|Year : 2017 | Volume
| Issue : 4 | Page : 720-724
Supplemental conventional transarterial embolization/chemoembolization therapy via extrahepatic arteries for hepatocellular carcinoma
Yuanqan Huang1, Zhongzhi Jia2, Jianfei Tu3, Tao Shen4, Feng Tian2, Guomin Jiang2
1 Department of Interventional Radiology, The Third Hospital Affiliated to Soochow University, Changzhou 213003, China
2 Department of Radiology, No. 2 People's Hospital of Changzhou, Nanjing Medical University, China
3 Department of Radiology and Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Li Shui 323000, China
4 Department of Interventional Radiology, Wujin Hospital, Jiangsu University, Changzhou 213003, China
|Date of Web Publication||13-Sep-2017|
Department of Radiology, Changzhou No.2 People's Hospital, Nanjing Medical University, Changzhou 213003
Source of Support: None, Conflict of Interest: None
Purpose: To assess the value of conventional transarterial embolization/chemoembolization (cTAE/TACE) therapy via extrahepatic arteries for patients with unresectable hepatocellular carcinoma (HCC).
Methods: Patients with unresectable HCC who underwent cTAE/TACE therapy via extrahepatic arteries between May 2008 and July 2016 across 4 medical centers were identified. The technical success, serum alpha-fetoprotein (AFP) levels changes, tumor response, disease control rate, survival rate, and major complication were analyzed.
Results: A total of 185 patients (167 male and 18 female) were included in this study. A total of 401 procedures were performed of the 185 patients, with 2.2 ± 0.4 procedures for each patient. A total of 197 extrahepatic arteries were identified, including inferior phrenic artery (n = 80), omental artery (n = 39), gastric artery (n = 22), right renal capsular artery (n = 21), adrenal artery (n = 13), cystic artery (n = 11), and right internal mammary artery (n = 11). The technical success rate was 96.8% (179/185). The serum AFP levels were significantly reduced at 1 month after treatment in 71 patients whose AFP ≥400 ng/mL preprocedure (P < 0.01). The disease control rate was 93% (172/185) at 3 months after cTAE/TACE, with partial response, stable disease, or progressive disease of 115, 57, and 13 patients, respectively. The cumulative survival rate from the time of cTAE/TACE via extrahepatic arteries was 100% at 6 months. There were no embolization-related major complications.
Conclusion: cTAE/TACE therapy via the extrahepatic arteries can reduce the incidence of presence of residual HCC, and improve the therapeutic efficacy of cTAE/TACE.
Keywords: Extrahepatic artery, hepatocellular carcinoma, transcatheter arterial chemoembolization
|How to cite this article:|
Huang Y, Jia Z, Tu J, Shen T, Tian F, Jiang G. Supplemental conventional transarterial embolization/chemoembolization therapy via extrahepatic arteries for hepatocellular carcinoma. J Can Res Ther 2017;13:720-4
|How to cite this URL:|
Huang Y, Jia Z, Tu J, Shen T, Tian F, Jiang G. Supplemental conventional transarterial embolization/chemoembolization therapy via extrahepatic arteries for hepatocellular carcinoma. J Can Res Ther [serial online] 2017 [cited 2018 May 22];13:720-4. Available from: http://www.cancerjournal.net/text.asp?2017/13/4/720/214484
| > Introduction|| |
Conventional transarterial embolization/chemoembolization (cTAE/TACE) has been widely accepted as a treatment option for patients with unresectable hepatocellular carcinoma (HCC),,, and has been considered as an effective and safe treatment modality for unresectable HCC. However, the incidence of residual HCC remain high with this technique, and repeat cTAE/TACE with/without other regional therapies are often needed., Recent studies have shown that extrahepatic collaterals to the tumor play an important role in the presence of residual HCC, which can limit the effectiveness of cTAE/TACE therapy.,,, To reduce the incidence of presence of residual HCC, these extrahepatic collaterals need to be adequately embolized.,,,,,,,
Our previous study suggested cTAE/TACE therapy via omental artery can improve the degree of lipiodol uptake of the tumors. However, the value of cTAE/TACE therapy via extrahepatic collaterals for patients with unresectable HCC are largely unknown. The purpose of this retrospective study was to assess the value of cTAE/TACE therapy via extrahepatic arteries for the treatment of unresectable HCC.
