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   复旦学报(医学版)  2022, Vol. 49 Issue (2): 180-188      DOI: 10.3969/j.issn.1672-8467.2022.02.004
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肝细胞腺瘤常规超声及超声造影特征分析:单中心回顾性研究
陈凯玲1,2 , 朱宇莉1 , 董怡1 , 李翠仙1 , 包静文1 , 汪瀚滔1,2 , 王文平1,2     
1. 复旦大学附属中山医院超声科 上海 200032;
2. 上海市影像医学研究所 上海 200032
摘要目的 分析肝细胞腺瘤(hepatocellular adenoma,HCA)的常规超声(B-model ultrasound,BMUS)和超声造影(contrast-enhanced ultrasound,CEUS)图像特征,并探讨炎症型HCA(I-HCA)和HNF-1α失活型HCA(H-HCA)图像特征差异,旨在提高HCA的术前诊断率。方法 分析2012年3月—2020年12月在复旦大学附属中山医院病理确诊为HCA的103例患者共103个病灶的BMUS特征,其中65例患者共65个病灶完成CEUS检查,分析CEUS动脉期增强方式、包膜下增强血管影、门脉期及延迟期的增强减退等特征并比较不同分子分型之间的差异。结果 I-HCA在BMUS主要表现为低回声(68.4%,26/38)而H-HCA以高回声为主要表现(78.6%,11/14,P < 0.001),脂肪肝背景在I-HCA的显示率高于H-HCA(P=0.025)。半环状或环状血流信号在I-HCA的显示率高于H-HCA(分别为50.0%和14.3%,P=0.030)。HCA的CEUS特征包括动脉期整体高增强(73.8%,48/65),达峰时均匀增强(86.2%,56/65),门脉期15.4%(10/65)呈低增强,延迟期40.0%(26/65)呈低增强,另有50.8%(33/65)见包膜下增强血管影。I-HCA在延迟期呈低增强的比例高于H-HCA(P=0.019),且包膜下增强血管影在I-HCA的显示率高于H-HCA(分别为54.2%和12.5%,P=0.040)。以“BMUS高回声、CEUS动脉期均匀高增强、延迟期等增强或高增强”为特征诊断H-HCA,灵敏度、特异性分别为0.500和0.962。以“BMUS低回声伴脂肪肝背景、CDFI半环状或环状血流信号、CEUS动脉期高增强、包膜下增强血管影”为特征诊断I-HCA,灵敏度、特异性分别为0.545和0.875。结论 H-HCA的特征为BMUS高回声,CEUS动脉期均匀高增强,延迟期持续增强;I-HCA的特征性表现为低回声伴脂肪肝背景,CDFI半环状或环状血流信号、CEUS动脉期高增强及包膜下增强血管影。BMUS及CEUS对HCA的术前诊断及分型具有一定的提示作用。
关键词肝细胞腺瘤(HCA)    超声造影(CEUS)    分子分型    包膜下增强血管影    
Analysis of B-model ultrasound and contrast-enhanced ultrasound findings of hepatocellular adenoma: a single-center retrospective study
CHEN Kai-ling1,2 , ZHU Yu-li1 , DONG Yi1 , LI Cui-xian1 , BAO Jing-wen1 , WANG Han-tao1,2 , WANG Wen-ping1,2     
1. Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
2. Shanghai Institute of Medical Imaging, Shanghai 200032, China
Abstract: Objective To analyze the B-model ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) characteristics of hepatocellular adenoma (HCA) and explore the features of inflammatory HCA (I-HCA) and HNF-1α-inactivated HCA (H-HCA). Methods The BMUS features of 103 HCA patients definited by pathology from Mar 2012 to Dec 2020 in Zhongshan Hospital, Fudan University were analyzed retrospectively.A total of 65 patients with 65 lesions underwent CEUS.The enhancement pattern, subcapsular enhancement in arterial phase, enhancement degree in arterial, portal venous and late phase were compared between different molecular classifications of HCA. Results On BMUS, I-HCA was mainly hypoechoic (68.4%, 26/38), while H-HCA was mainly hyperechoic (78.6%, 11/14, P < 0.001).Fatty liver was more frequently in I-HCA than that in H-HCA (P=0.025).The detection rate of semicirular or annular blood flow signal in I-HCA was higher than that in H-HCA (50.0% vs 14.3%, P=0.030).The CEUS characteristics of HCA included overall hyper-enhancement (73.8%, 48/65) in arterial phase, homogeneous enhancement (86.2%, 56/65) at the peak, hypo-enhancement in portal venous (15.4%, 10/65) and late phase(40.0%, 26/65). Subcapsular enhancement was detected in 50.8% (33/65) of all lesions. The detection rate of subcapsular enhancement in I-HCA was higher than that of H-HCA (54.2%, 12.5%, P=0.040).In late phase, the appearance of hypo-enhancement in I-HCA was higher than that of H-HCA (P=0.019).With the characteristic of "hyperechoic on BMUS, homogeneous hyper-enhancement enhancement in arterial phase of CEUS, continuous hyper- or iso-enhancement in late phase" for H-HCA, the sensitivity and specificity were 0.500 and 0.962, respectively.With the characteristic of "hypoechoic with fatty liver on BMUS, semicircular or annular blood flow signal on CDFI, hyper-enhancement in arterial phase of CEUS, and subcapsular enhancement" for I-HCA, the sensitivity and specificity of I-HCA were 0.545 and 0.875, respectively. Conclusion H-HCA is characterized by hyperechoic on BMUS, homogeneous hyper-enhancement enhancement in arterial phase of CEUS continuous hyper- or iso-enhancement in late phase.I-HCA is hypoechoic with fatty liver on BMUS, semicircular or annular blood flow signal on CDFI, hyper-enhanced in arterial phase of CEUS and subcapsular enhancement.BMUS and CEUS are helpful for the preoperative diagnosis of HCA.
Key words: hepatocellular adenoma (HCA)    contrast-enhanced ultrasound (CEUS)    molecular subtype    subcapsular enhancement in arterial phase    

