Contrast-Enhanced Ultrasound in the Characterization of Hepatocellular Carcinomas Treated by Ablation: Comparison with Contrast-Enhanced Magnetic Resonance Imaging

The purpose of this study was to evaluate the clinical utility of low-mechanical-index contrast-enhanced ultrasound (CEUS) in assessing the response to percutaneous microwave ablation in patients with hepatocellular carcinoma by comparing the results with those of contrast-enhanced magnetic resonance imaging (CEMRI). Between August 2005 and July 2011, 182 patients with 231 lesions treated by microwave ablation were included in the study. One month after microwave ablation, CEUS and CEMRI were performed to evaluate therapeutic responses. The difference in diagnostic accuracy between the two methods was analyzed to evaluate the value of contrast-enhanced ultrasound after microwave ablation. The final diagnosis was based on computed tomography and MRI typical findings of therapeutic response of hepatocellular carcinoma, proven serum tumor marker levels and additional follow-up. The sensitivity of CEUS and CEMRI in evaluating the therapeutic effect of hepatocellular carcinoma was 86.5% and 84.6%; the specificity, 98.3% and 98.9%; and the accuracy, 95.7% and 95.7%.There was no significant statistical disparity between CEUS and CEMRI (p > 0.05).The sensitivity, specificity and accuracy were 98.1, 97.2 and 97.8% when CEUS was used in combination with CEMRI to evaluate the therapeutic response of hepatocellular carcinoma to microwave ablation. CEUS examination was proven to be a tolerable and easy modality for assessment of the therapeutic effect of microwave ablation and can provide results comparable to those obtained with CEMRI. Combining the results of these two examinations may reduce false-positive and false-negative diagnoses.     

原发性肝癌实时谐波超声造影初始强化形式的临床研究

目的探讨原发性肝癌实时谐波超声造影(CEUS)动脉早期初始强化形式及意义。方法观察完整时相,分析初始强化形式及与二维图像、CDFI的关系。结果肝癌病灶的超声造影初始强化表现大致分为“树枝型”、“环绕型”、“混合型”。二维图像“树枝型”多表现为形态不整、边界不清;“环绕型”病灶边界清晰或伴有声晕;CDFI“树枝型”内部血供较丰富,“环绕型”周围血管较丰富。“混合型”二维图像及CDFI表现介于二者之间。结论将超声增强初始强化表现与二维图像、CDFI相结合,为研究肿瘤的影像学表现与生物学行为之间的关系提供了有利的帮助。     

The Degree of Contrast Washout on Contrast-Enhanced Ultrasound in Distinguishing Intrahepatic Cholangiocarcinoma from Hepatocellular Carcinoma

We aim to assess the role and degree of contrast washout in the differential diagnosis of intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). Fifty-six histopathology-confirmed ICC nodules and 184 HCC nodules were included in this study. The nodules' washout degree on CEUS at 1, 2 and 3 min was semi-quantitatively and qualitatively assessed using gray-scale video signal intensity. Semi-quantitative assessment showed that the washout degree of ICCs at 1, 2 and 3 min were significantly lower than those of HCCs (p < 0.001) and similar results were found in the same size range subgroups. There were no significant differences in the washout degree of ICCs between patients with chronic hepatitis and those without. The areas under receiver operating characteristic curves, using the nodules' washout degree at 1, 2 and 3 min to differentiate ICC from HCC, were 0.957, 0.979 and 0.982, respectively. The qualitative assessment showed the washout of ICCs was more rapid and obvious than that of HCCs. At 3 min, moderate and marked washout were observed in all ICCs, but in only 12.5% HCCs (p < 0.001). In conclusion, ICCs displayed much higher degree of contrast washout than HCCs on CEUS, which allowed for differentiation from HCCs.     

原发性肝癌实时超声造影时间窗的临床研究

目的 探讨原发性肝癌（HCC）超声造影（CEUS）时间窗及影响因素。 方法 经左肘静脉团注造影剂SonoVue 2．4ml后，分别以肝动脉、门脉主干或二、三级分支显影作为动脉相（AP）、门脉相（PVP）的开始，肝实质回声增强达峰值视为实质相（PP）的开始，2min后为延迟相（DP）。 结果 肝癌CEUS各时相出现的早晚及持续时间的长短，主要与HCC血供性质有关，血管间短路亦有一定影响。HCC血供分2种形式，第一型最多见，呈动态变化过程。初期以门静脉供血为主，动脉呈低血供，而后二者均减少，随着瘤体的增大，动脉供血逐渐增加呈等血供，直至高血供。第二型则主要以门静脉供血为主。以动脉供血为主的HCC，AP快速强化，PVP消退，该表现见于大多数HCC。以门静脉供血为主者，AP、PVP均强化，至PP方消退，该现象见于小肝癌（sHCC）。动门瘘时可使AP缩短，PVP提前显影。 结论 以相关血管显影作为时相的起始及时段，能较全面反映肿瘤特征，有助于定性诊断。主供血管的性质将影响时相的起始及长短。     

