Gestational Trophoblastic Disease

What Is Gestational Trophoblastic Disease?

Gestational trophoblastic disease (GTD) is a group of rare tumors that involve abnormal growth of cells inside a woman's uterus. GTD does not develop from cells of the uterus like cervical cancer or endometrial (uterine lining) cancer do. Instead, these tumors start in the cells that would normally develop into the placenta during pregnancy. (The term "gestational" refers to pregnancy.)

GTD begins in the layer of cells called the trophoblast that normally surrounds an embryo. (Tropho- means "nutrition," and -blast means "bud" or "early developmental cell.") Early in normal development, the cells of this layer form tiny, finger-like projections known as villi. These villi grow into the lining of the uterus. In time, the trophoblast layer develops into the placenta, the organ that protects and nourishes a growing fetus.

Most GTDs are benign (non cancerous) and they don't invade deeply into body tissues or spread to other parts of the body. But some are cancerous. Because not all of these tumors are cancerous, this group of tumors may be referred to as gestational trophoblastic disease, gestational trophoblastic tumors, or gestational trophoblastic neoplasia. (The word neoplasia simply means "new growth.")

All forms of GTD can be treated. And in most cases the treatment produces a complete cure.

Types of gestational trophoblastic disease

The main types of gestational trophoblastic diseases are:

• hydatidiform mole (complete or partial)
• invasive mole
• choriocarcinoma
• placental site trophoblastic tumor

Hydatidiform mole

The most common form of GTD is called a hydatidiform mole, also known as a molar pregnancy. The moles are actually villi that have become swollen with fluid. The swollen villi grow in clusters that look like bunches of grapes. Although this is called a molar "pregnancy," it is not possible for a normal baby to form. Hydatidiform moles are not cancerous, but they may develop into cancerous GTDs.

There are 2 types of hydatidiform moles: complete and partial.

A complete hydatidiform mole most often develops when either 1 or 2 sperm cells fertilize an "empty" egg cell (a cell that contains no nucleus or DNA). All the genetic material comes from the father's sperm cell. Therefore, there is no fetal tissue.

Surgery can totally remove most complete moles, but in as many as 1 in 5 women there will be some persistent molar tissue (see "Persistent gestational trophoblastic disease" below). Most often this is an invasive mole, but in rare cases it is a choriocarcinoma, a malignant (cancerous) form of GTD. In either case it will require further treatment.

A partial hydatidiform mole develops when 2 sperm fertilize a normal egg. These tumors contain some fetal tissue, but this is often mixed in with the trophoblastic tissue. It is important to know that a viable (able to live) fetus is not being formed.

Partial moles are usually completely removed by surgery. Only a small number of women with partial moles need further treatment after initial surgery. Partial moles rarely develop into malignant GTD.

Persistent gestational trophoblastic disease

This is not a separate type of GTD, but a term used to describe GTD that is not cured by initial surgery. Persistent GTD occurs when the tumor has grown into the muscle layer of the uterus (myometrium). Surgery to scrape the inside of the uterus (called suction dilation and curettage, or D&C) removes only the inner layer of the uterus. It does not remove the tumor deep in the muscular wall of the uterus.

Most cases of persistent GTD are invasive moles, although in rare cases they are choriocarcinomas or placental site trophoblastic tumors (see below).

Invasive mole

An invasive mole (formerly known as chorioadenoma destruens) is a hydatidiform mole that grows into the myometrium. Invasive moles can be either complete or partial, but complete moles become invasive much more often than partial moles. Invasive moles develop in a little less than 1 out of 5 women who have had a complete mole removed. The risk of developing an invasive mole in these women increases if:

• There is a long time (more than 4 months) between the last menstrual period and treatment.
• The uterus has become very large.
• The woman is older than 40 years.
• The woman has had GTD in the past.

Because these moles have grown into the uterine muscle layer, they aren't completely removed by surgery. Invasive moles sometimes go away on their own, but most require treatment with chemotherapy.

A tumor or mole that grows completely through the myometrium may result in bleeding, which can be life threatening.

In about 15% of cases, the tumor spreads (metastasizes) to other parts of the body, most often the lungs.

Choriocarcinoma

Choriocarcinoma is a malignant form of GTD. It is much more likely than other types of GTD to grow quickly and spread to organs away from the uterus.

Although choriocarcinoma most often develops from a complete hydatidiform mole, it can also occur after a partial mole, a normal pregnancy, or a pregnancy in which the fetus is lost early.

Rarely, choriocarcinomas can develop in other parts of the body in both men and women. These are not related to pregnancy. They may develop in the ovaries, testicles, chest, or abdomen. In these cases, choriocarcinoma is usually mixed with other types of cancer, forming a mixed germ cell tumor. Choriocarcinomas starting in these locations are not considered to be gestational and are not discussed in this document. Non-gestational choriocarcinoma tends to be less responsive to chemotherapy and has a less favorable prognosis (outlook) than gestational choriocarcinoma. For more information, see the American Cancer Society documents, Ovarian Cancer and Testicular Cancer.

Placental site trophoblastic tumor

Placental site trophoblastic tumor (PSTT) is a very rare form of GTD that develops where the placenta attaches to the uterus. This tumor most often develops after a normal pregnancy or abortion, but it may also develop after a complete or partial mole is removed.

Most PSTTs do not spread to other sites in the body. But these tumors have a tendency to invade the muscle layer of the uterus.

Although most forms of GTD are very sensitive to chemotherapy drugs, PSTTs are not. Instead, they are treated with surgery, aimed at completely removing disease.

Do We Know What Causes Gestational Trophoblastic Disease?

All forms of gestational trophoblastic disease (GTD) begin after an egg cell is fertilized by a sperm cell. Normally, the sperm and egg cells each provide a set of 23 chromosomes (bits of DNA that contain our genes) to create a cell with 46 chromosomes. This cell will start dividing to eventually become a fetus.

In complete hydatidiform moles, the problem most often arises when a sperm cell fertilizes an abnormal egg cell that contains no chromosomes. The reason the egg contains no chromosomes is not known. After fertilization, the chromosomes from the sperm duplicate themselves, so there are 2 copies of identical chromosomes that both come from the sperm. This situation prevents normal development, and no fetus is formed. Instead, a complete hydatidiform mole develops. Less often, a complete mole forms when an abnormal egg without any chromosomes is fertilized by 2 sperm cells. Again, there are 2 copies of the father's chromosomes and none from the mother, and no fetus forms.

Partial hydatidiform moles result when 2 sperm cells fertilize a normal egg at the same time. The fertilized egg contains 3 sets of chromosomes (69) instead of the usual 2 sets (46). An embryo with 3 sets of chromosomes cannot grow into a fully developed infant. This situation leads to an abnormal (malformed) fetus along with some normal placental tissue and a partial hydatidiform mole.

Invasive moles are hydatidiform moles that begin to grow into the muscle layer of the uterus. They develop more often from complete moles than from partial moles. It's not clear exactly what causes this to happen.

Most choriocarcinomas develop from persistent hydatidiform moles (usually complete moles). They can also develop when bits of tissue are left behind in the uterus after spontaneous (miscarriage) or intended abortion or after delivery of a baby following an otherwise normal pregnancy. Researchers have found changes in certain genes that are commonly found in choriocarcinoma cells, although it is not clear what causes these changes.

Can Gestational Trophoblastic Disease Be Found Early?

The best way to find gestational trophoblastic disease (GTD) early is to have routine prenatal care by a qualified health care professional. Usually, a woman has certain signs and symptoms, such as vaginal bleeding, that suggest something may be wrong. (These symptoms are discussed in the section, "How is gestational trophoblastic disease diagnosed?") These signs will prompt the doctor to look for the cause of trouble.

Often, moles or tumors cause swelling in the uterus that seems like a normal pregnancy. But a doctor can usually tell that this isn't a normal pregnancy during a routine ultrasound exam. A blood test for human chorionic gonadotropin (HCG) can also show that something is abnormal. This substance is normally elevated in the blood of pregnant women, but it may be very high if there is GTD.

Fortunately, even if it is not detected early, GTD is a very treatable (and usually curable) form of cancer.

Because women who have had one molar pregnancy are at increased risk, doctors can be especially careful in checking their future pregnancies with beta-HCG tests and transvaginal or pelvic sonograms. (These tests are described in the next section.)

How Is Gestational Trophoblastic Disease Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

The first part of this section describes the various types of treatments used for gestational trophoblastic disease (GTD). This information is followed by a description of the most common approaches used for these cancers based on the type and classification of GTD.

Making treatment decisions

After GTD is diagnosed and staged, your medical team can recommend one or more treatment options. Choosing a treatment plan is an important decision, so be sure to take time and think about all of the choices.

