Additional Info
- Audio Fileuf_health_shands/ufhs059.mp3
- DoctorsFriedman, Jeffrey
- Featured SpeakerJeffrey Friedman, M.D., FACS
- Guest BioJeffrey Friedman, M.D. F.A.C.S., is an assistant professor in the division of gastrointestinal surgery and the director of UF Health Bariatric Surgery Center. Dr. Friedman earned his medical degree from the University of Mississippi and completed his residency in general surgery at Carraway Methodist Medical Center in Birmingham, Alabama and Mary Imogene Bassett Healthcare in Cooperstown, New York. He served as a research fellow at the Mary Imogene Bassett Research Institute and as a minimally invasive surgery/bariatric surgery fellow at Sacred Heart Health System in Pensacola, Florida.
Dr. Friedman has previously worked as assistant medical director of the Sacred Heart Institute for Medical Weight Loss, as medical director of the Baptist Healthcare Bariatric Program in Pensacola and as chief of the minimally invasive surgery/bariatric program at Previty Clinic for Surgical Care in Beaumont, Texas. He has twice received the American Medical Association’s Physician’s Recognition Award and is a member of the American College of Surgeons, the Society of American Gastrointestinal and Endoscopic Surgeons, the Pensacola Surgical Society and the American Society of Metabolic and Bariatric Surgeons.
Dr. Friedman’s clinical interests include bariatric surgery, revisional bariatric surgery, metabolic surgery, advanced endoscopy, minimally invasive surgery and foregut surgery. His research interests include the metabolic and cognitive effects of bariatric surgery, resolution of comorbidities following bariatric surgery, and long-term effects of bariatric surgery. - TranscriptionAnnouncer: The University of Florida, College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME to provide continuing medical education for physicians. The University of Florida, College of Medicine Designates this enduring material for a maximum of 0.25 AMA PRA category one credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie Cole (Host): Welcome to UF Health Med Ed Cast with UF Health Shands Hospital. I'm Melanie Cole. And today we're discussing weight loss, surgery and transdermal vitamin patches. Joining me is Dr. Jeffrey Friedman. He's an Assistant Professor in the Division of Gastrointestinal Surgery at the University of Florida College of Medicine and the Director of UF Health Shands Hospital Bariatric Surgery Center. Dr. Friedman, it's such a pleasure to have you join us today. As we get into the topic of weight loss surgery, and transdermal vitamin patches, I'd like you to define obesity for other providers and the comorbid conditions that can arise from it and other diseases that either are exacerbated by it or contribute to it.
Jeffrey Friedman, M.D., FACS (Guest): Well, thank you for having me, Melanie. Obesity is a problem that the entire world faces. It's epidemic. It costs our country billions of dollars in healthcare related expenses and cuts people's lives short, by up to 20 years. Obesity is calculated by body mass index, which is your weight in kilograms, divided by your height in meters squared. That's difficult to calculate for a lot of people, and you can just simply Google body mass calculator and input your height in feet and inches and weight in pounds. And it'll calculate your body mass index.
For patients to qualify for surgery, their body mass index has to be over 35 with associated co-morbidities. Some of the comorbidities associated with obesity, migraine headaches, pseudotumor cerebri, hypertension, hyperlipidemia, sleep apnea, Pickwickian syndrome, which is a hypoventilation syndrome, gastroesophageal reflux disease, diabetes, hypothyroidism, low back pain, urinary stress incontinence, menstrual irregularities, infertility, peripheral edema, joint pain. Your risk of developing multiple different cancers go up and your life expectancy goes down by as much as 20 years, when you're morbidly obese. When you are morbidly obese and your body mass index is 40 or greater, the patients referred don't necessarily need to have the co-morbidities listed, but, by the time they hit 40, a lot of patients, as you guys know, do have some of those comorbidities.
Host: Thank you, Dr. Friedman. So, as you're telling us about clinical criteria for bariatrics and letting other providers know who can qualify, as they're working with their patients, along with the things that they must do; I'd like you to speak a little bit about your program and how you work with the patients on things that you'd like them to do in advance of the surgery, whether it's weight loss, exercise, starting an exercise program, prehab. So please let other providers know your clinical criteria for your program and what they can expect from the program.
Dr. Friedman: So there are two sets of criteria that we work with really. The criteria that we put our patients through, and then there is also the criteria that the insurance company will require to qualify or be approved for surgery. So, the patients basically have to satisfy both requirements, our requirements and the insurance company requirements in order to get approved for surgery.
The insurance companies are policy dependent. So, not all insurance policies will provide coverage for weight loss surgery, number one. Number two, a lot of companies who do provide coverage will require their patients have what's called a six months supervised weight loss trial and what that involves is six months of documentation of weight loss attempts with a physician. These do not have any value. They've been proven to not have any value in terms of weight loss or predictive factors, in terms of success after weight loss surgery. But they are a roadblock for patients.
They have to see their primary care doctor for the determined amount of time without missing a month, also to have these things documented. That can be the rate limiting step in this process for patients. And if a patient is interested in pursuing this and has a weight loss trial, it is helpful for them to go ahead and get the weight loss trial initiated.
Once they come and see us, we'll order a full panel of blood work, including multiple vitamin levels. We typically order an upper GI swallow study. Some patients may require an endoscopy. All patients who are in need of a colonoscopy should have an up-to-date colonoscopy. We have our own dietician with our program dedicated to our bariatric patients and all patients have to see and get approved by our dietician. And also our psychologist as well. Some insurance companies will have some other requirements, that is policy dependent and can be different from insurance policy to insurance policy.
Host: Thank you so much. So, this is such important information. Now tell us about the options for weight loss surgery that you're doing there at your program at UF Shand's Hospital. Because that's changed over the years, right? There are things we used to do that we're not doing now.
Dr. Friedman: Correct. Surgery evolves over time and bariatric or metabolic surgery is no different. We had mentioned the lap band. You and I had talked about the lap band briefly. The lap band has grown largely out of favor and is not done much anymore. Certainly, I don't do the lap band and haven't done the lap band in over 10 years. We remove lap bands and in some cases with patients with lap bands, convert that to a different procedure if indicated. We've seen a big increase in the number of sleeve gastrectomies that we do these days. The sleeve gastrectomy has been around for approximately 15 years now. There's good long-term data available. It is a good standalone procedure for weight loss. Patients can expect on average to lose about 50 to 60% of their excess weight following surgery. This involves dividing the stomach and removing three quarters of the stomach. The patients are left with a banana shaped stomach. This is mostly restrictive procedure, meaning it restricts the amount patients can eat or drink. It has beneficial effects on diabetes and high blood pressure and hyperlipidemia and all the other comorbidities associated with obesity as well.
The gastric bypass has been around for 80 years. It's been modified as time has gone by, and the mortality rate with a gastric bypass is less than that of having your gallbladder out after 30 days. In the United States. People are surprised to hear that. I do a gastric bypass through five small incisions. Patients stay in the hospital overnight. This offers better weight loss than the sleeve gastrectomy. And on average, people lose about 60 to 70% of their excess weight. This involves, dividing the stomach into a small pouch that's about the size of an egg and dividing the small bowel. The distal aspect of the small bowel gets attached to the new little stomach and the remnant stomach and the duodenum drain through the proximal end of the small bowel, which gets connected further downstream.
