If the tumor is detected at an early stage, when it is typically a single lesion, and there is no significant liver disease, surgeons at the CLDT may be able to surgically remove the tumor. This is called resection. For tumors which are very small, typically less than 2-3 cm, sometimes the tumor can be ablated, or destroyed, most often using radiofrequency ablation. Resection is an option for about 10 to 20% of patients in the US with HCC.
Surgery: Liver Transplantation
Because most patients with primary hepatocellular carcinoma in this country have underlying liver disease, liver transplantation allows the best chance for cure. NewYork-Presbyterian/Columbia also offers liver transplantation for select patients with bile duct cancers (we are one of only a few centers in the nation to offer this option). For patients whose bile duct cancer can not be removed surgically, transplantation can offer an unprecedented chance for cure.
The Milan Criteria is the internationally accepted guideline used to select patients for liver transplantation. According to these criteria, patients may be eligible for liver transplantation if they have a single tumor 5 cm or smaller, or 3 or fewer tumors that are each 3 cm or less in size, and no obvious invasion of the blood vessels on imaging before the transplant. Patients who have more than one tumor above the sizes specified by these criteria are usually not eligible for transplantation unless the tumor can be “downsized” or shrunk. In some cases, tumors can be reduced sufficiently through chemoembolization, radiation, or other approaches.
Liver Transplantation at the Center for Liver Disease and Transplantation
NewYork-Presbyterian/Columbia University Medical Center boasts one of the largest and most experienced liver transplantation programs in the nation, offering living donor liver transplantation and employing minimally invasive surgical approaches whenever possible.
Liver transplant procedures at the CLDT take advantage of the most sophisticated medical knowledge and surgical technology available today, including living donor transplantation, partial liver transplantation, advanced organ preservation techniques, liver transplantation in HIV- and Hepatitis C co-infected individuals, and antiviral therapy to prevent or treat recurrent hepatitis C after liver transplantation.
Jean C. Emond, MD, Vice Chair and Chief of Transplantation, was a member of the team that pioneered living donor liver transplantation, now considered one of the most important advances in the treatment of severe liver disease. The Living Donor Liver Transplant program is now one of the largest living donor liver programs in North America, and has performed more than 220 living donor liver transplants since its inception. We have performed more left lobe donations than any other living donor liver program inNorth America and introduced fully laparoscopic donation for all pediatric liver donor liver transplants in 2009. Approximately 15 to 20 percent of the center's transplant patients currently receive a liver from a living donor.
Our program routinely achieves excellent outcomes for donors and recipients. Our recipients have 97.1 percent one-year survival after transplantation and a three-year survival of 93.3 percent. Additionally, nearly all donors are very satisfied or satisfied with the experience of donating a portion of their liver. After surgery, we also offer specialized nursing, nutritional support, smoking cessation, weight loss and pain management.
Learn more about liver transplantation here.
ERCP for Management of Bile Duct Obstruction
Blockage of the bile duct is a potential complication of liver tumors, liver surgery, and bile duct cancer. Our interventional endoscopists often utilize endoscopic retrograde cholangiopancreatography (ERCP) to relieve bile duct obstructions. During this procedure, a physician inserts a stent into the duct to relieve the obstruction and allow drainage to proceed into the intestine, sparing the patient from having to wear an external bag on the abdomen to drain fluids. This approach improves the patient’s quality of life and relieves symptoms associated with jaundice.
Localized therapy, also called locoregional therapy, includes the following approaches:
Radiofrequency or Microwave Embolization
The tumor is destroyed with highly targeted radiowave or microwave energy.
Radio arterial embolization
Tiny spheres of a radioactive substance (yttrium-90) are delivered to the tumor site via the hepatic arterial system. The radioactive substance then kills cancer cells at the tumor site.
Several centers, including ours, are also examining new forms of targeted external beam radiation, particularly for trying to shrink the tumor out of the portal vein. This also looks very promising, potentially with less toxicity than with Y-90.
