What are pancreatic cystic neoplasms (PCNs) and how are they usually discovered?
Pancreatic cystic neoplasms, or PCNs, are a subset of all pancreatic cysts that are found on the pancreas. PCNs are neoplastic cysts that span a biological spectrum from benign to malignant.
PCNs are being increasingly discovered on abdominal imaging studies performed for unrelated indications. These are known as incidental PCNs.
According to Medicare records, approximately 120,000 fine needle aspirations of pancreatic cysts are performed each year in the United States alone.
What are the main differences between mucinous and non-mucinous incidental PCNs?
PCNs are generally categorized as mucinous or non-mucinous. Differentiating between these two types is important because PCNs that are non-mucinous are generally regarded as benign without risk of malignancy. Mucinous forms of PCN are considered to have an appreciable, though low, risk of malignant transformation.
Given the high rate of mortality associated with pancreatic malignancy, as well as the high cost and risk potential of surgery on benign cysts, it is crucial that strategies are implemented to identify PCNs as having a high or low risk for cancer.
How effective are current methods for differentiating between these two cyst types?
Differentiating between the two main types of pancreatic cysts, as well as sub-types, represents a formidable clinical challenge.
Traditionally, methods for categorizing PCNs have been limited to current standard diagnostic modalities such as imaging, specifically endoscopic ultrasound (EUS), carcinoembryonic antigen (CEA) testing and cytology.
Each of these modalities has limitations in differentiating the PC and PCN sub-types and the malignant potential of these cysts is difficult to determine. As a result, clinicians generally are required to choose between surveillance versus surgery, taking into account that progression to cancer is a concern, or recognizing the risks of surgery, which itself has high associated morbidity.
Many resected cysts are benign, causing excessive and unnecessary costs to the healthcare system.
What is integrated molecular pathology (IMP)?
Integrated molecular pathology (IMP) is a promising new risk-stratification tool used to predict the malignant potential of pancreatic cysts. IMP of patient cyst fluid may improve the ability to distinguish mucinous from non-mucinous cysts and is particularly helpful in predicting the malignant potential of pancreatic cysts.
Commercially available IMP diagnostic tests classify PCs as benign, mucinous or aggressive based on the level of mutational change in cyst fluid. Use of IMP can help clinicians more accurately determine which patients’ cysts have a greater potential to progress to cancer, providing significant improvements in risk stratification.
This leads to improvements in patient management decisions and can help reduce unnecessary surgeries and the morbidities and costs associated with these surgeries.
How many studies have been carried out on IMP of patient cyst fluid and what have they shown?
IMP is a relatively new commercial diagnostic modality but its use is quickly gaining clinical validation. Most recently, results of a multicenter study published in the February 2015 issue of Endoscopy showed that the IMP PancraGenTM, which utilizes the PathFinderTG platform to provide a full mutational analysis on aspirate fluids from the free, or released, DNA in cyst fluid specimens, is 90% accurate at predicting benign and malignant disease in patients with pancreatic cysts.
The PathFinderTG platform has been clinically validated in over 200 peer-reviewed articles, with more than 27,000 specimens analyzed using PathFinderTG technology.
Please can you outline your recent research published in Endoscopy International? What were your main aims?
A study recently published in Endoscopy International Open was initiated to evaluate the cost-effectiveness of IMP in comparison to other strategies for diagnosing and managing asymptomatic PCNs using healthcare economic modeling.
What were your key findings and were you surprised by the results of this analysis?
Data on the benefits of current standards used to manage diagnosis of pancreatic cysts in the context of healthcare costs and patient outcomes was published online in Endoscopy International Open. In the study, we evaluated cost-effective, quality-enhancing cyst management over the surveillance of patients using IMP with the molecular diagnostic PancraGen ™ (formerly PathFinderTG® Pancreas) to help diagnose pancreatic cysts.
Our study found that the use of IMP was the most cost-effective strategy for diagnosing and managing asymptomatic PCN, supporting its routine clinical use.