肝细胞腺瘤(hepatocellular adenoma,HCA)是罕见的肝脏良性上皮肿瘤[1]。HCA的确切发病率及致病因素尚不明确,已有研究表明其在亚洲人群的发病率低于西方国家,并与雌激素摄入、糖原累积症、代谢综合征、肝血管疾病等存在一定的相关性[2-5]。HCA具有高度异质性,根据基因突变及临床病理特征分为4种类型:肝细胞因子失活型HCA(HNF1α-inactivated HCA,H-HCA)、β-链蛋白激活型HCA(β-catenin-activated HCA,B-HCA)、炎症型HCA(inflammatory HCA,I-HCA)及未分类型HCA(unclassified HCA,U-HCA)[4]。由于HCA发病率低而且不同分型之间影像学表现差异较大,其术前诊断仍是临床工作中的挑战。常规超声(B-model ultrasound,BMUS)是肝脏局灶性病变(focal liver lesions,FLLs)的首选影像学检查方法,超声造影(contrast-enhanced ultrasound,CEUS)对FLLs的定性诊断具有较高的灵敏度和特异性,但目前关于HCA的CEUS特征的报道较少而且多为基于小样本量的研究[5-8]。本文通过总结近年来在复旦大学附属中山医院确诊为HCA病灶的BMUS及CEUS表现并结合分子分型进行分析,旨在提高HCA的术前诊断率。

资料和方法

研究对象  回顾性分析2010年6月—2020年12月在我院经手术或穿刺后病理确诊为HCA的103例共103个病灶的超声图像特征及临床病理资料,其中男性59例,女性44例,年龄19~83岁,平均(35.16±15.27)岁,103例患者均行BMUS检查,其中65例行CEUS检查;85例为单发病灶,18例为多发病灶,多发病灶仅计入最大者。本研究经复旦大学附属中山医院伦理委员会批准(编号:B2021-051),豁免知情同意。

纳入标准:经病理明确诊断为HCA;超声检查前未行任何治疗;BMUS可清晰显示肝脏病灶;BMUS及CEUS图像资料保存完整。排除标准:BMUS肝脏病灶显示不清;CEUS动态图像存储时间短等因素所致无法分析。

仪器与方法  使用PHILPS IU22、EPIQ7、GE LOGIQ E9等超声诊断仪,配备凸阵探头频率2.5~ 5.0 MHz,机械指数(mechanical index,MI) < 1.0。患者检查时呈仰卧位或左侧卧位,BMUS扫查病灶的位置、大小、内部回声、回声均匀性、边界、形态;彩色多普勒血流成像(color doppler flow imaging,CDFI)检测病灶的血流信号并测量阻力指数(resistance index,RI);在显示病灶最大切面时切换至CEUS模式,通过头静脉注射对比剂声诺维(SonoVue®,意大利Bracco公司)1.5~2.4 mL,随后使用5 mL无菌生理盐水冲管,观察时间至少5 min。重复注射时,间隔时间>15 min。