乙型肝炎及丙型肝炎病毒对肝细胞癌临床病理特征及预后的影响

目的：探讨乙肝病毒及丙肝病毒感染对肝细胞癌的临床病理特征及预后的影响。方法：收集1995—2000年在复旦大学肝癌研究所行手术切除的355例肝细胞癌患者临床病理资料及术后随访资料。其中乙肝相关肝细胞癌163例（HBV组）,丙肝相关肝细胞癌73例（HCV组）,119例非病毒相关肝细胞癌作为对照组（NBNC组）,分析乙型肝炎病毒及丙型肝炎病毒对肝细胞癌的临床病理特征及预后的影响。结果：临床病理特征：乙肝相关肝细胞癌患者年龄轻,男性患者比例高,甲胎蛋白（AFP）均值高;丙肝相关肝细胞癌患者年龄最大,术前丙氨酸氨基转移酶（ALT）升高伴白蛋白降低者比例高,体检发现的小肝癌居多,肿瘤分期相对较早;NBNC组患者由于无肝病背景,往往缺乏定期体检,多因出现临床症状就诊,故发现时以大肝癌为主,合并血管侵犯,肿瘤突破包膜者比例高。术后生存情况：HBV-HCC组患者中位生存期为15个月,1-,3-,5～7-年生存率分别为：71.0%,34.0%,30.7%和11.53%;HCV-HCC组中位生存期为19个月,1-,3-,5～7-年生存率分别为90.3%,68.2%,41.9%和31.41%。提示丙肝病毒相关肝细胞癌总体预后好于乙肝病毒相关肝细胞癌（χ2=10.92,P〈0.001）。多因素分析提示病毒感染类型是肝细胞癌预后的独立影响因素。相对于无病毒感染肝细胞癌患者而言,乙肝相关肝细胞癌术后死亡的风险是前者的1.5倍（P=0.03）,而丙肝相关肝细胞癌术后死亡的风险是其0.85（P=0.58）。结论：乙肝病毒与丙肝病毒相关肝细胞癌的临床病理特征及预后有显著差异。丙肝相关肝细胞癌总体预后好于乙肝相关肝细胞癌。     

Intensity-Based Assessment of Microbubble-Enhanced Ultrasonography: Phase-Related Diagnostic Ability for Cellular Differentiation of Hepatocellular Carcinoma

This prospective study aimed to elucidate the effect of phase-related quantitative parameters of contrast-enhanced ultrasound (CEUS) with perflubutane microbubble agent to assess the cellular differentiation of hepatocellular carcinoma (HCC). Intensity was analyzed in 94 lesions (19.4 ± 4.9 mm, 86 patients), 47 well-differentiated HCCs (wHCCs) and 47 moderately-differentiated HCCs (mHCCs): I_e (early phase) = I_te (tumor) − I_le (liver), I_p (post-vascular phase) = I_tp (tumor) − I_lp (liver), I_ep = I_e − I_p. The area under the receiver operating characteristic curve with the best cutoff value (I_e, 13.2, I_p, −4.5, I_ep, 21.3) for discriminating between wHCC and mHCC was 0.6922 for I_e, 0.7680 for I_p and 0.7925 for I_ep, which indicated a significantly greater ability to differentiate between wHCC and mHCC compared with visual/qualitative assessment (early phase, 0.6170, p = 0.04; post-vascular phase, 0.6702, p = 0.01; both phases, 0.7021, p = 0.04). In conclusion, I_ep was found to have the highest diagnostic ability, suggesting it is a promising parameter for the cellular differentiation of HCCs with CEUS.     

