- Acute Pancreatitis
- Acute Pancreatitis Symptoms
- Acute Pancreatitis Diagnosis at Johns Hopkins
- Laboratory Testing
- Imaging Scans for Pancreatitis
- Endoscopic Retrograde Cholangiopancreatography (ERCP)
- ERCP and Sphincter of Oddi Manometry
- Acute Pancreatitis Treatment at Johns Hopkins
- For more on acute pancreatitis:
- Johns Hopkins researchers use deep learning to combat pancreatic cancer
- Acute pancreatitis
- Chronic pancreatitis
- What causes pancreatitis?
- Other causes of pancreatitis include:
- What are the symptoms of pancreatitis?
- How is pancreatitis diagnosed?
- How is pancreatitis treated?
- What are the complications of pancreatitis?
- Key points about pancreatitis
- Next steps
- Johns Hopkins University
- Title of the PCDC Project
- Description of the Project
- Resources for Sharing (e.g., description of cohorts, technologies)
- Opportunities for Collaboration
- Earlier, More Frequent Removal of Some Pancreatic Cysts May Decrease Cancer Risk for Some Patients
- Test shown to improve accuracy in identifying precancerous pancreatic cysts
- Machine-Learning Assay May Improve Pancreatic Cyst Management – Promising Science
- A Pancreatic Cyst Evaluation Primer
- Enter CompCyst
- What’s Next
Linkedin Pinterest Liver Gallbladder and Pancreas
Pancreatitis is an inflammation of the pancreas. The pancreas produces juices that help digest food in the small intestine. It also produces insulin, which controls the sugar level in your blood.
Acute Pancreatitis Symptoms
The main symptom of acute pancreatitis is mild to severe abdominal pain. Patients with acute pancreatitis also have elevated pancreatic enzymes, which show up in blood and urine tests.
Other symptoms include:
- Nausea and vomiting
- Respiratory failure
- Mild jaundice
Acute Pancreatitis Diagnosis at Johns Hopkins
A diagnosis of pancreatitis begins with a comprehensive physical exam during which you describe your symptoms and medical history. Tests your doctor may order include:
- Laboratory Testing
- Imaging Scans
- Endoscopic Retrograde Cholangiopancreatography (ERCP)
- ERCP with Sphincter of Oddi Manometry
During an acute pancreatitis attack, the pancreas releases enzymes into the blood. Measuring these enzymes is helpful in diagnosing acute pancreatitis. Blood and urine tests look for the presence of these enzymes. The most common enzymes measured are amylase and lipase.
Imaging Scans for Pancreatitis
If you have severe abdominal pain, we may recommend an imaging study. Imaging studies use various different technologies to obtain enhanced, detailed pictures of your body. These studies will reveal an obstruction, fluid buildup, or an increased separation between your stomach and colon. These findings suggest an inflammation of the pancreas.
Imaging studies used to diagnose acute pancreatitis include:
- Ultrasound uses sound waves to create detailed images. It is not sensitive enough to detect pancreatic abnormalities, but it is useful in detecting gallstones and other obstructions.Computed tomography (CT) scan is a powerful X-ray and the best
- diagnostic test for acute pancreatitis. Your doctor may perform a contrast-enhanced CT scan because the contrast highlights any abnormalities.
Endoscopic Retrograde Cholangiopancreatography (ERCP)
An ERCP is an endoscopic technique that allows for visualization of the bile and pancreatic ducts. During this procedure, a special side-viewing endoscope is inserted into the duodenum.
This endoscope, called a duodenoscope, is specially designed to ease placement of endoscopic accessories into the bile and pancreatic ducts. Your doctor will also inject a dye into the ducts to obtain detailed X-ray images.
ERCP is a sensitive and specific diagnostic test for acute pancreatitis. It shows details of your pancreatic anatomy, including any strictures (narrowed areas), ruptures and cysts.
ERCP and Sphincter of Oddi Manometry
The sphincter of Oddi is a muscle that controls the flow of bile and pancreatic juices. Sphincter of Oddi manometry is a diagnostic procedure that allows your doctor to determine whether the sphincter is opening and closing normally.
Acute Pancreatitis Treatment at Johns Hopkins
Treatment for acute pancreatitis allows the pancreas to rest and recover from the inflammation. Learn more about acute pancreatitis treatment at Johns Hopkins.
For more on acute pancreatitis:
See illustration: Endoscopic major papilla sphincterotomy and stent placement.
See illustration: Endoscopic minor papilla sphincterotomy performed with a pull-type sphincterotome.
See illustration: Endoscopic sphincterotomy performed with a needle-knife sphincterotome over a stent.
Johns Hopkins researchers use deep learning to combat pancreatic cancer
Only 7 percent of patients live five years after diagnosis of pancreatic cancer, the lowest rate for any cancer, according to the American Cancer Society. Elliot K. Fishman, MD, a researcher and radiologist at Johns Hopkins, is on the forefront of trying to change this statistic, and he's using artificial intelligence to do it.