No matter what type or stage of GTD a woman has, treatment is available. Your treatment choice depends on many factors. The location and the extent of the disease are very important. So too are the type of GTD present, the level of human chorionic gonadotropin (HCG), duration of the disease, sites of metastasis if any, and the extent of prior treatment. In selecting a treatment plan, you and your medical team will also consider your age, general state of health, and personal preferences.

It is important to begin treatment as soon as possible after GTD has been detected. The main methods of treatment are surgery, chemotherapy, and radiation therapy. Sometimes the best approach uses a combination of 2 or more of these methods.

Gastrointestinal Stromal Tumors

What Are Gastrointestinal Stromal Tumors?

The Gastrointestinal (Digestive) System

The digestive system processes food for energy and rids the body of solid waste. After food is chewed and swallowed, it enters the esophagus, a tube that carries food through the neck and chest to the stomach. The esophagus joins the stomach just beneath the diaphragm (the breathing muscle under the lungs).

The stomach is a sac-like organ that holds food and begins the digestive process by secreting gastric juice. The food and gastric juices are mixed into a thick fluid called chyme that is then emptied into the small intestine. The small intestine continues breaking down the food and absorbs most of the nutrients. It is the longest section of the gastrointestinal (GI) tract, measuring over 20 feet.

The small intestine joins the colon, a muscular tube of about 5 feet long. The colon absorbs water and mineral nutrients from the food matter and serves as a storage place for waste. The waste left after this process goes into the rectum. From there it passes out of the body through the anus.

Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are fairly rare tumors of the GI tract. In the past, some were thought to start in the muscle layer of the GI tract, and some were thought to start in nerve cells. This is because the tumor cells look like muscle or nerve cells under the microscope. They were often thought to be related to sarcomas -- cancers that start in the muscle, bones of the legs and arms, or other connective tissues.

We now know that these tumors are in fact not true muscle or nerve tumors. Most doctors believe they start in special cells found in the wall of the GI tract, called the interstitial cells of Cajal (ICCs), or in very early cells that can develop into ICCs.

ICCs are part of the autonomic nervous system, which sends signals to the GI tract. Some have called these cells the "pacemakers" of the GI tract. The nerve signals they send cause muscles of the digestive organs to contract, which helps to move food and liquid through the GI tract.

Not all GISTs are cancerous. Some are benign -- they don't invade into other areas or spread to other parts of the body. Ways to try to determine whether a GIST is benign or cancerous are discussed further in the section "How Are Gastrointestinal Stromal Tumors Diagnosed?"

Difference Between GISTs and Other GI Tract Tumors

Cancers can occur anywhere in the GI tract from the esophagus to the anus.

Most cancers in the GI tract start in glandular cells lining the GI tract. These cells can develop into adenomas (non-cancerous tumors of gland cells) or adenocarcinomas (cancers of gland cells).

In some parts of the GI tract, mostly in the upper part of the esophagus and at the end of the anus, there are flat cells called squamous cells. These are the same type of cells that are found on the surface of the skin. Cancers starting in these cells are called squamous cell carcinomas.

Neuroendocrine cancers such as carcinoid tumors are a relatively uncommon type of cancer that can also occur in the gastrointestinal tract. They develop from neuroendocrine cells, which have some features of nerve cells and in other ways resemble hormone producing (endocrine) cells.

GISTs are different from these more common GI tract cancers, in large part because they start in different types of cells. GISTs are also quite different in their prognosis (outlook for survival) and their treatment. For these reasons, doctors need to figure out whether a patient has a GIST, an adenoma, an adenocarcinoma, a neuroendocrine cancer, some other type of tumor, or a non-cancerous condition.

It is important for patients to understand that GISTs are not the same as other, more common types of GI tumors. By learning more about GISTs, patients can better take part in their health care and make informed decisions about treatment options.

Do We Know What Causes Gastrointestinal Stromal Tumors?

In recent years, scientists have made great progress in learning how certain changes in DNA can cause normal cells to become cancerous. DNA is the chemical that carries the instructions for nearly everything our cells do. We look like our parents because they are the source of our DNA. But DNA affects more than our outward appearance. Some genes (parts of our DNA) contain instructions for controlling when cells grow and divide.

Every time a cell prepares to divide into 2 new cells, it must duplicate its DNA. This process is not perfect and, sometimes, copying errors (mutations) occur, especially if the cells are growing rapidly.

Certain genes that promote cell growth and division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. We know that cancers can be caused by DNA mutations (defects) that turn on oncogenes or turn off tumor suppressor genes.

Some people with certain types of cancer have DNA mutations they inherited from a parent, which increased their risk for the disease. There are a few families that have GISTs caused by inherited mutations. But most DNA mutations related to GISTs are not inherited. These mutations occur for no apparent reason.

We do not know the exact cause of GIST. However, we do know that there is a change in an oncogene called c-kit of almost all patients with GIST. The c-kit gene is found in all cells of the body. It leads to the formation of a protein called KIT. This protein causes the cell to grow and divide. Usually the c-kit gene is inactive. It is only activated if there is a need for more interstitial cells of Cajal (ICCs). In most GISTs the c-kit gene is mutated and is always active. This may explain why the cancer forms. The cells are always growing and dividing. In families that have many members with GISTs, doctors have found inherited mutations of the c-kit gene.

In some GISTs, a different gene mutation causes the cell to make too much of a protein called PDGFRA. This has the same effect on the cell as does KIT.

These proteins (KIT and PDGFRA) act as enzymes called tyrosine kinases. These are important in the diagnosis and treatment of GIST.

Can Gastrointestinal Stromal Tumors (GIST) Be Found Early?

Screening refers to tests and exams used to find a disease such as cancer in people who do not have any symptoms. The American Cancer Society has recommendations for screening tests to find several types of cancer as early as possible. But because GISTs occur so rarely, no effective screening tests have been found, so routine testing of people without any symptoms is not recommended.

GISTs may be found early by chance. Sometimes they are seen on an exam for another problem, such as during colonoscopy to look for colon cancer. Or a GIST may be seen on an imaging test, such as a CT scan or barium study, performed for another reason, but this is very uncommon.

GISTs may also be found incidentally (unexpectedly) during abdominal surgery for another problem.

How Are Gastrointestional Stromal Tumors Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

Gastrointestinal Carcinoid Tumors

What Is a Gastrointestinal Carcinoid Tumor?

The Gastrointestinal (Digestive) System

The digestive system processes food for energy and rids the body of solid waste. After food is chewed and swallowed, it enters the esophagus, a tube that carries food through the neck and chest to the stomach. The esophagus joins the stomach just beneath the diaphragm (the breathing muscle under the lungs). The stomach is a sac-like organ that holds food and begins the digestive process by secreting gastric juice. The food and gastric juices are mixed into a thick fluid, which is then emptied into the small intestine.

The small intestine continues breaking down the food and absorbs most of the nutrients. It is the longest section of the gastrointestinal (GI) tract, measuring more than 20 feet. The small intestine then joins the colon (large intestine). This is a wider, muscular tube about 5 feet long. The appendix is found near the junction of small intestine and colon. The colon absorbs water and mineral nutrients from the food matter and serves as a storage place for waste. The waste left after this process goes into the rectum. From there it passes out of the body through the anus.

The Diffuse Neuroendocrine System

Carcinoid tumors start from cells of the diffuse neuroendocrine system. This system consists of cells that are like nerve cells in certain ways and like hormone-making endocrine cells in other ways. These cells do not form an actual organ like the adrenal or thyroid glands. Instead, they are scattered throughout other organs like the esophagus, stomach, pancreas, intestines, and lungs. When neuroendocrine tumors develop in the pancreas, they are known as pancreatic islet cell tumors. Because of the size of the digestive system, it has the most neuroendocrine cells of any organ. This may explain why carcinoid tumors most often start in the digestive system.

Neuroendocrine cells help control the release of digestive juices and the speed at which food moves in the GI tract, and they may help control the growth of other types of digestive system cells.

Carcinoid (Neuroendocrine) Tumors and Cancers

Like most cells of the body, GI tract neuroendocrine cells sometimes go through certain changes that cause them to grow too much and form tumors. These are known as neuroendocrine tumors and neuroendocrine cancers.

In 2000, the World Health Organization (WHO) revised its classification of carcinoids. Before that time, most abnormal growths of neuroendocrine cells were called carcinoids. The WHO now divides these growths into neuroendocrine tumors (growths that are benign or have uncertain potential to spread to other parts of the body, and which may also be called carcinoids) and neuroendocrine cancers (which spread to other parts of the body). The WHO also subdivides neuroendocrine cancers (also known as neuroendocrine carcinomas) into well differentiated (tending to be less aggressive) and poorly differentiated (tending to be more aggressive) groups. Some doctors do not use this new terminology and use the term carcinoid to refer to either neuroendocrine tumors or well differentiated neuroendocrine cancers.

