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Scott Webb (Host): We all sort of know that the pancreas serves essential functions in our bodies, but what exactly does it do? Where is it located and what advances have been made in treating pancreatic cancer? And joining me today to answer these questions and more is Dr. Veeral Oza He's a gastroenterologist and interventional Endoscopist and Dr. Wes Jones. He specializes in Hepatobiliary and pancreatic surgery, and they're both with PRISMA Health.

This is Flourish, a podcast brought to you by PRISMA Health. I'm Scott Webb. So, doctors it's really great to have you both on, as I was mentioning before we got rolling, I had a friend of the family who died of pancreatic cancer, and it seems like pancreatic cancer used to be just an absolute death sentence, but it doesn't seem or appear that it is in modern medicine, which is encouraging. But it's great to have a couple of experts on. As we get rolling here, Dr. Jones, what is the pancreas and what does it do exactly?

Wes Jones, MD (Guest): Well, the pancreas is a very interesting organ. It is the only organ in the body that is both endocrine and exocrine function, meaning that it secretes hormones directly into the bloodstream. We'll go into what those are. And then it also secretes juices for lack of a better word out of the gland to help digest the food.

So it actually leaves the organ and enters the intestinal tract. The pancreas, with regard to endocrine function, most of us know that it's responsible for insulin secretion, which helps to regulate your blood sugar and various reasons, if that function decreases, we're almost all familiar with diabetics and diabetes, and that can either be an under secretion of the insulin or a resistance of the body to the insulin that's normally secreted. And then with regard to digestive enzymes that are secreted from the gland, they help break down proteins and amino acids. And for your digestion. The pancreas is an organ lies anatomically behind the stomach, the true stomach.

And it's in the first portion of your intestinal track. And it has a lot of blood supply feeding it and draining it. And so in a difficult anatomic location within the body. Because of all of this, any cancer or malignancy in this area, is often very hard to treat. And it's often a very brief interval between the start of a neoplasm or cancer, and then its progression to where we may not be able to cure it.

Host: Yeah, Dr. Oza, anything to add?

Veeral Oza, MD (Guest): Pancreas is just like Dr. Jones mentioned both an endocrine and exocrine organ and sits behind the stomach, difficult to access. But it's an organ that a lot of people discounted and don't really recognize the importance of in terms of day-to-day life and day-to-day functioning. You know, without the pancreas, you're not going to be able to digest a lot of food. You can have a lot of chronic pain, and that's where taking care of the pancreas long run becomes very important.

Host: Yeah, it is really important as you guys have identified here, it's a really important organ. It does a lot of a multitasking if you will, but it's problematic based on its location and we're going to get to all of that today. But as we go on here, staying with you, Dr. Oza, how does alcohol affect the pancreas?

Dr. Oza: So, you know, alcohol usage on an abuse level, meaning if you drink too much alcohol can result in pancreatitis, which is swelling of the pancreas itself. We're not going to get into the molecular biology of pancreatitis and pancreas itself in relation to alcohol. However, knowing that drinking too much alcohol can result in pancreatitis episodes is important and in not taking care of that and continuing to drink despite having pancreatitis, and you're having recurrent pancreatitis flare ups and over and over essentially results in scarring of the organ and fibrotic tissue, which then results in something called chronic pancreatitis, which literally translates to long-term swelling of the pancreas.

The issue with having chronic pancreatitis is the pancreas as an organ now can no longer work efficiently and make the digestive juices that we just talked about, which then results in patients starting to lose weight. And because there's chronic swelling that can also result in a risk for pancreatic cancer.

Host: And Dr. Jones staying here with alcohol and the pancreas, can heavy alcohol use lead directly to pancreatic cancer?

Dr. Jones: Well like Dr. Oza said, alcohol use, especially to excess can lead to pancreatitis and inflammation. From a layman's point of view, chronic inflammation can predispose organs to malignancy. So, if alcohol use causes acute and chronic pancreatitis by proxy, it can lead to a chronic inflammatory state of the pancreas, which can lead to an increased risk of pancreatic cancer.

So, it's not unusual for patients to be heavy alcohol users and be diagnosed with acute or chronic pancreatitis. And then if they do not undergo close surveillance with a heavy suspicion of the possibility of increased risk of cancer, sometimes this can be missed and often can be incurable. So the short answer to your question is, yeah, heavy alcohol use can lead to pancreatic cancer, usually by way of chronic inflammation.