超声造影分析二乙基亚硝胺诱发性大鼠肝癌模型的实验研究

目的探讨超声造影评估二乙基亚硝胺诱发性大鼠肝癌模型的可行性。方法20只雄性Wistar大鼠采用30mg/kg腹腔注射二乙基亚硝胺。第14周开始每周轮流抽取5只大鼠进行超声检查,发现肝脏结节的大鼠,进行超声造影(CEUS)检查。检查后处死取标本进行病理诊断。结果大鼠超声检查前死亡率45%(9/20),肝癌造模成功率80%(16/20)。肝细胞癌(HCC)病灶超声检出率72.5%(29/40)。55.2%(16/29)HCC病灶呈“高回声增强-无廓清”为主要CEUS增强模式。结论此动物肝癌模型成瘤率较高,CEUS可用于此模型的评估。     

肝细胞性肝癌超声造影的增强模式 --低机械指数连续实时成像技术的应用研究

目的　分析采用低机械指数连续实时成像技术时肝细胞性肝癌 (HCC)超声造影的增强模式。方法　 6 8例 HCC患者共 72个病灶接受了超声造影检查。采用对比脉冲序列 (CPS)成像技术 ,造影剂为 Sono Vue。结果　静脉注射 Sono Vue后 ,全部病灶均可见强化 ,绝大多数病灶 (70 /72 ,97.2 % )增强早于肝实质及门静脉 ;增强形态主要为均匀或不均匀增强 ;增强程度在动脉期高于肝实质 ,门静脉期和肝窦期则低于肝实质 ;动脉期 30 .6 % (2 2 /72 )的病灶可见包膜强化。结论　 HCC在各时相的增强模式具有特征性 ,采用 CPS技术及造影剂 Sono Vue能实时连续地描述 HCC的增强特点。     

肝细胞性肝癌超声造影表现与肿瘤病理分化关系的研究

目的探讨肝细胞性肝癌（HCC）超声造影（CEUS）表现与肿瘤病理分化的关系。方法121个HCC病灶接受了CEUS和病理学检查。CEUS使用造影剂声诺维和对比脉冲序列（CPS）成像技术，组织病理诊断按Edmonson法分类。结果肿瘤分化程度与肿瘤增强变低时间呈线性相关。不同分化程度的肿瘤增强变低的时间及延迟期肿瘤的增强水平均有明显差异（P=0．04、P=0．026），但肿瘤开始增强时间、增强变等时间以及动脉期和门脉期肿瘤的增强水平无明显差异（P=0．26、P=0．33、P=0．23、P=0．58）。结论在CEUS上HCC增强消退的时间与肿瘤分化程度相关。分化好的HCC病灶增强减退较慢，少数病灶门脉期或延迟期仍可呈等或高增强，分化差的肿瘤增强减退较快，绝大多数病灶门脉期或延迟期呈低增强。     

超声造影微血管成像技术评价肝细胞性肝癌微血管构筑及病理相关

目的评价微血管造影成像（micro flow imaging，MFI）对肝细胞性肝癌（HCC）微血管构筑的显示，探讨HCC血管构筑与病理分化程度的关系。 方法对37例病理确诊的HCC超声造影，造影剂为声诺维，成像方法为常规对比谐波成像（contrast harmonic imaging，CHI）以及MFI。观察2种成像方法对肿瘤内微血管的显示效果、微血管的形态及其与肿瘤病理分化的关系。组织病理诊断按Edmonson法分类。 结果37个病灶在CHI均为动脉期高增强、门脉期及延迟期低增强，动脉期肿瘤血管显示率为54．05％。MFI清晰显示全部病灶微血管构筑，形态分为3型：棉花型12（32．4％）、灌木型22（59．5％）、枯枝型3（8．1％）。肿瘤微血管构筑与病理分化程度相关：75．0％（3／4）EdmonsonⅠ级HCC表现为棉花型，75．0％（18／24）EdmonsonⅡHCC表现为灌木型，而枯枝型只见于EdmonsonⅢ、Ⅳ级HCC。 结论MFI可敏感地显示HCC微血管构筑。HCC肿瘤微血管构筑与病理分化程度相关。     

超声造影评估肝癌消融局部疗效价值的研究

目的评价超声造影判定肝癌消融局部疗效的价值。 方法对183例肝细胞性肝癌共248个结节行超声引导下经皮化学或热消融治疗，用超声造影判定局部疗效，造影剂为声诺维，使用低机械指数连续成像技术。以同期的增强CT或MRI作为金标准，作诊断性试验评估超声造影的判定效能。 结果增强CT或MRI判定78．2％（194／248）的病灶达到完全消融，21．8％（54／248）的肿瘤消融不全；超声造影判定79．O％（196／248）的病灶达到完全消融，21.0％（52／248）的病灶消融不全。同增强CT或MRI比较，超声造影诊断的敏感性、特异性、阳性预测值、阴性预测值、准确性分别为90．7％（49／54）、98．5％（191／194）、94．2％（49／52）、97．4％（191／196）、96．8％（240／248）。 结论超声造影判定肝癌消融局部疗效具有与增强CT或MRI同等的价值。     