| > Methods|| |
This study was approved by all participating institutional review boards with a waiver of informed consent. Retrospective reviewing of patients who underwent cTAE/TACE therapy via extrahepatic collaterals for the treatment of unresectable HCC was conducted in four different medical centers from May 2008 to July 2016. Cases were identified through the departmental procedural logs. Patient demographics, clinical information, and procedural data were gathered from patients' medical records. Imaging data were gathered from the Picture Archiving and Communications System of the four institutions.
Conventional transarterial embolization/chemoembolization procedure
cTAE/TACE was carried out according to the current practice guideline. After cTAE/TACE therapy via intrahepatic arteries, the inferior phrenic arteriography was routinely performed in patients who had a tumor located adjacent to diaphragm. Other extrahepatic collaterals were sought when the tumor stain corresponding to HCC depicted by contrast-enhanced computed tomography or magnetic resonance imaging (MRI) was not demonstrated on angiographys.
All patients underwent initial evaluation of the tumor arteries using a 5-Fr Rosch hepatic catheter (Cook, Bloomington, IN, USA). The procedure was performed using a 2.7-Fr microcatheter (Progreat; Terumo, Japan). All identified tumor feeding arteries, including intrahepatic and extrahepatic arteries, were embolized with an emulsion of iodized oil and epirubicin/oxaliplatin at a ratio of 10 ml of lipiodol to 10 mg epirubicin or 50 mg oxaliplatin. The dose of lipiodol used depended on the size and vascularity of the tumors. Emulsion injection was stopped when the flow stasis. Additional embolization of gelatin sponge particles (GSP, Alicon Pharm SCIandTEC Co., LTD, HangZhou, China) 350-560 μm/560-710 μm in diameter was performed as need until there was no longer any tumor staining during repeat angiography.
All patients were admitted after the cTAE/TACE procedure for postprocedural supportive treatment and to be observed for potential complications. Routine management included hydration, treatment with antiemetics, pain control, and monitoring for liver function changes.
According to the follow-up protocol established at four different hospitals, routine survey of procedure related complications was carried out on postdischarged from day 5 to 9 with telephone contact or clinic visits. Immediate clinical follow-up was required if there was suspicious for any major complications of cTAE/TACE therapy.
Clinical follow-up was scheduled on the 1st–3rd months after treatments and every 3 months thereafter. More frequent evaluations were done when needed. During follow-up, MRI was performed and routine laboratory values were assessed, including complete blood count, liver enzymes, bilirubin level, and serum alpha-fetoprote (AFP) level.
Technical success was defined as successful superselective catheterization of targeted arteries and performed cTAE/TACE therapy. Tumor response was assessed by the modified Response Evaluation Criteria in Solid Tumors. Disease control rate was defined as the percentage of patients who achieved complete response, partial response or stable disease after cTAE/TACE therapy. Survival was calculated from the date of initial cTAE/TACE procedures via extrahepatic arteries to the date of death or last follow-up. Major complications related to cTAE/TACE therapy as defined by the Society of Interventional Radiology  included admission to a hospital for therapy, higher level of care required, substantially longer hospital stay (>48 h) required, and the occurrence of permanent adverse sequelae or death.
