Adenocarcinoma of the ampulla of Vater (or ampullary adenocarcinoma) arises from the ampullary region, including the duodenal surface of the ampulla, the transitional ampullary epithelium, and the ampullary ducts (the very distal ends of the common bile duct and the pancreatic duct), that are lined by pancreatobiliary epithelium. 

Ampullary adenocarcinomas are typically diagnosed at an early stage, because the engulfment of the papillary orifice causes biliary ostruction and jaundice, or may result in acute pancreatitis. Papillary masses may be seen on upper endoscopy and on endoscopic ultrasound, and biopsied can be performed.

In jaundiced patients, it may be necessary to place a stent (a small tube made of plastic or of metal) to relieving the blocked common bile duct and resolve jaundice. This is usually done through an endoscopic procedure called ERCP (endoscopic retrograde cholangiopancreatography). The procedure consists of two distinct phases:

• Diagnostic phase: a very small catheter is endoscopically guided through the ampulla of Vater into the common bile duct. A small amount of contrast material is then injected, and x-rays are taken. This dye outlines the bile duct and the pancreatic duct, and shows the site and the morphology of biliary blockage that might be due to cholangiocarcinoma.
• Operative phase: a small cut is made on the ampullary orifice (papillotomy), then the stent is passed through the endoscope and is placed into the bile duct. The stent helps keep the common bile duct open and resists compression from the surrounding cancer.

Cross-sectional imaging confirms the diagnosis and is necessary to stage the neoplasm. A staging system is a standardized way in which the cancer care team describes the extent that a cancer has spread, and contains different pieces of information, including:

• Contrast-enhanced computed tomography (CT). The CT scan is an x-ray test (it uses ionizing radiations) that produces detailed cross-sectional images of the body. 3D reconstruction softwares allow detailed tumor characterization. CT scans show the ampullary region, the duodenum and the pancreas fairly clearly. A characteristic sign of ampullary cancer is the simultaneous dilation of the common bile duct and of the pancreatic duct, known as “double duct sign”. CT scans can also show the nearby organs, as well as lymph nodes and distant organs where the cancer might have spread
• Magnetic resonance imaging (MRI). MRI scan use radio waves and strong magnets instead of x-rays. It is a multiplanar imaging modality. MRI with cholangio-pancreatography is very useful to outline the biliary and pancreatic ductal system anatomy. The double duct sign is well evident on cholangio-pancreatography.
• Contrast-enhanced ultrasonography (CEUS). This is an new imaging technique that involves the use of microbubble contrast agents to show real-time tissue perfusion information. Both margins and size of the lesion are more visible, improving the detection of vascular infiltration. In addition, CEUS improves hepatic staging. 

The principal tumor marker measured in pancreatobiliary neoplasms is Ca 19.9, an antigen released by neoplastic cells. Ca 19.9 serum levels are elevated in many patients with ampullary adenocarcinoma. However, there are also some non-cancerous conditions that cause a high level of Ca 19.9, such as gallstones, pancreatitis, cystic fibrosis, liver disease, pulmonary and thyroid diseases. Furhermore, Ca 19.9 can be elevated in people with obstruction of the bile ducts, that is the case of many patients with ampullary adenocarcinoma. On the contrary, in patients who lack the Lewis antigen (a blood type protein on red blood cells), which is about 10% of the Caucasian population, Ca19.9 is not expressed, even in those with large tumors. That’s why Ca 19.9 is not particularly useful as a diagnostic test for pancreatobiliary neoplasms. After the diagnosis of ampullary adenocarcinoma is confirmed, and if the individual’s Ca 19.9 level was elevated before treatment, the Ca 19.9 test can be used as a prognostic factor.

Once the radiologic characterization has been obtained (tumor size, relation with peripancreatic vessels, lymph node status, presence of metastases), this information is combined to assign a stage. The current staging is based on the TNM system (tumor/node/metastasis), according to the American Joint Commitee on Cancer (AJCC, seventh edition, 2010, www.cancerstaging.org). Tumor stage is expressed in Roman numerals I through IV.

Most of ampullary adenocarcinomas are amenable of curative resection. As seen, these neoplasms are diagnosed early, when they are far enough from surrounding tissue and vessels. The procedure of choice is pancreaticoduodenectomy. Patients are given chemotherapy or chemo-radiotheraphy after the cancer has been surgically removed to try to eliminate any cancer cells that have been left behind. The chemotherapy regimen is tailored on the histologic subtype. This type of treatment is called adjuvant treatment, and lowers the chance that the cancer will recur. The treatment of locally advanced neoplasms is similar to that of pancreatic ductal adenocarcinoma and distal cholangiocarcinoma.

Ampullary adenocarcinoma may spread (metastasize) to the liver. Standard medical treatment for metastatic ampullary adenocarcinoma involves chemotherapy. Individualized medical treatment regimens as tailored by expert oncologists involving single agents or combination therapy may prolong survival and quality of life. And finally, clinical trials remain an option.

After radical resection, patients are enrolled in a strict surveillance protocol, including a detailed clinical examination, measurement of serum Ca 19.9, and cross-sectional imaging. Similarly, locally advanced and metastatic patients are followed-up periodically to check for possible response to therapy and to control symptoms.