Fishman aims to spot pancreatic cancers far sooner than humans alone can by applying GPU-accelerated deep learning artificial intelligence to the task.
Johns Hopkins is suited to developing a deep learning system because it has the massive amounts of data on pancreatic cancer needed to teach a computer to detect the disease in a CT scan.
Hospital researchers also have NVIDIA's DGX-1 AI Supercomputer.
Fishman is helping train deep learning algorithms to spot minute textural changes to tissue of the pancreas and nearby organs. These changes often are the first indication of cancer. Deep learning detection methods could mean earlier diagnosis. Fishman estimates that nearly a third of the cases he sees could have been detected four to 12 months sooner.
Where many other cancers are now in the process of being cured or survival is increasing significantly, pancreatic cancer has not had the same success. One of the challenges with pancreatic cancer is that early detection is difficult, especially in minimally symptomatic patients. The goal then would be early detection.
“The major treatment for pancreatic cancer for cure is surgery, but unfortunately, because of late detection, no more than 15-20 percent of patients at the time of presentation are surgical candidates,” said Fishman, professor of radiology, surgery, oncology and urology at Johns Hopkins Hospital. “A minimal goal would be to increase the number of eligible patients for surgical attempt at cure. This is the first challenge.”
When physicians review prior scans on patients who are eventually diagnosed with pancreatic cancer, in up to 30 percent of cases in retrospect physicians can see the tumor present.
“Sometimes it is indeed simply by a retrospectoscope that we see the findings and sometimes it was simply just not seen by the initial interpreter,” Fishman explained. “The goal of using GPU-accelerated deep learning would be to optimize lesion detection so that you can detect every lesion that is present at the earliest time.”
He also believes that by using deep learning artificial intelligence, Johns Hopkins can train the computer to not only be as good as the best radiologist but to be better. The ability to learn and detect even subtle changes texture and pattern rather than simply masses will be one thing for which Johns Hopkins looks to the supercomputers, he said.
“Our group has two NVIDIA DGX-1 supercomputers,” he explained. “The DGX-1 is the state of the art in AI and is necessary for our work. It allows us to review and study the results of hundreds of cases simultaneously and to be able to change parameters, develop algorithms that would be otherwise impossible.
“It is these algorithms that allow us to optimize the detection of tumor and to eventually be able to define specificity of tumor type and hopefully also allow us to determine better management strategies,” he added.
Through deep learning detection methods, in up to 30 percent of cases researchers can see the tumor that was present, Fishman said.
“I think one of the important things to recognize is that the detection of a tumor of the pancreas especially when the primary requisition is not 'rule out pancreatic mass' is often overlooked,” he said. “One of the things we are relying on the computer to do is do the optimal examination in every abdominal CT and look carefully at the pancreas whether or not this is the zone of suspected pathology.”
One of the challenges is in cases where pancreatic cancer is not suspected, the reader can easily overlook a subtle tumor. The ability to optimize interpretation and optimize the analysis of each and every study is one of the goals of the project and it is something that researchers believe they can accomplish.
“In an era of increasing study volumes where the radiologist spends less time on an individual case, there is no doubt that error rates are increasing,” Fishman said.
“We believe that we can decrease error, increase detection and change the outcome for many of our patients.
The goal of this project is nothing less than changing the trajectory of treatment of pancreatic cancer and ultimate patient survival.”
Email the writer: email@example.com
Linkedin Pinterest Liver Gallbladder and Pancreas
Pancreatitis is the redness and swelling (inflammation) of the pancreas. This happens when digestive juices or enzymes attack the pancreas.
The pancreas lies behind your stomach on the left side of your belly. It is close to the first part of your small intestine (the duodenum).
The pancreas is a gland. It does 2 main things:
- It makes enzymes and sends them into your small intestine. These enzymes help break down food.
- It makes the hormones insulin and glucagon and sends them into your bloodstream. These hormones control your body’s blood sugar level.
Pancreatitis may be sudden (acute) or ongoing (chronic).
- Is a sudden inflammation
- Lasts for a short time
- Lets the pancreas return to normal afterward
- May cause serious problems or be deadly in severe cases
- Is a long-lasting inflammation that comes and goes over time
- Causes permanent damage to the pancreas
- Often causes scarring of pancreatic tissue
- May cause the pancreas to stop making enzymes and insulin in severe cases
What causes pancreatitis?
The most common causes of pancreatitis include:
- Alcohol abuse
- Lumps of solid material (gallstones) found in the gallbladder. Gallstones block the pancreatic duct so the enzymes can’t get the pancreas.
