Dr. Keith E. Stuart is a medical oncologist specializing in the study and treatment of cancers involving the gastrointestinal tract, with a special interest in tumors involving the liver. He was educated at Harvard University (graduating magna cum laude) and Albert Einstein College of Medicine and did his medical training at the New England Deaconess Hospital.
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
The most commonly used systemic chemotherapeutic agents are doxorubicin
(Adriamycin) and 5-fluorouracil (5 FU). These drugs are used together or in
combination with new experimental agents. These drugs are quite toxic and
results have been disappointing. A few studies suggest some benefit with
tamoxifen (Nolvadex) but more studies show no advantage at all. Octreotide (Sandostatin) given as an injection was shown in one study to slow down the progression of large liver cancer tumors, but so far, no other studies have confirmed this benefit. Recent studies suggest that combinations of drugs such as gemcitabine, cisplatin, or oxaliplatin can shrink the tumors in some people.
Biotherapy
One of the most important recent advances in the filed of treating liver cancer has been the understanding of the genetic makeup of these tumors, as well as the cancer cells' reliance upon blood vessels and molecules produced in the body that can help them grow. Many cancers grow by causing the development and recruitment of tiny new blood vessels to feed the tumor and enable it to spread to other parts of the body. This is called angiogenesis, and this has become a very hot field in oncology and pharmaceutical development over the past decade. One drug, bevacizumab, has been approved for use in many cancers such as colon, lung, and breast, and is known to help standard chemotherapy shrink and control other types of cancer. It might be helpful in liver cancer as well, and similar drugs are still being investigated.
The best success so far has been with the oral drug sorafenib (Nexavar). This is a pill designed to block several components of the angiogenesis pathway, as well as other growth signals for individual cancer cells. Large studies have shown that patients taking this drug for advanced liver cancer live significantly longer than those taking a placebo pill. Although the difference was not very long (three months) and is shorter in sicker patients, this is still the first study in decades to show that there is a reliable way to slow down this cancer's growth and to prolong patients' lives. Sorafenib is thus the first, and so far, only, drug to be approved by the U.S. FDA to treat liver cancer. Current studies are under way to see if the drug works better when combined with other types of chemotherapy.
Hepatic arterial infusion of chemotherapy
The normal liver gets its blood supply from two sources: the portal vein
(about 70%) and the hepatic artery (30%). However, liver cancer gets its blood
exclusively from the hepatic artery. Making use of this fact, investigators have
delivered chemotherapy agents selectively through the hepatic artery directly to
the tumor. The theoretical advantage is that higher concentrations of the agents
can be delivered to the tumors without subjecting the patients to the systemic
toxicity of the agents.
In reality, however, much of the chemotherapeutic agents does end up in the
rest of the body. Therefore, selective intra-arterial chemotherapy can cause the
usual systemic (body-wide) side effects. In addition, this treatment can result
in some regional side effects, such as inflammation of the gallbladder
(cholecystitis), intestinal and stomach ulcers, and inflammation of the pancreas
(pancreatitis). Liver cancer patients with advanced cirrhosis may develop liver failure
after this treatment. Well then, what is the benefit of intra-arterial
chemotherapy? The bottom line is that fewer than 50% of patients will experience
a reduction in tumor size.
An interventional radiologist (one who does therapeutic procedures) usually
carries out this procedure. The radiologist must work closely with an oncologist
(cancer specialist), who determines the amount of chemotherapy that the patient
receives at each session. Some patients may undergo repeat sessions at six- to 12-week intervals. This procedure is done with the help of fluoroscopy (a type of
X-ray) imaging. A catheter (long, narrow tube) is inserted into the femoral
artery in the groin and is threaded into the aorta (the main artery of the
body). From the aorta, the catheter is advanced into the hepatic artery. Once
the branches of the hepatic artery that feed the liver cancer are identified,
the chemotherapy is infused. The whole procedure takes one to two hours, and
then the catheter is removed.
