FOR PATIENTS Other Treatment Options: Cryosurgery Cryosurgery Cryosurgery describes the destruction of cancer cells using sub-zero temperatures. During the procedure, multiple stainless steel probes are placed into the center of the tumor and liquid nitrogen is circulated through the end of the device positioned in the tumor, effectively freezing it. Cryosurgery involves a cycle of treatments in which the tumor is frozen, allowed to thaw and then refrozen. While cryosurgery is considered to be relatively effective, it use is limited because: • Patients unable to undergo a surgical procedure are not candidates for this procedure • Its complications include those typical of surgery, and can lead to liver fracture and hemorrhaging caused by the cycle of freezing and thawing • It is associated with mortality rates estimated to be between one and five percent • It is an expensive treatment relative to other methods

Resection
Resection is the surgical removal of a cancerous tumor and is the preferred therapy for any type of cancer, but it is not effective if the tumors are too small, spread out or encroaching on certain critical organs or arteries. Liver tumors are generally considered resectable if the tumors are limited to one of the two lobes of the liver. Because liver tumors tend to spread through both lobes, surgical removal is considered an option in less than 10% of diagnosed cases. Further factors limiting surgery as a viable treatment option include:

• A patient with limited liver function or who is in poor health

• The cancer is not localized within the organ

• The liver is suffering from another disease, for example cirrhosis

• The proximity of the cancerous tumor to a critical organ or artery or the size or location on the liver or number of tumors makes surgery not technically feasible

Where surgery is a viable option, there remain significant complications related to the procedure, including recurrence of tumors. If the tumors recur, surgery typically cannot be repeated.

Chemotherapy:
The most common treatment for cancer in the liver is intravenous chemotherapy. Several chemotherapeutic drugs have shown some effectiveness in shrinking tumor cells in the liver, but their effectiveness is limited by their side effects. While a higher dose of administered chemotherapy results in a greater ability to kill cancer cells, this higher dose correlates to increased damage to healthy tissues. Because the dosage of chemotherapy required to kill cancer cells can be lethal to patients, when administered systemically, the dose prescribed by the physician tends to be too low to shrink the tumors.

Intravenous chemotherapy’s limited effectiveness and its debilitating, often life-threatening, side-effects make the decision regarding pursuing it as a treatment a difficult one. In some instances, in an attempt to shrink tumors, a physician may prescribe a radically high-dose of chemotherapy, despite its side-effects. In other cases, recognizing the inevitable result of liver cancer, the physician and patient may choose only to manage the patient's discomfort from the cancer with pain killers while foregoing treatment. While chemotherapy may be effective under laboratory conditions, the inability to provide high enough dosing to kill the cancer cells without causing death to the patient limits the agent's effectiveness.

Radiation Therapy
Radiation therapy uses high dose x-rays or localized radiation to kill cancer cells or shrink tumors. Radiation therapy utilizing x-rays is not considered an effective means for treating liver cancer and thus is rarely used for this purpose. Multiple localized radiation delivery mechanisms are currently being used and tested, and may prove effective against certain types of liver cancers, but currently, radiation therapy is generally used in conjunction with other treatments for liver cancer. As with chemotherapy, radiation therapy has the potential for affecting non-cancerous tissue in the body and is often accompanied by side-effects including tiredness, nausea and vomiting.

Percutaneous Ethanol Injection
Percutaneous ethanol injection, or PEI, involves injection of alcohol into the center of the tumor, either through the skin or through a more invasive operation. The alcohol dries out cells leading to tumor cell death. PEI has shown some success in treating patients suffering from primary liver cancer, however, it is generally considered ineffective on large tumors.

In order to perform this treatment, tumors must be well vascularized. Unfortunately, many tumors have poor vascularity which prevents effective treatment with PEI. Complications include pain and the potential introduction of alcohol into the bile ducts and major blood vessels. In addition, this procedure can cause cancer cells to be deposited along the needle track when the needle is being withdrawn from the tumor.

 
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Radio Frequency Ablation
Radio Frequency Ablation uses electric current in the radio frequency range to destroy cancerous cells. The procedure utilizes an ultrasound or CT scan to guide the surgeon in directing several needles into the abdomen through small incisions. The needles are heated with an electric current once they reach the tumor – it is this process that destroys the cancerous cells. This procedure is used for patients with small, nonresectable hepatocellular tumors and sometimes for metastatic liver cancers.

Microwave Ablation
Microwave Ablation is an experimental therapy similar to Radio Frequency Ablation.

Chemoembolization
Chemoembolization involves the injection of a chemotherapeutic drug in combination with a chemical to obstruct the artery delivering blood to the liver in order to deprive the tumor of oxygen and nutrients. While chemoembolization can slow the growth of tumors, it has the disadvantage of destroying healthy liver tissue deriving blood from the obstructed arteries.

Liver Transplant
Transplanting a healthy donor liver into a patient with liver tumors is rarely performed due to the low availability of donor organs and the high probability of tumor recurrence within the transplanted liver. It is an option for those that have small and early-stage tumors.

Hepatic Artery Infusion
Hepatic artery infusion involves the injection of chemotherapeutic drugs directly into the artery supplying the liver. Because the chemotherapy agents pass from the liver into the patient's general circulation, hepatic arterial infusion has similar toxicities to systemic administration and does not enable physicians to prescribe higher doses of chemotherapy.

 
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Implanted Infusion Pumps
Implanted infusion pumps target the delivery of chemotherapy agents to the tumor. Implantable pumps may be used to treat colorectal cancer which has metastasized to the liver. The pump is surgically implanted under the skin and delivers regular doses of chemotherapeutic agents in a targeted area over time. This pump, however, lacks a means of preventing the entry of chemotherapy agents into the patient's general circulation after it passes through the liver. As a result, this technique does not enable physicians to prescribe higher doses of chemotherapy.

Surgically Isolated Perfusion
Physicians have made efforts to address the trade-off between the efficacy of intravenous chemotherapy treatment and its side effects. The overall goal has been to isolate the liver from the general circulatory system and to achieve a targeted delivery of chemotherapy agents to the liver. Surgically isolated perfusion, also known as IHP, involves an open surgical procedure in which arteries and veins supplying the liver are physically clamped, and blood flow is diverted from the liver while infusing high dosages of chemotherapy agents into the liver. A blood filtration circuit reduces drug concentrations before returning the diverted blood to the patient. IHP can provide improved dosing while sparing patients from some of the drug's side-effects on healthy areas of the body. The procedure is highly effective in some patients, but is limited in its use due to the invasive nature, prolonged recovery times, long hospital stays and very high costs. It further can only be performed once in a patient, so patients who respond to the therapy cannot be treated again once their tumor returns. It is a major operative procedure and can only be performed at highly specialized liver cancer centers.

Other Methods of Treatment
Other liver cancer treatments include gene therapy, hyperthermia and the use of biological response modulators, monoclonal antibodies and liposomes. Many of these treatment options are experimental, and their effectiveness is either limited or unknown, and many are not repeatable or have dose limiting side-effects.

 
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