Other causes of pancreatitis include:
- Belly injury or surgery
- High levels of fat particles (triglycerides) in the blood
- Very high levels of calcium in the blood
- Certain medicines, such as estrogens, steroids, and thiazide diuretics
- Infections, such as mumps, hepatitis A or B, or salmonella
- Cystic fibrosis
- A tumor
- Certain genetic defects
- Congenital abnormalities in the pancreas
- Trauma to the pancreas
- Cigarette smoking
What are the symptoms of pancreatitis?
Each person’s symptoms may vary. Symptoms may include:
- Severe belly pain that may spread to your back or chest (it may feel worse after you eat)
- Rapid heart rate
- Swelling and feeling sore or tender in your upper belly
- Fluid buildup in your belly
- Lowered blood pressure
- Yellowing of the skin and eyes (jaundice)
The symptoms of pancreatitis may look other health problems. Always see your healthcare provider to be sure.
How is pancreatitis diagnosed?
Your healthcare provider will look at your past health. He or she will give you a physical exam.
You may have some blood tests done. You may also have some imaging tests including:
- Belly X-ray. Makes images of internal tissues, bones, and organs.
- Ultrasound (also called sonography). Uses sound waves to see the internal organs of the belly. It also checks how blood is flowing through different blood vessels.
- EUS (endoscopic ultrasound). This is an internal type of ultrasound done through a flexible tube (endoscope) inserted through the mouth while you are sleeping.
- ERCP or endoscopic retrograde cholangiopancreatography. This is used to find and treat problems in your liver, gallbladder, bile ducts, and pancreas. It uses X-ray and a long, flexible tube with a light and camera at one end (an endoscope). The tube is put into your mouth and throat. It goes down your food pipe (esophagus), through your stomach, and into the first part of your small intestine (duodenum). A dye is put your bile ducts through the tube. The dye lets the bile ducts be seen clearly on X-rays.
- CT scan (computed tomography scan). This imaging test shows detailed images of any part of the body such as the bones, muscles, fat, and organs. CT scans are more detailed than regular X-rays.
- MRCP (magnetic resonance cholangiopancreatography). This uses MRI (magnetic resonance imaging) to make detailed images of your pancreas, gallbladder, and pancreatic and bile ducts. A dye is shot (injected) into your vein so that the images can be seen more clearly.
How is pancreatitis treated?
The treatment goal is to rest the pancreas and let it heal.
In most cases, you:
- Will be in the hospital for a few days
- Will be given IV (intravenous) fluids
- Will be given pain medicine and medicines that fight bacterial infections (antibiotics)
- If mild, you may be able to eat clear liquids or a low-fat diet. However, if severe, you may not be able to eat or drink for a few days to let your pancreas rest. A feeding tube may need to be used in some situations.
Pancreatitis often gets better in a few days.
If any problems happen, treatment may include:
- NG tube (nasogastric tube). This is a thin tube passed down your nose and into your stomach. It is used if vomiting is a problem. The tube can be used for a few weeks. It can be used to remove fluid and air and give your pancreas more time to heal. It can also be used to put liquid food into your stomach as you heal.
- ERCP (endoscopic retrograde cholangiopancreatography). This is used to find and treat problems in your liver, gallbladder, bile ducts, and pancreas. It uses X-ray and a long, flexible, lighted tube (an endoscope). The tube is put into your mouth and throat. It goes down your food pipe (esophagus), through your stomach, and into the first part of your small intestine (duodenum). A dye is injected into the bile ducts through the tube. The dye lets the bile ducts be seen clearly on X-rays. The tube has tools in it. The tools can remove fluid and blockages and take out gallstones. They can also put stents (firm tubes) in the ducts to keep them open.
- Surgery to remove gallstones or your gallbladder. This is done if gallstones or your gallbladder are causing pancreatitis.
If you have chronic pancreatitis you may also:
- Have to avoid alcohol (if your pancreatitis is caused by alcohol abuse)
- Have to stop smoking
- Need enzyme supplements to help digest your food
- Need insulin (if you get diabetes)
- Need to eat small high-protein, low-fat meals
- Need surgery to remove the permanently damaged part of your pancreas. In advanced situations, a special transplant called islet cell transplant is done.
- Need medicine for chronic pain
What are the complications of pancreatitis?
Acute pancreatitis usually gets better on its own over time. Most people recover without any problems. A small number of cases end up with fluid collections around the pancreas that require drainage.
Chronic pancreatitis may also get better on its own. But that can take longer, after a few attacks. Chronic pancreatitis has a greater risk of long-term problems such as:
- Chronic pain
- Weight loss
- Low vitamin levels from malabsorption
- A collection of fluid (pseudocyst) around the pancreas
- Bile duct blockages
- Permanent pancreas damage
- Pancreatic cancer
Key points about pancreatitis
- Pancreatitis is the redness and swelling (inflammation) of the pancreas.
- It may be sudden (acute) or ongoing (chronic).