Neuroendocrine tumors and cancers act like the cells they come from. They often release certain hormone-like substances into the bloodstream. In about 1 out of 10 people with carcinoid tumors, they spread and grow very large and release high amounts of those hormones. This can cause symptoms such as facial flushing (redness and warm feeling), wheezing, diarrhea, and a fast heartbeat. These symptoms are grouped together and called the carcinoid syndrome. While most types of cancer cause symptoms only in the organs they start in or spread to, neuroendocrine tumors and neuroendocrine cancers can cause symptoms throughout the body.

Most tumors in the GI tract start from different glandular cells (the kind of gland cell that produce mucus rather than hormones) of the inner lining of the digestive system. These tumors can be either adenomas (benign) or adenocarcinomas (malignant). They are quite different from carcinoid tumors in their symptoms, their prognosis (course of the disease and outlook for survival), and their treatment. For these reasons, it is important for doctors to find out whether a patient has a neuroendocrine tumor or neuroendocrine cancer, an adenoma, an adenocarcinoma, some other type of tumor, or a non-cancerous condition. And it is important for patients to understand that neuroendocrine tumors and neuroendocrine cancers are not the same as other, more common types of GI tract tumors.

In general, neuroendocrine tumors and neuroendocrine cancers grow more slowly than other cancers in the GI tract. But there is a wide range among these tumors in how they grow and whether or not they spread to other areas. This depends to some extent on which part of the body the tumor starts in.

Do We Know What Causes Gastrointestinal Carcinoid Tumors?

Researchers have made great progress in understanding how certain changes in DNA can cause normal cells to become cancerous. DNA is the chemical in each cell that carries our genes - the instructions for how our cells function. We resemble our parents because they are the source of our DNA. But DNA affects more than our outward appearance. Some genes contain instructions for controlling when our cells grow and divide. Certain genes that promote cell division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA mutations (defects) that turn on oncogenes or turn off tumor suppressor genes.

Mutations of 2 tumor suppressor genes are responsible for many inherited cases of neuroendocrine tumors and neuroendocrine cancers. Most inherited cases are due to changes in the MEN1 gene. A smaller number are caused by inherited changes in the NF1 gene.

Most cases of neuroendocrine tumors and neuroendocrine cancers are caused by DNA mutations of oncogenes or tumor suppressor genes that occur after a person is born, rather than having been inherited. These mutations often affect the MEN1 gene, the same gene that is responsible for most familial neuroendocrine tumors and neuroendocrine cancers. In many other types of cancer, researchers have shown that these acquired mutations are the result of cancer-causing chemicals in our environment, diet, or tobacco smoke. Relatively little is known, however, about factors that cause new mutations in genes that lead to neuroendocrine tumors and neuroendocrine cancers.

Doctors do know that carcinoid tumors start out very small and grow slowly. When patients have parts of their stomach or small intestine removed to treat other diseases, taking a close look under the microscope often shows small groups of neuroendocrine cells that look like tiny carcinoids. Researchers still do not know why some remain so small and others begin to grow and become large enough to cause symptoms.

Can Gastrointestinal Carcinoid Tumors Be Found Early?

Because carcinoid tumors usually grow and spread slowly, about half of all gastrointestinal carcinoid tumors are found at an early or localized stage, usually before they cause any problems.

Incidental Diagnosis of Carcinoid Tumors

In many cases, carcinoid tumors are found incidentally when looking for something else. The tumors don't cause any symptoms but are found during tests done for other diseases or because parts of the digestive system are removed to treat other diseases.

For example, a person with stomach symptoms may have a test called an upper endoscopy, where the doctor looks at the stomach lining through a flexible lighted tube. During this test, the doctor may incidentally notice a small bump in the stomach wall that turns out to be a carcinoid tumor.

Sometimes during colorectal cancer screening a routine sigmoidoscopy or colonoscopy (looking at the large bowel through a flexible lighted tube) will incidentally find a small carcinoid tumor.

When a person's appendix is removed to treat appendicitis (inflammation of the appendix), doctors may incidentally find a small carcinoid, as well as the expected inflammation. Some studies have found that about 1 of every 300 people who have appendix surgery done for other diseases turn out to have a tiny carcinoid near the tip of their appendix. In most of these cases, the carcinoid was too small to have caused any symptoms.

How Are Gastrointestinal Carcinoid Tumors Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

Once a neuroendocrine tumor/cancer is found and staged, the cancer care team will suggest one or more treatment plans. This is an important decision, so you should take time and think about all of your options.
The main factors in selecting treatment options for a gastrointestinal (GI) neuroendocrine tumor/cancer are:

• its size and location
• whether it has spread to lymph nodes, liver, bones, or other organs
• whether you have any other serious medical conditions
• whether the tumor is causing bothersome symptoms

It is often a good idea to seek a second opinion. A second opinion may provide more information and help you feel more confident about the treatment plan that is chosen.

The first part of this section describes the various types of treatments used for GI neuroendocrine tumors/cancers. This is followed by a description of the most common approaches used for these tumors/cancers based on their stage and primary site.

Gallbladder Cancer

What Is Gallbladder Cancer?

Gallbladder cancer is a cancer that starts in the gallbladder. In order to understand this cancer, it helps to know about the normal structure and function of the gallbladder.

About the gallbladder

The gallbladder is a small, pear-shaped organ located under the right lobe of the liver. Both the liver and the gallbladder are behind the right lower ribs. The gallbladder is usually about 3 to 4 inches long and normally no wider than 1 inch.

The gallbladder concentrates and stores bile, a fluid made in the liver. Bile helps digest the fats in foods as they pass through the small intestine. Bile may be released from the liver directly into the small intestine, or it may be stored in the gallbladder and released later. When food (especially fatty food) is being digested, the gallbladder contracts and releases bile through a small tube called the cystic duct. The cystic duct joins up with the hepatic duct, which comes from the liver, to form the common bile duct. The common bile duct empties into the small intestine.

The gallbladder is helpful, but it is not essential for life. Many people live normal lives after having their gallbladders removed.

Types of gallbladder cancers

More than 9 out of 10 gallbladder cancers are adenocarcinomas. An adenocarcinoma is a cancer that starts in cells with gland-like properties that line many internal and external surfaces of the body (including the inside of the digestive system).

A type of gallbladder adenocarcinoma that deserves special mention is called papillary adenocarcinoma (or just papillary cancer). These are gallbladder cancers whose cells are arranged in finger-like projections when viewed under a microscope. In general, papillary cancers are not as likely to invade the liver or nearby lymph nodes. They tend to have a better prognosis (outlook) than most other kinds of gallbladder adenocarcinomas. About 6% of all gallbladder cancers are papillary adenocarcinomas.

There are other types of cancer that can develop in the gallbladder, such as adenosquamous carcinomas, squamous cell carcinomas, and small cell carcinomas, but these are uncommon.

Do We Know What Causes Gallbladder Cancer?

Researchers have found several risk factors that make a person more likely to develop gallbladder cancer (see the section, "What are the risk factors for gallbladder cancer?"). They are also making progress in understanding how some of these risk factors lead to gallbladder cancer.

Most doctors studying the subject think that chronic inflammation is the major cause of gallbladder cancer. When gallstones are present, the gallbladder may release bile more slowly. This means that gallbladder tissue is exposed to the bile for longer than usual. This may lead to irritation and inflammation. Scientists also suspect that this longer exposure to possible cancer-causing substances in the bile could also be responsible. Certain abnormalities in the ducts that carry fluids from the gallbladder and pancreas to the small intestine can cause juices from the pancreas to flow backward into the gallbladder and bile ducts. Researchers suspect that this reflux (backward flow) of pancreatic juices may irritate the cells lining the gallbladder and bile ducts in a way that causes irritation and inflammation. This may stimulate their growth and perhaps make them more sensitive to cancer-causing substances.

Scientists have begun to understand how risk factors such as inflammation may lead to certain changes in the DNA of cells, causing them to grow abnormally and form cancers. DNA is the chemical in each of our cells that makes up our genes -- the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look.

Some genes contain instructions for controlling when cells grow and divide. Genes that promote cell division are called oncogenes. Genes that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes (mutations) that turn on oncogenes or turn off tumor suppressor genes.

Some people inherit DNA mutations from their parents that greatly increase their risk for certain cancers. But inherited gene mutations are not believed to cause very many gallbladder cancers.

Gene mutations related to gallbladder cancers are usually acquired during life rather than being inherited. For example, acquired changes in the p53 tumor suppressor gene are found in most cases of gallbladder cancer. Other genes that may play a role in gallbladder cancers include k-ras, b-RAF, FHIT, CDKN2, and HER2.

Many newer cancer drugs target cells with specific gene changes. Knowing which genes are abnormal in gallbladder cancer cells may help doctors determine which of these new drugs might be effective.

Can Gallbladder Cancer Be Found Early?

