TACE联合索拉非尼治疗后原发性肝细胞癌的血流灌注变化
|
摘要
背景临床上常常采用经导管肝动脉化疗栓塞(transcatheter artery chemoembolization, TACE)联合索拉非尼等分子靶向药物治疗不能手术切除的晚期原发性肝细胞癌(hepatocellular carcinoma,HCC),并取得确切疗效.超声造影具有便捷、无创等优点,能实时反映肿瘤的血流灌注状态,在疗效评估方面发挥着重要作用,可为临床疗效评估提供血流动力学信息.目的运用超声造影评估TACE联合索拉非尼治疗后原发性HCC的血流灌注变化,探讨其临床应用价值.方法选取浙江萧山医院收治并经肝穿刺病理证实的86例HCC患者作为研究对象(共86个病灶),按照不同治疗方法随机分为TACE治疗组(A组, 43例)和TACE+索拉非尼治疗组(B组, 43例),所有患者于治疗前1 d及治疗后3 mo行超声造影检查,比较病灶治疗前后血流灌注参数变化.结果 B组病灶治疗后增强强度、曲线下面积均较治疗前减少,差异有统计学意义(P<0.05); B组病灶治疗后增强强度、曲线下面积均较A组病灶治疗后明显减少,差异有统计学意义(P<0.05).结论超声造影能定量评估TACE联合索拉非尼治疗后HCC血流灌注变化,可为临床早期评估疗效提供有价值的血流动力学信息.
BACKGROUND Transcatheter artery chemoembolization(TACE)combined with molecular targeted drugs(sorafenib) are often used in the treatment of unresectable hepatocellular carcinoma(HCC) with definite efficacy. Contrastenhanced ultrasound(CEUS) has the advantages of convenience and non-invasiveness and can reflect the blood perfusion status of tumors in real time, playing an important role in the evaluation of clinical efficacy.AIM To evaluate the changes of blood perfusion after TACE combined with sorafenib for HCC by CEUS, and to explore its clinical value. METHODS A total of 86 HCC patients who were admitted to our hospital and confirmed by liver puncture pathology were selected as the subjects(86 lesions). According to the treatment method used, they were randomly divided into a TACE alone group(group A, 43 cases) or a TACE + sorafenib group(group B, 43 cases). All patients underwent CEUS examinations one day before and three months after treatment, and blood perfusion parameters before and after treatment were compared. RESULTS The enhancement intensity and the area under the curve in both groups A and B after treatment were significantly lower than those before treatment(P < 0.05). The enhancement intensity and the area under the curve in group B after treatment were significantly lower than those in group A after treatment(P < 0.05). CONCLUSION CEUS can quantitatively evaluate the changes of blood perfusion after TACE combined with sorafenib for HCC, and provide valuable hemodynamic information for early clinical evaluation.
BACKGROUND Transcatheter artery chemoembolization(TACE)combined with molecular targeted drugs(sorafenib) are often used in the treatment of unresectable hepatocellular carcinoma(HCC) with definite efficacy. Contrastenhanced ultrasound(CEUS) has the advantages of convenience and non-invasiveness and can reflect the blood perfusion status of tumors in real time, playing an important role in the evaluation of clinical efficacy.AIM To evaluate the changes of blood perfusion after TACE combined with sorafenib for HCC by CEUS, and to explore its clinical value. METHODS A total of 86 HCC patients who were admitted to our hospital and confirmed by liver puncture pathology were selected as the subjects(86 lesions). According to the treatment method used, they were randomly divided into a TACE alone group(group A, 43 cases) or a TACE + sorafenib group(group B, 43 cases). All patients underwent CEUS examinations one day before and three months after treatment, and blood perfusion parameters before and after treatment were compared. RESULTS The enhancement intensity and the area under the curve in both groups A and B after treatment were significantly lower than those before treatment(P < 0.05). The enhancement intensity and the area under the curve in group B after treatment were significantly lower than those in group A after treatment(P < 0.05). CONCLUSION CEUS can quantitatively evaluate the changes of blood perfusion after TACE combined with sorafenib for HCC, and provide valuable hemodynamic information for early clinical evaluation.