SPSS version 17.0 (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. The serum AFP level was recorded as mean ± SD. A t-test was used to compare the changes of serum AFP before and after TAE/TACE therapy. A P < 0.05 was considered to be statistically significant.
| > Results|| |
From May 2008 to July 2016, a total of 185 patients underwent cTAE/TACE therapy via extrahepatic collaterals for HCC were identified and included in this study. Of the 185 patients, there were 167 male and 18 female, with mean age of 50.7 ± 7.3 years (range, 32–81 years). [Table 1] summarizes the demographic information and baseline characteristics of the 185 patients. The mean tumor diameter was 7.3 ± 2.5 cm (range, 2–17 cm), and all the tumors of 185 patients located at the surface of the liver. A total of 401 cTAE/TACE procedures were performed of the 185 patients, with mean procedures of 2.2 ± 0.4 (range, 1–7) per patient. Lipidol as an embolic agent was used in all patients with mean 11.6 ± 3.4 ml (range, 7–30 ml), and additional GSP was used in 41 patients.
|Table 1: The demographic information and baseline characteristics of the 185 patients|
Click here to view
Among the 185 patients, a total of 197 extrahepatic arteries were identified, including 173 patients with one and 12 patients with two extrahepatic arteries. Although there was no significant difference of max tumor diameter between two subgroups patients, all the 12 patients who with two extrahepatic arteries were in multiple lesions. The extrahepatic collaterals were identified during initial treatment in 37 patients, and during repeat treatment in 148 patients. The extrahepatic arteries were inferior phrenic artery (n = 80), (right inferior phrenic artery = 63, and left inferior phrenic artery = 17), [Figure 1], omental artery (n = 39), [Figure 2], gastric artery (n = 22), right renal capsular artery (n = 21), adrenal artery (n = 13), cystic artery (n = 11), and right internal mammary artery (n = 11).
|Figure 1: A 53-year-old man presented with a huge hepatocellular carcinoma in the right lobe of the liver, and the tumor was located at the surface of the liver. (a) Partial defective lipiodol deposition of the tumor was seen after conventional transarterial chemoembolization via the hepatic artery (arrowhead). (b and c) Tumor staining was demonstrated by right inferior phrenic arteriography (arrowhead). (d) Lipiodol deposition in the whole tumor was identified after conventional transarterial chemoembolization via the right inferior phrenic artery (arrowhead)|
Click here to view
|Figure 2: A 57-year-old man presented with multiple hepatocellular carcinoma in the right lobe of the liver. (a and b) Omental artery forward to the right lobe of the liver was identified by the common hepatic arteriography (arrowheads). (c) Tumor staining was demonstrated by omental arteriography (arrowheads). (d) Lipiodol deposition in the tumor was identified after conventional transarterial chemoembolization via the omental artery|
Click here to view
The technical success rate was 96.8% (179/185) of this group patients, and 3.2% (6/185) extrahepatic arteries failed of superselective catheterization. Of the 197 extrahepatic arteries, total occlusion was achieved in 83.2% (164/197), and injection of emulsion had to be terminated before achieved complete occlusion of the remaining 33 extrahepatic arteries (including the six extrahepatic arteries failed of superselective catheterization) due to nontarget embolization (n = 28), and early drainage of the emulsion via the gastroepiploic vein of the omentum (n = 5).
The serum AFP levels were significantly reduced at 1 month after treatment (1240.1 ± 247.3 ng/mL vs. 121.3 ± 41.2 ng/mL, P < 0.01) in 71 patients whose AFP ≥400 ng/mL preprocedure. The disease control rate was 93% (172/185) at 3 months after TAE/TACE treatment, with partial response, stable disease, or progressive disease of 115, 57, and 13 patients, respectively. The cumulative survival rate from the time of cTAE/TACE was 100% at 6 months. There were no embolization-related major complications.
| > Discussion|| |
In this study, we found that (1) multiple extrahepatic arteries can develop and supply the tumor lesions, and the most common extrahepatic artery is inferior phrenic artery, followed by omental artery, gastric artery, renal capsular artery, adrenal artery, cystic artery, and internal mammary artery; (2) the technical success rate was 96.8% of cTAE/TACE via extrahepatic arteries; (3) the serum AFP levels were significantly reduced at 1 month after treatment; (4) the disease control rate was 93% at 3 months after cTAE/TACE treatment, and the cumulative survival rate from the time of TAE/TACE was 100% at 6 months.
