Tumour of ampulla of Vater, also called ampullary cancer, is a rare and fast-growing cancer that develops in a small but crucial area of the digestive system where the liver and pancreas connect to the small intestine. While this type of cancer is uncommon, early recognition of symptoms like jaundice can make a significant difference in treatment outcomes.
Epidemiology
Ampullary cancer is a very rare type of cancer that affects the digestive system. The ampulla of Vater is a small opening where two important tubes meet: the bile duct that carries digestive fluid from the liver, and the pancreatic duct that carries enzymes from the pancreas. Both of these fluids empty through this opening into the first part of the small intestine, called the duodenum, where they help break down food.[1]
This cancer accounts for less than 1% of all cancers affecting the gastrointestinal tract, which is the series of organs that process food in the body. The incidence rate is approximately 0.49 to 0.9 per 100,000 people, which means that in a population of 100,000 individuals, fewer than one person per year will develop this cancer. In the United Kingdom, around 550 people are diagnosed with ampullary cancer each year.[2][5][9]
What makes this cancer particularly noteworthy is that its incidence has been slowly increasing. Research has shown that the occurrence of ampullary cancer has been rising at an annual percentage rate of 0.9%, meaning that each year there are slightly more cases than the year before.[5]
The disease tends to affect older adults more commonly. People over the age of 70 are at higher risk of developing this cancer. Additionally, ampullary cancer appears to be more common in males than in females, though the reasons for this difference are not fully understood.[2]
Causes
The exact cause of ampullary cancer remains unclear to medical experts. Like many cancers, ampullary cancer begins when cells in the ampulla of Vater develop changes in their DNA, which is the genetic material inside cells that acts like an instruction manual telling the cell what to do.[1]
In healthy cells, DNA provides instructions for the cell to grow and multiply at a controlled rate, and tells the cell when it should die. This orderly process keeps the body functioning properly. However, when cancer develops, changes in the DNA give different instructions. These abnormal instructions tell the cells to grow and multiply much faster than they should, and to keep living when they would normally die.[1]
As these abnormal cells accumulate, they can form a lump or mass called a tumor. If left unchecked for long enough, these cancer cells can grow into nearby healthy tissues and organs, damaging them in the process. Eventually, cancer cells can break away from the original tumor and travel through the bloodstream or lymphatic system to other parts of the body, a process called metastasis.[3]
Researchers continue to study the specific types of DNA changes associated with ampullary cancer. Understanding these genetic mutations helps scientists develop treatments that can target these abnormalities and kill cancer cells more effectively. However, this research is still in its early stages, and much more needs to be learned.[2]
Risk Factors
A risk factor is anything that may increase the chance of developing a disease. For ampullary cancer, there are no strongly established risk factors, meaning that doctors cannot point to specific behaviors or conditions that clearly cause this cancer. However, some factors appear to be associated with a possible increased risk.[3]
One of the most significant risk factors involves certain inherited genetic conditions that run in families. People who have familial adenomatous polyposis, or FAP, face a higher risk of ampullary cancer. This inherited condition causes numerous growths called polyps to develop throughout the digestive system. Over time, some of these polyps can become cancerous.[2]
Another inherited condition that may increase risk is Lynch syndrome, also known as hereditary nonpolypotic colorectal cancer. This genetic syndrome increases the risk of several types of cancer. Additionally, Peutz-Jeghers syndrome, another inherited condition characterized by polyps in the digestive tract and dark spots on the skin, has been linked to higher ampullary cancer risk.[2]
People with inflammatory bowel disease, which includes conditions like Crohn’s disease and ulcerative colitis that cause long-term inflammation of the digestive tract, may also have a slightly increased risk. As mentioned earlier, older age is a risk factor, with most cases occurring in people over 70 years old.[3][6]
Symptoms
The most common and often the first symptom of ampullary cancer is jaundice, which is a yellowing of the skin and the whites of the eyes. This happens because the tumor growing in the ampulla of Vater blocks the bile duct, preventing bile from flowing into the intestines as it normally should. When bile cannot drain properly, it backs up and enters the bloodstream instead, causing the characteristic yellow color to appear in the skin and eyes. This yellow pigment comes from a substance in bile called bilirubin.[1][2]
Jaundice is often what leads people to see a doctor, and it may be more noticeable in some skin tones than others. On black or brown skin, the yellowing may be less obvious but can still be seen in the whites of the eyes. Along with the yellowing, jaundice often causes other uncomfortable symptoms including very itchy skin, which can be quite bothersome and affect daily activities.[9]
When bile is blocked from flowing into the intestines, it also affects the color of a person’s stools and urine. Stools may become pale, clay-colored, or greasy-looking instead of their normal brown color. At the same time, urine typically becomes very dark, almost tea-colored. These changes happen because the bile that normally colors stool brown is not reaching the intestines, while extra bilirubin is being filtered out through the urine.[1][9]
Many people with ampullary cancer experience pain in the abdomen, which is the area of the body between the chest and pelvis. This pain may be in the upper part of the abdomen and can sometimes spread to the back. Some people also develop pain specifically in the back without significant abdominal discomfort.[2]
Unexplained weight loss is another common symptom. People may notice they are losing weight even though they have not changed their diet or exercise habits. This often happens because the cancer affects how the body processes food and nutrients. Along with weight loss, many people experience a loss of appetite, meaning they simply do not feel hungry or interested in eating.[2]
Nausea and vomiting can occur as the tumor interferes with normal digestion. Some people develop diarrhea, or loose, watery stools that occur more frequently than normal. Fever may also develop, sometimes accompanied by chills, which can make a person feel alternately hot and cold.[1][2]
