Name: transradial access chemoembolization for hepatocellular carcinoma patients
Uploaded: 2020-09-20T13:00:00
Description: Watch this Scientific Journal Video about Transradial Access Chemoembolization for Hepatocellular Carcinoma Patients at JoVE.com

This work was supported by the clinical research special fund from Zhongshan Hospital, Fudan University (2016ZSLC17). The authors are very grateful to Dr. Xianglin Hu in Zhongshan Hospital of Fudan University for his very professional suggestions to English writing.

This single-center retrospective study was approved by the local Institutional Review Board of Zhongshan Hospital, Fudan University.
1. Obtaining informed consent
<ol>
	<li>Before the TRA interventions, have interventional radiologists (IRs) explain the benefits and potential complications of TRA to the patients.</li>
</ol>
2. Patient evaluation
<ol>
	<li>After obtaining informed consent, evaluate the RA for the feasibility of puncture and cannulati...

<ol>
	<li>Yoon, S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+and+Safety+of+Transarterial+Chemoembolization+Plus+External+Beam+Radiotherapy+vs+Sorafenib+in+Hepatocellular+Carcinoma+with+Macroscopic+Vascular+Invasion+A+Randomized+Clinical+Trial.">Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma with Macroscopic Vascular Invasion A Randomized Clinical Trial.</a> JAMA Oncology. 4 (5), 661-669 (2018).</li><li>Global Burden of Disease. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Global+Burden+of+Cancer+2013.">The Global Burden of Cancer 2013.</a> JAMA Oncology. 1 (4), 505-527 (2015).</li><li>Iezzi, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transradial+versus+Transfemoral+Access+for+Hepatic+Chemoembolization:+Intrapatient+Prospective+Single-Center+Study.">Transradial versus Transfemoral Access for Hepatic Chemoembolization: Intrapatient Prospective Single-Center Study.</a> Journal of Vascular and Interventional Radiology. 28 (9), 1234-1239 (2017).</li><li>Rao, S. V., Cohen, M. G., Kandzari, D. E., Bertrand, O. F., Gilchrist, I. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+transradial+approach+to+percutaneous+coronary+intervention:+historical+perspective,+current+concepts,+and+future+directions.">The transradial approach to percutaneous coronary intervention: historical perspective, current concepts, and future directions.</a> Journal of the American College of Cardiology. 55 (20), 2187-2195 (2010).</li><li>Hamon, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Consensus+document+on+the+radial+approach+in+percutaneous+cardiovascular+interventions:+position+paper+by+the+European+Association+of+Percutaneous+Cardiovascular+Interventions+and+Working+Groups+on+Acute+Cardiac+Care+and+Thrombosis+of+the+European+Society+of+Cardiology.">Consensus document on the radial approach in percutaneous cardiovascular interventions: position paper by the European Association of Percutaneous Cardiovascular Interventions and Working Groups on Acute Cardiac Care and Thrombosis of the European Society of Cardiology.</a> EuroIntervention. 8 (11), 1242-1251 (2013).</li><li>Feldman, D. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adoption+of+radial+access+and+comparison+of+outcomes+to+femoral+access+in+percutaneous+coronary+intervention:+an+updated+report+from+the+national+cardiovascular+data+registry+(2007-2012).">Adoption of radial access and comparison of outcomes to femoral access in percutaneous coronary intervention: an updated report from the national cardiovascular data registry (2007-2012).</a> Circulation. 127 (23), 2295-2306 (2013).</li><li>Jolly, S. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Radial+versus+femoral+access+for+coronary+angiography+and+intervention+in+patients+with+acute+coronary+syndromes+(RIVAL):+a+randomised,+parallel+group,+multicentre+trial.">Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial.</a> Lancet. 377 (9775), 1409-1420 (2011).</li><li>Valgimigli, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Radial+versus+femoral+access+in+patients+with+acute+coronary+syndromes+undergoing+invasive+management:+a+randomised+multicentre+trial.">Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial.</a> Lancet. 385 (9986), 2465-2476 (2015).</li><li>Du, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transradial+access+chemoembolization+for+hepatocellular+carcinoma+in+comparation+with+transfemoral+access.">Transradial access chemoembolization for hepatocellular carcinoma in comparation with transfemoral access.</a> Translational Cancer Research. 8 (5), 1795-1805 (2019).</li><li>Galyfos, G., Sigala, F., Filis, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transradial+versus+Transfemoral+access+in+patients+undergoing+peripheral+artery+angioplasty/stenting:+A+meta-analysis.">Transradial versus Transfemoral access in patients undergoing peripheral artery angioplasty/stenting: A meta-analysis.</a> Cardiovascular Revascularization Medicine. 19 (4), 457-465 (2018).</li><li>Barbeau, G. R., Arsenault, F., Dugas, L., Simard, S., Lariviere, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+the+ulnopalmar+arterial+arches+with+pulse+oximetry+and+plethysmography:+comparison+with+the+Allen's+test+in+1010+patients.">Evaluation of the ulnopalmar arterial arches with pulse oximetry and plethysmography: comparison with the Allen's test in 1010 patients.</a> American Heart Journal. 147 (3), 489-493 (2004).</li><li>Kiemeneij, F., Laarman, G. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Percutaneous+transradial+artery+approach+for+coronary+Palmaz-Schatz+stent+implantation.">Percutaneous transradial artery approach for coronary Palmaz-Schatz stent implantation.</a> American Heart Journal. 128 (1), 167-174 (1994).</li><li>Achenbach, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transradial+versus+transfemoral+approach+for+coronary+angiography+and+intervention+in+patients+above+75+years+of+age.">Transradial versus transfemoral approach for coronary angiography and intervention in patients above 75 years of age.</a> Catheterization and Cardiovascular Interventions. 72 (5), 629-635 (2008).