引文
1王卉,张弢,李文刚,段学章.原发性肝细胞癌系统化疗研究进展.传染病信息2016;29:241-248[DOI:10.3969/j.issn.1007-8134.2016.04.011]
2王仕模,胡永浩,李强.AFP水平与原发性肝细胞癌手术患者预后的相关分析.中华肝胆外科杂志2017;23:134[DOI:10.3760/cma.j.issn.1007-8118.2017.02.016]
3 Sherman M.Hepatocellular carcinoma:epidemiology,surveillance,and diagnosis.Semin Liver Dis 2010;30:3-16[PMID:20175029 DOI:10.1055/s-0030-1247128]
4 Xu L,Zhang M,Zheng X,Yi P,Lan C,Xu M.The circular RNAci RS-7(Cdr1as)acts as a risk factor of hepatic microvascular invasion in hepatocellular carcinoma.J Cancer Res Clin Oncol 2017;143:17-27[PMID:27614453 DOI:10.1007/s00432-016-2256-7]
5张明娟,刘佳,向晓星,邓登豪,王甦.TACE联合索拉非尼治疗晚期肝癌的Meta分析.中华肿瘤防治杂志2015;22:148-154[DOI:10.3969/j.issn.1001-5256.2014.08.037]
6张鹏,顾爱丽,石东梅.TACE联合索拉非尼治疗晚期肝癌的疗效观察.北方药学2017;14:109-110[DOI:10.3969/j.issn.1672-8351.2017.05.088]
7 Ozakyol A.Global Epidemiology of Hepatocellular Carcinoma(HCC Epidemiology).J Gastrointest Cancer 2017[PMID:28626852 DOI:10.1007/s12029-017-9959-0]
8 van Zijl F,Zulehner G,Petz M,Schneller D,Kornauth C,Hau M,Machat G,Grubinger M,Huber H,Mikulits W.Epithelialmesenchymal transition in hepatocellular carcinoma.Future Oncol 2009;5:1169-1179[PMID:19852728 DOI:10.2217/fon.09.91]
9 Sidhu PS,Cantisani V,Dietrich CF,Gilja OH,Saftoiu A,Bartels E,Bertolotto M,Calliada F,Clevert DA,Cosgrove D,Deganello A,D’Onofrio M,Drudi FM,Freeman S,Harvey C,Jenssen C,Jung EM,Klauser AS,Lassau N,Meloni MF,Leen E,Nicolau C,Nolsoe C,Piscaglia F,Prada F,Prosch H,Radzina M,Savelli L,Weskott HP,Wijkstra H.The EFSUMB Guidelines and Recommendations for the Clinical Practice of ContrastEnhanced Ultrasound(CEUS)in Non-Hepatic Applications:Update 2017(Long Version).Ultraschall Med 2018;39:e2-e44[PMID:29510439 DOI:10.1055/a-0586-1107]
10 Liu XS,Gu LH,Du J,Li FH,Wang J,Chen T,Zhang YH.Differential diagnosis of polypoid lesions of the gallbladder using contrast-enhanced sonography.J Ultrasound Med 2015;34:1061-1069[PMID:26014326 DOI:10.3748/wjg.v24.i6.744]
11 Goumard C,Komatsu S,Brustia R,Fartoux L,Soubrane O,Scatton O.Technical feasibility and safety of laparoscopic right hepatectomy for hepatocellular carcinoma following sequential TACE-PVE:a comparative study.Surg Endosc 2017;31:2340-2349[PMID:27655376 DOI:10.1007/s00464-016-5225-y]
12 Bettinger D,Gkika E,Schultheiss M,Glaser N,Lange S,Maruschke L,Buettner N,Kirste S,Nestle U,Grosu AL,Thimme R,Brunner TB.Comparison of local tumor control in patients with HCC treated with SBRT or TACE:a propensity score analysis.BMC Cancer 2018;18:807[PMID:30092781 DOI:10.1186/s12885-018-4696-8]