- The most common causes are alcohol abuse and lumps of solid material (gallstones) in the gallbladder.
- The goal for treatment is to rest the pancreas and let it heal.
- You will ly be in the hospital for a few days.
- You may need drainage of abnormal fluid collections, imaging tests to evaluate the pancreas for disease, and rarely surgery to permanently damaged part of the pancreas.
- It is very important to stop smoking and drinking or the pancreatitis will usually happen again and worsen.
Tips to help you get the most from a visit to your healthcare provider:
- Know the reason for your visit and what you want to happen.
- Before your visit, write down questions you want answered.
- Bring someone with you to help you ask questions and remember what your provider tells you.
- At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.
- Know why a new medicine or treatment is prescribed, and how it will help you. Also know what the side effects are.
- Ask if your condition can be treated in other ways.
- Know why a test or procedure is recommended and what the results could mean.
- Know what to expect if you do not take the medicine or have the test or procedure.
- If you have a follow-up appointment, write down the date, time, and purpose for that visit.
- Know how you can contact your provider if you have questions.
Johns Hopkins University
Principal Investigator (contact): Michael G. Goggins, MD
Institution: Johns Hopkins University
Title of the PCDC Project
USING MARKERS TO IMPROVE PANCREATIC CANCER SCREENING AND SURVEILLANCE
Since most patients with pancreatic cancer present with advanced disease, pancreatic screening is needed to detect asymptomatic early-stage potentially curable lesions. In our CAncer of the Pancreas Screening (CAPS) clinical studies we have screened ~600 individuals at increased risk of developing pancreatic cancer using family history or gene mutation criteria.
Screening can identify precancerous lesions and pancreatic cancers, but better circulating and pancreatic juice markers are needed to aid in pancreatic evaluation.
Pancreatic juice collected from the duodenum during routine endoscopic ultrasound reveals that this sample is a rich source of biomarkers of pancreatic neoplasia and the analysis of pancreatic juice could be a useful diagnostic test. Thus, GNAS mutations are highly specific for IPMNs are specifically detected in the juice samples of patients with IPMNs.
KRAS mutations are commonly found not only in the pancreatic juice of patients with pancreatic cancer, but in patients undergoing pancreatic screening even when they do not have evidence of pancreatic neoplasia by imaging.
Many of these mutations are thought to arise in PanIN, which are not detected by pancreatic imaging tests because these lesions are very small and do not form masses. Thus, pancreatic juice analysis has the potential to indicate the presence of PanIN.
More valuable would be a test that would indicate the grade of pancreatic neoplasia since in the absence of cancer, this is usually not possible to determine without analyzing the resected pancreas. We know that TP53 and SMAD4 mutations emerge in high-grade dysplasia and invasive pancreatic cancer tumors and can find TP53 and SMAD4 mutations in pancreatic juice samples in patients with pancreatic cancer and high-grade dysplasia, not in disease controls or those with low- grade dysplasia.
Description of the Project
Our project, which helps support the CAPS screening program, is a joint collaboration between Johns Hopkins University, University of Pittsburgh, University of Pennsylvania, Dana Farber Cancer Institute and Case Western Medical Reserve.
Our goals is to develop and follow our CAPS screening cohort, to evaluate biomarkers of pancreatic cancer, and to perform PROBE-based analysis of our best biomarkers of cases within our cohort that progress to pancreatic cancer or high-grade dysplasia during follow-up vs those who do not progress.
The main biomarkers we are evaluating are pancreatic juice mutations determined by digital next-generation sequencing and circulating biomarkers, primarily ctDNA.
Specifically, we propose: Aim #1: To determine the diagnostic accuracy of mutations detected in pancreatic fluid as markers of pancreatic cancer and precancerous lesions.
We will use novel nextgen sequencing methods to detect mutations in patients with pancreatic cancer, IPMNs, chronic pancreatitis, or normal pancreata. Aim #2: To evaluate circulating markers as diagnostic tests for the early detection of pancreatic cancer.
We will evaluate ctDNA and exosomal markers. Aim #3: To evaluate pancreatic fluid and serum markers as tests to detect PanIN-3 and/or pre-clinical pancreatic cancer among high-risk individuals undergoing pancreatic screening and surveillance.
We will develop a tissue repository of precious samples to aid in the evaluation of candidate pancreatic cancer markers, including samples from high-risk subjects and PanIN-3 lesions.
Resources for Sharing (e.g., description of cohorts, technologies)
The CAPS sites are primarily following high-risk individuals, but we are also enrolling patients with incidentally identified pancreatic cysts and patients who are undergoing pancreatic evaluation routinely for non-pancreatic indications (such as those who undergo endoscopic ultrasound for other upper GI indications). The Johns Hopkins group also has an extensive biobank of tissues and blood samples from patients who have undergone pancreatic reseection. Technologies such as digital next-generation sequencing developed in the Goggins lab will be used to detect low-abundance mutations.
