Malignant Neoplasm of Ampulla of Vater

Ampullary cancer, Ampullary carcinoma, Ampulloma, Carcinoma of the ampulla of Vater

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10048853

Ampullary cancer is a rare type of cancer that develops in a small but critical part of the digestive system where bile and digestive juices meet before entering the intestine.

Table of contents

• What is ampullary cancer?
• Location and anatomy
• How common is ampullary cancer?
• What causes ampullary cancer?
• Risk factors
• Signs and symptoms
• How is ampullary cancer diagnosed?
• Cancer staging
• Treatment options
• Outlook and survival

What is ampullary cancer?

Ampullary cancer is a rare type of cancer that starts as a growth of cells in the ampulla of Vater, which is a small opening in the wall of the first part of the small intestine^[1]. This cancer may also be called ampulla of Vater cancer or ampulloma^[8].

Ampullary cancer is a rare and aggressive type of carcinoma, which means a cancer that starts in the lining of tissues^[2]. Most ampullary cancers are adenocarcinomas, which are cancers that develop from gland cells^[7].

Location and anatomy

• Ampulla of Vater
• Bile duct
• Pancreatic duct
• Duodenum (small intestine)
• Liver
• Pancreas

The ampulla of Vater is located where two important ducts meet. The bile duct carries digestive fluid called bile from the liver, and the pancreatic duct carries digestive juices from the pancreas. These ducts join together at the ampulla of Vater before emptying into the first part of the small intestine, called the duodenum^[1][2].

Because ampullary cancer forms so close to the liver, pancreas and other digestive system organs, it can easily spread to these areas^[2]. When ampullary cancer grows, it may affect these other organs^[1].

How common is ampullary cancer?

This type of cancer is rare. Ampullary cancer accounts for less than 1% of all cancers affecting the gastrointestinal tract^[2]. These cancers represent 0.2% of all gastrointestinal cancers^[5].

The disease has an incidence of 0.5 to 0.9 per 100,000 persons^[10]. Ampullary cancer is more common in adults older than 70 years of age^[1][2]. Men are more likely to develop this cancer than women^[2].

What causes ampullary cancer?

Experts are not sure what causes ampullary cancer specifically^[2][4]. Ampullary cancer happens when cells in the ampulla of Vater develop changes in their DNA, which is the material inside cells that holds the instructions that tell a cell what to do^[1].

In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the changes give different instructions. The changes tell the cancer cells to make many more cells quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells^[1].

The cancer cells might form a lump or mass called a tumor. The tumor can grow to invade and destroy healthy body tissue. In time, cancer cells can break away and spread to other parts of the body. When cancer spreads, it is called metastatic cancer^[1][4].

Experts continue to learn more about the specific types of mutations, or changes in DNA, associated with ampullary cancer. This information helps them develop treatments that target the abnormalities and kill cancer cells. But this research is still in its early stages^[2].

Risk factors

A risk factor is anything that may increase your chance of having a disease. The exact cause of someone’s cancer may not be known. But risk factors may make it more likely for a person to have cancer. Some risk factors may not be in your control, but others may be things you can change^[4].

There are no known clear risk factors for ampullary cancer^[4][6]. However, factors that can increase your risk of developing ampullary cancer include^[2][4]:

• Being over the age of 70
• Being male
• Having certain inherited health problems that cause growths called polyps in the digestive system
• Having inherited syndromes that increase your overall cancer risk, such as familial adenomatous polyposis (FAP), Lynch syndrome and Peutz-Jeghers syndrome
• Having inflammatory bowel disease

Signs and symptoms

The most common symptom of ampullary cancer is jaundice, which is yellowing of the skin and whites of the eyes^[1][2][4]. This happens because the tumor in the ampulla of Vater blocks the bile duct. If bile flow is blocked from going into the intestines, it goes into the blood and causes yellowing of the skin and eyes^[4][6].

Because tumors in the ampullary region cause biliary obstruction, meaning blockage of bile flow, when the primary tumor is relatively small, one would expect patients with ampullary cancer to be diagnosed earlier in their disease course than patients with tumors of the pancreas^[5].

Other symptoms of ampullary cancer include^[1][2][4]:

• Unexplained weight loss
• Loss of appetite
• Abdominal pain or belly pain
• Back pain
• Nausea and vomiting
• Diarrhea
• Itchy skin
• Fever or chills
• Anemia, which means low red blood cell counts
• Pancreatitis, which is inflammation of the pancreas
• Rectal bleeding or blood in the stool
• Pale, greasy stools that are clay-colored
• Fatigue or tiredness

Many of these symptoms may be caused by other health problems. So it is important to see your healthcare provider if you have these symptoms. Your provider will do exams and specific testing to find out if you have cancer^[4][6].

How is ampullary cancer diagnosed?

Jaundice is the most common symptom of this cancer. It is often what leads people to see a healthcare provider^[4][6]. Your provider will ask you about your health history, symptoms, risk factors, and family history of disease. They will do a physical exam^[4].

You may also have one or more of these tests^[4][6][9]:

Blood and urine tests. These are used to look for anemia, bilirubin levels (the yellow substance in bile), and other changes that may be signs of this cancer. Tests may also check for tumor markers, which are substances in the blood that can suggest cancer^[2][7].