13周学士,任雷,彭蕾,叶阳群,朱晓黎,冯婷婷,赵卫峰.索拉非尼联合肝动脉化疗栓塞术治疗中晚期肝细胞癌疗效观察.实用肝脏病杂志2015;11:59-62[DOI:10.3969/j.issn.1672-5069.2015.01.0]
14 Chen L,Zheng Y,Zhang H,Pan H,Liu Q,Zhou X,Wei W,Liu Y,Zhen M,Wang J,Zhou J,Zhao Y.Comparative analysis of tumor-associated vascular changes following TACE alone or in combination with sorafenib treatment in HCC:A retrospective study.Oncol Lett 2018;16:3690-3698[PMID:30127979 DOI:10.3892/ol.2018.9055]
15 Duffy AG,Ulahannan SV,Makorova-Rusher O,Rahma O,Wedemeyer H,Pratt D,Davis JL,Hughes MS,Heller T,ElGindi M,Uppala A,Korangy F,Kleiner DE,Figg WD,Venzon D,Steinberg SM,Venkatesan AM,Krishnasamy V,Abi-Jaoudeh N,Levy E,Wood BJ,Greten TF.Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma.J Hepatol 2017;66:545-551[PMID:27816492 DOI:10.1016/j.jhep.2016.10.029]
16 El Kassas M,Funk AL,Salaheldin M,Shimakawa Y,Eltabbakh M,Jean K,El Tahan A,Sweedy AT,Afify S,Youssef NF,Esmat G,Fontanet A.Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort:A comparative analysis.J Viral Hepat 2018;25:623-630[PMID:29274197 DOI:10.1016/j.dld.2018.01.054]
17王小琴,彭玲,罗丹,王艳,谢莎.血清ANGPTL2及DCP用于HCC诊断的临床价值研究.河北医药2018;40:485-488[DOI:10.3969/j.issn.1002-7386.2018.04.001]
18程亚,荚卫东,邢松歌,许戈良.解剖性肝切除术治疗合并微血管侵犯肝细胞癌的临床疗效.中华消化外科杂志2017;16:144-150[DOI:10.3760/cma.j.issn.1673-9752.2017.02.008]
19陈洁,黎乐群.术前预测肝细胞癌并微血管侵犯的研究进展.中国普通外科杂志2017;26:921-925[DOI:10.3978/j.issn.1005-6947.2017.07.017]
20丁光宇,朱小东,施国明,沈英皓,蔡加彬,孙惠川,周俭,樊嘉,黄成.微血管侵犯在复发性肝细胞癌中的临床价值.肝胆胰外科杂志2018;30:182-186[DOI:10.11952/j.issn.1007-1954.2018.03.002]
21 Keating GM.Sorafenib:A Review in Hepatocellular Carcinoma.Target Oncol 2017;12:243-253[PMID:28299600DOI:10.1007/s11523-017-0484-7]
22雷学芬,柯阳,鲍天昊,林劼,王琳.索拉非尼治疗肝细胞癌的研究进展.实用医学杂志2017;33:3851-3853[DOI:10.3969/j.issn.1006-5725.2017.23.001]
23高斌成,郭卉,孙乐,周洁,蒋冬梅.舒尼替尼与索拉非尼治疗晚期肝细胞癌的效果比较.临床肝胆病杂志2018;34:104-107[DOI:10.3969/j.issn.1001-5256.2018.08.19]
24 Bruix J,Cheng AL,Meinhardt G,Nakajima K,De Sanctis Y,Llovet J.Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma:Analysis of two phase III studies.J Hepatol 2017;67:999-1008[PMID:28687477DOI:10.1016/j.jhep.2017.06.026]
25石洁琼,康马飞,李碧慧,骆梅青,石援援.全量或半量索拉非尼联合卡培他滨治疗肝细胞肝癌的临床观察.现代肿瘤医学2018;26:90-93[DOI:10.3969/j.issn.1672-4992.2010.02.047]
26王建,陈卫东,刘兴洲,吴永丰.经导管动脉化疗栓塞治疗与联合索拉非尼治疗肝细胞癌合并门静脉癌栓的疗效观察.转化医学杂志2017;6:160-163[DOI:10.3969/j.issn.2095-3097.2017.03.008]