Host: Yeah, I see what you mean sort of by proxy. If we connect those dots, you can see how one can lead to the other or more often than not. And, switching back to you, Dr. Oza, when we talk about both alcohol use and how it can lead directly to pancreatic cancer, what are some of the other risk factors for pancreatic cancer?

Dr. Oza: So So that's an excellent question. Alcohol abuse is obviously one big risk factor, but the other big risk factor is smoking. The smoking and tobacco use has been shown to be a high risk for really all malignancies and pancreatic cancer is no exception. You know, these carcinogens or chemicals that lead to cancer are prevalent in cigarette smoke. In fact, I think I read one article which said that some cigarettes have as many as 2000 different types of carcinogens. Now these don't cause cancer like overnight. It's more of the long-term accumulation, over time that results in higher risk for developing pancreatic cancer or really any cancer. Outside of that, there are genetic factors that predispose certain individuals to getting the recurrent pancreatitis which we talked about, which then in itself, results in a state of chronic inflammation or chronic swelling.

Which then leads to cancer at an earlier age. In addition to that, there are other risk factors such as obesity. Being overweight and obese and having a sedentary lifestyle has now been shown to be an independent risk factor for certain kinds of malignancies and pancreatic cancer is one of them. So, there are other risk factors outside of just alcohol, but generally speaking, whether it's recurrent pancreatitis or genetic factors, or auto-immune pancreatitis, where the body's attacking itself, kind of like rheumatoid arthritis or lupus; all of these conditions end up resulting in the pancreas being swollen over a long period of time, and results in changes that leads to cancer.

Host: Yeah, Dr. Jones. When we think about the chronic swelling, the pancreatitis, how does somebody know if they have both pancreatitis, but also pancreatic cancer? Like what are the symptoms of pancreatic cancer? And why is early diagnosis so critical?

Dr. Jones: Well, I think this is one of the challenges. The symptoms of pancreatic cancer are often subtle in most patients. Typically, in retrospect, someone will say, well, I've had some vague abdominal pain, often diagnosed with gastritis or just irritable bowel symptoms. And often that's kind of treated at home and then even with some medical guidance often treated empirically, medically, as well, just to give a trial of medical treatment, dietary and lifestyle changes. See if that helps it. Some of the more sinister symptoms are unexplained weight loss. Most patients will tell you they've lost, you know, 10, 20, 30 pounds over several months. Another symptom is new onset diabetes. A patient who has normal blood sugar levels. They go to their regular doctor. And they're found to have a markedly elevated blood glucose level 200, 300. No real reason for that. They're not necessarily obese. They haven't had a predisposed symptom or early symptoms of diabetes Type 2, diabetes have been managing with their doctor for several years.

Often they'll have loose stools, what we call fatty diarrhea because the pancreas secretes that digestive enzyme, if those enzymes are absent, the food will be undigested and cause usually cramps, gas and loose stools or, rust colored globules of oil like stools. And then one of the more dramatic symptoms of pancreatic cancer, can be jaundice, the patient who his family or friends noticed that he has a yellow tinge to his skin or eyes, that is often less subtle than some of the ones I've already kind of listed. And then one other symptom or a sign would be someone who had acute pancreatitis with no real risk factors for pancreatitis. They've had no history of gallstones. They don't drink alcohol at all, and they have an unexplained cause for pancreatitis that can be another sign or symptom of pancreatic cancer.

Host: Dr. Oza why is early diagnosis so critical when it comes to pancreatic cancer?

Dr. Oza: So that's a great question. Before I answer that question. I just want to reemphasize what Dr. Jones just said about a couple of different symptoms of pancreatic cancer. The two things he mentioned that I think are often overlooked, it kind of ties into what you just asked me are this new symptom of diabetes. I can't tell you the number of times, I see the patients who tell me that. Yeah. You know, we were just diagnosed with diabetes and you ask them more about that and they will tell you that they were told they're pre-diabetic about eight or nine months ago. And then they got diabetes about six months ago, and then six months later, the CT scans and MRIs now show a pancreatic mass, and that's actually been shown now over and over again, that what Dr. Jones mentioned that, you know, when you get diabetes, the United States Preventive Task Force, or USPTF recommends considering pancreatic imaging in anybody who gets a new diagnosis of diabetes after the age of 50. Now that's a little bit more dramatic in terms of 50, but I, in my practice, if somebody is over the age of 60 and they're just seeing them in clinic for something else, and if they mention that they were just diagnosed with diabetes, I certainly think about, should I do a pancreatic cancer screen on these patients despite them having no other risk factor simply because I have seen a lot of patients where the diabetes tends to precede pancreatic cancer. So, that's one big symptom that Dr. Jones mentioned I wanted to emphasize on.

