.720-0.902,P<0.001)](Z=4.254,P=0.005;Z=3.850,P=0.021;Z=4.008,P=0.008).When the optimal cut-off values of the regression time,serum AFP-L3and CA125 were 75.62s,56.36μg/L and 83.14u/mL,the AUCof combined detection for diagnosing moderately differentiated small HCC was0.899(95%CI:0.855-0.900,P<0.001),which was higher than that of single detection[0.685(95%CI:0.602-0.700,P<0.001),0.669(95%CI:0.653-0.690,P<0.001),0.702(95%CI:0.668-0.725,P<0.001)](Z=6.035,P=0.001;Z=4.850,P=0.001;Z=3.968,P=0.017).When the optimal cut-off values of the regression time,serum AFP-L3and CA125were 100.52s,35.21μg/L and 70.22u/mL,the AUCof combined detection for diagnosing highly differentiated small HCC was 0.860(95%CI:0.823-0.889,P<0.001),higher than that of single detection[0.800(95%CI:0.711-0.820,P<0.001),0.690(95%CI:0.671-0.712,P<0.001),0.715(95%CI:0.700-0.752,P<0.001)](Z=6.960,P<0.001;Z=8.171,P<0.001;Z=5.780,P=0.001).Conclusions The levels of AFP-L3and CA125increase with the decrease of differentiation degree in patients with small HCC.The low enhancement ratios in the portal phase and delayed phase are higher in patients with poorly and moderately differentiated small HCC.The regression time combined with AFP-L3and CA125detection has a high value to the diagnosis of small HCC with different differentiation degrees.