2王仕模,胡永浩,李强.AFP水平与原发性肝细胞癌手术患者预后的相关分析.中华肝胆外科杂志2017;23:134[DOI:10.3760/cma.j.issn.1007-8118.2017.02.016]
3 Sherman M.Hepatocellular carcinoma:epidemiology,surveillance,and diagnosis.Semin Liver Dis 2010;30:3-16[PMID:20175029 DOI:10.1055/s-0030-1247128]
4 Xu L,Zhang M,Zheng X,Yi P,Lan C,Xu M.The circular RNAci RS-7(Cdr1as)acts as a risk factor of hepatic microvascular invasion in hepatocellular carcinoma.J Cancer Res Clin Oncol 2017;143:17-27[PMID:27614453 DOI:10.1007/s00432-016-2256-7]
5张明娟,刘佳,向晓星,邓登豪,王甦.TACE联合索拉非尼治疗晚期肝癌的Meta分析.中华肿瘤防治杂志2015;22:148-154[DOI:10.3969/j.issn.1001-5256.2014.08.037]
6张鹏,顾爱丽,石东梅.TACE联合索拉非尼治疗晚期肝癌的疗效观察.北方药学2017;14:109-110[DOI:10.3969/j.issn.1672-8351.2017.05.088]
7 Ozakyol A.Global Epidemiology of Hepatocellular Carcinoma(HCC Epidemiology).J Gastrointest Cancer 2017[PMID:28626852 DOI:10.1007/s12029-017-9959-0]
8 van Zijl F,Zulehner G,Petz M,Schneller D,Kornauth C,Hau M,Machat G,Grubinger M,Huber H,Mikulits W.Epithelialmesenchymal transition in hepatocellular carcinoma.Future Oncol 2009;5:1169-1179[PMID:19852728 DOI:10.2217/fon.09.91]
9 Sidhu PS,Cantisani V,Dietrich CF,Gilja OH,Saftoiu A,Bartels E,Bertolotto M,Calliada F,Clevert DA,Cosgrove D,Deganello A,D’Onofrio M,Drudi FM,Freeman S,Harvey C,Jenssen C,Jung EM,Klauser AS,Lassau N,Meloni MF,Leen E,Nicolau C,Nolsoe C,Piscaglia F,Prada F,Prosch H,Radzina M,Savelli L,Weskott HP,Wijkstra H.The EFSUMB Guidelines and Recommendations for the Clinical Practice of ContrastEnhanced Ultrasound(CEUS)in Non-Hepatic Applications:Update 2017(Long Version).Ultraschall Med 2018;39:e2-e44[PMID:29510439 DOI:10.1055/a-0586-1107]
10 Liu XS,Gu LH,Du J,Li FH,Wang J,Chen T,Zhang YH.Differential diagnosis of polypoid lesions of the gallbladder using contrast-enhanced sonography.J Ultrasound Med 2015;34:1061-1069[PMID:26014326 DOI:10.3748/wjg.v24.i6.744]
11 Goumard C,Komatsu S,Brustia R,Fartoux L,Soubrane O,Scatton O.Technical feasibility and safety of laparoscopic right hepatectomy for hepatocellular carcinoma following sequential TACE-PVE:a comparative study.Surg Endosc 2017;31:2340-2349[PMID:27655376 DOI:10.1007/s00464-016-5225-y]
12 Bettinger D,Gkika E,Schultheiss M,Glaser N,Lange S,Maruschke L,Buettner N,Kirste S,Nestle U,Grosu AL,Thimme R,Brunner TB.Comparison of local tumor control in patients with HCC treated with SBRT or TACE:a propensity score analysis.BMC Cancer 2018;18:807[PMID:30092781 DOI:10.1186/s12885-018-4696-8]
