Transcatheter arterial chemoembolization

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Transcatheter arterial chemoembolization
Other namesTransarterial chemoembolization
Specialty Interventional radiology

Transcatheter arterial chemoembolization (TACE) is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery directly supplying the tumor. These particles both block the blood supply and induce cytotoxicity, attacking the tumor in several ways.[ citation needed ]

Contents

The radiotherapeutic analogue (combining radiotherapy with embolization) is called radioembolization or selective internal radiation therapy (SIRT).[ citation needed ]

Clinical trials determine what type of therapy is generally most successful for treating any particular type of tumor. Panels of physicians, such as the National Comprehensive Cancer Network, determine what therapies to recommend for a given tumor type based on the outcomes of these trials. Although in theory TACE can be applied to any tumor, currently TACE is used primarily for tumors of the liver. [1]

Principles

TACE of liver tumors derives its beneficial effect by two primary mechanisms. [2] 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. [3]

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 ]

Therapeutic applications

Transcatheter arterial chemoembolization has most widely been applied to hepatocellular carcinoma for patients who are not eligible for surgery. [4] 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 ]

Procedure

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. [5]

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. [6] 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. [7]

Agents

Lipiodol – mixed with chemotherapeutic agents (Lipiodol is nonocclusive, combined with Gelfoam, Ivalon, or other particles)

Drug eluting particles – slow, sustained release of loaded drug locally with embolic effect leading to tumor ischemia

EmboCept S - 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 after two hours after procedure, limiting the risk of ischemia to other healthy liver cells. [8]

Epirubicin [9]

Other types of cancer besides liver cancer

TACE has also been used to treat people with

Adverse effects

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. [12] Transaminases may elevate 100-fold, and a leukemoid reaction is not uncommon.[ citation needed ]

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. [13]

History

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. [14]

See also

Related Research Articles

<span class="mw-page-title-main">Hepatocellular carcinoma</span> Medical condition

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.

Liver tumors are abnormal growth of liver cells on or in the liver. Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. Liver tumors can be classified as benign (non-cancerous) or malignant (cancerous) growths. They may be discovered on medical imaging, and the diagnosis is often confirmed with liver biopsy. Signs and symptoms of liver masses vary from being asymptomatic to patients presenting with an abdominal mass, hepatomegaly, abdominal pain, jaundice, or some other liver dysfunction. Treatment varies and is highly specific to the type of liver tumor.

<span class="mw-page-title-main">Interventional radiology</span> Medical subspecialty

Interventional radiology (IR) is a medical specialty that performs various minimally-invasive procedures using medical imaging guidance, such as x-ray fluoroscopy, computed tomography, magnetic resonance imaging, or ultrasound. IR performs both diagnostic and therapeutic procedures through very small incisions or body orifices. Diagnostic IR procedures are those intended to help make a diagnosis or guide further medical treatment, and include image-guided biopsy of a tumor or injection of an imaging contrast agent into a hollow structure, such as a blood vessel or a duct. By contrast, therapeutic IR procedures provide direct treatment—they include catheter-based medicine delivery, medical device placement, and angioplasty of narrowed structures.

<span class="mw-page-title-main">Embolization</span> Passage and lodging of an embolus within the bloodstream

Embolization refers to the passage and lodging of an embolus within the bloodstream. It may be of natural origin (pathological), in which sense it is also called embolism, for example a pulmonary embolism; or it may be artificially induced (therapeutic), as a hemostatic treatment for bleeding or as a treatment for some types of cancer by deliberately blocking blood vessels to starve the tumor cells.

<span class="mw-page-title-main">Uterine artery embolization</span>

Uterine artery embolization is a procedure in which an interventional radiologist uses a catheter to deliver small particles that block the blood supply to the uterine body. The procedure is primarily done for the treatment of uterine fibroids and adenomyosis. Since uterine fibroids are the most common indication, it is also often referred to as uterine fibroid embolization. Compared to surgical treatment for fibroids such as a hysterectomy, in which a woman's uterus is removed, uterine artery embolization may be beneficial in women who wish to retain their uterus. Other reasons for uterine artery embolization are postpartum hemorrhage and uterine arteriovenous malformations.

Lipiodol, also known as ethiodized oil, is a poppyseed oil used by injection as a radio-opaque contrast agent that is used to outline structures in radiological investigations. It is used in chemoembolization applications as a contrast agent in follow-up imaging. Lipiodol is also used in lymphangiography, the imaging of the lymphatic system. It has an additional use in gastric variceal obliteration as a dilutant that does not affect polymerization of cyanoacrylate.

Percutaneous hepatic perfusion (PHP) is a regionalized, minimally-invasive approach to cancer treatment currently undergoing Phase II and Phase III clinical testing. PHP treats a variety of hepatic tumors by isolating the liver and exposing the organ to high-dose chemotherapy. As demonstrated in clinical trials, patients treated by PHP can tolerate much higher doses of chemotherapeutic agents than those receiving traditional systemic chemotherapy without increased toxicities.

