Pancreatic Cancer Prevention
A groundbreaking program at UT Southwestern Medical Center is striving to offer the best possible outcome for people at risk for pancreatic cancer: keeping deadly tumors from gaining a foothold in the first place.
With that purpose, the Pancreatic Cancer Prevention Program at UT Southwestern and Harold C. Simmons Comprehensive Cancer Center has assembled a diverse team of experts from specialties including radiology, gastroenterology, surgical oncology, and cancer genetics. The group’s goals are to identify patients with known risk factors for pancreatic malignancies and to develop personalized plans of action. These plans include education and outreach; imaging of the pancreas and lifetime surveillance for abnormalities; sampling of tissue or cyst fluid; “banking” of biological samples for future reference or research; and surgery, if needed.
Patients treated and followed in the program have an elevated risk for developing pancreatic cancer due to:
- A family history of the disease, or of certain other malignancies that can be linked to pancreatic cancer risk;
- Genetic testing showing mutations associated with an increased risk of the disease; and/or
- The presence of one or more so-called mucinous cysts within the pancreas, which typically behave in a benign manner but which can develop into a cancer over time.
A Proactive Approach
A core component of the Pancreatic Cancer Prevention Program is ongoing assessment of such cysts for characteristics indicating that they have, or are likely to, become cancerous.
Identifying cysts demonstrating signs of malignant degeneration allows surgeons to intervene early, before a cancer can develop or advance.
“Pancreatic cancer is an absolutely devastating disease, and it’s because it’s typically not picked up until it’s too far gone,” says gastroenterologist and interventional endoscopist Dr. Nisa Kubiliun, Assistant Professor of Internal Medicine and Co-Director of the UT Southwestern Pancreatic Cancer Prevention Program. The pancreas, she notes, is situated deep in the belly, and a common symptom of pancreatic cancer – back pain – is not necessarily associated with the organ or considered cause for alarm. “This is part of the problem we face as clinicians; we end up finding the disease once it’s widely metastasized, when our treatment strategies are largely less effective.”
Although pancreatic cancer is on the rise – with new cases increasing 0.6 percent KP1 per year on average in the last decade – it is still relatively rare, so it’s ineffective to screen the general population for the disease, says Professor of Surgery Dr. Rebecca Minter, who co-directs the Pancreatic Cancer Prevention Program with Dr. Kubiliun. She adds, however, that “patients with identified precursor lesions to pancreatic cancer such as mucinous cysts, or an underlying genetic condition placing them at risk, represent an enriched patient population that we believe is effective to screen and surveil. Our greatest opportunity to intervene or cure pancreatic cancer is before it develops into an invasive cancer.”
Finding and Assessing Lesions
Radiologists often identify pancreatic lesions incidentally, typically on abdominal imaging performed for some other purpose, such as to investigate urgent medical problems in the emergency room or for follow-up of other cancers that may be under control, says Assistant Professor of Radiology Dr. Gaurav Khatri, lead radiologist for the Pancreatic Cancer Prevention team.
“We’re still learning a lot about these lesions, which are common in the general population,” Dr. Khatri says. “They can grow very slowly and can continue to develop over multiple years. Until the last couple of years, they have not gotten a lot of attention, but now some experts are wondering whether they carry higher risk than previously thought.”
At Simmons Cancer Center, ensuring further assessment of cysts or other anomalies is baked into the system – radiologists embed specific boilerplate language into the patient’s electronic medical record that flags the finding, provides referral and contact information for the Prevention Program, alerts program team members, and directs referring physicians to management guidelines for pancreatic abnormalities.
“If we didn’t have the Prevention Program, these patients might not get the correct follow-up from their referring physician,” Dr. Khatri notes.
The program’s close collaboration with radiologists to initiate follow-up care “is totally a game changer,” Dr. Kubiliun adds. “Now we capture every one of these patients and can continue to follow them and try to ensure that they don’t develop features that are worrisome for malignancy.”
