Cancer Center Pancreatic
Cancer Center Pancreatic
Pancreatic cancer is a malignant neoplasm of the pancreas. Each year in the United States, about 42,470 individuals are diagnosed with this condition and 35,240 die from the disease. The prognosis is relatively poor but has improved; the three-year survival rate is now about thirty percent, but less than 5 percent of those diagnosed are still alive five years after diagnosis. Complete remission is still rather rare.
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 cancers are far more common than endocrine pancreatic cancers (also known as islet cell carcinomas), which make up about 1% of total cases.
Signs and symptoms
Presentation
Pancreatic cancer is sometimes called a "silent killer" because early pancreatic cancer often does not cause symptoms, and the later symptoms are usually non-specific 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 that 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.
Causes
Risk factors for pancreatic cancer include:
- Age (particularly over 60)
- Gender Male
- African-American ethnicity
- Smoking. Cigarette smoking has a risk ratio of 1.74 with regard to pancreatic cancer; a decade of non-smoking 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
- 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 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, but "chronic pancreatitis that is due to alcohol doesn't increase risk 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".
Diagnosis
Most patients with pancreatic cancer experience pain, weight loss, or jaundice.
Pain is present in 80 to 85 percent of patients with locally advanced or advanced metastic disease. The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back. It may be intermittent and made worse by eating. Weight loss can be profound; it can be associated with anorexia, early satiety, diarrhea, or steatorrhea. Jaundice is often accompanied by pruritus and dark urine. Painful jaundice is present in approximately one-half of patients with locally unresectable disease, while painless jaundice is present in approximately one-half of patients with a potentially resectable and curable lesion.
The initial presentation varies according to location of the cancer. Malignancies in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present with steatorrhea, weight loss, and jaundice. The recent onset of atypical diabetes mellitus, a history of recent but unexplained thrombophlebitis (Trousseau sign), or a previous attack of pancreatitis are sometimes noted.
Courvoisier sign defines the presence of jaundice and a painlessly distended gallbladder as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer from gallstones.
Tiredness, irritability and difficulty eating due to pain also exist. Pancreatic cancer is usually discovered during the course of the evaluation of aforementioned symptoms.
Liver function tests can show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, γ-glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in pancreatic cancer. However, it lacks sensitivity and specificity. When a cutoff above 37 U/mL is used, this marker has a sensitivity of 77% and specificity of 87% in discerning benign from malignant disease. CA 19-9 might be normal early in the course, and could be elevated due to benign causes of biliary obstruction.
Imaging studies, such as computed tomography (CT scan) and endoscopic ultrasound (EUS) can be used to identify the location and form of the cancer. However, percutaneous needle biopsy of the cancerous pancreatic tissue is necessary to establish a definitive diagnosis. Endoscopic ultrasound is often used to visually guide the needle biopsy procedure.
In the September 2009 issue of the journal Cancer Prevention Research, scientists from the University of Texas M.D. Anderson Cancer Center identified microRNAs associated with pancreatic cancer from blood samples of pancreatic cancer patients, leading to a new and minimally invasive approach to early detection. Expression of higher levels of miR-155 circulating in blood was identified as a potential early stage biomarker, and expression of miR196a was shown to increase during disease progression. Using a panel of 4 miRNA biomarkers, miR-21, miR-210, miR-155, and miR-196a, the study achieved 64% sensitivity and 89% specificity in a sample of 28 pancreatic cancer patients and 19 healthy controls.
Prevention
According to the American Cancer Society, there are no established guidelines for preventing pancreatic cancer, although cigarette smoking has been reported as responsible for 20–30% of pancreatic cancers.
The ACS recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains while decreasing red meat intake, although there is no consistent evidence that this will prevent or reduce pancreatic cancer specifically. In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association. The evidence in support of this lies mostly in small case-control studies.
In September 2006, a long-term study concluded that taking Vitamin D can substantially cut the risk of pancreatic cancer (as well as other cancers) by up to 50%, but this study needs to evaluate fully the risks, costs and potential benefits of taking Vitamin D.
Several studies, including one published on 1 June 2007, indicate that B vitamins such as B12, B6, and folate, can reduce the risk of pancreatic cancer when
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