Opportunities for Collaboration
There are a number of other CAPS sites who are ongoing collaborators with the CAPS program including Dr. James Farrell at Yale University and Dr. Fay Kastrinos at Columbia University.
Several other sites have approached us and are interested in collaborating as part of the CAPS program.
In addition, screening centers across the world have joined the International CAPS registry to share data and experience.
Earlier, More Frequent Removal of Some Pancreatic Cysts May Decrease Cancer Risk for Some Patients
CT scan of a pancreas that shows enlarged pancreatic duct Credit: Johns Hopkins Medicine
By analyzing medical records of 901 adults who had surgery for a certain type of precancerous pancreatic cyst, researchers at Johns Hopkins Medicine and The Karolinska Institute in Sweden have updated parameters for an anatomical “marker” that can tell more precisely if these cysts are ly to develop into lethal pancreatic cancers.
The findings, they say, are not yet proof of the concept, but do strongly suggest that removing so-called intraductal papillary mucinous neoplasms as soon as the main pancreatic duct is enlarged beyond 5 millimeters in diameter has the potential to prevent these precancers before they become malignant.
The pancreas is shaped vaguely a revolver, with a duct –normally about 3 millimeters in diameter — that runs all the way down the barrel of the gun and carries digestive enzymes. When inflamed or populated by cysts or other growths, the duct enlarges.
The vast majority of pancreatic cysts, including intraductal papillary mucinous neoplasms, are benign and cause no symptoms, the researchers note.
In fact, most are diagnosed “incidentally” during MRIs or CT scans for non-pancreas-related conditions.
But some can cause significant inflammation and damage to the duct that runs the length of the pancreas — a process that dilates, or enlarges, the duct — and are more ly precancerous or even cancerous.
Pancreatic cancer is the third leading cause of cancer deaths, affecting more than 55,000 Americans each year.
The disease is difficult to diagnose and treat, and five-year survival rates after diagnosis are around 9%, according to the U.S. National Cancer Institute.
As a result, efforts to identify early markers of the disease — biological or structural — are a priority for pancreatic disease specialists.
Guidelines set in 2012 by the International Cancer of the Pancreas Screening Consortium call for surgical removal of these cysts when there are one or more and when dilation of the duct is at or greater than 10 millimeters. But the new Johns Hopkins study findings are in support of the more recent European guidelines published in 2018, which encourage surgical removal when dilation is in a range much smaller than that.
Specifically, the researchers report in the Annals of Surgery published online this past winter, their analysis offers indirect evidence that for people who can safely undergo surgery, the best option for preventing cancer is to remove cysts when the duct is anywhere over 5 millimeters because many of those removed cysts had precancerous cells or cancer tissue.
“If we continue using the more conservative cutoff point of 10 millimeters dilation for deciding when to remove these cysts, this study suggests we will miss a lot of people who will go on to develop cancer,” says Ross Beckman, M.D.
, a resident and postdoctoral fellow in the Department of Surgery at the Johns Hopkins University School of Medicine and one of the lead authors on the paper.
“Changing to more aggressive guidelines will lead to more surgeries, but would ly save more lives.”
For their study, the researchers collected data from the medical records of 901 patients who underwent some form of pancreas-related surgery at The Johns Hopkins Hospital between 2004 and 2017 and the Karolinska University Hospital in Sweden from 2008 to 2017. Both hospitals have the highest volume of such operations for the U.S. and Europe, respectively.
Overall, the patients’ average age was 69 years, and 52% were women.
Of the types of pancreatic surgery underwent by the participants, some 58% had Whipple procedures, which remove the head of the pancreas and parts of the small intestine and stomach, along with the gallbladder and bile duct. Another 29% had the end of the pancreas removed; 11% had complete pancreas removal; and 2% had other types of pancreas surgeries.
Each hospital used a specialized pancreatic pathologist who analyzed the cysts removed from surgery and reported the findings in the medical charts. reviews of the medical charts, about 60% of the patients had noncancerous cysts, 23% had precancerous cysts and 17% had cancerous cysts.
Then, the researchers gathered information on the widths of each pancreatic duct in the 901 patients using CT scans and MRIs taken for any reason within 30 days prior to the patients’ surgeries.
The researchers found that the 286 people with pancreatic ducts dilated from 5–9.9 millimeters were 1.7 times more ly to develop precancerous cells and 3.4 times more ly to develop pancreatic cancer than people with less than 5 millimeter dilation.
Among the 150 patients with 10 millimeter or wider pancreatic ducts, the records showed they were 7.5 times more ly to develop precancerous cells and 14 times more ly to develop pancreatic cancer than the people with dilations of less than 5 millimeters.
The researchers caution that their study was designed to show associations between dilation levels and the lihood of having or developing precancer or cancer. Their findings, they emphasize, don’t prove that removing pancreatic cysts before they dilate ducts beyond 5 millimeters will in fact prevent cancer.