Entering the Program
Patients with a pancreatic cyst, as well as those who have a hereditary risk for pancreatic cancer, can be referred to the program. The Prevention Program’s first point of contact is its patient intake specialist, Naomi Chambell, who schedules patients and connects them with patient nurse navigator Chris Bishop, B.S.N., RN. Working closely with physician assistants Veronica Coleman, M.P.A.S., PA-C, Assistant Professor with the Department of Physician Assistant Studies, and Lan Vu, M.P.A.S., PA-C, Mr. Bishop reviews each patient’s medical and family histories, previous imaging, genetic tests, and details about any cysts that have been detected and whether symptoms are present in relation to these cysts. In addition, he answers any questions that a patient may have about the program and the purpose of surveilling pancreatic cysts.
Mr. Bishop also gathers patients’ records, imaging, and additional test results from other health care providers, making sure everything is on hand for specialists in the Prevention Program to review before a patient arrives for a consultation. Any needed procedures, such as endoscopic ultrasound or additional imaging, are scheduled in the interim, and appointments are set with the specific providers each patient needs to see. Mr. Bishop also coordinates patients’ care on the day of their visit, helps put the specialists’ recommendations into action, and remains the primary contact for questions and follow-up.
To help assess patients with a pancreatic lesion, both initially and in follow-up surveillance, UT Southwestern has a dedicated group of about a dozen abdominal radiologists who use state-of-the-art imaging techniques designed to better capture changes within the lesion, within the pancreatic duct, or within the remainder of the pancreas parenchyma (the functional portion of the organ), Dr. Khatri says. Those techniques include magnetic resonance (MR) cholangiopancreatography and additional dedicated high-resolution MR imaging sequences looking for the earliest signs of pancreatic cancer within the gland.
“The radiologists associated with the Prevention Program are accustomed to looking for findings that a general radiologist might not be attuned to looking for,” Dr. Khatri says. For instance, the radiologists note whether a cyst, which is normally fluid-filled, has developed solid material or septations in its interior; whether the septations have changed since the prior examination; if its walls are thick, or “nodular”; or whether the pancreatic duct is obstructed or dilated.
Probing More Deeply
To further help determine risk, or to establish a diagnosis, a patient might also undergo an endoscopic ultrasound. For the procedure, Dr. Kubiliun uses a long, thin camera with an ultrasound probe embedded on the tip of the scope, which is passed through the mouth and esophagus and into the stomach and small intestine. From there, the pancreas can be visualized, and cysts or other lesions, including possible cancers, can be sampled in a minimally invasive manner.
Extracted samples, typically fine-needle aspirates, allow physicians to more closely assess cyst fluid for molecular markers or other precancerous features, offering added clarity about the biologic behavior of a pancreatic cyst. Endoscopic ultrasound also can sample solid pancreatic masses to see whether tumor cells are present and, if so, to determine the type of tumor the lesion represents. (If a lesion turns out to be cancerous, the patient is referred to the Pancreatic Cancer Multidisciplinary Program for treatment.)
The Search for Biomarkers
With patients’ consent, samples of fluid extracted from cysts, along with blood samples and detailed information about how each case unfolds, are being banked in a biorepository for future research. Such research might examine, for instance, whether there’s some biological clue, or marker, in the fluid or blood that might help predict who will go on to develop pancreatic cancer.
Finding biomarkers that suggest who is likely to develop cancer will bring new precision to the process of determining which at-risk patients truly need surgery for a pancreatic lesion, says surgical oncologist Dr. Adam Yopp, Assistant Professor of Surgery and Director of the UT Southwestern Tissue Repository. So far, no such biomarkers have been validated for pancreatic cysts, he says: “It’s all investigational right now.”
Doing the research needed to identify pancreatic cancer biomarkers is likely to require collaboration among multiple institutions, Dr. Yopp adds. “The reality is that to do any of these studies we’ll need thousands and thousands of patients. Collecting these samples positions us to work with other institutions” to identify predictors of progression to pancreatic cancer.
Once imaging and testing are completed, each individual case is reviewed in the Prevention Program’s Multidisciplinary Conference, where radiologists, gastroenterologists, surgical oncologists, and genetic counselors meet in order to decide the best next steps for care. The conference includes the same group of experts reviewing each person’s case over time, relying on imaging that is consistently acquired from visit to visit – allowing for, as Dr. Minter says, “apples-to-apples” comparisons.