</li><li>Agostoni, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Radial+versus+femoral+approach+for+percutaneous+coronary+diagnostic+and+interventional+procedures;+Systematic+overview+and+meta-analysis+of+randomized+trials.">Radial versus femoral approach for percutaneous coronary diagnostic and interventional procedures; Systematic overview and meta-analysis of randomized trials.</a> Journal of the American College of Cardiology. 44 (2), 349-356 (2004).</li><li>Caputo, R. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transradial+cardiac+catheterization+in+elderly+patients.">Transradial cardiac catheterization in elderly patients.</a> Catheterization and Cardiovascular Interventions. 51 (3), 287-290 (2000).</li><li>Cox, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+the+risk+of+vascular+complications+associated+with+femoral+and+radial+access+coronary+catheterization+procedures+in+obese+versus+nonobese+patients.">Comparison of the risk of vascular complications associated with femoral and radial access coronary catheterization procedures in obese versus nonobese patients.</a> American Journal of Cardiology. 94 (9), 1174-1177 (2004).</li><li>Titano, J. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+and+Feasibility+of+Transradial+Access+for+Visceral+Interventions+in+Patients+with+Thrombocytopenia.">Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia.</a> Cardiovascular and Interventional Radiology. 39 (5), 676-682 (2016).</li><li>Mortensen, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prospective+Study+on+Total+Fluoroscopic+Time+in+Patients+Undergoing+Uterine+Artery+Embolization:+Comparing+Transradial+and+Transfemoral+Approaches.">Prospective Study on Total Fluoroscopic Time in Patients Undergoing Uterine Artery Embolization: Comparing Transradial and Transfemoral Approaches.</a> Cardiovascular and Interventional Radiology. 42 (3), 441-447 (2019).</li><li>Iezzi, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Operator+learning+curve+for+transradial+liver+cancer+embolization:+implications+for+the+initiation+of+a+transradial+access+program.">Operator learning curve for transradial liver cancer embolization: implications for the initiation of a transradial access program.</a> Diagnostic and Interventional Radiology. 25 (5), 368-374 (2019).</li><li>Mounsey, C. A., Mawhinney, J. A., Werner, R. S., Taggart, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Does+Previous+Transradial+Catheterization+Preclude+Use+of+the+Radial+Artery+as+a+Conduit+in+Coronary+Artery+Bypass+Surgery.">Does Previous Transradial Catheterization Preclude Use of the Radial Artery as a Conduit in Coronary Artery Bypass Surgery.</a> Circulation. 134 (9), 681-688 (2016).</li><li>Hibbert, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transradial+versus+transfemoral+artery+approach+for+coronary+angiography+and+percutaneous+coronary+intervention+in+the+extremely+obese.">Transradial versus transfemoral artery approach for coronary angiography and percutaneous coronary intervention in the extremely obese.</a> JACC: Cardiovascular Interventions. 5 (8), 819-826 (2012).</li><li>Fischman, A. M., Swinburne, N. C., Patel, R. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Technical+Guide+Describing+the+Use+of+Transradial+Access+Technique+for+Endovascular+Interventions.">A Technical Guide Describing the Use of Transradial Access Technique for Endovascular Interventions.</a> Techniques in Vascular and Interventional Radiology. 18 (2), 58-65 (2015).</li><li>Caputo, R. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transradial+arterial+access+for+coronary+and+peripheral+procedures:+executive+summary+by+the+Transradial+Committee+of+the+SCAI.">Transradial arterial access for coronary and peripheral procedures: executive summary by the Transradial Committee of the SCAI.</a> Catheterization and Cardiovascular Interventions. 78 (6), 823-839 (2011).</li><li>Shiozawa, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transradial+approach+for+transcatheter+arterial+chemoembolization+in+patients+with+hepatocellular+carcinoma+-+Comparison+with+conventional+transfemoral+approach.">Transradial approach for transcatheter arterial chemoembolization in patients with hepatocellular carcinoma - Comparison with conventional transfemoral approach.</a> Journal of Clinical Gastroenterology. 37 (5), 412-417 (2003).</li><li>Mitchell, M. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+review+and+cost-benefit+analysis+of+radial+artery+access+for+coronary+angiography+and+intervention.">Systematic review and cost-benefit analysis of radial artery access for coronary angiography and intervention.</a> Circulation: Cardiovascular Quality and Outcomes. 5 (4), 454-462 (2012).</li><li>Shoji, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stroke+After+Percutaneous+Coronary+Intervention+in+the+Era+of+Transradial+Intervention.">Stroke After Percutaneous Coronary Intervention in the Era of Transradial Intervention.</a> Circulation: Cardiovascular Interventions. 11 (12), 006761 (2018).</li><li>Jurga, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+microembolism+during+coronary+angiography:+a+randomized+comparison+between+femoral+and+radial+arterial+access.">Cerebral microembolism during coronary angiography: a randomized comparison between femoral and radial arterial access.</a> Stroke. 42 (5), 1475-1477 (2011).</li><li>Bishay, V. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transradial+Approach+for+Hepatic+Radioembolization:+Initial+Results+and+Technique.">Transradial Approach for Hepatic Radioembolization: Initial Results and Technique.</a> AJR: American Journal of Roentgenology. 207 (5), 1112-1121 (2016).</li><li>Bernat, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ST-segment+elevation+myocardial+infarction+treated+by+radial+or+femoral+approach+in+a+multicenter+randomized+clinical+trial:+the+STEMI-RADIAL+trial.">ST-segment elevation myocardial infarction treated by radial or femoral approach in a multicenter randomized clinical trial: the STEMI-RADIAL trial.</a> Journal of the American College of Cardiology. 63 (10), 964-972 (2014).</li></ol>

