Transcatheter arterial chemoembolization

TACE of liver tumors derives its beneficial effect by two primary mechanisms.{{cite journal|vauthors=Miraglia R, Pietrosi G, Maruzzelli L |title=Efficacy of transcatheter embolization/chemoembolization (TAE/TACE) for the treatment of single hepatocellular carcinoma|journal=World J Gastroenterol|year=2007|volume=13|issue=21|pages=2952–5|display-authors=etal|doi=10.3748/wjg.v13.i21.2952|pmid=17589945|pmc=4171147 |doi-access=free }} Most tumors within the liver are supplied by the proper hepatic artery, so arterial embolization preferentially interrupts the tumor's blood supply and stalls growth until neovascularization. Secondly, focused administration of chemotherapy allows for delivery of a higher dose to the tissue while simultaneously reducing systemic exposure, which is typically the dose-limiting factor. This effect is potentiated by the fact that the chemotherapeutic drug is not washed out from the tumor vascular bed by blood flow after embolization. Effectively, this results in a higher concentration of drug to be in contact with the tumor for a longer period of time.{{cite journal|vauthors=Rammohan A, Sathyanesan J, Ramaswami S |title=Embolization of liver tumors: Past, present and future|journal=World Journal of Radiology|year=2012|volume=4|issue=9|pages=405–12|doi=10.4329/wjr.v4.i9.405|display-authors=etal|pmid=23024842|pmc=3460228 |doi-access=free }}

Park et al. conceptualized carcinogenesis of hepatocellular carcinoma (HCC) as a multistep process involving parenchymal arterialization, sinusoidal capillarization, and development of unpaired arteries (a vital component of tumor angiogenesis). All these events lead to a gradual shift in tumor blood supply from portal to arterial circulation. This concept has been validated using dynamic imaging modalities by various investigators. Sigurdson et al. demonstrated that, when an agent was infused via the hepatic artery, intratumoral concentrations were ten times greater compared to when agents were administered through the portal vein. Hence, arterial treatment targets the tumor while normal liver is relatively spared. Embolization induces ischemic necrosis of tumor causing a failure of the transmembrane pump, resulting in a greater absorption of cytotoxic agents by the tumor cells. Tissue concentration of agents within the tumor is greater than 40 times that of the surrounding normal liver.{{citation needed|date=March 2022}}

Transcatheter arterial chemoembolization has most widely been applied to hepatocellular carcinoma for patients who are not eligible for surgery.{{cite journal|vauthors=Brown DB, Geschwind JF, Soulen MC, Millward SF, Sacks D |title=Society of Interventional Radiology position statement on chemoembolization of hepatic malignancies|journal=J Vasc Interv Radiol|year=2006|volume=17|issue=2|pages=217–23|doi=10.1097/01.rvi.0000196277.76812.a3|pmid=16517767|doi-access=free}} TACE has been shown to increase survival in patients with intermediate HCC by BCLC criteria. It has also been used as an alternative to surgery for resectable early stage HCC and in patients with regional recurrence of the tumor after previous resection. TACE may also be used to downstage HCC in patients who exceed the Milan criteria for liver transplantation.

Other treated malignancies include neuroendocrine tumors, ocular melanoma, cholangiocarcinoma, and sarcoma. Transcatheter arterial chemoembolization plays a palliative role in patients with metastatic colon carcinoma. There is a possible benefit for liver-dominant metastases from other primary malignancies.{{citation needed|date=March 2022}}

TACE is an interventional radiology procedure performed in the angiography suite. The procedure involves gaining percutaneous transarterial access by the Seldinger technique to the hepatic artery with an arterial sheath, usually by puncturing the common femoral artery in the right groin and passing a catheter guided by a wire through the abdominal aorta, through the celiac trunk and common hepatic artery, and finally into the branch of the proper hepatic artery supplying the tumor.

The interventional radiologist then performs a selective angiogram of the celiac trunk and possibly the superior mesenteric artery to identify the branches of the hepatic artery supplying the tumor(s) and threads smaller, more selective catheters into these branches. This is done to maximize the amount of the chemotherapeutic dose that is directed to the tumor and minimize the amount of the chemotherapeutic agent that could damage the normal liver tissue.{{Cite web |last=Miyayama |first=Shiro |title=Applying Superselective Conventional TACE |url=https://evtoday.com/articles/2017-apr/applying-superselective-conventional-tace |access-date=2023-05-26 |website=Endovascular Today |language=en}}

When a blood vessel supplying the tumor has been selected, alternating doses of the chemotherapy dose and of embolic particles, or an infusion of embolic particles containing the chemotherapy agent, are injected through the catheter .

