About 95% of exocrine pancreatic cancers are adenocarcinomas (M8140/3). The remaining 5% include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells. Exocrine pancreatic tumors are far more common than pancreatic endocrine tumors, which make up about 1% of total cases.
What are the Causes and Risk factors of Pancreatic Cancer?
Risk factors for pancreatic cancer include:
- Age (particularly over 60)
- Male sex (likeliness of up to 30% over females)
- Smoking. Cigarette smoking has a risk ratio of 1.74 with regard to pancreatic cancer; a decade of nonsmoking after heavy smoking is associated with a risk ratio of 1.2.
- Diets low in vegetables and fruits
- Diets high in red meat
- Diets high in sugar-sweetened drinks (soft drinks) risk ratio 1.87. In particular, common soft drink sweetener fructose has been linked to growth of pancreatic cancer cells.
- Obesity
- Diabetes mellitus is both risk factor for pancreatic cancer, and, as noted earlier, new onset diabetes can be an early sign of the disease.
- Chronic pancreatitis has been linked, but is not known to be causal. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.
- Helicobacter pylori infection
- Family history, 5–10% of pancreatic cancer patients have a family history of pancreatic cancer. The genes responsible for most of this clustering in families have yet to be identified. Pancreatic cancer has been associated with the following syndromes; autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 gene and PALB2 gene, Peutz-Jeghers syndrome due to mutations in the STK11 tumor suppressor gene, hereditary non-polyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, and the familial atypical multiple mole melanoma-pancreatic cancer syndrome (FAMMM-PC) due to mutations in the CDKN2A tumor suppressor gene.
- Gingivitis or periodontal disease
Australia and Canada, being members of the International Cancer Genome Consortium, are leading efforts to map pancreatic cancer’s complete genome.
Alcohol
It is controversial whether alcohol consumption is a risk factor for pancreatic cancer. Drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer. However, chronic pancreatitis associated with alcohol consumption does not increase risk of pancreatic cancer as much as other types of chronic pancreatitis. Overall, the association is consistently weak and the majority of studies have found no association.
Some studies suggest a relationship, with risk increasing with increasing amount of alcohol intake. Risk is greatest in heavy drinkers mostly on the order of four or more drinks per day. But there appears to be no increased risk for people consuming up to 30g of alcohol a day, so most of the U.S. consumes alcohol at a level that “is probably not a risk factor for pancreatic cancer”.
Several studies caution that their findings could be due to confounding factors. Even if a link exists, it “could be due to the contents of some alcoholic beverages” other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk.
A pooled analysis concluded, “Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day”.
What are the Symptoms of Pancreatic Cancer?
Pancreatic cancer is sometimes called a “silent killer” because early pancreatic cancer often does not cause symptoms, and the later symptoms are usually nonspecific and varied. Therefore, pancreatic cancer is often not diagnosed until it is advanced. Common symptoms include:
- Pain in the upper abdomen that typically radiates to the back (seen in carcinoma of the body or tail of the pancreas)
- Loss of appetite and/or nausea and vomiting
- Significant weight loss
- Painless jaundice (yellow skin/eyes, dark urine) when a cancer of the head of the pancreas (about 60% of cases) obstructs the common bile duct as it runs through the pancreas. This may also cause pale-colored stool and steatorrhea.
- Trousseau sign, in which blood clots form spontaneously in the portal blood vessels, the deep veins of the extremities, or the superficial veins anywhere on the body, is sometimes associated with pancreatic cancer.
- Diabetes mellitus, or elevated blood sugar levels. Many patients with pancreatic cancer develop diabetes months to even years before they are diagnosed with pancreatic cancer, suggesting new onset diabetes in an elderly individual may be an early warning sign of pancreatic cancer.
- Clinical depression has been reported in association with pancreatic cancer, sometimes presenting before the cancer is diagnosed. However, the mechanism for this association is not known.
Diagnosis
If your doctor suspects pancreatic cancer, you may have one or more of the following tests to diagnose the cancer:
- Ultrasound. Ultrasound uses high-frequency sound waves to create moving images of your internal organs, including your pancreas. The ultrasound sensor (transducer) is placed on your upper abdomen to obtain images.