图像分析  由两名具有5年以上腹部超声检查经验的医师在不知病理结果的情况下单独分析,意见不一致时经协商达成共识。分析病灶在BMUS的位置(左叶/右叶)、大小、内部回声(高/等/低/混合回声)、回声均匀性(均匀/不均匀)、边界(清晰、不清晰)及形态(规则/不规则);根据2020年世界医学生物学超声联合会(World Federation of Ultrasound in Medicine and Biology,WFUMB)肝脏超声造影指南[9],评估HCA在动脉期(10~45 s)增强方式(整体、向心性、离心性增强)、门脉期(45~120 s)和延迟期(120~300 s)的增强程度(高、等、低增强)、包膜下增强血管影以及病灶内部灌注缺损区。

统计学分析  使用SPSS 23.0统计学软件进行分析,符合正态分布的定量资料用x±s表示,组间比较采用t检验;不符合正态分布的定量资料采用M(IQR)表示,组间比较采用秩和检验。定性资料以例数或占比(%)表示,组间比较采用χ2或Fisher精确检验,组内两两比较采用χ2检验,P值用Boferroni法进行校正。P < 0.05为差异有统计学意义。

结果

HCA病灶的BMUS特征  HCA病灶在BMUS主要表现为低回声(68.9%,71/103)、内回声不均匀(55.3%,57/103)、边界清晰(73.8%,81/103)、形态规则(78.6%,81/103),13.6%(14/103)的病灶内部见斑片状高回声,3.9%(4/103)内见点状钙化,4.9%(5/103)见无回声区,12.6%(13/103)的病灶周边见暗环。79.6%(82/103)的病灶可测及血流信号,阻力指数0.40~0.82,平均0.62±0.17,血流信号分布以周边型(62.1%,64/1063)最为常见,血流形态分别为点状(25.2%,26/103)、短线状(27.2%,28/103)、半环状或环状(25.2%,26/103)。

103例患者中59例行免疫组化检查进行分子分型,包括38例I-HCA,14例H-HCA,3例B-HCA,4例U-HCA纳入研究。因B-HCA及U-HCA的病例数较少,本研究仅比较I-HCA与H-HCA之间的BMUS特征差异。其中I-HCA主要表现为低回声(68.4%,26/38),但H-HCA以高回声为主要表现(78.6%,11/14,P < 0.001)。52.6%(20/38)的I-HCA合并脂肪肝背景而85.7%(12/14)的H-HCA肝实质背景正常(P=0.025)。I-HCA病灶半环形或环形血流信号的显示率高于H-HCA(分别为50.0%和14.3%,P=0.030),两者在病灶内部回声均匀性、边界清晰度等方面无显著差异,见表 1。I-HCA的BMUS图像见图 1