The physician removes the catheter and access sheath, applying pressure to the entry site to prevent bleeding. The patient must lie stationary for several hours after the procedure to allow the punctured artery to heal. The clinician can apply pressure using a Femostop or close the artery using a vascular sealing device.{{Cite journal |last1=Walker |first1=Sandra Beverley |last2=Cleary |first2=Sonja |last3=Higgins |first3=Monica |date=December 2001 |title=Comparison of the FemoStop device and manual pressure in reducing groin puncture site complications following coronary angioplasty and coronary stent placement |url=https://doi.org/10.1046/j.1440-172X.2001.00291.x |journal=International Journal of Nursing Practice |volume=7 |issue=6 |pages=366–375 |doi=10.1046/j.1440-172x.2001.00291.x |pmid=11785439 |issn=1322-7114}} The patient will often be kept overnight for observation and will likely be discharged the following day. The procedure is normally followed up with a CT scan several weeks later to check the response of the tumor to the procedure.{{cite journal |last1=Guan |first1=YS |last2=He |first2=Q |last3=Wang |first3=MQ |title=Transcatheter arterial chemoembolization: history for more than 30 years. |journal=ISRN Gastroenterology |date=2012 |volume=2012 |pages=480650 |doi=10.5402/2012/480650 |pmid=22966466|pmc=3433134 |s2cid=15761122 |doi-access=free }}

TACE may be either conventional TACE (cTACE) or TACE with drug-eluting beads (DEBs) (DEB-TACE).{{cite journal | vauthors = Raoul JL, Forner A, Bolondi L, Cheung TT, Kloeckner R, de Baere T | title = Updated use of TACE for hepatocellular carcinoma treatment: How and when to use it based on clinical evidence | journal = Cancer Treat Rev | volume = 72 | issue = | pages = 28–36 | date = January 2019 | pmid = 30447470 | doi = 10.1016/j.ctrv.2018.11.002 | url = }}

cTACE involves intra-arterial injection of cytotoxic chemotherapy drugs emulsified in Lipiodol, an oily radio-opaque agent. Following this, an embolic agent, for instance gelatin sponge, polyvinyl alcohol particles, or microspheres, is intra-arterially injected.

DEB-TACE involves intra-arterial injection of DEBs, which are non-resorbable embolic microspheres that are loaded with chemotherapy drugs. DEBs allow for more sustained local chemotherapy drug release (e.g., 1{{nbsp}}month) along with concomitant embolization. They are alternatively known as drug-eluting embolic (DEE) microspheres.{{cite journal | vauthors = Mikhail AS, Negussie AH, Mauda-Havakuk M, Owen JW, Pritchard WF, Lewis AL, Wood BJ | title = Drug-eluting embolic microspheres: State-of-the-art and emerging clinical applications | journal = Expert Opin Drug Deliv | volume = 18 | issue = 3 | pages = 383–398 | date = March 2021 | pmid = 33480306 | pmc = 11247414 | doi = 10.1080/17425247.2021.1835858 | url = }}

Examples of specific types of DEBs include the following:

• Polyvinyl alcohol microspheres – loaded with doxorubicin
• Superabsorbent polymer microspheres – loaded with doxorubicin
• Gelatin microspheres – loaded with cisplatin

EmboCept S is an embolic agent made up of degradable starch microspheres (DSM). It can be mixed with low-volume chemotherapeutic agents such as doxorubicin and mitomycin and high-volume chemotherapeutic agents such as cisplatin and irinotecan to be administered into a subject. It is a short-acting, thus will be degraded 2{{nbsp}}hours after procedure, limiting the risk of ischemia to other healthy liver cells.{{cite web |title=EmboCept S - the universal short-term embolizate |url=https://servei.org/wp-content/uploads/Embocept_S_Cat_3.pdf |publisher=The Spanish Society of Vascular and Interventional Radiology (SERVEI) |access-date=12 March 2022 |archive-url=https://web.archive.org/web/20220312072404/https://servei.org/wp-content/uploads/Embocept_S_Cat_3.pdf |archive-date=12 March 2022}}

The most commonly used chemotherapy agents in TACE for HCC are (in decreasing order of frequency): doxorubicin, cisplatin, epirubicin, mitoxantrone, and mitomycin C.{{cite journal | vauthors = Hulin A, Stocco J, Bouattour M | title = Clinical Pharmacokinetics and Pharmacodynamics of Transarterial Chemoembolization and Targeted Therapies in Hepatocellular Carcinoma | journal = Clin Pharmacokinet | volume = 58 | issue = 8 | pages = 983–1014 | date = August 2019 | pmid = 31093928 | doi = 10.1007/s40262-019-00740-w | url = }} Less frequently used drugs include anthracyclines, like pirarubicin, nemorubicin, and idarubicin, and platinum-based agents, like miriplatin, carboplatin, and lobaplatin. No evidence-based guidelines exist to guide choice of chemotherapy agents or their dosages and none of the preceding drugs are explicitly approved by regulatory authorities for loco-regional treatment of HCC. The choices of agents, doses, and procedures vary widely between centers and surgeons. There are few studies defining dose-limiting toxicity of these agents, which may explain the widely varying practices. Single-agent therapy (e.g., doxorubicin alone) is appropriate in most cases, but some centers use two- or three-drug combinations (e.g., doxorubicin plus mitomycin C, or doxurubicin plus mitomycin C plus gemcitabine).{{cite journal | vauthors = Sacco R, Tapete G, Simonetti N, Sellitri R, Natali V, Melissari S, Cabibbo G, Biscaglia L, Bresci G, Giacomelli L | title = Transarterial chemoembolization for the treatment of hepatocellular carcinoma: a review | journal = J Hepatocell Carcinoma | volume = 4 | issue = | pages = 105–110 | date = 2017 | pmid = 28795053 | pmc = 5538681 | doi = 10.2147/JHC.S103661 | doi-access = free | url = }}

