Κυριακή, 22 Νοεμβρίου 2015

BIOLOGY OF PANCREATIC CYSTS

In a retrospective analysis of data from 130 patients with pancreatic cysts, scientists at Johns Hopkins have used gene-based tests and a fixed set of clinical criteria to more accurately distinguish precancerous cysts from those less likely to do harm. The findings may eventually help some patients safely avoid surgery to remove harmless cysts. A report on the findings was published by Springer et al in Gastroenterology.
Currently, physicians must perform an endoscopic ultrasound-guided biopsy and test fluid collected from the cyst for levels of proteins associated with cancerous cysts. In addition, pathologists look for atypical cells signifying cancer. However, recent studies show that these methods are accurate only 63% of the time, said Anne Marie Lennon, MD, PhD, Associate Professor of Medicine at the Johns Hopkins University School of Medicine and Director of the Multidisciplinary Pancreatic Cyst Program.
Study Background
In 2011, Dr. Lennon’s team had developed preliminary genetic tests that measure the presence of pancreatic cancer–linked genetic markers in cyst fluid samples. For the current study, they expanded the panel of genetic markers and tested them on cyst fluid from 130 patients who had surgery to remove cysts at The Johns Hopkins Hospital and 16 other hospitals in the United States and abroad.
In addition to using genetic markers, the researchers developed a mathematic model that identifies various types of pancreatic cysts and their potential for malignancy by taking into account patient characteristics such as age and symptoms, as well as the appearance and location of cysts, based on medical record information from 1,026 patients who had surgery to remove cysts at The Johns Hopkins Hospital.
“The combination of genetic tests and clinical evaluation of patients’ cysts may change the way we guide patients on whether surgery to remove cysts is necessary,” said Dr. Lennon.
Key Findings
To evaluate the validity of the new combination approach, the team performed genetic tests on the cyst fluid samples and evaluated clinical criteria of the 130 patients. They were able to identify 12 benign cysts, called serous cystadenomas, with 98% specificity and 100% sensitivity.
The researchers identified 10 cysts called solid pseudopapillary neoplasms, which should be surgically removed, with 89% sensitivity and 92% specificity. Their tests also identified 12 mucinous cystic neoplasms, which are often removed, with 97% specificity and 90% sensitivity.
Finally, the team identified 96 of the more common intraductal papillary mucinous neoplasms with 94% sensitivity and 84% specificity. The low- and intermediate-risk varieties of these cysts are often monitored carefully when patients have no symptoms. When the malignancy risk level is high, doctors recommend surgical removal.
Typical Cyst Screening and Treatment
In the United States, Dr. Lennon said, doctors find pancreatic cysts in approximately 2.6% of people who undergo computed tomography (CT) scans (usually for nonspecific symptoms such as chronic pain, injury, or infection) and in 3% to 13.5% of people who undergo magnetic resonance imaging scans. Based on U.S. population statistics for people aged 65 and older, this amounts to more than 1 million people who may face uncertainty about the malignant potential of a pancreatic cyst. Currently, Dr. Lennon said, approximately 665,600 new pancreatic cysts are identified via CT scan each year in the United States.
Some harmless cysts should be removed because of their large size or tendency to cause swelling in the organ or jaundice, but Dr. Lennon estimates that more than 20% of surgically removed pancreatic cysts thought to be cancerous are later found to be benign.
“Most people who are evaluated for pancreatic cysts are older adults in their 60s and 70s and have comorbidities that can make surgery more risky,” said Dr. Lennon. “We want to avoid unnecessary surgery whenever we can.” Surgical complications that may arise include fistulas, infections, and death.
The researchers caution that 40% of the time, doctors are unable to collect enough cyst fluid for standard analysis, a problem that they believe their genetic testing method solves by requiring only very small samples of cystic DNA. But they caution that cyst fluid removal is not risk-free and can cause bleeding, infection, and inflammation in a very small percentage of patients.
Comparative Testing
To determine whether DNA changes present in the cyst could be accurately detected before surgery, Dr. Lennon and her colleagues compared genetic tests on cyst fluid samples obtained during endoscopic ultrasound before surgery and from cyst specimens surgically removed in 24 of the 130 study subjects. They found a similar number of genetic changes in 21 of the samples before surgery and 20 of the surgically removed cyst specimens.
Dr. Lennon said the team plans to study the combination approach on more varieties of pancreatic cysts, especially the rare types. To further validate the findings, they must test the approach on larger numbers of patients, determine how well the approach identifies cysts that need to be removed in newly diagnosed patients, and evaluate its cost-effectiveness.

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