Encyclopedia of Cancer 2016
Pancreatic cancer is an adenocarcinoma of the pancreas (carcinoma of the pancreas). Cancer of the pancreas is usually lethal. The pancreas is a gland that secretes both digestive enzymes and insulin (from special cells called islet cells). Estimated new cases and deaths from pancreatic cancer in the United States in 2009 are as follows:
- New cases: 42,470
- Deaths: 35,240
The pancreas is located on the upper abdomen located in the midst of many vital organs, including the liver, spleen, stomach, small bowel, and large bowel. Because of its central location, it is very problematic when cancer spreads from the pancreas directly into the adjacent organs. In addition, the head of the pancreas (the portion on the patient’s right side) covers the common bile duct. The common bile duct is the duct through which bile runs from the liver and gall bladder and is mixed with pancreatic juices and then emptied into the small bowel. Blockage of this common bile duct can lead to one of the early symptoms of pancreatic cancer.
In addition, the location of the pancreas near the back (in an area called the retroperitoneum) is problematic as that is the area which contains important vessels, such as the superior mesenteric artery and veins and the celiac plexus. This means that a cancer in the pancreas will frequently (and very early in the course of the disease) invade these vessels, which enables the tumor to spread to distant sites by these vessels (such as to the liver or lung). Vessel invasion also makes the pancreas cancer inoperable. There are also many nerves that are located behind the pancreas, and those nerves are frequently affected by cancer of the pancreas.
The cause of pancreatic cancer is unknown. In about 8 % of patients, the disease appears to be inherited (familial pancreatic cancer). The primary risk factor for pancreatic cancer that is not inherited is smoking. Other risk factors include alcohol consumption, a history of surgical procedures for peptic ulcer disease,
and a history of inflammation of the pancreas (pancreatitis). Diabetes is frequently associated with cancer of the pancreas. However, it is unclear if diabetes is a risk factor for the development of pancreatic cancer or whether it is just a result of the pancreatic cancer damaging the insulin-producing (islet cells) cells of the pancreas.
It is very important to determine what type of cancer of the pancreas one is talking about. The types of cancer involving the pancreas are as follows:
- Ductal adenocarcinoma of the pancreas: This is the most common (accounts for more than 90 %) and the most lethal form of the disease. It is believed that this type of cancer arises in the cells that line the ducts of the pancreas. Ductal adenocarcinoma rapidly invades blood vessels, nerves, and other organs. It is frequently at an advanced stage when it is diagnosed and has a bad prognosis.
- Mucinous cystadenocarcinoma: This pathologic type is an uncommon form of pancreas cancer. It tends to be less invasive and mainly causes problems because of its size. The usual treatment is surgical removal, unless other vital organs, blood vessels, or nerves are involved. It is not a benign condition.
- Islet cell tumor: These are cancers that appear to arise from the small clusters of cells called islets, which are scattered throughout the normal pancreas. Islets have cells capable of making many different hormones including insulin and glucagon. Islet cell tumors can cause symptoms as the excessive hormones that they make (such as insulin) can cause severe physiologic problems (such as hypogly- cemia or low blood sugar). In general, islet cell tumors have a far better prognosis than other types of cancer of the pancreas.
The sections below will only deal with the most common type of pancreas cancers – ductal adenocar- cinoma of the pancreas.
Unfortunately, the symptoms associated with ductal adenocarcinoma of the pancreas are fairly nonspecific and appear late. They include pain in the midepigastric (stomach area) or the back (usually due to nerve invasion by the tumor), nausea and/or vomiting, fatigue, loss of appetite, and weight loss. A change in bowel habits with light-colored stools is also a sign of the disease, as is a severe darkening of the urine. One rather drastic symptom is the appearance of jaundice (a yellowness of the whites of the eyes and skin), which is caused by the tumor closing off the bile drainage such that the bile (containing the pigment bilirubin) cannot be secreted, builds up in the blood, and is deposited in the skin.