But they said the findings give supporting evidence that it may be time to update the guidelines to call for surgery when dilation is in a range of 5–7 millimeters.
The researchers can’t really say for sure how many people will be saved from cancer to any certain degree as their study wasn’t designed to determine this.
“By 2025, experts predict that pancreatic cancer will be the second leading cause of cancer death in the U.S.,” says Beckman.
“Since pancreatic cancer is so aggressive, survival rates remain low despite improvements in medical and surgical treatment.
But one place where we may really be able to make significant improvements is in early detection and prevention — that is, removing these precancerous growths before they progress to cancer.”
If someone has a pancreatic duct dilated less than 5 millimeters, the researchers say the risk of cancer is relatively low and the risks of surgery ly outweigh the risk of cancer. In these situations, they would recommend watchful waiting with yearly surveillance with an MRI or CT scan.
Others involved in the study were Marco Del Chiaro, Zeeshan Ateeb and Urban Arnelo of CLINITEC; Nicola Orsini of Karolinska Institutet; Neda Rezaee, Lindsey Manos, Richard Burkhart, Matthew Weiss, and Jun Yu and of Johns Hopkins, including Ding Ding, Georgios Margonis, Martin Makary, Jin He, John L. Cameron and Christopher Wolfgang of the Sidney Kimmel Comprehensive Cancer Center; Roberto Valente of Sapienza University of Rome; Chunhui Yuan of Peking University Third Hospital and Lingdi Yin of the First Affiliated Hospital of Nanjing Medical University.
The research was supported by the National Cancer Institute (5T32CA126607-09), Cancerfonden Sweden (CAN 2014/634, CAN 2014/621) and ALF medel Stockholm (20150113).
The researchers don’t have any conflicts to report.
Test shown to improve accuracy in identifying precancerous pancreatic cysts
In a proof-of-concept study, an international scientific team led by Johns Hopkins Kimmel Cancer Center researchers has shown that a laboratory test using artificial intelligence tools has the potential to more accurately sort out which people with pancreatic cysts will go on to develop pancreatic cancers.
The test, dubbed CompCyst (for comprehensive cyst analysis), incorporates measures of molecular and clinical markers in cyst fluids, and appears to be on track to significantly improve on conventional clinical and imaging tests, the research team says.
Using information from more than 800 patients with pancreatic cysts who had cyst fluid analysis and cyst removal surgery at The Johns Hopkins Hospital and 15 other medical centers around the world, investigators say CompCyst more often than standard current methods correctly identified which patients needed and ly had a chance to benefit from surgery, and which were unly to benefit from surgery or needed further monitoring only. Specifically, they found that using the test would have spared from surgery more than half of patients who underwent cyst removal later deemed unnecessary because the cysts were unly to have caused cancer.
A description of the work is published in the July 17 issue of Science Translational Medicine.
“Our study demonstrates the potential role of CompCyst as a complement to existing clinical and imaging criteria when evaluating pancreatic cysts,” says Anne Marie Lennon, M. B. B. Ch., Ph.D.
, professor of medicine and director of the Johns Hopkins multidisciplinary pancreatic cyst clinic.
“It could provide a greater degree of confidence for physicians when they advise patients that they do not require follow-up and can be discharged from surveillance.”
“Although we still need to prospectively validate this test, our results are exciting because they document a new and more objective way to manage the many patients with this disease,” she adds. Plans are underway to begin a prospective validation study in the next year.
Pancreatic cysts are common. They are found in 4% of people in their 60s and 8% of people over age 70, according to other published research. That means some 800,000 people with a pancreatic cyst are identified each year in the U.S. alone. By contrast, only a small fraction of cysts progress to cancer.
“The dilemma facing patients and their physicians is the ability to distinguish precancerous cysts from cysts that will not progress to cancer,” says Lennon.
“Currently available clinical and imaging tests often fail to distinguish precancerous cysts from cysts that have little or no potential to turn cancerous, which makes it difficult to determine which patients will not require follow-up and which patients will need long-term follow-up or immediate surgical resection,” says study investigator Christopher Wolfgang, M.D., Ph.D., M.S., John L. Cameron Professor of Surgery, director of surgical oncology at the Johns Hopkins Kimmel Cancer Center and co-director of the Johns Hopkins Precision Medicine Center of Excellence for Pancreatic Cancer. “As a result, essentially all people diagnosed with a cyst are followed long-term. Surgeons are faced with making recommendations to patients the risks and benefits of surgery with limited information. We seldom miss a cancer, but it is at the expense of performing an operation that in hindsight may not have been necessary. This study directly addresses these fundamental problems in management of pancreatic cysts.”
In the study, the precise nature of the cysts examined was confirmed through histopathological analysis of resected surgical specimens.