Only about 1 out of 3 gallbladder cancers are found before they have spread to other tissues and organs. Many of these early cancers are found unexpectedly when a person's gallbladder is removed as treatment for gallstones. When the gallbladder is looked at in the lab after it is removed, small cancers or pre-cancerous changes are sometimes found that did not cause any symptoms.

Because the gallbladder is located deep inside the body, early tumors cannot be seen or felt by health care providers during routine physical exams. There are currently no blood tests or other tests that can reliably detect gallbladder cancers early enough to be useful as screening tests. Without effective screening tests, most gallbladder cancers are found only when the cancer has grown enough to cause symptoms.

How Is Gallbladder Cancer Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

The first part of this section describes the various types of treatments used for gallbladder cancers. This is followed by a description of the most common approaches used for these cancers based on different situations.

Making treatment decisions

After gallbladder cancer is found and staged, your cancer care team will discuss your treatment options with you. It is important for you to take time and think about your choices. In choosing a treatment plan, factors to consider include the type and stage of the cancer, the likely side effects of treatment, your overall health, and the chances of curing the disease, extending life, or relieving symptoms.

If time permits, it is often a good idea to seek a second opinion, particularly for an uncommon cancer such as gallbladder cancer. A second opinion can provide more information and help you feel more confident about your chosen treatment plan.

Nearly all doctors agree that surgery offers the only reasonable chance for curing people with gallbladder cancer. But there are differences of opinion about how advanced a gallbladder cancer may be and still be curable. Therefore, it may be especially important for people with gallbladder cancer to seek a second opinion when considering treatment options. Finding a doctor experienced in treating this disease may have other benefits as well. Most studies have found that more extensive surgeries tend to result in higher survival rates, but such operations are most often done at major cancer centers and may not be available in every community.

In general, spread of the cancer beyond the gallbladder does not make it incurable by surgery unless the cancer has spread too far or into major blood vessels. For instance, if the cancer has invaded the liver -- but only in one area and not too deeply -- it may be possible to remove all of the cancer by surgery. If the cancer has spread to both sides of the liver, to the lining of the abdominal cavity, to organs farther away from the gallbladder than the liver, or if it surrounds a major blood vessel, surgery is unlikely to remove it all.

Eye Cancer

What Is Eye Cancer?

Parts of the Eye

The eye has 3 major parts: the globe, the orbit, and the adnexal structures.

The globe (eyeball) is filled with a jelly-like material called vitreous. The uvea and the retina are 2 important parts of the globe.

The uvea has 3 parts:

• iris -- the colored or pigmented part surrounds the pupil, the opening that controls the amount of light that enters the eyeball.
• choroid -- a thin, pigmented layer lining the eyeball that nourishes the retina and the front of the eye with blood.
• ciliary body -- contains the muscles inside the eye that change the shape of the lens so that the eye can focus on near or distant objects and cells that produce aqueous humor ( the fluid in the eye)..

The retina is like the film in a camera. It is in the back of the eyeball and has specialized nerve cells that are sensitive to light. These light-sensing cells are connected to the brain by the optic nerve. The pattern of light (image) appearing on the retina is sent from the retina to an area of the brain called the visual cortex, allowing us to see. Cancers that affect the eyeball are called intraocular (within the eye) cancers.

The second part of the eye, called the orbit, consists of the tissues surrounding the eyeball. These tissues include muscles that make the globe move in different directions and the nerves attached to the eye. Cancers of these tissues are called orbital cancers.

Finally, there are adnexal (or accessory) structures such as the eyelids and tear glands. Cancers that develop in these tissues are called adnexal cancers.

Cancers of the orbit and adnexa develop from tissues such as muscle, nerve, and skin and are just like their counterparts in other parts of the body. These are described in other American Cancer Society documents on cancers of muscle, nerve, skin, etc. For example, a cancer of the eyelid is usually a skin cancer like other skin cancers and is described in the American Cancer Society documents on skin cancers ("Melanoma " and "Nonmelanoma Skin Cancers"). Muscle cancer, called rhabdomyosarcoma, is described in another American Cancer Society document, "Rhabdomyosarcoma." Intraocular cancers are unique to the eye and are described here.

Types of Primary and Secondary Intraocular Cancers

Primary intraocular cancers are cancers that start inside the eyeball. Melanoma is the most common primary intraocular cancer in adults, followed by primary intraocular lymphoma. In children, retinoblastoma (a cancer arising from cells in the retina) is the most common primary intraocular cancer, and medulloepithelioma is the next most common. Retinoblastoma is discussed in a separate American Cancer Society document "Retinoblastoma." Medulloepitheliomas are extremely rare and are discussed briefly below.

Secondary intraocular cancers are cancers that have spread to the eye from another part of the body. The most common cancers that spread to the eye are breast and lung cancers. This occurs quite often when these diseases metastasize (spread). Usually these cancers spread to the part of the eyeball called the uvea. For more information on these types of cancers, refer to the specific American Cancer Society documents on these cancers.

Intraocular Melanoma (Melanoma of the Eye)

Intraocular melanoma (also called uveal melanoma) although rare, is the most common type of cancer that develops within the eyeball in adults. Melanomas of the skin are much more common than uveal melanomas and develop from pigment-producing cells called melanocytes. When melanoma develops in the eyeball, it is usually in the part of the uvea called the choroid. Choroid cells have the same kind of pigment as melanocytes in the skin, so it is not surprising that these cells sometimes form melanomas. Approximately 90% of intraocular melanomas develop in the choroid.

Nearly all of the remaining 10% of intraocular melanomas are melanomas of the iris. They are the easiest for the patient and doctor to see because they often arise in a pigmented spot on the iris that has been present for many years and then begins to grow. These melanomas usually are relatively slow growing, and they rarely spread to other parts of the body. For these reasons, people with iris melanomas generally have a good prognosis (outlook for survival).

Intraocular melanomas are generally composed of 2 different kinds of cells.

• spindle cells -- These are elongated cells.

• epithelioid cells -- These cells are almost round but with some straight edges.

Most of the tumors are composed of both kinds of cells. The outlook is best if the tumors are mostly spindle cells and worse if they are mostly epithelioid cells. Epithelioid tumors are more likely to metastasize (spread) to distant sites and be fatal. If you have ocular melanoma, your doctor can tell you which type of cells were found.

Primary Intraocular Lymphoma (Lymphoma of the Eye)

Lymphoma is a type of cancer that generally starts in lymph nodes, which are bean-sized collections of immune system cells. Lymphomas can also start in internal organs such as the stomach, lungs, and rarely in the eyes. There are 2 main categories of lymphoma -- Hodgkin disease and non-Hodgkin lymphoma. Primary intraocular lymphoma is always a non-Hodgkin lymphoma. Most people with primary intraocular lymphoma are elderly or have immune system problems such as the acquired immunodeficiency syndrome (AIDS). For more information about non-Hodgkin lymphoma in general, refer to the American Cancer Society document on that subject.

Medulloepithelioma

Medulloepithelioma is a very rare tumor that usually occurs in young children. Although most medulloepitheliomas are malignant, they rarely metastasize (spread). They usually cause eye pain and decreased vision. The diagnosis is made when a doctor finds a tumor mass in the eye by using an ophthalmoscope (instrument that helps doctors to look inside the eye). A biopsy (a procedure in which cells from the tumor are removed and examined under a microscope) is often performed to confirm the diagnosis. Treatment is with surgery. The doctor normally tries to remove only the tumor. If that is not possible, then the eye is removed.

Do We Know What Causes Eye Cancer?

During the past few years, scientists have made great progress in understanding how certain changes in a person's DNA can cause cells to become cancerous. DNA carries the instructions for nearly everything our cells do. We usually resemble our parents because they are the source of our DNA. However, DNA affects more than our outward appearance. It influences our risks for developing certain diseases, including some kinds of cancer.

Some genes (parts of our DNA) contain instructions for controlling when our cells grow and divide. Genes that promote cell division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. DNA mutations (defects) that activate oncogenes or inactivate tumor suppressor genes can cause cancer. Some people with cancer have DNA mutations they inherited from a parent. These mutations increase their risk for the disease. Usually, however, DNA mutations are acquired during life rather than inherited before birth.

Scientists have found several changes in oncogenes and tumor suppressor genes in cells from eye cancers such as melanoma and lymphoma. However, they are still not certain why these changes occur in some people, exactly how the changes occur, and how the changes cause or promote cancer formation if at all.

Can Eye Cancer Be Found Early?

Often melanomas of the eye are found during a routine eye exam. When the doctor looks through the pupil at the back of the eye, he or she may be able to see a dark spot that may indicate an early melanoma. Because they are rare, there is no screening test for them other than routine eye exams. People who find a dark spot on their iris (colored part of the eye) that is enlarging should have a doctor look at it.

