Overview of Hepatic Chemoembolization
Chemoembolization is a procedure that involves injecting cancer-fighting drugs (chemotherapy) directly into the blood vessels that feed a tumor, along with special particles that help slow or even stop the flow of blood and nutrients to the tumor. This technique has been in use since the late 1970s. It is often used as a way to treat either the primary liver cancer or cancer that has spread (metastasized) to the liver.
The most common type of primary liver cancer is called hepatocellular carcinoma (HCC). Some common types of cancer that can spread to the liver include tumors originally from the colon, breast, carcinoid (rare types of slow-growing tumors), soft tissue sarcomas (cancer that starts in the muscles, fat, or blood vessels), and melanoma (a serious type of skin cancer). You might also hear this chemoembolization procedure referred to as transarterial chemoembolization (TACE).
Anatomy and Physiology of Hepatic Chemoembolization
The liver is made up of different parts called lobes and segments. Various methods can categorize these parts, but the most common one is the Couinaud classification. This model outlines the segments and lobes based on their specific blood supply from the portal veins and their blood drainage system.
The blood supply to the liver can differ from person to person. In most cases, there’s a single main artery, known as the proper hepatic artery, that comes from another artery called the common hepatic artery, which is sourced from an artery named the celiac artery. This main artery then splits into two branches – right and left – supplying blood to the right and left lobes of the liver.
However, less than half of all humans actually have this configuration. Some disagreements exist about what to call the artery that provides blood to a specific part of the liver called segment 4. Some call this a middle hepatic artery, while others refer to it as a segment four branch. The part of the liver known as the caudate lobe can have a particularly complex blood supply, often sourced from multiple branches of both the right and left hepatic arteries.
There are three commonly recognized alternative paths by which blood can flow to liver tumors: The right phrenic artery (sometimes called the inferior phrenic artery), a replaced or additional left hepatic artery, and the right internal mammary artery (also sometimes referred to as the internal thoracic artery).
Moreover, there are four arteries that are important to keep in mind. These arteries can unintentionally receive a treatment involving the blocking of blood vessels called chemoembolization, resulting in the potential damage to healthy tissues. These arteries include: The cystic artery, the right gastric artery, the falciform artery, and the duodenal (or supraduodenal) artery.
Why do People Need Hepatic Chemoembolization
The National Comprehensive Network (NCCN), a non-profit organization made up of selected hospitals and doctors from multiple specialties, has created some of the most widely used guidelines in the US for treating cancer patients.
According to the NCCN’s guidelines, a treatment called Transarterial Chemoembolization (TACE) could be suitable for some cancer patients. This process involves injecting chemotherapy drugs directly into the blood vessels feeding a cancer tumor. While not considered as a curative (fully healing) treatment, TACE can be more effective in relieving symptoms compared to other treatment options that focus on patient comfort rather than curing the disease. In some cases, TACE could shrink the tumor enough to allow for surgical removal or achieve complete permanent tumor death.
Identifying the right patient for TACE involves considering various factors. A typical candidate for TACE has advanced cancer and/or overall poor health that surgery might not be beneficial. However, they also need to be healthy enough to withstand the potential side effects of TACE treatment and potentially extend their life by at least several months while maintaining a reasonable quality of life.
The NCCN uses different scoring systems to evaluate a patient’s condition and suitability for different treatments. These scores relate to liver function (Child-Pugh score) and liver and kidney function (Model for End-stage Liver Disease (MELD) score). These are primarily used to decide whether a person’s liver cancer or metastatic disease (cancer that has spread) can benefit from TACE.
Determining which treatment best suits an individual patient can vary and often depends on the patient’s specific conditions. However, guidelines help doctors maintain some level of objectivity when making these decisions.
The NCCN also uses the Milan criteria to decide whether a patient should receive a liver transplant as a primary treatment for liver cancer. This criteria considers the size and number of tumors in the liver.
That said, the prognosis for a person with Hepatocellular Carcinoma (HCC), a type of liver cancer, isn’t entirely reliant on tumor size and number. Other factors such as the underlying cause of liver cancer (hepatitis B/C or alcohol-induced, for example), and molecular markers are crucial. Consequently, the tumor staging system (which classifies the severity of cancer) used should ideally be based on patients with similar circumstances to the patient being evaluated.
The Barcelona Clinic Liver Cancer (BCLC) staging system, a well-regarded system supported by the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL), is probably the most popular in the US. This system consolidates other methods, like the Child-Pugh score and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), which assess a patient’s general well-being.
There are five stages in the BCLC system (0, A, B, C, and D), which represent a progression from least to most severe cases of liver disease. BCLC stage-B patients are very diverse in terms of their medical condition.
The BCLC and EASL guidelines recommend TACE as the primary treatment in cases where the patient is in the intermediate stage (Stage B), retains good liver function and has an ECOG-PS of zero (meaning they are fully active). This is also applied when the liver cancer does not meet the resection (surgical removal) or transplantation criteria.
