Pancreatic cancer is the fourth most common cause of cancer-related mortality in the US after lung and colorectal cancers.[1][2]

Approximately 85% of pancreatic cancers are ductal adenocarcinomas, which are 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 sign (a palpable, nontender gallbladder) may be present.[3]

Unfortunately, by the time symptoms appear, the cancer is usually unresectable. 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 distant metastases, resulting in a poor long-term survival rate. Most patients die within a year of diagnosis.

Risk Factors

Age. The condition is rare before age 45 but increases thereafter with age.[4]

Gender. Males have a slightly higher risk than females with a ratio of 1.3 to 1.[5]

Race. In the US, Blacks have a slightly higher incidence of pancreatic cancer than Whites.[4]

Smoking. Cigarette smoking is one of the major risk factors for developing pancreatic cancer and accounts for approximately 25% of all cases.[6]

Obesity: Excess weight increases the risk of pancreatic cancer.[7]

Physical inactivity. Lack of physical activity is a risk factor.[8]

Diabetes and insulin resistance. Both diabetes and insulin resistance are associated with an increased risk of pancreatic cancer.[9][10] There is also some evidence that diabetes can be a consequence of pancreatic cancer, rather than the cause.[11]

Chronic pancreatitis. The presence of chronic inflammation of the pancreas increases the risk of pancreatic cancer. One study showed that individuals with chronic pancreatitis had a standardized incidence ratio (the ratio of observed to expected cases) of 26.3.[12]

Family history. About 5-10% of patients with pancreatic cancer have a first-degree relative with the disease.[13] Most of these cases have no clearly defined gene mutation. There are, however, several clearly defined genetic syndromes, including Peutz-Jeghers syndrome, hereditary breast/ovarian cancer syndrome, and familial adenomatous polyposis, that carry a predisposition for pancreatic and other types of cancer.[14] Hereditary pancreatitis (autosomal dominant) is a rare form of chronic pancreatitis which carries an increased risk of pancreatic cancer.[15]

ABO blood type. Having a non-O blood type carries an increased risk for pancreatic cancer.[16]

Periodontal disease. Several studies show that periodontal disease is associated with an increased risk of pancreatic cancer.[17][18]

Alcohol. Heavy or chronic alcohol use is also associated with increased pancreatic cancer risk,[19] and is most likely due to increased inflammation and recurrent pancreatitis.

Dietary factors. (see Nutritional Considerations).

Diagnosis

Patients with unexplained weight loss, painless jaundice, or subacute epigastric pain without other obvious cause should undergo further evaluation with laboratory testing for liver function. Tests for lipase and amylase should also be done if pain is the presenting symptom. An abdominal CT scan should be performed, and though less sensitive, abdominal ultrasound is also sometimes used. CT imaging will demonstrate a hypodense mass, sometimes with a double duct sign (dilation of both the biliary and pancreatic ducts) in a pancreatic head mass. If a mass is found on imaging, an endoscopic ultrasound guided fine needle aspiration can be performed to analyze the tissue and diagnose the presence of cancerous cells. Additionally, serum testing of Ca19-9 and CEA may be informative.

For patients with a suspicious pancreatic mass who are reasonable surgical candidates, surgical resection is the best approach unless a lymphoma is suspected. Once a diagnosis is made, the tumor is staged using the tumor-node-metastasis system to determine if it is resectable. This is usually done with CT, MRI, PET scanning, or staging laparoscopy, depending on the clinical situation.

Treatment

Despite advances in treatment, the prognosis for pancreatic cancer remains poor, and surgical resection is the only curative treatment. Only about 15% of pancreatic cancers are found to be potentially resectable at the time of diagnosis. Common surgical procedures include pancreaticoduodenectomy (Whipple procedure), which involves removal of the duodenum and gallbladder, for pancreatic head/periampullary tumors, and distal pancreatectomy for body/tail tumors. Treatment with chemotherapy and/or radiation following surgery may improve survival rates.