TRA interventional therapy has grown significantly worldwide in recent years, especially in diagnostic and Interventional cardiology procedures12. Moreover, there has been increasing attention to peripheral vascular disease intervention. Without compromising procedural success rates, TRA to cardiac intervention can effectively reduce the rates of bleeding and vascular complications compared with TFA13,14. Compared with TFA, TRA is superior...

Hepatocellular carcinoma (HCC) is a very common malignancy, with the sixth highest incidence rate worldwide. It is also the second leading cause of cancer mortality around the world1. Because only 5%&#8211;20% of patients can receive curative therapy, transarterial chemoembolization (TACE) is the most popular palliative treatment for patients with unresectable HCC2. TACE has been recognized as the most commonly used and effective treatment approach for HCC patients at the intermediate stage3. Transfemoral access (TFA) chemoembolization is the most common approach for TACE4. However, there are risks associated with TFA intervention, including bleeding at the access site and major vascular complications5. These complications lead to prolonged hospitalization and increased costs. Moreover, TFA requires immobilization for at least 6 h, which increases discomfort and dissatisfaction for the patients.&#160;
Transradial access (TRA) is an alternative approach that has been used in percutaneous coronary intervention (PCI) for more than two decades5,6. TRA PCI has several advantages: increased procedure comfort, decreased access site-related bleeding, decreased major vascular complications, and decreased mortality7,8. The radial artery (RA) is easy to access and puncture because of its superficial location7. Hemostasis is easy to conduct after intervention and there is no strict immoblization9. Despite encouraging evidence for TRA intervention in cardiac catheterization, to date only a few studies used TRA in peripheral disease intervention. TRA interventions for malignant liver tumors are even rarer. Here, the clinical feasibility and safety of TRA hepatic embolization is analyzed. One institution&#8217;s experience with the step-by-step TRA protocol provided is also described.

