What are the other Names for this Condition? (Also known as/Synonyms)

• Pancreatobiliary-type Adenocarcinoma of Ampulla of Vater

What is Pancreatobiliary-type Ampullary Adenocarcinoma? (Definition/Background Information)

• Invasive adenocarcinoma of the ampullary region is a rare and malignant tumor of the epithelium with glandular differentiation, typically affecting older adults. The tumor arises in the ampulla of Vater, which is a region in the small intestine, around the mouth, where the common bile duct and pancreatic duct discharge into the duodenum
• There are two main histological subtypes (phenotypes) of invasive adenocarcinoma of the ampullary region, which include:
  • Intestinal-type ampullary adenocarcinoma
  • Pancreatobiliary-type Ampullary Adenocarcinoma
• Pancreatobiliary-type Ampullary Adenocarcinoma is one of the more common malignancies among ampullary carcinomas. The tumor is diagnosed under a microscope, on examination of the cancer cells by a pathologist. Some of the tumors are seen with a precursor lesion, such as an adenoma or a noninvasive pancreatobiliary papillary neoplasm
• The cause of development of the carcinoma is generally unknown, but it is believed to be associated with genetic defects and certain food and lifestyle factors. The presence of premalignant lesions or certain genetic disorders (such as familial adenomatous polyposis or neurofibromatosis type 1) are major risk factors for cancer growth and development
• The signs and symptoms of Pancreatobiliary-type Ampullary Adenocarcinoma may include abdominal pain, blood in stool, fatigue, and unexplained weight loss. Complications, such as tumor metastasis to distant sites, are known to occur
• The mainstay of treatment is surgical excision of the tumor, especially when diagnosed during early stages. However, in many cases a combination of measures that include surgery, chemotherapy, and radiation therapy may be needed to treat the condition
• The prognosis of Pancreatobiliary-type Ampullary Adenocarcinoma is assessed on a case-by-case basis. The prognosis chiefly depends on the tumor stage, tumor grade, and whether it is associated with an adenoma (since tumors associated with adenomas are diagnosed earlier and are generally smaller)

Who gets Pancreatobiliary-type Ampullary Adenocarcinoma? (Age and Sex Distribution)

• Pancreatobiliary-type Ampullary Adenocarcinoma is generally seen during the 7th and 8th decade. However, a wide age range of presentation may be noted
• When younger individuals are affected, it is mostly seen in the background of a predisposing (genetic) factor such as familial adenomatous polyposis or neurofibromatosis type 1
• Both males and females are affected, although slightly more number of cases are observed in males
• All races and ethnic groups are at risk for the condition

What are the Risk Factors for Pancreatobiliary-type Ampullary Adenocarcinoma? (Predisposing Factors)

The following factors are known to increase the risk for Pancreatobiliary-type Adenocarcinoma of Ampulla of Vater:

• Presence of premalignant lesions that may include intestinal-type adenoma, non-invasive papillary neoplasm, or flat intraepithelial neoplasia (flat dysplasia). In a few cases, the adenocarcinoma is associated with an adenoma or a non-invasive papillary neoplasm. Although, it is important to note that the carcinoma can arise in the absence of such precursor lesions too
• Presence of an associated genetic disorder such as:
  • Familial adenomatous polyposis (FAP)
  • Gardner syndrome (which is a variant of FAP)
  • Lynch syndrome
  • Neurofibromatosis type 1 (NF1) or von Recklinghausen disease

Other risk factors, in general, for carcinomas of the gastrointestinal tract may include:

• Longstanding inflammation of the small intestine such as due to inflammatory bowel disease (Crohn’s disease) and celiac disease
• Smoking tobacco may increase the risk
• Alcohol consumption
• Aging: The greater the age, the higher is the risk
• Radiation therapy to the abdominal or pelvic region for cancer

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pancreatobiliary-type Ampullary Adenocarcinoma? (Etiology)

The cause of development of Pancreatobiliary-type Ampullary Adenocarcinoma is generally unknown.