Multiple extrahepatic collaterals can develop and supply the HCC,,,,,,,,,, which play an important role in the residual HCC, and can limit the effectiveness of cTAE/TACE therapy.,, The incidence of extrahepatic collaterals feeding the HCC has been reported to be 17%–27%.,, Therefore, it is important for interventional radiologists to familiar with the extrahepatic collaterals and perform cTAE/TACE via the extrahepatic collaterals.
Although extrahepatic collaterals feeding HCC have been reported in the literature,,,,,,,, the underlying risk factors are still unclear.,,,,,,, It was reported there is a close relationship between repeat cTAE/TACE therapy and the formation of extrahepatic collaterals, the repeat cTAE/TACE therapy damaged the hepatic artery which induced the formation of extrahepatic collaterals; also, tumor located at the surface of the liver were likely to be fed by the extrahepatic collaterals. Our study showed 81.1% (150/185) patients had previously undergone cTAE/TACE therapy or surgical resection, and all the tumors of the 185 patients located at the surface of the liver, which consistent with previous reports.,
The inferior phrenic artery and internal mammary artery are known to communicate with branches of the hepatic arterial system through the diaphragm.,,, The inferior phrenic artery is the major source of diaphragmatic blood supply to the liver, and tumors located at the posterior surface of the right lobe and beneath the diaphragm or at the anterior chest wall were likely to be fed by the right inferior phrenic artery and/or internal mammary artery.,, The collaterals via the omental artery probably enter the liver by direct adhesion of the omentum to the liver,, and tumors located at the anterior surface of the right lobe or at the lower edge of the medial segment of the liver were likely fed by the omental artery. The right and left gastric arteries anastomose with each other and enter the liver via the hepatoduodenal ligament, and tumors in the lateral segment of the liver were likely fed by the gastric artery. The right renal capsular artery and adrenal artery run through the hepatorenal ligament and enter the liver. The tumors located near the right renal fossa were likely fed by the right renal capsular artery and/or right adrenal artery. A deep branch of the cystic artery connects with the branch of a hepatic artery, and tumors located near the gallbladder fossa were likely fed by the cystic artery. In addition, a small hepatic artery branches from the cystic artery and directly penetrates the liver through the gallbladder fossa. The branches of the right and middle colic artery may enter the liver through the right paracolic gutter, especially when adhesion between the liver and colon is present. Our study showed the most common extrahepatic artery is inferior phrenic artery, followed by omental artery, gastric artery, renal capsular artery, adrenal artery, cystic artery, and internal mammary artery; however, the colic or left internal mammary artery was not found in this group patients.,
The extrahepatic collaterals are usually of small caliber, long way and branch at acute angles. Not only unsuccessful catheterization but also blockage of blood flow due to catheter insertion makes cTAE/TACE of small feeding branches difficult. We introduced a 2.7-Fr micro-catheter into the small vessels and underwent cTAE/TACE therapy, and the technical success rate was 96.8%; the serum AFP levels were significantly reduced at 1 month after treatment (P < 0.01); the disease control rate was 93% at 3 months after TAE/TACE treatment, and the cumulative survival rate from the time of TAE/TACE was 100% at 6 months, all of which suggested cTAE/TACE via extrahepatic collaterals additionaly has a high technical success rate, and can get satisfactory therapeutic efficacy in patients with extrahepatic collaterals feeding the HCC.
When extrahepatic collaterals are embolized, there is a risk of nontarget embolization, especially in the patients who falied of superselective catheterization. It was reported that cTAE/TACE via inferior phrenic artery can cause singultus, pleural effusion, and basal atelectasis; also, cutaneous complications can occur as a result of embolization of vessels supplying the skin. cTAE/TACE via cystic artery can cause cholecystitis or gallbladder infarction. cTAE/TACE via branches supplying the alimentary tract can cause ulcer. In the present study, there were 33 extrahepatic arteries injection of emulsion had to be terminated before achieved complete occlusion of the extrahepatic arteries due to early drainage of the emulsion via the gastroepiploic vein of the omentum (n = 5), and nontarget embolization (n = 28), and there was no major complications that related to the extrahepatic arteries embolization.
