Ampullary cancer is a rare type of gastrointestinal cancer that arises in the ampulla of Vater, the small but vital opening where the bile duct and pancreatic duct empty into the duodenum, the first portion of the small intestine. Although uncommon, it is important because of its unique location and the tendency to cause noticeable symptoms early in the disease process. Unlike many other gastrointestinal cancers that remain silent until advanced, ampullary cancer frequently presents with jaundice and digestive changes that prompt earlier medical evaluation.

While it accounts for less than 1% of all gastrointestinal cancers, ampullary cancer makes up about 7% of cancers in the periampullary region. Because of this, physicians and researchers study it closely to better understand its development, improve diagnosis, and develop treatment strategies. This article provides an in-depth look at ampullary cancer, including what it is, how it develops, risk factors, signs and symptoms, diagnostic methods, treatment options, prognosis, and ways to live with the condition.

Ampullary cancer, also known as ampullary carcinoma, originates in the ampulla of Vater. This small structure serves as the entry point for bile and pancreatic enzymes into the small intestine, aiding in digestion. When cancer develops here, it can block the flow of bile and pancreatic juices, leading to symptoms such as yellowing of the skin and eyes (jaundice), pale stools, and abdominal pain.

Ampullary cancer differs from cancers of the pancreas or bile ducts in several ways. Because of its position, symptoms tend to appear sooner, making early detection more common. This gives patients a better chance of successful treatment. However, despite earlier detection, ampullary cancer can be aggressive and still requires timely medical attention and careful management.

It can occur as a single, sporadic case or as part of inherited cancer syndromes. Most diagnoses occur in older adults, usually over age 70, though younger individuals with genetic predispositions are also at risk.

The exact cause of ampullary cancer is not completely understood. Like most cancers, it results from genetic mutations that cause cells in the ampulla of Vater to grow uncontrollably and form tumors. These mutations may occur randomly or be influenced by inherited syndromes, chronic inflammation, or environmental exposures.

Some of the most recognized risk factors include:

• Familial adenomatous polyposis (FAP), a hereditary condition characterized by numerous colon polyps and associated with a high risk of gastrointestinal cancers
• Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), which increases risk for several cancers including ampullary cancer
• Peutz-Jeghers syndrome, a rare condition involving benign intestinal polyps and higher lifetime cancer risks
• Chronic inflammation of the bile or pancreatic ducts, such as from chronic pancreatitis or cholangitis
• Pre-existing adenomas in the ampulla of Vater, which may evolve into cancer if not treated
• Lifestyle factors such as smoking, heavy alcohol use, and diets high in fat and low in fiber
• Environmental exposure to carcinogenic chemicals or toxins

Although these factors increase risk, not everyone with them will develop ampullary cancer. Conversely, some individuals without known risk factors may still develop the disease.

Ampullary cancer begins with genetic mutations in the epithelial cells lining the ampulla of Vater. These mutations disrupt normal cell regulation, causing cells to multiply abnormally. Over time, clusters of these abnormal cells form tumors that can invade nearby tissues such as the pancreas, bile ducts, and duodenum.

The progression of ampullary cancer often resembles the development of colorectal cancer. In many cases, it begins as an adenoma, a benign tumor, which can transform into cancer over years or decades as more genetic mutations accumulate. This progression underscores the importance of identifying and removing adenomas before they become malignant.

Factors that contribute to its development include:

• Family history of gastrointestinal cancers
• Genetic syndromes such as FAP and Lynch syndrome
• Older age, particularly over 70
• Male sex, which shows a slightly higher incidence
• Chronic inflammation from pancreatitis or bile duct disease
• Previous gastrointestinal surgery, which may alter anatomy and increase risk

Understanding this pathway helps explain why individuals with inherited conditions are often monitored closely with regular screenings.

Ampullary cancer is very rare. It represents less than 1% of all cancers of the gastrointestinal tract but accounts for about 7% of cancers in the periampullary region. Most cases are diagnosed in people over 70 years of age, although individuals with genetic predispositions may be diagnosed earlier.

There does not appear to be a strong geographic or ethnic pattern, but access to screening and healthcare may influence detection rates. Men are slightly more likely to be affected than women. Despite its rarity, ampullary cancer has become increasingly recognized due to advances in diagnostic imaging and endoscopic techniques.

Unlike many gastrointestinal cancers, ampullary cancer frequently causes noticeable symptoms at an early stage. This is because a tumor in this location can block bile and pancreatic ducts, leading to rapid changes in digestion and appearance.

Common signs and symptoms include:

• Jaundice, or yellowing of the skin and eyes, often the first noticeable sign
• Dark urine caused by excess bilirubin excreted through the kidneys
• Pale or clay-colored stools due to reduced bile flow
• Itching, caused by bile salts accumulating under the skin
• Abdominal or back pain, ranging from mild discomfort to persistent aches
• Unintentional weight loss without dietary or lifestyle changes
• Nausea and vomiting, particularly if the duodenum is obstructed
• Loss of appetite and fatigue, often related to metabolic changes or nutrient deficiencies
• Episodes of pancreatitis if the pancreatic duct is blocked, with symptoms including pain, fever, nausea, and vomiting
• Low-grade or intermittent fever linked to infections or inflammation
• Diarrhea or greasy stools due to poor fat absorption

Because jaundice often appears early, ampullary cancer is more likely to be detected before spreading widely, improving chances for effective treatment.