Making the diagnosis
The most effective way to determine whether or not there is a mass in the pancreas is via a special X-ray known as a spiral CT scan. Another, perhaps more sensitive method, is called an endoscopic ultrasound (or EUS) in which a tube (endoscope) is passed through the mouth into the stomach and an ultrasound device at the end of the tube sends out signals that are used to detect a mass in the pancreas. If a mass is detected, it is critical to obtain a histologic diagnosis to determine if the mass is cancer (or just a benign inflammation). A histologic diagnosis is obtained by inserting a needle into the mass to look for tumor cells, or the histologic diagnosis is obtained by performing an open surgical procedure and biopsy of the pancreas.
Staging of the Disease
Pancreatic cancer is staged as being localized, locally advanced, or metastatic (with distant spread).
- Localized: This stage means the tumor is confined within the pancreas with no major blood vessel involvement or involvement of areas outside of the pancreas.
- Locally advanced: Tumor involves major blood vessels or regional lymph nodes, but no cancer in other organs. In general, the tumor can be encompassed by a radiotherapy port. There can be no spread to distant organs.
- Metastatic: The pancreatic cancer has spread beyond the pancreas (usually into the liver, other surrounding organs, or lung).
Pancreatic cancer has the worst survival of any cancer. The overall 1-year survival for all patients is about 18 % with fewer than 2 % of patients living 5 years. For patients with localized pancreatic cancer who have surgical resections of their disease and no evidence of tumor spread beyond the pancreas in their pathology resections, there may be as many as 20 % who survive 2 years. However, it is rare to find that the pancreatic cancer is truly localized. For patients with locally advanced pancreatic cancer, the average survival is about 10 months if the patient is treated with radiation to the area in addition to chemotherapy. For patients with advanced metastatic pancreatic cancer, the average survival (with treatment) is about 6 months.
Thus, the diagnosis of pancreatic cancer comes with a terrible prognosis. In order to make progress against the disease, it is important that new therapies be developed.
- For patients with localized disease, the treatment is surgical resection. This gives the patient their only chance for prolonged survival (if the patient is fortunate to have truly localized disease). The surgical resection of the pancreas with surrounding organs and bowel reconstruction is frequently referred to as the Whipple procedure. Even with localized disease with no invasion noted on scans at the time of surgery, the pancreatic cancer frequently is found to have spread beyond the pancreas. Therefore, an important area of research is to use a neoadjuvant therapy approach. The idea with neoadjuvant therapy is to give therapy, such as radiation therapy, chemotherapy, or both, before surgery to try to “downstage” the disease. Hopefully, this approach will help make more patients truly operable with complete removal of their tumor.
- For patients with locally advanced disease, there is controversy in terms of what constitutes the best treatment. The standard treatment is considered to be radiation plus chemotherapy (usually the drug 5- fluorouracil) to sensitize the tumor to the radiation. This treatment has been reported to increase the average survival for a patient with locally advanced disease from 5 up to 10 months. However, the radiation plus chemotherapy regimen is associated with substantial side effects. Therefore, a better approach (perhaps chemotherapy alone) for patients with locally advanced pancreatic cancer is being investigated.
- For patients with metastatic pancreatic cancer, treatment is usually chemotherapy or supportive care (pain control and treatment of other medical problems) only. Until recently, there has been no chemotherapy that has improved patient survival. The anticancer agent, gemcitabine, has been shown to improve the survival of patients with advanced pancreatic cancer, plus improve the quality of life of the patient (decreased pain, improvement of performance status). When patients with advanced pancreatic cancer were treated with gemcitabine, their survival was improved from 2 % (in the control arm treated with 5-fluorouracil) up to 18 % for patients receiving gemcitabine. Currently, investigators are building on this modest advance against advanced disease by combining gemcitabine with other new cancer therapy approaches.
Familial pancreatic cancer
Only about 3–8 % of pancreatic cancers are thought to be familial. It is an area of intense study to determine if you have a parent or brother and/or sister with the disease, what type of monitoring, and/or if treatment is necessary. It is clear that some type of monitoring, such as endoscopic ultrasound, should be performed at special centers.
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