Hepatocellular Carcinoma- HCC

Hepatocellular Carcinoma
Liver Cancer
This section has been reviewed and approved by the Cancer.Net Editorial Board, 3/11
Treatment
This section outlines treatments that are the standard of care (the best proven treatments available) for this specific type of cancer. When making treatment plan decisions, patients are also encouraged to consider clinical trials as an option. A clinical trial is a research study to test a new treatment to evaluate whether it is safe, effective, and possibly better than standard treatment. Your doctor can help you review all treatment options. For more information, visit the Clinical Trials and Current Research sections.
Treatment overview
In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team.
Treatment options and recommendations depend on several factors:
• Whether the cancer is only in the liver
• Whether the cancer is only in the area where it started or has spread widely throughout the liver
• The patient’s preferences and overall health
• The damage to the remaining (tumor-free) area of the liver
When a tumor is found at an early stage and the patient’s liver is working well, treatment is aimed at slowing, stopping, or eliminating the cancer (also called disease-directed treatment). When liver cancer is found at a later stage, or the patient’s liver is not working well, the patient and doctor should talk about the goals of each treatment recommendation. At this point, the goals of treatment may focus on slowing growth of the cancer and relieving symptoms to improve quality of life.
Descriptions of the most common treatment options, both disease-directed and supportive care therapies, are listed below. Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, and the patient’s preferences and overall health.
Learn more about making treatment decisions.
Surgery
Surgery is the removal of the tumor and surrounding tissue during an operation. It is likely to be the most successful disease-directed treatment, particularly for patients with small tumors (smaller than 5 cm). A surgical oncologist is a doctor who specializes in treating cancer using surgery.
Two types of surgery are used to treat HCC. The part of the liver with the cancer may be removed in a hepatectomy, or a liver transplantation may be done. Both procedures are described below. However, if the tumor has spread outside the liver, or if the patient has other serious illnesses, surgery may not be an option. Learn more about cancer surgery.
• Hepatectomy. When a portion of the liver is removed, the surgery is called a hepatectomy. A hepatectomy can be done only if the cancer is only in one part of the liver, and the liver is working well. The remaining section of liver takes over the functions of the entire liver and may regrow to its normal size within a few weeks. A hepatectomy may not be possible if the patient has advanced cirrhosis even if the tumor is small.
The side effects of a hepatectomy may include pain, weakness, and fatigue, and a temporary liver failure. The health care team will watch for signs of bleeding, infection, liver failure, or other problems that need immediate treatment.
• Liver transplantation. Sometimes, a liver transplantation can be done. This procedure is possible only when the cancer has not spread out of the liver, a suitable donor is found, and very specific criteria are met.
After a transplant, the patient will be watched closely for signs that the body might be rejecting the new liver, or that the tumor has come back. The patient must take medication to prevent rejection, and the drugs can have side effects, such as puffiness in the face, high blood pressure, or increased body hair.
Liver transplantation is a particularly effective treatment for people with small tumors because transplantation removes the tumor and the damaged liver. However, there are few donors, and people waiting for a liver transplant may have to wait a long time before a liver becomes available. During this time, the disease may get worse. The transplant center will advise you how long the wait is likely to be and what rules are used to prioritize people on the waiting list.
Radiation therapy
Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. A radiation therapy regimen (schedule) usually consists of a specific number of treatments given over a set period of time. External-beam radiation therapy is radiation given from a machine outside the body. External-beam radiation therapy is not often used for HCC.
Internal radiation therapy or brachytherapy may be used for HCC. Brachytherapy is radiation treatment using implants. Internal radiation therapy for HCC involves placing radioactive beads into the artery that supplies the tumor with blood in a manner similar to chemoembolization (see below).
Depending on the type of radiation therapy used, your doctor will explain ways to help protect your other organs from radiation during treatment and the side effects that may be expected. The general side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished. For internal radiation therapy, the side effects may include damage to the stomach and lungs. However, these can often be avoided by special pre-treatment preventive measures. Learn more about radiation therapy.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells, usually by stopping the cancer cells’ ability to grow and divide. Chemotherapy is given by a medical oncologist, a doctor who specializes in treating cancer with medication. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of drugs at the same time. Chemotherapy for HCC may be given in the two different ways described below:
• Systemic chemotherapy treatment. Systemic chemotherapy is typically injected into a vein, so that it reaches the whole body with the aim of killing cancer cells both inside and outside the liver.
• Regional chemotherapy treatment. A small pump is surgically placed in the body to deliver chemotherapy directly to the blood vessels that feed the tumor.
The side effects of chemotherapy depend on the individual and the dose used, but they can include nausea and vomiting, loss of appetite, diarrhea, fatigue, low numbers of blood cells, bleeding or bruising after minor cuts or injuries, numbness and tingling in the hands or feet, headaches, hair loss, and darkening of the skin and fingernails. These side effects usually go away once treatment is finished.
Learn more about chemotherapy and preparing for treatment. The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions by using searchable drug databases.
Targeted therapy
Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells while limiting damage to normal cells, usually leading to fewer side effects than other cancer medications.
Recent studies show that not all tumors have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your tumor. As a result, doctors can better match each patient with the most effective treatment whenever possible. In addition, many research studies are taking place now to find out more about specific molecular targets and new treatments directed at them. Learn more about targeted treatments.
For HCC, anti-angiogenic drugs are the most common targeted therapy. Anti-angiogenesis therapy is focused on stopping angiogenesis, which is the process of making new blood vessels. Because a tumor needs the nutrients found in blood vessels to grow and spread, the goal of anti-angiogenesis therapies is to “starve” the tumor. This is one of the ways sorafenib (Nexavar) is thought to work. Sorafenib is the standard treatment for advanced HCC that cannot be removed with surgery. It is given orally (by mouth). The side effects of sorafenib include diarrhea and certain skin problems.
Other treatment options
All treatments are more effective when the tumor is small; many doctors will not use the following treatments if the tumor is larger than 5 cm.
• Percutaneous ethanol injection uses alcohol injected directly into the liver tumor to kill it. Side effects include fever and pain after the procedure, but the procedure is generally very simple, safe, and particularly effective for tumors smaller than 3 cm. If the alcohol escapes from the liver, however, a person may have brief but severe pain.
• Radiofrequency ablation (RFA) and microwave therapy both use heat to kill the cancer cells. It may be given through the skin, through laparoscopy, or during a surgical operation while a patient is sedated.
• Cryosurgery uses extreme cold to freeze and kill cancer cells.
• Hepatic arterial infusion uses an anticancer drug injected into a catheter that has been placed in the major artery supplying blood to the liver. This treatment is a type of chemotherapy, but it does not have as many side effects.
• Chemoembolization is a procedure similar to hepatic arterial infusion. However, with this method, the flow of blood through the artery is blocked for a short time, so the chemotherapy stays in the tumor longer. Blocking the blood supply to the tumor also kills cancer cells. Recently, two clinical trials have provided evidence that this treatment can increase survival for some patients. In addition to being used as a primary treatment for HCC, chemoembolization may be used to slow tumor growth for people who are on the waiting list for liver transplantation.
• Immunotherapy therapy (also called biologic therapy) is designed to boost the body's natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to bolster, target, or restore immune system function. Side effects of biologic therapy are similar to the flu and can include fatigue, fever, chills, muscle pain, and headache. Learn more about immunotherapy.
In addition to the treatment options described above, the doctor may suggest that the patient enroll in a clinical trial, which is a research study that evaluates new treatments.
Recurrent HCC
Once your treatment is complete and there is a remission (absence of cancer symptoms; also called “no evidence of disease” or NED), talk with your doctor about the possibility of the cancer returning. Many survivors feel worried or anxious that the cancer will come back. Learn more about coping with this fear.
If the cancer does return after the original treatment, it is called recurrent cancer. It may come back in the same place (called a local recurrence), nearby (regional recurrence), or in another place (distant recurrence).
When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence. After testing is done, you and your doctor will talk about your treatment options. Often the treatment plan will include the therapies described above (such as surgery, chemotherapy, and radiation therapy) but may be used in a different combination or given at a different pace. Your doctor may also suggest clinical trials that are studying new ways to treat this type of recurrent cancer.
People with recurrent cancer often experience emotions such as disbelief or fear. Patients are encouraged to talk with their health care team about these feelings and ask about support services to help them cope. Learn more about dealing with cancer recurrence.
Metastatic HCC
If cancer has spread to another location in the body, it is called metastatic cancer.
Patients with this diagnosis are encouraged to talk with doctors who are experienced in treating this stage of cancer, because there can be different opinions about the best treatment plan. Learn more about seeking a second opinion before starting treatment, so you are comfortable with the treatment plan chosen. This discussion may include clinical trials studying new treatments.
Your health care team may recommend a treatment plan that includes a combination of chemotherapy (including sorafenib, see Targeted therapy above), radiation therapy, and/or other options. At this stage, the goal of treatment is typically not to cure the cancer, but to slow its growth.
In addition to disease-directed treatment, an important part of cancer care is relieving a person’s symptoms and side effects. It includes supporting the patient with his or her physical, emotional, and social needs, an approach called palliative or supportive care. People often receive disease-directed therapy and treatment to ease symptoms at the same time.
If disease-directed treatment is not successful, this may also be called advanced cancer. This diagnosis is stressful, and it may be difficult to discuss. However, it is important to have open and honest conversations with your doctor and health care team to express your feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families. Learn more about advanced cancer care planning.
Find out more about common terms used during cancer treatment.
Cancer Surgery—What to Expect
This article—the second in a three-part series—outlines what you will experience before, during, and after treatment. Other articles in this series provide an overview of surgery—including the various types—and describe side effects of the treatment.
