Periampullary Carcinoma (Periampullary Cancer)

The ampulla of Vater is a mound-like opening in the duodenum. The duodenum is a C shaped loop of bowel at the beginning of the intestine. It is where the bile duct bringing bile from the liver and pancreatic duct which brings pancreatic juice from pancreas meets and then opens into the intestine.

Periampullary cancer is a term used to refer to cancer that occurs in the vicinity of the ampulla of Vater. This includes cancer affecting the head of the pancreas, distal bile duct (cholangiocarcinoma), duodenum, and ampulla. It may also be called a periampullary tumour (tumor) or periampullary mass depending on clinical suspicion. These cancers are grouped together because they share similar clinical features and treatment options. Although they are all adenocarcinomas, their prognosis varies. Surgical removal of these tumors, if possible, offers the best chances of a cure.

Anything that increases your risk of getting a disease is called a risk factor. The risk of someone getting periampullary cancer increases with age. Another common risk factor is regular smoking and drinking of alcohol. Some patients get this disease because they are genetically more prone. The risk factors are slightly different for all these four cancer types.

Periampullary cancers compress the bile duct, blocks the flow of bile and cause yellowing of eyes and urine called jaundice. This is usually accompanied by pale stools and itching. Other warning signs of periampullary cancer can be weight loss, loss of appetite and abdominal pain. Besides, duodenal and ampullary cancers bleed causing black stools (melena) and anaemia.

Once a periampullary mass, growth, or tumour is suspected, it is diagnosed and staged using either a high-resolution, thin-cut, triple-phase CT scan of the abdomen combined with a CT scan of the chest, or a PET-CT scan. We prefer to perform a high-resolution, thin-cut PET-CT with a dedicated triple-phase contrast-enhanced CT protocol, which accurately evaluates the local tumour extent and detects distant metastases. Your surgeon will also do tests to quantify your jaundice, check your kidney function, haemoglobin and blood clotting parameters. A tumour marker called CA19.9 will also be checked.

Additional investigations may be required to confirm the diagnosis, accurately stage the disease, and plan the most appropriate treatment. Depending on the clinical situation, these may include the following:

Staging is based on the TNM classification and determines whether the cancer is localized, locally advanced or metastatic. Accurate staging helps decide whether surgery, chemotherapy or both are required.

Treatment depends on the stage of the disease, the degree of jaundice, and the patient's overall fitness. Every patient is discussed in a multidisciplinary team (MDT) meeting to determine the most appropriate treatment strategy. Surgery (Whipple procedure or pancreaticoduodenectomy) offers the best chance of cure and is recommended when the cancer can be completely removed.

If jaundice is severe, your surgeon may advise endoscopic retrograde cholangiopancreatography (ERCP) with stenting before surgery. During this procedure, a plastic or metallic stent is placed across the blocked bile duct to relieve jaundice and improve liver function before definitive treatment.

For patients with borderline resectable or locally advanced disease, neoadjuvant treatment (chemotherapy with or without radiotherapy) may be recommended after reducing jaundice to shrink the tumour, improve the likelihood of complete surgical removal, and achieve better long-term outcomes. In some cases, this approach can downstage the disease sufficiently to make curative surgery possible.

Patients with metastatic disease are usually treated with palliative systemic therapy, supportive care, and metallic stenting to relieve jaundice and improve quality of life.

The operation performed to remove periampullary cancer is called the Whipple procedure, also known as pancreaticoduodenectomy. It is a complex and major abdominal surgery that involves careful dissection around important blood vessels near the pancreas and is typically performed in specialised centres by experienced surgical teams. During this operation, the head of the pancreas, duodenum, distal bile duct, gallbladder, part of the stomach (in a standard Whipple procedure), a small segment of the small intestine, and the adjacent lymph nodes are removed. The aim of the surgery is to completely remove the tumour along with surrounding tissues that may contain microscopic disease, thereby offering the best chance of long-term survival.

The digestive tract is then reconstructed by joining the remaining pancreas, bile duct, and stomach (or duodenum in selected patients undergoing a pylorus-preserving pancreaticoduodenectomy) to the small intestine. This is done through pancreaticojejunostomy (PJ), where the pancreas is connected to the small intestine, or pancreaticogastrostomy (PG), where the pancreas is connected to the stomach; hepaticojejunostomy (HJ), where the bile duct is connected to the small intestine; and gastrojejunostomy (GJ), where the stomach is connected to the small intestine, allowing normal digestion to continue.

In appropriately selected patients, the Whipple procedure can be performed using minimally invasive techniques, including laparoscopic or robotic surgery. We prefer the robotic Whipple approach because of its advantages. Robotic Whipple uses advanced systems that provide the surgeon with a clear 3D view and enhanced dexterity through wristed instruments that allow 360-degree movement, filter hand tremors, and stabilize movements for precise dissection, enabling more accurate surgery. This helps reduce blood loss and complications. Minimally invasive approaches are associated with smaller incisions, reduced postoperative pain, shorter hospital stays, and faster recovery, while maintaining comparable oncological outcomes when performed in experienced centres.

For patients with cancer that has spread to other parts of the body (metastatic periampullary cancer), the aim of treatment is to relieve symptoms, maintain quality of life, and prolong survival. Systemic chemotherapy is the main treatment and is usually started after confirmation of the diagnosis by biopsy. In addition, molecular profiling using next-generation sequencing (NGS) is increasingly recommended to identify actionable genetic alterations. This can help guide the use of targeted therapies and immunotherapy in selected patients, such as those with specific mutations or biomarkers (e.g., MSI-high/dMMR, HER2 amplification, or other targetable alterations), offering a more personalized treatment approach.

If obstructive jaundice is present, biliary drainage is performed before chemotherapy, usually by endoscopic retrograde cholangiopancreatography (ERCP), during which a plastic or self-expanding metallic stent is placed across the blocked bile duct to relieve jaundice, improve liver function, and reduce symptoms such as itching, thereby helping patients become fit to receive chemotherapy. In cases where ERCP is not feasible or unsuccessful, percutaneous transhepatic biliary drainage (PTBD) may be required.

If the tumour causes gastric outlet obstruction and prevents food from passing normally, an endoscopic duodenal stent may be inserted to restore oral intake. Endoscopic gastrojejunostomy (EUS-guided GJ) is another minimally invasive option to bypass the obstruction. If endoscopic methods are not feasible or unsuccessful, a surgical bypass may be required.

It is often measured as 5-year survival. It is the percentage of people with the same type and stage of cancer who are alive 5 years after diagnosis. These estimates are generated from many patients. The overall long-term survival rate for ampullary and duodenal carcinoma after the Whipple procedure is 55-60%. For pancreatic cancer and distal cholangiocarcinoma, the overall long-term survival rate after surgery is 35-45%.