Pancreatic cancer is the fourth leading cause of cancer death in the United States and is associated with a poor prognosis. Endocrine tumors affecting the pancreas are discussed in Chap. 51. Infiltrating ductal adenocarcinomas, the subject of this Chapter, account for the vast majority of cases and arise most frequently in the head of pancreas. At the time of diagnosis, 85–90% of patients have inoperable or metastatic disease, which is reflected in the 5-year survival rate of only 6% for all stages combined. An improved 5-year survival of up to 24% may be achieved when the tumor is detected at an early stage and when complete surgical resection is accomplished.
Pancreatic cancer represents 3% of all newly diagnosed malignancies in the United States. The most common age group at diagnosis is 65–84 years for both sexes. Pancreatic cancer was estimated to have been diagnosed in approximately 45,220 patients and accounted for approximately 38,460 deaths in 2013. Although survival rates have almost doubled over the past 35 years for this disease, overall survival remains low.
An estimated 278,684 cases of pancreatic cancer occur annually worldwide (the thirteenth most common cancer globally), with up to 60% of these cases diagnosed in more developed countries. It remains the eighth most common cause of cancer death in men and the ninth most common in women. The incidence is highest in the United States and western Europe and lowest in parts of Africa and South Central Asia. However, increasing rates of obesity, diabetes, and tobacco use in addition to access to diagnostic radiology in the developing world are likely to increase incidence rates in these countries. In this situation, consideration of the cost implications of adoption of current treatment paradigms in resource-constrained environments will be necessary. Primary prevention such as limiting tobacco use and avoiding obesity may be more cost effective than improvements in treatment of preexisting disease.
Cigarette smoking may be the cause of up to 20–25% of all pancreatic cancers and is the most common environmental risk factor for this disease. A longstanding history of type 1 or type 2 diabetes also appears to be a risk factor; however, diabetes may also occur in association with pancreatic cancer, possibly confounding this interpretation. Other risk factors may include obesity, chronic pancreatitis, and ABO blood group status. Alcohol does not appear to be a risk factor unless excess consumption gives rise to chronic pancreatitis.
GENETIC AND MOLECULAR CONSIDERATIONS
Pancreatic cancer is associated with a number of well-defined molecular hallmarks. The four genes most commonly mutated or inactivated in pancreatic cancer are KRAS (predominantly codon 12, in 60–75% of pancreatic cancers), the tumor-suppressor genes p16 (deleted in 95% of tumors), p53 (inactivated or mutated in 50–70% of tumors), and SMAD4 (deleted in 55% of ...