As a result, you can't eat as much and what you do eat, doesn't mix with the digestive juices until further down in your small bowel so you don't absorb as much of what you eat. This operation offers a better weight loss on average than the sleeve, and also better control or amelioration of comorbidities, such as diabetes, high blood pressure and high cholesterol.
And then a Type 2 or non-insulin dependent diabetic, who has had that diagnosis for less than seven years, they have about an 80% chance of the diabetes going into remission following this procedure. The numbers are fairly similar with high blood pressure and high cholesterol following a gastric bypass.
We also offer a newer procedure called the single anastomosis duodenal switch or the SADI procedure. This is a hybrid procedure where we perform a sleeve, and then divide the pylorus and do a distal bypass, a single anastomosis distal bypass to the small bowel at the pylorus. This offers very, very good weight loss in the order of 90 plus percent excess weight loss, and very, very good improvement or amelioration or remission of certain co-morbidities such as diabetes, high blood pressure and hyperlipidemia. We also offer revisional and corrective procedures here. Those are difficult to generalize about. That is a case by case, procedure.
Host: Well, that was an excellent, comprehensive answer about the options available at UF Health Shands Hospital. And thank you for telling us about restrictive malabsorption or a combination of the two. So as we're talking about that, what about right after surgery? Speak about patient lives after these kinds of surgery and their nutrition requirements. I'd like you to tell us about transdermal vitamin patches. Is there data to support their efficiency? Tell us a little bit about that.
Dr. Friedman: So these procedures are restrictive and some are malabsorptive as well. Restrictive, meaning they can't eat or drink as much as what they could before. It restricts the amount they can eat or drink. And initially after surgery in the, especially in the first two to three weeks, when there's inflammation and swelling, dehydration is a very, very common complication. And it's something we fight, and educate our patients to avoid. That being said, our patients are educated to focus on liquids, their liquid intake, following the weight loss operation of their choice. They meet with our dietician and know how much liquids they should be taking as well as how much protein they should be taking as well.
They also have to take multivitamins, calcium and vitamin B12. Every bariatric patient should take that. That's recommended by the American Society of Metabolic and Bariatric Surgery. It's very difficult for some of these patients to maintain their hydration status and nutritional status and get their pills and vitamins in. And that's where these vitamin patches are such a good product for patients, especially in the initial post-op phase. The patches can be put on transdermally like any patch. They are absorbed through the skin. And that takes care of the vitamin requirements. That avoids the necessity for two multivitamins a day, three to four different calcium pills and whichever route they're taking the B12 through. So up to six, seven pills a day less through these patches. With any of these surgeries, there is a risk for vitamin deficiencies and whichever route the patient chooses to do their vitamins, it's important that their vitamin panels and vitamin levels be followed after surgery and with our patients who choose or elect to use the patch post-operatively, we check their vitamin levels at three months after surgery and every three months after.
We've found that this really helps patients avoid problems with dehydration, which can cause nausea and headaches and cause patients to need to go to the emergency room in that initial post-operative phase. This has helped them avoid that, while still getting their vitamins, in the initial postoperative phase.
Host: Now I'd like you to speak, you touched on it a little bit before, about the nutritionist and dietician. How important is multidisciplinary management for these patients? As you're letting other providers know what they can expect from your program, who all will be working with them? And how does it work as far as follow-up as well?
Dr. Friedman: Right. So, we believe that obesity is a very complicated disease. It's multifactorial, it's genetically related. It's related to the environment. It's complicated and it requires a lot of different providers, to treat successfully the disease. And here we have a multidisciplinary team, GI doctors and medicine doctors, and endocrinologists and surgeons and our nutritionists and psychologists, respiratory doctors as well, who all weigh in and will help evaluate and teach and prepare the patient for their life after surgery. In terms of our followup, well, we believe, and it's been well-documented, that the followup of these patients is very important and is directly related to their postoperative success and their long-term success in terms of maintaining weight loss.
We tell our patients that we expect to see them for the rest of their life. We see them in our practice after surgery, two weeks after surgery, six weeks after surgery, three months after surgery, six months after surgery and every six months after that, and we check our post-op vitamin levels on our patients very frequently as well.
Host: What a comprehensive program that is. Dr. Friedman, as we wrap up, what would you like to summarize for other providers about the program at UF Health Shands Hospital, bariatric surgery options, nutrition requirements, and transdermal patches, and how all of this really fits into the practice of care for obesity.
Dr. Friedman: Well, again, I think that obesity is a very severe health problem that not just America, but the world faces. We have hundreds of thousands, if not millions of people who are morbidly obese. This is now effecting our kids. The average life expectancy of Americans is decreasing instead of increasing. Certainly obesity is playing a major role in that. It is costing our country, billions of dollars in healthcare related expenses. Rates of heart disease and diabetes and sleep apnea are skyrocketing and will continue to skyrocket and unless we reverse this trend. I think that it's very important to talk to patients about options for obesity. Surgery's not the first step in the treatment. Certainly diet and exercise and other methods of weight loss need to be tried, but we know that diet and exercise is only successful roughly one to 2% of the time in people with obesity in terms of long-term sustained weight loss. When patients fail to maintain successful weight loss, that's when they should be considered for surgery. Surgery is safe. It's effective. It offers sustained weight loss for patients with obesity and can also get rid of some of the co-morbidities related to obesity as well, and ultimately will make the provider, the primary care doctor's job easier in managing these patients in your practice.
Host: Certainly is an exciting time to be in your field, Dr. Friedman, and thank you for joining us and sharing your expertise on weight loss and obesity and the surgical options available. To refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. And that concludes today's episode of UF Health Med Ed Cast with UF Health Shands Hospital. Please also remember to subscribe, rate and review this podcast and all the other UF health Shands Hospital podcasts. I'm Melanie Cole. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
Additional Info
- Audio Fileuf_health_shands/ufhs060.mp3
- DoctorsCusi, Kenneth
- Featured SpeakerKenneth Cusi, MD, FACP, FACE
- Guest BioDr. Kenneth Cusi serves as Chief of the Division of Endocrinology, Diabetes & Metabolism in the Department of Medicine at the University of Florida. He received his medical degree in Argentina from the University of Buenos Aires School of Medicine and is board certified in both Internal Medicine and Endocrinology, Diabetes & Metabolism.
Learn more about Kenneth Cusi, MD, FACP, FACE - TranscriptionAnnouncer: The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie: Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole, and I invite you to listen as we discuss the practical clinical care pathway for non-alcoholic fatty liver disease. Joining me is Dr. Kenneth Cusi. He's the Chief of the Division of Endocrinology, Diabetes, and Metabolism in the Department of Medicine at the University of Florida College of Medicine and he practices at UF Health Shands Hospital.
Dr. Cusi, it's a pleasure to have you join us again. We've talked, you and I, before in previous podcasts about non-alcoholic fatty liver disease. Can you help us in this one to understand, as we get into this topic, the magnitude of the epidemic of NAFLD and what it means to primary care physicians and patients? What are we seeing in the trends now?
Dr. Kenneth Cusi: Well, Melanie, thank you for having me again. And as you said, endocrinologists are now facing a new problem, that is an accumulation of fat in the liver that can lead to cirrhosis. So to some extent, this is something that endocrinologists and primary care physicians have somehow overlooked because we didn't have the tools to identify it earlier. But recent studies suggest that this new epidemic related to the epidemics of obesity and type 2 diabetes can lead to a substantial number of adults developing cirrhosis. And it is soon to be the number one cause of liver transplantation. So there's been a lot of activity in the last year and lots of good things are happening that will help us in our clinic -- I'm an endocrinologist -- to identify these people. And it's exciting because there are many new drugs in development, so the clinical care pathway tries to support the work of clinicians in the trenches to do this better.