Many doctors feel that skin and eye melanomas start from a nevus, which is a benign (non-cancerous) tumor of pigment cells. (Nevus is the medical name for a mole -- the plural form is nevi.) If an eye nevus is present, it should be observed regularly by an ophthalmologist (specialist in eye diseases).

How Is Eye Cancer Treated?

his information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

After an eye cancer is found and staged, the cancer care team will recommend a treatment plan. In choosing a treatment plan, factors that are considered include the location and stage of the cancer, as well as a person's overall physical health. Certain treatment options may involve the risk of some loss of vision, which must also be considered.

Because intraocular melanomas and lymphomas are rare, it is often a good idea to seek an opinion from a doctor who has had a lot of experience in treating people with these cancers. A second opinion can provide more information and help a person feel more confident about the treatment plan that is chosen.

Because any treatment of the eye may interfere with or cause complete loss of vision, many treatments have been developed to preserve it. Cancers of the eye, however, can be fatal and treatment in some cases must be given regardless of the damage to the eye. On the other hand, some eye melanomas are small, grow very slowly if at all, and can be watched carefully without treatment. It is important to get the opinion of a skilled specialist in this field.

Esophagus Cancer

What Is Cancer of the Esophagus?

The esophagus is a muscular tube that connects the mouth to the stomach. It carries food and liquids to the stomach. It is about 10-13 inches long. At its smallest point, it is a little less than
one inch wide.

The wall of the esophagus has several layers. Cancer of the esophagus starts from the inner layer and grows outward.

At the top of the esophagus is a special muscle that relaxes to let food or liquid enter. This muscle is called a sphincter. The lower part of the esophagus connects to the stomach. Another muscle here opens to allow food to enter the stomach. This muscle also keeps stomach acid and juices out of the esophagus. When stomach juices escape into the esophagus, we feel heartburn. The medical term for heartburn is reflux.

Long-term reflux of stomach acid into the esophagus sets up a special problem. It can change the cells in the lower end of the esophagus. They become more like the cells that line the stomach. These changed cells produce a condition called Barrett esophagus. The altered cells can change into cancer, so they should be closely watched by a doctor.

There are 2 main types of cancer of the esophagus. One type grows in the cells that form the top layer of the lining of the esophagus. These are called squamous cells, and cancer that starts there is known as squamous cell carcinoma. Squamous cell cancer can grow anywhere along the length of the esophagus. It accounts for about half of all cancers of the esophagus.

The other type usually starts near the opening to the stomach. It is called adenocarcinoma. This type of cancer cannot start unless squamous cells have been changed by acid reflux.

What Causes Cancer of the Esophagus?

While we don't know the exact cause of esophageal cancer, we do know some of the risk factors that make this cancer more likely. A risk factor is something that increases a person's chance of getting cancer. Some risk factors, such as smoking, can be controlled. Others, like a person's age or race, can't be changed.

Risk Factors for Cancer of the Esophagus

Age: The risk of this cancer goes up with age. It is rarely found in people under 40.

Sex: Men are 3 times more likely to get this cancer than women.

Race: African Americans are 50% more likely to develop cancer of the esophagus than whites.

Barrett esophagus: This occurs because of long-term reflux of fluid from the stomach into the lower esophagus. Some people feel heartburn from this reflux and others do not. Over time this reflux can change the cells at the end of the esophagus. This raises the risk of adenocarcinoma of the esophagus. But not everyone with Barrett esophagus will get cancer of the esophagus.

Heartburn: Long-standing heartburn, also called reflux (or GERD: gastroesophageal reflux disease), increases the risk of this cancer even if it hasn�t progressed to Barrett esophagus.

Tobacco: Using any form of tobacco raises the risk of this cancer. The longer a person uses tobacco, the greater the risk. More than half of all squamous cell esophageal cancer is linked to smoking.

Alcohol: Long-term heavy drinking is a major risk factor for cancer of the esophagus. For people who both smoke and drink, the risk is further increased.

Overweight: The risk of this cancer is higher for people who are overweight or obese.

Diet: Diets that don�t include enough fruits or vegetables and certain minerals and vitamins can raise the risk of this cancer. Overeating, which leads to being overweight, also raises the risk of this cancer.

Very hot liquids: Drinking lots of very hot liquids might increase the risk of this cancer.

Chemicals: Working with a chemical used in dry cleaning may lead to a greater risk of this cancer. Dry cleaning workers have a higher rate of cancer of the esophagus. Also, breathing in many other chemical fumes may also increase the risk.

Lye: Lye is found in strong cleaners like drain cleaners. It can burn and destroy cells. If a child accidentally drinks one of these cleaning liquids, the lining of the esophagus will scar. A child who has swallowed lye has a higher risk of squamous cell cancer as an adult.

Achalasia: In this disease, the muscle at the bottom of the esophagus does not open to release food into the stomach. So the lower end of the esophagus expands. Food collects there instead of moving into the stomach. This raises the risk for squamous cell cancer.

Tylosis: This is a rare, inherited disease. Extra skin grows on the palms of the hands and soles of the feet. People with tylosis are at a very high risk for esophageal cancer. They should be seen by a doctor regularly.

Esophageal webs: These are abnormal pieces of tissue that extend into the esophagus. They can make it hard to swallow. People who have these usually have other symptoms as well. They can have problems with the tongue, fingernails, spleen, and other organs. About 1 in 10 people with this problem will get cancer of the esophagus.

How Is Cancer of the Esophagus Found?

People with Barrett esophagus and others at high risk should have exams to look for cancer of the esophagus. The doctor might recommend surgery (or other methods) if certain abnormal cells (dysplasia) are found.

In most cases, this type of cancer is found because of the symptoms it causes. But often these symptoms don't appear until the cancer is advanced, making a cure less likely. If the cancer is found early, it is often a result of tests done for other reasons.

Below are the most common symptoms of this type of cancer:

Trouble with swallowing (dysphagia: dis-FAY-jee-uh): This is the most common symptom of cancer of the esophagus. It means that you feel as if food is lodged in the chest. By this time, if cancer is present it has grown to fill about half the opening of the esophagus. Solid foods like bread and meat often get stuck. People with dysphagia often switch to softer foods or even liquids to help with swallowing. To help the food go down, the body makes more saliva. This causes some people to bring up lots of thick mucus or saliva.

Pain: Rarely, pain in the mid-chest, or a feeling of pressure or burning, can be a sign of cancer. But these symptoms can also be caused by something else, such as heartburn. Pain while swallowing is usually a late sign of a large cancer.

Weight loss: About half of people with esophageal cancer lose weight without trying. This is because they are not getting enough food since they have trouble swallowing. Also, they may find they have less appetite.

Other symptoms: Hoarseness, hiccups, pneumonia, and high calcium levels are usually signs of more advanced cancer. Of course, these symptoms can be caused by other diseases as well.

How Is Cancer of the Esophagus Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

After the cancer is found and staged, your doctor will talk to you about a treatment plan. There is a lot for you to think about when choosing the best way to treat or manage your cancer. There may be more than one treatment to choose from. You may feel that you need to make a decision quickly. But give yourself time to absorb the information you have learned. Talk to your doctor. Look at the list of questions at the end of this piece to get some ideas. Then add your own.

You may want to get a second opinion. A second opinion can provide more information and help you feel good about the treatment you choose. Some insurance companies require you to get a second opinion before they will agree to pay for treatments.

Surgery, chemotherapy, and radiation are used to treat early cancer of the esophagus. There are also treatments to help relieve pain and help with symptoms.

The best choice for you will depend on the stage of the cancer as well as your general health. Each kind of treatment might have side effects. Your cancer care team will be glad to discuss the side effects with you.

Surgery

How much surgery is done depends on the stage of the cancer. Surgery can also be used along with other treatments such as chemotherapy and radiation treatment.

There are 2 common types of operations for this cancer. In one, esophagectomy (ee-sof-uh-JEK-tuh-me), the part of the esophagus with cancer and nearby lymph nodes are removed. The esophagus is attached either to the stomach or the surgeon may replace the removed part of the esophagus with a piece of the small or large intestine.

The other surgery, esophagogastrectomy (ee-sof-uh-go-gas-TREK-tuh-me), is done to remove part of the lower esophagus, nearby lymph nodes, and the upper part of the stomach. The esophagus is again connected to the remaining part of the stomach.

While surgery can cure some patients whose cancer has not spread beyond the esophagus, often these cancers are not found early enough. So it�s important to know the goal of surgery: is it to try to cure the cancer or to ease symptoms?

Both of these operations are complex. Some surgeons are able to do the operation using a laparoscopic approach. This means that small cuts are made through which the doctor uses a tiny instrument something like a telescope to look inside the body. The surgery itself is done through even smaller incisions.

Surgeons who do this surgery must be quite expert. You should feel free to ask your surgeon about his or her experience with these operations and what percent were successful. The success rate is greater when the surgery is done in a hospital where it is done more often.