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			<td height="21" style="height:21px;width:141px;">Reagents</td>
			<td style="width:127px;"></td>
			<td style="width:123px;"></td>
			<td style="width:163px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Embosphere</td>
			<td style="width:127px;">Merit</td>
			<td style="width:123px;">20173776165</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Gelfoam</td>
			<td style="width:127px;">Alicon</td>
			<td style="width:123px;">20143771056</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Heparin</td>
			<td style="width:127px;">Hepatunn</td>
			<td style="width:123px;">H51021209</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Injection syringe</td>
			<td style="width:127px;">KDL</td>
			<td style="width:123px;">20163150518</td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:141px;">Iodinated oil</td>
			<td style="width:127px;">Yantai Luyin Pharmaceutical Co.Ltd</td>
			<td style="width:123px;">H37022398</td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:141px;">Lidocaine</td>
			<td style="width:127px;">Shandong Hualu Pharmaceutical Co.Ltd</td>
			<td style="width:123px;">H37022147</td>
			<td></td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:141px;">Lobaplatin</td>
			<td style="width:127px;">Hainan Changan International Pharmaceutical Co.Ltd</td>
			<td style="width:123px;">H20050308</td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:141px;">Nitroglycerin</td>
			<td style="width:127px;">Brijing Yimin Pharmaceutical Co.Ltd</td>
			<td style="width:123px;">H11020289</td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:141px;">Normal saline</td>
			<td style="width:127px;">Anhui Shuanghe Pharmaceutical Co.Ltd</td>
			<td style="width:123px;">H34023609</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Pharmorubicin</td>
			<td style="width:127px;">Pfizer</td>
			<td style="width:123px;">H20000496</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Ultravist 370</td>
			<td style="width:127px;">Bayer</td>
			<td style="width:123px;">H20171333</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Material</td>
			<td></td>
			<td></td>
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		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:141px;">Hydrophilic Guide Wire</td>
			<td style="width:127px;">Merit</td>
			<td style="width:123px;">LWSTDA38180</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Injection syringe</td>
			<td style="width:127px;">KDL</td>
			<td style="width:123px;">20163150518</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:141px;">Maestro Microcatheter</td>
			<td style="width:127px;">Merit</td>
			<td style="width:123px;">28MC24150SN</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">MPA1 (I) catheter</td>
			<td style="width:127px;">Cordis</td>
			<td style="width:123px;">451-406P0</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Sheath Introducer</td>
			<td style="width:127px;">Merit</td>
			<td style="width:123px;">PSI-4F-11-035</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Steerable Guidewire</td>
			<td style="width:127px;">Merit</td>
			<td style="width:123px;">TNR2411</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">TR Band</td>
			<td style="width:127px;">Terumo</td>
			<td style="width:123px;">XX*RF06</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Equipment</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">DSA</td>
			<td style="width:127px;">Toshiba</td>
			<td style="width:123px;">INFX-9000V</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:141px;">Ultrasonic machine</td>
			<td style="width:127px;">SonoScape</td>
			<td style="width:123px;">20172231180</td>
			<td></td>
		</tr>
	</tbody>
</table>

transradial access chemoembolization for hepatocellular carcinoma patients

Transarterial chemoembolization (TACE) is the most common modality for treatment of hepatocellular carcinoma (HCC) at the intermediate stage. TACE is typically performed via transfemoral access (TFA). However, transradial access (TRA) is preferred in coronary artery interventions due to decreased complications and mortality. Whether the advantages of TRA can be applied to TACE required investigation.
Patients receiving TRA TACE at a single center were retrospectively enrolled for study. Procedural details, technical success, radial artery occlusion (RAO) rate, and access site-related bleeding complications were evaluated. From October 2017 to October 2018, 112 patients underwent 160 TRA TACE procedures. The overall technical success rate was 95.0% (152/160). The rate of crossover from TRA to TFA was 1.9%. No access site-related bleeding complications were found in any cases. Asymptomatic RA occlusion occurred in three patients (2.7%). Compared with TFA, TRA can increase safety and patient satisfaction while decreasing access site-related bleeding complications. Moreover, TRA interventions can benefit patients with advanced age, obesity, or a high risk of bleeding complications.

From October 2017 to October 2018, 112 patients underwent 160 TRA TACE procedures, and the overall technical success rate was 95.0% (152/160). Eight cases were met with technical failure. Of these, five cases were caused by left RA puncture failure and subsequently underwent successful TACE with right RA access. The other three cases were caused by cannulation failure, and underwent subsequent successful intervention by crossover to right FA access. The crossover rate of RA access to FA access was only 1.9%. No access si...

Watch this Scientific Journal Video about Transradial Access Chemoembolization for Hepatocellular Carcinoma Patients at JoVE.com

Transradial Access Chemoembolization for Hepatocellular Carcinoma Patients

Transarterial chemoembolization (TACE) is the standard therapy for patients in the intermediate stage of hepatocellular carcinoma and is typically performed through femoral artery access. Compared with transfemoral access, transradial access (TRA) can decrease the rate of bleeding complications and improve patient tolerance. A method is presented here to perform transarterial chemoembolization via radial artery access.

Transarterial chemoembolization (TACE) is the most common modality for treatment of hepatocellular carcinoma (HCC) at the intermediate stage. TACE is ...