Melanie: Such an interesting topic and thank you for explaining that to us. So as this epidemic is growing, with the epidemic of obesity and type 2 diabetes, these things are all kind of happening at the same time. How important is early diagnosis and referral to prevent those future cirrhosis in millions of patients, as you just discussed? So help us to understand how fatty liver impacts the care of every patient that also has these co-morbidities of obesity and type 2 diabetes and cardiovascular disease and all the things that are going along with it.
Dr. Kenneth Cusi: Thanks, Melanie. The key thing is early diagnosis, just as you mentioned, and I'm going to tell you in a moment how we get to that early diagnosis. But just to emphasize, because I have many peers in the endocrinology field, sometimes I give talks to my friends in primary care. They are sometimes skeptical. I mean, I have not seen somebody with cirrhosis in my clinic lately. And what happens once they develop cirrhosis, they go just from the liver specialist to the hospital for an admission and back. I work, you know, at UF Health Shands Hospital. I see a lot of people with cirrhosis that have this from NASH. And I wished they would have been diagnosed earlier because there are things you can do.
So what I tell the clinicians is that seven out of 10 people with type 2 diabetes and a close number of those with obesity alone without diabetes have a fatty liver. And about half of them have a chronic inflammation that's going to lead them potentially to cirrhosis. Actually, we published a paper earlier this year in Diabetes Care, which is the official journal of the American Diabetes Association, that showed that about one in every five to six patients with type 2 diabetes have scarring of the liver, what we call fibrosis; and one in ten, it's almost either cirrhosis or pre-cirrhosis.
So answering your question, it's key to identify these people earlier. And that's where this pathway development together with friends in the gastroenterology field, from the American Gastroenterological Association, from primary care, key primary care organizations with the ADA, the Endocrine Society, and the American Association of Clinical Endocrinologists came together to make a simple and practical approach for the early diagnosis of people at risk.
Melanie: So important. So when do you feel it's important to refer to a liver specialist? And tell us a little bit about screening, whether patients that are suspected of being at intermediate or high risk may need liver imaging study. Tell us about that and the role and limitations of current diagnostics and screenings, Dr. Cusi.
Dr. Kenneth Cusi: Yeah. So typically, we've learned in medical school that you only have liver disease if your liver enzymes are elevated and the cutoff used in clinical labs is about 40, but that's a very high cutoff. We know now that if your alanine aminotransferase or ALT is greater than 19 in women or 30 in men, you probably have a problem. So we start by identifying patients at risk. Those with type 2 diabetes are at the highest risk followed by those with obesity and metabolic syndrome or anyone with already elevated liver enzymes. But in our studies and those of others, only a minority of people have elevated liver enzymes.
So we have to take a good history, get some routine labs, and there's a test called the fibrosis-4 index that is calculated based on your age, your liver enzymes, AST and ALT, and your platelet count. This is an equation that you can put on your phone or on your computer. It's on many websites. And that helps you stratify if your risk is high, intermediate or low. And then there's some imaging studies that I'll tell you in a moment that you can do in the clinic, or you can refer to be done in the same way that you order an ultrasound. The test is called elastography, and I'll tell you more in a moment. And that test can tell relatively well if you are near cirrhosis or you're free of that risk. So with those two steps that fit for an elastography, the most common device is called Fibroscan. There are others called shear wave. And I can tell to my friends in endocrinology that are listening or primary care, your hepatologist already has that Fibroscan to do the test and they've done it to their patients for the past 10 or 15 years from the hepatitis C field and now from NASH. They do it in the same way that they take the blood pressure of patients. So that's an easy test to do. And between the FIB-4 and Fibroscan test, you pretty much can tell how close or not to developing cirrhosis your patient is.
Melanie: So then tell us what's exciting in your field right now. What treatments are available? What's coming in the drug development pipeline? Tell us a little bit about what's going on that's really exciting for this condition.
Dr. Kenneth Cusi: Well, great. I was hoping you would ask me that because, in reality, it's a very exciting time. Number one, because we identified this, and again, if about 15% of patients have significant liver disease from NASH, that's four or five million people with type 2 diabetes, so there are things to do.
Number one, diet that reduces caloric intake and induces weight loss is going to improve the liver in proportion to the amount of weight loss. So the more weight loss, the better. Second, we are now learning that for people in whom the obesity is very significant, they might be candidates for bariatric surgery. It works for the liver disease in the same way it has worked to reduce cardiovascular risk and promote weight loss.
Second, that's the weight loss approach alone. There are some diabetes medications that have shown to work very well. Pioglitazone, which was marketed in the past or it's still available as Actos, is now a generic medication, which costs less than $5 a month. That generic medication starting at 15 and building up to 30 milligrams a day improves NASH and the inflammation in about two-thirds of the patients. And we published in March in the New England Journal of Medicine a new approach also based on a diabetes medication, which is a glucagon-like peptide-1 receptor agonist or GLP-1 receptor agonist with a study with semaglutide, that has been very exciting. And there are a number of new drugs too under the belt.
Melanie: Yeah, that's certainly an exciting time to be in your field, Dr. Cusi. And as you and I have talked before, diagnosis is important as many interventions are available, as you've just stated. So many different imaging modalities and tests and screenings, lifestyle modification, weight loss agents, all of these things are working. Can you explain how these modalities are just as important as many of those interventions and a multidisciplinary approach for these patients, why that is so important?
Dr. Kenneth Cusi: Thank you. It's very important to understand that about half of the people with diabetes and obesity could be low risk. So we need to focus on the lifetime intervention, always to promote weight loss but also, more than anything, prevent cardiovascular disease. So a typical mistake is discontinuing the statin. And that's why in the clinical care pathway, we have a very nice table. And again, this clinical care pathway has been published in gastroenterology a few weeks ago. And we want people also, not only to keep them on the statin, to reduce cardiovascular disease, but if they treat the diabetes to use these diabetes medications, pioglitazone and semaglutide, because that is what we see that has really worked very well.
Now, in people with higher risk, we're going to emphasize even more the importance of weight loss, and we're going to emphasize the role of medication. So again, semaglutide showed that about almost 60% of patients responded and what's more important is that the FDA approved in June a weight loss indication for semaglutide. The higher dose of 2.4 milligrams a week promotes weight loss in people without diabetes up to 15%, somewhat less in people with diabetes.
So these are important resources that the primary care and endocrinologists need to know. Treating obesity treats fatty liver. And pioglitazone, by reversing insulin resistance, removes fat out of the liver and has the same effect. So typically now what we're doing is combining both drugs to really help our people. And I have to say there are a lot of new drugs in the pipeline along these lines promoting weight loss. Just last week in the New England Journal of Medicine, lanifibranor, which is a PPAR gamma, alpha and delta, has also shown to improve fatty liver disease. So we're going to see a lot more going on in 2022. And my friends understand that the early diagnosis is something that can be done today in your clinic. And there are things that you can do to prevent progression to cirrhosis in your patients with NASH.
Melanie: What an informative episode and a great educator you are, Dr. Cusi. Thank you so much for joining us. And to refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters.