Watch the Cancer.Net Video: Basics of Cancer Surgery with Robert Sticca, MD, adapted from this content.
The surgical team
When a patient with cancer undergoes surgery, a team of highly trained medical professionals works together to provide the best possible care. This team is led by a surgeon, often a surgical oncologist. However, the type of surgeon will vary based on the type and stage of cancer. For example, urologists and urologic oncologists specialize in treating urologic cancers—including prostate, bladder, and kidney cancer—with surgery. Meanwhile, neurosurgeons treat brain cancers, thoracic surgeons treat lung cancers, and dermatologic surgeons treat some types of skin cancer. General surgeons also perform many cancer surgeries, including surgeries for breast cancer, skin cancer, colorectal cancer, and many other gastrointestinal cancers.
Additional members of your health care team may include the following medical professionals:
Anesthesiologist. An anesthesiologist is a doctor who cares for patients immediately before, during, and after surgery. The anesthesiologist gives you anesthesia (medication that blocks the awareness of pain during surgery and, in some cases, makes you unconscious) and monitors your vital signs (breathing, heart rate, and blood pressure) while identifying and treating any medical problems that may arise during the surgery or recovery period.
Certified registered nurse anesthetist (CRNA). A nurse anesthetist (a nurse who has received specialized training in anesthesia and passed a national certification exam) may also care for you before, during, and after surgery, often under the direction of an anesthesiologist. This nurse monitors your vital signs and modifies the anesthesia when necessary to ensure your safety and comfort.
Operating room (OR) nurse/circulating nurse. OR nurses are registered nurses who assist the surgeon during surgery.
Recovery room nurses and staff. Recovery room nurses care for and monitor patients who have undergone major or minor surgery.
Other health care professionals. Other specialists who work to meet the full spectrum of your physical and psychological needs during treatment can include pharmacists, social workers, nutritionists or dietitians, and physical therapists. Learn more about the oncology team.
Before surgery
Consultation and informed consent. Before treatment, you will meet with a surgeon who will review your record, perform a physical examination, evaluate the need for surgery, and discuss the potential risks and benefits of surgery. You will be asked to provide written permission for your doctor to perform surgery after you have been informed about your treatment options. This process is called informed consent, and it gives you the opportunity to ask questions about the surgery. Your consent also means that you understand that there is no guarantee that the surgery will achieve the intended results.
Preoperative tests. Before surgery, you may need certain tests. For example, you may have a blood test to identify your blood type (in case a blood transfusion is necessary), assess your risk of bleeding or infection, and check liver and kidney function. In addition, you may be asked to give a urine sample, have an electrocardiogram (EKG), or undergo imaging scans, such as computerized tomography (CT), magnetic resonance imaging (MRI), ultrasound, bone scan, or positron-emission tomography (PET). Talk with your doctor to learn what tests you will need.
Restrictions. If you smoke, you are encouraged to quit smoking at least two weeks before surgery, which can help your body recover more quickly after surgery. In addition, talk with your doctor to learn what you should or should not eat or drink during the 24 hours before surgery. And mention any medications and dietary or herbal supplements you are taking, including prescription drugs and over-the-counter drugs. Your doctor and anesthesiologist will tell you whether to continue taking those medications before surgery.
What to wear/bring. When you arrive at the hospital, you may need to change into a hospital gown or remove clothing or jewelry that could interfere with the surgery. Leave jewelry and other valuables at home or with a family member in the waiting area. In addition, wear your eyeglasses on the morning of your surgery, rather than contact lenses, as it is easier to remove your glasses before surgery. You may choose to bring your contact lenses, case, and solution to use once you are recovering from surgery. In most cases, you will also be asked not to wear makeup on the day of the surgical procedure.
Other considerations.
• Check with your insurance provider to learn whether you need to get preapproval of coverage before the surgery.
• If there is a risk of blood loss during the operation and your procedure is more than four weeks away, you may want to bank (store) your own blood for use during your operation.
• Consider bringing a family member or friend on the day of surgery. After the surgery, your doctor will provide him or her with an update about how it went.
• Arrange for care during your recovery phase, including transportation home from the hospital.
• If you have any questions, clarify instructions with the doctor or nurse.
During surgery
You will likely receive some type of anesthesia during surgery. Local anesthesia means that the area near the site of the operation is numbed. Most procedures that take place in a doctor’s office, such as the removal of a mole, are done with local anesthesia. Regional anesthesia is used to block sensation from a larger area, such as an arm or leg. It often involves blocking specific nerves. Patients receiving local or regional anesthesia are often given a sedative to help them relax and sometimes sleep during the procedure. General anesthesia causes a person to feel no pain and to be unaware of the surgery. This is the type of anesthesia most people think of when having an operation.
Initially, general anesthesia is delivered through either a face mask or an intravenous (IV) needle (a needle placed in a vein in your arm). The anesthesiologist then places a tube in your throat to assist with breathing, provide oxygen, and sometimes deliver anesthesia. The anesthesiologist carefully monitors your heart rate, blood pressure, and oxygen during the operation. Generally, you are not aware of anything until the anesthesia wears off after the operation.
In the operating room, after the anesthesia has been given, the area of your body around the location of the surgery will be thoroughly cleaned and shaved to reduce the risk of infection. Once the operation is finished, you will be moved to the recovery area.
Recovery
Recovery time usually depends on the type of surgery performed and the type of anesthesia given during surgery. For example, patients who received local anesthesia may be permitted to go home shortly after the procedure. Patients who have received regional or general anesthesia are monitored carefully in a recovery room until the anesthesia wears off, usually in one to two hours.
After procedures done under general or sedation anesthesia, you may feel groggy for some time after surgery. You may gradually become aware of soreness in your throat from the anesthesia tube, the tubes at the site of surgery for draining excess fluid, and perhaps a catheter (tube) in your bladder, which allows urine to exit your body. You may also become aware of pain as you awaken and may be given medication to relieve it. When your condition is stable you will be either transported to your hospital room or discharged home.
Before you leave the hospital, schedule follow-up appointments so that your doctor can monitor your ongoing recovery.
In addition, it is important to follow recovery instructions from your doctor or nurse. The following suggestions can help speed recovery:
• Walk as soon as you can to circulate blood and prevent clots.
• Work with your doctor and/or nurse to manage pain.
• Perform deep breathing exercises to prevent pneumonia if your doctor recommends it. And do not smoke during recovery.
• Talk with your nurse or hospital dietitian about getting the right nutrition and returning to your regular foods.
• Be alert for complications, such as excessive bleeding, infections, and allergic reactions to anesthesia or drugs, including nausea, shortness of breath, dizziness.
• If you develop a fever, excessive drainage from your surgical incision, redness or excessive swelling at your incision site, or persistent nausea and vomiting, call your surgeon’s office.
• Ask your doctor about engaging in physical activity after your surgery. Physical therapy (PT) may become an important part of your recovery because it can help build strength and flexibility, and it can begin as early as the day following surgery. Some patients are given a home exercise program to continue their progress, but it is important to follow the specific directions given by your doctor.
• Ask your doctor or nurse when and how to change your dressing (bandage). Although a dressing is used to help a surgical incision heal and to guard against infection, leaving it on too long may actually delay healing or lead to infection.
Don't hesitate to contact your health care providers if you have questions.
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Understanding Cancer Surgery
Watch the Cancer.Net Video: Basics of Cancer Surgery with Robert Sticca, MD, adapted from this content.
This is the first article in a three-part series, and it provides an overview of the basics of surgery. Other articles in this series address what to expect when undergoing surgery and side effects of the treatment.
Surgery (the removal of cancerous tissue from the body) is the oldest type of cancer therapy, and it remains an effective treatment for many types of cancer today. The goal of surgery varies. It can be used to diagnose cancer; determine where it is located, whether it has spread, and whether it is affecting the functions of other organs in the body; remove all or some of the cancerous tissue; restore the body's appearance or function; or relieve side effects.
A doctor who specializes in treating cancer using surgery is called a surgical oncologist. Some types of surgery can be performed in a doctor's office, clinic, or surgery center. This is called outpatient surgery. For other types of surgery, patients are admitted to the hospital for a period of time. This is called inpatient surgery.
Types of conventional surgery
Diagnostic. For most cancers, a biopsy is needed to make an accurate diagnosis. A surgical biopsy involves a surgeon making an incision in the skin and removing some or all of the suspicious tissue. There are two main categories of surgical biopsies. An incisional biopsy removes a piece of the suspicious area for examination. An excisional biopsy removes the entire lump. Learn more about types of biopsies and what to expect during the procedure.
After a biopsy, a pathologist (a doctor who specializes in interpreting laboratory tests and evaluates cells, tissues, and organs to diagnose disease) examines the tissue with a microscope and provides a pathology report to the surgeon or oncologist, who then makes the diagnosis.
Staging. Staging surgery determines the size of the tumor and whether it has spread to lymph nodes and other organs in the area. Together with the physical examination, biopsy, and results of laboratory and imaging tests, it allows the doctor to accurately determine the extent of disease, which can then be used to determine the best treatment options.
Tumor removal (also called curative or primary surgery). The most common type of cancer surgery is to remove the tumor and surrounding tissue (called a margin). Tumor removal may be the sole treatment, or it may be combined with chemotherapy or radiation therapy, which can be given before or after surgery. In some cases, doctors can use surgical techniques that are less invasive, which can speed your recovery. Learn more about types of minimally invasive surgery below.
Debulking. When the complete removal of a tumor is not possible or might cause excessive damage to the body, surgery can be used to remove as much of the tumor as possible. Other treatments, such as radiation therapy or chemotherapy, are then used to address the remaining cancer.