• Research scientists believe that the cause of the condition is mostly due to genetic mutations, influenced by factors that include food and lifestyle habits such as high-fat, high-calorie diet and sedentary lifestyle
• The carcinoma may develop sporadically, or in the presence of a genetic disorder, such as familial adenomatous polyposis (FAP) or neurofibromatosis type 1 (NF1). When FAP is seen, the carcinoma may arise from adenomas (that may be more than one) present in the ampulla of Vater and peri-ampullary regions

A wide range of genetic defects may be noted such as:

• KRAS gene mutations
• SMAD4 tumor suppressor gene involvement (loss of gene expression)
• Rarely, gene abnormalities on the APC, CTNNB1 (beta-catenin), ERBB2, and ERBB3 genes are observed
• In later stages of cancer progression, many tumors show involvement of the TP53 gene
• High levels of microsatellite instability (MSI-H) are occasionally noted
• Invasive carcinomas show EGF gene overexpression in many cases

What are the Sign and Symptoms of Pancreatobiliary-type Ampullary Adenocarcinoma?

In some individuals, Pancreatobiliary-type Ampullary Adenocarcinoma is detected while conducting diagnostic imaging tests for other medical conditions, since no symptoms may be observed during the early stages of cancer development.

The signs and symptoms may include:

• Tumors at the ampulla of Vater may cause obstructive and persistent jaundice, even at small tumor sizes
  • Obstruction of the bile ducts leading to jaundice also results in weight loss and pain in the abdomen
  • Yellowing of the skin and eye whites
  • It may also lead to pruritus, an intense itching sensation all over the body
• Inflammation of the pancreas (or pancreatitis) may be noted in some individuals. This may be manifested as abdominal pain, back pain, and presence of fat in stool
• The presence of a polypoid, nodular, or ulcerated mass (on upper GI endoscopy)
• Some pancreatobiliary-type adenocarcinomas are noted in the background of an adenoma or a non-invasive papillary neoplasm (which are precursor lesions)
• GI tract bleeding: Bleeding through stool may take place over a long period, which can result in anemia. The common symptoms of anemia include pale skin, tiredness, and shortness of breath
• Large tumors can frequently cause:
  • Abdominal (cramping) pain and discomfort
  • Swollen abdomen
  • Nausea and vomiting
• Presence of a palpable mass, when tumors are large
• Unexplained weight loss
• Narrowing of the intestine that can lead to intestinal obstruction in severe cases
• When tumors are greater than 4 cm, it may involve the surrounding structures such as duodenum, pancreas, and extra-hepatic bile duct

Sometimes, simultaneously multiple primary tumors may be present at the duodenum, pancreas, gallbladder, or extra-hepatic biliary duct (called synchronous tumors); or, the tumors may form after a period of 1-3 months (called metachronous tumors). Such tumors can cause a variety of additional symptoms.

How is Pancreatobiliary-type Ampullary Adenocarcinoma Diagnosed?

A diagnosis of Pancreatobiliary-type Ampullary Adenocarcinoma may be undertaken using the following tests and exams:

• Complete evaluation of family (medical) history, along with a thorough physical examination
• Stool sample analysis
• X-ray of the abdomen and pelvic region
• Barium enema X-ray
• Endoscopy for tumors in the duodenum (upper part of the small intestine). Capsule endoscopy is an effective tool for observing the small intestine along its entire length
• Liver function blood test: Ampullary carcinomas obstructing the pancreatic and bile duct may present an increase in serum levels of compounds, such as bilirubin, glutamic transaminase, and alkaline phosphatase, in many individuals
• Test for serum bilirubin levels
• Blood tests that may involve tumors markers such as:
  • Carcinoembryonic antigen (CEA) test
  • CA 19.9 blood test
  • CA 15.3 blood test
  • Alpha feto-protein (AFP) tumor marker test
• CT or MRI scan of the abdomen and pelvic region: CT scan with contrast or enteroclysis is a reliable procedure for diagnosis and staging of tumor
• Abdominal ultrasound scan
• Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the gastrointestinal tract
• Endoscopic ultrasonography: During this procedure, fine needle aspiration biopsy (FNAB) can be performed on the affected area. This is good technique for tumor detection, including tumor invasion parameters, and whether nearby lymph nodes are affected
• Imaging studies, such as MRI scan, scintigraphy, and PET scan, may be performed to detect tumor invasion and metastasis
• Additionally, imaging studies for synchronous tumors may be necessary. For metachronous tumors, close follow-up, such as imaging studies, and follow-up surveillance endoscopy procedures may be required
• Endoscopic retrograde cholangiopancreatography (ERCP): This technique is used when symptoms of pancreatic cancer are present in the individual. A special equipment and dye injections are used to obtain a series of images. If required, a biopsy sample may also be collected during the procedure
• Tissue biopsy of the tumor:
  • A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis
  • The tumors may be well-differentiated, moderately-differentiated, or poorly-differentiated (i.e., low-grade or high-grade tumors)
  • If carcinoma arises in an adenoma, then a superficial biopsy may not be sufficient for diagnosis, since the carcinoma may be missed
• It is important to rule-out metastatic tumors, such as malignant melanoma that has metastasized to the ampullary region, by undertaking a differential diagnosis

Note: Based on cell studies, most invasive adenocarcinomas have intestinal phenotype differentiation (in 50 to 80% of the cases) or pancreatobiliary phenotype differentiation (in 15 to 20% of the cases). Some tumors show both intestinal and pancreatobiliary phenotypes (mixed tumors).

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pancreatobiliary-type Ampullary Adenocarcinoma?

Some potential complications of Pancreatobiliary-type Ampullary Adenocarcinoma include:

• Emotional and psychological stress due to cancer diagnosis
• Iron-deficiency anemia, due to excess loss of blood
• Perforation of the small intestine by advanced tumors - this can lead to fluid in the peritoneal cavity (ascites), peritonitis, and blockage in the large intestine/colon
• Complications may arise from the underlying genetic disorder, if any present
• Large-sized tumors may compress adjoining tissues and structures resulting in additional complications
• Involvement of lymph nodes of the pancreatic region is commonly noted
• Metastasis or spread of carcinoma may occur to the liver, peritoneal cavity, and lungs
• Recurrence of the tumor after treatment, especially due to partial surgical removal
• Damage to the muscles, vital nerves, and blood vessels, during surgery
• Post-surgical infection at the wound site is a potential complication
• Side effects due to chemotherapy and/or radiation therapy

Note: Tumors that are confined to the mucosal surface of the intestine (superficially-invasive tumors) are rarely associated with lymph node metastasis.

How is Pancreatobiliary-type Ampullary Adenocarcinoma Treated?

The treatment of cancer of the ampullary region may depend upon a consideration of the following set of factors:

• The histological subtype of the cancer
• Stage of the cancer
• Size and location of the tumor
• Severity of the signs and symptoms
• Age of the individual
• Overall health status of the individual
• The treatment preferences of the individual

The treatment measures for Pancreatobiliary-type Ampullary Adenocarcinoma may include the following:

• Surgery:
  • When the tumor is confined to the surface, then endoscopic mucosal/submucosal resection (or surgical removal via endoscopy) is undertaken
  • Surgical removal of the entire tumor may be the preferred method of treatment (polypectomy or surgical resection)
  • If lesions are large, then it may not be possible to remove through endoscopy. In such cases, they are removed through transduodenal ampullectomy or pancreatoduodenectomy
  • Cancers in the duodenum and near the pancreatic duct outlet may be treated through a surgical technique termed pancreaticoduodenectomy (or Whipple procedure)
• Chemotherapy: This approach uses a combination of drugs to kill the cancerous cells and can be used in patients, for all stages of the tumor
  • There can be severe side effects including fatigue, nausea, hair loss, anemia, high risk of infection, and drug-specific reactions
  • Chemotherapy can be administered as a pill, liquid, shot, or intravenously
• Tumors that have metastasized and where a complete surgical removal is not possible may be treated using anti-metabolites and platinum compounds
• Radiation: Radiation therapy is the use of high-energy radiation waves to kill cancer cells, by destroying their DNA
  • This treatment modality may be used in combination with chemotherapy
  • The radiation may be administered by a machine placed outside the body, or by placing a radioactive material inside the body
  • The side effects of radiation therapy include nausea, vomiting, fatigue, pain, risk of cancer later in life, and risk of heart disease
  • Radiation can damage healthy cells in addition to cancer cells, causing further complications
• Supportive treatment: Steroids, blood transfusions, anti-nausea medications, and antibiotics, may be used as supportive therapy. In combination with other treatment measures, these can help combat the symptoms of immunodeficiency
• Palliative care for advanced tumors
• Undertaking treatment of any underlying inflammatory bowel diseases/genetic disorders, as necessary

Regular observation and periodic checkups to monitor the condition is strongly recommended following treatment.

How can Pancreatobiliary-type Ampullary Adenocarcinoma be Prevented?

Presently, there are no specific methods or guidelines to prevent the formation of Pancreatobiliary-type Ampullary Adenocarcinoma. However, if it is associated with a genetic disorder, the following points may be considered:

• Genetic counseling and testing: If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Regular health check-ups might help those individuals with a history of the condition in the immediate family and help diagnose the tumor early

Factors that can help prevent or reduce incidence of the Pancreatobiliary-type Ampullary Adenocarcinoma (according to studies) include:

• Taking early and appropriate treatment for inflammatory bowel diseases, if any
• Consuming a diet that is rich in whole grains, vegetables, and fruits
• Taking foods rich in vitamin D and calcium
• Physical activities and regular exercising
• Avoidance of smoking; consuming alcohol in moderation
• In order to avoid a relapse, or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory. Often several years of active vigilance are crucial and necessary.

What is the Prognosis of Pancreatobiliary-type Ampullary Adenocarcinoma? (Outcomes/Resolutions)

• The overall prognosis of Pancreatobiliary-type Ampullary Adenocarcinoma is typically guarded. The prognosis is reportedly comparable to the prognosis of similar adenocarcinomas arising in the pancreas and extra-hepatic bile ducts
• Typically, the outcome of pancreatobiliary-type of adenocarcinoma is slightly poorer than that of intestinal-type of adenocarcinoma
• In general, the prognosis depends upon a set of several factors, which include:
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Histological subtype of the tumor
  • Presence of certain genetic abnormalities or mutations. An unfavorable prognosis is noted with high levels of microsatellite instability (or MSI-H)
  • Whether the tumor has developed at the site of an adenoma or not: Carcinomas associated with a precursor lesion, such as an adenoma, have better prognosis than those not associated with one
  • Grade of the tumor: Poorly-differentiated tumors (high-grade) have poorer prognosis than well-differentiated tumors (low-grade)
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of vital organs may complicate the condition, including the involvement of the vascular and nervous system (vascular and perineural invasion)
  • The surgical resectability of the tumor (meaning if the tumor can be removed completely): Tumors that can be completely removed have better outcomes
  • Whether the tumor is occurring for the first time or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

An early diagnosis and prompt treatment of Pancreatobiliary-type Adenocarcinoma of Ampulla of Vater generally yields better outcomes than a late diagnosis and delayed treatment.

Additional and Relevant Useful Information for Pancreatobiliary-type Ampullary Adenocarcinoma:

The following article link will help you understand other cancers and benign tumors:

http://www.dovemed.com/diseases-conditions/cancer/