Liver Cancer - from Liver Review - Issue 4
Numerous surgical advances and the involvement of surgeons early in the evaluation of liver lesions have resulted in the ability to resect more liver malignancies with lower rates of operative mortality. At California Pacific, a medical-surgical team including an oncologist, hepatologist, radiologist and surgeon work together on all HCC cases, evaluating patients' ability to tolerate a liver resection or other treatment regimens. Because time is critical after the diagnosis of HCC, patients who are not candidates for resection should be referred immediately for possible ablative therapy, chemotherapy and/or liver transplantation if indicated.
Detection and Risk Factors
Rising Hepatitis Rates Lead to Increased Incidence of Hepatocellular Carcinoma (Liver Cancer)
In the past 30 years, the number of deaths caused by cancer of the liver (hepatocellular carcinoma) has increased in the United States, probably due to the impact of hepatitis C-induced cirrhosis in at-risk patient populations. The American Cancer Society estimates that 15,300 new cases of liver cancer will be diagnosed in the U.S. in 2000 and of those, about 13,800 people or 90% will die of the disease. In areas such as Africa, Southeast Asia and China, hepatocellular carcinoma (HCC) is a major health problem, causing up to 75% of all cancer cases because of the high percentage of hepatitis B virus carriers.
Risk Factors
Patients who have chronic infection with hepatitis B and/or hepatitis C virus are more likely to develop liver cancer than non-carriers. For those with HBV, relatives and personal contacts should be tested for the hepatitis B antigen and antibodies. If no hepatitis B antibodies or infection are present, contacts should receive the hepatitis B vaccine to protect them from both the virus and possibly liver cancer. Because a vaccine isn't available for HCV, relatives and personal contacts of those infected should be aware of how the virus is spread (blood transfusions, contaminated needles, mother-to-baby transmission and unprotected sexual intercourse) and regularly visit their doctor.
Certain toxins and chemicals, including aflatoxin and polyvinyl chloride, can also cause liver cancer. Iron overload cirrhosis (hemochromatosis) and alcoholic cirrhosis have also been associated with the development of HCC, as well as some other rare inherited liver diseases.
Detection
Initially, liver cancer is hard to detect. The first symptom is usually pain that extends from the abdomen to the back and shoulder. Weight loss is common and sometimes patients have episodes of severe pain, fever and nausea. Rapidly deteriorating health, weakness, tenderness and jaundice may also imply HCC.
Because of the liver's size and location, it is impossible to detect liver tumors upon physical examination. Instead, an alpha-fetoprotein (AFP) blood test and ultrasound are used for initial screening. AFP is a protein produced by the liver and an elevated level can indicate tumor growth. For patients at risk for liver cancer, California Pacific recommends an AFP blood test and liver ultrasound every six months.
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Staging
Determining the Size, Stage and Scope of a Liver Lesion
Once blood tests reveal elevated AFP levels or ultrasound shows a lesion in the liver, it is important for patients to undergo a surgical consultation. This pre-operative evaluation includes diagnosis and localization of the lesion, staging and a determination of resectability.
California Pacific Medical Center uses a variety of work-up techniques to help determine the location and stage of hepatocellular carcinoma (HCC). Diagnostic imaging procedures, along with the AFP blood test are the most accurate methods. While attempts at obtaining a histologic diagnosis are tempting, a liver biopsy is a relative contradindication because of the risk of cancerous cells migrating elsewhere in the body. Instead, the following imaging procedures are employed:
Diagnostic Imaging
At California Pacific, liver imaging begins with multi-phase computed tomography (CT), including spiral CT scans obtained during hepatic arterial and portal venous phases following intravenous contrast administration. This technique can accurately demonstrate the number of primary tumors within the liver and their relationship to vascular structures. In some patients, state-of-the-art magnetic resonance imaging (MRI) and Doppler ultrasound are used as complementary imaging techniques. FDG positron emission tomography (PET) has been helpful in characterizing atypical hepatic masses as well as in detecting extrahepatic malignancy.
Metastatic Work-Up
Patients with HCC require a metastatic work up to determine if cancer has spread to surrounding tissue. This work-up includes a chest CT scan and nuclear bone scan. Patients who do not undergo resection or ablation, or those waiting for a transplant, should continue having a chest CT and bone scan performed every six months.
Diagnostic Laparopscopy with Ultrasound (Staging Laparoscopy)
This technique involves looking directly at the liver surface with a laparoscope and using laparoscopic ultrasound to obtain detailed images of the liver lesion. The laparoscopic surgeon can view nodules and tumors that cannot be reached or seen by CT scan. Staging laparoscopy is particularly useful for patients with liver malignancies. Studies show that without laparoscopy, about 20% of patients undergo a laparotomy in which abdominal exploration is performed through a large incision, only to learn their tumor is unresectable or has spread to adjacent lymph nodes. In comparison, staging laparoscopy obtains the same information while avoiding the large incision. Patients with unresectable disease benefit because their recovery is minimized.
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Surgical Options
Surgical Interventions for Liver Cancer
When determining treatment options for hepatocellular carcinoma (HCC), our team evaluates the lesion work-up results, along with patients' age and overall health, to recommend appropriate treatment options. Because choosing a treatment plan is an important decision, we review all options with patients and their families, explaining the benefits and disadvantages of each to help determine the best option.