Palliation. Palliative surgery is used to relieve side effects caused by a tumor. It plays an important role in extending survival or improving quality of life for patients with advanced cancer or widespread disease. Examples include:
• Surgery to relieve pain. If a tumor presses on a nerve or the spinal cord, blocks the bowel (intestine), or creates pressure or blockage elsewhere in the body, surgery can help relieve pain or restore physical function.
• Surgery to stop bleeding. Certain cancers are more likely to cause bleeding because they occur in areas (such as the uterus) with a high concentration of blood vessels or organs (such as the esophagus, stomach, and bowel) in which the tumors are very fragile and can easily bleed due to the passage of food and waste products. In addition, bleeding can be a side effect of some drugs that are used to treat cancer. When surgery is needed to stop bleeding, a common technique is suture ligation, which involves tying off blood vessels using surgical thread.
• Surgery to insert a feeding tube or tubes for delivering medications. If the cancer or cancer treatment has made it difficult for the patient to eat, a feeding tube may be inserted directly into the stomach or intestine through the abdominal wall. Or a tube may be inserted into a vein to deliver pain medication or chemotherapy.
• Surgery to prevent broken bones. Bones weakened by cancer or cancer treatment can break easily and tend to heal slowly. A metal rod can help prevent fractures of weak bones and relieve pain during healing. Learn more about bone health during cancer treatment.
Reconstruction. After primary cancer surgery, additional surgery is sometimes an option to restore the body's appearance or function. Examples of reconstructive (plastic) surgery include breast reconstruction after a mastectomy and surgery to replace normal tissue and nerves that were removed in the head and neck area.
Prevention. Some surgeries are performed to reduce the risk of developing cancer. For instance, the removal of precancerous polyps in the colon is recommended to prevent colon cancer. In addition, women with a strong family history of breast and/or ovarian cancers and those who carry mutations (changes) in the BRCA1 and BRCA2 breast/ovarian cancer genes may decide to have a prophylactic (preventive) mastectomy (removal of the breast) and/or oophorectomy (removal of the ovaries) to reduce their risk of future cancer.
Learn more about types of surgery that are commonly used for specific cancer types.
Types of minimally invasive surgery
Conventional surgery requires larger incisions (cuts) through skin, muscle, and sometimes bone, which can make recovery slow and painful. However, in some cases, minimally invasive surgery may be an option. Such procedures are performed through one or more small incisions and generally have shorter recovery times and less postoperative pain. Below are some examples of minimally invasive procedures and surgeries:
Endoscopy. This is a general name for a procedure in which a doctor inserts a small tube with a light and camera on the end into an opening of the body (such as the mouth, rectum, or vagina) to examine the internal organs. During an endoscopic procedure, it is possible to remove samples of potentially abnormal tissue for further examination. Learn more about endoscopic techniques.
Laparoscopic surgery. With this type of surgery, the surgeon makes small incisions in the skin to insert a lighted tube with a camera. A laparoscopy refers to a minimally invasive surgery of the abdomen. Mediastinoscopy and thoracoscopy are terms used when the same type of procedure is performed in the chest.
Laser surgery. A narrow beam of high-intensity light is used to remove cancerous tissue.
Cryosurgery. Liquid nitrogen is used to freeze and kill abnormal cells.
Mohs micrographic surgery. Also called microscopically controlled surgery, Mohs micrographic surgery involves shaving off a skin cancer one layer at a time until all cells in a layer appear to be normal cells when viewed under a microscope.
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Additional Resources
American College of Surgeons: Patient Resources
Side Effects of Cancer Surgery
This article—the third in a three-part series—describes the side effects of this treatment. Other articles in the series provide an overview of surgery—including the various types—and address what to expect when undergoing surgery.
Cancer surgery, like all cancer treatments, comes with benefits, risks, and side effects. The types and intensity of side effects vary from person to person and with the type and location of the cancer, the type of surgery, and the person’s health. If you and your doctor decide that surgery will be a part of your cancer treatment, you will be given information about all aspects of your treatment before you consent to surgery, including the side effects you may experience.
With recent advances and less invasive surgical techniques, the side effects of surgery are often milder, and patients usually recover faster. In addition, doctors have made major strides in recent years in reducing pain and other physical side effects from all types of surgery. Your health care team will work with you to ease or prevent side effects.
Common side effects of cancer surgery
Common side effects of cancer surgery may include the following:
Pain. It is common to have some pain after any surgery. The amount and location of the pain depends on many factors, including the site of surgery, the size of the incision, and the amount of tissue removed. Pain after surgery resolves gradually as the body heals. Pain medications are given after surgery to decrease the discomfort that the patient feels while the healing occurs.
Fatigue. Many patients feel very tired after major surgery, especially when the surgery involves the abdomen or chest. This is due to a combination of factors, including the anesthesia, the body’s tendency to divert energy to the healing process after the surgery, the reduction in the amount of food eaten in the period immediately after the surgery, and the stress of the surgery. Fatigue usually resolves gradually within two to four weeks after the surgery is performed.
Loss of appetite. Poor appetite after surgery is very common, especially when general anesthesia was used. This generally lasts for two to four weeks after surgery and may be associated with a temporary weight loss. Most patients regain their appetite and return to their normal weight as the effects of the surgery wear off.
Swelling around the site of surgery. A surgical incision (cut in the skin) is a form of injury to the body, and the body’s natural response to injury is the inflammatory process, which results in swelling. Swelling occurs because fluid containing chemicals from white blood cells accumulates in the injured tissues to attack foreign substances. As the healing occurs after the surgical procedure, the inflammation resolves, and the swelling goes down. It is natural to experience some swelling after any surgical procedure.
Drainage from the site of surgery. Sometimes the fluid that accumulates at the surgery site drains through the surgical wound. This is normal. However, if the drainage is foul smelling or associated with fevers and redness, it may be a sign of infection, and you should contact your surgeon’s office to have it evaluated.
Ecchymosis (bruising) around the site of surgery. After any surgical incision, there may be some leakage of blood from the small blood vessels under the skin. This can cause bruising, which is a common occurrence after a surgical procedure. However, if there is a significant swelling associated with the bruising, contact your surgeon’s office to have it evaluated.
Bleeding. In every surgical procedure, there is some blood loss. In most cases the amount of blood loss is minimal, and it does not affect the normal function of the body. In some surgical procedures, a larger amount of blood loss is expected, and the surgical team may have blood available for transfusion. Occasionally, you may experience some bleeding from the wound after a surgical procedure. If this occurs, cover it with a clean, dry dressing, and contact your surgeon’s office. If there is a large amount of bleeding, it is helpful to apply pressure until you can be evaluated in your surgeon’s office or the local emergency room.
Infection. This may occur at the site of the incision, or cut. Surgeons take great care to minimize the risk of infection during the operation, and your health care team will teach you how to care for yourself during recovery. Signs of infection in a surgical incision include redness, warmth, increased pain, and, in some cases, drainage from the wound. If these signs occur, contact your surgeon’s office to have the wound evaluated. Antibiotics, in pill form or by injection, are effective in treating most infections.
Lymphedema. This is another common side effect that may occur after a lymph node dissection (the removal of lymph nodes). Lymph nodes are small glands that filter bacteria and other harmful substances from the lymph fluid, a colorless fluid in most tissues of the body. Sometimes, when the lymph nodes are removed, lymphatic fluid collects in the surrounding tissues, causing them to swell; this is called lymphedema, and it can result in discomfort and tightness. Lymphedema occurs in less than one third of all patients who undergo lymph node dissection procedures. Your surgeon will discuss the risk of lymphedema with you before a planned lymph node procedure.
Organ dysfunction. Cancer surgery in some areas of the body, such as the abdomen or chest, can sometimes cause temporary problems with the organs in that area. For example, when surgery is performed in the abdomen, the bowels may become paralyzed for a short time (also called an ileus), not allowing the contents of the bowels to pass through. This can result in nausea and vomiting until the bowels begin to function again. Organ dysfunction after surgery is usually temporary and resolves as the healing process proceeds.
Other Concerns after Cancer Surgery
Dietary concerns. During recovery, the body needs extra calories and protein for healing; however, eating your regular food may be difficult, depending on the location where the surgery was performed. Resection (removal) of any part of the mouth, throat, stomach, small intestine, colon, or rectum decreases appetite, limits the body's ability to absorb nutrients, and/or increases problems after eating, such as gas, cramping, or constipation. Some patients may have difficulty chewing or swallowing food. In addition, surgery for stomach cancer may affect the body's ability to absorb certain vitamins. Doctors usually prescribe vitamin supplements, some of which can be given only by injection, to help ease this problem.
Body image. Cancer surgery causes physical changes that may change the way your body looks and feels and how it functions. For example, surgery for bladder and colorectal cancers may affect the removal of waste products from the body. If the bladder is removed, a new way to store and remove urine is needed. A urostomy (connection between the urinary organs and the skin) may be created during the surgery to divert urine to the outside of the body. Similarly, if the lower part of the rectum is removed, a temporary or permanent colostomy may be needed. A colostomy is a surgical opening, or stoma, through which the colon is connected to the skin surface to provide a pathway for waste to exit the body. Such waste is collected in a pouch worn by the patient.
Some people may feel insecure about these changes and struggle with their body image. The emotional side effects of cancer surgery are as important to treat as physical side effects. Talk with your doctor about options for reconstructive surgery and prostheses. Some patients find it helpful to join a support group of other patients in similar situations.