While there are no formal, validated screening guidelines for pancreatic cysts, the multidisciplinary group, using an evidence-based approach, works in concert to determine each patient’s risk level, then reaches a consensus on an individualized course of action for that patient. “It’s not a one-size-fits-all approach,” Dr. Kubiliun says.
If a cyst or other lesion appears worrisome, the Prevention Program’s experts will carefully weigh potential risks versus benefits. In some cases, the team may recommend excision. In other instances, long-term surveillance with a shorter interval between imaging might be advised.
Patients with elevated risk for pancreatic cancer due to certain genetic predispositions might also undergo regular MRI surveillance in search of new or growing lesions. Over time, some patients might have no changes while others have rapidly developing changes and still others have a previously dormant aberration that suddenly becomes active.
“Ideally we’d catch any lesions – if not prior to tumor formation, then in the very early stages,” Dr. Kubiliun says, adding that because MRI does not involve radiation, such surveillance is safe over the long term.
Parkland Health and Hospital System, Dallas County’s safety-net health care provider and the primary teaching facility for UT Southwestern, is developing similar cyst follow-up and other prevention services through its Multidisciplinary Pancreas Clinic. Biological samples from that clinic also are banked at UT Southwestern.
The Riskiest Cysts
Pancreatic cysts grow increasingly common with age; as many as one-quarter of patients over age 65 have them. While most are benign, two types of mucinous cysts are more prone to develop into cancer. Intraductal papillary mucinous neoplasms, or IPMNs, can affect the entire pancreas, sometimes necessitating complete removal of the organ to excise all at-risk tissue, Dr. Minter says. More commonly, only portions of the pancreas are involved, although ongoing surveillance is required because the growths might recur elsewhere in the organ. By contrast, mucinous cystic neoplasms, or MCNs, are unifocal (single-site), and following surgical resection do not require ongoing surveillance of the remaining pancreas.
Besides structural features of a cyst, decisions to operate hinge on presence of symptoms such as pancreatic inflammation (pancreatitis) or difficulty eating. And cysts greater than 3 centimeters warrant closer attention.
“Only a small number of patients with pancreatic cysts need an operation,” Dr. Minter says. “Most will require surveillance, but it’s important to consider both options.”
Education is another key component of the Prevention Program, she adds. Patients with mucinous cysts – along with those who have a hereditary risk for pancreatic cancer – should understand that cancer can develop and lifetime surveillance might be necessary, along with what symptoms to watch for.
The Prevention Program provides genetic counseling and testing for patients suspected of having a hereditary risk for pancreatic cancer. Patients come from across North Texas as well as from out of state, says cancer genetic counselor Elise Watson, M.S., CGC, who advises people who seek care in the program. Patients can be self-referred or referred by a physician from within or outside UT Southwestern.
As many as 10 percent of pancreatic cancers are thought to result from inherited mutations, although only about one-fifth of those genetic causes have been pinpointed. Hereditary syndromes linked to pancreatic cancer are associated with other cancers, as well (see sidebar). For instance, mutations in the BRCA1 or BRCA2 genes – which can underlie breast and ovarian cancers – are also associated with exocrine pancreatic cancer, the predominant form of the disease.
“These different cancers can be so important,” Ms. Watson says. “People think, ‘I don’t have a family history of pancreatic cancer,’ but that’s not the only cancer that matters here.”
Where appropriate, genetic testing is recommended for mutations in more than a dozen genes linked to pancreatic cancer, plus a handful associated with hereditary pancreatitis, which can also predispose patients to developing cancer. Patients found to have a hereditary risk are counseled on lifestyle changes, such as quitting smoking, that can help reduce their odds of developing pancreatic cancer.
For patients with hereditary syndromes, proven surveillance techniques can be implemented for those other cancers, such as mammography or breast MRI for people with BRCA mutations, colonoscopy in connection with a condition know as Lynch syndrome, and skin cancer screenings for patients with familial atypical multiple mole melanoma (FAMMM) syndrome. Such patients also are counseled on prevention strategies, such as sun-safety precautions for FAMMM syndrome, Ms. Watson says. And the genetic counseling team will guide patients on how to talk to family members about also getting tested for mutations.