唾液酸化的路易斯-X抗原和PTEN表达与肝细胞癌转移和预后的关系

目的 :探讨唾液酸化的路易斯 -X抗原 (sialylLewis -X ,SLeX)和PTEN表达与肝细胞癌 (HCC)转移和预后的关系。方法 :应用免疫组织化学方法 ,检测分析 110例HCC组织中SLexPTEN蛋白表达 ,结合随访资料分析。结果 :在HCC中 ,SLeX和PTEN阳性表达率分别为 39 1%和 33 6 %。SleX阳性表达的HCC转移率高 (P<0 0 5 )、分化程度和患者 >5年生存率低 (P <0 0 5 ) ;PTEN阳性表达的HCC转移率低 (P <0 0 5 )、分化程度和患者 >5年生存率高 (P <0 0 5 )。SLeX表达与PTEN表达呈负相关 (r=- 0 5 7,P <0 0 0 5 )。结论 :SLeX和PTEN表达与HCC转移和患者生存期密切相关 ,检测和PTEN蛋白的表达可作为判断HCC预后的参考指标     

超声造影与对比增强CT诊断肝细胞癌的比较研究

目的采用超声造影(CEUS)新技术诊断肝细胞性肝癌(HCC),与对比增强CT(CECT)比较其增强表现,评估CEUS的临床应用价值。方法98个HCC病灶接受了CEUS和CECT检查。CEUS造影剂为声诺维,对比脉冲序列(CPS)成像技术。CECT造影剂为优维显,常规双期增强扫描。结果98个(100%)病灶在CEUS和CECT动脉期均显示增强,表现为高增强分别为98个(100%)和94个(95.9%,P=0.121),CECT4个(4.1%)病灶表现为等增强。在门脉期,CEUS和CECT显示病灶消退至低增强分别为82个(83.7%)和83个(84.7%),P=0.845。CEUS和CECT显示肿瘤周边薄环状增强的病灶数目分别为30个(30.6%)和31个(31.6%,P=0.877),显示瘤内血管的病灶数目分别为94个(95.9%)和36个(36.7%,P=0.000)。结论HCC的CEUS增强表现与CECT一致,为临床提供了一种简便易行的HCC定性诊断手段。     

超声造影谐频成像与螺旋CT对肝癌非手术治疗后疗效的评价

目的　评价比较超声造影双向脉冲谐频成像和螺旋CT在判断肝肿瘤治疗效果方面的价值。方法　对经多种非手术治疗后的肝癌患者 72例共 82个肿瘤分别进行超声造影和螺旋CT检查 ,比较两种影像技术的结果。结果　超声造影谐频成像的连续成像和间歇成像可分别显示肝肿瘤的血管影像和血流灌注情况。超声造影显示造影增强者 5 4.9% (4 5 /82 ) ,负性增强者 45 .1% (3 7/82 ) ;螺旋CT显示不完全治愈者 5 3 .7% (4 4 /82 ) ,完全治愈者 40 .2 % (3 3 /82 ) ,其余 6.1% (5 /82 )因碘油沉积而不能明确判断。结论　与螺旋CT相比 ,超声造影揭示治疗后的肿瘤内血流信号的敏感性、特异性和准确性均较高 ;由于超声声像图较少受碘油沉积的影响以及其影像可直接引导进一步的穿刺局部治疗 ,超声造影更适宜于TAE术后肿瘤的疗效判断     

超声监控超声聚焦刀治疗肝癌及疗效评价研究

目的 :评价声像图引导定位、实时监控超声聚焦刀治疗肝癌的可靠性和实用性。方法 :应用超声聚焦刀治疗原发性肝癌 5 6例 ,转移性肝癌 12例。结果 :超声引导焦点定位准确可靠。实时监控显示的回声增强是判断治疗有效的可靠指标。治疗后超声显示回声增强 ,随后中心回声减低 ,边缘回声增强 ,血供消失或明显减少 ,最终回声不均匀增强是疗效显著地特征性表现。结论 :超声能准确有效地引导焦点定位、实时疗效监控及治疗后的疗效评价     

Irregular Defects in Hepatocellular Carcinomas During the Kupffer Phase of Contrast-Enhanced Ultrasonography with Perfluorobutane Microbubbles: Pathological Features and Metastatic Recurrence After Surgical Resection