Chemotherapy (injected into the hepatic artery via a catheter) may be used to target larger tumors. The chemotherapy is combined with a substance that temporarily blocks off the hepatic artery, trapping much of the chemotherapy near the tumor. This approach spares nearby healthy tissue from the toxic effects of chemotherapy.
In some cases, chemotherapy can reduce the size of a tumor enough that it can be surgically removed. Most often, this is delivered locally using beads treated with different types of chemotherapy agents, a therapy called chemoembolization. By inserting them into the tiny blood vessels that feed the tumor, the radiation effectively targets the cancer cells without affecting the whole body. Chemoembolization therapies most commonly include drug-eluting beads labelled with doxorubicin or irinotecan.
Chemotherapy (systemic therapy) is offered to patients who are not good candidates for surgery or locoregional therapy. Chemotherapy drugs are designed to kill cancer, and are generally given in cycles, with a period of treatment followed by a period of rest. These drugs can be administered before surgery, after surgery, or both. When given before surgery, chemotherapy is called neoadjuvant. When given after surgery, chemotherapy is called adjuvant. Chemotherapy can be administered orally, by injection, or intravenously depending on the regimen and the drug. The best course of therapy is selected after considering the specific characteristics of the patient's cancer to maximize the results of the treatment and increase survival.
Traditional chemotherapy medications historically have not been very successful in HCC patients because many are metabolized in the liver, which is not functioning normally in many patients, and because many HCCs have “pumps” which can get the chemotherapy out of the cancer cells, and thus make them resistant.
Adjuvant chemotherapy is usually administered after surgery or liver transplantation, although there adjuvant therapy in HCC has not yet been proven effective. A large trial of sorafenib found it to be ineffective after surgery (STORM Trial). The CLDT has just completed a multi-center dose-finding trial of sorafenib after liver transplant (NewYork-Presbyterian/Columbia was the lead site), which found the maximum tolerated dose is 200 mg twice a day (half of the usual dose). Both sorafenib and m-TOR inhibitors (which also work as immunosuppressants) are being studied to determine whether they prevent recurrent liver cancers after transplant.
For advanced liver cancer with blood vessel invasion or metastatic disease, the standard of care now is a drug called sorafenib (nexavar), which has been shown to improve survival for patients with advanced liver cancer, kidney cancer, and thyroid cancer. It acts by blocking pathways that cause blood vessels to grow. As such, it is considered a “targeted” therapy. Given in pill form, it is usually taken twice a day on an empty stomach. Side effects include redness of the hands and feet (which can be lessened by using urea cream twice a day while on the drug), diarrhea, fatigue, and high blood pressure.
Combinations of particular chemotherapy agents may be more effective than single drugs, and are under study at our center and elsewhere. Based on a study from Asia, a regimen called FOLFOX (oxaliplatin and 5-fluorouracil) has now been approved there. The Center for Liver Disease and Transplantation is currently conducting clinical trials assessing sorafenib in combination with other agents for patients with hepatocellular carcinoma. Our center has completed the first ever dose-finding study of sorafenib in the post-transplant setting, and we led a multicenter study using bevacizumab in HCC. Together with our colleagues at several other centers, we recently completed a randomized trial of sorafenib compared with bevacizumab and erlotinib, another targeted therapy, in patients with advanced HCC.
Molecular and targeted therapies
Many other targeted agents are being studied in clinical trials. These include MET-inhibitors, mTOR inhibitors, demethylating agents, and immunotherapies, among many other types of targeted therapies. Our center is actively involved in pursuing all of these options, and also in developing the science to identify which subjects may benefit from which targeted therapies. We now have the capability to identify novel targets in each cancer patient’s tumor, so that we can try to identify new therapies which might not have ordinarily been considered for them.
Patients with advanced liver cancer or invasion of the blood vessels may be eligible to participate in one of the clinical trials underway at NewYork-Presbyterian/Columbia.