And the second one that he mentioned was having this pancreatitis episode with no other risk factors. That is another key. That is sometimes missed when some people have pancreatitis and they have no other risk factors, people are oftentimes forgotten or they really just go home and like heh we feel great. There's no reason for us to go to see these doctors. People may not have insurance because they've lost jobs because of the pandemic. And they're like, forget it. We don't want to get it checked out but that's when bad things happen when we just ignore it or patients just ignore it. So, you generally, after somebody has had a pancreatitis episode and you haven't found a cause for it, you know, six to eight weeks after that episode, doing imaging or CT scan or an MRI or something called an endoscopic ultrasound is certainly indicated to go looking for a cause.

So those are the two things I wanted to mention. But to answer your question about why is it so important to pick these up early? I want to give you some numbers. And I think that those numbers will explain why it's key to pick these up early. You know, in 2021 American Cancer Society estimates that about 60,000 people in the United States will get diagnosis of a pancreatic cancer. Of those, approximately 49,000 will die, the same year. So in 2021 itself. So that's in the United States. Now we are in South Carolina. When you filter down those statistics from American Cancer Society to state level, in South Carolina that essentially translates to about a thousand people, thousand to 1100 people, new diagnoses of pancreatic cancer of which about 900 will pass away. Our state is not exactly a big state by numbers. And somebody will know somebody, or at least, you know, two degrees of separation will know somebody else who has either been diagnosed or will pass away from pancreatic cancer.

And the reason for that is that the survival rate of pancreatic cancer of all comers, meaning of all stages, localized, regional, or distant. Those are the main stages in layman's terms then, of all comers, the survival rate at five years of pancreatic cancer is estimated to be about 9.1%. Meaning of a hundred people diagnosed with pancreatic cancer today at any stage, only nine of those will actually be with us in about five years.

So that's a pretty dramatic unfortunate number that 91% of patients will not make it five years. And that survival depends on the stage at which we make the diagnosis. The earlier we make the diagnosis, the better the outcome. If they're localized, meaning the tumor is not involving any other organs, such as the liver or the lung, does not involve any major blood vessels in the area and is just really focal in one specific spot, then that five-year survival rate goes up to almost 40 to 42%. Which is pretty high. And that's the whole point of trying to pick up, make the diagnoses early, and being aware of some of these risk factors and being aware of your body, really.

Host: I'm just up processing these numbers. I wrote these down because I want to remember these. Dr. Jones, tell listeners what's being done, you know, how is pancreatic cancer treated? What are the latest treatment options?

Dr. Jones: There's been a sea change in the treatment of pancreatic cancer over the last 20 years. Initially, if a patient presented with pancreatic cancer, they were often taken to surgery as an attempt to cure them. And today, still surgery is the way to cure patients. There is not a chemotherapeutic regimen with, or without radiation that will cure patients in and of itself. And in the last 20 years, most people had noticed that a lot of these patients that went to the operating room were not cured. And in fact, the operations that they underwent were very morbid. They had a lot of side effects. They had a lot of life altering complications. There was a significant amount of patients who didn't survive surgery at that time. And so work was being done to try to avoid doing an operation on someone that would not be helped by it. And to try to identify those patients that would be the most favorable candidates for cure, and worth the risk of having operative intervention on this. And this is not only in pancreatic cancer, there are other types of diseases, this has migrated towards, but we've adopted now it's called a neoadjuvant chemotherapy approach, which means that when a patient's diagnosed with pancreatic cancer, they're fully assessed like Dr. Oza said, to see the relation to the tumor to blood vessels, to see if there's any disease outside of the abdomen, such as in the lungs or in other organs within the abdomen, and they're staged initially. And if those patients are kind of stratified as the either incurable or unresectable, obviously resectable straight out or somewhere in between what we call borderline resectable.

Initially, if patients were felt to be resectable, meaning that they could have surgery, the thought was that the operation would remove all of the cancer and they could be cured. Although the chances were that not all patients would be cured, even if they did have that operation. Traditionally those patients went straight to surgery.

