TREATMENT

Surgery
Every patient with a liver tumor should be evaluated for a resection. It is the only chance for
cure. Removing the tumor will rid the body of the cancer and also prevent further spread to
other regions. Unfortunately, not all patients are eligible for a liver resection.

The liver is a privileged organ in that it has the ability to regenerate if part of it is removed and
this allows surgeons to operate upon it successfully. In patients with colon cancer that has
spread to the liver, liver resection can cure 25 - 45% of the patients. The operative mortality is
less than 2%. To achieve these outcomes requires (1) appropriate selection of surgical
candidates and (2) an experienced surgical team (surgeon, anesthesiologist, intensive care
staff, etc.) that performs liver operations frequently. Only those patients who are likely to benefit
from resection should undergo a surgical procedure.

Patients may also develop metastatic colorectal cancer to both the lungs and liver. In select
patients, simultaneous resection of metastases from the lung and liver can provide significant
benefit.

Other indications for liver resection are metastases from other sites such as breast, kidney,
lung, selected tumors of the pancreas and small intestine and sarcomas. Although these
diagnoses are controversial indications, 2 year survival rates of 90% have been obtained. This
improved survival occurs in patients who respond to chemotherapy and have disease only in the
liver. Other indications for resection are tumors that originated in the liver, called hepatocellular
cancer and cholangiocarcinoma.

To be considered for a liver resection, the cancer must be confined only to the liver so that
removal will eliminate all disease from the body. Removing a tumor from the liver and leaving
other areas in the body with cancer will not be curative. An exception is a patient with a
metastatic carcinoid tumor as they can benefit (i.e., improvement in symptoms) from removal of
greater than 90% of the liver tumor.

A liver surgeon will devote a significant amount of time to make sure that the appropriate patient
is selected for surgery. Routine tests may include a CT scan of the abdomen, pelvis, chest,
colonoscopy (if the patient has had a colon cancer). Other important information necessary to
make a decision is the number, size, and location of the liver tumors. Only when the surgeon
has determined that the cancer is limited to the liver will a recommendation be given to proceed
with surgery. To be effective, all tumors must be removed with a margin of 1/2 inch of normal
liver in order to remove microscopic cancer cells that may surround the obvious tumor.

A variety of liver resections can be performed. The options range from resection of a lobe (left or
right) to segments (or small portions) of the liver. Resection of segments of the liver (called
segmentectomy) permit a surgeon to effectively treat multiple liver tumors..

A liver resection can take 2 - 5 hours to perform. In the majority of patients, a liver resection
does not require a blood transfusion. The patient will be able to drink fluids on the first post-
operative day and often is discharged in 4 - 6 days.

A CT scan from a patient with hepatic metastases from colon cancer is shown here. The tumor
isdelineated by the dark area and shown by the arrow. This is in marked contrast to the normal
gray color of the liver.
This patient underwent resection of a segment of the liver and the next two images show the
specimen with a 1 cm. margin.

Cryosurgery
Cryosurgery is a new technique that can destroy tumors in a variety of sites (brain, breast,
kidney, prostate, liver). Cryosurgery is the destruction of abnormal tissue using sub-zero
temperatures. The tumor is not removed and the destroyed cancer is left to be reabsorbed by
the body. Initial results in properly selected patients with unresectable liver tumors are
equivalent to those of resection.

Cryosurgery involves the placement of a stainless steel probe into the center of the tumor.
Liquid nitrogen is circulated through the end of this device. A picture of the cryoprobe is shown.

The tumor and a half inch margin of normal liver are frozen to -190°C for 15 minutes, which is
lethal to all tissues. The area is thawed for 10 minutes and then re-frozen to -190°C for another
15 minutes. After the tumor has thawed, the probe is removed, bleeding is controlled, and the
procedure is complete. The patient will spend the first post-operative night in the intensive care
unit and typically is discharged in 3 - 5 days.
Proper selection of patients and attention to detail in performing the cryosurgical procedure are
mandatory in order to achieve good results and outcomes. Frequently, cryosurgery is used in
conjunction with liver resection as some of the tumors are removed while others are treated with
cryosurgery. Patients may also have insertion of a hepatic intra-arterial artery catheter for post-
operative chemotherapy. As with liver resection, your surgeon should have experience with
cryosurgical techniques in order to provide the best treatment possible.