表 1 不同分子分型HCA的BMUS特征 Tab 1 BMUS features of different molecular subtypes of HCA 
[n(%)]
BMUS features Total (n=103) I-HCA (n=38) H-HCA (n=14) B-HCA (n=3) U-HCA (n=4) χ2 P
Site 0.049 0.825
  Left lobe 34 (33.0) 15 (39.5) 6 (42.9) 2 (66.7) 1 (25.0)
  Right lobe 69 (67.0) 23 (60.5) 8 (57.1) 1 (33.3) 3 (75.0)
Internal echoic 28.155 < 0.001
  Hyper-echoic 14 (13.6) 2 (5.3) 11 (78.6) 1 (33.3) 0
  Iso-echoic 6 (5.8) 7 (18.4) 1 (7.1) 0 1 (25.0)
  Hypo-echoic 71 (68.9) 26 (68.4) 1 (7.1) 1 (33.3) 2 (50.0)
  Mixed echoic 12 (11.7) 3 (7.9) 1 (7.1) 1 (33.3) 1 (25.0)
Homogeneity 0.464 0.496
  Homogeneous 46 (44.7) 15 (39.5) 7 (50.0) 1 (33.3. 1 (25.0)
  Heterogeneous 57 (55.3) 23 (60.5) 7 (50.0) 2 (66.7) 3 (75.0)
Boundary 3.351 0.109
  Well-defined 76 (73.8) 33 (86.8) 9 (64.3) 3 (100.0) 2 (50.0)
  Ill-defined 27 (26.2) 5 (13.2) 5 (35.7) 0 2 (50.0)
Shape 0.018 0.894
  Regular 81(78.6) 32 (84.2) 12 (85.7) 3 (100.0) 3 (75.0)
  Irreglar 22 (21.4) 6 (15.8) 2 (14.3) 0 1 (25.0)
Patchy hyperechoic area 1.802 0.179
  Yes 14 (13.6) 9 (23.7) 1 (7.1) 1 (33.3) 0
  No 89 (86.4) 29 (76.3) 13 (92.9) 2 (66.7) 4 (100.0)
Calcification 0.376 0.540
  Yes 4 (3.9) 1 (2.6) 0 0 1 (25.0)
  No 99 (96.1) 37 (97.4) 14 (100.0) 3 (100.0) 3 (75.0)
Dark ring 1.000 0.317
  Yes 13 (12.6) 7 (18.4) 1 (7.1) 1 (33.3) 0
  No 90 (87.4) 31 (81.6) 13 (92.9) 2 (66.7) 4 (100.0)
Anechoic area 1.173 0.279
  Yes 5 (4.9) 3 (7.9) 0 0 3 (75.0)
  No 98 (95.1) 35 (92.1) 14 (100.0) 3 (100.0) 1 (25.0)
Blood flow signals 4.146 0.227
  Peripheral 64 (62.1) 23 (60.5) 5 (35.7) 1 (33.3) 2 (50.0)
  Interior 6 (5.8) 1 (2.6) 2 (14.3) 0 1 (25.0)
  Peripheral and interior 12 (11.7) 6 (15.8) 3 (21.4) 1 (33.3) 1 (25.0)
  No 21 (20.4) 8 (21.1) 4 (28.6) 1 (33.3) 0
Blood flow pattern 8.398 0.030
  Point-like 26 (25.2) 5 (13.2) 6 (42.8) 0 1 (25.0)
  Short-linear 28 (27.2) 6 (15.8) 4 (28.6) 2 (66.7) 2 (50.0)
  Semi-annular or annular 26 (25.2) 19 (50.0) 2 (14.3) 0 1 (25.0)
  No 23 (22.3) 8 (21.0) 2 (14.3) 1 (33.3) 0
Fatty liver 6.163 0.025
  Yes 37 (35.9) 20 (52.6) 2 (14.3) 1 (33.3) 1 (25.0)
  No 66 (64.1) 18 (47.4) 12 (85.7) 2 (66.7) 3 (75.0)
χ2 and P value were the results compared between I-HCA and H-HCA.All of the 103 cases finished BMUS,and 59 of them underwent molecular typing.
A: A 39-year-old female patient presented with a well-defined hypoechoic mass in the left lobe of the fatty liver; B: CDFI showed annular blood flow signal around the lesion.C: It was proven to be I-HCA by postoperative pathology (HE staining, 40×). Microscopically, hepatocyte hyperplasia, partial hepatocyte degeneration and sinusoidal dilatation were observed. 图 1 炎症型肝细胞腺瘤BMUS图像 Fig 1 BMUS image of inflammatory hepatocellular adenoma

HCA病灶的CEUS特征  65例HCA患者完成CEUS检查,其中37例患者行免疫组化检查进行分子分型,24例为I-HCA,8例为H-HCA,2例为B-HCA,3例为U-HCA。所有HCA病灶在动脉期表现为高增强,18.5%(12/65)呈向心性增强,7.7%(5/65)呈离心性增强,73.8%(48/65)呈整体增强,达峰时86.2%(56/65)呈均匀增强,13.8%(9/65)呈不均匀增强。门脉期15.4%(10/65)呈低增强,延迟期40.0%(26/65)呈低增强。另有50.8%(33/65)的病灶见包膜下增强血管影,6.2%(4/65)内部见始终未增强区。通过两两比较,在延迟期I-HCA呈低增强的比例高于H-HCA,两者差异具有统计学意义(P=0.019),且I-HCA病灶包膜下增强血管影的显示率高于H-HCA(分别为54.2%和12.5%,P=0.040),见表 2。具体图像见图 2图 3

