2. 上海市影像医学研究所 上海 200032
2. Shanghai Institute of Medical Imaging, Shanghai 200032, China
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。
[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. |
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。
[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. |
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。
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。
(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 |
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。
[1] |
SEARS HF, SMITH G, POWELL RD. Hepatic adenoma associated with oral contraceptive use: an unusual clinical presentation[J]. Arch Surg, 1976, 111(12): 1399-1403.
[DOI]
|
[2] |
RENZULLI M, CLEMENTE A, TOVOLI F, et al. Hepatocellular adenoma: An unsolved diagnostic enigma[J]. World J Gastroenterol, 2019, 25(20): 2442-2449.
[DOI]
|
[3] |
BIOULAC-SAGE P, SEMPOUX C, BALABAUD C. Hepatocellular adenoma: Classification, variants and clinical relevance[J]. Semin Diagn Pathol, 2017, 34(2): 112-125.
[DOI]
|
[4] |
NAULT JC, PARADIS V, CHERQUI D, et al. Molecular classification of hepatocellular adenoma in clinical practice[J]. J Hepatol, 2017, 67(5): 1074-1083.
[DOI]
|
[5] |
GARCOVICH M, FACCIA M, MELONI F, et al. Contrast-enhanced ultrasound patterns of hepatocellular adenoma: an Italian multicenter experience[J]. J Ultrasound, 2019, 22(2): 157-165.
[DOI]
|
[6] |
TAIMR P, BROKER M, DWARKASING RS, et al. A model-based prediction of the probability of hepatocellular adenoma and focal nodular hyperplasia based on characteristics on contrast-enhanced ultrasound[J]. Ultrasound Med Biol, 2017, 43(10): 2144-2150.
[DOI]
|
[7] |
DONG Y, ZHU Z, WANG WP, et al. Ultrasound features of hepatocellular adenoma and the additional value of contrast-enhanced ultrasound[J]. Hepatobiliary Pancreat Dis Int, 2016, 15(1): 48-54.
[DOI]
|
[8] |
MANICHON AF, BANCEL B, DURIEUX-MILLON M, et al. Hepatocellular adenoma: evaluation with contrast-enhanced ultrasound and MRI and correlation with pathologic and phenotypic classification in 26 lesions[J]. HPB Surg, 2012, 2012: 418745.
|
[9] |
DIETRICH CF, NOLSOE CP, BARR RG, et al. Guidelines and good clinical practice recommendations for contrast-enhanced ultrasound (CEUS) in the Liver-Update 2020 WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS[J]. Ultrasound Med Biol, 2020, 46(10): 2579-2604.
[DOI]
|
[10] |
TORBENSON M. Hepatic adenomas: classification, controversies, and consensus[J]. Surg Pathol Clin, 2018, 11(2): 351-366.
[DOI]
|
[11] |
MARRERO JA, AHN J, RAJENDER RK. ACG clinical guideline: the diagnosis and management of focal liver lesions[J]. Am J Gastroenterol, 2014, 109(9): 1328-1347, 1348.
[DOI]
|
[12] |
EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER (EASL). EASL Clinical Practice Guidelines on the management of benign liver tumours[J]. J Hepatol, 2016, 65(2): 386-398.
[DOI]
|
[13] |
韩晶, 陈伶俐, 张欣, 等. 单中心肝细胞核因子1A失活型肝细胞腺瘤临床病理特征[J]. 中国临床医学, 2020, 27(3): 457-460. [CNKI]
|
[14] |
KLOMPENHOUWER AJ, DE MAN RA, THOMEER MG, et al. Management and outcome of hepatocellular adenoma with massive bleeding at presentation[J]. World J Gastroenterol, 2017, 23(25): 4579-4586.
[DOI]
|
[15] |
BROKER M, GASPERSZ MP, KLOMPENHOUWER AJ, et al. Inflammatory and multiple hepatocellular adenoma are associated with a higher BMI[J]. Eur J Gastroenterol Hepatol, 2017, 29(10): 1183-1188.
[DOI]
|
[16] |
DIETRICH CF, TANNAPFEL A, JANG HJ, et al. Ultrasound imaging of hepatocellular adenoma using the new histology classification[J]. Ultrasound Med Biol, 2019, 45(1): 1-10.
[DOI]
|
[17] |
LAUMONIER H, CAILLIEZ H, BALABAUD C, et al. Role of contrast-enhanced sonography in differentiation of subtypes of hepatocellular adenoma: correlation with MRI findings[J]. AJR Am J Roentgenol, 2012, 199(2): 341-348.
[DOI]
|
[18] |
ZARZOUR JG, PORTER KK, TCHELEPI H, et al. Contrast-enhanced ultrasound of benign liver lesions[J]. Abdom Radiol (NY), 2018, 43(4): 848-860.
[DOI]
|
[19] |
MULLER-PELTZER K, RUBENTHALER J, NEGRAO DFG, et al. CEUS-diagnosis of benign liver lesions[J]. Radiologe, 2018, 58(6): 521-527.
[DOI]
|
[20] |
GUO Y, LI W, CAI W, et al. Diagnostic value of gadoxetic acid-enhanced MR imaging to distinguish HCA and its subtype from FNH: a systematic review[J]. Int J Med Sci, 2017, 14(7): 668-674.
[DOI]
|