Most people stay in the hospital for 2 weeks after surgery. And there can be risks and side effects. For example, after the operation the stomach may empty very slowly, causing nausea and vomiting. The place where the esophagus connects to the stomach can become more narrow, making it hard for the person to swallow. Also, acid from the stomach can enter the esophagus causing heartburn. Anyone who has problems with side effects should talk with their doctor or nurse as there are often ways to help.

Some complications from surgery can be very serious, even fatal. It is important to have a surgeon with experience in a hospital where these operations are done more often. Don�t be afraid to ask the surgeon about his or her experience and about the survival rates at the hospital.

Radiation Therapy

Radiation therapy is treatment with high energy rays (such as x-rays) to kill or shrink cancer cells. External radiation uses a beam from outside the body. This is the kind most often used for cancer of the esophagus. For internal or implant radiation, radioactive �seeds� are placed directly inside the body near the cancer.

Radiation therapy by itself will not cure esophageal cancer. Often it is combined with surgery and/or chemotherapy. It is also used to relieve problems with swallowing, pain, or other symptoms of this cancer.

Side effects of radiation treatment may include skin problems, upset stomach, diarrhea, and fatigue. Often these side effects go away when treatment ends. Radiation to the chest may cause lung damage and lead to trouble breathing and shortness of breath. If you have these or other side effects, talk with your doctor since there are often ways to relieve them.

Chemotherapy

Chemotherapy refers to the use of drugs to kill cancer cells. Usually the drugs are given into a vein or by mouth. Once the drugs enter the bloodstream, they spread throughout the body.

Chemotherapy alone cannot cure cancer of the esophagus unless radiation treatment (and in some cases surgery) are also used. Chemotherapy is used in 3 ways:

• It can be used to ease the symptoms of advanced cancer.
• It can be given along with radiation to shrink the cancer.
• It can be used before surgery to shrink a tumor. This use is still being studied.

Chemotherapy can have some side effects. These side effects will depend on the type of drugs given, the amount taken, and how long treatment lasts. The most common side effects can include:

• nausea and vomiting
• loss of appetite
• hair loss
• mouth sores
• increased chance of infection (from a shortage of white blood cells)
• bleeding or bruising after minor cuts or injuries (from a shortage of blood platelets)
• tiredness or shortness of breath (from a shortage of red blood cells)

Most side effects go away once treatment is over. Anyone who has problems with side effects should talk with their doctor or nurse as there are often ways to help.

PDT (photodynamic therapy): This method may be used when the cancer has been found very early or has come back after other treatment. First, a harmless chemical is injected into the bloodstream. It collects in the tumor for a few days. Then a special type of laser light is focused on the cancer through an endoscope. The light changes the chemical into a new chemical that can kill cancer cells.

PDT is useful because it can kill cancer cells with very little harm to normal cells. But because the light must be used, it can reach only cancers near the surface of the esophagus. It doesn�t work for cancers that have spread deeper or into other organs.

Side effects of PDT include redness or discoloration of the skin and sensitivity to the sun or other light sources. Because of this, people having this treatment may be told to stay indoors for 6 weeks.

At this time, the main use of PDT is to relieve symptoms of advanced cancer that are blocking the esophagus. It is also being used to treat Barrett esophagus and very early cancers found in Barrett esophagus. Researchers are looking at the use of PDT in comparison to other treatments such as surgery or the use of lasers.

Survival Rates by Stage (from the National Cancer Data Base; based on 11,154 patients diagnosed in 1998)

Because this cancer is usually found at an advanced stage, many people will die of the disease. But survival rates have been getting better. Talk with your cancer care team if you have questions about your own chances of a cure, or how long you might survive your cancer. They know your situation best.

The 5-year survival rate is the percentage of patients who are alive 5 years after diagnosis (leaving out those who die of other causes). Of course, patients might live more than 5 years after diagnosis.

Stage	5-year relative survival rate
0	52%
I	41%
II	26%
III	13%
IV	3%

Endometrial Cancer

What Is Endometrial Cancer?

Endometrial cancer is a cancer that starts in the inner lining of the womb (uterus). This lining is called the endometrium. The pictures below show where the uterus is found and then a closer look at the uterus.

The uterus is a hollow organ, about the size and shape of a medium-sized pear. It has 2 main parts. The lower part, which extends into the vagina, is called the cervix. The upper part is the body of the uterus, also known as the corpus. The body of the uterus has 2 layers. The inner layer is called the endometrium.

During a woman's menstrual cycle this inner layer changes. In the early part of the cycle it gets thicker in case the woman becomes pregnant. If she does not become pregnant, the tissue is shed from the uterus and becomes the menstrual flow. This cycle repeats throughout a woman's life until change of life (menopause).

Types of cancers of the uterus and endometrium

Nearly all cancers of the uterus start in the endometrium. They are called endometrial carcinomas. Cancers can also start in the muscle layer of the uterus. These cancers belong to the group of cancers called sarcomas.

Carcinomas

Most carcinomas are cancers that start in the cells that form glands in the lining of the uterus. They are called adenocarcinomas. Among these there are 2 types. In the first and most common type, the cancer cells look a lot like normal cells. This is called endometrioid adenocarcinoma. This type can be less likely to spread, which makes it less dangerous. The other type of endometrial cancer is less common and more likely to grow and spread quickly.

Uterine sarcomas

Less common uterine cancers that do not come from glandular tissue of the endometrium are called uterine sarcomas. These can involve the endometrium. These types of cancer are not covered here because their treatment and outlook for survival are different from the most common cancers of the endometrium. If you would like to know more about this type of cancer you can get our document called Uterine Sarcoma.

Cervical cancers

Cancers of the cervix are different from cancers of the body of the uterus and are described in our document, Cervical Cancer.

What Causes Endometrial Cancer?

We do not yet know what causes most cases of endometrial cancer. But we do know that certain risk factors are linked to this disease. A risk factor is anything that changes a person's chance of getting a disease such as cancer. Different cancers have different risk factors. For example, being in strong sunlight without protection is a risk factor for skin cancer. Smoking is a risk factor for many cancers. But risk factors don't tell us everything. Someone can have several risk factors and still not get a disease. Also, not having any risk factors doesn't mean that you won't get the disease.

Risk factors for endometrial cancer

Hormone levels

A woman's hormone balance plays a part in most endometrial cancers. Many of the risk factors for endometrial cancer affect estrogen levels. Before change of life, the ovaries are the main source of the 2 main types of female hormones -- estrogen and progesterone. The balance between these hormones changes during a woman's menstrual cycle each month. A shift in the balance of these 2 hormones toward more estrogen increases a woman's risk for getting endometrial cancer.

After change of life, the ovaries stop making these hormones, but a small amount of estrogen is still made in fat tissue. Female hormones can also be taken as birth control pills to prevent pregnancy and as hormone therapy to treat symptoms of menopause.

Estrogen therapy: Using estrogen to treat symptoms of change of life is known as estrogen therapy or menopausal hormone therapy. Estrogen treatment can reduce hot flashes, improve vaginal dryness, and help prevent the weakening of the bones (osteoporosis) that can happen with menopause. But the use of estrogen alone increases a woman's risk of getting endometrial cancer. Studies show that giving progesterone-type drugs along with the estrogens helps lower this risk. But studies also show that giving this combination of the hormones increases a woman's chance of getting breast cancer and blood clots.

It is important to discuss the pros and cons of estrogen therapy with your doctor. If you choose to take it, you should use the lowest dose that is needed for the shortest period of time. You should also have follow-up exams for cancer at least every year. Let your doctor know right away if you have any vaginal bleeding or discharge that isn't normal.

Birth control pills: Using birth control pills lowers the risk of endometrial cancer. The risk is lowest in women who take the pill for a long time. And this protection continues for at least 10 years after a woman stops taking this form of birth control. But you need to look at all of the pros and cons when choosing a birth control method -- endometrial cancer risk is only one factor to think about. It's a good idea to talk to your doctor about the different methods of birth control to find the one that is best for you.

Total number of menstrual cycles (periods): Having more periods during a woman's lifetime raises her risk of endometrial cancer. Starting periods before age 12 or going through change of life late raises the risk. Starting periods early is less a risk factor for women with early change of life. Likewise, late change of life may not lead to a higher risk in women whose periods began later in their teens.

Pregnancy: During pregnancy, the hormonal balance shifts toward more progesterone. So having many pregnancies reduces endometrial cancer risk. Women who have not been pregnant have a higher risk.

Obesity (being very overweight): Most of a woman's estrogen is made by her ovaries, but fat tissue can change some other hormones into estrogens. Having more fat tissue can increase a woman's estrogen levels and, as a result, increase her endometrial cancer risk.