Sexuality and Reproduction
Certain types of surgery can affect fertility (a woman’s ability to conceive a child or maintain a pregnancy and a man’s ability to father a child). Before treatment begins, talk with your doctor about the possible fertility-related side effects of your treatment and the available options for preserving fertility.
In addition, depending on the location of the surgery, both men and women may experience other sexual side effects. For example, men undergoing surgery for prostate, bladder, colorectal, or other types of cancer may experience changes in their sexual desire and production of semen. The ability to have an erection or the ability to ejaculate may be affected. Meanwhile, some gynecologic surgical procedures may affect sexual function for women, as well. And many women experience a range of feelings after such surgery, including loss, sadness, or anxiety. It is important to discuss the symptoms you experience with your doctor. There are various options available to help manage the sexual problems you may encounter.
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Nguồn: http://www.cancer.net/patient/Cancer+Types/Liver+Cancer?sectionTitle=Treatment
Surgery for hepatocellular carcinoma: does it improve survival?
Liu JH, Chen PW, Asch SM, Busuttil RW, Ko CY.
Source
Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. jerome8@ucla.edu
Abstract
BACKGROUND:
The incidence and mortality of hepatocellular carcinoma (HCC) are increasing in the United States. Whether surgery is associated with improved survival at the population level is relatively unknown. To address this question, we used a population-based cancer registry to compare survival outcomes between patients receiving and not receiving surgery with similar tumor sizes and health status.
METHODS:
By using the Surveillance, Epidemiology, and End Results database, we identified HCC patients who had surgically resectable disease as defined by published expert guidelines. After excluding patients with contraindications to surgery, we performed both survival analysis and Cox regression to identify predictors of improved survival.
RESULTS:
Of the 4008 patients diagnosed with HCC between 1988 and 1998, 417 were candidates for surgical resection. The mean age was 63.6 years; mean tumor size was 3.3 cm. The 5-year overall survival with surgery was 33% with a mean of 47.1 months; without surgery, the 5-year overall survival was 7% with a mean of 17.9 months (P <.001). In the multivariate Cox regression, surgery was significantly associated with improved survival (P <.001). Specifically, patients who received surgery had a 55% decreased rate of death compared with patients who did not have surgery, even after controlling for tumor size, age, sex, and race. CONCLUSIONS: This study shows that surgical therapy is associated with improved survival in patients with unifocal, nonmetastatic HCC tumors <5 cm. If this is confirmed in future studies, efforts should be made to ensure that appropriate patients with resectable HCC receive high-quality care, as well as the opportunity for potentially curative surgery. Nguồn: http://www.ncbi.nlm.nih.gov/pubmed/14993025 Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters Ke Hao1* , John M Luk2,5* , Nikki PY Lee2 , Mao Mao1 , Chunsheng Zhang1 , Mark D Ferguson1 , John Lamb1 , Hongyue Dai1 , Irene O Ng3 , Pak C Sham4 and Ronnie TP Poon2 1 Rosetta Inpharmatics LLC, Merck Research Laboratories, Seattle, WA, USA 2 Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, PR China 3 Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong SAR, PR China 4 Department of Psychiatry and Genome Research Center, The University of Hong Kong, Pokfulam, Hong Kong SAR, PR China 5 Department of Pharmacology and Department of Surgery, National University Health System, National University of Singapore, Singapore author email corresponding author email* Contributed equally BMC Cancer 2009, 9:389doi:10.1186/1471-2407-9-389 The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2407/9/389 © 2009 Hao et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background Surgical resection is one important curative treatment for hepatocellular carcinoma (HCC), but the prognosis following surgery differs substantially and such large variation is mainly unexplained. A review of the literature yields a number of clinicopathologic parameters associated with HCC prognosis. However, the results are not consistent due to lack of systemic approach to establish a prediction model incorporating all these parameters. Methods We conducted a retrospective analysis on the common clinicopathologic parameters from a cohort of 572 ethnic Chinese HCC patients who received curative surgery. The cases were randomly divided into training (n = 272) and validation (n = 300) sets. Each parameter was individually tested and the significant parameters were entered into a linear classifier for model building, and the prediction accuracy was assessed in the validation set Results Our findings based on the training set data reveal 6 common clinicopathologic parameters (tumor size, number of tumor nodules, tumor stage, venous infiltration status, and serum α-fetoprotein and total albumin levels) that were significantly associated with the overall HCC survival and disease-free survival (time to recurrence). We next built a linear classifier model by multivariate Cox regression to predict prognostic outcomes of HCC patients after curative surgery This analysis detected a considerable fraction of variance in HCC prognosis and the area under the ROC curve was about 70%. We further evaluated the model using two other protocols; leave-one-out procedure (n = 264) and independent validation (n = 300). Both were found to have excellent prediction power. The predicted score could separate patients into distinct groups with respect to survival (p-value = 1.8e-12) and disease free survival (p-value = 3.2e-7). Conclusion This described model will provide valuable guidance on prognosis after curative surgery for HCC in clinical practice. The adaptive nature allows easy accommodation for future new biomarker inputs, and it may serve as the foundation for future modeling and prediction for HCC prognosis after surgical treatment. Background Hepatocellular carcinoma (HCC) is the fifth most common malignancies in the world, accounting for approximately one million deaths with an increasing trend of new incidences annually [1-3] Surgery is regarded as the one of the standard curative treatments of HCC if the tumor is resectable [4,5]. However, prognosis following surgery differs substantially and such large variation is mostly unexplained. This variation becomes a hurdle in searching for effective and efficacious therapies and cancer management strategies. There is an ongoing search for predictive biomarkers of cancer prognosis, where pathological parameters, protein biomarkers, mRNA expression level, and genomic DNA abnormalities, etc. are surveyed [6-9]. Among these factors, the clinicopathologic parameters are routinely recorded for cancer surgery. Clearly, building a predictive model based on such parameters would be a cost-effective and widely applicable protocol. The most important prognostic endpoints are overall survival (time to death) and disease free survival ([DFS] time to tumor recurrence). There are only a handful of studies identifying tumor size [3,10], staging systems [11] and α-fetoprotein (AFP) [2] in association with these endpoints to date. However, there are no reports on a prediction model systematically built to incorporate all such informative factors. We have surveyed a number of potential predictors to quantify their association with overall survival and DFS. Our primary goal is to develop and validate models that use clinicopathologic parameters and common biomarkers observed at the time of surgery to predict the HCC prognosis. Further, such model must be flexible in accommodating addition factors (e.g. protein biomarkers, gene or microRNA expression signatures) when becoming available. Methods Study Subjects In this retrospective study, we analyzed common clinicopathologic data from 600 HCC patients at Queen Mary Hospital, Pokfulam, Hong Kong in the period of 1990 to 2007. These patients were diagnosed with primary HCC and received hepatic surgery as the primary treatment option. Some patients with ≥6 tumor nodules also received surgery and included in this study, given that good liver functions were indicated and the tumors were not near any major vessels and grouped into 1 or 2 clusters. Patients with other malignancies and non-resectable HCC were excluded. Preoperative investigation of the patients included blood biochemistry, alpha-fetoprotein assay, chest x-ray, percutaneous ultrasonography, computed tomography (CT), and hepatic angiography in selected patients. Liver function was assessed by the Child's-Pugh grading. All patients were treated and received the same postoperative care by the same team of surgeons, and had postoperative follow-up every month for the first year, and every 3-6 months thereafter. The minimal duration of follow-up time of the surviving patients was 12 months. Those cases lacking sufficient clinical and follow-up data were not included. Disease-free survival time was calculated from the date of hepatectomy to the date when recurrence was diagnosed. First, we randomly selected in the training set, 300 patients with available frozen tissue samples (both tumor and adjacent non-tumor) for biomarkers exploration studies by genotyping and mRNA expression profiling. 28 cases that were found missing clinical data or poor sample quality were thus excluded. Table 1 summarizes the demographic and clinicopathologic features of the remaining 272 patients in the training set. The other 300 cases were included in the validation set. There were no significant differences (p-value > 0.05, two-sided tests) in the demographic and clinicopathologic features of HCC patients between the training and validation dataset. The study protocol was approved by the Institutional Review Board of Queen Mary Hospital, and informed consent was obtained from patients regarding to the use of the liver specimens for research.
Table 1. Demographic and clinicopathologic characteristics of HCC patients in the initial training set
Clinicopathological Parameter Measurements
The clinicopathological features of the patients analyzed were sex, age, tumor size, number of tumor nodules, cellular differentiation according to the Edmondson classification, venous infiltration without differentiation into portal or hepatic venules, tumor node metastasis stage (pTNM and AJCC), serum hepatitis B surface antigen (HBsAg) status, and background liver disease in nontumorous liver tissue. They were analyzed as we previously described [12]. In addition we also obtained self-reported life-style parameters such as cigarette smoking (moderate smoking: ≤1 pack/day; heavy smoking: >1 pack/day) and alcohol drinking (moderate drinking ≤: drinks/per day; heavy drinking: >2 drinks/per day).
Statistical Analysis
We examined whether the clinicopathologic phenotypes that were recorded at the time of surgery might predict cancer prognosis. There are a number of statistical learning techniques able to serve as classifier to make predictions. These include linear model, vector machine, neuron networks, and others. However, many of these methods do not directly accommodate two-dimensional outcome (e.g. survival and DFS). Herein, we used the univariate parameter selection and multivariate Cox model classifier, as previously described [7,8].
In brief, we applied Cox regression models to screen the initial training dataset for clinicopathologic parameters associated with survival outcomes. All significant clinicopathologic parameters were included into a multivariate Cox model. The output of this approach is a linear predictor that could serve as the classifier. Clearly, such a model can separate long vs. short survival patients in the training data. The potential for an over-fitting bias was acknowledged by assessing the prediction accuracy of the leave-one-out (LOO) procedure. In parallel, we also evaluated the prediction performance on an independent testing set.