Below is a picture of an iceball in a patient with a metastases from a colon cancer.

Following resection or cryosurgery, your physician may recommend chemotherapy.

Chemotherapy
Chemotherapy uses drugs to treat the cancer. These drugs work by interfering with the growth
of cancer cells and lends to cell death. Chemotherapy can be administered in a variety of ways.
Treatment of the entire body is called systemic chemotherapy, while treatment of localized
areas is called regional chemotherapy. If more than one anti-cancer drug is administered at
once, the treatment is called combination chemotherapy. Oftentimes, chemotherapy will be
used in conjunction with other treatments like radiation and surgery and is termed adjuvant
chemotherapy.

Chemotherapy is administered in a variety of ways: orally, intravenously or intra-arterially. In

some cases, drugs will be administered intra-arterially with the use of a sophisticated pump. The
actual treatment will depend on the type of cancer, the level of cancer invasion, and the extent
of the disease. A drug may be taken every day, every week, or every month. A drug may be
taken in cycles alternated with a rest period when no drug is taken.

Effectiveness of treatment is evaluated regularly with physical exams, blood tests and x-rays. A
drug is considered effective if it causes the cancer cells to shrink, to stop growing, or to die.

Because anti-cancer drugs attempt to kill cancer cells, many of them will also attack and kill
healthy cells. Side effects are a direct result of the killing of healthy cells. Certain cells are more
susceptible to damage than others, including bone marrow cells, cells in the digestive tract,
reproductive system and hair follicles. Although many patients never experience symptoms,
possible side effects include nausea and vomiting, hair loss, fatigue, increased chance of
bleeding and/or getting an infection, and anemia. Most of these side effects will disappear in a
few days or weeks after chemotherapy ends.

Metastatic colon cancer to the liver can be treated with chemotherapy in a variety of ways. One
of the most common regimens is the systemic or intravenous administration of 5 - Fluorouracil
(5 FU) and Leucovorin. This drug combination is given in the vein as an outpatient and is
effective in killing metastatic cancer in 20 - 30% of patients and can potentially prolong life for
approximately twelve months. Other systemic drug regimens include continuous infusion of 5
FU, Tomudex, Mitomycin C, CPT-1 1 and other experimental drugs. In addition, active research
protocols are investigating the effectiveness of administering chemotherapy by mouth with the
goal of making the treatment easier for the patient.
Chemotherapy can also be administered directly into the liver artery and is called intra-arterial
chemotherapy. Liver tumors derive their blood supply from the hepatic artery, and intra-arterial
administration will expose the tumor to very high doses of chemotherapy (100 - 400 times
higher values than systemic infusion).This increased drug exposure achieves tumor shrinkage
in 50 - 70% of patients. The two most commonly used drugs are 5 FU and FUDR. Administering
combinations of drugs can improve the chance of tumor shrinkage.

In the majority of cases, intra-arterial chemotherapy is given through an implanted pump that will
deliver drugs at a rate of 2 -3 cc/day and does not require a battery. A picture of the pump is
shown.

Drugs are loaded into the pump with a needle placed in the middle of the device. A picture of a
patient with a device is shown and the arrows depicts the location of the pump.

The last photograph shows the pump being loaded with chemotherapy drugs. Intra-arterial
chemotherapy is given as an outpatient and once the chemotherapy has been placed into the
pump (which takes 15 minutes), the patient returns to their normal activity.

The first two CT images are from a patient with liver metastases from colon cancer prior to
beginning intra-arterial chemotherapy. Tumors are indicated by the arrows.
The next two images are from the same patient after two months of intra-arterial chemotherapy.
They demonstrate a significant shrinkage in the size of the liver metastases.