The cysts were then classified into three groups: those with no potential to turn cancerous, for which patients would not require periodic monitoring; mucin-producing cysts that have a small risk of progressing to cancer, for which patients can receive periodic monitoring for progression to possible cancer; and cysts for which surgery is recommended because there is a high lihood of progression to cancer.
The CompCyst test, developed by the Johns Hopkins Kimmel Cancer Center-led investigators, was created with patient data including clinical impressions and symptoms, images from CT scans and molecular features such as DNA alterations within cyst fluid.
In the study, the researchers evaluated the molecular profiles, including DNA mutations and chromosome changes, of a large number (862) of pancreatic cysts. They then fed the molecular information, along with clinical and radiologic data, into a computer-based program that used artificial intelligence to classify patients into the three groups noted previously.
histopathological analysis of the surgically resected cysts, the researchers found that surgery was not needed for 45% of the patients that underwent surgery for their cysts.
This unnecessary surgery was performed because the clinicians could not determine if the cysts were dangerous.
In these patients, if CompCyst had been used, the researchers estimated that 60% to 74% of the patients (depending on the cyst type) could have been spared these unnecessary surgeries.
The study had several limitations, the researchers note, including that pancreatic cyst fluid was obtained at the time of surgery, and that the cysts evaluated are more atypical than those seen in routine clinical practice.
“We think CompCyst has the capacity to substantially reduce unnecessary surgeries for pancreatic cysts.
Over the next five years, we hope to use CompCyst in many more patients with cysts in an effort to guide surgical treatment — to determine when surgery is needed and when it is not needed — and evaluate how well the test performs,” says Bert Vogelstein, M.D.
, Clayton Professor of Oncology, co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center and a Howard Hughes Medical Institute investigator.
Materials provided by Johns Hopkins Medicine. Note: Content may be edited for style and length.
- Simeon Springer, David L. Masica, Marco Dal Molin, Christopher Douville, Christopher J. Thoburn, Bahman Afsari, Lu Li, Joshua D. Cohen, Elizabeth Thompson, Peter J. Allen, David S. Klimstra, Mark A. Schattner, C. Max Schmidt, Michele Yip-Schneider, Rachel E. Simpson, Carlos Fernandez-Del Castillo, Mari Mino-Kenudson, William Brugge, Randall E. Brand, Aatur D. Singhi, Aldo Scarpa, Rita Lawlor, Roberto Salvia, Giuseppe Zamboni, Seung-Mo Hong, Dae Wook Hwang, Jin-Young Jang, Wooil Kwon, Niall Swan, Justin Geoghegan, Massimo Falconi, Stefano Crippa, Claudio Doglioni, Jorge Paulino, Richard D. Schulick, Barish H. Edil, Walter Park, Shinichi Yachida, Susumu Hijioka, Jeanin van Hooft, Jin He, Matthew J. Weiss, Richard Burkhart, Martin Makary, Marcia I. Canto, Michael G. Goggins, Janine Ptak, Lisa Dobbyn, Joy Schaefer, Natalie Sillman, Maria Popoli, Alison P. Klein, Cristian Tomasetti, Rachel Karchin, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Christopher L. Wolfgang, Ralph H. Hruban, Anne Marie Lennon. A multimodality test to guide the management of patients with a pancreatic cyst. Science Translational Medicine, 2019; 11 (501): eaav4772 DOI: 10.1126/scitranslmed.aav4772
Machine-Learning Assay May Improve Pancreatic Cyst Management – Promising Science
Pancreatic cysts are all too common, and the numbers seem to be growing.
One of the culprits in this increasing incidence is the sheer numbers of people who undergo abdominal imaging for a variety of ills. Pancreatic cysts are then being found incidentally.
Although most cysts cause few, if any, symptoms and won’t progress to cancer, some will, especially two types of mucin-producing cysts, called intraductal papillary mucinous neoplasms (IPMNs) or mucin-producing neoplasms (MCNs).
Methods for figuring out what type of cyst a patient has and which of these mucin-producing cysts may be headed toward malignancy are imperfect. This results in extensive monitoring, imaging, and too often, complicated and unnecessary surgeries.
A new assay called CompCyst, developed by researchers at Johns Hopkins’ Sidney Kimmel Comprehensive Cancer Center (Baltimore, Maryland), could potentially change how doctors manage these cysts, according to a study published in the journal Science Translational Medicine. CompCyst is a branch of artificial intelligence called machine learning, which essentially teaches a computer to “learn” for itself and improve with experience.
In this proof-of-concept study, the Johns Hopkins researchers, who led an international scientific team, tested millions of combinations of features to identify markers that predict the best treatment pathway for an individual cyst. The test showed high degrees of sensitivity and specificity, which means that CompCyst appears to be able to correctly identify those cysts that are very ly to turn into cancer as well as those that will remain benign.
