Gastrointestinal Cancers

Pancreatic Cancer

Background

Pancreatic cancer is an aggressive form of cancer that forms in the tissues of the pancreas. The pancreas is located behind your stomach and the first part of the small intestine (duodenum). The roles of the pancreas include secreting enzymes that aid in digestion (exocrine function) and secretion of hormones that help regulate blood sugar levels within the body (endocrine function).

Pancreatic cancer is the ninth most commonly diagnosed cancer in the United States. Though pancreatic cancer is initially difficult to detect, approximately 29,000 people living in the United States are diagnosed each year. Pancreatic cancer often has a poor prognosis, as most people are diagnosed at advanced stages. There are two types of pancreatic cancer, that of the exocrine gland and that of the endocrine gland. About 95 percent of pancreatic cancers begin in the exocrine cells of the pancreas.

Exocrine tumors
Most tumors affecting the exocrine gland are called adenocarcinomas. This type of cancer forms in the pancreas ducts.

Endocrine tumors
These tumors are less common and are most often benign. Though rare, cancer stemming from an endocrine tumor affects hormone-producing cells.

Pancreatic cancers that begin in the endocrine cells are very rare. Most functional endocrine tumors, meaning that they still produce hormones, are often benign (not cancerous). Symptoms, however, are a result of the overproduction of specific hormones related to the tumor.

Malignant islet cell tumors typically are non-functional. Thus, symptoms are more often related to the spread of the cancer rather than the over-production of a particular hormone.

Endocrine cell tumor cancers
Pancreatic cancers may be caused by excess hormones produced by islet cell tumors (cancer occurring in the pancreatic endocrine cells). Only about 5 percent of all pancreatic cancers develop in endocrine cells. Pancreatic tumors that produce excess hormones include:

  • Gastrinomas: A tumor that produces gastrin may cause the body to make too much stomach acid, which may result in stomach ulcers. Abdominal pain, nausea and a decreased appetite are common stomach ulcer symptoms. Numerous gastric/small bowel ulcerations with associated gastrointestinal bleeding may result. This condition is also known as Zollinger-Ellison syndrome.
  • Glucagonomas: Responsible for regulating the levels of glucose in the blood, glucagnomas increase the production of the hormone glucagon. Symptoms and conditions that may result in an excess of glucagon include: diabetes (increased blood sugar), malnutrition, diarrhea, weight loss, and irritation of the tongue or mouth (glossitis or angular cheilosis).
  • Insulinoma: Whereas glucose raises blood sugar levels, insulin lowers the amount of glucose in the blood. A tumor producing insulin may lower the blood sugar too much, causing a condition called hypoglycemia. Symptoms of hypoglycemia may include weakness, confusion or unusual sweating. In extreme cases, low blood sugar levels can cause a person to pass out or go into coma.
  • Somatostatinomas: This affects the regulation of other hormones, including glucagon and insulin. These types of tumors can also cause diabetes, as well as problems with the gallbladder.
  • Vasoactive Intestinal Peptide Tumors (VIPomas): These tumors, often referred to as VIPomas, may cause digestive problems. The low levels of stomach acid and decreased levels of potassium in the blood inhibit the digestive process. At first, this may cause diarrhea. As the tumor develops, the severity of the diarrhea may increase to the point where someone may have more than a dozen bowel movements per day.
  • Pancreatic polypeptide (PPomas): This hormone is involved with both exocrine and endocrine functions. Malignant PPomas may cause abdominal pain and may lead to an enlarged liver.

Symptoms

The majority of pancreatic cancers develop in the exocrine cells that produce the enzymes that aid in digestion. Pancreatic cancer symptoms may not develop until the cancer has reached advanced stages or spread to other parts of the body. Symptoms can include:

  • Yellowing of the skin and whites of the eyes (jaundice)
  • Digestive problems, including diarrhea, nausea or vomiting
  • Pain in the upper abdomen that can extend to the back
  • Loss of appetite
  • Nausea
  • Sudden weight loss
  • Blood clots (deep vein thrombosis/DVT)
  • Diabetes

Risk Factors

The more common type of pancreatic cancer usually occurs in the exocrine cells. The majority of exocrine pancreatic cancers occur in people over the age of 45, and the average age of diagnosis is 72. For an unknown reason, men are somewhat more likely to develop pancreatic cancer than women.