Repetitive TACE is a common effective treatment for unresectable hepatocellular carcinoma, and is often performed via femoral artery access. However, the clinical feasibility or repeated transradial artery usage has not been confirmed. This technique reduces the risk bleeding, facilitates easier hemostasis, is easier to monitor, does not require lying in bed, enhances safety and improves patient comfort.Demonstrating the procedure will be Dr.Zhang and Dr.Yang. For radial artery access, first place the patient in a supine position on the angiography table, and position the left arm parallel to the body, close to the left waist. Locate the distal radial artery by palpation, and clean the skin surface with 10%povidone iodine surgical scrub solution.When the solution is air dried, cover the left arm with a surgical drape. In case of potential left radial artery puncture failure, sterilize and drape the right arm or right inguinal region to prepare an alternative access route. Apply topical anesthesia, proximal to the styloid process along the axis of the most powerful pulsation of the left radial artery, and extend the wrist.Using a 20-gauge needle and modified Seldinger technique, puncture the radial artery. When pulsatile arterial blood return is observed, gently introduce a 0.021-inch hydrophilic guidewire into the vessel. Once access is obtained, remove the needle, and use the guidewire to introduce a four French hydrophilic sheath.After sheath insertion, use a syringe to gently pump back a small amount of arterial blood to confirm that the sheath tip is located within the vessel, and inject the cocktail. To perform a superselective catheterization and chemoembolization, use a high pressure injector to perform an angiogram through the common catheter to confirm an adequate embolization and the location of the catheter tip within the common hepatic artery, then inject nine to 12 milliliters of the contrast agent at a three-to-four milliliter per second flow rate, and a fluoroscopy time of about 15 seconds, and remove the catheter of the guidewire to avoid damage to radial artery. To induce radial artery hemostasis, remove the catheter over the guidewire to avoid damage to the radial artery, and administer the remaining two milliliters of vasodilation cocktail solution through the radial artery sheath.Immediately after all of the solution has been delivered, retract the sheath about five centimeters, and place a TR band over the radial access site on the left wrist, use the accompanying syringe to adequately inflate the TR band air bag with air, and completely remove the sheath. Slowly deflate the air bag when leaking is observed at the access site at one milliliter of air back into the cuff, then confirm that there is no bleeding or leakage while also checking that the distal radial artery pulse is palpable during hemostasis, and using a pulse oximeter to confirm the arterial wave form on the left thumb. In this table, the baseline clinical data of representative cases with technical success or failure are compared.An increased number of catheters were required for patients suffering radial artery access technical failure. No significant correlations were found between the technical success or failure of the procedure and patient age, sex, or combined medical comorbidities. In this table, the numbers of transradial access transarterial chemoembolization procedures were compared.Due to the low frequency of radial artery occlusions, no significant correlation was found between the increased rate of occlusion and the number of transradial access procedures. It is important to stay calm and collected while performing the procedure. After watching this video, you should have the confidence and ability to perform that technique.We use ultrasound to improve the efficiency of the radial archery location, especially when the vessel is particularly small.

transradial-access-chemoembolization-for-hepatocellular-carcinoma

Research

JoVE Journal

Cancer Research

Study of Viral Vectors in a Three-dimensional Liver Model Repopulated with the Human Hepatocellular Carcinoma Cell Line HepG2

This protocol describes the generation of a three-dimensional (3D) ex vivo liver model and its application to the study and development of viral vector systems. The model is obtained by repopulating the extracellular matrix of a decellularized rat liver with a human hepatocyte cell line. The model permits studies in a vascularized 3D cell system, replacing potentially harmful experiments with living animals. Another advantage is the humanized nature of the model, which is closer to human physiology than animal models.
In this study, we demonstrate the transduction of this liver model with a viral vector derived from adeno-associated viruses (AAV vector). The perfusion circuit that supplies the 3D liver model with media provides an easy means to apply the vector. The system permits monitoring of the major metabolic parameters of the liver. For final analysis, tissue samples can be taken to determine the extent of recellularization by histological techniques. Distribution of the virus vector and expression of the delivered transgene can be analyzed by quantitative PCR (qPCR), Western blotting and immunohistochemistry. Numerous applications of the vector model in basic research and in the development of gene therapeutic applications can be envisioned, including the development of novel antiviral therapeutics, cancer research, and the study of viral vectors and their potential side effects.

The recellularized extracellular matrix of a decellularized rat liver can be used as a humanized, three-dimensional ex vivo model to study the distribution and transgene expression of a virus or viral vector.

This protocol describes the generation of a three-dimensional (3D) ex vivo liver model and its application to the study and development of viral vector ...

A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma

Perineural invasion (PNI) is found in approximately 40% of head and neck squamous cell carcinomas (HNSCC). Despite multimodal treatment with surgery, radiation, and chemotherapy, locoregional recurrences and distant metastases occur at higher rates, and overall survival is decreased by 40% compared to HNSCC without PNI. In vitro studies of the pathways involved in HNSCC PNI have historically been challenging given the lack of a consistent, reproducible assay. Described here is the adaptation of the dorsal root ganglion (DRG) assay for the examination of PNI in HNSCC. In this model, DRG are harvested from the spinal column of a sacrificed nude mouse and placed within a semisolid matrix. Over the subsequent days, neurites are generated and grow in a radial pattern from the cell bodies of the DRG. HNSCC cell lines are then placed peripherally around the matrix and invade preferentially along the neurites toward the DRG. This method allows for rapid evaluation of multiple treatment conditions, with very high assay success rates and reproducibility.

Perineural invasion (PNI) is a common feature of head and neck squamous cell carcinoma (HNSCC), conferring lower survival rates. Its mechanisms are poorly understood. Utilizing neurites generated from murine dorsal root ganglia confined to a semisolid matrix, the pathways involved in the PNI of HNSCC cell lines can be investigated.