TheraSphere is a radiotherapy treatment for hepatocellular carcinoma (HCC) that consists of millions of microscopic, radioactive glass microspheres being infused into the arteries that feed liver tumors. These microspheres then embolize, lodging themselves in the liver's capillaries and bathing the malignancy in high levels of yttrium-90 radiation. It is currently approved as a Humanitarian Device, meaning effectiveness has not been proven, for patients as a neoadjuvant to surgery or transplantation by the U.S. Food and Drug Administration and is being used at a number of clinical centers in the United States.

Hepatic arterial infusion (HAI) is a medical procedure that delivers chemotherapy directly to the liver. The procedure, mostly used in combination with systemic chemotherapy, plays a role in the treatment of liver metastases in patients with colorectal cancer (CRC). Although surgical resection remains the standard of care for these liver metastases, majority of patients have lesions that are unresectable.

<span class="mw-page-title-main">Selective internal radiation therapy</span>

Selective internal radiation therapy (SIRT), also known as transarterial radioembolization (TARE), radioembolization or intra-arterial microbrachytherapy is a form of radiation therapy used in interventional radiology to treat cancer. It is generally for selected patients with surgically unresectable cancers, especially hepatocellular carcinoma or metastasis to the liver. The treatment involves injecting tiny microspheres of radioactive material into the arteries that supply the tumor, where the spheres lodge in the small vessels of the tumor. Because this treatment combines radiotherapy with embolization, it is also called radioembolization. The chemotherapeutic analogue is called chemoembolization, of which transcatheter arterial chemoembolization (TACE) is the usual form.

Yttrium-90 is an isotope of yttrium. Yttrium-90 has found a wide range of uses in radiation therapy to treat some forms of cancer.

Hepatic artery embolization, also known as trans-arterial embolization (TAE), is one of the several therapeutic methods to treat primary liver tumors or metastases to the liver. The embolization therapy can reduce the size of the tumor, and decrease the tumor's impact such its hormone production, effectively decreasing symptoms. The treatment was initially developed in the early 1970s. The several types of hepatic artery treatments are based on the observation that tumor cells get nearly all their nutrients from the hepatic artery, while the normal cells of the liver get about 70-80 percent of their nutrients and 50% their oxygen supply from the portal vein, and thus can survive with the hepatic artery effectively blocked. In practice, hepatic artery embolization occludes the blood flow to the tumors, achieving significant tumor shrinkage in over 80% of people. Shrinkage rates vary.

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Portal vein embolization (PVE) is a preoperative procedure performed in interventional radiology to initiate hypertrophy of the anticipated future liver remnant a couple weeks prior to a major liver resection procedure. The procedure involves injecting the right or left portal vein with embolic material to occlude portal blood flow. By occluding the blood flow to areas of the liver that will be resected away, the blood is diverted to healthy parts of the liver and induces hyperplasia. This may allow for a more extensive resection or stage bilateral resections that would otherwise be contraindicated resulting in better oncological treatment outcomes.

Radiation lobectomy is a form of radiation therapy used in interventional radiology to treat liver cancer. It is performed in patients that would be surgical candidates for resection, but cannot undergo surgery due to insufficient remaining liver tissue. It consists of injecting small radioactive beads loaded with yttrium-90 into the hepatic artery feeding the hepatic lobe in which the tumor is located. This is done with the intent of inducing growth in the contralateral hepatic lobe, not dissimilarly from portal vein embolization (PVE).

Ultrasonography of liver tumors involves two stages: detection and characterization.

Transarterial bland embolization is a catheter-based tumor treatment of the liver. In this procedure, a variety of embolizing agents can be delivered through the tumor’s feeding artery in order to completely occlude the tumor’s blood supply. The anti-tumor effects are solely based on tumor ischemia and infarction of tumor tissue, as no chemotherapeutic agents are administered. The rationale for the use of bland embolization for hepatocellular carcinoma(HCC) and/or other hyper-vascular tumors is based on the fact that normal liver receives a dual blood supply from the hepatic artery (25%) and the portal vein (75%). As the tumor grows, it becomes increasingly dependent on the hepatic artery for blood supply. Once a tumor nodule reaches a diameter of 2 cm or more, most of the blood supply is derived from the hepatic artery. Therefore, bland embolization and transarterial chemoembolization (TACE) consist of the selective angiographic occlusion of the tumor arterial blood supply with a variety of embolizing agents, with or without the precedence of local chemotherapy infusion. The occlusion by embolic particles results in tumor hypoxia and necrosis, without affecting the normal hepatic parenchyma.

Bronchial artery embolization is a treatment for hemoptysis, abbreviated as BAE. It is a kind of catheter intervention to control hemoptysis by embolizing the bronchial artery, which is a bleeding source. Embolic agents are particulate embolic material such as gelatin sponge or polyvinyl alcohol (PVA), and liquid embolic material such as NBCA, or metallic coils.