If the tumor is unresectable, palliation may be attempted via radiation, chemotherapy, or surgical intervention to relieve bile duct and GI tract obstructions. Adequate pain control is also an important part of palliative care.

Nutritional Considerations

The risk for pancreatic cancer appears to be significantly related to insulin resistance. Obesity, diabetes, lack of exercise, and diets known to impact insulin resistance and risk for malignancy in general are known to moderate risk. Evidence indicates that the major dietary determinants of increased pancreatic cancer risk include meat and other sources of animal fat, while fruits, vegetables, and whole grains appear to reduce risk.[20][21]

Avoiding animal products. In the NIH-AARP Diet and Health Study, the risk for pancreatic cancer was 20% greater in those eating the most meat, compared with those eating the least. Red meat, high-temperature cooked meat, and heme iron from red meat were all associated with roughly 20% greater risk. This increased to over 30% in frequent consumers of "well done” or “very well done” meat, compared with those who generally avoid meat cooked in this fashion.[19] Part of this risk has been attributed to the proinflammatory effects of advanced glycation end products found in meat.[21] Conversely, intake of beans, lentils, other plant foods is associated with significantly reduced risk for pancreatic cancer.[3]

Reducing fat intake. Higher compared with lower intakes of animal fat were associated with a 43% greater risk for pancreatic cancer in the NIH-AARP Diet and Health Study.[22][23] Similar findings have emerged in other studies.[24] On the other hand, evidence indicates that individuals consuming the highest amount of polyunsaturated fat have a 13% lower risk for pancreatic cancer, compared with those eating the least.[25]

Increasing consumption of fruits, vegetables, and whole grains. Higher compared with lower fruit and vegetable intakes are associated with a roughly 25% lower risk for pancreatic cancer, and cruciferous vegetables may be especially protective.[26][27] Consuming the highest dietary amounts of selenium, vitamin C, vitamin E, β-carotene, and β-cryptoxanthin was associated with a 30-53% lower risk for pancreatic cancer.[28][29] Intake of the highest amount of whole grains was associated with a roughly 25% lower risk for pancreatic cancer, compared to the lowest intakes.[30]

Flavonoids. Flavonoids from fruits and vegetables have been associated with reduced risk of developing pancreatic cancer and inhibiting metastases and cancerous cell growth. Apigenin and luteolin can arrest cancer cell growth by interrupting glucose uptake and inhibiting protein expression over extracellular migration and proliferation. Dietary sources of apigenin include rosemary, basil, and other leafy greens.[31]

Quercetin, a flavonoid found in tea, red onions, and cruciferous greens, has been associated with preventing cancerous cell growth by interfering with transcription of growth factors and inducing apoptosis in cancer cells.

Genistein, a flavonoid found in soybeans and other legumes, is associated with inducing cancer cell death and interfering with extracellular migration and growth. Genistein can enhance the effectiveness of chemotherapeutic drugs used in the treatment of pancreatic cancer, such as gemcitabine, erlotinib, and cisplatin.[32]

Weight control. Individuals at a body mass index (BMI) of 25 kg/m2 and below are at low risk for pancreatic cancer. The risk increases by 10% as BMI increases from 25 to 30 kg/m2, and the risk is greatest at a BMI over 35 kg/m2.[33] Exercise is weakly yet statistically significantly associated with a lower risk for pancreatic cancer.[34]

Limiting or avoiding alcohol. As noted above, heavy alcohol use is associated with pancreatic cancer risk. Avoiding or limiting alcohol use has many potential benefits, in addition to potentially reducing pancreatic cancer risk.[35]

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, legumes, and small amounts of fruit) compared with those eating omnivorous diets.[36] Other studies have revealed a longer survival in patients taking an omega-3 fatty-acid-containing supplement when compared with those on conventional nutrition therapy.[37] Further studies are needed to establish relationships between diet and pancreatic cancer survival.

Orders

See Basic Diet Orders chapter.

Smoking cessation.

Exercise prescription.

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.

References