The patients who were not curable or resectable, just had palliative chemotherapy, meaning they were given chemotherapy to help them live longer. And those patients in between, did a neoadjuvant approach. Over the last 10 years or so, we've gone to those patients felt that to be resectable or borderline resectable to have a neoadjuvant approach now. So almost every patie will undergo chemotherapy. Radiation is not often used. That's a change as well. Initially radiation played a part and right now radiation is not routinely given upfront. And then after they undergo a regimen of chemotherapy and there's several regimens to choose from, some that are experimental, including research trials, they're restaged, and we stage people by CT scans with contrast, that have high definition imaging of the pancreas. And if they have not had progression of their tumor to a higher stage or, to the degree of unresectability, they undergo surgery. And, again, that surgery depends on the location of the tumor within the pancreas. And is invariably complex and has a certain amount of risk to it. But when performed by people who performed the operations fairly frequently, more than 10 to 12 times a year, that have acceptable outcomes. And there are a distinct population that are cured like Dr. Oza said, depending on their stage. I tell patients when they come to see me with a new diagnosis of pancreatic cancer, about one out of eight or approximately 15% are resectable, initially. The remaining seven out of eight will either be unresectable or borderline resectable. And then out of the one out of eight, if you take eight of those patients, so 15% of the ones who are resectable about one out of those eight will be alive at five years, for all comers. I think another thing that bears repeating that Dr.Oza hinted at was that we have a 9% five-year overall survival. That's been up to 10% and I can tell you that there's a lot of people that are pretty proud of that number, given the historically dismal outcomes associated pancreatic cancer, before the neoadjuvant approach and some of the multimodal chemotherapeutic approaches that are used now. But it's still nothing to necessarily celebrate with just a 10% five-year overall survival rate.

Host: Yeah, I think you're so right. And I know you guys are working on this every day. I want to give you a chance, Dr. Oza, when we talk about pancreatic cancer treatment, and the future and levels of optimism that folks should have. Where are you at with this?

Dr. Oza: I think the future is looking very, very promising. And the reason I say that, though even though I have that 9% number that I quoted earlier, you know, 25 years ago, that number was about 7%. So in about 25 years, we really haven't made that much progress when you compare it to all the other different types of cancers, breast cancer, colon cancer, cervical cancer, lung cancer, et cetera. Their survivors have improved dramatically in double digits, across the board except pancreatic cancer. However, our progress in the last few years actually has shown success in terms of this number, starting to tick up slowly. One is chemotherapy drugs that are coming out. There's something called immunotherapy that is starting to show some promise in many different types of cancers. And I think trials are underway for pancreatic cancer as well. But outside of that, there's new devices that are being invented and they're coming down the pipeline that will allow us to, in patients who have advanced disease, previously when to do radiation therapy, for example, you know, it tends to scar, not just kill the tumor, but also kills the healthy cells around.

So we have some new things that we can do to place markers in the tumor itself, so that radiation oncologists can target their beam in a specific area. We have some new needles that are coming out that will allow us to inject chemotherapy directly into the tumor itself, as opposed to giving chemotherapy in, in the patient's blood.

So there's definitely some new advances coming that'll I think help, not just patients who have regional or localized pancreatic cancer, but will also help patients who have more advanced disease or metastatic disease. So, I think when you combine all the efforts from all the scientists around the world, in terms of devices, drugs, techniques, then I think all that essentially results in improved survival for pancreatic cancer.

Dr. Jones: And I think one other point that ought to be hammered home too, is that people are living longer with incurable, pancreatic cancer. Previously six, eight months was kind of the mean life expectancy. We routinely see patients live 18, 20, 24 months on palliative chemotherapeutic options with well tolerated treatment regimens. So, although they may be incurable, they live to see two more Christmases, two more birthdays, children and weddings, and they actually, not everyone, but there's a fair amount of folks that tolerate their treatment very well with limited side effects. So, we follow up in the office and they have surveillance and it's impressive to see how well patients are doing just with some of the new chemotherapeutic regimens that have been started in the last five years or so.

Host: Yeah, it is impressive. And I have heard about immunotherapy and the first time I heard about it, I thought it was like something out of science fiction, like something out of Star Trek, you know, like CAR-T cell immunotherapy. But the more I talk to doctors, the more I talk to experts, it seems like there's reason for optimism, that it can grow beyond, you know, where it initially started.

