Correlation between Arterial Enhancement Fraction on CT and Efficacy of Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma
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摘要: 目的:探讨CT动脉增强分数(AEF)与肝癌经导管动脉化疗栓塞(TACE)治疗效果的相关性。方法:对我院2019年1月至2020年1月43例原发性肝细胞癌(HCC)患者临床资料进行回顾性分析,所有患者均接受TACE治疗,术前及术后1个月均行CT动态增强扫描检查,根据治疗效果分为治疗有效组及无效组,采用电化学发光法检测各组甲胎蛋白(AFP)水平,比较两组治疗前后AEF、AFP、肿瘤大小变化;采用Pearson系数探究AEF、AFP与肿瘤大小变化的相关性,采用受试者工作特征曲线(ROC)及曲线下面积(AUC)分析肝脏动态增强扫描联合AEF彩图对TACE疗效的评估价值。结果:有效组治疗后AEF、AFP、肿瘤大小均小于治疗前、无效组;Pearson相关性分析结果显示,TACE治疗后AEF、AFP均与肿瘤大小呈正相关;ROC曲线分析结果显示,肝脏动态增强扫描联合AEF评估TACE疗效的AUC为0.902,明显高于肝脏动态增强扫描及AEF单独评估的0.793和0.771。结论:AEF对TACE治疗效果具有良好的评估价值,联合肝脏动态增强扫描能进一步提高准确度,可作为TACE治疗HCC疗效评估的辅助手段,值得临床推广。Abstract: Objective: To explore the correlation between arterial enhancement fraction (AEF) on Computed Tomography (CT) and the curative effect of Transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods: We enrolled 43 patients who presented with HCC to our hospital between January 2019 and January 2020 and extracted their clinical data. Three-phase contrast-enhanced CT was performed 1 month before and after TACE; based on TACE efficacy, the enrolled patients were divided into the “effective” and “ineffective” groups. The alpha-fetoprotein (AFP) level was determined using electrochemical luminescence. Changes in the AEF, AFP level, and tumor size before and after treatment were compared between the two groups. The correlation among AEF, AFP level, and tumor-size changes was explored using Pearson’s correlation coefficient. Receiver operating characteristic (ROC) curves and the area under these curves (AUCs) were used to determine the evaluation value of dynamic enhanced scanning combined with AEF for TACE efficacy. Results: After TACE, the AEF, AFP level, and tumor size decreased in the effective group and were lower than the corresponding values in the ineffective group. Pearson’s correlation analysis revealed that AEF and the AFP level were positively correlated with the tumor size after TACE. ROC analysis revealed that the AUC for dynamic enhanced scanning combined with AEF for TACE efficacy evaluation was 0.902; this was significantly greater than the AUC of dynamic enhanced scanning (0.793) and AEF (0.771) alone. Conclusion: AEF is a reliable parameter for evaluating the therapeutic effect of TACE. The evaluation of TACE efficacy can be further improved by combining AEF with dynamic enhanced scanning; this approach should be used as an auxiliary method for evaluating TACE efficacy for HCC.
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新型冠状病毒感染(COVID-19)具有较强传染性[1],根据《新型冠状病毒感染诊疗方案(试行第十版)》,将有心血管疾病(含高血压)、慢性肺疾病病、糖尿病、慢性肝病、肾脏疾病、肿瘤等基础病者定义为重型/危重型高危人群[2]。
本文回顾分析柳州市柳铁中心医院收治COVID-19患者584例,其中糖尿病患者肺部COVID-19 225例;无糖尿病患者感染COVID-19 359例,比较两组COVID-19胸部高分辨CT表现特点;定义发病与CT检查间隔7 d为急性期,分析糖尿病患者合并COVID-19感染急性期肺部影像特点。提高糖尿病者感染COVID-19影像学认识,进一步为临床诊断提供依据并改善预后。