Tamoxifen: Tamoxifen is a drug that is used to treat women with breast cancer. It is also used to reduce the risk in women who are at a high risk of getting breast cancer. The drug acts like estrogen in the uterus. It can cause the uterine lining to grow and increase the risk of endometrial cancer in women who take this drug.

The risk of getting endometrial cancer in women taking tamoxifen is fairly small (about 1 in 500). It must be balanced against the value of this drug in treating breast cancer and reducing the chances of the woman getting cancer in the other breast. This is something women may want to talk about with their doctors. If you decide to take tamoxifen, you should have yearly pelvic exams. You should also be sure to tell your doctor if you have any endometrial cancer symptoms, such as discharge or bleeding that isn't normal.

Ovarian tumors: Certain ovarian tumors make estrogen. Women who have these tumors have higher than normal estrogen levels and lower levels of progesterone. The increase in estrogen compared to progesterone can increase a woman's chance of getting endometrial cancer.

Polycystic ovarian syndrome: Women with polycystic ovarian syndrome (PCOS) have hormone levels that are not normal, such as higher estrogen levels and lower levels of progesterone. The increase in estrogen compared to progesterone can increase a woman's chance of getting endometrial cancer.

Age

The risk of endometrial cancer goes up as a woman gets older.

A diet high in animal fat

A high-fat diet can increase the risk of several cancers, including endometrial cancer. Because fatty foods are also high-calorie foods, a high-fat diet can lead to obesity, which is an endometrial cancer risk factor. Some doctors think that fatty foods may also have a direct effect on estrogen levels, which can also increase risk.

Diabetes

Diabetes is more common in people who are overweight. This could be why diabetes is a risk factor for endometrial cancer. But some studies suggest that diabetes by itself could be a risk factor.

Family history

This cancer appears to run in some families who also tend to get a certain type of colon cancer. A small number of endometrial cancers may be due to this inherited factor. Women who have had several family members with colon cancer or endometrial cancer might think about having genetic counseling and testing. This kind of testing can help show if you (or members of your family) are at high risk. If you are, your doctor may suggest a hysterectomy once you are through having your children. Your doctor may also recommend endometrial sampling (biopsy) every year for women age 35 or older.

Breast or ovarian cancer

Women who have had breast cancer or ovarian cancer may have a higher risk of getting endometrial cancer. Some of the risk factors for breast and ovarian cancer also increase endometrial cancer risk.

Earlier pelvic radiation therapy

Radiation used to treat some other cancers can damage the DNA of cells. This could increase the risk of getting a second type of cancer, such as endometrial cancer.

Endometrial hyperplasia

Endometrial hyperplasia is an increased growth of the endometrium. The most common type has a very small risk of becoming cancer. It may go away on its own or after treatment with hormones. If the hyperplasia is called "atypical," it has a higher chance of becoming a cancer.

It is important to keep in mind that although these factors may increase a woman's risk for getting endometrial cancer, they do not always cause the disease. Many women with one or more of these risk factors never get endometrial cancer, and some women with endometrial cancer do not have any of these risk factors.

How Is Endometrial Cancer Found?

Most women are diagnosed because they have symptoms. Watching for any signs and symptoms of this cancer and telling your doctor about them right away allows the cancer to be found at an early stage. Finding it early improves the chances that it will be treated with success. But sometimes this cancer can reach an advanced stage before it causes any symptoms.

Early detection tests

Early detection refers to testing to find a disease such as cancer in people who do not have symptoms of that disease.

Women at average endometrial cancer risk

Women should talk to their doctors about getting regular pelvic exams, including Pap tests. Although the Pap test can find some female cancers early, most cases of endometrial cancer are not found by this test. But the Pap test is very good at finding early cancer of the cervix (the lower part of the uterus).

After menopause you should tell your doctor if you have any discharge or bleeding that is not normal. This could be a sign of endometrial cancer.

Women who have a higher risk of endometrial cancer

Women at high risk for this cancer should see their doctor whenever they have any vaginal bleeding that is not normal. This includes women who:

• are older
• had late menopause
• never had children
• are unable to get pregnant (infertile)
• are obese
• have diabetes
• have high blood pressure
• are using estrogen treatment
• are taking tamoxifen therapy

Women who have (or are at risk for) a certain type of colon cancer (hereditary nonpolyposis colon cancer, or HNPCC), should have yearly testing with an endometrial biopsy beginning at age 35. Another option would be for the woman to have a hysterectomy once she is finished having children.

Signs and symptoms of endometrial cancer

Unusual bleeding, spotting, or other discharge

If you have gone through change of life (menopause) it is very important to tell your doctor about any bleeding or spotting that is not normal. About 9 out of 10 women with endometrial cancer have some type of abnormal vaginal bleeding, but some have discharge that does not look like blood. Abnormal discharge also can be caused by something other than cancer.

Pelvic pain or a mass and weight loss

These symptoms usually happen in the later stages of the disease. Still, you should see the doctor right away because a delay in getting treatment can allow the cancer to get worse. This lowers the chance for successful treatment.

What will happen next?

History and physical exam

The doctor will ask about your symptoms, risk factors, and family medical history. The doctor will also do a physical and a pelvic exam.

Seeing a specialist

If the doctor thinks you might have endometrial cancer, you should see a gynecologist--a doctor with special training in finding and treating diseases of the female reproductive system.

Getting a sample of endometrial tissue

To find out whether the problem is endometrial hyperplasia or endometrial cancer, the doctor must remove some tissue so that it can be looked at under the microscope. Tissue can be taken out by doing an endometrial biopsy or by a D & C (this stands for dilation and curettage). These are described below.

Endometrial biopsy

This kind of biopsy can be done in a doctor's office. A very thin flexible tube is placed into the uterus through the cervix. Then suction is used to remove a small amount of endometrium. The suction usually takes less than a minute. The discomfort is much thing like menstrual cramps and can be helped by taking a drug like ibuprofen before the test.

Hysteroscopy

This is a way that doctors can look inside the uterus. The doctor puts a tiny telescope into the uterus through the cervix. The uterus is then filled with salt water (saline). This lets the doctor see and take a sample of anything that might be causing a problem, such as a cancer or a polyp. You stay awake for this, and the biopsy is done after the area is numbed with medicine.

Dilation and curettage (D & C)

If the biopsy sample doesn't get enough tissue, or if the doctor can't tell for sure whether it is cancer, a D & C must be done. To do this, the cervix is opened (dilated) and a special instrument is used to scrape tissue from inside the uterus. The test takes about an hour and you may need medicine to make you sleep (general anesthesia). D & C is most often done in an outpatient surgery area of a clinic or hospital. Most women have little pain after this procedure.

Testing the tissue

Tissue that has been removed is looked at under a microscope to see whether there are cancer cells in it. If cancer is found, the cells will be studied to learn more about the cancer. The lab report will give these details.

The lab will also assign a grade to the cancer. If most of the cancer cells look like normal tissue, it’s given a grade 1. If most of the cells look very different from normal cells, it's given a grade of 3. Grade 2 tumors fall somewhere in between. The grade is important because women with lower grade cancers are less likely to have advanced disease or to have the cancer come back after treatment.

Imaging tests for endometrial cancer

Ultrasound

Ultrasound is the use of sound waves to take pictures of the inside of the body. For this test, a probe is placed into the vagina. It gives off sound waves that echo off the tissue of the pelvic organs to create a picture on a video screen. This test can be used to see if there is a tumor. It could also show whether the tumor is growing into the outer muscle layer of the uterus. Salt water (saline) might be put into the uterus before the test to give a clearer picture.

Cystoscopy and proctoscopy

If a woman has signs that suggest the cancer may have spread, the doctor can use a lighted tube to look at the inside of the bladder or rectum. Small pieces of tissue can be removed to be looked at under a microscope.

CT scan

This is a special type of x-ray that creates detailed pictures of the inside of the body. CT scans are rarely used to find endometrial cancer. But they may be helpful if it looks as if the cancer has come back or has spread into the liver or other organs. CT scans can also be used to guide a biopsy needle into the area that could be cancer.

CT scans take longer than regular x-rays. You will need to lie still on a table while the scans are done. You may also have an IV (intravenous) line through which a contrast "dye" is injected. Some people are allergic to the dye and get hives or, rarely, problems like trouble breathing and low blood pressure. Be sure to tell the doctor if you have ever had a problem from any dye used for x-rays. You may also be asked to drink 1 to 2 pints of a liquid that helps outline the intestine so that it is not mistaken for tumors.

MRI scan (magnetic resonance imaging)

MRI scans use radio waves and strong magnets instead of x-rays. MRI scans are helpful in looking at the brain and spinal cord. They take longer than CT scans, and you may have to be placed inside a tube-like machine. This can be upsetting for some people. Sometimes newer "open MRI" machines are used. The machine makes thumping or buzzing noises that you may find disturbing. Many places will give you headphones with music to block this out. A contrast dye might be used, just as with CT scans.