表 2 不同分子分型HCA的CEUS特征 Tab 2 CEUS features of different molecular subtypes of HCA 
[n(%)]
CEUS features Total (n = 65) I-HCA (n = 24) H-HCA (n = 8) B-HCA (n = 2) U-HCA (n = 3) χ2 P
Enhancement degree in arterial phase
Hyper-enhancement 65 (100.0) 24 (100.0) 8 (100.0) 2 (100.0) 3 (100.0)
Enhancement pattern in arterial phase 0.569 1.000
  Centripetal 12 (18.5) 4 (16.7) 1 (12.5) 1 (50.0) 0
  Centrifugal 5 (7.7) 2 (8.3) 0 0 1 (33.3)
  Overall 48 (73.8) 18 (75.0) 7 (87.5) 1 (50.0) 2 (66.7)
Enhancement homogeneity 1.103 0.555
  Homogeneous 56 (86.2) 21 (87.5) 8 (100.0) 1 (50.0) 2 (66.7)
  Heterogeneous 9 (13.8) 3 (12.5) 0 1 (50.0) 1 (33.3)
Enhancement degree in portal venous phase 4.842 0.070
  Hyper-enhancement 12 (18.5) 3 (12.5) 4 (50.0) 1 (50.0) 1 (33.3)
  Iso-enhancement 43 (66.1) 16 (66.7) 4 (50.0) 1 (50.0) 1 (33.3)
  Hypo-enhancement 10 (15.4) 5 (20.8) 0 0 1 (33.3)
Enhancement degree in late phase 7.328 0.019
  Hyper-enhancement 6 (9.2) 0 2 (25.0) 1 (50.0) 1 (33.3)
  Iso-enhancement 33 (50.8) 11 (45.8) 5 (62.5) 1 (50.0) 2 (66.7)
  Hypo-enhancement 26 (40.0) 13 (54.2) 1 (12.5) 0 0
Subcapsule enhancement 4.233 0.040
  Yes 33 (50.8) 13 (54.2) 1 (12.5) 2 (100.0) 1 (33.3)
  No 32 (49.2) 11 (45.8) 7 (87.5) 0 2 (66.7)
Unenhanced area 0.711 0.399
  Yes 4 (6.2) 2 (8.3) 0 0 0
  No 61 (93.8) 22 (91.7) 8 (100.0) 2 (100.0) 3 (100.0)
P value was the result compared between I-HCA and H-HCA.A total of 65 cases finished CEUS,and 37 of them underwent molecular typing.
A: A 29 mm hypoechoic mass was detected in the left lobe of the liver, with clear boundary, irregular shape, and background of fatty liver.B: CDFI showed annular blood flow signal around the lesion.In the arterial phase of CEUS, subcapsule enhancement was observed (C, indicated by arrow), the lesion showed uneven enhancement at the peak, and the unenhanced area was observed (D, indicated by arrow).E: In the portal venous phase, the lesion showed hypo-enhancement.F: During late phase, the lesion was hypo-enhanced inside the lesion, subcapsular vascular enhancement was also observed.It was confirmed to be I-HCA by postoperative pathology.The patient was a 36-year-old man. 图 2 炎症型肝细胞腺瘤CEUS图像 Fig 2 CEUS image of inflammatory hepatocellular adenoma
A: BMUS showed hyperechoic lesions in the left lobe of liver with clear boundaries.B: In arterial phase, the lesion was hyper-enhanced.It was iso-enhanced in portal venous phase (C, indicated by arrow), and continuous iso-enhancement in late phase (D). 图 3 HNF-1a失活型肝细胞腺瘤CEUS图像 Fig 3 CEUS image of HNF-1α inactivated hepatocellular adenoma

BMUS及CEUS对不同分子分型HCA的诊断率  具有“CEUS动脉期高增强、门脉期及延迟期不减退”及“包膜下增强血管影”特征的HCA病灶占50.7%。以“BMUS高回声、CEUS动脉期均匀高增强、延迟期等增强或高增强”为特征诊断H-HCA,灵敏度、特异性、阴性预测值、阳性预测值、准确性分别为0.500、0.962、0.750、0.895、0.877,与病理结果对照的四格表见表 3

表 3 BMUS及CEUS诊断H-HCA的四格表 Tab 3 Fourfold table of BMUS and CEUS for diagnosis of H-HCA 
(n)
BMUS and CEUS Pathology Total
H-HCA Non-H-HCA
H-HCA 6 2 8
Non-H-HCA 6 51 57
Total 12 53 65