Perineural invasion (PNI) is found in approximately 40% of head and neck squamous cell carcinomas (HNSCC). Despite multimodal treatment with surgery, ...

Automated Multiplex Immunofluorescence Panel for Immuno-oncology Studies on Formalin-fixed Carcinoma Tissue Specimens

Continued developments in immuno-oncology require an increased understanding of the mechanisms of cancer immunology. The immunoprofiling analysis of tissue samples from formalin-fixed, paraffin-embedded (FFPE) biopsies has become a key tool for understanding the complexity of tumor immunology and discovering novel predictive biomarkers for cancer immunotherapy. Immunoprofiling analysis of tissues requires the evaluation of combined markers, including inflammatory cell subpopulations and immune checkpoints, in the tumor microenvironment. The advent of novel multiplex immunohistochemical methods allows for a more efficient multiparametric analysis of single tissue sections than does standard monoplex immunohistochemistry (IHC). One commercially available multiplex immunofluorescence (IF) method is based on tyramide-signal amplification and, combined with multispectral microscopic analysis, allows for a better signal separation of diverse markers in tissue. This methodology is compatible with the use of unconjugated primary antibodies that have been optimized for standard IHC on FFPE tissue samples. Herein we describe in detail an automated protocol that allows multiplex IF labeling of carcinoma tissue samples with a six-marker multiplex antibody panel comprising PD-L1, PD-1, CD68, CD8, Ki-67, and AE1/AE3 cytokeratins with 4&#8242;,6-diamidino-2-phenylindole as a nuclear cell counterstain. The multiplex panel protocol is optimized in an automated IHC stainer for a staining time that is shorter than that of the manual protocol and can be directly applied and adapted by any laboratory investigator for immuno-oncology studies on human FFPE tissue samples. Also described are several controls and tools, including a drop-control method for fine quality control of a new multiplex IF panel, that are useful for the optimization and validation of the technique.

A detailed protocol for a six-marker multiplex immunofluorescence panel is optimized and performed, using an automated stainer for more consistent results and a shorter procedure time. This approach can be directly adapted by any laboratory for immuno-oncology studies.

Continued developments in immuno-oncology require an increased understanding of the mechanisms of cancer immunology. The immunoprofiling analysis of ...

Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression

Tumor-stroma interactions play a critical role in the development of lung squamous carcinoma (LUSC). However, understanding how these dynamic interactions contribute to tissue architectural changes observed during tumorigenesis remains challenging due to the lack of appropriate models. In this protocol, we describe the generation of a 3D coculture model using a LUSC primary cell culture known as TUM622. TUM622 cells were established from a LUSC patient-derived xenograft (PDX) and have the unique property to form acinar-like structures when seeded in a basement membrane matrix. We demonstrate that TUM622 acini in 3D coculture recapitulate key features of tissue architecture during LUSC progression as well as the dynamic interactions between LUSC cells and components of the tumor microenvironment (TME), including the extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs). We further adapt our principal 3D culturing protocol to demonstrate how this system could be utilized for various downstream analyses. Overall, this organoid model creates a biologically rich and adaptable platform that enables one to gain insight into the cell-intrinsic and extrinsic mechanisms that promote the disruption of epithelial architectures during carcinoma progression and will aid the search for new therapeutic targets and diagnostic markers.

An in vitro model system was developed to capture tissue architectural changes during lung squamous carcinoma (LUSC) progression in a 3-dimensional (3D) co-culture with cancer-associated fibroblasts (CAFs). This organoid system provides a unique platform to investigate the roles of diverse tumor cell-intrinsic and extrinsic changes that modulate the tumor phenotype.

Tumor-stroma interactions play a critical role in the development of lung squamous carcinoma (LUSC). However, understanding how these dynamic interactions ...

Analysis of Liver Microenvironment During Early Progression of Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in Zebrafish

Liver cancer is currently the third&#160;leading cause of cancer related death worldwide, and Hepatocellular Carcinoma (HCC) accounts for 75-90% of all liver cancer cases. With the introduction of effective treatments to prevent and treat hepatitis B/C, non-alcoholic fatty liver disease (NAFLD), and the more aggressive form know as non-alcoholic steatohepatitis (NASH), are quickly becoming the number one risk factors to develop HCC in modern societies. To better understand the role NASH has on the development of HCC we designed a NASH-associated HCC zebrafish. The optical clarity and genetic tractability of the zebrafish larvae make them an appealing and powerful model to study the liver microenvironment and immune cell composition using non-invasive fluorescent live imaging. This protocol describes how to use a NASH-associated HCC zebrafish model to investigate the effect of cholesterol surplus in the liver microenvironment and its impact on immune cell composition at early stages of the disease. First, we feed HCC larvae (s704Tg), which express hepatocyte-specific activated beta-catenin, with a 10% high cholesterol diet for 8 days to develop a NASH-associated HCC model. Here we describe how to make use of different transgenic lines to evaluate several early malignancy features in the liver by non-invasive confocal microscopy, such as liver area, cell, and nuclear morphology (hepatocytes area, nuclear area, nuclear:cytoplasmic ratio (N:C ratio), nuclear circularity, micronuclei/nuclear herniation scoring) and angiogenesis. Then, using transgenic lines with tagged immune cells (neutrophils, macrophages, and T cells) we show how to analyze liver immune cell composition in NASH-associated HCC larvae. The described techniques are useful to evaluate liver microenvironment and immune cell composition at early hepatocarcinogenesis stages, but they can also be modified to study such features in other liver disease models.