When a Person Should Avoid Hepatic Chemoembolization
In simpler terms, TACE – short for Transarterial Chemoembolization (a procedure used to treat liver cancer), may not be given to certain individuals under certain conditions such as:
– A poor life expectancy. This happens when a patient cannot take care of themselves or they’re limited to a bed or chair.
– If they are not suitable for chemotherapy due to heart or kidney failure or low white blood cell count (leukopenia).
– If they can’t or won’t adhere to post-treatment checkup schedules.
– If the cancer has spread to other parts of the body (Extra-hepatic metastases).
– Presence of fluid in the abdomen due to cancer (Malignant ascites).
– Cancerous tumors larger than 5 cm.
– Poor liver function or end-stage liver disease (cirrhosis).
– Encephalopathy, a term for brain disease, damage, or malfunction.
– If the patient has yellow skin or eyes from a buildup of bilirubin, a term for a symptom called jaundice.
– If they regularly consume alcohol.
– If the tumor appears as having a less vascular nature (fewer blood vessels) on an MRI or a CT scan.
– If there’s a blockage in the main blood vessel supplying the liver (known as portal vein thrombosis), which can lead to increased risk of liver failure after treatment.
TACE should be avoided when there is a blockage in the bile duct causing an increase in bilirubin level in the blood, unless injections can be performed into the segment involved. It’s also not advised if the patient is a good candidate for a potentially better treatment.
Normally, only half of the liver at the most should be treated with TACE at one time. Thus, if the tumor involves more than 50% of the liver, it is better to have two TACE procedures.
TACE is generally not suitable for patients with progressed cirrhosis, which refers to severe liver disease causing symptoms such as fluid build-up in the abdomen, brain dysfunction, jaundice, or bleeding veins in the esophagus.
TACE doesn’t usually harm the normal liver tissue not involved with the tumor as this type of liver cancer usually gets its blood from the hepatic artery, which is the main target of TACE, while normal liver tissue gets its blood from the portal vein.
Deaths due to TACE are very rare, usually less than 1%, mostly resulting from liver failure. Therefore, it’s critical to choose the right patients for this procedure.
To prevent the possibility of causing a worse bile duct obstruction, many doctors treat bile duct obstructions before suggesting TACE. The National Comprehensive Cancer Network (NCCN) does not suggest TACE as a treatment for primary cholangiocarcinoma (bile duct cancer).
Equipment used for Hepatic Chemoembolization
TACE, a treatment used to deliver chemotherapy, can be divided into two main methods:
1. TACE with drug-releasing particles, and
2. TACE where the chemotherapy drug and particles used to block the blood supply are separate agents.
In the conventional method of TACE, three things are mixed together: a substance called lipiodol that helps to see the areas being treated on images, a chemotherapy drug, and a substance used to block the blood supply to the tumor. Another type of TACE uses tiny beads made of resin that slowly release chemotherapy.
As of now, the FDA has only approved two chemotherapy drugs to be used this way. Doxorubicin is used to treat certain types of liver tumors and cancer that has spread. Irinotecan is used for cancer that has spread from the colon and rectum.
While using resin beads that slowly release chemotherapy has been found to be just as effective and have fewer side effects compared to the conventional method, using a method where only the blocking substance is administered without chemotherapy is still up for debate.
Preparing for Hepatic Chemoembolization
Before undergoing transarterial chemoembolization (TACE), doctors may use specific scans like CT or MRI scans to better understand your condition and plan your treatment effectively. These scans are important because they can spot any issues that may make the TACE treatment less safe or effective, such as a blockage in the main portal vein, a large vein in your liver.
Not all patients will need a biopsy, which is a procedure that involves removing a small sample of tissue for examination. If the tumor in your liver matches certain characteristics on the CT or MRI scan, or if the scans show clear indications of a primary tumor outside the liver, doctors typically won’t need a biopsy.
However, in some specific situations, doctors may consider a biopsy beneficial – for example, if the scan results are suspicious for cancer, but don’t meet the typical characteristics of hepatocellular carcinoma (HCC), a common type of liver cancer.
In order to deliver the chemoembolization safely to the targeted location, physicians may, at times, use small metallic devices called coils to block off the neighboring arteries temporarily. This helps to prevent chemotherapy from entering unintended areas in the body, a situation referred to as non-target chemoembolization.
TACE is typically performed while the patient is under conscious sedation, which means you’ll be in a state of deep relaxation but still awake. Doctors use a scoring system to determine your anesthesia risk based on a combination of physical checks and medical history.
Hydration is necessary before this procedure and is often administered via an intravenous line, where a saline solution is directly infused into your bloodstream.
