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Cancer Medicine :: Gastrointestinal Carcinoid Tumor

Gastrointestinal Carcinoid Tumor

General approach to treatment

Once a gastrointestinal (GI) carcinoid tumor is found and staged, the cancer care team will suggest one or more treatment plans. Take your time and think about all of your options when you make this important decision.

The main types of treatment for GI carcinoid tumors are:

Surgery for gastrointestinal carcinoid tumors

Most GI carcinoid tumors can be cured by surgery alone. The type of operation will depend on a number of factors, including the size and location of the tumor, whether the person has any other serious diseases, and whether the tumor is causing the carcinoid syndrome.

Surgeons often try to cure localized carcinoid tumors by removing them completely, which is usually successful. The options for GI carcinoid tumors that have spread locally or distantly are more complex. Because most carcinoid tumors grow very slowly and some do not cause any symptoms, completely removing all metastatic carcinoid tumors may not always be needed. In some patients, surgery to remove all visible cancer is the best option. This is particularly true if removing most of the cancer will reduce the level of hormone-like substances causing symptoms.

Several types of operations may be used to treat GI carcinoid tumors. Some of these remove the primary tumor (where the cancer started), while others remove or destroy cancer spread (metastases) in other organs.

Fulguration (electrofulguration)

This treatment destroys a tumor by heating it with electric current. It is sometimes used for small rectal carcinoid tumors, which can be reached fairly easily.

Endoscopic mucosal resection

In this procedure, the cancer is removed through an endoscope. This is most often used to treat small carcinoid tumors of the stomach and duodenum (the first part of the small intestine) and it can be used to remove small carcinoid tumors of the rectum.

Local excision

This operation removes the primary tumor and some normal tissue around it. The edges of the defect are then sewn together. This usually doesn’t cause any prolonged problem with eating or bowel movements. This operation may be done for small carcinoid tumors (no larger than 2 cm, or a little less than an inch).

Carcinoid tumors are sometimes removed during an operation for some other reason. This often occurs with carcinoid tumors of the appendix. When the appendix is removed (for some other reason), it is examined after surgery, and sometimes a carcinoid tumor is found. Most doctors believe that if the tumor is small — 2 cm or less — removing the appendix (appendectomy) is curative and no other surgery is needed. If the tumor is larger than 2 cm, more surgery may be needed.

Rectal carcinoid tumors may be excised (taken out) through the anus, without cutting the skin. Other GI carcinoid tumors can sometimes be locally excised through an endoscope but usually it is done through an incision (cut) in the skin.

More extensive surgeries

For larger tumors, a larger incision (cut) is needed to remove the tumor along with nearby tissues. This also gives the surgeon the chance to see whether the tumor has grown into other tissues in the abdomen (belly). If it has, the surgeon may be able to remove the areas of cancer spread.

Partial gastrectomy: In this operation, part of the stomach is removed. If the upper part is removed, sometimes part of the esophagus is removed as well. If the lower part of the stomach is removed, sometimes the first part of the small intestine (the duodenum) is also taken. Nearby lymph nodes are also removed. This operation is also known as asubtotal gastrectomy.

Small bowel resection: This is an operation to remove a piece of the small intestine (also called the small bowel). When it is used to treat a small bowel carcinoid, this surgery includes removing the tumor and the small bowel around it (called a wide margin resection), plus removing nearby (regional) lymph nodes and the supporting connective tissue (called the mesentery) that contains lymph nodes and vessels that carry blood to and from the intestine. Tumors in the terminal ileum (the last part of the small bowel) may require removing the right side of the colon (hemicolectomy).

Segmental colon resection or hemicolectomy: This operation removes between ⅓ and ½ of the colon, as well as the nearby mesentery (which includes blood vessels and lymph nodes).

Low anterior resection: This operation can be used for some tumors in the upper part of the rectum. It removes some of the rectum and the remaining ends are sewn together. This does not have much effect on digestive function.