Here, we present how to generate a non-alcoholic fatty liver disease (NAFLD)-associated Hepatocellular Carcinoma (HCC) zebrafish model to study the impact of cholesterol surplus on liver microenvironment and immune cell landscape.

Liver cancer is currently the third&#160;leading cause of cancer related death worldwide, and Hepatocellular Carcinoma (HCC) accounts for 75-90% of all ...

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma

The aggressiveness and lack of well-tolerated and widely effective treatments for advanced hepatocellular carcinoma (HCC), the predominant form of liver cancer, rationalize its rank as the second most common cause of cancer-related death. Preclinical models need to be adapted to recapitulate the human conditions to select the best therapeutic candidates for clinical development and aid the delivery of personalized medicine. Three-dimensional (3D) cellular spheroid models show promise as an emerging in vitro alternative to two-dimensional (2D) monolayer cultures. Here, we describe a 3D tumor spheroid&#160;model which exploits the ability of individual cells to aggregate when maintained in hanging droplets, and is more representative of an in vivo environment than standard monolayers. Furthermore, 3D spheroids can be produced by combining homotypic or heterotypic cells, more reflective of the cellular heterogeneity in vivo, potentially enabling the study of environmental interactions that can influence progression and treatment responses. The current research optimized the cell density to form 3D homotypic and heterotypic tumor spheroids by immobilizing cell suspensions on the lids of standard 10 cm3 Petri dishes. Longitudinal analysis was performed to generate growth curves for homotypic versus heterotypic tumor/fibroblasts spheroids. Finally, the proliferative impact of fibroblasts (COS7 cells) and liver myofibroblasts (LX2) on homotypic tumor (Hep3B) spheroids was investigated. A seeding density of 3,000 cells (in 20 &#181;L media) successfully yielded Huh7/COS7 heterotypic spheroids, which displayed a steady increase in size up to culture day 8, followed by growth retardation. This finding was corroborated using Hep3B homotypic spheroids cultured in LX2 (human hepatic stellate cell line) conditioned medium (CM). LX2 CM triggered the proliferation of Hep3B spheroids compared to control tumor spheroids. In conclusion, this protocol has shown that 3D tumor spheroids can be used as a simple, economical, and prescreen in vitro tool to study tumor-stromal interactions more comprehensively.

Comprehensive in vitro models that faithfully recapitulate the relevant human disease are lacking. The current study presents three-dimensional (3D) tumor spheroid creation and culture, a reliable in vitro tool to study the tumor-stromal interaction in human hepatocellular carcinoma.

The aggressiveness and lack of well-tolerated and widely effective treatments for advanced hepatocellular carcinoma (HCC), the predominant form of liver ...

Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Preclinical experimental models of hepatocellular carcinoma (HCC) that recapitulate human disease represent an important tool to study tumorigenesis and evaluate novel therapeutic approaches. Non-invasive whole-body imaging using positron emission tomography (PET) provides critical insights into the in vivo characteristics of tissues at the molecular level in real-time. We present here a protocol for orthotopic HCC xenograft creation with and without hepatic artery ligation (HAL) to induce tumor hypoxia and the assessment of their tumor metabolism in vivo using [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluorodeoxyglucose ([18F]FDG) PET/magnetic resonance (MR) imaging. Tumor hypoxia could be readily visualized using the hypoxia marker [18F]FMISO, and it was found that the [18F]FMISO uptake was higher in HCC mice that underwent HAL than in the non-HAL group, whereas [18F]FDG could not distinguish tumor hypoxia between the two groups. HAL tumors also displayed a higher level of hypoxia-inducible factor (HIF)-1&#945; expression in response to hypoxia. Quantification of HAL tumors showed a 2.3-fold increase in [18F]FMISO uptake based on the standardized value uptake (SUV) approach.

Here, we present a protocol to create orthotopic hepatocellular carcinoma xenografts with and without hepatic artery ligation and perform non-invasive positron emission tomography (PET) imaging of tumor hypoxia using [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluorodeoxyglucose ([18F]FDG).

Preclinical experimental models of hepatocellular carcinoma (HCC) that recapitulate human disease represent an important tool to study tumorigenesis and ...