That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. Please always remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
Additional Info
- Audio Fileuf_health_shands/ufhs058.mp3
- DoctorsTuli, Sonal
- Featured SpeakerSonal Tuli, MD, MEd
- Guest BioSonal Tuli, MD, MEd is a Professor and Chair of Ophthalmology for the University of Florida College of Medicine.
Learn more about Sonal Tuli, MD, MEd - TranscriptionPreroll: The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME, to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie Cole (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole. And today, we're discussing corneal transplant surgery for improved vision. Joining me is Dr. Sonal Tuli. She's a professor and the Chair of Ophthalmology for the University of Florida College of Medicine.
Dr. Tuli, it's a pleasure to have you with us today. So I'd like you to start by giving us a little bit of a history lesson here. How long have corneal transplants been around and how commonly are they done now?
Dr Sonal Tuli: Thank you for having me here today, Melanie. Corneal transplantation has actually got a fascinating history. And corneas, I don't know if you know this, were actually the first solid human tissue to be transplanted nearly 120 years ago for the first time. Corneas are also the most frequently transplanted solid organ in the United States, in fact, the entire world. So nearly 200,000 corneal transplants are performed globally every year. And over 50,000 of those are done in the US alone. But unfortunately, because corneal problems are one of the leading causes of blindness in the world. There are still about 13 million people worldwide who are blind awaiting corneal transplant.
Melanie Cole (Host): That's fascinating. I am sure that myself and other providers did not know the history of corneal transplants. That's so interesting. Tell us some of the major differences between corneal transplants and other organ transplants as far as outcomes are concerned.
Dr Sonal Tuli: So corneas are unique in the sense that, unlike other solid organs, they don't have a blood supply and they get all their nutrition from the aqueous fluid in the eye and the tears on the surface of the eye, which means there's a significantly lower risk of rejection of corneal transplants compared to other organs, since they're usually not recognized as foreign by the body's immune system.
It also means that corneal transplants don't have to be matched unlike other transplants, other kidney or heart transplants, before implantation. So patients can actually receive transplants from virtually any donor. You don't have to match that or wait for a donor. And additionally, even in high-risk cases where there's vascularization of the cornea, there are blood vessels in the cornea due to some pathology, we can prevent rejection just by using topical steroids or immunomodulatory eye drops and don't need systemic immunosuppression. So it's much safer for patients in the long run because they don't have to take medications orally or IV to prevent rejections. At the University of Florida, we have an over 95% success rate of corneal transplants.
So one of the things that makes corneas different is that they're viable for two weeks in storage. What that means is that corneal transplant surgeries can be planned well in advance and thorough testing can be performed to rule out infectious diseases, such as hepatitis or HIV. And in fact, another cool bit of information is that one of the first storage media was actually invented at the University of Florida called the MK Media. And that is one of the reasons that corneal transplantation became widely available to people.
Melanie Cole (Host): What an interesting episode we're doing here today. So please identify for us conditions that would benefit from or result in cornea transplant.
Dr Sonal Tuli: So we broadly divide the indications for corneal transplants into three major categories. So there's some overlap there. So the most common is optical, so where the transplant is done to create an optically clear cornea to improve vision. This can happen in cases where you have corneal scars from trauma or corneal infections that can lead to scarring. It can also be done to treat some of the inherited corneal conditions and these are pretty common, such as Fuchs dystrophy where you have these guttae on the cornea that acts like frosting on the cornea and they can scatter light or decrease vision or other conditions like keratoconus where the cornea, because it's irregularly protruded, can cause irregular astigmatism and poor vision that's not correctable with glasses or contact lenses. And this indication has decreased recently due to the advent of corneal cross-linking that can stabilize these corneas. But in advanced cases, you do have to do transplants.
The other very common indication for transplants is what's called therapeutics where the procedure is done to treat conditions that cause corneal damage resulting in corneal decompensation and thereby you can get corneal edema and bullae, which are like blisters on the cornea. They can get painful, but also affect the vision significantly. And this can happen in patients who've had multiple eye surgeries or complications during their eye surgery and also for corneal infections that are not responding to medical management.
And then finally, transplant can be done for what are called tectonic reasons. And those are in order to maintain the structural integrity of the eye. So these are in cases of very severe infections or injuries or certain autoimmune conditions or viral infections that can cause melting and perforation of the cornea. And in Florida, we see much higher numbers of corneal ulcers and infections than other parts of the country because of a warm and humid environment that causes infectious organisms to flourish.
So one of the very common reasons we see really severe ulcers or corneal infections is from improper contact lens use. And often these require urgent or emergent corneal transplants.
Melanie Cole (Host): Wow. So obviously, the type of transplant a patient receives depends on which part of the cornea is damaged and why. Can you tell us some of the options available, Dr. Tuli, and the reasons for performing the different types of cornea transplant, why you might choose one over the other?
Dr Sonal Tuli: I don't know if you know this, but for nearly a hundred years, the predominant type of transplant was what's called a penetrating keratoplasty. And this is still most commonly done in many countries in the world. In this procedure, you punch out a central corneal button of about seven to eight millimeters using what's called a trephine and then it's replaced with a similar size with a slightly larger button, which is punched out from the donor tissue. It's sutured to the patient's eye using 10-0 or 11-0 non-absorbable sutures. These are sutures that are thinner than the human hair, so very, very tiny sutures. They're left in the eye for several months to allow the cornea to heal. And then we remove them strategically a few at a time to reduce the astigmatism or the irregularity of the cornea over the next few months. What this means is that it takes about a year for the patient to recover vision enough to be able to use the eyes for activities such as reading or driving. Also the eyeglass prescription following the transplantation can be unpredictable and patients often need rigid gas permeable or scleral contact lenses for best vision correction because they might have a clear cornea, but it could be irregular.
Also the other thing that patients need to be aware of is that the eye does not achieve full structural integrity lifelong, and the patients have to be careful about trauma to the eye, even years down the road. So we still do these frequently for tectonic reasons or where the entire cornea is involved in the pathology or if the eye is perforated or has a severe infection or injury.
But about 20 years ago, this ophthalmologist from Netherlands, Gerrit Melles, introduced what's called a posterior lamellar keratoplasty. And this has completely revolutionized the management of disorders that only affect the endothelium and that's the back layer of the cornea. And that's one of the most common reasons why corneal transplants are done currently. And this has undergone several iterations, but to result in the what's the most commonly performed procedure, at least in the United States, called a Descemet's stripping endothelial keratoplasty or DSEK. And now, what we do is called Descemet membrane endothelial keratoplasty or DMEK. So you'll hear me talk about DSEKs and DMEKs, and that's what these are. And currently in the US, nearly twice as many endothelial transplants, DSEKs and DMEKs, are performed now as penetrating keratoplasty.
What's different in these procedures is that instead of removing the entire cornea in patients where the rest of the cornea is completely normal, and it's just the endothelium that's abnormal, you make a very tiny incision at the corneal limbus and go in and strip out or peel off the Descemet's membrane and the endothelium that's underlying the center of the cornea. And then you replace it with a layer that contains either the posterior corneal stroma, the Descemet's membrane, the endothelium, as in the case of DSEK or just the Descemet's membrane and endothelium in case of DMEK. So in the DMEK, you're basically replacing what you've removed. And what's nice is that because these tissues are really thin, they can be folded or rolled and then inserted into the eye where they're unfolded or unrolled and approximated to the cornea using an air or gas bubble. So you basically float them up on this gas bubble and it sticks to the patient's own cornea.