The study compared four management strategies in a hypothetical cohort of 1,000 asymptomatic patients with a 3-cm solitary pancreatic cystic lesion.
Strategy I used cross-sectional imaging, recommending surgery only if symptoms or risk factors emerged; Strategy II considered patients for resection without initial EUS; Strategy III referred only those with mucinous cysts determined via CEA for resection; and Strategy IV implemented IMP classification based on the level of mutational change in cyst fluid—benign and mucinous patients were followed with surveillance; aggressive patients were referred for resection. Quality-adjusted life years and incremental cost-effectiveness ratios were calculated. The study’s results were consistent with our hypothesis.
In what ways was this study limited and what further research is needed?
Our study had several limitations, many of which are inherent in any healthcare economic model. In lieu of a prospective, randomized clinical trial, this study used healthcare economic modeling to evaluate the costs and benefits of different strategies for diagnosing and managing PCNs. A controlled, randomized study examining different strategies of managing PCNs with long-term follow up is not a viable option for the future, so to conduct healthcare economic modeling based on available clinical data is the only practical way to develop management recommendations.
In addition, because the natural history of PCN is not fully understood, our model needed to make assumptions about some of the variables in which data are lacking, and we recommend that the surgical risk score developed for this analysis undergo further clinical validation. Lastly, our study only examined direct versus indirect costs, and did not consider postoperative morbidity and complications related to EUS-FNA procedures.
What do you think the future holds for IMP and managing incidental PCNs?
Based on this study and others, IMP appears to have significant clinical value for physicians and their patients with pancreatic cysts.
Due to the limitations of current standard diagnostic modalities in providing consistent, meaningful prediction of malignant potential of PCNs, IMP represents the most cost-effective strategy for managing PCNs and holds tremendous potential as a risk-stratification tool for clinicians with pancreatic cyst patients.
Where can readers find more information?
Readers can access our study in Endoscopy International Online here: https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-1392016
Readers can also visit www.PancraGen.com for more information about IMP and pancreatic cysts, clinical studies and this commercially available product.
About Dr Ananya Das
Ananya Das, MD, is a nationally renowned gastroenterologist in Gilbert, Arizona, who is affiliated with multiple hospitals and is the Chief of Section of Gastroenterology at St. Joseph’s Hospital Medical Center in Phoenix, Arizona. Dr. Das has held numerous academic appointments, including Professor of Medicine at the Mayo Clinic College of Medicine, Associate Chair of the Department of Medicine at Mayo Clinic, Scottsdale, and Affiliate Professor of Medicine, Creighton University, Omaha, NE. He has also held leadership roles as the Medical Director of Endoscopic Ultrasound (EUS) at Scottsdale Shea Medical Center’s Virginia Piper Cancer Center and Director of Endoscopy at Mayo Clinic, Scottsdale. He is a Fellow of the American College of Gastroenterology (FACG) and the American Society for Gastrointestinal Endoscopy (FASGE) and served as the Associate Editor of Gastrointestinal Endoscopy.
Dr. Das has authored or co-authored more than 300 original research publications, abstracts and presentations in the areas of advanced endoscopy, endoscopic ultrasound, cancer outcomes and health disparities. His clinical expertise includes pancreatobiliary disorders, gastrointestinal cancer, esophageal disease, gastrointestinal bleeding, colon cancer screening and health care outcomes. He performs endoscopic procedures such as endoscopic ultrasound (EUS), therapeutic endoscopic retrograde cholangio-pancreatography (ERCP), endoscopic mucosal resection (EMR), complex polypectomy, stent placement, enteroscopy, upper endoscopy (EGD) and colonoscopy.
Dr. Das received a medical degree from Silchar Medical College in Assam, India, and completed his postgraduate education at the Postgraduate Institute of Medical Education & Research and the Sanjay Gandhi Post-Graduate Institute of Medical Sciences of India. He completed fellowships in Gastroenterology with the Case University Hospitals of Cleveland, where he went on to complete an additional fellowship in Advanced Endoscopy.
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