“We’re available as a support resource for patients throughout the whole process,” Ms. Watson says.
Across medical specialties, integrated support and guidance for at-risk patients at every opportunity is what distinguishes UT Southwestern’s Pancreatic Cancer Prevention Program in the fight against the disease. “There are only a handful of pancreas programs around the country similar to this one, where radiologists, gastroenterologists, surgical oncologists, and other team members work together so closely,” Dr. Khatri says.
KP1 see Trends tab here: seer.cancer.gov/statfacts/html/pancreas.html
Pancreatic Cancer Risks
The risk of pancreatic cancer increases with age. Men and African-Americans of both genders have a slightly elevated risk of developing the disease.
Other potential risk factors are:
- Being overweight or obese;
- Smoking and use of smokeless tobacco;
- Chronic pancreatitis (inflammation of the pancreas);
- Type 2 diabetes;
- Cirrhosis (scarring) of the liver;
- Infection of the stomach with the ulcer-causing bacterium Helicobacter pylori; and
- Exposure to chemicals in dry cleaning and metalworking industries.
A family history of pancreatic cancer can increase risk of the disease, as can certain hereditary cancer predisposition syndromes. Those syndromes include:
- Hereditary breast and ovarian cancer syndrome (BRCA1/BRCA2 gene mutations), which is associated with an increased risk for breast, ovarian, pancreatic, melanoma, and prostate cancers;
- Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM mutations), which is associated with higher risk of a number of malignancies, including colorectal, uterine (endometrial), stomach, ovarian, small bowel, pancreatic, urinary tract, hepatobiliary tract, and central nervous system cancers;
- Familial atypical multiple mole melanoma syndrome (CDKN2A mutations), which is linked to an increased risk of melanoma and can also be associated with an increased risk of pancreatic cancer;
- Familial pancreatitis (typically PRSS1 mutations);
- Peutz-Jeghers syndrome (STK11 mutations), which is associated with an elevated risk for cancers or polyps of the gastrointestinal tract, as well as pancreatic, breast, and certain types of cervical or ovarian cancer; and
- Von Hippel-Lindau syndrome (VHL mutations), which is associated with noncancerous tumors of the brain, spinal cord, and retina, as well as kidney cancer, pheochromocytomas, pancreatic neuroendocrine tumors, and pancreatic cysts.
Other genes, such as PALB and ATM, have also been linked to an increased risk of pancreatic cancer. Individuals should consult with a cancer genetics counselor if someone in the family has been diagnosed with a hereditary cancer predisposition syndrome, more than one type of cancer, or if pancreatic cancer has occurred in:
- Several members of the same or multiple generations of a family;
- At least two generations on the same side of the family; and/or
- Family members who were diagnosed at an age younger than 50.
Pancreatic Cancer Symptoms
Pancreatic cancer is difficult to detect because few symptoms are noticed early in the course of the disease. Symptoms that do arise are similar to those of other diseases and should be evaluated by a physician.
Symptoms of the most common form of the disease, exocrine pancreatic cancer or pancreatic adenocarcinoma, include:
- Jaundice (yellowing of eyes and skin; dark urine; pale or gray stools)
- Pain in the upper abdomen or mid-back
- Sudden onset or worsening of existing diabetes, especially in patients who lack risk factors for the condition
- Poor appetite
- Unexplained weight loss
- Nausea, vomiting
- Digestive discomfort, such as a burning sensation or bloating in the abdomen
- Pancreatitis without clear cause
- Blood clot in a large vein, such as in the leg, developing for no clear reason
Pancreatic neuroendocrine tumors, which account for only about 5 percent of pancreatic tumors, can be benign or malignant. Tumors that are malignant can cause similar symptoms to pancreatic exocrine cancer.
The majority of neuroendocrine tumors are classified as non-functioning; however, some are functional and can release an excess of various hormones into the bloodstream, causing hormone-related symptoms such as:
- Abdominal pain
- Acid reflux
- Peptic ulcer disease
- High or low blood sugar
- Electrolyte abnormalities