Abdominoperineal (AP) resection: This surgery is done for large or very invasive cancers in the lower part of the rectum. It removes the anus, rectum, and lower part of the colon. After this operation, the end of the colon is connected to an opening on the skin on the abdomen (called a colostomy). A bag attached over this opening collects stool (feces) as it leaves the body.

Treatment for liver metastases

Ablation: These methods are often useful in destroying carcinoids that have spread to the liver, especially if their number or location makes removing them difficult or impossible. CT scan images are used to guide a needle precisely into the tumor deposits. The cells can then be destroyed by:

Cryotherapy (cryoablation): Injecting liquid nitrogen through the needle to kill the carcinoid cells by freezing.

Radiofrequency ablation: Using high-energy radio waves released from the end of the needle, which destroy the cancer cells.

Percutaneous ethanol injection: Injecting concentrated alcohol through the needle kills the cancer cells.

Another approach that can be useful in shrinking these tumors is hepatic artery embolization. Material is injected to block off a branch of the hepatic artery, which cuts off the tumor's blood supply. Chemotherapy is sometimes injected into the artery before it is blocked off. This is known as chemoembolization (see the "Chemotherapy for gastrointestinal carcinoid tumors" section).

Liver resection: In this operation, one or more pieces of the liver that contain areas of cancer spread are removed. When it is not possible to remove all areas of cancer spread, surgery may still be done to remove as much tumor as is possible. This is sometimes called cytoreductive surgery. If enough tumor can be removed, the surgery can help reduce symptoms of carcinoid syndrome. Removing liver metastases may help some patients with carcinoid tumors to live longer, but more than 9 out of 10 patients who have this surgery develop new liver metastases within 10 years.

Liver transplant: This operation removes the patient's liver and puts a liver (or a piece of a liver) from someone else in its place. It is rarely used to treat neuroendocrine cancers that have only spread to the liver after the primary tumor has been completely cut out. It is generally only an option for young patients who are otherwise healthy. Although this is very difficult treatment for patients to go through, it can be curative and should be considered for young patients. For more information on liver transplants see the

Chemotherapy for gastrointestinal carcinoid tumors

Chemotherapy (chemo) uses anti-cancer drugs that are injected into a vein or a muscle or taken by mouth to kill cancer cells. These drugs enter the bloodstream and reach all areas of the body, making this treatment useful for some types of cancers that have spread to other organs.

Unfortunately, carcinoid tumors often do not respond well to chemo. Because of this, chemo generally is used only for tumors that have spread to other organs, are causing severe symptoms, and have not responded to other medicines.

Some of the chemo drugs used to treat GI carcinoid include: Capecitabine (Xeloda®), 5-fluorouracil (5-FU), Doxorubicin (Adriamycin®), Etoposide (VP-16), Dacarbazine (DTIC), Streptozocin, Temozolomide, Cisplatin, Cyclophosphamide (Cytoxan®)

Some tumors, especially “high-grade” tumors, may be treated with more than one drug. For these, combinations of etoposide plus carboplatin or temozolomide plus capecitabine may be used.

Chemo drugs kill cancer cells but also damage some normal cells, which can cause some side effects. Side effects depend on the type of drugs, the amount taken, and the length of treatment. Short-term side effects might include: Nausea and vomiting, Loss of appetite, Hair loss, Mouth sores, Low blood counts

Because chemo can damage the blood-making cells of the bone marrow, you may have low blood cell counts. This can result in

Increased risk of infection (from too few white blood cells)

Bleeding or bruising after minor cuts or injuries (from a shortage of blood platelets)

Fatigue or shortness of breath (from too few red blood cells)

Most side effects go away a short time after treatment. Often medicines can help prevent or minimize many of the side effects. For example, your doctor can prescribe drugs to help prevent or reduce nausea and vomiting.