Computerized tomography (CT) scan. CT scan uses X-ray images to help your doctor visualize your internal organs. In some cases you may receive an injection of dye into a vein in your arm to help highlight the areas your doctor wants to see.- Magnetic resonance imaging (MRI). MRI uses a powerful magnetic field and radio waves to create images of your pancreas.
- Endoscopic retrograde cholangiopancreatography (ERCP). This procedure uses a dye to highlight the bile ducts in your pancreas. During ERCP, a thin, flexible tube (endoscope) is gently passed down your throat, through your stomach and into the upper part of your small intestine. Air is used to inflate your intestinal tract so that your doctor can more easily see the openings of your pancreatic and bile ducts. A dye is then injected into the ducts through a small hollow tube (catheter) that’s passed through the endoscope. Finally, X-rays are taken of the ducts. A tissue or cell sample (biopsy) can be collected during ERCP.
- Endoscopic ultrasound (EUS). EUS uses an ultrasound device to make images of your pancreas from inside your abdomen. The ultrasound device is passed through an endoscope into your stomach in order to obtain the images. Your doctor may also collect a sample of cells (biopsy) during EUS.
- Percutaneous transhepatic cholangiography (PTC). PTC uses a dye to highlight the bile ducts in your liver. Your doctor carefully inserts a thin needle into your liver and injects the dye into the bile ducts. A special X-ray machine (fluoroscope) tracks the dye as it moves through the ducts.
- Removing a tissue sample for testing (biopsy). A biopsy is a procedure to remove a small sample of tissue from the pancreas for examination under a microscope. A biopsy sample can be obtained by inserting a needle through your skin and into your pancreas (fine-needle aspiration). Or it can be done using endoscopic ultrasound to guide special tools into your pancreas where a sample of cells can be obtained for testing.
Staging pancreatic cancer
Once a diagnosis of pancreatic cancer is confirmed, your doctor will work to determine the extent, or stage, of the cancer. Your cancer’s stage helps determine what treatments are available to you. In order to determine the stage of your pancreatic cancer, your doctor may recommend:
- Using a scope to see inside your body. Laparoscopy uses a lighted tube with a video camera to explore your pancreas and surrounding tissue. The surgeon passes the laparoscope through an incision in your abdomen. The camera on the end of the scope transmits video to a screen in the operating room. This allows your doctor to look for signs cancer has spread within your abdomen.
- Imaging tests. Imaging tests may include chest X-ray, CT and MRI.
- Blood test. Your doctor may test your blood for specific proteins (tumor markers) shed by pancreatic cancer cells. One tumor marker test used in pancreatic cancer is called CA19-9. Some research indicates that the more elevated your level of CA19-9 is, the more advanced the cancer. But the test isn’t always reliable, and it isn’t clear how best to use the CA19-9 test results. Some doctors measure your levels before, during and after treatment. Others use it to gauge your prognosis.
Stages
Using information from staging tests, your doctor assigns your pancreatic cancer a stage. The stages of pancreatic cancer are:
- Stage I. Cancer is confined to the pancreas.
- Stage II. Cancer has spread beyond the pancreas to nearby tissues and organs and may have spread to the lymph nodes.
- Stage III. Cancer has spread beyond the pancreas to the major blood vessels around the pancreas and may have spread to the lymph nodes.
- Stage IV. Cancer has spread to distant sites beyond the pancreas, such as the liver, lungs and the lining that surrounds your abdominal organs (peritoneum).
Methods of Treatment
Treatment for pancreatic cancer depends on the stage and location of the cancer as well as on your age, overall health and personal preferences. The first goal of pancreatic cancer treatment is to eliminate the cancer, when possible. When that isn’t an option, the focus may be on preventing the pancreatic cancer from growing or causing more harm. When pancreatic cancer is advanced and treatments aren’t likely to offer a benefit, your doctor may suggest ways to relieve symptoms and make you as comfortable as possible.
Surgery
Surgery may be an option if your pancreatic cancer is confined to the pancreas. Operations used in people with pancreatic cancer include:
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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). The Whipple procedure involves removing the head of your pancreas, as well as a portion of your small intestine (duodenum), your gallbladder and part of your bile duct. Part of your stomach may be removed as well. Your surgeon reconnects the remaining parts of your pancreas, stomach and intestines to allow you to digest food.
