Overview and Risk Factors
Pancreatic cancer is the fourth most common cancer and the fifth most common cause of cancer-related mortality. Little is known about etiologic agents, but tobacco use is probably the most important modifiable risk factor.
More than 90% of pancreatic cancers are adenocarcinomas, which will be discussed here. Less common pancreatic tumors include endocrine tumors, carcinoid tumors, and lymphoma.
The characteristic presentation includes an insidious onset of weight loss, fatigue, anorexia, and gnawing abdominal or back pain. The most common symptom is epigastric pain with radiation to the back, which often improves upon bending forward. In addition, painless jaundice, dark urine, acholic stools, pruritis, migratory thrombophlebitis, or Courvoisier's sign (a palpable, nontender gallbladder) may be present.
Unfortunately, by the time symptoms appear, the cancer has generally become quite advanced. At the time of diagnosis, more than 80% of patients have advanced tumors marked by either local extension into adjacent organs (such as the liver) or solitary or multiple distant metastases, resulting in a very poor long-term survival rate. Most patients die within a year of diagnosis.
Males and African Americans have a slightly higher risk. Additional factors associated with risk include the following:
Age. The condition is rare before 45 years old. Incidence increases with age.
Family history. About 5% to 10% of patients with pancreatic cancer have a first-degree relative with the disease.
Genetics. Mutations in the p16, K-ras, CDKN2A, p53, and BRCA genes appear to increase the risk.
Dietary factors (see Nutritional Considerations).
Diagnosis and Treatment
Abdominal CT scan is the most common diagnostic test for pancreatic cancer. It will reveal the extent of the disease and may identify metastases.
Biopsy is necessary for a definitive diagnosis.
MRI (with or without angiography) or laparoscopy may determine resectability.
Ultrasound, endoscopic ultrasound, and endoscopic retrograde cholangiopancreatography (ERCP) are used for tumor staging.
Laboratory analysis should include a complete blood count, liver function tests, amylase, lipase, and tumor-associated antigens such as carcinoembryonic antigens (CEA) and cancer antigen (CA) 19-9. Levels of alkaline phosphatase and bilirubin will be elevated if the bile duct is obstructed or if liver metastases are present.
Despite advances in therapies, prognosis for pancreatic cancer remains poor, and surgical resection is the only curative treatment. However, curative operations are only possible in 10% to 15% of patients. Common surgical procedures include:
Pancreaticoduodenectomy (Whipple procedure), which involves removal of the duodenum, head of the pancreas, and gallbladder.
If the tumor is unresectable, palliation may be attempted via radiation, chemotherapy, or surgical intervention to relieve bile duct and GI tract obstructions.
Allow for liberal use of narcotic analgesics for pain control.
Despite advances in cancer therapies, the prognosis for pancreatic cancer remains poor and surgery is the only curative treatment. Curative operations are only possible in 10% to 15% of patients. Common procedures include:
- Pancreaticoduodenectomy (Whipple procedure), which involves removal of the duodenum, head of the pancreas, and gallbladder.
- Total pancreatectomy.
- Distal pancreatectomy.
If the tumor is unresectable, treatment includes palliation via radiation, chemotherapy, or surgical intervention to relieve bile duct and gastrointestinal (GI) tract obstructions.
Liberal use of narcotic analgesics for pain control is indicated.
The risk for pancreatic cancer appears to be significantly related to insulin resistance. Obesity, diabetes, lack of exercise, and macronutrients known to worsen insulin resistance (saturated fat, high glycemic index carbohydrates) are associated with increased risk.
The risk for pancreatic cancer also appears to be lower in persons who eat more fiber, fruits, and vegetables, and in persons following vegetarian diets.1-3 In epidemiologic studies, several dietary factors are associated with reduced risk. These are discussed below.
