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Cancer of the Pancreas
Andrew H. Ko, MD

Types
How it spreads

What Causes It
Staging and treatment
Common signs and symptoms
Supportive care

Important questions to ask your doctor

Pancreatic cancer is the fifth leading cause of cancer-related mortality in the United States, with an estimated 33,370 deaths attributable to this disease in 2007. In fact, the annual mortality rate almost approximates the annual incidence rate, which reflects the generally short survival time associated with pancreatic cancer, most often less than one year. On a stage for stage basis, cancer of the pancreas is met with the shortest median survival time out of all cancer types.


Types
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The pancreas, an organ situated deep in the abdominal cavity, serves several critical functions. The exocrine compartment of the pancreas, comprised of acinar and ductal cells, produces a number of enzymes that are delivered directly into the small intestine and aid in the digestion of food. The endocrine compartment consists of clusters of cells within the pancreas (referred to as islets of Langerhans) which produce several different hormones, including insulin and glucagon, that are secreted into the bloodstream and are responsible for controlling glucose (sugar) levels in the body. When we talk about pancreatic cancer, we are most frequently referring to cancer that arises from the ductal (exocrine) cells of the pancreas. The medical term for this type of cancer is ductal adenocarcinoma. Much less often, cancers may arise from the endocrine compartment of the pancreas, and are referred to as pancreatic endocrine tumors, islet cell tumors, or more specifically by the type of hormone-producing cell involved (insulinoma, glucagonoma, etc.)


How it spreads
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Cancer cells may spread by direct extension from the pancreas to adjacent structures, such as the bile duct, duodenum (small intestine), spleen, colon, adrenal gland, kidney, or vertebra. Cancer cells may also spread to regional lymph nodes. Most common sites of distant metastatic spread include the liver and the lungs (via the bloodstream) and the peritoneum (abdominal cavity).


What causes it
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Advancing age is the strongest risk factor for pancreatic cancer, with the vast majority of cases occurring after the age of 60 years. There is also a clear association between cigarette smoking and pancreatic cancer; however, the roles of diet, alcohol, and coffee have not been substantiated and should not be considered proven risk factors.

Two common diseases which have been actively studied regarding their possible association with pancreatic cancer are diabetes and chronic pancreatitis. Multiple studies have come up with conflicting results, and so at present we cannot say that these diseases definitely are risk factors for the development of pancreatic cancer. More commonly, these diseases may represent an early symptom of pancreatic cancer rather than a direct cause of it.

There are also several genetic syndromes that have been associated with an increased incidence of pancreatic cancer, including hereditary non-polyposis colorectal cancer, familial atypical multiple mole-melanoma, and certain types of hereditary breast cancer (those caused by the BRCA2 mutation).


Staging and treatment
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Although a TNM staging system exists for pancreatic cancer, most clinicians stage the disease in reference to its treatment implications: local/resectable, locally advanced/unresectable, and metastatic. Staging evaluation typically should always include a high-quality computerized tomography (CT) scan to assess the extent of disease and whether the cancer may be resectable. In certain instances an endoscopic ultrasound may be useful when the pancreatic cancer is not well-visualized on CT. For cancers located in the pancreatic tail, surgeons will oftentimes first perform a diagnostic laparoscopy to look for the presence of any metastases that cannot be seen by CT.

Stage Description Approx. % of pancreatic cancer cases Treatment options Median survival
Local/resectable Disease is confined to the pancreas and is clearly separated from surrounding blood vessels 10% Surgery; postoperative chemotherapy and/or radiation may also be offered 17 months
Locally advanced/unresectable Disease encases or compresses surrounding blood vessels, or has directly extended into adjacent structures 30% Chemotherapy (most commonly gemcitabine-based) and/or radiation. In very rare instances, cancers that respond well to initial treatment may subsequently be surgically resected. 8-9 months
Metastatic Evidence of extrapancreatic spread to distant organs (liver, lungs, etc.) 60% Chemotherapy (most commonly gemcitabine-based); investigational trials 4-6 months


Common signs and symptoms
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Obstructive jaundice (yellowing of the skin and eyes, itching, dark urine, clay-colored stool) - occurs frequently when the cancer is located at the head of the pancreas
Weight loss and anorexia
Fatigue
Abdominal pain, frequently radiating to the back
Change in bowel habits (constipation or diarrhea)

Supportive therapy measures
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Even if surgical resection is not possible, other minimally invasive procedures can help relieve some of the common signs and symptoms associated pancreatic cancer. These include:
Stenting of the common bile duct, usually by endoscopic retrograde cholangiopancreaticography (ERCP), to relieve obstructive jaundice symptoms. This is usually performed early on when cancer located at the head of the pancreas is blocking normal drainage of the bile, and should be done by an experienced gastroenterologist.
Celiac plexus block, to control cancer pain. This is done by a skilled anesthesiologist/pain specialist and is usually reserved in the cases of patients who have unremitting pain not well-controlled by narcotics and other pain medicines.
Enteral stenting, to help with gastric outlet or duodenal obstruction. This is performed by an experienced gastroenterologist when the pancreatic cancer is blocking the stomach or intestine and preventing normal passage of food through the digestive tract.
Other critical supportive measures for patients with advanced pancreatic cancer include supporting their nutritional status, as rapid weight loss, muscle wasting, and anorexia are very common problems associated with this disease. Consultation with a nutritionist early on is often very helpful. Digestive enzyme supplements such as pancrease or Viokase can sometimes provide good relief for patients who have problems with abdominal bloating, diarrhea, or gas after meals. Frequent small meals are oftentimes better tolerated than three large meals each day. Supplementation with dense-calorie drinks like Ensure, Boost, or milkshakes are also recommended.

For patients with advanced pancreatic cancer, pain is often the major problem and needs to be treated aggressively. This may require escalating doses of narcotics, which can be given as pills, oral solution, or as transdermal patches (placed on the skin). In general, long-acting narcotics should be given to provide a baseline degree of round-the-clock pain control, with more short, immediate-acting narcotics on hand for use as needed for breakthrough pain. These narcotics can cause a fair amount of drowsiness, confusion (particularly in older patients), and constipation, so the simultaneous regular use of stool softeners should be encouraged while patients are taking narcotics. As noted above, in cases of refractory pain, referral to pain management specialists for celiac plexus block is recommended.

It should also be noted that chemotherapy itself (gemcitabine) can sometimes lead to improvement in cancer-related symptoms, including improvement in weight, pain, and overall functional status.

Important questions to ask your doctor
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What is the stage of my cancer, and am I a surgical candidate? Should I see another surgeon to confirm that my cancer can or cannot be resected?
(For patients who are potential surgical candidates): How experienced is my surgeon in performing this type of operation?
What clinical trials/investigational studies are being performed at this institution or at other institutions for which I may be eligible?
What side effects should I expect from treatment? How would I weigh these in comparison to the potential advantages in terms of survival and quality of life I might expect?



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