To prevent infections from developing, antibiotics are usually prescribed after TACE. The antibiotics help combat infections caused by various bacteria. In some cases, you may also be given a bowel cleansing preparation.
To prevent bleeding complications, doctors follow a set of guidelines provided by the Society of Interventional Radiology.
Depending on the type of your tumor and individual health condition, certain medications might be administered before the procedure. These could include drugs to prevent or reduce side effects, nausea, or inflammation, though these are sometimes given only after the procedure.
How is Hepatic Chemoembolization performed
First, a doctor will need to gain access to your arteries in order to carry out a visual examination – this is a procedure often referred to as an arteriography. This helps the doctor identify the arteries supplying blood to the liver tumor or tumors, if there are multiple.
If there are any arteries which could potentially lead to unwanted areas being affected by the procedure, the doctor will close off or “occlude” these, commonly using small metal spirals known as coils. Doing this helps to minimize the chance of harming healthy surrounding tissues.
To get to the arteries within the liver that are supplying the tumor with blood, the doctor will often need to use a very tiny tube called a microcatheter. This tube is around 1 mm wide, roughly the size of a fine-tipped pen.
Once the catheter or microcatheter is properly positioned, it should be directly near the location that the doctor believes will yield the best results. At this point, substances called embolization particles, special dyes known as “contrast”, and chemotherapy drugs are sent through the catheter until the blood flow seen under x-ray (fluoroscopy) slows down to a stop in the area serving the tumor.
After this step, the doctor will carry out another arteriography. This allows them to document whether blood is still flowing to the area of interest, or if it has stopped as intended.
The maximum amount of chemotherapy given, such as 75 mg of a drug called doxorubicin, is calculated ahead of time based on whether the tumor is present in one or two sections of the liver – these sections are known as lobes.
Possible Complications of Hepatic Chemoembolization
In around 5 to 10 out of 100 people who have a TACE, or Transarterial Chemoembolization, serious complications can happen. The most common of these are:
* Liver failure, which is when the liver stops working correctly.
* Death from any reason.
* Abscess, or a localized collection of pus.
There are also other serious complications that, although rare, can affect patients. These include:
* Tumor rupture, which is when a tumor in the liver breaks open.
* Cholecystitis, an inflammation of the gallbladder.
* Biloma, a collection of bile outside of the bile ducts.
* Permanent biliary stricture, a narrowing of the bile duct.
* Arterial dissection, a tear inside the wall of an artery.
* Pulmonary emboli, which are blood clots in the lungs.
* Tissue injury from non-target embolization; this means that the therapy is mistakenly targeting healthy tissue instead of the tumor. This can result in complications like gastrointestinal hemorrhage, or internal bleeding in the digestive tract.
What Else Should I Know About Hepatic Chemoembolization?
There are no published figures on the number of people who need a particular treatment to prevent one death over a timeframe, such as a year, especially when it comes to an approach called TACE. That’s because there haven’t been studies that measure this specific risk reduction and the actual number might be quite large.
The Society of Interventional Radiology defines technical success as proper placement of the catheter (a small flexible tube) and the right dosage of medication and particles used in the procedure. They expect this technical success rate to be at least 98%.
Clinical success, on the other hand, is defined as achieving effective tumor death, which may either downgrade the severity of the disease or prolong the patient’s life. There aren’t any established national standards for this. The patient’s chances of survival significantly improve if they narrowly miss the criteria for surgery and have the following:
- An overall good health condition,
- Good liver function, and
- Lower tumor load.
In an approach to reduce the severity of liver cancer, using the best minimally invasive methods (like RFA, TACE, PEI) worked for 21 of 30 patients who either had one tumor from 5 to 8 cm size, two or three lesions with one between 3 to 5 cm in total less than 8 cm, or four to five lesions all under 3 cm with total less than 8 cm.
In a study focusing on patients younger than 65 with liver cancer who could possibly be considered for liver transplants, 34 out of 62 were successfully downgraded in severity.
It’s important to understand that a patient’s chances of successful downgrading may be lower if they do not have similar health predictors as the patients in these studies.
Three different studies have shown improved patient survival after TACE versus not treating liver cancer at all. However, the patients from these studies underwent more than one TACE session, so it’s unclear if a single session of TACE could lead to improved survival. Intermediate stage patients (BCLC stage-B) typically survive about 16 months. However, with one or more TACE sessions, the survival time could extend to about 19 to 20 months.
If the cancer has spread to the liver from other parts of the body, the expected survival time can vary widely. The results are generally less promising than for patients only with liver cancer. In such cases, TACE is typically used only for alleviating symptoms after a full course of chemotherapy.
There are also alternative treatments to TACE depending on the patient’s condition. This can include chemotherapy, targeted radiation therapy, tumor ablation using heat or cold, or a method called embolization that blocks the tumor’s blood supply. The NCCN lists these alternatives as potential mainstream therapies for patients.