The patient generally stays in the hospital overnight for observation. A
sandbag is placed over the groin to compress the area where the catheter was
inserted into the femoral artery. The nurses periodically check for signs of
bleeding from the femoral artery puncture. They also check for the pulse in the
foot on the side of the catheter insertion to be sure that the femoral artery is
not blocked as a result of the procedure. (Blockage would be signaled by the
absence of a pulse.)
Generally, the liver enzyme tests increase (get worse) during the two to three days
after the procedure. This worsening of the liver tests is actually due to death
of the tumor (and some non-tumor) cells. The patient may experience some
post-procedure abdominal pain and low-grade fever. However, severe abdominal
pain and vomiting suggest that a more serious complication has developed.
Imaging studies of the liver are repeated in six to 12 weeks to assess the size of
the tumor in response to the treatment. For more, please read the
chemotherapy
article.
Abdominal pain is pain in the belly and can be acute or chronic. Causes include inflammation, distention of an organ, and loss of the blood supply to an organ. Abdominal pain can reflect a major problem with one of the organs in the abdomen such as the appendix, gallbladder, large and small intestine, pancreas, liver, colon, duodenum, and spleen.
Cirrhosis of the liver refers to a disease in which normal liver cells are replaced by scar tissue caused by alcohol and viral hepatitis B and C. This disease leads to abnormalities in the liver's ability to handle toxins and blood flow, causing internal bleeding, kidney failure, mental confusion, coma, body fluid accumulation, and frequent infections. Symptoms include yellowing of the skin, itching, and fatigue.
Hepatitis C is an inflammation of the liver due to the hepatitis C virus (HCV), which is usually spread by
blood transfusion, hemodialysis, and needle sticks, especially with intravenous
drug abuse. Chronic hepatitis C may be treated with interferon, usually in combination with anti-virals.
Cholesterol is naturally produced by the body, and is a building block for cell membranes and hormones. Low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol, conversely, high-density lipoprotein (HDL) cholesterol is the "good" cholesterol. High cholesterol treatment includes lifestyle changes (diet and exercise), and medications such as statins, bile acid resins, and fibric acid derivatives.
Jaundice is a yellowish staining of the skin and whites of the eyes (sclerae) with bilirubin, the pigment found in bile. Jaundice can be an indicator of liver or gallbladder disease, or it may result from the rupture of red blood cells (hemolysis).
Alcoholism is a disease that includes alcohol craving and continued drinking despite repeated alcohol-related problems, such as losing a job or getting into trouble with the law.
The hepatitis B virus is a unique, coated DNA virus belonging to the Hepadnaviridae family of viruses. The course of the virus is determined primarily by the age at which the infection is acquired and the interaction between the virus and the body's immune system. Successful treatment is associated with a reduction in liver injury and fibrosis (scarring), a decreased likelihood of developing cirrhosis and its complications, including liver cancer, and a prolonged survival.
Ascites, the accumulation of fluid in the abdominal cavity is most commonly caused by cirrhosis of the liver. Some of the other causes of ascites include portal hypertension, congestive heart failure, blood clots, and pancreatitis. The most common symptoms include increased abdominal girth and size, abdominal bloating, and abdominal pain. Treatment depends on the cause of ascites.
Polycythemia (elevated red blood cell count) causes are either primary (aquired or genetic mutations) or secondary (diseases, conditions, high altitude). Treatment of polycythemia depends on the cause.
Cancer is a disease caused by an abnormal growth of cells, also called malignancy. It is a group of 100 different diseases, and is not contagious. Cancer can be treated through chemotherapy, a treatment of drugs that destroy cancer cells.
Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis (NASH), to cirrhosis (irreversible, advanced scarring of the liver). All of the stages of NAFLD have in common the accumulation of fat (fatty infiltration) in the liver cells (hepatocytes).