Diet and Risk
Avoiding animal products. Several studies found that risk increases with higher intake of meat and of saturated fat from animal products. These relationships may result from the carcinogenic effects of heterocyclic amines (HCAs) frequently found in poultry, fish, and red meat4 or of nitrates used in some prepared meat products.5 The ability of saturated fat to increase insulin-like growth factor 1,6 a known risk factor for pancreatic cancer mortality,7 may also explain these findings. In international studies, per capita consumption of meat, eggs, and milk correlated with mortality rates for pancreatic cancer.8 In a cohort study of 17,633 white men in the United States followed for 20 years, those eating the most meat had 3 times the risk for developing pancreatic cancer as those eating the least amount.9 In a group of 27,111 male smokers aged 50-69 years followed for a 12-year period, those who ate the most saturated fat had a significantly higher risk for pancreatic cancer, compared with nonsmokers who eat the least saturated fat.10
Reducing fat intake. Although the relationships do not appear to be as strong for total fat as for animal fat, even fat from nonanimal sources may increase pancreatic cancer risk. In a Swedish study, fried foods were associated with greater risk for pancreatic cancer,11 and women who ate the most fat had three times the risk for this cancer compared with those eating the least fat.12 The relationship may be due to the effect of high-fat diets on insulin resistance, a risk factor for pancreatic cancer.13
Increasing consumption of fruits, vegetables, and fiber. Numerous data link consumption of fruits, vegetables, and fiber with lower risk for pancreatic cancer. One report implicated oxidative stress and associated inflammation as causes of pancreatic cancer.14 This association may explain the correlation between high intakes of fruits, vegetables, and certain antioxidants found in these foods with lower risk for this cancer. Another study found that women who ate the most fruit had a 63% lower risk, and those who ate the most vegetables and fiber had a 70% lower risk for pancreatic cancer, compared with women eating the smallest quantities of these foods.12 Risk for pancreatic cancer was also lower among individuals with higher serum levels of lycopene (a carotenoid particularly prevalent in tomato products and watermelon),15 and men whose lycopene intake was highest had a 69% lower risk than men with the lowest lycopene intake.
Persons with the highest intake of beta-carotene and total carotenoids had a 40% lower risk than those getting the least amounts in their diets.1 Persons eating the highest amount of vitamin C appear to have about half the risk for pancreatic cancer as those getting the least vitamin C in their diets.3,16 It is unclear, however, whether these associations relate specifically to these food constituents or to another aspect of vegetables and fruits. Persons with the highest intake of fiber had 55% lower risk for pancreatic cancer than those eating the least fiber,3 a relationship that may be mediated by the beneficial effect of fiber on insulin sensitivity.17
Vegetarian diets. Studies of dietary patterns in relation to the risk for pancreatic cancer indicated that beans, lentils, other vegetarian protein sources, peas, and dried fruits significantly reduced risk for pancreatic cancer.2
Weight control. Exercise and weight control also appear to reduce risk for pancreatic cancer. Individuals who performed the greatest amount of moderate to strenuous physical activity had roughly half the risk as those getting the least exercise.13 Overweight individuals may derive the most protection from exercise; the risk for pancreatic cancer is inversely related to physical activity in persons with a body mass index >25.18
Diet and Prognosis for Pancreatic Cancer
Few studies have examined the effect of dietary changes on survival after diagnosis. One study found a 4-fold increase in median survival (13 months versus 3 months) in patients with pancreatic cancer who followed a macrobiotic diet (composed mainly of whole grains, land and sea vegetables, beans, and legumes and small amounts of fruit) compared to those eating omnivorous diets.19 Further studies are needed to establish relationships between diet and pancreatic cancer survival.
What to Tell the Family
Pancreatic cancer typically has a poor prognosis. While dietary factors appear to play a role in risk and possibly in survival, further studies are necessary to clarify these relationships.
1. Nkondjock A, Ghadirian P, Johnson KC, Krewski D, and the Canadian Cancer Registries Epidemiology Research Group. Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr. 2005;135:592-597.
6. Giovannucci E, Pollak M, Liu Y, et al. Nutritional predictors of insulin-like growth factor I and their relationships to cancer in men. Cancer Epidemiol Biomarkers Prev. 2003;12:84-89.
9. Zheng W, McLaughlin JK, Gridley G, Bjelke E, Schuman LM, Silverman DT. A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States). Cancer Causes Control. 1993;4:477-482.
11. Gerhardsson de Verdier M. Epidemiologic studies on fried foods and cancer in Sweden. Princess Takamatsu Symp. 1995;23:292-298.
13. Hanley AJ, Johnson KC, Villeneuve PJ, Mao Y, and the Canadian Cancer Registries Epidemiology Research Group. Physical activity, anthropometric factors, and risk of pancreatic cancer: results from the Canadian enhanced cancer surveillance system. Int J Cancer. 2001;94:140-147.
16. Lin Y, Tamakoshi A, Hayakawa T, Naruse S, Kitagawa M, Ohno Y. Nutritional factors and risk of pancreatic cancer: a population-based case-control study based on direct interview in Japan. J. Gastroenterol. 2005;40:297-301.
17. McKeown NM. Whole grain intake and insulin sensitivity: evidence from observational studies. Nutr Rev. 2004;62:286-291.
18. Michaud DS, Giovannucci E, Willett WC, Colditz GA, Stampfer MJ, Fuchs CS. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA. 2001;286:921-929.
19. Carter JP, Saxe GP, Newbold V, Peres CE, Campeau RJ, Bernal-Green L. Hypothesis: dietary management may improve survival from nutritionally linked cancers based on analysis of representative cases. J Am Coll Nutr. 1993;12:209-226.