The log rank p-values did not directly reflect the prediction accuracy, because the sample sizes were different in the training and testing datasets. Instead, utilization of the time-dependent ROC and AUC was used to measure prediction performance [13]. In detail, at a given time t, we define

where c denotes the cutoff value and T denotes the survival time. By these means, we generated ROC for every time point and calculated the AUC.
Results
Table 1 summarizes the demographic and pathologic parameters of the 272 patients that were used as the initial training set. Nearly 2/3 of the patients were right-censored (67.8%) and 1/3 (32.2%) of the patients ceased (failure) upon data analysis. Half of the patients (51.1%) suffered from tumor recurrence during the follow-up period. The primary endpoints employed were overall survival (Table 2) and DFS (Table 3). In a simple Cox model, the endpoints were found to be significantly associated with tumor size, serum AFP levels of alpha fetoprotein (AFP), total albumin concentration (ALBU), venous infiltration (VENINV), tumor stage (pTNM and AJCC), and the number of tumor nodule (NOTN). Most notably, pTNM stage and AJCC stage were highly correlated with the primary endpoints. As expected, overall survival was strongly associated with tumor recurrence and since this could not be observed at the time of surgery, it was decided not to include this factor into the prediction model.
Table 2. Effect of demographic and clinical parameters on survival outcome in the initial training set (N = 272)
Table 3. Effect of demographic and clinical parameters on disease free survival in the initial training set
After evaluating all variables in Tables 2 &3, we selected those of significant association with survival and DFS into the multiple regression model (proportional hazards regression). This Cox model employed AFP, ALBU, VENINV, tumor size, new AJCC and NOTN to predict HCC prognosis (survival and DFS). The pTNM stage was not included into the model since this is an old staging system and is currently highly correlated with the new AJCC stage in our dataset. Attempts to incorporate pTNM stage into the prediction models had little impact on results.
The prediction model performed well on the training data, but was subject to an over-fitting bias from the standpoint of machine-learning. Therefore, the prediction performance was assessed using the leave-one-out (LOO) method. The LOO procedure was performed on 264 patients who have complete survival and covariates data. The analysis consisted of 264 loops. The first step within each loop is to reserve one patient (i.e. patienti) for testing and use the remaining 263 patients to fit a multivariate Cox model (termed as model-i). This approach allows model-i to be independent from patienti. Secondly, the relative hazard (denoted as hi) was predicted for patienti based on his/her covariates and model- Upon completion of the 264 loops, hi for every patient is obtained. Lastly, equal division of the testing samples into two groups based on hi, was followed by evaluating the prediction accuracy using a Kaplan Meier plot and log rank test. The LOO procedure was also conducted for DFS with 267 patients. The Cox model based on clinicopathologic parameters offered substantial prediction power as shown in Figure 1. The high and low-risk groups were significantly different in terms of survival and DFS (log rank p-values of 1.2e-6 and 5.0e-9, respectively). About 80% patients in the predicted low-risk group survived over 60 months after surgery. Conversely, only about 40% patients in the high-risk group survived 60 months (Figure 1A). To further demonstrate robustness of the data, the patients were divided into three equal sized groups according to hi (Figures 1C and 1D). The results of this additional grouping further demonstrate separation in terms of survival and DFS.
Figure 1. Kaplan-Meier survival curves of HCC patients in the training set. Relative hazard (h) was predicted for cancer survival (A) and disease-free survival (B) using a leave-one-out procedure. Patients were equally divided into two groups based on h, and their Kaplan-Meier survival functions were compared by log-rank test. Alternatively, we divided patients into three equal-sized groups based on their h, and observed excellent separation. Such results suggest the prediction is rather robust, and not sensitive to choice of grouping. The vertical bars on the survival curve denote censored patients.
Motivated by the significant findings in the initial training dataset, we further tested this model independently in the validation set of separate 300 patients. This test set consisted of 272 patients who had complete outcome and covariate information. Analysis of both the training and testing samples clearly show similar results in terms of survival, DFS (see Additional file 1) and covariates distribution (see Additional file 2). The selected covariates were significantly associated with cancer prognosis in the testing set with respect to overall survival (Table 4) and disease-free survival (Table 5). As a result of this association, it was concluded that the variable distributions in the testing patients were similar to the training patients and are therefore suitable for independent validation. The entire training data set was used to fit a multivariate Cox model and then employed to predict the relative hazard for the testing samples. The next step involved equally divided the testing samples into two groups based on predicted hazard followed by a log rank test (Figure 2). The predicted high and low-risk groups were significantly different in survival (log-rank p-value = 1.8e-12) and DFS (log-rank p-value = 3.2e-7).
Additional file 1. Clinical outcomes of HCC patients from the training and validation set. The distribution of overall survival rate (A) and disease-free survival rate DFS (B) reveals no significant difference among the HCC patients between the training and validation samples.
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Additional file 2. Characteristics of validation dataset (N = 300). The demographic and clinicopathologic parameters of HCC patients in the validation set show no significant difference from the initial training set.
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Table 4. Effect of clinical parameters on survival outcome in the testing set
Table 5. Effect of clinical parameters on disease free survival in the validation cohort
Figure 2. Kaplan-Meier survival curves of HCC patients in the validation set. We first fit a multivariate Cox model using the initial training set focusing on overall cancer survival (A) and disease-free survival (B). This model was used to predict the relative hazard (h) for an independent testing set. Next, the testing patients were equally divided into two groups based on predicted h, and their Kaplan-Meier survival functions were compared by log-rank test.
Lastly, the time-dependent ROC curves (in Figure 3A, t = 60 months for survival; in Figure 3B, t = 30 months for DFS) were derived along with the area under the curve (AUC) for all time points. The average AUC was 0.7 for the testing set, indicating considerable predicting power. The AUC was slightly higher (0.75) in the training dataset, reflecting the over-fitting bias.
Figure 3. ROC curve analyses of HCC patients in the training and testing datasets. Multivariate Cox model built on the initial training set was used to predict cancer prognosis in the training set and testing set. Time-dependent ROC and AUC were computed in the intervals of (A) 60 months and (B) 30 months to quantify the prediction accuracy.
Discussion
The purpose of our study was to develop a systematic model according to universally recognized clinicopathologic parameters for improved accuracy of prognostic outcome prediction in HCC patients after curative surgery. Therefore, all acknowledged factors associated with outcomes were evaluated. Notably, certain important parameters, such as tumor staging and venous infiltration status, would require postoperative histological examination of the resected tissues or biopsy samples of the patients, unless future radiological examination using dynamic MRI could provide such definitive diagnosis. Nevertheless our primary contribution is the modeling framework which incorporates multiple parameters in prediction prognosis. Its flexible nature allows us to easily remove parameters (e.g. VENINV when either biopsy samples are not available or diagnostic radiography data is not affirmative) or to add new biomarkers (e.g. newly identified gene signatures). Several studies of HCC have reported the ability to use clinicopathologic parameters or biomarkers towards grouping subjects and predicting survival outcomes [2,3,14]. However, most studies were small or without an independent validation set. Likewise, there are no models built to systematically incorporate all factors to predict outcome. In addition, the existing prediction rules appear to be ad hoc, involve multiple arbitrary cutoffs and lack statistical rigor. Lastly, the performance of such rules has not been formally assessed by such analyses, e.g., ROC.
The salient contribution of this publication is the identification of certain common clinicopathologic parameters and biomarkers strongly associated with the prognostic outcome that are further confirmed by two different protocols: LOO and independent validation. Previous studies have revealed some of these predictors, but often lack reproducibility which may due to the difference among patient populations. For example, the majority of the Chinese patients carry hepatitis B [15], while hepatitis C virus is prevalent in Western Europe [16]. The relatively small sample sizes of the aforementioned data sets contribute to the inconsistent results. Herein, we provide confirmation to a previous report using a large sample size and validation data. The first group of predictors highlighted in this paper is the tumor stage. There are growing numbers of staging systems available but unfortunately not one is perfect with each having individual strengths and weakness. Conversely, our data sets show staging systems are highly correlated. The following parameters were found to be strongly associated with prognosis and prediction value: AFP, albumin level, venous infiltration and the number of tumor nodules. Among these predictors, the serum albumin level may reflect the conditions of patients liver physiology, while the rest of other factors hint to the biology or characteristics of the HCC tumor per se. This may reflect the importance of both the host (or the microenvironment) and tumor factors contributing to the outcomes. The self-reported variable alcohol consumption was marginally significant in a univariate model but was not used and determined to be non-significant in our multivariate Cox model. This finding is highly consistent with previous report on Chinese HCC patients [15,17] where dichotomized serum albumin and tumor size, number of tumor nodules, venous infiltration, and tumor stage were significantly associated with cancer prognosis after surgery.