And to think that it may also find its way into pancreatic cancer treatment is really amazing because it's just too many people dying of pancreatic cancer, despite everything that you guys do, on a daily basis. As we wrap up here, Dr. Oza, this has maybe a million dollar question and maybe a difficult question to answer, but can pancreatic cancer we prevented? Is there screening, is there anything folks can do, especially if they have a family history or, you know, the genetics play a factor for them?

Dr. Oza: The easy answer to this is if you have a family history of pancreatic cancer, then yes. You know, you do qualify for pancreatic cancer screening and there's two different screening modalities that we use. One is a MRI studies and the other is endoscopic ultrasound, which is an endoscopy procedure. Scope goes in from the mouth into the stomach and has an ultrasound tip, which we use to see the entire pancreas, from head to tail. That's actually the different parts of the pancreas head to tail. But, those are two main ways to screen for pancreatic cancer, do screening. There's another test that has recently been developed that we are actually, starting to offer now in some patients. And that's a blood test and the blood test has shown some promise as well, in high-risk individuals, especially when they don't qualify for EUS endoscopicopic ultrasound or MRI. Then those patients, a blood test is a reasonable option. It's an expensive blood test at the moment. And hopefully over time it will be covered by insurance and the prices have also come down. So those are three main ways to screen for pancreatic cancer at the present time. If you don't have a family history of pancreatic cancer, however, but you have a history of other cancers such as say breast cancer or colon cancer, or a parathyroid cancer or even thyroid cancer, then you may have a gene mutation that runs in the patient's family and those particular gene mutations also make the patient a little bit higher risk for developing a pancreatic cancer. So, the most notable one that the public tends to know about is the BRCA gene or the BRCA gene. There's many different types of BRCA genes, but the most popular ones in the public opinion in the media is BRCA1 and BRCA2.

And these genes are oftentimes associated with breast cancer, but they also carry a higher risk of other cancers and pancreatic cancer is one of them. So depending on your genetics that are in your family, even though you may not have a history of pancreatic cancer in your family, you may qualify for pancreatic cancer screening simply because of the genetics. As far as what you can do to reduce the risk of pancreatic cancer; quite frankly, just have a healthy lifestyle, exercise regularly, you know, be like Dr. Jones, go running every day. Don't smoke. Don't get drunk and avoid alcohol as much as possible. I think and eat a diet, which is high fruits and vegetables. And I think those are all things that will over time that one can do to really reduce that risk as much as possible. You know, genetics is something you cannot change, you're born with it. So once you have those genes, there's no point being anxious about it.

What we can do is be aware of the risks. The symptoms of pancreatic cancer, ones that Dr. Jones and I mentioned earlier during our chat today. But short of that, I think not doing stuff to screw it up even more, don't smoke and use tobacco, things like that and having a healthy lifestyle. I think those are the main things that patients can do to negate that risk as much as possible.

Host: Yeah, you're so right. We can't outrun our family history and genetics, but there are things that we can do as you say, just a healthy lifestyle, just to be as healthy as possible. Be like Dr. Jones go for a run. He may be jogging in place right now for all we know.

Dr. Oza: Ah, it's very possible.

Host: It's very possible. So Dr. Jones, this has been really illuminating, really educational today. I'm going to give the last word to you. When it comes to pancreatic cancer, the present, the future, final thoughts for listeners.

Dr. Oza: I would echo what Dr. Oza said, moderation in all things, clean healthy lifestyle, be aware of symptoms, be your own advocate. If you have abdominal pain, weight loss, these are things to watch for in your friends and family. See experts who take care of this disease, seek counsel from your friends and from your colleagues. I think that's all you do.

Host: Yeah, and as we've discussed today, there is screening available. And especially if you're in a high risk group. Early diagnosis is so key. Live that healthy lifestyle. Be like Dr. Jones, take care of yourself, run, don't smoke. Don't drink too much and so on. It's been really great having you both on today. Thank you so much. You both stay well.

Dr. Jones: Yeah, thank you for your time.

Dr. Oza: Thank you so much for having us.

Host: For more information and other podcasts, just like this one, head over to Prismahealth.org. This has been Flourish, a podcast brought to you by PRISMA Health. I'm Scott Webb. Stay well.