1. 材料与方法
1.1 研究人群
收集2022年12月14日至2023年1月10日期间在柳州市柳铁中心医院以上呼吸道感染就医患者2679例,其中胸部CT表现阳性且抗原或核酸检测阳性的患者1099例,排除图像伪影较重者;无空腹血糖或糖化血红蛋白者;最终纳入584例患者,其中男性359例,女性225例,年龄范围60~99岁,平均年龄(76±9)岁;无糖尿病患者359例;糖尿病患者225例,糖尿病病史不等,本组病例中以病史10年以上者多见,糖尿病病史10年以上102人;225例患者住院期间糖化血红蛋白HbA1c>6.5%。
本研究经柳州市柳铁中心医院伦理委员会批准,同意开展本项研究(意见号KY2023-056-01),且本研究不需要患者知情。
1.2 CT扫描技术
采用西门子drive扫描仪,患者仰卧位,头先进或足先进,吸气后屏气,扫描范围从肺尖到膈顶。扫描参数:管电压120 kV,管电流80~120 mA,层间距0.625 mm,层厚1 mm。图像采用高分辨算法重建。
1.3 影像分析
有两名主治及以上放射科诊断医师独立完成,并由1名主任医师审核,在PACS工作站上分别选择肺窗(窗宽和窗位为1600和 -600),纵隔窗(窗宽和窗位为350和45)观察并分析图像。
具体指标包括:①病变分布:单叶、单肺和双肺;②病变部位:周围(即胸膜下)、中央(沿支气管血管束)及混合;③病变形态:结节(1 cm以内)、斑片(3 cm)、大片(大于3 cm);④病变密度:磨玻璃样、网格状、实变、混合型、病变密度均匀、不均匀;⑤病变边缘:模糊、清晰;⑥伴随病变:膜增厚、胸腔积液。
1.4 统计学分析
采用SPSS 21.0软件,根据患者有无糖尿病将患者分为两组,比较两组患者相关的HRCT表现特征。定义发病与CT检查时间间隔<7 d为急性期,分析急性期糖尿病合并COVID-19与非糖尿病合并COVID-19两组患者HRCT表现特征。
组间计数资料统计采用分类变量的卡方检验,定量数据进行独立样本t检验,P<0.05表示差异有统计学意义。
2. 结果
糖尿病患者感染COVID-19与非糖尿病患者感染COVID-19两组患者肺部病变密度(网格、密度不均匀)、边缘(病灶边缘模糊)比较差异均有统计学意义,糖尿病组肺内病灶实变多见,且病灶密度均匀且边缘清晰(图1和图2)。两组病变在发病部位、分布、形态及伴随征象差异无统计学意义;急性期肺内病变在糖尿病患者肺部COVID-19与非糖尿病患者肺部COVID-19两组患者肺部HRCT表现比较,网格影在急性期非糖尿病组患者中更多见。两组具体影像学征象对照及比较结果详见表1、表2和表3。
表 1 有无糖尿病两组患者的HRCT表现特征一览表Table 1. HRCT features in patients with and without diabetes mellitus项目 组别 统计检验 无糖尿病/例(%) 有糖尿病/例(%) $\chi^2 $ P 病变数量 多发 359(100.00) 224(99.50) 1.590 0.206 累及部位 单叶 3(0.84) 0(0.00) 1.890 0.169 单肺 7(1.95) 2(0.89) 1.026 0.311 双肺 351(97.77) 220(97.78) 0.000 0.996 病变分布 周围(胸膜下) 114(31.75) 83(36.89) 1.631 0.202 中央(血管周) 6(1.67) 6(2.67) 0.681 0.409 混合性 239(66.57) 137(60.89) 1.949 0.163 病变形态 结节(1 cm) 159(44.29) 109(48.44) 0.962 0.327 斑片状(3 cm) 275(76.60) 178(79.11) 0.501 0.479 大片状(>3 cm) 240(66.85) 149(66.22) 0.025 0.875 病变密度 GGO 314(87.47) 189(84.00) 1.390 0.238 实变 41(11.42) 37(16.44) 3.017 0.082 网格影 127(35.38) 54(24.00) 8.369 0.004** 不均匀 313(87.19) 181(80.44) 4.823 0.028** 均匀 77(21.45) 59(26.22) 1.764 0.184 病变边缘 模糊 344(95.82) 205(91.11) 5.448 0.020* 清晰 19(5.29) 18(8.00) 1.709 0.191 伴随病变 血管增粗 26(7.24) 25(11.11) 2.597 0.107 胸膜增厚 203(56.55) 130(57.78) 0.086 0.770 胸水形成 54(15.04) 27(12.00) 1.071 0.301 注:*-P<0.05,**-P<0.01。 表 2 COVID-19急性期糖尿病患者与非糖尿病患者的临床信息Table 2. Clinical information on patients with and without diabetes in the acute phase of COVID-19项目 组别 统计检验 无糖尿病(n=221) 有糖尿病(n=142) t P 发病时间/d 4.74±2.12 4.45±2.28 1.211 0.227 年龄 78.00±9.37 75.85±8.63 2.203 0.028* 注:急性期定义为发病时间<7 d。*-P<0.05。 表 3 COVID-19急性期糖尿病患者与非糖尿病患者的HRCT特征一览表Table 3. HRCT characteristics in patients with and without diabetes in the acute phase of COVID-19项目 特征 组别 统计检验 无糖尿病(n=221)
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例(%)有糖尿病(n=142)