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma

Patient-derived xenograft (PDX) models faithfully preserve the histological and genetic characteristics of the primary tumor and maintain its heterogeneity. Pharmacodynamic results based on PDX models are highly correlated with clinical practice. Anaplastic thyroid carcinoma (ATC) is the most malignant subtype of thyroid cancer, with strong invasiveness, poor prognosis, and limited treatment. Although the incidence rate of ATC accounts for only 2%-5% of thyroid cancer, its mortality rate is as high as 15%-50%. Head and neck squamous cell carcinoma (HNSCC) is one of the most common head and neck malignancies, with over 600,000 new cases worldwide each year. Herein, detailed protocols are presented to establish PDX models of ATC and HNSCC. In this work, the key factors influencing the success rate of model construction were analyzed, and the histopathological features were compared between the PDX model and the primary tumor. Furthermore, the clinical relevance of the model was validated by evaluating the in vivo therapeutic efficacy of representative clinically used drugs in the successfully constructed PDX models.

The present protocol establishes and characterizes a patient-derived xenograft (PDX) model of anaplastic thyroid carcinoma (ATC) and head and neck squamous cell carcinoma (HNSCC), as PDX models are rapidly becoming the standard in the field of translational oncology.

Patient-derived xenograft (PDX) models faithfully preserve the histological and genetic characteristics of the primary tumor and maintain its ...

Optimizing HCC Organoid Formation for Target Identification and Drug Development

Development and Optimization of A Human Hepatocellular Carcinoma Patient-Derived Organoid Model for Potential Target Identification and Drug Discovery

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal tumor worldwide and its late discovery and lack of effective specific therapeutic agents necessitate further research into its pathogenesis and treatment. Organoids, a novel model that closely resembles native tumor tissue and can be cultured in vitro, have garnered significant interest in recent years, with numerous reports on the development of organoid models for liver cancer. In this study, we have successfully optimized the procedure and established a culture protocol that enables the formation of larger-sized HCC organoids with stable passaging and culture conditions. We have comprehensively outlined each step of the procedure, covering the entire process of HCC tissue dissociation, organoid plating, culture, passaging, cryopreservation, and resuscitation, and provided detailed precautions in this paper. These organoids exhibit genetic similarity to the original HCC tissues and can be utilized for diverse applications, including the identification of potential therapeutic targets for tumors and subsequent drug development.

Author Spotlight: Investigating Liver Cancer Pathogenesis Using Patient-Derived Organoids 

We provide a comprehensive overview and refinement of existing protocols for hepatocellular carcinoma (HCC) organoid formation, encompassing all stages of organoid cultivation. This system serves as a valuable model for the identification of potential therapeutic targets and the assessment of drug candidate effectiveness.

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal tumor worldwide and its late discovery and lack of effective specific therapeutic agents ...

Prognostic Significance of Immune Cell Infiltration in Hepatocellular Carcinoma

Mast Cells in the Microenvironment of Hepatocellular Carcinoma Confer Favorable Prognosis: A Retrospective Study using QuPath Image Analysis Software

The insights provided by in-situ detection of immune cells within hepatocellular carcinoma (HCC) might present information on patient outcomes. Studies investigating the expression and localization of immune cells within tumor tissues are associated with several challenges, including a lack of precise annotation for tumor regions and random selection of microscopic fields of view. QuPath is an open-source, user-friendly software that could meet the growing need for digital pathology in whole-slide image (WSI) analysis.
The infiltration of HCC and adjacent tissues by CD1a+ immature dendritic cells (iDCs), CD117+ mast cells, and NKp46+ natural killer cells (NKs) cells was assessed immunohistochemically in representative specimens of 67 patients with HCC who underwent curative resection. The area fraction (AF) of positively stained cells was assessed automatically in WSIs using QuPath in the tumor center (TC), inner margin (IM), outer margin (OM), and peritumor (PT) area. The prognostic significance of immune cells was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS).
The AF of mast cells was significantly greater than the AF of NKs, and the AF of iDCs was significantly lower compared to NKs in each region of interest. High AFs of mast cells in the IM and PT areas were associated with longer DFS. In addition, high AF of mast cells in IM was associated with longer OS.
Computer-assisted analysis using this software is a suitable tool for obtaining prognostic information for tumor-infiltrating immune cells (iDCs, mast cells, and NKs) in different regions of HCC after resection. Mast cells displayed the greatest AF in all regions of interest (ROIs). Mast cells in the peritumor region and IM showed a positive prognostic significance.

Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment &#8212; Challenges and Innovations in Cancer Prognosis

The presence of mast cells in the inner margin and peritumor areas of hepatocellular carcinoma after resection confers a favorable prognosis. This study endorses QuPath image analysis software as a promising platform that could meet the need for reproducibility, consistency, and accuracy in digital pathology.

The insights provided by in-situ detection of immune cells within hepatocellular carcinoma (HCC) might present information on patient outcomes. Studies ...