Intra-arterial therapy and chemoembolization

Normally, chemo drugs enter the bloodstream and can travel throughout the body. When carcinoid cancer has spread to the liver, it is sometimes treated by directly injecting the chemo drug into the hepatic artery, which supplies blood to parts of the liver. This exposes the liver tumors to high doses of the drug but limits exposing the rest of the body. This lets patients avoid severe side effects. Sometimes the chemo drug is injected together with a material that plugs up the artery (an approach called chemoembolization). When the arteries leading to them are blocked, the tumors become starved for nutrients and oxygen and many die off.

Other drugs for treating carcinoid tumors

Several medicines can help control the symptoms of carcinoid syndrome in patients with metastatic neuroendocrine cancers.

Octreotide (Sandostatin®) is an agent chemically related to a natural hormone, somatostatin. It is very helpful in treating flushing, diarrhea, and wheezing from carcinoid syndrome. While this drug rarely shrinks carcinoid tumors, it may slow or stop their growth. Although this is not curative, it can prolong life. The main side effects are pain at the site of the injection and − rarely − stomach cramps, nausea, vomiting, headaches, dizziness, and fatigue. Octreotide causes sludging (thickening or crystallizing) of bile in the gallbladder which can lead to gallstones (cholelithiasis). It can also result in insulin resistance that can make pre-existing diabetes more difficult to control.

This drug comes in a short-acting version that is given 2 to 4 times a day. It is also available as a long-acting injection (Sandostatin LAR) given only once a month, which may help patients more than the short-acting version. A similar drug, lanreotide (Somatuline®), is also available. It is also given as an injection once a month. A newer drug, pasireotide, that acts in a similar way, is currently being studied.

Interferons are natural substances that normally activate the body's immune system. They also slow the growth of tumor cells. Interferon-alfa is sometimes helpful in shrinking or slowing the growth of metastatic neuroendocrine cancers and improving symptoms of carcinoid syndrome. Its usefulness is sometimes limited by its flu-like side effects, which may be severe. The drug is given by injection.

Cyproheptadine is an antihistamine that can help relieve some of the symptoms of carcinoid syndrome.

Other medicines are also available to control specific symptoms. Please ask your doctor about these, or describe your symptoms and ask about medicines to control them.

Radiation therapy for gastrointestinal carcinoid tumors

External beam radiation therapy

In this form of radiation therapy, a beam of high-energy rays (or particles) is used to kill cancer cells. A machine aims this beam at a specific part of the body. This is the type of radiation used most often for most types of GI cancers. It is like having a regular x-ray except it takes longer and uses much higher amounts of radiation. Patients typically have treatments for 5 days a week for several weeks.

Unfortunately, this type of radiation therapy is not very effective against most GI carcinoid tumors. It is used mainly to treat pain from cancers that have spread to the bones or other parts of the body. Although surgery is the first option for most carcinoid cancers, those who can't have surgery might choose radiation therapy.

The main side effects of GI radiation therapy are tiredness (fatigue), nausea, vomiting, diarrhea, and mild, sunburn-like skin changes.

Radioembolization

This technique combines embolization with radiation therapy and is used to treat liver metastases. Embolization reduces blood flow to the cancer cells by blocking the artery feeding the area of the liver containing the tumor. This artery is a branch of the hepatic artery, the artery that feeds the liver. Blood flow is blocked (or reduced) by injecting materials that plug up the artery. Most of the healthy liver cells will not be affected because they get their blood supply from another blood vessel (the portal vein).

In this procedure a catheter is put into an artery in the inner thigh and threaded up into the liver. A dye is usually injected into the bloodstream at the same time to allow the doctor to monitor the path of the catheter via angiography, a special type of x-ray. Once the catheter is in place, small particles called microspheres are injected into the artery to plug it up.

In radioembolization, the microspheres are attached to a radioactive element called yttrium-90 or 90Y. After they are injected, the beads travel in the liver blood vessels until they get stuck in small blood vessels near the tumor. There they give off radioactivity for a short while, killing tumor cells.

