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The most common symptoms of pancreatic cancer are pain in your abdomen or back, weight loss and jaundice.??

But these issues can also be caused by other conditions, such as gallstones, hepatitis or even heavy drinking. So, when should you see a doctor about them??

¡°Most people with abdominal pain won¡¯t have pancreatic cancer,¡± says pancreatic cancer surgeon ¡°But any pain that persists beyond a couple of weeks should still get checked out. And, if you¡¯re experiencing rapid weight loss without trying, you should mention it to your doctor as soon as you notice it. Anyone whose skin or eyes turn yellow should be evaluated immediately.¡±?

Here¡¯s how some patients knew they had pancreatic cancer, in their own words.??

Abdominal pain that radiates to your back?

¡°I had a little dull pain start just below my left breast in September of 2016,¡± adds Reneata Benjamin, a retired elementary school librarian who was 53 when she was diagnosed with stage III pancreatic cancer. ¡°I was rubbing it so much that people started asking me what was wrong. Finally, my daughter told me I needed to see a doctor because it just kept getting worse.¡±?

Sometimes, the combination of back and abdominal pain can make pancreatic cancer patients feel like there¡¯s a belt of pain wrapped around their middle. ¡°The classic presentation is to have abdominal pain that radiates to the back,¡± explains Katz.?

Jaundice?

Jaundice, or yellowing of the skin or eyes, is another telltale sign of pancreatic cancer.?

¡°My wife noticed my skin turning yellow while putting calamine lotion on my back to soothe some itching,¡± remembers Steven Adami, a Wyoming rancher who was 62 when he was diagnosed with stage II pancreatic cancer. ¡°I called the doctor, and he was so concerned that he told me to be at his office in an hour.¡±?

Unexplained weight loss?

Unintentional weight loss is a common symptom of many gastrointestinal cancers, including pancreatic cancer.?

This weight loss could be due to:?

• inflammatory proteins secreted by the cancer?
• jaundice, pain or other symptoms?
• physical obstructions in the gastrointestinal tract??

All of these can limit a person¡¯s appetite and ability to get enough nourishment.?

If you experience rapid, unintentional weight loss, it¡¯s important to tell your doctor. So, what counts as rapid weight loss???

¡°Losing 5% or more of your body weight in a month would be very concerning,¡± says Katz. ¡°But losing anything over 10 pounds, even if it¡¯s over an extended period, such as 3 to 6 months, should be investigated if it can¡¯t be explained by a change in diet, activity level or medications.¡±?

Don¡¯t dismiss non-specific symptoms?

Other symptoms of pancreatic cancer include:?

• Dark urine or light-colored stools?
• Bloating, or a feeling of fullness?
• Nausea, vomiting or indigestion?
• Fatigue?
• Lack of appetite?
• Sudden-onset diabetes?

Unfortunately, pancreatic cancer doesn¡¯t often produce symptoms in its earliest stages. So, by the time they start appearing, the disease is often advanced, when it¡¯s harder to treat. That¡¯s why Katz says you shouldn¡¯t dismiss even vague symptoms.??

¡°I can¡¯t tell you the number of patients I¡¯ve seen who had aches and pains or diarrhea for months and just didn¡¯t think it was worth mentioning to their doctor,¡± Katz says. ¡°Don¡¯t dismiss these symptoms, particularly if they¡¯re persistent or in the elderly. While they may turn out to be caused by something other than pancreatic cancer, they¡¯re worth evaluating.¡±?

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Many cancers have been linked to genetic mutations, whether they¡¯re inherited or occur spontaneously.

Certain BRCA mutations, for instance, have been shown to increase the risk of breast and ovarian cancers in the people who carry them. The mutation associated with Lynch syndrome, on the other hand, increases a person¡¯s chances of developing colorectal and endometrial cancers. And mutations in the TP53 gene are often found in people with Li Fraumeni syndrome, which makes them more likely to develop multiple cancers over the course of their lifetimes.

But have any particular genetic mutations been linked to pancreatic cancer? And is pancreatic cancer ever hereditary? We checked in with , a gastrointestinal medical oncologist who specializes in pancreatic cancer.

So, is pancreatic cancer hereditary?