Factors that increase the risk of liver cancer include:

  • Increasing age, especially over age 60
  • Being African American
  • Being overweight or obese
  • Chronic inflammation of the pancreas (pancreatitis)
  • Diabetes
  • Family history of genetic syndromes that can increase cancer risk
  • BRCA2 gene mutation (hereditary breast and ovarian cancer syndrome)
  • p16 gene mutation (familial melanoma)
  • PRSS1 gene mutation (familial pancreatitis)
  • Peutz-Jeghers syndrome
  • Lynch syndrome (HNPCC - hereditary non-polyposis colon cancer)
  • Familial atypical mole-malignant melanoma (FAMMM)
  • Personal or family history of pancreatic cancer
  • Smoking

Staging

Stage I: Cancer has formed and is found in the pancreas only. Stage I is divided into Stage IA and IB, based on the size of the tumor.

    Stage IA: The tumor is 2 centimeters or smaller.

    Stage IB: The tumor is larger than 2 centimeters.

Stage II: Cancer may have spread to nearby tissue and organs, and may have spread to lymph nodes near the pancreas. Stage II is divided into Stages IIA and IIB, based on where the cancer has spread.

    Stage IIA: Cancer has spread to nearby tissue and organs but has not spread to nearby lymph nodes.

    Stage IIB: Cancer has spread to nearby lymph nodes and may have spread to nearby tissue and organs.

Stage III: Cancer has spread to the major blood vessels near the pancreas and may have spread to nearby lymph nodes.

Stage IV: Cancer may be of any size and has spread to distant organs, such as the liver, lung, and peritoneal cavity. It may have also spread to organs and tissues near the pancreas or to lymph nodes.

Treatment

Surgery
Surgery may be an option if the cancer is confined to the pancreas. Operations used in people with pancreatic cancer include:

  • Surgery for tumors in the pancreatic head. If your pancreatic cancer is located in the head of the pancreas, you may consider an operation called a Whipple procedure (pancreatoduodenectomy), which involves removing the head of the pancreas, as well as a portion of the small intestine (duodenum), the gallbladder and part of the bile duct. Part of the stomach may be removed, as well. A surgeon would reconnect the remaining parts of the pancreas, stomach, and intestines to allow for food digestion.
  • Surgery for tumors in the pancreatic tail and body. An operation to remove the tail of the pancreas, or the tail and a small portion of the body, is called distal pancreatectomy. A surgeon may also remove the spleen.

Radiation therapy
A doctor may recommend radiation treatment before or after surgery, often in combination with chemotherapy. A combination of radiation and chemotherapy can also be recommended for advanced pancreatic cancer that cannot be treated surgically.

Chemotherapy
Chemotherapy can be given alone or combined with radiation therapy to treat pancreatic cancer that has spread beyond the pancreas and is, therefore, surgically nonresectable. This treatment is considered palliative, (not meant to be curative). Chemotherapy and radiation may also be used after surgery to reduce the reoccurrence of pancreatic cancer.

Targeted therapy
Targeted therapy uses drugs that attack specific abnormalities within cancer cells. The targeted drug erlotinib (Tarceva) blocks chemicals that signal cancer cells to grow and divide. Erlotinib is usually combined with chemotherapy for use in people with advanced pancreatic cancer. Other targeted drug treatments are being investigated through clinical trials.

Clinical trials
The National Cancer Institute provides more detailed information about pancreatic cancer and available clinical trials.

References
National Cancer Institute, Mayo Clinic, Cancer Treatment Centers of America.