Ductal adenocarcinoma – Overview

Ductal adenocarcinoma is by far the most common type of pancreatic neoplasms. It is a very aggressive disease, representing the fourth leading cause of cancer death in the Western world. The risk of developing pancreatic ductal adenocarcinoma increases as people age (the median age at the time of diagnosis is 71), and men are 30% more likely to develop this neoplasm than women. The vast majority of ductal adenocarcinomas is sporadic, only a small fraction being familial.

Ductal adenocarcinoma begins when, because of damage to the DNA, cells in the pancreas start to grow out of control and form a tumor. The genetic and molecular basis of pancreatic ductal adenocarcinoma are still poorly understood and represent the focus of intense research.  

Known risk factors for pancreatic ductal adenocarcinoma are:

  • Age (> 60 years)
  • Male sex
  • Cigarette smoking
  • Alcohol abuse
  • Obesity and diabetes mellitus
  • Chronic pancreatitis
  • Other pancreatic neoplasms (intraductal  papillary mucinous neoplasms)
  • Family history of pancreatic cancer
  • Genetic syndromes such as BRCA2 mutation and colonic polyposis

Unfortunately very few of pancreatic ductal adenocarcinomas are found early. Patients usually have poorly specific symptoms or even no symptoms until the cancer has spread to other organs. Routine radiologic investigation (such as ultrasound) or physical examination are not able to detect small tumors. Right now, there are no blood tests to find early cancers of the pancreas. The most common gastrointestinal symptoms associated with pancreatic ductal adenocarcinoma are:

  • Weakness
  • Digestive problems (lack of appetite, dyspepsia; pale, bulky and greasy stools)
  • Epigastric and back pain 
  • Weight loss
  • Sudden onset of diabetes mellitus

Cancers that begin in the head of the pancreas usually cause symptoms while they are still fairly small. These include jaundice and duodenal obstruction, which may allow these tumors to be found in an earlier stage.

Jaundice: it is the yellowing of the eyes and skin caused by the buildup of bilirubin in the body. Bilirubin is a dark yellow-brown substance that is made in the liver. Normally, the liver excretes bilirubin into bile, which flows through the common bile duct into the intestines. When the portion of common bile passing within the pancreatic head becomes compressed or infiltrated by the tumor, bile can’t reach the intestines, and the level of bilirubin builds up. The first sign of jaundice is darkening of the urine, which becomes brown in color. Furthermore, a person may notice their stools becoming lighter in color. When bilirubin builds up in the skin, it turns yellow and starts to itch. Of note, pancreatic ductal adenocarcinoma and other tumors arising in the periampullary area, including ampullary cancer and distal cholangiocarcinoma, are not the most common cause of jaundice. Other causes, such as gallstones, hepatitis, and other liver diseases, are much more common.

Intestinal obstruction: the neoplasm may infiltrate the far end of the stomach or the duodenum, partly blocking them. This can cause nausea, vomiting, and pain that tend to be worse after a meal. 

Cancers that begin in the body or tail of the pancreas do not compress the biliary duct until they have spread through the pancreas. By this time, the cancer may have also spread beyond the pancreas.

When a pancreatic ductal adenocarcinoma is suspected by a physician, referral to a multidisciplinary team with experience in the field is strongly advised. Estimation of the extent of disease on cross-sectional imaging (tumor staging) is the most important factor in choosing treatment options and predicting a patient’s outlook. A biopsy to be sure about the diagnosis may be also performed. For more information about the diagnostic work-up and staging of pancreatic ductal adenocarcinoma click here.