Diagnosing ampullary cancer involves a combination of laboratory tests, imaging studies, endoscopic procedures, and biopsies. Accurate diagnosis allows doctors to determine the stage of cancer and plan the best treatment strategy.

Tests and procedures include:

• Blood tests such as liver function tests (LFTs) to detect elevated bilirubin and abnormal liver enzymes
• Tumor markers like CA 19-9 and CEA, which may be elevated but are not specific to ampullary cancer
• Imaging studies including abdominal ultrasound, CT scans, and MRI/MRCP to visualize ducts and identify obstructions or masses
• Endoscopic ultrasound (EUS) to obtain high-resolution images and guide fine-needle aspiration biopsies
• Endoscopic retrograde cholangiopancreatography (ERCP) to inject dye into the ducts and obtain tissue samples
• Duodenoscopy for direct visualization of the ampulla and possible biopsy
• Biopsy and histological analysis to confirm cancer type and subtype
• Staging tests such as PET-CT scans, chest X-rays, or laparoscopy to check for local invasion or metastasis

Ampullary cancer is staged using the TNM system, which evaluates tumor size, lymph node involvement, and metastasis. Stages range from I (localized) to IV (metastatic).

Differential diagnosis for Ampullary Cancer

Because its symptoms overlap with other gastrointestinal conditions, ampullary cancer must be distinguished from:

• Pancreatic cancer
• Bile duct cancer (cholangiocarcinoma)
• Gallbladder cancer
• Benign bile duct obstruction from gallstones
• Chronic pancreatitis
• Other gastrointestinal tumors

Accurate differentiation is essential because treatment and prognosis vary significantly between these conditions.

Treatment depends on stage, tumor type, and patient health. Surgery is the primary curative option, but additional therapies may be needed to improve outcomes or manage symptoms.

Surgical treatments

• Whipple procedure (pancreaticoduodenectomy), the most common surgery, involves removing the head of the pancreas, duodenum, gallbladder, bile duct, and sometimes part of the stomach
• Ampullectomy, which removes only the ampulla, may be appropriate for early tumors or adenomas
• Endoscopic surgery for small, early-stage tumors, using minimally invasive techniques

Adjuvant therapy

• Chemotherapy with drugs such as fluorouracil (5-FU), capecitabine, or gemcitabine
• Radiation therapy, sometimes combined with chemotherapy for better local control

Palliative treatment

• Endoscopic stenting to relieve jaundice by reopening obstructed ducts
• Palliative chemotherapy to slow disease progression and manage symptoms
• Pain management and nutritional support to maintain comfort and quality of life

Immunotherapy

• Pembrolizumab, a checkpoint inhibitor, for tumors with microsatellite instability-high (MSI-high) or mismatch repair deficiency (dMMR)

Targeted therapy

• Specific treatments for tumors with actionable genetic mutations, though these are less common and require molecular testing

Ampullary cancer and its treatments can cause significant complications. These include:

• Obstructive jaundice and related infections
• Cholangitis or recurrent bile duct infections
• Pancreatitis caused by duct obstruction
• Malnutrition and unintended weight loss
• Post-surgical complications such as leakage or delayed stomach emptying
• Spread of cancer to the liver, lungs, or peritoneum

Managing complications is a central part of patient care, especially in advanced disease.

The outlook for ampullary cancer is generally better than for pancreatic cancer due to earlier detection. Survival rates depend on stage at diagnosis, surgical success, and tumor subtype. Patients who undergo the Whipple procedure, followed by chemotherapy or radiation when appropriate, have the best long-term outcomes. Even with treatment, recurrence remains possible, so lifelong follow-up is necessary.

There is no guaranteed way to prevent ampullary cancer, but risk can be reduced through lifestyle changes and medical surveillance in high-risk groups. Strategies include:

• Regular screenings for individuals with genetic syndromes such as FAP or Lynch syndrome
• Endoscopic removal of adenomas before they progress to cancer
• Treatment and management of chronic pancreatitis or cholangitis
• Avoiding smoking and limiting alcohol use
• Following a diet rich in fiber, fruits, and vegetables and low in processed fats

Living with ampullary cancer requires both medical treatment and emotional support. Patients may experience physical, psychological, and social challenges. Supportive care improves quality of life and helps patients cope with the impact of their diagnosis.

Strategies include:

• Participating in support groups to share experiences with others
• Seeking counseling for emotional and mental health support
• Working with dietitians to maintain nutrition and manage digestive changes
• Staying physically active as tolerated to improve strength and energy
• Regular medical checkups to monitor treatment effectiveness and detect recurrence

Ampullary cancer is a rare but significant gastrointestinal cancer that often causes early symptoms due to its location at the junction of the bile and pancreatic ducts. Early detection improves the chances for curative treatment, especially with surgery such as the Whipple procedure. For advanced cases, palliative care and supportive therapies help manage symptoms and maintain quality of life.

Although rare, awareness of ampullary cancer is important for individuals with unexplained jaundice or gastrointestinal symptoms. Advances in diagnostics, minimally invasive surgery, and targeted therapies continue to improve outcomes. Patients and families should know they are not alone—support networks, healthcare teams, and ongoing research provide hope and resources for managing this challenging condition.

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