<span class="mw-page-title-main">Liver angiosarcoma</span> Medical condition

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<span class="mw-page-title-main">Miriplatin</span> Chemical compound

Miriplatin is a drug used to treat hepatocellular carcinoma (HCC). It is a lipophilic platinum complex that is used in transcatheter arterial chemoembolization (TACE). Miriplatin was approved by Japan's Pharmaceuticals and Medical Devices Agency in 2009.

References

  1. ↑ Young, Michael; John, Savio (2023), "Hepatic Chemoembolization", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   29939599 , retrieved 2023-11-24
  2. ↑ Miraglia R, Pietrosi G, Maruzzelli L, et al. (2007). "Efficacy of transcatheter embolization/chemoembolization (TAE/TACE) for the treatment of single hepatocellular carcinoma". World J Gastroenterol. 13 (21): 2952–5. doi: 10.3748/wjg.v13.i21.2952 . PMC   4171147 . PMID   17589945.
  3. ↑ Rammohan A, Sathyanesan J, Ramaswami S, et al. (2012). "Embolization of liver tumors: Past, present and future". World Journal of Radiology. 4 (9): 405–12. doi: 10.4329/wjr.v4.i9.405 . PMC   3460228 . PMID   23024842.
  4. ↑ Brown DB, Geschwind JF, Soulen MC, Millward SF, Sacks D (2006). "Society of Interventional Radiology position statement on chemoembolization of hepatic malignancies". J Vasc Interv Radiol. 17 (2): 217–23. doi: 10.1097/01.rvi.0000196277.76812.a3 . PMID   16517767.
  5. ↑ https://fyra.io. "Applying Superselective Conventional TACE". Endovascular Today. Retrieved 2023-05-26.{{cite web}}: External link in |last= (help)
  6. ↑ Walker, Sandra Beverley; Cleary, Sonja; Higgins, Monica (December 2001). "Comparison of the FemoStop device and manual pressure in reducing groin puncture site complications following coronary angioplasty and coronary stent placement". International Journal of Nursing Practice. 7 (6): 366–375. doi:10.1046/j.1440-172x.2001.00291.x. ISSN   1322-7114. PMID   11785439.
  7. ↑ Guan, YS; He, Q; Wang, MQ (2012). "Transcatheter arterial chemoembolization: history for more than 30 years". ISRN Gastroenterology. 2012: 480650. doi: 10.5402/2012/480650 . PMC   3433134 . PMID   22966466. S2CID   15761122.
  8. ↑ "EmboCept S - the universal short-term embolizate" (PDF). The Spanish Society of Vascular and Interventional Radiology (SERVEI). Archived from the original (PDF) on 12 March 2022. Retrieved 12 March 2022.
  9. ↑ Ikeda, Masafumi; Inaba, Yoshitaka; Tanaka, Toshihiro; Sugawara, Shunsuke; Kodama, Yoshihisa; Aramaki, Takeshi; Anai, Hiroshi; Morita, Shinichi; Tsukahara, Yoshinori; Seki, Hiroshi; Sato, Mikio; Kamimura, Kenya; Azama, Kimei; Tsurusaki, Masakatsu; Sugihara, Eiji (2020-05-20). "A prospective randomized controlled trial of selective transarterial chemoembolization using drug-eluting beads loaded with epirubicin versus selective conventional transarterial chemoembolization using epirubicin-lipiodol for hepatocellular carcinoma: The JIVROSG-1302 PRESIDENT study". Journal of Clinical Oncology. 38 (15_suppl): 4518. doi:10.1200/JCO.2020.38.15_suppl.4518. ISSN   0732-183X. S2CID   219780597.
  10. ↑ Boas FE, Kemeny NE, Sofocleous CT, Yeh R, Thompson VR, Hsu M, Moskowitz CS, Ziv E, Yarmohammadi H, Bendet A, Solomon SB (2021). "Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial". Radiology. 301 (2): 474–84. doi:10.1148/radiol.2021210213. PMC   8574062 . PMID   34463550.
  11. ↑ Gao F, Gao J, Wang K, Song L (2022). "Efficacy and safety of transarterial chemoembolization with CalliSpheres Microspheres in head and neck cancer". Frontiers in Surgery. 9: 938305. doi:10.3389/fsurg.2022.938305. PMC   9452835 . PMID   36090318.
  12. ↑ Stuart K (2003). "Chemoembolization in the management of liver tumors". Oncologist. 8 (5): 425–37. doi: 10.1634/theoncologist.8-5-425 . PMID   14530495. S2CID   38536397.
  13. ↑ Guan, YS; He, Q; Wang, MQ (2012). "Transcatheter arterial chemoembolization: history for more than 30 years". ISRN Gastroenterology. 2012: 480650. doi: 10.5402/2012/480650 . PMC   3433134 . PMID   22966466. S2CID   15761122.
  14. ↑ Guan YS, He Q, Wang MQ (2012). "Transcatheter arterial chemoembolization: history for more than 30 years". ISRN Gastroenterology. 2012: 1–8. doi: 10.5402/2012/480650 . PMC   3433134 . PMID   22966466.
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