Radiopharmaceuticals

In this form of radiation therapy, a drug is linked to a radioactive element. The drug travels throughout the body, attaches to the cancer cells, and gives off radiation to kill them. This type of treatment has been used for a long time to treat some cancers, but is now also being used to treat carcinoid tumors. One option is to use I-131 MIBG in higher doses than are normally used to image carcinoid.

Another radiopharmaceutical being studied is a drug like octreotide called edotreotide labeled with the element yittrium.

Clinical trials for gastrointestinal carcinoid tumors

You may have had to make a lot of decisions since you've been told you have cancer. One of the most important decisions you will make is choosing which treatment is best for you. You might have heard about clinical trials being done for your type of cancer. Or maybe someone on your health care team has mentioned a clinical trial to you.

Clinical trials are carefully controlled research studies that are done with patients who volunteer for them. They are done to get a closer look at promising new treatments or procedures.

If you would like to take part in a clinical trial, you should start by asking your doctor if your clinic or hospital conducts clinical trials.

There are requirements you must meet to take part in any clinical trial. If you do qualify for a clinical trial, it is up to you whether or not to enter (enroll in) it.

Clinical trials are one way to get state-of-the art cancer treatment. They are the only way for doctors to learn better methods to treat cancer. Still, they are not right for everyone.

Some of the factors that will influence your treatment options for a GI carcinoid tumor are:

Its size and location.

Whether it has spread to lymph nodes, liver, bones, or other organ.

Whether you have any other serious medical conditions.

 Whether the tumor is causing bothersome symptoms

It is often a good idea to get a second opinion. A second opinion may give you more information and help you feel more confident about the treatment plan you choose.

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

After Treatment

What happens after treatment for gastrointestinal carcinoid tumors?

For some people with gastrointestinal (GI) carcinoid tumor, treatment may remove or destroy the cancer. Completing treatment can be both stressful and exciting. You may be relieved to finish treatment, but find it hard not to worry about cancer coming back. (When cancer comes back after treatment, it is called recurrence.) This is a very common concern in people who have had cancer.

It may take a while before your fears lessen. But it may help to know that many cancer survivors have learned to live with this uncertainty and are leading full lives.

For other people, the cancer may never go away completely. These people may stay on drug therapy or get regular treatments with chemotherapy, radiation therapy, or other therapies to try to help keep the cancer in check. Learning to live with cancer that does not go away can be difficult and very stressful. It has its own type of uncertainty. Follow-up care

When treatment ends, your doctors will still want to watch you closely. It is very important to go to all of your follow-up appointments. During these visits, your doctors will ask questions about any problems you may have and may do exams and lab tests or x-rays and scans to look for signs of cancer or treatment side effects. Almost any cancer treatment can have side effects. Some may last for a few weeks to months, but others can last the rest of your life. This is the time for you to talk to your cancer care team about any changes or problems you notice and any questions or concerns you have.

Doctors often advise most people who have had their GI carcinoid tumors completely removed to return after about 3 to 12 months for a complete physical exam and imaging tests to look for any signs of recurrence. Blood and or urine tests may be helpful for some patients. Further visits may be recommended every 6 to 12 months after that. For small rectal tumors, proctoscopy is often recommended 6 and 12 months after treatment. Small tumors of the appendix, when adequately treated, usually don't require close follow-up, as they are very unlikely to recur. Repeat upper endoscopy every 6 to 12 months is usually recommended for patients with stomach carcinoids who have high gastrin levels. Your doctor may follow one of these schedules, but he or she might have reasons to recommend a different schedule as well.

It is important to keep your health insurance. Tests and doctor visits cost a lot, and even though no one wants to think about their cancer coming back, this could happen.

Seeing a new doctor

At some point after your cancer diagnosis and treatment, you may find yourself seeing a new doctor who does not know anything about your medical history. It is important that you be able to give your new doctor the details of your diagnosis and treatment. Make sure you have the following information handy:

A copy of your pathology report(s) from any biopsies or surgeries.