And the cool thing is that these grafts then adhere to the cornea by the suction that's created by these now healthy endothelial cells pumping fluid out of the cornea and you don't need any sutures. Also once you start pumping normally, the vision starts clearing up very rapidly.
So given that there are several advantages of these lamellar grafts, since incision is very small, the eye is structurally intact and there's low risk even down the road if there's any future trauma. Because there's a much smaller amount of donor tissue transplanted, the risk of rejection is also much lower because there's less tissue for the body to recognize as foreign. And because the majority of the cornea is not replaced, the refractive power of the cornea does not change significantly. So you don't have these very interesting changes in the eyeglass prescription or need contact lenses.
And most importantly, for the patient, the recovery of vision is much quicker, usually within one to two months. So at UF, patients with endothelial pathology basically get DSEK and DMEK, and that is the most commonly done procedure here, though we do quite a few penetrating keratoplasties too because of the infections that we see.
Another procedure that's done a lot less frequently is what's called a deep anterior lamellar keratoplasty or DALK. And this is done for conditions where the endothelium is healthy, but the superficial corneal layers are scarred. It's technically much harder. And there are very few patients that actually meet the criteria for this procedure. So it's rarely done in the US and we do it in a select few cases of keratoconus or scarring, but not very commonly.
So basically to summarize, if the entire cornea is affected or there's a perforation, you do a penetrating keratoplasty only. If just the endothelium is damaged, then a DSEK or DMEK are done. And if the anterior cornea is affected with an intact endothelium, then you do a deep lamellar anterior keratoplasty.
Melanie Cole (Host): Dr. Tuli, cool is hardly the word for this. Amazing is more the word for what you just described as the different procedures and the different ways of doing cornea transplant and the history as well. Now, do you have any patient selection criteria you'd like other providers to know about?
Dr Sonal Tuli: So, fortunately, there are very few patients with corneal problems that are not candidates for corneal transplantation of some sorts, so that could be some one of these procedures. Rarely, we might have patients whose general health is too poor to go through surgery, but that's very unusual because we can do this procedure under local anesthesia, which is a lot less risky than general anesthesia. So most patients are candidates for this procedure even health-wise, unless they cannot lie flat for some reason or have enough risk that even local anesthesia would be problematic.
But in some cases, along with corneal problems, patient may have retinal or glaucomatous damage that limits their vision. So even if you do a corneal transplant, their vision would not improve. And in those cases, we don't do corneal transplants given the limited amount of corneas available.
At the University of Florida, actually, we do see many patients that have very, very complex eye pathology or chemical burns that may not be amenable to routine transplantations, any of the types that I mentioned earlier. Some of these patients have also had repeated rejections of their transplants because their corneas have vascularized or their lack limbal stem cells. Or they get recurrent infections, viral infections, for example, herpes or shingles in their eye. And for these patients, we perform what's called a keratoprosthesis or an artificial cornea.
So this keratoprosthesis is made of an anterior plate and stem that's made out of a PMMA plastic. And it looks somewhat like a transparent mushroom and then there's a titanium back locking plate. And what we do is sandwich the donor cornea between these two plates and snap it into place. And then this entire apparatus is sutured to the eye similar to a penetrating keratoplasty. This are complex procedures and it requires very complex post-operative management and coordinated care with several subspecialists in ophthalmology. So it's done by very few cornea specialists and UF is one of those centers that does several of these every year.
But what's great about this procedure is that the recovery of vision is almost immediate and it's often superior to regular corneal transplants. And also, these can be life-changing for patients because these patients have often been told that nothing can be done for them because their eyes have such complex eye problems. And so we've had a lot of patients that had been sort of written off by other physicians and we were able to provide keratoprosthesis surgeries for them and got them to see again.
Melanie Cole (Host): doctor since we're discussing transplantation, what role can our listeners play in the donation process?
Dr Sonal Tuli: corneal transplantation is life-altering and a miraculous surgery. It's only possible because caring individuals donated their corneas after they died. I would encourage everyone to register to be an organ donor and not only transform a life, but also leave a legacy and let someone see life through your eyes.
Melanie Cole (Host): Well, Dr. Tuli, before we wrap up this absolutely fascinating episode, tell us about any innovative or future technology in corneal transplant, current emerging therapies for these kinds of issues, any game changers, any of the latest or most exciting advances that you would like other providers to know about and why it's so important that they refer to the incredible specialists at the University of Florida College of Medicine and UF Health Shands Hospital.
Dr Sonal Tuli: So some of the exciting procedures that we're doing at UF are called DWEK, we love these acronyms, so that's called Descemet stripping without endothelial keratoplasty. In some select patients with endothelial dysfunction, we strip just the central four to five millimeters off the Descimet membrane. And then we use medications called Rho-kinase inhibitors and steroids to let the patient's own endothelial cells migrate across the defect without needing a transplant in several of these patients. We just completed a clinical trial on this procedure and now offering it to patients who meet the criteria for this procedure.
There's work being done on 3D printing corneas and expanding patient's own endothelial cells ex vivo or outside the eye, and then re-injecting them back in the eye. But those are not ready for prime time yet, but coming down the pike. And we're also doing research on ways to prevent corneal scarring and preventing some of the viral infections that cause corneal scars from causing infections and thereby trying to reduce the need for transplants altogether.
So the University of Florida offers the entire spectrum of corneal transplant procedures for patients. So any patient with a corneal problem can usually undergo one of these procedures that we offer and recover their vision. So if you're not sure if the patient can be helped, we are happy to see them and see if they would be candidates for any of these new, innovative, or even traditional transplants that are being done at the University of Florida.
Melanie Cole (Host): Well, thank you so much, Dr. Tuli, for joining us today and sharing your incredible expertise for other providers today. And to refer your patient to Dr. Tuli, you can call (352) 265-2020 or visit ufhealth.org/eyecenter for more information. And to listen to more podcasts from our experts, you can visit ufhealth.org/medmatters.
That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. And please remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
Additional Info
- Audio Fileuf_health_shands/ufhs057.mp3
- DoctorsRamirez-Zamora, Adolfo
- Featured SpeakerAdolfo Ramirez-Zamora, MD
- Guest BioDr. Adolfo Ramirez-Zamora is currently an Associate Professor of Neurology, Program Director and Division Chief of Movement Disorders at the Norman Fixel Institute for Neurological Diseases at the University of Florida.
Learn more about Adolfo Ramirez-Zamora, MD - TranscriptionPreroll: The University of Florida, College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA category one credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie Cole (Host): Welcome to UF Health Med Ed Cast with UF Shands Hospital. I'm Melanie Cole and today we're addressing diversity challenges in Parkinson's Disease treatment. Joining me is Dr. Adolfo Ramirez-Zamora. He's an Associate Professor in the Department of Neurology and Division Chief of Movement Disorders at the University of Florida College of Medicine. Dr. Ramirez-Zamora also practices at UF Health Shands Hospital in Gainesville, Florida. Dr. Ramirez-Zamora, thank you so much for being with us today.
This is such a great topic. And as we get into the diversity challenges that these patients face, can you help us to recognize the clinical symptoms of Parkinson's Disease, some of the early signs and symptoms, the clinical presentation, just set the stage for us a little bit, if you would.