I¡¯d say roughly 20-30% of patients diagnosed with pancreatic cancer may have a hereditary cancer. But only about 7% will have an inheritable germline mutation, such as BRCA, detected in testing. Another 5% or so will have a family history of pancreatic cancer, not a known mutation.

Which genetic mutations are associated with pancreatic cancer?

The most common one is BRCA (BRCA1 and BRCA2). But there are others, including CDKN2A, STK11, TP53, and PRSS1.

How do most people learn that they have one of these genetic mutations?

Current guidelines recommend universal germline testing for every patient who¡¯s diagnosed with pancreatic cancer. At MD Anderson, we have a video-based program that allows efficient testing followed by consultation with a genetics counselor for positive cases.

Healthy close relatives of patients with pancreatic cancer who had positive genetic testing would usually qualify for screening under current guidelines.

What should an otherwise healthy person do if they find out they have a mutation through testing?

If their test results are positive, there may be an opportunity to enter a screening program for high-risk individuals. So, they should talk to their doctor to discuss screening options for pancreatic cancer, as well as other types of cancer, depending on the mutation identified.

What causes pancreatic cancer?

It¡¯s probably a combination of things, including genetic predisposition and lifestyle factors, such as smoking and alcohol use.

Is there anything people can do to reduce their risk of developing pancreatic cancer?

Obesity, diabetes and smoking can all cause inflammation, which is linked to an increased risk of pancreatic cancers. So, maintaining a healthy weight, eating a balanced diet, and avoiding tobacco products are all things individuals can do to lower their risk.

By closely following people with certain mutations and doing regular imaging through high-risk screening programs, we can also spot any concerning lesions early, do surgery to intercept them, and hopefully, prevent them from progressing to fully fledged cancer.

Are any symptoms specific to hereditary pancreatic cancers?

Pancreatic cancer is often asymptomatic in its earliest stages, regardless of mutation status. So, by the time symptoms start appearing, the cancer is usually fairly advanced. The most common symptoms of pancreatic cancer are:

• Abdominal/back pain (sometimes feels like a ¡°belt¡± of pain around the middle)
• Unintentional weight loss
• Jaundice (yellow coloration of skin or eyes)

Are pancreatic cancers with genetic mutations treated any differently from those without mutations?

In general, pancreatic cancer patients with germline mutations do tend to have better outcomes. Some mutations may affect genes required for DNA-repair, for instance, increasing their sensitivity to certain drugs. An example of this would be the use of PARP inhibitors in patients with a BRCA mutation.

Some mutations can also indicate higher sensitivity to particular chemotherapy agents ¡ª like platinum-based therapies such as oxaliplatin ¡ª so regimens containing this drug could become first-line treatment in those patients.

Are there any clinical trials available for patients with mutation-driven pancreatic cancers?

Many clinical trials are available. The most exciting ones involve new combinations of immunotherapy and other drugs that target DNA-repair mechanisms. While the individual drugs may not be new, the combinations are, and that¡¯s what could make them more potent.

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Insulin is a hormone produced by clusters of cells in the pancreas called islets. It helps our bodies use sugars from food for energy. When we¡¯re active, we burn that energy and use up the sugar. But a poor diet and an inactive lifestyle can lead to an overload of sugar in the bloodstream and, with time, lead to insulin resistance.

¡°That means the insulin produced doesn¡¯t work as efficiently as it normally would, so the pancreas goes into overdrive to produce more insulin,¡± says gastroenterologist ?Eventually, it fails to keep up and leads to Type 2 diabetes.

Although insulin resistance is most commonly caused by obesity, it can also be caused by pancreatic cancer. Additionally, pancreatic cancer prevents islets from producing insulin in response to insulin resistance. This can lead to Type 3c diabetes, which is caused by diseases of the pancreas, including chronic pancreatitis and cystc fibrosis, as well as pancreatic surgery.

¡°Type 3c diabetes is hard to distinguish from Type 2 diabetes,¡± Chari says. But fewer than 1% of patients with newly developed diabetes will be diagnosed with pancreatic cancer within three years.

Chari is working to spread the word that there is a possible cause-and-effect relationship between diabetes and pancreatic cancer.