以“BMUS低回声伴脂肪肝背景、CDFI环状或半环状血流信号、CEUS动脉期高增强、包膜下增强血管影”为特征诊断I-HCA,灵敏度、特异性、阴性预测值、阳性预测值、准确性分别为0.545、0.875、0.818、0.651、0.708,与病理结果对照的四格表见表 4

表 4 BMUS及CEUS诊断I-HCA的四格表 Tab 4 Fourfold table of BMUS and CEUS for diagnosis of I-HCA 
(n)
BMUS and CEUS Pathology Total
I-HCA Non-I-HCA
I-HCA 18 4 22
Non-I-HCA 15 28 43
Total 33 32 65
讨论

HCA是肝细胞增生引起的良性肿瘤,因其缺乏明显临床症状且具有高度异质性,与肝细胞来源的常见良恶性肿瘤如肝细胞癌(hepatocellular carcinoma,HCC)、肝脏局灶性结节性增生(focal nodular hyperplasia,FNH)等难以鉴别[6, 10]。既往研究认为HCA具有恶变潜能及出血破裂的风险,确诊后应手术切除;近年来随着分子病理的发展和个性化诊疗方案的提出,HCA的分子分型已被2016年欧洲肝脏病学会(European Association for the Study of the Liver,EASL)《肝脏良性肿瘤管理指南》推荐为治疗方案选择的重要参考因素,因此术前明确诊断HCA并预测其分子分型也成为对影像医师的更高要求[11-12]。本研究通过回顾近十年复旦大学附属中山医院诊治的HCA患者的超声影像资料,观察到HCA在BMUS主要表现为低回声(68.9,71/103)、内部回声不均匀(55.3%,57/103)、边界清晰(73.8%,76/103)、形态规则(78.6%,81/103)等良性FLLs的特征,且因脂肪含量、血窦扩张不同及假汇管区形成等因素表现为内部回声不均匀[13]。分别有13.6%(14/103)病灶内见斑片状高回声及3.9%(4/103)见点状钙化,可能与肿瘤组织内出血坏死诱发炎症反应并吸收有关[7]。另有4.9%(5/103)的HCA因出血见无回声区[14]。本研究还观察到78.6%(11/14)的H-HCA表现为高回声,可能由肿瘤细胞脂肪变性所致[13]。I-HCA病灶中呈“低回声且合并脂肪肝背景”的比例高于H-HCA,与Broker等[15]的研究结果一致。CDFI显示血流信号主要分布于病灶周边及内部,约25.2%(26/103)形态为半环状或环状血流,平均阻力指数 < 0.60。尽管常规超声在病灶大小、内部回声及无回声区方面可提示HCA出血等特征,但在显示病灶微循环灌注方面价值有限。

注射对比剂后,本组HCA在CEUS动脉期主要表现为整体高增强73.8%(48/65),仅有少部分病灶表现为向心性增强(18.5%,12/65)或离心性增强(7.7%,5/65)。而Dong等[7]观察到46.2%的病灶呈向心性增强,Garcovich等[5]报道89%的HCA表现为向心性增强,与本研究结果不同。Dietrich等[16]认为HCA动脉期的增强方式因病灶大小、血窦扩张、病理类型及炎性浸润程度而异。部分研究者报道H-HCA呈整体增强,向心性增强是I-HCA的特征性表现(特异性约91%)[5, 17]。而本组病例中两者增强方式无显著差异,可能与H-HCA的样本量较少有关,我们在接下来的研究中将增加样本量进一步探索不同类型HCA的CEUS特征差异。

门脉期84.6%(55/65)的HCA呈持续高增强或等增强,而延迟期仅约60.0%(39/65)呈持续增强,文献报道约37%~53%的HCA在延迟期减退[5, 16, 18]。门脉期或延迟期出现减退的HCA病灶与HCC等恶性肿瘤表现相似,但在减退时间上HCC通常较早(在门脉期减退),而HCA减退时间较晚(出现在延迟期)。“延迟期减退”也被认为是HCA的特征之一[7, 19]。值得关注的是,在延迟期12.5%(1/8)的H-HCA和54.2%(13/24)的I-HCA呈低增强,组内两两比较显示两者差异具有统计学意义。Garcovich等[5]的研究纳入14例I-HCA,其中50%(7/14)呈持续增强,21.4%(3/14)和28.6%(4/14)分别在门脉期或延迟期减退。Laumonier等[17]的研究中也观察到类似结果。曾有研究报道B-HCA的增强减退模式与HCC类似[20],本组2例B-HCA在门脉期及延迟期均未减退,但因B-HCA样本量过小尚不能定论,U-HCA也如此。