13周学士,任雷,彭蕾,叶阳群,朱晓黎,冯婷婷,赵卫峰.索拉非尼联合肝动脉化疗栓塞术治疗中晚期肝细胞癌疗效观察.实用肝脏病杂志2015;11:59-62[DOI:10.3969/j.issn.1672-5069.2015.01.0]
14 Chen L,Zheng Y,Zhang H,Pan H,Liu Q,Zhou X,Wei W,Liu Y,Zhen M,Wang J,Zhou J,Zhao Y.Comparative analysis of tumor-associated vascular changes following TACE alone or in combination with sorafenib treatment in HCC:A retrospective study.Oncol Lett 2018;16:3690-3698[PMID:30127979 DOI:10.3892/ol.2018.9055]
15 Duffy AG,Ulahannan SV,Makorova-Rusher O,Rahma O,Wedemeyer H,Pratt D,Davis JL,Hughes MS,Heller T,ElGindi M,Uppala A,Korangy F,Kleiner DE,Figg WD,Venzon D,Steinberg SM,Venkatesan AM,Krishnasamy V,Abi-Jaoudeh N,Levy E,Wood BJ,Greten TF.Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma.J Hepatol 2017;66:545-551[PMID:27816492 DOI:10.1016/j.jhep.2016.10.029]
16 El Kassas M,Funk AL,Salaheldin M,Shimakawa Y,Eltabbakh M,Jean K,El Tahan A,Sweedy AT,Afify S,Youssef NF,Esmat G,Fontanet A.Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort:A comparative analysis.J Viral Hepat 2018;25:623-630[PMID:29274197 DOI:10.1016/j.dld.2018.01.054]
17王小琴,彭玲,罗丹,王艳,谢莎.血清ANGPTL2及DCP用于HCC诊断的临床价值研究.河北医药2018;40:485-488[DOI:10.3969/j.issn.1002-7386.2018.04.001]
18程亚,荚卫东,邢松歌,许戈良.解剖性肝切除术治疗合并微血管侵犯肝细胞癌的临床疗效.中华消化外科杂志2017;16:144-150[DOI:10.3760/cma.j.issn.1673-9752.2017.02.008]
19陈洁,黎乐群.术前预测肝细胞癌并微血管侵犯的研究进展.中国普通外科杂志2017;26:921-925[DOI:10.3978/j.issn.1005-6947.2017.07.017]
20丁光宇,朱小东,施国明,沈英皓,蔡加彬,孙惠川,周俭,樊嘉,黄成.微血管侵犯在复发性肝细胞癌中的临床价值.肝胆胰外科杂志2018;30:182-186[DOI:10.11952/j.issn.1007-1954.2018.03.002]
21 Keating GM.Sorafenib:A Review in Hepatocellular Carcinoma.Target Oncol 2017;12:243-253[PMID:28299600DOI:10.1007/s11523-017-0484-7]
22雷学芬,柯阳,鲍天昊,林劼,王琳.索拉非尼治疗肝细胞癌的研究进展.实用医学杂志2017;33:3851-3853[DOI:10.3969/j.issn.1006-5725.2017.23.001]
23高斌成,郭卉,孙乐,周洁,蒋冬梅.舒尼替尼与索拉非尼治疗晚期肝细胞癌的效果比较.临床肝胆病杂志2018;34:104-107[DOI:10.3969/j.issn.1001-5256.2018.08.19]
24 Bruix J,Cheng AL,Meinhardt G,Nakajima K,De Sanctis Y,Llovet J.Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma:Analysis of two phase III studies.J Hepatol 2017;67:999-1008[PMID:28687477DOI:10.1016/j.jhep.2017.06.026]
25石洁琼,康马飞,李碧慧,骆梅青,石援援.全量或半量索拉非尼联合卡培他滨治疗肝细胞肝癌的临床观察.现代肿瘤医学2018;26:90-93[DOI:10.3969/j.issn.1672-4992.2010.02.047]
26王建,陈卫东,刘兴洲,吴永丰.经导管动脉化疗栓塞治疗与联合索拉非尼治疗肝细胞癌合并门静脉癌栓的疗效观察.转化医学杂志2017;6:160-163[DOI:10.3969/j.issn.2095-3097.2017.03.008]