The major limitation of this retrospective study is that its retrospective nature; the risk factors of the formation extrahepatic collaterals can't be analysis due to the amount of patients was small, and the observation time was short; also, some extrahepatic collaterals may be missed.
Considering the results of this study, we offer several recommendations. First, if one finds of subcapsular location, adjacent organ infiltration, exophytic growth pattern of the tumor, it is mandatory to perform selective extrahepatic artery arteriography. Second, if one finds defective staining of the tumor on the hepatic arteriogram or defective lipiodol retention of the tumor, it is also mandatory to perform selective extrahepatic artery arteriography. Third, patients who had undergone repeated cTAE/TACE therapy and subcapsular location of the tumor should be careful observation of both the imagings and the angiograms to reduce the missed of collaterals. Finaly, lipiodol embolization should be performed carefully to avoid nontarget embolization.
| > Conclusion|| |
cTAE/TACE therapy via extrahepatic arteries can reduce the incidence of residual HCC, and improve the therapeutic efficacy of cTAE/TACE therapy.
Financial support and sponsorship
This study was supported by the High-Level Medical Talents Training Project of Changzhou (2016CZBJ009) and the Jiangsu Provincial Medical Youth Talent (QNRC2016270). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Zou JH, Zhang L, Ren ZG, Ye SL. Efficacy and safety of cTACE versus DEB-TACE in patients with hepatocellular carcinoma: A meta-analysis. J Dig Dis 2016;17:510-7.
Sacco R, Mismas V, Marceglia S, Romano A, Giacomelli L, Bertini M, et al.
Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives. World J Gastroenterol 2015;21:6518-25.
Miyayama S, Matsui O. Superselective conventional transarterial chemoembolization for hepatocellular carcinoma: Rationale, technique, and outcome. J Vasc Interv Radiol 2016;27:1269-78.
Ishikawa M, Yamagami T, Kakizawa H, Hieda M, Toyota N, Fukumoto W, et al.
Transarterial therapy of hepatocellular carcinoma fed by the right renal capsular artery. J Vasc Interv Radiol 2014;25:389-95.
Lencioni R, de Baere T, Soulen MC, Rilling WS, Geschwind JF. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data. Hepatology 2016;64:106-16.
Charnsangavej C, Chuang VP, Wallace S, Soo CS, Bowers T. Angiographic classification of hepatic arterial collaterals. Radiology 1982;144:485-94.
Michels NA. Collateral arterial pathways to the liver after ligation of the hepatic artery and removal of the celiac axis. Cancer 1953;6:708-24.
Jia Z, Tian F, Li S, Wang K, Zhao J, Wang Y, et al.
Supplemental transcatheter arterial chemoembolization for hepatocellular carcinoma fed by collateral omental artery. Hepatogastroenterology 2014;61:2042-6.
Jia Z, Tu J, Cao C, Wang W, Zhou W, Ji J, et al
. Liver abscess following transarterial chemoembolization for the treatment of hepatocellular carcinoma: A retrospective analysis of 23 cases. J Cancer Res Ther 2017. [Epub ahead of print].
Miyayama S, Matsui O, Akakura Y, Yamamoto T, Nishida H, Yoneda K, et al.
Hepatocellular carcinoma with blood supply from omental branches: Treatment with transcatheter arterial embolization. J Vasc Interv Radiol 2001;12:1285-90.
Chung JW, Park JH, Han JK, Choi BI, Kim TK, Han MC. Transcatheter oily chemoembolization of the inferior phrenic artery in hepatocellular carcinoma: The safety and potential therapeutic role. J Vasc Interv Radiol 1998;9:495-500.
Tanigawa N, Sawada S, Okuda Y, Shinzato S, Mishima K, Asai T, et al.
A case of small hepatocellular carcinoma supplied by the cystic artery. AJR Am J Roentgenol 1998;170:675-6.