In some cases, ampullary cancer can cause inflammation of the pancreas, a condition called pancreatitis. This occurs when the tumor blocks the pancreatic duct, preventing pancreatic juices from draining properly. Pancreatitis causes severe abdominal pain, nausea, vomiting, and fever. It may actually be the first sign that brings a person to medical attention.[2][8]
Less commonly, the tumor in the ampulla can ulcerate or break down, leading to bleeding into the digestive tract. This might cause blood to appear in the stool, which could look bright red or very dark and tarry. Some people may vomit blood, which might appear bright red or dark brown like coffee grounds. Even if bleeding is not visible, it can lead to anemia, which is a condition where the body does not have enough healthy red blood cells. Anemia causes fatigue, weakness, and shortness of breath.[2][9]
Fatigue, or extreme tiredness that does not improve with rest, is another symptom that many patients experience. This can significantly affect quality of life and the ability to carry out daily activities.[3]
Prevention
Unfortunately, because the exact causes of ampullary cancer are not well understood, there are no specific proven strategies to prevent this disease. Unlike some other cancers where lifestyle changes such as not smoking, maintaining a healthy weight, or getting vaccinated can reduce risk, no such clear preventive measures have been established for ampullary cancer.[1]
For people who have inherited genetic conditions that increase their risk, such as familial adenomatous polyposis, Lynch syndrome, or Peutz-Jeghers syndrome, working closely with healthcare providers is important. These individuals may benefit from more frequent monitoring and screening to detect any problems early. Genetic counseling can help families understand their risks and make informed decisions about testing and surveillance.[2]
People with inflammatory bowel disease should continue to work with their doctors to manage their condition effectively. While controlling inflammation may not directly prevent ampullary cancer, good management of chronic digestive conditions is generally beneficial for overall health.[3]
Being aware of the symptoms of ampullary cancer and seeking medical attention promptly if they develop is perhaps the most important step people can take. Early detection, when the cancer is still confined to the ampulla and has not spread to other parts of the body, offers the best chance for successful treatment.[2]
Pathophysiology
To understand how ampullary cancer affects the body, it helps to know what normally happens in the ampulla of Vater. This small opening, located in the wall of the duodenum, is where two crucial digestive fluids meet before entering the small intestine. Bile from the liver, which travels through the bile duct, and digestive enzymes from the pancreas, which travel through the pancreatic duct, join together at this point. These fluids then flow into the duodenum to help break down fats and other nutrients in the food we eat.[1]
The ampulla is lined with a layer of tissue made up of special cells called epithelial cells. These cells form a protective barrier and help keep the tissue moist. Most ampullary cancers are adenocarcinomas, which means they start in these epithelial cells. The epithelial cells in the ampulla can be similar to cells found in different parts of the digestive system, which explains why ampullary cancer can have different characteristics.[9]
Researchers have found that ampullary cancers can be classified into different histological subtypes based on which type of cells they most closely resemble. Some ampullary cancers have cells that look like the cells lining the intestine, while others have cells that look more like those found in the pancreas and bile ducts. Sometimes the cancer contains a mix of both types. This distinction is important because cancers with cells that resemble pancreatic and bile duct tissue, called the pancreaticobiliary subtype, tend to have a worse prognosis and shorter survival times compared to those that resemble intestinal tissue, called the intestinal subtype.[5][11]
When cancer develops in the ampulla, it disrupts the normal flow of bile and pancreatic juices. As the tumor grows, it can block one or both of the ducts that empty through the ampulla. When the bile duct becomes blocked, bile cannot drain into the intestines and instead backs up into the liver and enters the bloodstream. This is what causes jaundice and the associated symptoms of itchy skin, pale stools, and dark urine.[2]
If the pancreatic duct becomes blocked, pancreatic enzymes cannot reach the intestines. These powerful enzymes normally help digest food, but when they cannot drain properly, they can back up and start digesting the pancreas itself. This causes pancreatitis, which is painful and can lead to serious complications. Additionally, without pancreatic enzymes reaching the intestines, the body cannot properly break down and absorb fats from food, leading to fatty, pale stools and nutritional deficiencies.[2]
Because the ampulla is located in such a central position in the digestive system, tumors that develop there are close to several vital organs including the liver, pancreas, duodenum, and important blood vessels. As the cancer grows larger, it can invade these nearby structures. The cancer may grow into the wall of the duodenum, spread to lymph nodes in the area, or extend into the pancreas. If cancer cells enter blood vessels or lymphatic channels, they can travel to distant parts of the body such as the liver, lungs, or other organs, causing metastatic disease.[1][2]
At the molecular level, researchers have identified several genetic changes that are commonly found in ampullary cancer cells. Mutations in genes called KRAS and TP53 are frequently detected. Changes in a gene called SMAD4 and a characteristic called microsatellite stability are also associated with how aggressive the cancer behaves. Cancers with certain molecular features tend to be more aggressive and have poorer outcomes. Understanding these genetic and molecular changes helps doctors predict how the cancer might behave and may eventually lead to more targeted treatment approaches.[5]
The five-year survival rate for ampullary cancer varies greatly depending on the stage at which it is diagnosed. For cancers that are caught early and are still confined to the ampulla, the five-year survival rate ranges from 41% to 45%. However, if the cancer has spread to distant parts of the body, the five-year survival rate drops dramatically to only 4% to 7%. This stark difference highlights how important early detection is for improving survival.[11]
Interestingly, patients with ampullary cancer generally have better overall survival compared to patients with pancreatic cancer, even though the two cancers are located near each other and can be difficult to tell apart. This is partly because ampullary cancer tends to cause symptoms like jaundice earlier in its course, leading to earlier diagnosis and treatment.[8]