TACE may be used in conjunction with systemic chemotherapy agents.{{cite journal | vauthors = Eugen K | title = Current treatment options for hepatocellular carcinoma | journal = Klin Onkol | volume = 33 | issue = Supplementum 3 | pages = 20–25 | date = 2020 | pmid = 33213161 | doi = 10.14735/amko20203S20 | url = | doi-access = free }}

TACE has also been used to treat people with:

• Lung primary cancer or metastases.{{cite journal | vauthors = Boas FE, Kemeny NE, Sofocleous CT, Yeh R, Thompson VR, Hsu M, Moskowitz CS, Ziv E, Yarmohammadi H, Bendet A, Solomon SB | title = Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial | journal = Radiology | volume = 301 | issue = 2 | pages = 474–84 | date = 2021 | doi = 10.1148/radiol.2021210213 | pmid = 34463550 | pmc = 8574062 }}
• Head and neck cancer.{{cite journal | vauthors = Gao F, Gao J, Wang K, Song L | title = Efficacy and safety of transarterial chemoembolization with CalliSpheres Microspheres in head and neck cancer | journal = Frontiers in Surgery | volume = 9 | pages = 938305 | date = 2022 | doi = 10.3389/fsurg.2022.938305 | pmid = 36090318 | pmc = 9452835 | doi-access = free }}

As with any interventional procedure, there is a small risk of hemorrhage and/or damage to blood vessels. Pseudoaneurysm can develop at the site of puncture in the femoral artery. During this procedure contrast media is utilized, to which patients may develop an allergic reaction. Symptomatic hypothyroidism may result from the high retained iodine load of the contrast.

Off-target delivery of embolic agents such as reflux into healthy surrounding tissue is a potential side effect that may cause complications such as ulceration of the gut or cholecystitis. Specialized techniques and devices may decrease the risk.

TACE induces tumor necrosis in more than 50% of patients; the resulting necrosis releases cytokines and other inflammatory mediators into the bloodstream. A self-limiting postembolization syndrome of pain, fever, and malaise may occur due to hepatocyte and tumor necrosis.{{cite journal|last=Stuart K|title=Chemoembolization in the management of liver tumors|journal=Oncologist|year=2003|volume=8|issue=5|pages=425–37|doi=10.1634/theoncologist.8-5-425|pmid=14530495|s2cid=38536397 |doi-access=free}} Transaminases may elevate 100-fold, and a leukemoid reaction is not uncommon.{{citation needed|date=March 2022}}

Intrahepatic abscess (treated by percutaneous drainage) and gallbladder ischemia are extremely rare. Rising bilirubin is a warning sign of irreversible hepatic necrosis, generally occurring in the setting of cirrhosis. In an effort to reduce the likelihood of significant hepatic toxicity, chemoembolization should be restricted to a single lobe or major branch of the hepatic artery at one time. The patient may be brought back after 1 month, once toxicities and abnormal chemistries have resolved, to complete the procedure in the opposite lobe. Retreatment of new lesions may be necessary, if patients fulfill the original eligibility criteria.{{cite journal |last1=Guan |first1=YS |last2=He |first2=Q |last3=Wang |first3=MQ |title=Transcatheter arterial chemoembolization: history for more than 30 years. |journal=ISRN Gastroenterology |date=2012 |volume=2012 |pages=480650 |doi=10.5402/2012/480650 |pmid=22966466|pmc=3433134 |s2cid=15761122 |doi-access=free }}

In 1972, surgical ligation of the hepatic artery was first used to treat recurrent hepatic tumors followed by infusion of 5-fluorouracil into the portal vein. Due to the liver's dual blood supply from the hepatic artery and portal vein, interruption of the flow through the hepatic artery was demonstrated to be safe in patients. Tumor embolization eventually developed, blocking the vascular supply to a tumor by primarily endovascular approaches. The application of angiography with embolization followed, and the administration of chemotherapeutic agents with embolic particles evolved into transcatheter arterial chemoembolization.{{cite journal|vauthors=Guan YS, He Q, Wang MQ |title=Transcatheter arterial chemoembolization: history for more than 30 years|journal=ISRN Gastroenterology|volume=2012|pages=1–8|year=2012|doi=10.5402/2012/480650|pmid=22966466|pmc=3433134 |doi-access=free }}

• Bland embolization

{{Reflist|2}}

{{DEFAULTSORT:Transcatheter Arterial Chemoembolization}}

Category:Hepatology

Category:Interventional radiology