Park SI, Lee DY, Won JY, Lee JT. Extrahepatic collateral supply of hepatocellular carcinoma by the intercostal arteries. J Vasc Interv Radiol 2003;14:461-8.
Kim JH, Chung JW, Han JK, Park JH, Choi BI, Han MC. Transcatheter arterial embolization of the internal mammary artery in hepatocellular carcinoma. J Vasc Interv Radiol 1995;6:71-4.
Nakai M, Sato M, Kawai N, Minamiguchi H, Masuda M, Tanihata H, et al.
Hepatocellular carcinoma: Involvement of the internal mammary artery. Radiology 2001;219:147-52.
Kodama Y, Shimizu T, Endo H, Hige S, Kamishima T, Holland GA, et al.
Spontaneous rupture of hepatocellular carcinoma supplied by the right renal capsular artery treated by transcatheter arterial embolization. Cardiovasc Intervent Radiol 2002;25:137-40.
Miyayama S, Matsui O, Nishida H, Yamamori S, Minami T, Shinmura R, et al.
Transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma fed by the cystic artery. J Vasc Interv Radiol 2003;14(9 Pt 1):1155-61.
Brown DB, Nikolic B, Covey AM, Nutting CW, Saad WE, Salem R, et al.
Quality improvement guidelines for transhepatic arterial chemoembolization, embolization, and chemotherapeutic infusion for hepatic malignancy. J Vasc Interv Radiol 2012;23:287-94.
Miyayama S, Matsui O, Taki K, Minami T, Ryu Y, Ito C, et al.
Extrahepatic blood supply to hepatocellular carcinoma: Angiographic demonstration and transcatheter arterial chemoembolization. Cardiovasc Intervent Radiol 2006;29:39-48.
Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52-60.
Sznol M. Reporting disease control rates or clinical benefit rates in early clinical trials of anticancer agents: Useful endpoint or hype? Curr Opin Investig Drugs 2010;11:1340-1.
Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003;14(9 Pt 2):S199-202.
Hu S, Tu J, Jia Z, Huang Y, Jiang G. Transarterial embolization/chemoembolization therapy for hepatocellular carcinoma fed by adrenal artery: Preliminary results. Medicine (Baltimore) 2016;95:e5762.
Kim HC, Chung JW, Lee W, Jae HJ, Park JH. Recognizing extrahepatic collateral vessels that supply hepatocellular carcinoma to avoid complications of transcatheter arterial chemoembolization. Radiographics 2005;25 Suppl 1:S25-39.
Chung JW, Kim HC, Yoon JH, Lee HS, Jae HJ, Lee W, et al.
Transcatheter arterial chemoembolization of hepatocellular carcinoma: Prevalence and causative factors of extrahepatic collateral arteries in 479 patients. Korean J Radiol 2006;7:257-66.
Komatsu T, Matsui O, Kadoya M, Yoshikawa J, Gabata T, Takashima T. Cystic artery origin of the segment V hepatic artery. Cardiovasc Intervent Radiol 1999;22:165-7.
Miyayama S, Yamashiro M, Shibata Y, Hashimoto M, Yoshida M, Tsuji K, et al.
Variations in feeding arteries of hepatocellular carcinoma located in the left hepatic lobe. Jpn J Radiol 2012;30:471-9.
Tajima T, Honda H, Kuroiwa T, Yabuuchi H, Okafuji T, Yosimitsu K, et al.
Pulmonary complications after hepatic artery chemoembolization or infusion via the inferior phrenic artery for primary liver cancer. J Vasc Interv Radiol 2002;13(9 Pt 1):893-900.
Arora R, Soulen MC, Haskal ZJ. Cutaneous complications of hepatic chemoembolization via extrahepatic collaterals. J Vasc Interv Radiol 1999;10:1351-6.
Chung JW, Park JH, Han JK, Choi BI, Han MC, Lee HS, et al.
Hepatic tumors: Predisposing factors for complications of transcatheter oily chemoembolization. Radiology 1996;198:33-40.
[Figure 1], [Figure 2]