Insulin resistance is the diminished ability of cells to respond to the action of insulin in transporting glucose (sugar) from the bloodstream into muscle and other tissues. Causes of insulin can include conditions such as stress, obesity, metabolic syndrome, and steroid use. Some of the risk factors for insulin resistance include fatty liver, heart disease, strokes, peripheral vascular disease, high cholesterol, and smoking. Treatment for insulin resistance are lifestyle changes and if necessary, medication.
Hepatitis is most often viral, due to infection with one of the hepatitis viruses (A, B, C, D, E, F (not confirmed), and G) or another virus (such as those that cause infectious mononucleosis, cytomegalovirus disease). The main nonviral causes of hepatitis are alcohol and drugs. Many patients infected with hepatitis A, B, and C have few or no symptoms of illness. For those who do develop symptoms of viral hepatitis, the most common are flu- like symptoms including: loss of appetite, nausea, vomiting, fever, weakness, tiredness, and aching in the abdomen. Treatment of viral hepatitis is dependant on the type of hepatitis.
Hereditary hemochromatosis (iron overload) is an inherited disorder in which there is excessive accumulation of iron in the body. Individuals may have no symptoms or signs, or they can have severe symptoms and signs of iron overload. The most effective treatment for hemochromatosis is therapeutic phlebotomy.
Primary Biliary Cirrhosis is a chronic disease characterized by progressive inflammation and destruction of small bile ducts within the liver. The bile ducts transport bile from the liver to the intestine for the absorption of fat and elimination of waste products. The causes of Primary Biliary Cirrhosis may involve autoimmunity, infection, or genetic predisposition, acting alone or in combination. There are many medications and treatment options available for those with this and other associated diseases of Primary Biliary Cirrhosis.
The liver is the largest solid organ in the body, and is actually an gland. The liver has a wide variety of critical functions such as manufacturing proteins and metabolizing fats and carbohydrates. The liver also eliminates harmful biochemical waste products from the body (alcohol, drugs, toxins). The liver secretes bile that aids in digestion. Examples of diseases of the liver include cirrhosis, hepatitis, cancer, and fatty liver. Symptoms of liver disease include bleeding, easy bruising, edema, fatigue, and jaundice.
Mold exposure may cause symptoms in people who are sensitive to molds. Symptoms of mold allergy include sneezing, runny nose, wheezing, coughing, redness of the eyes, and rash. Prevent mold growth by keeping indoor humidity low, between 30%-50%, using bathroom fans when showering, repairing plumbing leaks quickly, and using an air conditioner during humid seasons.
Primary sclerosing cholangitis (PSC) is a chronic, progressive disease of the bile ducts that channel bile from the liver into the intestines. There is an association between primary sclerosing cholangitis and ulcerative colitis and Crohn's disease. Symptoms of primary sclerosing cholangitis include abnormal liver blood tests, itching, fatigue, and jaundice. Primary sclerosing cholangitis is treated with medications and in some cases, liver transplant.
Anabolic steroids are synthetic substances that are related to testosterone and promote skeletal muscle growth and the development of male sexual characteristics in both men and women. In the 1930s, it was discovered that anabolic steroids could promote skeletal muscle growth in lab animals, which lead to anabolic steroid abuse by bodybuilders and weight lifters.
Digestion is the complex process of turning food you eat into the energy you need to survive. The digestive process also involves creating waste to be eliminated, and is made of a series of muscles that coordinate the movement of food.
Alpha-1 antitrypsin deficiency is an inherited disorder that may cause liver and lung disease in adults. Signs and symptoms include shortness of breath, wheezing, weight loss, respiratory infections, fatigue, vision abnormalities. Advanced lung disease from alpha-1 antitrypsin deficiency include emphysema. Liver damage from alpha-1 antitrypsin deficiency causes a swollen abdomen, swollen legs or feet, and jaundice.
Hepatitis A and hepatitis B are the two most commnon viruses that infect the liver. Hepatitis A and Hepatitis B can be prevented and treated with immunizations (vaccinations) such as Havrix, Vaqta, Twinrix, Comvax, Pediarix, and hepatitis b immune globulin (HBIG).
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