Imaging tests. These can be used to look for a tumor inside the ampulla of Vater. Imaging tests make pictures of the body. They can show the location and size of ampullary cancer^[4][9]. Imaging tests may include:

• Ultrasounds or abdominal ultrasonography
• CT scans, also called computed tomography scans
• MRI scans, also called magnetic resonance imaging
• Magnetic resonance cholangiopancreatography (MRCP)
• Endoscopic ultrasound

Endoscopy. This is a procedure to examine the digestive system. It uses a long, thin tube with a tiny camera, called an endoscope. The endoscope passes down the throat, through the stomach and into the small intestine. It allows the healthcare team to see the ampulla of Vater. Special tools can pass through the endoscope to collect a sample of tissue for testing^[4][9].

Endoscopic retrograde cholangiopancreatography (ERCP). This test uses an endoscope to look at the pancreatic and bile ducts to see if they are blocked. Sometimes a dye is injected into the bile duct using endoscopy. The dye shows up on X-rays. It can help look for blockages in the bile duct or pancreatic duct^[4][9].

Biopsy. A biopsy is the only way to confirm this cancer. It is a procedure to remove a small sample of tissue for testing in a lab. Small tissue samples are removed then examined under a microscope to find out if cancer cells are present and what type of cancer cells are present^[4][9]. Healthcare providers often collect the sample during an endoscopic test^[2].

It can be hard to tell the difference between pancreatic cancer and ampullary cancer^[4]. Cancers of the area around the ampulla, called periampullary cancers, include tumors of the pancreas, distal bile duct, ampulla of Vater, and the duodenum near the ampulla. Before surgical removal, these are often difficult or impossible to tell apart from cancer of pancreatic origin^[5].

Cancer staging

After a diagnosis of ampullary cancer, you will likely need more tests. These help your healthcare providers learn more about the cancer. They can help find out the stage of cancer. The stage is how much and how far the cancer has spread in your body^[4].

The tests that allow healthcare providers to diagnose cancer also help with cancer staging. Staging gives information about the size of the tumor, whether it has spread to nearby lymph nodes, and whether it has spread to distant parts of the body^[2]. The stage is one of the most important things to know when deciding how to treat the cancer^[4].

The current system for staging ampullary cancer is the TNM staging system. This system looks at the tumor size (T), whether cancer has spread to lymph nodes (N), and whether it has spread to distant organs, meaning metastasis (M)^[5].

Several features of the tumor predict survival. For patients who undergo a potentially curative removal of the cancer, the presence of lymph node metastases, poorly differentiated appearance under the microscope, positive margins of removal meaning cancer cells at the edge of removed tissue, and tumor invasion into the pancreas are associated with a less favorable outcome^[5]. The presence of tumor ulceration and perineural invasion, which means cancer growing along nerves, are also adverse features^[5].

Treatment options

Ampullary cancer treatment often involves surgery to remove the cancer. Treatment also may include radiation therapy and chemotherapy to kill cancer cells^[1]. The best treatment for your ampullary cancer depends on several factors. These include the size of the cancer, your overall health and your preferences^[9].

Surgery. Surgical removal of ampullary cancer is the primary way of treatment. The highest cure rates are achieved if the tumor is localized to the ampullary region and complete removal is achieved^[11]. Surgery to remove the cancer and nearby structures is often needed^[9].

The main surgical procedure is called the Whipple procedure, also known as pancreaticoduodenectomy. This involves removing the cancer by removing the head of the pancreas, part of the bile duct, part of the small intestine, and sometimes part of the stomach^[9]. Another option is pylorus preserving pancreaticoduodenectomy, which keeps more of the stomach^[22].

Treating ampullary cancer with surgery before it spreads offers the best outlook for the disease^[2]. There are cases where the cancer cannot be removed by surgery. These include when there is spread to the liver, spread to the lining of the abdomen, fluid buildup in the abdomen called ascites, lymph node involvement outside the area that can be removed, and major blood vessel invasion^[11].

Chemotherapy. Chemotherapy uses medicines to kill cancer cells. The role of treatment after surgery, called adjuvant therapy, remains controversial^[11]. Some studies have shown that chemotherapy with drugs such as 5-fluorouracil or capecitabine following surgery may improve overall survival, although more research is needed^[11].

Radiation therapy. Radiation therapy uses high-energy beams to kill cancer cells. Some studies suggest that radiation therapy combined with chemotherapy after surgery may improve local control of the cancer, particularly in patients with high-risk features such as lymph node involvement, although the benefit for overall survival is not clear^[11].

Palliative treatment. For patients with advanced or cancer that cannot be removed, treatment options focus on relieving symptoms. These may include endoscopic procedures to place stents, which are small tubes that keep ducts open, to relieve blockage^[22]. Palliative therapy can be oriented to the published treatment strategies for cancer of the colon, pancreas, and bile duct^[10].

Outlook and survival

Ampullary cancer has a poor prognosis overall, with a 5-year survival rate of 41% to 45% for locally confined disease and 4% to 7% for metastatic disease^[10].

However, patients who undergo removal of the head of the pancreas for localized cancer that has not spread from the ampulla have a superior survival compared with similarly treated patients who have cancer of pancreatic origin^[5]. Median survival averages 3 to 4 years compared to 18 to 24 months for pancreatic cancer. Five-year survival averages 35% to 55% compared to 10% to 20% for pancreatic cancer^[5].

This improved survival may be due to both earlier diagnosis and more favorable tumor biology^[5]. Ampullary cancer generally has better overall survival than patients with pancreatic cancer^[7].

Five-year overall survival after surgery is between 10% and 75% depending on the stage^[10]. Most ampullary tumors are of an intestinal or a pancreaticobiliary type based on how they look under the microscope. The pancreaticobiliary type has a worse prognosis, with median survival of 72 to 80 months for the intestinal type versus 33 to 41 months for the pancreaticobiliary type^[10].