The prediction power of the predicted hazard (h) was demonstrated in this report, which is literally the linear combination of many predictors. A number of studies were conducted quantifying the predictive power of clinicopathological parameters, and our results are consistent with previous reports on vascular invasion [18,19], AFP level [15,19] and tumor size [19] in term of hazard ratios. However, this study did not measure some variable, e.g., portal hypertension and bilirubin [20], therefore, we could not directly assess their predictive value. 97.3% of our patients were classified as Child-Pugh grade A, and we found Child-Pugh grade not to be a significant predictor (possibly due to lack of statistical power). Nevertheless, our primary goal is to develop the objective and flexible framework, which can easily accommodate additional biomarkers when becoming available. There are well known scoring systems to classify HCC, including Child-Pugh [18], the Oku [11], Advanced Liver Cancer Prognostic System (ALCPS, applicable to patients with advanced HCC who were not amendable to surgery or locoregional therapy) [21], and Barcelona Clinic Liver Cancer Group [20,22]. As the drawback, these scores have been devised by a series of ad hoc rules. In the other hand, predicted hazard is objective and can readily incorporate a new patient and biomarkers information. This can be simply performed by updating the linear model and the set of coefficients and will allow us to continuously update the model when new data becomes available. This is particularly important as new biomarkers based on molecular studies of HCC could be incorporated into the model. HCC has a heterogeneous etiology and many factors (e.g. patients' ethnicity and genetic background) may affect prognosis. Therefore, this model may not be directly applicable to a different HCC cohort in the Western countries. This approach should serve as a general framework, where the Cox linear classifier can be trained on a particular cohort and applied to future patients.
A considerable fraction of our HCC patients achieved 5+ years of DFS after surgery, especially for those with favorable clinicopathologic profiles as highlighted in our previous reports [15]. The cutoff of 5 or 10 years is widely used to define the cure of HCC, however, such thresholds are arbitrary. The categorization of a patient with 5 year of DFS as a cure, while classifying another patient with 4.9 year DFS as a failure does not lead to valid conclusions. Therefore, treatment of survival and DFS as quantitative traits was performed without the application of any cutoffs or subjective dichotomization of the clinicopathologic parameters. HCC patient follow-up is a non-trivial task given the ever increasing mobility of an urban population. Due to improved treatment and management, HCC patients live longer and thus make follow-up evaluations a challenge. One strategy is to only analyze the patients with observed events [15,23], but this approach would greatly reduce the sample size (as well as statistical power), since many of the data point were censored (Figure 1). Instead, we employed of time-to-event methods (e.g. Cox model), where the censored data also contributed to the test and improved statistical power. Moreover, the Cox model also quantifies the strength of the association between clinicopathologic parameters and prognosis (in the form of relative hazard), which is actually the foundation for prediction.
In the past decade we have observed a fast growth of literature using gene expression profiles and DNA abnormality to predict cancer prognosis. However, these approaches have not achieved real clinicopathologic applicability because of the inter-institutional variation caused by numerous factors such as; array platform, statistical algorithm, reagent, laboratory condition/protocol. In contrast, clinicopathologic parameters are more standard, robust, and available worldwide. Models built on clinicopathologic factors can be more readily used in today's hospital practice. Further, the linear model should certainly include new biomarkers (to improve prediction power if there is conclusive evidence that a biomarker gives additional information conditioning on known factors. Recent studies [24,25] revealed gene expression in tumor and adjacent normal liver tissues (suggesting a so called "field-effect") were predictive for HCC prognosis. It has been suggested that mechanistically these signatures capture tumor status, damage to liver tissue and the state of inflammation which relates to the likelihood of subsequent tumors arising [23,25]. However, all such studies failed to incorporate clinicopathological and expressional predictors together. In such cases, the identified expressional predictors first capture the same information as clinicopathological parameters (e.g. cancer stage), and the performance for the expressional biomarkers would not necessarily outperform clinicopathological predictors (unpublished results). Herein, we argue that in order to capture information from gene expression that was not redundant to clinicopathologic data, the clinicopathologic parameters would be included during the search for expression signatures, and our hazard score model will serve for this purpose.
In summary, we have retrospectively analyzed the association of common clinicopathologic parameters with clinical outcomes in a large sample cohort (n = 572) of HCC patients after curative surgery. We quantified the strength of the association and then built a classifier based on multi-variates Cox regression. This approach has excellent prediction power. Nonetheless, there is still a large fraction of variance that has not been explained since the area under the ROC is around 70% in validation data. The search for other biomarker to improve the prediction of HCC survival will certainly be an important direction for future research. As a caveat, the models that employ clinicopathologic parameters are often competitive with most of the models incorporating gene expression data. This is due to both set of predictors capturing the tumor stage [8]. Hence, the model described in this paper should serve as a foundation for future work when biomarkers at the protein, mRNA or DNA level are considered. Furthermore, the selection of additional biomarkers should be based on common clinicopathologic parameters; otherwise, they may recapture similar information and provide little extra predictive value.
Conclusion
The present study described a Cox linear regression model based on common clinicopathologic parameters, which provides valuable guidance on prognosis after curative surgery for primary HCC among Chinese patients in clinical practice. The adaptive nature allows easy accommodation for future new biomarker inputs, and it may serve as the foundation for future modeling and prediction for HCC prognosis after surgical treatment.
Competing interests
KH, CZ, MDF, JRL, MM and HD engaged in this work as employees of Merck & Co., Inc., a leading pharmaceutical company; other than that, all other authors disclose no competing interest.
Authors' contributions
JL and RP contributed to the study design and conception. NL contributed in study execution. IN helped in the pathological definition. RP was responsible for acquisition of clinical samples and gave advices on samples' clinical background. PS provided statistical advice and critique. JL and RP carried out critical revision of the manuscript. KH conducted the analysis. MM, CZ, MF, JL, HD and RP provided critical review on the manuscript. The manuscript was drafted and written by KH and JL. MM, CZ, MF, JL, HD and RP provided critical review on the manuscript. All the authors approved this manuscript.
Acknowledgements
The work was supported by Research Grants Council of Hong Kong and Innovation and Technology Fund of the Hong Kong Government to J.M.L. We would like to thank for the technical supports from Ashley Wong and Kit-Yuk Mak of the Queen Mary Hospital. IOL Ng is a Loke Yew Professor in Pathology.
Nguồn: http://www.biomedcentral.com/1471-2407/9/389
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Hepatocellular carcinoma is now the third leading cause of cancer deaths worldwide, with over 500,000 people affected. The incidence of hepatocellular carcinoma is highest in Asia and Africa, where the endemic high prevalence of hepatitis B and hepatitis C strongly predisposes to the development of chronic liver disease and subsequent development of hepatocellular carcinoma.
The presentation of hepatocellular carcinoma has evolved significantly over the past few decades. While, in the past, hepatocellular carcinoma generally presented at an advanced stage with right upper quadrant pain, weight loss, and signs of decompensated liver disease, hepatocellular carcinoma is now increasingly recognized at a much earlier stage as a consequence of the routine screening of patients with known cirrhosis, using cross-sectional imaging studies and serum alpha-fetoprotein measurements.
Resection may benefit certain patients, albeit mostly transiently. Many patients are not candidates given the advanced stage of their cancer at diagnosis or their degree of liver disease and, ideally, could be cured by liver transplantation. Globally, only a fraction of all patients have access to transplantation, and, even in the developed world, organ shortage remains a major limiting factor. In these patients, local ablative therapies, including radiofrequency ablation, chemoembolization, and potentially novel chemotherapeutic agents, may extend life and provide palliation.
Nguồn: http://emedicine.medscape.com/article/197319-overview
Hepatocellular carcinoma (HCC, also called malignant hepatoma) is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis).[1]
Compared to other cancers, HCC is quite a rare tumor in the United States. In countries where hepatitis is not endemic, most malignant cancers in the liver are not primary HCC but metastasis (spread) of cancer from elsewhere in the body, e.g., the colon. Treatment options of HCC and prognosis are dependent on many factors but especially on tumor size and staging. Tumor grade is also important. High-grade tumors will have a poor prognosis, while low-grade tumors may go unnoticed for many years, as is the case in many other organs, such as the breast, where a ductal carcinoma in situ (or a lobular carcinoma in situ) may be present without any clinical signs and without correlate on routine imaging tests, although in some occasions it may be detected on more specialized imaging studies like MR mammography.
[edit] Signs and symptoms
HCC may present with jaundice, bloating from ascites, easy bruising from blood clotting abnormalities or as loss of appetite, unintentional weight loss, abdominal pain,especially in the upper -right part, nausea, emesis, or fatigue.[2]

[edit] Risk factors
The main risk factors for hepatocellular carcinoma are
• Alcoholism
• Hepatitis B
• Hepatitis C
• Aflatoxin
• Cirrhosis of the liver
• Hemochromatosis
• Wilsons disease (while some theorize the risk increases,[3] case studies are rare[4] and suggest the opposite where Wilson's disease actually may confer protection[5])
• Type 2 Diabetes (probably aided by obesity)[6]
Ther risk of hepatocellular carcinoma in type 2 diabetics is greater (from 2.5[6] to 7.1[7] times the non diabetic risk) depending on the duration of diabetes and treatment protocol. A suspected contributor to this increased risk is circulating insulin concentration such that diabetics with poor insulin control or on treatments that elevate their insulin output (both states that contribute to a higher circulating insulin concentration) show far greater risk of hepatocellular carcinoma than diabetics on treatments that reduce circulating insulin concentration.[6][7][8] On this note, some diabetics who engage in tight insulin control (by keeping it from being elevated) show risk levels low enough to be indistinguishable from the general population.[7][8] This phenomenon is thus not isolated to diabetes mellitus type 2 since poor insulin regulation is also found in other conditions such as metabolic syndrome (specifically, when evidence of non alcoholic fatty liver disease or NAFLD is present) and again there is evidence of greater risk here too.[9][10] While there are claims that anabolic steroid abusers are at greater risk[11] (theorized to be due to insulin and IGF exacerbation[12][13]), the only evidence that has been confirmed is that anabolic steroid users are more likely to have hepatocellular adenomas (a benign form of HCC) transform into the more dangerous hepatocellular carcinoma.[14][15]
When hepatocellular adenomas grow to a size of more than 6–8 cm, they are considered cancerous and thus become a risk of hepatocellular carcinoma. Although hepatocellular carcinoma most commonly affects adults, children who are affected with biliary atresia, infantilecholestasis, glycogen-storage diseases, and other cirrhotic diseases of the liver are predisposed to developing hepatocellular carcinoma.