Treatments for HCC include surgical resection, transplant, ablation and chemotherapy. While a liver transplant represents the best cure for most patients, the limited organ supply makes this option unattainable for some patients. If patients can withstand surgery and have enough liver reserve, a resection is typically the next alternative, since this intervention also offers the chance to cure liver cancer. 
Surgical Resection (Tumor Removal)
Surgical resection involves the removal of one or more sections of the liver in which a tumor(s) exists. Typically, surgeons can remove up to 70% of a cancerous liver (if there is no fibrosis) and it will regenerate in about two to six weeks following surgery.
For surgical purposes, the liver is divided into eight segments, based on vascular inflow and bile duct drainage. Branches of the hepatic artery and portal vein supply each segment. Prior to surgery, some resection patients undergo pre-op portal vein embolization, a procedure in which a coil is inserted into the portal vein of the cancerous segments to block blood flow to those regions. This technique results in the enlargement of the remaining liver segments on which the patient will depend after resection. Portal vein embolization is recommended for patients who may not have enough liver reserve for sufficient re-growth following resection.
During resection, the surgeon first uses ultrasound to determine the tumor(s) proximity to hepatic structures. The surgeon's goal is to remove the tumor(s) and as little liver as possible, while ensuring a margin free of tumor. Using vascular occlusion and isolation techniques that cut off blood flow to the liver during surgery, it is now possible to perform major hepatic resections with minimal blood loss. However, such extensive resections are more likely to result in post-operative complications such as bleeding and bile leaks from the cut edge of the liver.
Transplant Options
Liver transplantation is an effective treatment for patients with small, unresectable HCC and cirrhosis. The eligibility criteria for transplantation is the presence of a single hepatocellular carcinoma (HCC) tumor 5 cm or less in diameter, or three or fewer tumor nodules, each 3 cm or less in diameter. This criteria can elevate a patient's status on the transplant list. While waiting for transplantation due to HCC, patients should have a chest CT and bone scan every six months. The four-year overall transplant survival rate for patients with HCC is 85 percent and the recurrence-free survival rate is 92 percent.
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Ablation and Chemotherapy
Ablation and Chemotherapy Offer Non-Surgical Treatment Options
Although transplant and surgical resection of hepatocellular carcinoma (HCC) offer the best possibility of a cure, many patients are not surgical candidates due to inadequate liver reserve, large or multiple lesions in multiple lobes, fibrosis or cirrhosis. For these patients, several minimally invasive techniques offer effective treatment options.
Ablation (Radiofrequcy Ablation or Cryoablation)
Ablative therapies use either extreme heat or cold to destroy liver tumors. They are ideal for:
- benign tumors of the liver;
- malignant tumors that are not resectable;
- malignant tumors in patients who are too ill to undergo resection.
Radiofrequency (RF) ablation uses a needle electrode to deliver microwave energy to the tumor, causing cell necrosis. This technique can be used via computed tomography (CT) by an interventional radiologist or laparoscopically with ultrasound guidance by a surgeon depending on the size and location of the lesion.
With both laparoscopic RF ablation and cryoablation, doctors use ultrasound visualization to precisely target tumors within the liver. During cryoablation, argon gas is delivered through thin probes inserted into the liver, creating an ice ball that freezes the tumor and destroys its cells. Both RF and cryoablation are applied via small incisions in the chest, into which the probes are inserted, rather than the large incision that accompanies resection.
Percutaneous Ethanol Injection Therapy (PEIT)
Percutaneous ethanol injection is another option for patients who are not surgical candidates. This procedure, performed by an interventional radiologist, involves the injection of alcohol into the tumor, causing immediate dehydration of the cytoplasm with consequent coagulation necrosis and fibrous reaction. PEIT results in complete ablation in up to 75% of selected patients with HCC less than 5 cm in size.
Hepatic Artery Chemoembolization
Patients with HCC and cirrhosis are frequently treated with hepatic artery chemoembolization, a process in which a plastic catheter is inserted into the groin and threaded up to the hepatic artery off the aorta. A thick oily substance called lipiodol or ethiodol is mixed with chemotherapy (platinol, mitomycin-c, and adriamycin) and injected under radiological guidance directly into the tumor, followed by a foamy substance called gellfoam. This process "locks in" the chemotherapy, prolonging the dwell time of the chemotherapeutic agent and enhancing drug delivery to liver tumors 10- to 100-fold compared to systemic infusion. The response rates for HCC are 60%-80% with an average duration of one year. This therapy can be repeated multiple times before transplantation with excellent disease-free survival.
Chemotherapy
Systemic chemotherapy uses a mixture of anti-cancer drugs injected into a vein or taken by mouth. Typically, this alternative is reserved for patients with metastatic disease or those who are not candidates for other procedures. Depending on any underlying disease, different drugs are applied. Patients in better health may respond to gemcitabine. For those in poorer health, the use of tamoxifen and pravachol may result in prolonged survival. HCC patients with hepatitis B have responded well to a combination of platinol, adriamycin, fluorouracil and alpha-interferon.
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