PET scan (positron emission tomography)

In this test, a type of radioactive sugar is given to look for cancer cells. The cancer cells take in large amounts of the sugar. A special camera can then detect where it goes in the body. PET is sometimes useful in finding small collections of cancer cells. But PET is not often used for endometrial cancer.

Chest x-ray

This can show if the cancer has spread to the lungs. It may also be used to look for serious lung or heart problems.

IVP (intravenous pyelogram)

An IVP may be done if the doctor thinks the cancer might have spread to the urinary tract or nearby tissues. An IVP is an x-ray that outlines the urinary system. But CT scans are used more often than IVP.

Blood tests

Complete blood count (CBC)

This test measures the different cells in the blood, such as the red blood cells, white cells, and platelets. Many times women who have lost blood from the uterus will have low red blood cell counts. This is called anemia.

CA 125 blood test

CA 125 is a substance that many endometrial and ovarian cancers release into the bloodstream. Very high blood CA 125 levels are a sign that the cancer has likely spread beyond the uterus. If CA 125 levels are high before surgery, some doctors will track this number to find out how well the treatment is working. The levels will go down after surgery if treatment is killing the cancer cells. CA 125 levels may also be watched to see if the cancer has come back after treatment is done.

How Is Endometrial Cancer Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

After going over your test results, your doctor will recommend one or more treatment options. Don't feel rushed about making a decision. If there is anything you do not understand, ask to have it explained again. The choice of treatment mostly depends on the type of cancer and stage of the disease when it is found. Other factors that could play a part might include your age, your overall health, whether you plan to have children, and other personal matters. Be sure you understand all the risks and side effects of the different treatments before making a decision.

You may want to get a second opinion. This can give you more information and help you feel more certain about the treatment plan you choose. Some insurance companies say you must get a second opinion before they will pay for some treatments, but most of the time a second opinion is not needed for routine cancer treatments.

There are 4 basic types of treatment for women with endometrial cancer: surgery, radiation therapy, hormone therapy, and chemotherapy (chemo). Surgery is the main treatment for most women with endometrial cancer. But sometimes one or more of these treatments is combined.

Surgery

Hysterectomy

The main treatment for endometrial cancer is an operation to remove the uterus and cervix. This is called a hysterectomy. Most often, the ovaries and fallopian tubes are also removed. If both ovaries are removed, you will go into menopause (change of life) if you have not done so already.

To decide what stage the cancer is in, lymph nodes in the pelvis and around the aorta will also need to be removed (see below). This can be done at the same time as the hysterectomy or as a separate procedure.

Lymph node surgery

Lymph node removal: When lymph nodes are taken out it is called "lymph node dissection." In this operation, lymph nodes from the pelvis and the area around the main artery that carries blood from the heart (the aorta) are removed. They are looked at to see if they contain cancer cells. This can be done at the same time as the hysterectomy or with a laparoscope (explained below).

Laparoscopic lymph node sampling: When only a few of the lymph nodes are removed, it is called "lymph node sampling." Thin tubes are put into the belly (abdomen) through very small incisions. Small tools can be controlled through the tubes and the doctor can take out some lymph nodes. Studies are going on to find out whether this method is as good as removing all the lymph nodes to treat endometrial cancer.

Pelvic washings

To do a pelvic washing, the surgeon "washes" the abdominal and pelvic areas with salt water (saline) and then sends the fluid to the lab to see if it contains cancer cells.

Other tests that may be used for staging

Omentectomy: The omentum is a layer of fatty tissue that covers the abdominal contents like an apron. Cancer sometimes spreads to this tissue. When this tissue is removed, it is called an omentectomy. Sometimes the omentum is removed during a hysterectomy to see if cancer has spread there.

Peritoneal biopsies: The tissue lining the pelvis and abdomen is called the peritoneum. Peritoneal biopsies remove small pieces of this lining to check for cancer cells.

Tumor debulking

If cancer has spread throughout the abdomen, the surgeon may try to remove as much of the tumor as possible. This is called debulking. Debulking a cancer can help other treatments work better. Tumor debulking is helpful for other types of cancer, but it isn't clear yet if it will help women with endometrial cancer live longer.

Recovery after surgery

For an abdominal hysterectomy, the hospital stay is usually 3 to 7 days. Complete recovery takes about 4 to 6 weeks.

Side effects

A woman cannot become pregnant after a hysterectomy. If change of life had not happened before surgery, removing the ovaries will cause it to happen. Problems from surgery are rare but could include too much bleeding, wound infection, and damage to the urinary or intestinal systems.

Radiation therapy

Radiation therapy is treatment with high energy rays (such as x-rays) to kill or shrink cancer cells. The radiation may come from outside the body (external radiation). Or it can come from radioactive materials placed near the tumor. This is called brachytherapy. In some cases, both types of radiation treatment are used.

How much of the pelvis needs to have radiation treatment depends on how far the cancer has spread.

Brachytherapy

In cases where only the upper third of the vagina needs to be treated after surgery, radioactive pellets or seeds can be put into place for a short time. They are put in through the vagina. With brachytherapy there is little effect on nearby structures, such as the bladder or rectum.

This treatment is given in the radiation suite of the hospital or care center. About 4 to 6 weeks after surgery, the doctor puts the pellets of radioactive material into the vagina. More than one treatment may be needed. The number of treatments depends on the strength of the dose. For endometrial cancer, high dose radiation is often given weekly or even daily for at least 3 doses.

External radiation

This method of giving radiation is like a regular x-ray but it takes longer. It is most often given 5 times a week, for 4 to 6 weeks. While treatment itself takes less than a half-hour, the daily trips may hard to manage.

Side effects of radiation therapy

• tiredness (fatigue)
• upset stomach
• loose bowels (diarrhea)
• nausea and vomiting
• skin changes like redness and soreness
• problems passing urine
• the vagina may become dry, or shorter, or more narrow (this is called vaginal stenosis), causing pain during sex
• early menopause
• weakened bones in the pelvis

Radiation can also lead to low blood counts, causing low red blood cells and low white blood cells. The blood counts usually return to normal after radiation is stopped.

If you are having side effects from radiation, talk to your doctor. There are things you can do to get relief from these problems or to prevent them from happening.

Chemotherapy

Chemotherapy (often called "chemo") is the use of cancer-fighting drugs to kill cancer cells. Usually these drugs are given into a vein or by mouth. Once the drugs enter the bloodstream they spread throughout the body. Chemo is useful in treating cancer that has spread. One or more drugs may be used.

While these drugs kill cancer cells, they can also damage some normal cells. This can cause side effects. Which side effects happen will depend on the type of drugs given, the amount or dose, how often treatment is done, and how long treatment lasts. Common side effects are:

• nausea and vomiting
• loss of appetite
• hair loss
• mouth sores
• vaginal sores
• a higher chance of infection (from low white blood cell counts)
• bleeding or bruising after minor cuts or injuries (from a shortage of blood platelets)
• shortness of breath or tiredness (from low red blood cell counts)

Most side effects go away after treatment ends. If you have problems with side effects, talk with your doctor or nurse, as there are often ways to help.

Hormone therapy

Hormone therapy is the use of hormones or hormone-blocking drugs to fight cancer. Below are some of the types of hormone therapy that might be used.

Progestins: Progesterone-like drugs can be used to slow the growth of cancer cells. The drugs are usually taken as pills or injections.

Tamoxifen: Tamoxifen is a drug often used to treat breast cancer. It may also be used to treat advanced endometrial cancer or endometrial cancer that has returned (recurrent endometrial cancer).

GNRH (Gonadotropin-releasing hormone): These drugs switch off the estrogen made by the ovaries in women who have not gone through change of life. The drugs are injected every 1 to 3 months.

Aromatase inhibitors: After the ovaries are removed (or if they are not working), estrogen is still made in fat tissue. This becomes the body's main source of estrogen. Drugs called aromatase inhibitors can stop this estrogen from being formed and lower estrogen levels even further. These drugs are still being studied, and their role in endometrial cancer treatment is not clear.

Endometrial cancer survival by stage

The 5-year relative survival rate is the percentage of patients who have not died from endometrial cancer at least 5 years after the cancer is found. Those who die of other causes are not counted. Of course, patients might live more than 5 years after diagnosis.

When all cases of endometrial cancer are looked at together, the 5-year relative survival rate is about 88%. Most of these cancers are found at an early stage, which has a 5-year survival rate of over 95%. But the outlook (prognosis) for any one woman depends on the stage of her cancer as well as several other factors.

These numbers give you an overall picture, but keep in mind that every woman's situation is unique and the statistics can't predict exactly what will happen in your case. Talk with your cancer care team if you have questions about your personal chances of a cure, or how long you might survive your cancer. They know your situation best.