Whipple surgery carries a risk of infection and bleeding. After the surgery, some people experience nausea and vomiting that can occur if the stomach has difficulty emptying (delayed gastric emptying). Expect a long recovery after a Whipple procedure. You’ll spend 10 days or more in the hospital and then recover for several weeks at home.
- Surgery for tumors in the pancreatic tail and body. Surgery to remove the tail of the pancreas or the tail and a small portion of the body is called distal pancreatectomy. Your surgeon may also remove your spleen. Surgery carries a risk of bleeding and infection.
Research shows pancreatic cancer surgery tends to cause fewer complications when done by experienced surgeons. Don’t hesitate to ask about your surgeon’s experience with pancreatic cancer surgery. If you have any doubts, get a second opinion.
Radiation therapy
Radiation therapy uses high-energy beams to destroy cancer cells. You may receive radiation treatments before or after cancer surgery, often in combination with chemotherapy. Or, your doctor may recommend a combination of radiation and chemotherapy treatments when your cancer can’t be treated surgically.
Radiation therapy can come from a machine outside your body (external beam radiation), or it can be placed inside your body near your cancer (brachytherapy). Radiation therapy can also be used during surgery (intraoperative radiation).
Chemotherapy
Chemotherapy uses drugs to help kill cancer cells. Chemotherapy can be injected into a vein or taken orally. You may receive only one chemotherapy drug, or you may receive a combination of chemotherapy drugs.
Chemotherapy can also be combined with radiation therapy (chemoradiation). Chemoradiation is typically used to treat cancer that has spread beyond the pancreas, but only to nearby organs and not to distant regions of the body. This combination may also be used after surgery to reduce the risk that pancreatic cancer may recur.
In people with advanced pancreatic cancer, chemotherapy may be combined with targeted drug therapy.
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 under investigation in clinical trials.
Clinical trials
Clinical trials are studies to test new forms of treatment, such as new drugs, new approaches to surgery or radiation treatments, and novel methods such as gene therapy. If the treatment being studied proves to be safer or more effective than are current treatments, it can become the new standard of care.
Clinical trials can’t guarantee a cure, and they may have serious or unexpected side effects. On the other hand, cancer clinical trials are closely monitored by the federal government to ensure they’re conducted as safely as possible. And they offer access to treatments that wouldn’t otherwise be available to you.
Talk to your doctor about what clinical trials might be appropriate for you.
New treatments currently under investigation in clinical trials include:
- Drugs that stop cancer from growing new blood vessels. Targeted drug treatments that work by stopping cancer from growing new blood vessels are called angiogenesis inhibitors. Without new blood vessels, cancer cells may be unable to get the nutrients they need to grow. Blood vessels also give cancer cells a pathway to spread to other parts of the body.
- Pancreatic cancer vaccines. Cancer vaccines are being studied to treat cancer, rather than prevent disease, as vaccines are traditionally used. Cancer treatment vaccines use various strategies to enhance the immune system to help it recognize cancer cells as intruders. In one example, a vaccine may help train the immune system to attack a certain protein secreted by pancreatic cancer cells. Studies of pancreatic cancer vaccines are still in the very early stages.
Drugs rating:
| Title | Votes | Rating | ||
| 1 | Tarceva (Erlotinib) | 40 | (8.0/10) | |
| 2 | Zanosar (Streptozocin) | 0 | (0/10) | |
| 3 | Vantas (Histrelin Implant) | 0 | (0/10) | |
| 4 | Pancreatin 4X (Pancreatin) | 0 | (0/10) | |
| 5 | Mutamycin (Mitomycin) | 0 | (0/10) | |
| 6 | Adrucil (Fluorouracil) | 0 | (0/10) | |
| 7 | Gemzar (Gemcitabine) | 0 | (0/10) |
Prognosis
Patients diagnosed with pancreatic cancer typically have a poor prognosis, partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis. Median survival from diagnosis is around 3 to 6 months; 5-year survival is less than 5%. With 37,170 cases diagnosed in the United States in 2007, and 33,700 deaths, pancreatic cancer has one of the highest fatality rates of all cancers, and is the fourth-highest cancer killer in the United States among both men and women. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year.
Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered, and it has been suggested the cancer can also prompt the onset of diabetes and vice versa. Thus, diabetes is both a risk factor for the development of pancreatic cancer and an early sign of the disease in the elderly.
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