Children and adolescents are unlikely to have chronic liver disease, however, if they suffer from congenital liver disorders, this fact increases the chance of developing hepatocellular carcinoma.[16]
[edit] Pathogenesis
See also: Carcinogenesis
Hepatocellular carcinoma, like any other cancer, develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and/or results in the cell avoiding apoptosis. In particular, chronic infections of hepatitis B and/or C can aid the development of hepatocellular carcinoma by repeatedly causing the body's own immune system to attack the liver cells, some of which are infected by the virus, others merely bystanders.[17] While this constant cycle of damage followed by repair can lead to mistakes during repair which in turn lead to carcinogenesis, this hypothesis is more applicable, at present, to hepatitis C. Chronic hepatitis C causes HCC through the stage of cirrhosis. In chronic hepatitis B, however, the integration of the viral genome into infected cells can directly induce a non-cirrhotic liver to develop HCC. Alternatively, repeated consumption of large amounts of ethanol can have a similar effect. Besides, cirrhosis is commonly caused by alcoholism, chronic hepatitis B and chronic hepatitis C. The toxin aflatoxin from certain Aspergillus species of fungus is a carcinogen and aids carcinogenesis of hepatocellular cancer by building up in the liver. The combined high prevalence of rates of aflatoxin and hepatitis B in settings like China and West Africa has led to relatively high rates of heptatocellular carcinoma in these regions. Other viral hepatitides such as hepatitis A have no potential to become a chronic infection and thus are not related to hepatocellular carcinoma.
[edit] Diagnosis
Hepatocellular carcinoma (HCC) most commonly appears in a patient with chronic viral hepatitis (hepatitis B or hepatitis C, 20%) or/and with cirrhosis (about 80%). These patients commonly undergo surveillance with ultrasound due to the cost-effectiveness.
In patients with a higher suspicion of HCC (such as rising alpha-fetoprotein and des-gamma carboxyprothrombin levels), the best method of diagnosis involves a CT scan of the abdomen using intravenous contrast agent and three-phase scanning (before contrast administration, immediately after contrast administration, and again after a delay) to increase the ability of the radiologist to detect small or subtle tumors. It is important to optimize the parameters of the CT examination, because the underlying liver disease that most HCC patients have can make the findings more difficult to appreciate.
On CT, HCC can have three distinct patterns of growth:
• A single large tumor
• Multiple tumors
• Poorly defined tumor with an infiltrative growth pattern
A biopsy is not needed to confirm the diagnosis of HCC if certain imaging criteria are met.
The key characteristics on CT are hypervascularity in the arterial phase scans, washout or de-enhancement in the portal and delayed phase studies, a pseudocapsule and a mosaic pattern. Both calcifications and intralesional fat may be appreciated.
CT scans use contrast agents, which are typically iodine or barium based. Some patients are allergic to one or both of these contrast agents, most often iodine. Usually the allergic reaction is manageable and not life threatening.
An alternative to a CT imaging study would be the MRI. MRI's are more expensive and not as available because fewer facilities have MRI machines. More important MRI are just beginning to be used in tumor detection and fewer radiologists are skilled at finding tumors with MRI studies when it is used as a screening device. Mostly the radiologists are using MRIs to do a secondary study to look at an area where a tumor has already been detected. MRI's also use contrast agents. One of the best for showing details of liver tumors is very new: iron oxide nano-particles appears to give better results. The latter are absorbed by normal liver tissue, but not tumors or scar tissue.
In a review article of the screening, diagnosis and treatment of hepatocellular carcinoma, 4 articles were selected for comparing the accuracy of CT and MRI in diagnosing this malignancy.[18] Radiographic diagnosis was verified against post-transplantation biopsy as the gold standard. With the exception of one instance of specificity, it was discovered that MRI was more sensitive and specific than CT in all four studies.
[edit] Pathology
Micrograph of hepatocellular carcinoma. Liver biopsy. Trichrome stain.
Macroscopically, liver cancer appears as a nodular or infiltrative tumor. The nodular type may be solitary (large mass) or multiple (when developed as a complication of cirrhosis). Tumor nodules are round to oval, grey or green (if the tumor produces bile), well circumscribed but not encapsulated. The diffuse type is poorly circumscribed and infiltrates the portal veins, or the hepatic veins (rarely).
Microscopically, there are four architectural and cytological types (patterns) of hepatocellular carcinoma: fibrolamellar, pseudoglandular (adenoid), pleomorphic (giant cell) and clear cell. In well differentiated forms, tumor cells resemble hepatocytes, form trabeculae, cords and nests, and may contain bile pigment in cytoplasm. In poorly differentiated forms, malignant epithelial cells are discohesive, pleomorphic, anaplastic, giant. The tumor has a scant stroma and central necrosis because of the poor vascularization.[19]
[edit] Staging
Important features that guide treatment include: -
• size
• spread (stage)
• involvement of liver vessels
• presence of a tumor capsule
• presence of extrahepatic metastases
• presence of daughter nodules
• vascularity of the tumor
MRI is the best imaging method to detect the presence of a tumor capsule.

[edit] Prevention
Since hepatitis B or C is one of the main causes of hepatocellular carcinoma, prevention of this infection is key to then prevent hepatocellular carcinoma. Thus, childhood vaccination against hepatitis B may reduce the risk of liver cancer in the future.[20]
In the case of patients with cirrhosis, alcohol consumption is to be avoided. Also, screening for hemochromatosis may be beneficial for some patients.[21]

[edit] Management
This article's factual accuracy may be compromised due to out-of-date information. Please help improve the article by updating it. There may be additional information on the talk page. (January 2010)
• Liver transplantation to replace the diseased liver with a cadaveric liver or a living donor graft. Historically low survival rates (20%-36%). During 1996–2001 the rate had improved to 61.1% , likely related to adoption of the Milan criteria at US transplantation centers. Expanded Shanghai criteria in China resulted in overall survival and disease-free survival rates similar to the Milan criteria.[22] Studies from the late 2000 obtained higher survival rates ranging from 67% to 91%.[23] If the liver tumor has metastasized, the immuno-suppressant post-transplant drugs decrease the chance of survival. Considering this objective risk in conjunction with the potentially high rate of survival, some recent studies conclude that: "LTx can be a curative approach for patients with advanced HCC without extrahepatic metastasis".[24] For those reasons, and others, it is considered nowadays that patient selection is a major key for success.[25]
• A new receptor tyrosine kinase inhibitor, Sorafenib may be used in patients with advanced hepatocellular carcinoma.[26] Sorafenib is a small molecule that inhibits tumor-cell proliferation and tumor angionesis. It has been shown in a Spanish phase III clinical trial to add two months to the lifespan of late stage HCC patients with well preserved liver function.[27] It also increases the rate of apoptosis in other tumor models. The results indicated that single-agent sorafenib might have a beneficial therapeutic effect. In this study, for instance, the median overall survival was of 9.2 months and the median time to progression was of 5.5 months. Also, the survival benefit represented a 31% relative reduction in the risk of death.[28]
• Surgical resection to remove a tumor together with surrounding liver tissue while preserving enough liver remnant for normal body function. This treatment offers the best prognosis for long-term survival, but unfortunately only 10-15% of patients are suitable for surgical resection. This is often due to extensive disease or poor liver function. Resection in cirrhotic patients carries high morbidity and mortality. The expected liver remnant should be more than 25% of the total size for a non-cirrhotic liver, while that should be more than 40% of the total size for a cirrhotic liver. The overall recurrent rate after resection is 50-60%.
• Percutaneous ethanol injection (PEI) well tolerated, high RR in small (<3 cm) solitary tumors; as of 2005, no randomized trial comparing resection to percutaneous treatments; recurrence rates similar to those for postresection. However a comparative study found that local therapy can achieve a 5-year survival rate of around 60% for patients with small HCC.[29] • Transcatheter arterial chemoembolization (TACE) is usually performed for unresectable tumors or as a temporary treatment while waiting for liver transplant. TACE is done by injecting an antineoplastic drug (e.g. cisplatin) mixed with a radioopaque contrast (e.g. Lipiodol) and an embolic agent (e.g. Gelfoam) into the right or left hepatic artery via the groin artery. As of 2005, multiple trials show objective tumor responses and slowed tumor progression but questionable survival benefit compared to supportive care; greatest benefit seen in patients with preserved liver function, absence of vascular invasion, and smallest tumors. TACE is not suitable for big tumors (>8 cm), presence of portal vein thrombus, tumors with portal-systemic shunt and patients with poor liver function.