The present study aimed to elucidate the association between post-vascular–phase (Kupffer-phase) images from contrast-enhanced ultrasonography (CEUS) with perfluorobutane microbubbles and metastatic recurrences after the resection of hepatocellular carcinoma (HCC). The study examined 73 patients with solitary HCC ≤5 cm in diameter who underwent CEUS before resection. HCC was defined as irregular type (including an irregular defect on Kupffer-phase images) or non-irregular type. Intrahepatic metastatic recurrence was defined as >3 intrahepatic recurrences. Metastatic recurrence included both extrahepatic and intrahepatic recurrences. Frequencies of microscopic portal invasion and intrahepatic metastasis were significantly higher in the irregular group than in the non-irregular group. Cumulative 5-y metastatic recurrence rates in the irregular and non-irregular groups were 43% and 7% (p = 0.028), respectively. Multivariate analyses identified Kupffer-phase findings as a factor significantly related to metastatic recurrence. In conclusion, HCCs with an irregular defect during Kupffer-phase CEUS are characterized by more frequent microscopic vascular invasion and intrahepatic metastasis and are significantly associated with metastatic recurrence after resection.     

肝细胞肝癌化疗栓塞后二期切除22例临床分析

目的：为探讨一期不能切除的肝细胞肝癌（HCC）经肝动脉化疗栓塞及经门静脉插管化疗缩小后再切除的疗效,总结1997年10月至1998年10月间22例治疗经验。方法：经皮肝动脉穿刺化疗栓塞（TACE）后切除17例,经肝动脉结扎加插管栓塞化疗（HACE）后再切除3例,肝动脉结扎加肝动脉、门静脉双插管栓塞化疗后再切除2例。化疗栓塞前叶瘤直径6.7～18cm,平均9．85cm。平均接受化疗栓塞治疗2.45次,手术切除时瘤径缩小至5.77cm。末次化疗距手术时间1～7个月,平均3．47个月。化疗栓塞前甲胎蛋白（AFP）阳性15例,阴性7例,化疗栓塞后11例降至正常,手术切除后2个月均降至正常。手术方法：左半肝切除2例,右半肝切除3例,尾状叶切除1例,其他均为肝脏部分切除。切除肿瘤病理大体所见40％～90％坏死,14例周边出现新癌灶,镜下仍见癌组织。结果：本组病例无手术死亡,经随访均无瘤生存至今,治疗效果满意。结论：原发性肝癌化疗栓塞后再切除已成为一种提高HCC手术切除率,延长HCC患者生存时间的有效措施。     

Utility of Contrast-enhanced Ultrasonography with Perflubutane for Determining Histologic Grade in Hepatocellular Carcinoma

The purpose of this study was to clarify the diagnostic value of contrast-enhanced ultrasonography (CEUS) with perflubutane in determining the histologic grade in hepatocellular carcinoma (HCC). A total of 147 surgically resected HCCs were dichotomized as well differentiated HCC (wd-HCC) and moderately- or poorly-differentiated HCC (mp-HCC). CEUS findings were evaluated during the arterial phase (vascularity, level and shape of enhancement), portal phase (presence or absence of washout) and post-vascular phase (echo intensity and shape). Receiver operating characteristic (ROC) curve analysis for the diagnosis of mp-HCC yielded area under the ROC curve (A_z) values for arterial phase vascularity and portal phase washout of 0.910 and 0.807, respectively. The A_z value for the combination of vascularity and washout for the diagnosis of mp-HCC was 0.956 (95% confidence interval, 0.910–0.979), corresponding to high diagnostic value. In conclusion, CEUS can provide high-quality imaging assessment for determining the histologic grade of HCCs.     

免疫脂质体超声造影剂增强荷肝癌裸鼠肿瘤显像的实验研究

目的探讨人肝细胞癌靶向脂质体超声造影剂对荷肝癌裸鼠肿瘤的增强显像效果。方法采用人肝癌细胞株HHCC接种于裸鼠皮下,建立荷人肝癌裸鼠模型;将靶向脂质体超声造影剂或普通脂质体超声造影剂经尾静脉注入荷瘤裸鼠体内,使用二次谐波显像模式观察并记录造影过程;采用目测观察和视频灰阶分析技术,以时间-强度曲线分析来定量评价肿瘤显像的增强效果。结果造影后目测观察,靶向造影剂对肿瘤有延迟增强显像效果,靶向造影剂组肿瘤的增强显影约在8min达到峰值,峰值灰阶强度值为(39.545±10.099)dB;普通造影剂组肿瘤增强显影达峰值时间约为10s,峰值灰阶强度值为(22.438±5.108)dB,与靶向造影剂造影后灰阶强度峰值比较相差显著(P<0.01)。结论人肝细胞癌靶向脂质体超声造影剂可以增强荷人肝癌裸鼠的肿瘤超声显像效果。