“I can honestly say that I am very excited about this,” explains Dr. Anne Marie Lennon, assistant professor of medicine and director of the Johns Hopkins Multidisciplinary Pancreatic Cyst Clinic.
“Our goal would be to be able to tell a patient you have a cyst which has no risk of turning into cancer, go home, don’t worry,” she says.
“But right now we can’t do that because the tests we have currently are not sufficiently accurate to determine this.”
With pancreatic cancer among the most deadly of diseases, finding an accurate method that could tell doctors that immediate surgery is necessary, or that patients need to be monitored for a period of time—generally several years—or that they can go home and don’t need to come back, could potentially revolutionize cyst management, she adds.
A Pancreatic Cyst Evaluation Primer
There are several types of pancreatic cysts, and some present a real clinical challenge.
Benign pancreatic pseudocysts aren’t new growths or even cysts, but rather are comprised of fluid that leaks the pancreas after an injury or as a result of a b pancreatitis.
Serous cystadenomas (SCAs) are true cysts, but carry no risk of becoming malignant. But doctors may do biopsies and endoscopic ultrasounds to figure if the cyst is actually an SCA.
Among the most worrying of cysts are mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs), which are both mucin-producing.
Mucin is a glycoprotein component of the mucous that coats the surfaces of cells lining body systems the respiratory and digestive tracts. MCNs are precancerous and can sometimes be confused with pseudocysts, and may require surgery, or follow-up per established guidelines.
IPMNs are the most common type of cyst and need to be evaluated and monitored regularly to make sure they don’t become malignant.
“The reason we’re interested in pancreatic cysts is because two types of the three precursors to pancreatic cancer are the IPMNs and MCNs,” says Lennon.
She adds that they are easily identified with CT and MRI and offer the opportunity to potentially screen for pancreatic cancer.
Current consensus guidelines recommend that patients with mucin-producing cysts undergo surveillance, and those mucin- producing cysts which harbor either cancer, or are at the stage just before cancer, called high-grade dysplasia, should undergo surgical resection.
Patients with a mucin-producing cyst without high-grade dysplasia or cancer should undergo surveillance, Lennon says. Occasionally, pancreatic ductal adenocarcinomas, what we know as the most common form of pancreas cancer, or neuroendocrine tumors can present as a cyst.
“From a clinical perspective the key decisions we need to make are: does the patient have a type of pancreatic cyst that has minimal or no risk of developing cancer and can be discharged, or do they have a cyst with cancer or high-grade dysplasia that requires surgical resection, or do they have a mucin-producing cyst which can be followed,” Lennon explains. “We always err on the side of caution.”
Erring on the side of caution is the real issue, since the majority of these cysts will never become malignant.
“There are so many patients with cysts and virtually all need to be followed since we can’t really accurately differentiate what type of cyst a patient has,” Lennon says. “If no surgery is performed, we might miss a cancer.
But a patient might also undergo surgery who truly doesn’t need it, and the surgery itself is tough and has the potential for some complications that can really affect quality of life.”
The researchers analyzed a cohort of 862 pancreatic cyst patients, all of whom had undergone surgical resection.
Molecular, clinical, and imaging data from 436 of these patients was used in the machine-learning algorithm to classify these patients into three cysts categories: those that had no risk of cancer and could be discharged; those that harbored cancer, or high-grade dysplasia and needed surgical resection; those with mucin-producing cysts (IPMNs and MCNs) with no cancer or high-grade dysplasia who could be safely watched. The CompCyst test was then compared with current clinical practice in the remaining 426 patients, which formed a validation cohort.
According to trial results, CompCyst outperformed current clinical practice in identifying all three patient groups.
Current clinical management correctly identified only 19 percent of patients with a benign cyst who could be discharged, whereas the CompCyst test correctly identified 60 percent of them.
For cysts that should be monitored—mucin-producing cysts without high-grade dysplasia or invasive cancer—current clinical management correctly identified 34 percent of these, whereas CompCyst correctly identified 49 percent.
CompCyst and current clinical management both performed well in identifying patients with cysts which required surgery, identifying 91 percent and 89 percent of patients respectively. Overall, the authors calculated that the use of CompCyst could have avoided unnecessary surgery in 60 percent of the patients included in the study.
The hope is to make CompCyst available to Johns Hopkins pancreatic cyst patients within the next nine to 12 months. From there, they plan to launch a prospective study of about 1,000 patients. The ultimate goal, of course, would be to add CompCyst to the resources doctors currently use in pancreatic cyst management.
The current study did have some limitations, including the fact that the types of cysts being analyzed were not those routinely found in clinical practice.
“There are more questions to be answered and we need to do a prospective study, but as a clinician I know we need better tools to help our patients,” Lennon says.
“What’s exciting is that we are adding to current knowledge through very sophisticated molecular analysis, without disregarding the tools we have now.”