Monitoring for pancreatic cancer should start at the first sign of elevated sugar levels

Diabetes is diagnosed when a person¡¯s A1C levels are 6.5% or higher. New-onset diabetes is the name for the three years following the first A1C test to show levels above 6.5%. During those three years, the risk of pancreatic cancer is higher than expected and then drops to the level of risk found in people with established diabetes.

But Chari stresses that the rise in A1C levels occurs months before a physician makes the diagnosis. Because they don¡¯t want to scare patients, physicians don¡¯t always tell patients when they have glucose or A1C levels that are in the diabetes range, he says. ¡°Instead, they often say, ¡®You have high blood sugar¡¯ or ¡®You have prediabetes,¡¯ so patients don¡¯t realize they have diabetes,¡± Chari says. ?

There¡¯s also the hope the patient can reverse diabetes with an improved diet and more physical activity. ¡°We want to give the patient the chance to reverse their course,¡± he says. ¡°But that only works for patients that really go after it and put in the effort.¡±

Sometimes, patients see changes thanks to their improved lifestyle, but in rare cases, those changes are caused by pancreatic cancer.

Rising sugar levels despite weight loss may indicate pancreatic cancer

Retrospective studies have helped identify two signs that suggest the development of pancreatic cancer.

First, sugar levels rise rapidly. Chari says about 40% of these patients have normal sugar levels five years before diagnosis of diabetes. ¡°When compared to typical Type 2 diabetes, it develops way faster when caused by the cancer,¡± he says. Patients with existing diabetes also see their numbers rise rapidly. The levels of sugars also spike higher than what¡¯s typically seen in Type 2 diabetes.

Secondly, patients lose a significant amount of weight, despite their rising insulin levels. ¡°I¡¯ve seen patient lose 50 to 60 pounds in just a few months,¡± Chari says. But if the patient has changed their diet and level of physical activity, the weight loss may be mistakenly attributed to those efforts.

¡°Patients typically feel good around this time, so we¡¯re patting them on the back for losing weight,¡± Chari says. But before applauding a patient¡¯s effort, Chari advises physicians to question whether the patient has experienced results like that with previous lifestyle changes. If not, there may be something else happening.

¡°This weight loss in the face of rising sugar levels is something that happens with pancreatic cancer,¡± Chari says.

Using these indicators as a guide, Chari aims to identify a subset of patients that are at high risk of developing pancreatic cancer. They hope this enables more interventions to be offered sooner, when there¡¯s a better chance of successful treatment.

Earlier detection can lead to more pancreatic cancer treatment options

A patient¡¯s age, fatigue level, health history and the stage of the pancreatic cancer all impact treatment options. Earlier detection ¨C even only four or five months before diagnosis ¨C increases the number of treatment options, Chari says.

¡°If we can turn the clock back a few months, we get a healthier patient who¡¯s not fatigued and can undergo surgery and chemotherapy,¡± Chari says. These approaches can offer the most benefit to patients, but they¡¯re often not options with later-stage pancreatic cancer.

With earlier detection improving access to more effective treatments, Chari hopes to extend the lives of more patients with pancreatic cancer. This, in turn, can help improve the understanding of pancreatic cancer. ¡°If we can get more people to surgery with earlier detection, we can have more clinical trials that can help us extend the lives of even more patients,¡± Chari says.

Clinical trials aim to establish pancreatic cancer screening guidelines

Although a link between new-onset diabetes and pancreatic cancer has been established, what physicians do with that information has yet to be determined.

In almost all cases,?new-onset diabetes is just new-onset Type 2 diabetes. It doesn't usually signal cancer. But Chari wants to build awareness within the physician community. He also hopes to develop screening guidelines.

Chari is co-leading two clinical trials working toward developing such guidelines. They¡¯re the first prospective trials in this area of study.

The first clinical trial?is collecting blood for future studies on 10,000 patients with new-onset diabetes. This will be the first prospective study to define the risk of developing pancreatic cancer in new-onset diabetes.

A second trial?will build on the first by identifying the subset of patients who have lost weight or whose A1C score is high who should be screened for cancer with a CT scan. If the first CT scan results are normal, patients receive a second scan three to nine months later.

The goal, Chari says, is to change practice by showing in the clinical trial that these patients benefit from early detection.

If there¡¯s one take-home message, it¡¯s that this is rare, but it¡¯s better to be aware of the connection between these anomalies than ignore the signs.

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