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例(%)$\chi^2 $ P 病变数量 多发 221(100.00) 141(99.50) 1.590 0.206 累及部位 单肺 6(2.71) 2(1.41) 0.685 0.408 双肺 214(96.83) 138(97.18) 0.036 0.849 病变分布 周围(胸膜下) 65(29.41) 49(34.51) 1.042 0.307 中央(血管周) 5(2.26) 5(3.52) 0.511 0.475 混合性 153(69.23) 90(63.38) 1.377 0.248 病变形态 结节/树丫(1 cm) 86(38.91) 63(44.37) 1.062 0.303 斑片状(3 cm) 161(72.85) 110(77.46) 0.973 0.324 大片状(>3 cm) 157(71.04) 100(70.42) 0.016 0.899 病变密度 GGO 190(85.97) 121(85.21) 0.041 0.840 实变 30(13.57) 28(19.72) 2.431 0.119 网格影 82(37.10) 35(24.65) 6.141 0.013* 不均匀 188(85.07) 117(82.39) 0.460 0.497 均匀 49(22.17) 38(26.76) 0.999 0.318 病变边缘 模糊 212(95.93) 130(91.55) 3.041 0.081 清晰 11(4.98) 11(7.75) 1.164 0.281 伴随病变 血管增粗 17(7.69) 18(12.68) 2.465 0.116 胸膜增厚 129(58.37) 85(59.86) 0.079 0.779 胸水形成 35(15.84) 20(14.08) 0.207 0.649 注:*-P<0.05。 3. 讨论
COVID-19是一种基因组结构不同于其他呼吸道病毒且侵袭性和传播性较强的β属特殊毒株,通过S蛋白与人血管紧张素转化酶-2(ACE2)互相作用感染人呼吸道黏膜上皮细胞、Ⅱ型肺泡上皮细胞和肺间质以及微血管血栓形成和多系统脏器受累等改变[3-4]。人群普遍易感,重型及危重型多见于合并基础病者如糖尿病。COVID-19感染主要依靠病毒核酸检测确诊,核酸检测存在时间长和假阴性,HRCT有助于提高COVID-19的检出率和诊断准确率[5],部分患者核酸阴性影像却具有典型病毒性肺炎征象,国家卫生健康委员会《新型冠状病毒感染的肺炎诊疗方案(试行第五版)》中[6],将CT表现纳入临床诊断依据。
本研究分析了584例新型冠状病毒感染(COVID-19)HRCT表现阳性的患者,统计结果显示多数影像学征象与文献一致[3-4,7-16]。225例糖尿病患者新型冠状病毒感染后双肺HRCT表现在发病部位、分布、形态及伴随征象与常规人群感染COVID-19无明显差异,均表现为双肺多发、周围(胸膜下)分布为主的结节、斑片及大片磨玻璃及实变影;病变密度均匀与否及病变边缘改变差异有统计学意义;发病与CT检查间隔小于7 d分组,糖尿病组患者COVID-19和非糖尿病组患者COVID-19之间,病变密度网格影改变差异有统计学意义。病变的HRCT征象如密度、形态和边缘因其病理特征和病变程度的不同多呈现不均匀磨玻璃、实变影及网格影,边缘多表现为模糊。
本研究结果显示糖尿病组患者COVID-19肺炎早期病变即出现密度均匀和病变边缘清晰的表现,文献报道较少。尸体解剖证实COVID-19主要是引起深部气道、间质和肺泡损伤为特征的炎性反应[17],糖尿病患者COVID-19感染肺部病变HRCT显示网格影少于非糖尿病组,说明糖尿病患者感染COVID-19时肺泡渗出为主,间质受累少见,有研究显示小叶内间隔增厚是COVID-19肺炎的独立预测因子之一[18-19],而糖尿病合并COVID-19感染,肺内网格影少见,这可能与糖尿病患者自身免疫有关。渗出为主是否是糖尿病患者易发生重症原因,需要进一步研究证实。
总之,糖尿病患者合并COVID-19肺炎,HRCT表现双肺多发,周围分布为主,渗出为主,网格影少见,病变密度均匀、病变边缘相对清晰。合并或者不合并胸膜改变。基础病是COVID-19感染后发生重症的主要原因之一,熟悉糖尿病患者合并COVID-19肺炎HRCT征象,为临床治疗及评估预后提供依据。
本研究的局限在性,两组病例未纳入临床指标及氧饱和度与患者影像改变进行相关性分析;糖尿病组患者病史长短及血糖控制情况感染后机体反应是否存在差异;此外糖尿病往往合并心脑血管病变,并发症有无是否与肺内病灶改变及预后的研究尚需进一步研究。
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表 1 两组治疗AEF、AFP、肿瘤大小比较(
$ \bar x \pm s $ )Table 1 Comparison of the AEF, AFP level and tumor size between the two groups (
$ \bar x \pm s $ )组别 AEF AFP/(ng/L) 肿瘤大小/cm 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 有效组 0.51±0.13 0.34±0.05* 385.12±10.29 84.89±8.39* 6.28±1.05 3.01±0.41* 无效组 0.52±0.09 0.48±0.07 382.87±21.54 373.25±17.82 6.05±1.13 5.96±1.05 t 0.265 7.594 0.420 72.436 0.667 13.209 P 0.792 0.000 0.676 0.000 0.509 0.000 注:与本组治疗前,*-P<0.05。 表 2 AEF、AFP与肿瘤大小的相关性
Table 2 Correlation between the AEF, AFP level and tumor size
指标 肿瘤大小 P AEF 0.537 0.002 AFP 0.649 0.000 表 3 肝脏动态增强扫描联合AEF对TACE疗效的评估价值
Table 3 Evaluation value of dynamic enhanced liver scanning combined with AEF for TACE efficacy
项目 AUC P 95% CI 肝脏动态增强扫描 0.793 <0.05 0.642~0.901 AEF 0.771 <0.05 0.618~0.885 肝脏动态增强扫描联合AEF 0.902 <0.05 0.773~0.972 -
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