James Farrell, MD, professor of medicine (digestive diseases) and surgery (surgical oncology) and director of the Yale Medicine Pancreatic Diseases Program, recently published a review on the current state of clinical care and research for pancreatic cysts in the New England Journal of Medicine.
The paper explains different types of these pancreatic cysts, guidance to determine cancer risks, when and how to use endoscopic ultrasound for evaluation, and approaches for managing patients with concerning cysts.
We spoke with him about this paper, the state of research around pancreatic cysts, and why he is inspired to learn more about this field.
What are pancreatic cysts?
Pancreatic cysts are small fluid-filled collections in the pancreas that can range in size from half a centimeter to up to four or five centimeters.
As imaging technology has advanced, we can identify more of them. Even still, we believe that they are becoming more common.
About 15% of adults in the U.S. have pancreatic cysts, and they are more common in older adults.
There are more than 20 different types of pancreatic cysts. About 15-25% of cysts are benign and require little management.
Unfortunately, we’ve learned that most pancreatic cysts are precancerous. These cysts are referred to as IPMN, which stands for intraductal papillary mucincous neoplasm. While only a small percentage of IPMN pancreatic cysts will lead to pancreas cancer, the medical community needs to understand how to identify and care for patients with them.
Why is it essential for the medical community to better understand pancreatic cysts?
One of the high-risk groups prone to developing pancreatic cancer are those who have pancreatic cysts. About 25% of all pancreatic cancers arise from pancreas cysts.
Pancreatic cancer is one of the deadliest forms of cancer, with a five-year survival rate of around 13%. Unfortunately, pancreatic cancer rates are rising. By 2030, estimates say that this cancer will be the second most common cause of cancer-related death.
If we can better identify and respond to pancreatic cysts, we may be able to prevent them from turning into a dangerous cancer.
How are pancreatic cysts identified?
While some of these cysts, especially large ones, can cause abdominal pain or pancreatitis, most people don't know they have a cyst on their pancreas until they receive an MRI or CT scan, often for a different, unrelated medical issue.
We are also learning that some patients with pancreatic cysts may have a higher risk of progressing to cancer. This information can help with identification and management. For example, people with pancreas cysts and new-onset diabetes may be at a higher risk for progressing to cancer. We’re not at the stage where everyone with new-onset diabetes should get a CT scan or MRI to look at their pancreas, but more research is certainly needed.
What does current research tell us about how physicians should respond to pancreatic cysts?
Our review article outlined appropriate surveillance approaches for patients with different types of pancreatic cysts based on cyst size and features.
Benign and low-risk cysts are much more common, and interventions often offer no benefit and may even be harmful to the patient.
Physicians must consider the cyst size and other imaging features, as well as patient cancer risk factors and other coexisting medical conditions. For example, patients with jaundice caused by biliary obstruction are at higher risk.
It’s also important to make care and treatment decisions with patients based on their personal risk tolerance.
What prompted you to write this article?
My collaborators, Tamas Gonda, MD, from New York, and Djuna Cahen, MD, from the Netherlands and I, were invited to bring everyone up to date on our current knowledge of pancreatic cysts and give better guidance on which patients should be referred to a surgeon, which patients should be referred for an endoscopic ultrasound evaluation, which patients should be followed and for how long.
I’ve been very fortunate to be involved with the multidisciplinary evaluation of pancreatic cysts since before training, and I’ve witnessed the evolution of our understanding and how best to treat them.
Fifteen years ago, the best practice was to surgically remove any pancreatic cyst over three centimeters. Pancreatic surgery is serious, and we learned that about four-fifths of those surgeries were probably unnecessary. More recently, the field decided that most cysts should undergo endoscopic ultrasound evaluation. We’ve learned even that is unnecessary and refined our indications for who should have endoscopic evaluation.
It's ultimately a balance between not missing a cancer and not sending too many patients for unnecessary surgery or tests. We’re not at a place of complete understanding, but we have a deeper maturity in managing this.
What other work is underway at Yale to advance our understanding of pancreatic cysts?
One of the things I’m most excited about is that we have developed an extensive pancreatic cyst biobank, which is a prospective collection of patient blood, cyst fluid, and tissue. This biobank is helping to support our research studies of pancreatic cyst, which has led to new developments in identifying molecular markers that can tell us if a patient has a higher or lower risk of having advanced cancer. This is still in development but could help shape how we treat and survey patients with pancreatic cysts.
We are also working with the Yale Chair of Surgery, Nita Ahuja, MD, MBA, and Research Scientist (Surgery), Anup Sharma, PhD, to understand why some cysts progress to cancer while other similar-sized cysts do not. We’re working to biopsy a pancreatic cyst and grow it outside the body in an organoid so we can better study this progression towards pancreas cancer.
I’m also working with my colleagues Dennis Shung, MD, PhD, assistant professor of medicine (digestive diseases) and Stephen Robinson, PhD, research affiliate (digestive diseases), on the use of generative artificial intelligence to help us extract key information from radiology reports and CT and MRI scan images to help identify and risk stratify large numbers of patients with pancreatic cysts and to help us more quickly identify those that require the most attention. This work is still in the early stages, but we’re encouraged by our initial results.
Through our Multidisciplinary Pancreas Cyst Clinic based in North Haven, we're involved with two clinical trials on caring for patients with pancreatic cysts. I'm the principal investigator of a clinical trial that compares frequent vs. less frequent monitoring to determine which leads to better patient outcomes, as well as prospective evaluation of novel blood-based biomarkers for detecting pancreatic cancer in pancreas cysts through our involvement in the international PRECEDE Pancreas Cancer Early Detection Consortium.
What inspires you to continue your work on pancreatic cysts?
Preventing or detecting early pancreatic cancer is a significant challenge. It would be easy to be overwhelmed and decide that effort is futile. But I decided long ago to do my bit to chip away at the problem. That’s why you come to a place like Yale.
I recently looked back at similar papers I co-authored on pancreatic cysts 10 and 20 years ago. My initial reaction was, “Yikes! What were we thinking?”
That’s how far this field has come in a relatively short time. We’ve made tremendous progress in our understanding of pancreatic cysts and pancreas cancer, and how I and my gastroenterology and surgical colleagues should care for these patients.
It’s hugely satisfying, but there’s always more to do. The journey is not over.
Gonda TA, Cahen DL, Farrell JJ. Pancreatic Cysts. N Engl J Med. 2024 Sep 5;391(9):832-843. doi: 10.1056/NEJMra2309041. PMID: 39231345.
Since forming one of the nation’s first sections of hepatology more than 75 years ago and then gastroenterology nearly 70 years ago, Yale School of Medicine’s Section of Digestive Diseases has had an enduring impact on research and clinical care in gastrointestinal and liver disorders. To learn more about their work, visit Internal Medicine: Digestive Diseases.