包膜下增强血管影是HCA的另一重要特征性,本组HCA病例中检出率为50.8%(33/65),与文献报道相符[7, 9]。Laumonier等[17]认为包膜下血管是快速向心性高增强的原因,也是I-HCA的特征性表现,而我们观察到包膜下增强血管影在各种类型HCA中均能检出,并且在I-HCA与H-HCA之间差异无统计学意义。此外,既往研究报道I-HCA自发性出血风险高于其他亚型,约5.6%~22%[5, 14],而本组病例中仅2例I-HCA见始终未增强区,可能因为部分以破裂出血为首发症状的患者行急诊手术而未行CEUS检查。

以“BMUS高回声、CEUS动脉期均匀高增强、延迟期等增强或高增强”为特征诊断H-HCA,虽然灵敏度较低,但特异性及阳性预测值均较高,由于H-HCA无须手术治疗,上述特征有助于识别H-HCA患者并避免不必要的手术切除。以“BMUS低回声伴脂肪肝背景、CDFI环状或半环状血流信号、CEUS动脉期高增强、包膜下增强血管影”为特征诊断I-HCA,特异性和阳性预测值可分别达87.5%和81.8%。因I-HCA是发病率最高的亚型且具有破裂出血和恶变风险,BMUS结合CEUS特征有助于HCA患者的危险分层,对疑似I-HCA的患者及时手术治疗或可改善预后。

本研究也存在一定的局限性,B-HCA和U-HCA因病例数较少而未比较其超声特征与H-HCA、I-HCA的差异,但本研究也是目前发表文献中[5, 7-8]纳入样本量最多的研究。

综上,HCA的BMUS特征包括低回声、内部回声不均匀、边界清晰、形态规则、RI < 0.6,CEUS特征主要包括动脉期整体均匀增强、包膜下增强血管影和部分延迟期减退。H-HCA的特征为BMUS高回声、CEUS动脉期整体高增强、门脉期及延迟期持续增强;而I-HCA的特征为BMUS低回声伴脂肪肝背景、CDFI环状或半环状血流信号、CEUS动脉期高增强、包膜下增强血管影部分门脉期及延迟期低增强。常规超声及超声造影对HCA的术前诊断及分型具有一定的提示作用。

作者贡献声明  陈凯玲  收集数据,统计分析,撰写论文。朱宇莉  论文修订,可行性分析。董怡  论文构思及修订。李翠仙  文献调研,可行性分析。包静文  数据收集、整理与保存。汪瀚滔  数据收集,可行性分析。王文平  获取资助,论文指导及修订。

利益冲突声明  所有作者均声明不存在利益冲突。

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文章信息

陈凯玲, 朱宇莉, 董怡, 李翠仙, 包静文, 汪瀚滔, 王文平
CHEN Kai-ling, ZHU Yu-li, DONG Yi, LI Cui-xian, BAO Jing-wen, WANG Han-tao, WANG Wen-ping
肝细胞腺瘤常规超声及超声造影特征分析:单中心回顾性研究
Analysis of B-model ultrasound and contrast-enhanced ultrasound findings of hepatocellular adenoma: a single-center retrospective study
复旦学报医学版, 2022, 49(2): 180-188.
Fudan University Journal of Medical Sciences, 2022, 49(2): 180-188.
Corresponding author
WANG Wen-ping, E-mail: puguang61@126.com.
基金项目
国家自然科学基金(81901750);上海市临床重点专科项目(shslczdzk03501);上海市自然科学基金(20ZR1452800);上海申康中心重大临床研究项目(SHDC2020CR1031B)
Foundation item
This work was supported by the National Natural Science Foundation of China (81901750), Key Clinical Specialty Project of Shanghai Municipality (shslczdzk03501), the Natural Science Foundation of Shanghai Municipal (20ZR1452800) and Shanghai Shenkang Center Major Clinical Research Project (SHDC2020CR1031B)

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