If you had surgery, a copy of your operative report(s)

If you were in the hospital, a copy of the discharge summary that doctors prepare when patients are sent home

If you were treated with radiation (including radiopharmacueticals), a copy of your treatment summary

Since some drugs can have long-term side effects, a list of your drugs, drug doses, and when you took them

Copies of your imaging tests (these can often be put on a DVD)

Copies of your lab results

The doctor may want copies of this information for his records, but always keep copies for yourself.

What’s new in gastrointestinal carcinoid tumor research and treatment?

There is always research going on in the field of gastrointestinal (GI) carcinoids. Scientists keep looking for the causes of, ways to prevent, and new approaches to diagnose and treat GI carcinoid tumors.

Genetics

Researchers are looking for the causes of GI carcinoid cancer in the hope that this knowledge can be used to help prevent or treat the disease in the future. A great deal of progress has been made in recent years. For example, scientists have found that changes in the MEN1 gene (the gene that causes multiple endocrine neoplasia, type 1) are seen in many people with GI carcinoids. Other genetic changes that seem to make tumors more aggressive are now being explored as well.

Diagnosis and staging

Because the outlook and treatment of GI carcinoid tumors/cancers and other cancers of the digestive tract are very different, accurate diagnosis is important. Researchers have made great progress in developing tests that can detect specific substances found in the cells of carcinoid tumors. Most of these tests treat tissue samples with special antibodies produced in the lab. The antibodies are designed to recognize specific substances that appear only in certain types of tumors.

OctreoScan is an imaging test commonly used to look for GI carcinoid cancers in the body. Researchers are now looking at other radionuclide methods to see if they can detect carcinoid tumors early.

Treatment

Surgery is the main treatment option for carcinoid tumors when possible. But better approaches are needed when surgery can't remove all of the tumors. Chemotherapy has had limited success. New chemotherapy drugs and combinations of drugs are being studied, but true advances are likely to come from other approaches.

Targeted therapy

Several newer types of drugs, known as targeted therapies, are now being studied for use against neuroendocrine tumors and cancers. Targeted therapy uses drugs or other substances to identify and attack cancer cells while doing little damage to normal cells. These therapies attack the cancer cells' inner workings − the programming that makes them different from normal, healthy cells. Each type of targeted therapy works differently, but all alter the way a cancer cell grows, divides, repairs itself, or interacts with other cells.

Everolimus (Affinitor®) is a targeted therapy drug that works by blocking a cell protein known as mTOR, which normally promotes cell growth and division. It is approved by the FDA to treat advanced pancreatic neuroendocrine tumors. Because it can be helpful in the treatment of neuroendocrine tumors that start in the pancreas, it was studied to see if it could help patients with GI carcinoids. In one study, adding everolimus to octreotide (Sandostatin) was better than octreotide alone in halting tumor growth.

Bevacizumab (Avastin®), is another type of targeted therapy drug that attacks a tumor's blood supply. It is already being used against some types of cancer and is being studied for carcinoid tumors. Other targeted therapies block the molecules that increase the growth of cancer cells. Some of these (such as erlotinib, temsirolimus, sorafenib) are used in other types of cancer and are now being tested against carcinoids.

Octreotide is the drug most commonly used to help treat symptoms of the carcinoid syndrome, but it doesn't work for everybody. Researchers are now looking at related drugs, such as pasireotide, which may be more potent and may help more people.

Radionuclide scans, such as the I-131 MIBG scan, can be helpful in finding neuroendocrine cancers because they use substances that are attracted to neuroendocrine cells. These substances are attached to slightly radioactive elements so that they can be detected with special cameras. Using higher doses of I-131 MIBG delivers more radiation to the tumor cells and is used in Europe to treat neurendocrine tumors and cancers. But doctors are now studying the use of a form of octreotide (or a similar drug called edotreotide) that has been attached to a radioactive form of the element yttrium called 90-Y. When injected into the body, the drug homes in on the tumor cells, allowing the radiation from the 90-Y to kill them. So far, results have been promising, but this approach is still only available in the United States as a part of a clinical trial.

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