Endoscopic Ultrasound Detects Pancreatic Lesions Common in People at High Risk for Hereditary Pancreatic Cancer

A team of scientists has discovered that more than four in 10 people thought to be at high risk for hereditary pancreatic cancer have small pancreatic lesions long before they have any symptoms of the deadly disease. Moreover, the frequency of the abnormal precancerous lesions increases with age and that ultrasound via endoscopy is better than magnetic resonance imaging (MRI) and considerably better than computed tomography (CT) scans at detecting the lesions.

The researchers reported that their research indicates some progress in reducing the death rate from hereditary pancreatic cancer, which is mostly fatal once the lesions become malignant and symptoms occur. At that point, just 25% of those eligible for surgery survive five years, while the rest have a less than 5% chance of surviving five years. The general population has a 0.5% lifetime risk of getting pancreatic cancer, while those in high-risk groups included in the study have risks that are 3.5 to 132 times higher. Researchers reported that about 10%-15% of all pancreatic cancers are hereditary.

“We now know that although these high-risk patients often tend to develop pancreatic lesions, we can detect the lesions, track them over time, and remove them before they become cancer,” says Marcia Irene Canto, MD, MHS, a professor of gastroenterology and oncology at the Johns Hopkins University School of Medicine (Baltimore, MD, USA).

Dr. Canto and her team--comprised of researchers from Johns Hopkins, Mayo Clinic (Rochester, MN, USA), Dana Farber Cancer Institute (Boston, MA, USA), MD Anderson Cancer Center (Houston, TX, USA), and the University of California, Los Angeles (UCLA; USA)--assessed 216 asymptomatic adults with a strong family history of pancreatic cancer, primarily those with two close blood relatives who have had the disease and those who have inherited genetic markers known to increase the risk of pancreatic cancer, including BRCA2 gene mutation that has also been linked to breast and ovarian cancers.

Clinicians at each medical center performed three types of screening on each participant using CT, MRI, and ultrasound conducted via endoscopy. Johns Hopkins screened more than half of the participants. Those interpreting the diagnostic images from any one test were kept unaware of the results of the others to reduce the chance of bias.

CT detected pancreatic abnormalities in 11% of the study participants, MRI found them in 33.3% and endoscopic ultrasound 42.6%. Five participants had what doctors determined were precancerous lesions and underwent surgery to remove them. These were lesions that would most likely not have been detected and removed, according to Dr. Canto.

Dr. Canto’s team discovered that the prevalence of pancreatic lesions increases with age, with doctors finding them in just 14% of high-risk subjects under the age of 50, 34% of those ages 50 to 59, and 53% of those 60- to 69-years old. Those with lesions who did not require surgery were recommended for regular follow-up screening to see if the lesions change in size or shape. Not all pancreatic cysts or lesions become pancreatic cancer.

The findings of the study, known formally as CAPS 3 Study, are published in April 2012 issue of the journal Gastroenterology. One advantage that endoscopic ultrasound has over MRI and CT, according to Dr. Canto, is that it can also be used to collect cells from the pancreatic lesions, secretions from the pancreas, and fluid from cysts to facilitate further study. The CAPS 3 study team collected pancreatic juice for biomarker research led by Michael Goggins, MD, aimed at better detection of pre-cancerous or cancerous lesions in the pancreas. Moreover, a Johns Hopkins research team led by Bert Vogelstein, MD, and Ralph Hruban, MD, are developing biomarkers from pancreatic cyst fluid that appear to determine the cyst’s malignant potential. Recently, they completed genomic sequences of pancreatic cysts that will help biologists determine how they develop and turn cancerous. Researchers hope those findings will enable them to find potentially deadly pancreatic tumors before they develop, saving people from a disease that has little chance for a cure.

For the endoscopic procedure, a clinician passes a thin, lighted tube from a sedated patient’s mouth through the stomach, and into the first part of the small intestine. At the tip of the endoscope is a device that utilizes sound waves that generate patterns of echoes as they bounce off internal organs. These ultrasonic patterns can help identify tumors that cannot be detected by a CT scan. Using ultrasound to help guide the way, a physician then inserts a thin needle into the pancreas to remove cells that can be later studied.

Unlike screening for colon cancer, pancreatic cancer screening is not recommended for the general population. Dr. Canto noted that this is because cysts and other possibly pre-cancerous lesions are far less typical in the pancreas than in the colon; because the pancreas is more difficult to reach than the colon; and because removing lesions requires extensive surgery, frequently including part of the pancreas. Potential complications are also more likely.

“Early detection is the way to go,” Dr. Canto concluded. “We need smart screening and individualized treatments based on family history, epidemiology, biomarkers, and genetics.”

Related Links:
Johns Hopkins University School of Medicine
Dana Farber Cancer Institute
University of California, Los Angeles