I believe that intra-arterial chemotherapy is valuable and is used frequently in the treatment of
my patients. I use it after performing a liver resection and/or cryosurgical ablation with the goal
of eliminating microscopic disease that may remain in the liver. In addition, intra-arterial
chemotherapy is effective in treating unresectable liver tumors. In patients who achieve
significant tumor shrinkage following intra-arterial therapy, I have been able to successfully
perform a liver resection at a later time. In patients who do not become resection candidates,
intra-arterial chemotherapy can prolong survival. However, only two prospective randomized
trials have demonstrated a statistically significant improvement in survival. Research is currently
ongoing in an attempt to identify the most effective drugs.

Chemoembolization
Embolization is the process of injecting a foreign substance into the tumor to stop the blood
flow. The lack of blood deprives the tumor of needed oxygen and nutrients and eventually
causes cells to die. The tumor blood supply is stopped with small pieces of material that have
been saturated with chemotherapy drugs. Once the blood flow has stopped, the tumor is soaked
in a very high concentration of drugs for a prolonged period of time. Thus, the tumor cells die
very quickly. Below is a sketch that demonstrates the mechanism of chemoembolization.
A variety of materials may be used in the embolization process. Most embolization materials
only cause temporary blockage of blood flow to the tumor cells, though in some cases materials
will be used that can cause permanent blockage.

Chemoembolization is most beneficial to patients whose disease is limited to the liver. Some
success has been demonstrated with patients whose cancer has spread to other areas. Patients
with kidney disease, blood coagulation problems, or known allergies to contrast agents are not
good candidates for this procedure.

Chemoembolization is considered to be a relatively safe and effective method of treating

unresectable liver tumors. The overall risk of the procedure is related to your general underlying
health. People with jaundice, severe cirrhosis or kidney failure have an increased chance of
complications.

Under x-ray guidance a small catheter is inserted into the femoral artery (located in the groin)
and advanced into the liver artery. The embolic material and drugs are then injected through the
catheter into the liver tumor. The procedure usually lasts 2 - 3 hours.

The majority of patients experience some side effects which may include abdominal pain,
nausea, vomiting or fever. Various drugs can be administered that will control these symptoms
and keep you comfortable. The symptoms will stop after 3 - 5 days. Studies show that patients
with hepatocellular cancer undergoing this procedure may experience tumor shrinkage as well
as an increased survival rate. The effectiveness of this therapy for patients with metastatic colon
cancer is currently undergoing active investigation.

Below is an example of a patient with a large liver tumor (depicted as the dark area) who
underwent chemoembolization.

Five months later the tumor was necrotic (depicted as a round and homogenous mass) and the
remainder of the liver had grown or hypertrophied. This patient subsequently underwent a liver
resection.
Ethanol Injection
Injection of 100% absolute alcohol into tumors can be beneficial as it is highly toxic to liver
tumors. It is injected into the center of the tumor through the skin (percutaneously) or at the time
of surgery. The alcohol causes cells to dry out and cellular protein to disintegrate, ultimately
leading to tumor cell death. This treatment is administered to patients who refuse surgery or
who have severe liver disease that prevents them from having liver surgery.

This procedure is often done in a hospital or clinic as the injections are done with the assistance
of ultrasound or CT scan. Each treatment consists of one injection, though a series of injections
may also be recommended to effectively treat the tumors. Side effects are mild and temporary
(5-10 minutes) and include localized pain and an overall feeling of alcohol intoxication.

Alcohol injection is a safe and easy procedure that has been shown to prolong survival (40 -
70% at three years) with small hepatocellular cancers. It provides palliative management of
metastatic liver cancer and can, in some cases, extend patient survival rate.