• Radiofrequency ablation (RFA) uses high frequency radio-waves to destroy tumor by local heating. The electrodes are inserted into the liver tumor under ultrasound image guidance using percutaneous, laparoscopic or open surgical approach. It is suitable for small tumors (<5 cm). A large randomised trial comparing surgical resection and RFA for small HCC showed similar 4 years-survival and less morbidities for patients treated with RFA.[30] • Focused External Beam Radiation Stereotactic Radiotherapy (SRT) is a technique of using highly focussed radiation to small target volume. SRT has been tried successfully in the liver for treatment of metastases, and currently clinical studies are underway to evaluate its efficacy in treating Hepatocellular Carcinoma. The early results are promising. With the advent of modern computer technology, it is now possible to direct treatment to involved areas of the liver, while sparing normal healthy liver tissue. • Selective internal radiation therapy can be used to destroy the tumor from within (thus minimizing exposure to healthy tissue). There are currently two products available, SIR-Spheres and TheraSphere The latter is an FDA approved treatment for primary liver cancer (HCC) which has been shown in clinical trials to increase survival rate of low-risk patients. SIR-Spheres are FDA approved for the treatment of metastatic colorectal cancer but outside the US SIR-Spheres are approved for the treatment of any non-resectable liver cancer including primary liver cancer. This method uses a catheter (inserted by a radiologist) to deposit radioactive particles to the area of interest. • Intra-arterial iodine-131–lipiodol administration Efficacy demonstrated in unresectable patients, those with portal vein thrombus. This treatment is also used as adjuvant therapy in resected patients (Lau at et, 1999). It is believed to raise the 3-year survival rate from 46 to 86%. This adjuvant therapy is in phase III clinical trials in Singapore and is available as a standard medical treatment to qualified patients in Hong Kong. • Combined PEI and TACE can be used for tumors larger than 4 cm in diameter, although some Italian groups have had success with larger tumours using TACE alone. • High intensity focused ultrasound (HIFU) (not to be confused with normal diagnostic ultrasound) is a new technique which uses much more powerful ultrasound to treat the tumour. Still at a very experimental stage. Most of the work has been done in China. Some early work is being done in Oxford and London in the UK. • Hormonal therapy Antiestrogen therapy with tamoxifen studied in several trials, mixed results across studies, but generally considered ineffective Octreotide (somatostatin analogue) showed 13-month MS v 4-month MS in untreated patients in a small randomized study; results not reproduced. • Adjuvant chemotherapy: No randomized trials showing benefit of neoadjuvant or adjuvant systemic therapy in HCC; single trial showed decrease in new tumors in patients receiving oral synthetic retinoid for 12 months after resection/ablation; results not reproduced. Clinical trials have varying results.[31] • Palliative: Regimens that included doxorubicin, cisplatin, fluorouracil, interferon, epirubicin, or taxol, as single agents or in combination, have not shown any survival benefit (RR, 0%-25%); a few isolated major responses allowed patients to undergo partial hepatectomy; no published results from any randomized trial of systemic chemotherapy. • 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. 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 catheter for post-operative chemotherapy. As with liver resection, the surgeon should have experience with cryosurgical techniques in order to provide the best treatment possible. • Interventional radiology • Agaricus blazei mushrooms inhibited abnormal collagen fiber formation in human hepatocarcinoma cells in an in vitro experiment.[32] • A systematic review assessed 12 articles involving a total of 318 patients with hepatocellular carcinoma treated with Yttrium-90 radioembolization.[33] Excluding a study of only one patient, post-treatment CT evaluation of the tumor showed a response ranging from 29 to 100 % of patients evaluated, with all but two studies showing a response of 71 % or greater. • Gallium maltolate demonstrated in vitro efficacy against several HCC cell lines[34] and produced very encouraging results in a clinical case of advanced HCC that had not responded to therapy with sorafenib.[35] Gallium is known, from gallium scanning results, to be taken up preferentially by many hepatocellular carcinoma tumors.[35] Therapeutic doses of gallium follow the same uptake pathway, causing inhibition of tumor growth and eventual apoptosis of tumor cells, while sparing healthy tissue.[35] [edit] Prognosis The usual outcome is poor, because only 10 - 20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 3 to 6 months.[36] This is partially due to late presentation with large tumours, but also the lack of medical expertise and facilities. However, survival can vary, and occasionally people will survive much longer than 6 months. The prognosis for metastatic or unresectable hepatocellular carcinoma has recently improved due to the approval of nexavar for advanced hepatocellular carcinoma. [edit] Epidemiology HCC is one of the most common tumors worldwide. The epidemiology of HCC exhibits two main patterns, one in North America and Western Europe and another in non-Western countries, such as those in sub-Saharan Africa, central and Southeast Asia, and the Amazon basin. Males are affected more than females usually and it is most common between the age of 30 to 50,[1] Hepatocellular carcinoma causes 662,000 deaths worldwide per year[38] about half of them in China. [edit] Africa and Asia In some parts of the world, such as sub-Saharan Africa and Southeast Asia, HCC is the most common cancer, generally affecting men more than women, and with an age of onset between late teens and 30s. This variability is in part due to the different patterns of hepatitis B and hepatitis C transmission in different populations - infection at or around birth predispose to earlier cancers than if people are infected later. The time between hepatitis B infection and development into HCC can be years, even decades, but from diagnosis of HCC to death the average survival period is only 5.9 months according to one Chinese study during the 1970-80s, or 3 months (median survival time) in Sub-Saharan Africa according to Manson's textbook of tropical diseases. HCC is one of the deadliest cancers in China where chronic hepatitis B is found in 90% of cases. In Japan, chronic hepatitis C is associated with 90% of HCC cases. Food infected with Aspergillus flavus (especially peanuts and corns stored during prolonged wet seasons) which produces aflatoxin poses another risk factor for HCC. [edit] North America and Western Europe Most malignant tumors of the liver discovered in Western patients are metastases (spread) from tumors elsewhere.[1] In the West, HCC is generally seen as a rare cancer, normally of those with pre-existing liver disease. It is often detected by ultrasound screening, and so can be discovered by health-care facilities much earlier than in developing regions such as Sub-Saharan Africa. Acute and chronic hepatic porphyrias (acute intermittent porphyria, porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria) and tyrosinemia type I are risk factors for hepatocellular carcinoma. The diagnosis of an acute hepatic porphyria (AIP, HCP, VP) should be sought in patients with hepatocellular carcinoma without typical risk factors of hepatitis B or C, alcoholic liver cirrhosis or hemochromatosis. Both active and latent genetic carriers of acute hepatic porphyrias are at risk for this cancer, although latent genetic carriers have developed the cancer at a later age than those with classic symptoms. Patients with acute hepatic porphyrias should be monitored for hepatocellular carcinoma. [edit] Society and culture [edit] Awareness The Jade Ribbon Campaign is used for awareness of liver cancer and hepatitis B in the Pacific Islands, where such illnesses are more widespread than elsewhere. [edit] Famous people • Johannes Brahms famous late Romantic German composer. Died April 3, 1897 of liver cancer. • Morihei Ueshiba founder of the Japanese martial art of aikido. Died in 1969 of hepatocellular carcinoma. • John Coltrane Jazz musician. Died in 1967 from liver cancer. • Jim Hutton Died in 1979 from liver cancer. • Mickey Mantle Hall of Fame Baseball player with the New York Yankees. • Chris LeDoux Country Music Hall of Fame legend, and former Pro Rodeo rider. • Munetaka Higuchi Drummer for Japanese heavy metal band Loudness, died in 2008 of hepatocellular carcinoma. • Mick Ronson British Rock'n'Roll guitarist who died in 1993 of hepatocellular carcinoma. • Erich Honecker former leader of East Germany who died in 1994 in exile. • Ray Charles famous recording soulful music artist, Rock And Roll Hall of Fame, died on June 10, 2004. • Sun Yat-sen Father of the Nation in mainland China and in Taiwan • Édith Piaf French singer and cultural icon who "is almost universally regarded as France's greatest popular singer.", died on 10 or 11 October 1963. • Gregory Hines Professional dancer, film actor, and choreographer. Died in August 2003 of liver cancer. • Dave Thomas Founder of Wendys, died in 2002 of liver cancer. • Joan Finney Governor of Kansas (1991–1995) died of liver cancer in 2001 [edit] Research Current research includes the search for the genes that are disregulated in HCC,[39] protein markers,[40] non-coding RNAs (such as TUC338)[41] and other predictive biomarkers.[42][43] As similar research is yielding results in various other malignant diseases, it is hoped that identifying the aberrant genes and the resultant proteins could lead to the identification of pharmacological interventions for HCC.[44] [edit] Abbreviations HCC, hepatocellular carcinoma; TACE, transarterial embolization/chemoembolization; PFS, progression-free survival; PS, performance status; HBV, hepatitis B virus; PEI, percutaneous ethanol injection; RFA, radiofrequency ablation; RR, response rate; MS, median survival. Nguồn: http://en.wikipedia.org/wiki/Hepatocellular_carcinoma Recurrence of hepatocellular carcinoma after surgery. Yamamoto J, Kosuge T, Takayama T, Shimada K, Yamasaki S, Ozaki H, Yamaguchi N, Makuuchi M. Source Department of Surgery, National Cancer Centre Hospital, Tokyo, Japan. Abstract A total of 386 patients who underwent complete resection of hepatocellular carcinoma over an 8-year period were assessed retrospectively for tumour recurrence. Some 219 (56.7 per cent) of the patients developed recurrence. Patients with a greater degree of cirrhosis showed a longer interval to recurrence; the median (range) interval until recurrence was 7.9 (1.8-84.2) months in patients with a normal liver, 13.4 (2.0-79.5) months in those with chronic hepatitis and 16.7 (1.5-73.1) months in those with cirrhosis. Intrahepatic recurrence was observed more frequently in either the same (26.4 per cent) or the adjacent (24.8 per cent) Healey segment than in the lobe contralateral to the primary tumour (17.8 per cent). The presence of portal venous invasion and/or intrahepatic metastasis, underlying liver cirrhosis and perioperative blood transfusion were determined to be independent predictors of recurrence by multivariate analysis. Because intrahepatic spread of hepatocellular carcinoma occurs in a segment-by-segment manner, surgeons should use an anatomically wide resection within the hepatic functional reserve. Nguồn: http://www.ncbi.nlm.nih.gov/pubmed/8983610