Adolfo Ramirez-Zamora, MD (Guest): Yeah, absolutely. Thank you so much, Melanie, for the invitation. This is really a pleasure and a great opportunity for me to talk a little bit about the challenges when understanding Parkinson's Disease in the setting of diverse population. But, like you suggested, let me just go over really quickly about how do we diagnose, what are the symptoms of Parkinson's Disease?
Parkinson's Disease has been considered a disease of movement for quite some time. The main features of Parkinson's, the ones that most of us may be able to recognize and relate to are difficulties with gait and balance, shuffling gait, problems with posture. Patients with Parkinson's tend to stoop forward.
And then they also have an inability to pick up their feet when they're taking rapid steps. Another common symptom of Parkinson's is the presence of tremor. A tremor that occurs like a rhythmic, regular, involuntary movement that tends to occur when you are moving your body. Finally, patients with Parkinson's Disease, typically have reduced speed of movements, which is actually what characterizes Parkinson's, is this inability to move fast and perform fine precise movement with the right amplitude and the rhythm of the movement. We now know that about 30% of patients with Parkinson's don't have tremor.
And despite all the advancements that we have seen in the field, when it comes down to brain physiology and genetics and molecular biology, et cetera, the diagnosis of Parkinson's remains a clinical diagnosis. You need to have the combination of the symptoms that I mentioned above, to really fulfill the diagnosis of Parkinson's.
And sometimes that could be quite challenging, particularly at the beginning. Finally, as a quick note, we now understand that Parkinson's is more than just a movement disorder. There's a variety of symptoms that are very common and prevalent in Parkinson's Disease that are what we call the non-motor symptoms. These are symptoms that affect other systems in the body and they range from disorders of the gastrointestinal tract with constipation being one of the most common symptoms in Parkinson's, to problems with emotion, problems with depression, anxiety, sleepiness, fatigue, trouble with sleep, which is also very, very common. So we now really see and understand Parkinson's as a disease that affects multiple organs. Although the diagnosis relies in some of these specific motor movement features.
Host: Well, thank you for that Doctor and for other providers that are working with Parkinson's patients, and data's shown that people from racial or ethnic minority groups are less likely to receive preventive health care and across the board, these ethnic groups have faced a disproportionate health burden. Can you talk to us a little bit about the unique challenges that these communities have faced in terms of healthcare disparities and some of those challenges specifically faced in patients with Parkinson's and you can also add in how common this is in diverse populations.
Dr. Ramirez-Zamora: Certainly. No thank you. That's a really great point. For the past decade, we are increasingly aware of the challenges of the disease in other racial and ethnic groups. One of the misconceptions for years was that Parkinson's Disease was much more common in people with Caucasian backgrounds. But now we recognize that Parkinson's is actually very common in other populations and African-American populations and the Hispanic populations as well. It's also becoming increasingly known that some of the symptoms, that there's a disparity of symptoms between these groups, that patients with minority or underrepresented communities, they appear to have more of these non-motor symptoms.
There's an increased burden of symptoms that are not necessarily motor, especially early in the disease. And also we are seeing trends when it comes down to management that the use of certain medications appears to be more prevalent in certain populations. The changes in quality of life related to treatment appears to be different among different groups.
This is just really the tip of the iceberg. We really don't have a lot of data when it comes down to management and research in these groups. There is a significant challenge in providing access for patients of underrepresented minorities in medicine to reach our clinics, to be part of clinical research. There are challenges that range from trust in the medical system, access to transportation, access to care, ability to participate in research studies based on language, transportation issues. In some instances now with the recent pandemic, health or technology literacy, the need of having somebody else in the house to allow you, to help you to be able to participate on some of these treatments. There are a variety of challenges that speak to the lack of research and understanding of how to better serve these other populations. There's very limited information and very limited data.
We also know that it's likely that the numbers that we have regarding the disease, they don't really represent the impact, the range of this problem. We estimate that there's about 50 to 60,000 new cases of Parkinson's Disease per year here in the US which comes down to maybe having a little over 1 million people with Parkinson's Disease living in the US. But as I mentioned before, because of the challenges on the diagnosis, because of the insidious nature of the disease, it's very likely that a lot of patients that are suffering or they're having the disease, are either misdiagnosed with other problems with tremor or other problems with walking, not necessarily Parkinson's. And it's also possible that they're just not looking for, they're not accessing medical care.
Part of it may be especially in the underserved populations related to ability to get to the clinics or problems with communications with different providers. So, there's a wide range of challenges that these populations are facing to really get into our clinics and trying to better understand the differences between patients from different backgrounds when it comes down to response to treatment, response to research and ability to access certain therapies. We know that looking at some of the available data, patients from underrepresented backgrounds have less access and less participation in behavioral or non-pharmacological strategies to help with their symptoms ranging from physical therapy, occupational therapy, participation in certain social activities and groups, et cetera, limited access to psychiatric care as well.
Host: So interesting. What great points that you've made. So, can you tell us about some initiatives that you're involved in, on how to increase diversity into your clinical practice, initiatives for Parkinson's patients that you'd like to share with other providers?
Dr. Ramirez-Zamora: One thing that I would like to mention to start, is that one of the largest observational studies in Parkinson's Disease, the Parkinson's Outcome Project, that study has been running for about over a decade. And it has over 13,000 patients that are followed longitudinally to try to get a sense of what are the best practices, how can we improve outcomes in patients with Parkinson's Disease? When the leadership of the study recently looked at the diversity within the cohort, it became very clear that most over 95% of the patients were white, Caucasian background. So, the leadership of the study is really shifting gears and looking at underrepresented populations and trying to encourage and facilitate research opportunities to learn more about why are these patients not getting into the study. And are there any differences in treatments, differences in outcomes or response to different medications on the intervention side? I think that's a great initiative that is gonna really give us a lot of information about the long-term outcomes and progression of the disease.
One local initiative that we have is that we recognize in our own clinics, the challenges to get a diverse population to our clinic. We are trying to increase educational activities in our area, including our county. And we submitted a couple of small proposals looking at funding opportunities to really reach out to the different populations locally, and something that we have recognized is then the strategy, it may be different among different populations. So, it's always helpful to know what are the under engaged or underrepresented minorities in your area to develop a strategy. We are trying to, we have this program where we're trying to reach the African-American community and we are discussing the importance of early diagnosis and access to adequate care. And we're bringing some of this information as educational opportunities, going to the local churches and talking about what is Parkinson's Disease. Why it's important to have a diagnosis and to engage with a provider that's an expert on the field.
And one critical point of that approach is that we need to open our doors. So, we're actually offering relatively faster appointments compared to someone that they will just pick up the phone and call our clinic with the idea that we can direct their care, even if they don't have Parkinson's, but just have a much more open dialogue between the community and the providers and open access as well to our clinics. In the Hispanic population, we're doing something very similar.
But we are trying to reach out to other leaders in the community that can spread the word and talk to other families and other patients to really try to get the right information to a larger group of people as much as possible, so we can also get them into our clinics. The Parkinson's Foundation, it's also really ahead trying to promote these initiatives when it comes down to research. And there are variety of groups across the countries that are called promotorres. That what they do is that it's a training program for family members that want to be engaged, that physician or other health care providers will educate and train somebody that can go then go back to the community to go to the local support groups, to go back to churches, to go back to community events and then be a promoter, being somebody that can promote education and understanding of the disease, and then facilitate that dialogue and connection with the local movement disorders center to really try to get into our clinics much more efficiently and facilitate some of those challenges, including, education and transportation and the needs that are specific to the diverse population.