Patients undergo an injection with a solution that contains alcohol and a chemotherapy drug
called BCNU. This drug combination is called DTI-015

Below is a CT scan of a patient with two liver tumors (depicted by the arrows). The patient
underwent an injection with DTI-0l5, which produced death of both tumors (depicted by the dark
homogenous masses and two white arrows).
Radiation Therapy
Radiation therapy plays a relatively minor role in the treatment of liver cancer. Most primary
tumors that metastasize to the liver are resistant to radiation therapy, while the healthy liver is
highly susceptible to radiation damage. Radiation therapy is often used to treat patients who
have tumors of the bile duct or gallbladder.

Most radiation therapy for liver cancer is used in conjunction with other forms of treatment like
surgery. Sometimes radiation therapy will be administered at the time of surgery and is called
Intraoperative Radiation. Radiation may also be used as palliative treatment to shrink tumors
and relieve pain.

Radiation is the process of transmitting energy in the form of waves or particles. Radiation
therapy uses radiation in large doses to kill cancer cells and to keep them from growing and
spreading.

A special doctor called a Radiation Oncologist determines the type of treatment you will receive
and supervises the treatment process. A Radiation Physicist will adjust the machine for the
correct dosage of radiation to be delivered to the patient.

There are two types of radiation therapy: external or internal.

External radiation therapy involves the use of a machine called a linear accelerator that directs
x-rays at cancer cells. This type of treatment is usually administered 5 days a week for 2 - 7
weeks depending upon the type of cancer and location. Because external radiation requires
directing x-rays at very specific parts of the body, the actual treatment process begins by
identifying the optimal areas to treat. This is done with several diagnostic tests like x-rays and
CT scans.

Once the areas are identified, the Radiation Oncologist marks the exact places with permanent
ink. These marks will remain on your body throughout the treatment period and are critical in
delivering proper treatment. The x-rays must be directed at the same area from session to
session for the treatment to be effective.

Internal Radiation Therapy, also called Brachytherapy, uses radioactive materials that are
implanted in your body, usually directly into the cancer sites. Such substances as radium,
cesium, iridium, iodine, phosphorus, and palladium are placed in or near the tumor.

Unlike external radiation therapy, internal radiation therapy does make your body radioactive.
While the implants are in place, they give off radioactive waves that can potentially affect other
people around you. Understand the goals and risks of this therapy prior to beginning this
treatment.

Radiofrequency Ablation
This is a new technique that destroys liver tumors by heating them to high temperatures (80 -
100 °C).Tumors up to 4 centimeters (approximately 2 inches) in diameter can be effectively
destroyed with this technique.

The patient undergoing radiofrequency ablation receives IV sedation and grounding pads are
placed on the legs. A thin needle is inserted into the tumor and electrical current is passed
through the tip of the needle which becomes very hot and destroys the tumor. The procedure
lasts 10 - 15 minutes and the patient goes home on the same day.The majority of patients do
not experience side effects and resume normal activity the following day.
Interstitial Laser Photocoagulation
This technique involves the insertion of a thin optical fiber into the center of the liver tumor and a
laser light is emitted from the tip. The exposed cells will then undergo thermal necrosis. Since
clinical experience with this technique are few, more studies are required before this treatment
can be recommended.

Isolated Liver Perfusion

This treatment for liver tumors was first described over thirty years ago but has had limited
clinical use. The basis of this treatment is to expose the liver to high doses of chemotherapy in
order to achieve maximal tumor shrinkage. The blood supply to the liver is completely isolated
from the systemic circulation so that the body is not exposed to the high dose of drugs. It
requires a lengthy operation to completely mobilize the liver and to insert catheters into the
hepatic artery, portal vein and hepatic veins.

Recently, initial results using different drugs have been encouraging and work continues with
this modality. This is experimental therapy and should only be used in a clinical trial.

Liver Transplantation
This treatment can not be recommended for patients with hepatic metastases. This aggressive
treatment will not cure patients as the majority will have early recurrence of the tumor. However,
liver transplantation has been shown to be effective treatment in patients with small
hepatocellular cancers and other rare tumors (i.e., epitheloid hemangioendothioloma,
neuroendocrine carcinoma).