Host: Wow, that was so informative. So, Dr. Ramirez-Zamora, given the complexity and increasingly complex treatment algorithms, and, you know, we're learning more about this disease all the time. Tell us a little bit about the importance of a multidisciplinary approach for these patients specifically, and also as physicians play a critical role in addressing all these public health concerns you've just brought up, tell us a little bit about how you would like physicians to work together, work with you all at UF Health Shands Hospital, and this multidisciplinary approach to tackle these diversity challenges.
Dr. Ramirez-Zamora: You're absolutely right. With the increasing complexities in the management and the understanding of this disease, we realize we recognize that you can not do it all. We need a team of providers and a team of physicians that can really help to target all the symptoms. As I mentioned before, Parkinson's has changed from a disease that will affect primarily movement into a disease that has a variety of motor and non-motor symptoms that requires the assistance and the help and the expertise of different providers ranging from pain management, psychiatry, psychology, urology, GI, you name it. So it's really critical to develop a multidisciplinary approach among physicians, but also among other providers that are critical for patient care, including occupational therapy, physical therapy, social work, speech therapy, swallowing providers.
And at Shands, at UF Health and Norman Fixel Institute, what we're trying to do is to create a center where the patient will be able to see most of the providers that they need in one visit, where when you come to the center, you can have access on the same day and on under the same roof to a physical therapist, a psychiatrist, a dietician, and maybe a neurologist or a neurosurgeon, if you need it, where they can all talk among them and then come up with a single unifying plan for the patient. There's nothing worse than having multiple providers with diverging decisions or suggestions. It's very confusing for the patient.
If I said, well, let's try to do this. And then they have another provider that says, no, I don't think that you should do that. And then another provider that is like, well, I don't know. You should try to listen to whoever the first person told you. So, it was very confusing. So having an open communication among all these different providers is key to come back to the patient and provide a unifying suggestion and a unifying plan of action.
And this is particularly critical in patients that are underrepresented. Part of that is because they may have problems with access and they're not used to this type of care, in general. The care is fragmented and there are challenges from insurance coverage or appointments that makes it quite challenging to be able to organize and coordinate this type of care. So, having that open communication and then having a single place where the patients may be able to get most of the care that they need at once, keeping in line with our hope that we see the patient as the sun and all the providers revolve around that, that may be able to break some of those barriers when it comes down to providing better care and access to patients of underrepresented minorities in medicine.
Host: Wow. So beautifully said, Doctor. That was really an excellent episode. Thank you so much. Do you have any final thoughts you'd like to leave other providers with about referral and the importance of these diversity challenges you've discussed here today for Parkinson's patients?
Dr. Ramirez-Zamora: I would like to say, that I've been talking a lot about access and for us to be able to provide care, we need to be able to communicate with everyone in the community and allow that dialogue. So there's the best doctor is not necessarily the smartest doctor, is the one that is available.
So we need to be available. And we're making that a big priority at our center that if somebody is referring patients and somebody needs to be seen, that we can actually have a policy that would allow these patients to come through our doors. We're also really increasing our diversity as well. I'm talking about diversity in all levels, making sure that when patients come to our clinic, they feel that they can talk to anyone. They can feel welcomed that they feel that somebody that looks at themselves and they can communicate freely and openly. That we have also part of our team, that diversity, cultural diversity, ethnic diversity, that would allow us to really engage these communities. And have them to come back and trust us so we can really provide better care and learn more about how can we really help them going forward.
Host: Thank you so much, Dr. Ramirez-Zamora. What a fascinating interview this was. Thank you for sharing your incredible expertise for other providers today. And to refer your patient or to listen to more podcasts from our experts, please visit UFhealth.org/medmatters. And that concludes today's episode of UF Health Med Ed Cast with UF Health Shands Hospital.
Please also remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
Additional Info
- Audio Fileuf_health_shands/ufhs056.mp3
- DoctorsAlzghoul, Bashar;Mehta, Hiren
- Featured SpeakerBashar Alzghoul, MD | Hiren Mehta, MD
- Guest BioBashar Alzghoul, MD is a Pulmonologist at UF Health and Assistant Professor of Medicine at UF College of Medicine.
Hiren Mehta, MD is a Pulmonologist, UF Health Assistant Professor of Medicine. - TranscriptionMelanie Cole (Host): Welcome to UF Health Med Ed Cast with UF Health Shands Hospital. I'm Melanie Cole, and I invite you to join us today, as we discuss COVID-19 from intensive care unit to outpatient clinic. Joining me in this thought leader conversation panel is Dr. Bashar Alzghoul, he's a Pulmonary and Critical Care Specialist at UF Health Shands Hospital and an Assistant Professor of Medicine at the University of Florida College of Medicine. And Hiren Mehta, he's a Pulmonologist and the Medical Director of the Intensive Care Unit at UF Health Shands Hospital. And he's an Associate Professor of Medicine at the University of Florida College of Medicine. Doctors, thank you so much for joining us today. What an important episode this is. Dr. Mehta, I'd like to start with you. Can you help us to understand the best practices and standard of care for COVID-19 patients in the ICU at UF Health Shands Hospital?
Hiren Mehta, MD (Guest): Thank you very much for having me on the call and on the podcast. So, you know, it's been more than 18 months that we've been dealing with COVID-19. And what we have seen is we have seen the disease evolve from the original surge early in the year to a new surge that we had later in the year, a month or two ago.
And when the patients end up in the intensive care unit, the main reason why they end up is because they're having severe respiratory distress. And as they approach the intensive care unit, we focus on a couple of aspects of management. One is from a breathing standpoint, how can we help a patient who is struggling to breathe and we quickly escalate based on patient's needs from high flow oxygen to non-invasive ventilation to having them on a mechanical ventilator.
Once the patients get on a mechanical ventilator, we closely follow their blood gases, see how their oxygenation is doing and if need be, we put them on high PEEP, high FIO2 settings. We start paralyzing them, if the compliance of the lung is not good. We also start them on inhaled pulmonary vasodilators like Flolan, nitric oxide.
And despite of all the measures, if the patient's still struggling to breathe and still struggling to oxygenate, then we prone them. And that's really the ventilator management aspect of it. From a medication aspect, we have all these patients on steroids, as we know that dexamethazone has improved mortality in patients with severe COVID-19 pneumonia.
We also have some form of IL6 inhibitors. The most common go-to is tocilizumab. As again, that's that has shown to improve mortality in these patients. Despite of all these measures, if we can not help the patients to oxygenate and ventilate then the rescue mortality really is veno venus ECMO. We do offer venovenus ECMO as a bridge to recovery or as a bridge to lung transplantation.
Bashar Alzghoul, MD (Guest): Yeah. I would like to, you know, to second, as you know, the second surge that you have the, of this year, we noticed a lot of, for example, pneumothorax and a lot of pneumomediastinum that we didn't see as, as often in the first. Which basically just adding to what Dr. Mehta said disease did evolve indeed. Maybe it's that because there's a different variant or maybe the patient population was a little bit different, but that's, what we noticed as well.
Host: Well, thank you so much, gentlemen. So Dr. Alzghoul, is there any available literature about long-term care, outpatient care for COVID-19 patients if and when they get out of the ICU? What do we know that we didn't know a year ago about long hauler complications, you know, post COVID complications?
Dr. Alzghoul: That's a very important question. And I'd like to, you know, to highlight that we as pulmonologists and it terms of this, we get to see the full spectrum of the disease. So when you see the patients, when they're at their sickest point in the ICU, when they are proned and paralyzed, and when everyone is starting to give up on those patients, but we, you know, we continue high standard care for them; and then we get to see them on the floor after they were downgraded from the medical ICU to the floor, with a tracheostomy tube. And then we get to see them after they leave the hospital in a long-term facility. And then we get to see them in our clinic and I've had, you know, extremely happy, the last two weeks when I was on the pulmonary consult service, taking care of these patients in the medical floor, and I've seen the patient that I took care of two or three months ago in the ICU. At that time when they where in the ICU, they were proned, on high ventillator settings. They were like on dialysis. And then I took care of them just last week, the same patients, I was like taking you know, decanulating their tracheostomy tubes while they were on the floor. I'd maybe decanulated at least five or six patients in one day, which is unprecedented. Like when generally speaking patients will get posts ICU tracheostomy, that thing usually stays for a prolonged period of time.
But these patients, because they got the and they got standard of care high quality care throughout the hospitalization; we were able to decanulate a lot of these patients. And to answer your question, you know, these longterm complications of post COVID infection actually depend, it does, there are a lot of valuables in the in discussion.
So it depends like when, how sick was the patient to start with, the comorbidities, the body mass index of the patient coming into the illness. And then how, how difficult was the hospital course? Whether it was it was complicated by acute kidney injury, whether he required the analysis, whether there was a superimposed infection and whether, you know, all of these variables play in, into the term complications and the long-term complications can vary from mild symptoms, like such as fatigue, shortness of breath, cough which even in the patients with mild COVID disease, it can be as high as maybe 30 to 40% of those patients suffer from symptoms like that. It can be also some other psychologic symptoms that are related to their stay in ICU. The ICU stay by itself can be extremely traumatic and these patients can have like post-traumatic stress disorder kind of symptoms, anxiety. They can start having flashbacks and then there are other long-term complications, you know, whether they had like a myocarditis during their stay, you can have a long term heart failure. Whether they had acute kidney injury. They can be on dialysis for a prolonged period of time and then relate it to the COVID infection itself of the lungs.
They can suffer from a long term, like fibrotic lung disease that sometimes can be irreversible and sometimes can be treatable and sometimes can be recoverable, but require a long period of time. So it's it's a wide spectrum of complications, that depends really on how, how bad was the disease to start with and, you know, the comorbidities of the patient and all that.
Dr. Mehta: May I say something Doctor Alzghoul. There've been some talk and some thought about the antifibrotic medications, like pirfenidone, et cetera, which is used for our interstitial lung disease patients and some people are looking into it. What are your thoughts on anti-fibrotic medications for post COVID fibrosis?
Dr. Alzghoul: Yeah, that's a, that's a really interesting and important question. So there's to my knowledge there are a couple of clinical trials now, clinical trials in India, and there was another international clinical trial looking at fibrotic medications that Dr. Mehta is referring to, pirfenidone and an antagonist, basically.
So there's, early in the pandemic even like, outside the US especially outside the US, there has been a lot of off label use of pirfenidone early on trying to see if it does have any benefit, because it does have some theoretical benefit that it might protect the pneumocytes and other cells if the patient is suffering from cytokine storm. There's a theoretical benefit it might prevent the lung fibrosis. So some people have been using it as off-label use, but to this date, I'm not aware of any clinical trial that's proves the benefit of these two medications. I think I'm going to stay optimistic.
I think maybe, or it makes sense to follow or to start using these medications early on, rather than wait after the patient comes and see them in the clinic. But I would wait for the results of the clinical trial.
Host: Dr. Mehta, then can you tell us what kinds of services and care you provide at the University of Florida College of Medicine, and UF Health Shands Hospital in terms of recovery and discharge. Tell us a little bit about the importance of the multidisciplinary approach for these patients.
Dr. Mehta: That's a great question, Melanie. As you know, anything that we do in intensive care unit requires a multi-disciplinary approach. Anytime you have the sickest of the sick patients that you're taking care of, you need all hands on deck. So to give you an example, when we were our surge and we took care of the COVID-19 patients, it truly was a team effort in the best sense that you will ever see. And this starts with the nurses who are taking care of these patients, constantly monitoring these patients, making sure they're oxygenating well, making sure that they're getting their medications, making sure that they are getting their blood draw and blood gases and everything.
The respiratory therapist who played a significant role in helping manage the airways of these patients. Also adjusting the ventilators, checking the blood gases, following up on the blood gases and taking care of the ventilators. In the acute phase, physicians who made admissions, who admitted these patients to the intensive care unit, took care of the medications that they need, did the procedures that they need, including, you know, dialysis catheters, central lines, intubations, everything that goes on along with it, monitoring these patients for response, updating the families. Then pharmacy played a significant role with all the medications. Some of these medications are highly specialized medications and they helped us work very closely with our teams and helped us get those medications through the pharmacy in a timely manner.
Once they got through that acute phase, and I apologize if I missed out on anyone because you know, when you're running an operation and taking care of these sick patients, everybody from supply chain to our environmental services; everybody plays a role in taking care of these patients to the highest administration. Once these patients started getting a little better and they moved along the system, that's when the physical therapy, occupational therapy, rehab, speech therapy, nutrition all that came into play and helped them because the patients being on ventilator and being in the ICU, lost a lot of muscle mass.
And so they all help mobilize the patients, get them stronger and get them through the next step to the, out of the intensive care unit to an intermediate care unit and eventually out of the hospital. So it, it truly was a team effort in the best sense that I've seen. Dr. Alzghoul, I don't know if I missed out on anybody or if you want to add on anyone.
Dr. Alzghoul: As I said earlier, we in the pulmonary and critical care division, we continue to see these patients, even when they leave the ICU, because you know, a lot of these patients end up with a tracheostomy tube and the tracheostomies, they need a respiratory therapist and they need a pulmonologist sometimes to take care of them.
Especially if they have complications, we have an advanced interventional pulmonary service. If there's like any tracheal stenosis or any airway complications, we have an interventional pulmonary service that can take care of that. And we, in the pulmonary service, we continue to see these patients on, on our consult service while they are in the hospital.
And when they leave to one of our sister LTak facilities until you know, we, we get them to the decannulation point. And if we reach a point where these patients are requiring a lot of oxygen after a prolonged period of time, let's say eight to 12 weeks or so we also have an advanced and high volume lung transplant program.
We worked with our colleagues in the lung transplant program and we refer those patients at that point to, for evaluation for lung transplant. A lot of the time, it's very important to recognize some of the other acute events that happened during the hospitalization. These post COVID patients, they can suffer from pulmonary embolism.
They can suffer from lung abscesses, super-imposed pneumonias, so sometimes they have long-term organizing pneumonia. So that's why we continue to see them. And we evaluate on case by case basis and we treat them accordingly. Once they leave the hospital, we see them in our clinic you know, depending on how sick the patient was and how old, and depending on the co-morbidities, we either see them six to eight weeks or so after discharge.
And we try to allocate them to, for the available resources, you know. If they need the psychology help, if they need cardiology assessment, if they need a extensive cardio, pulmonary rehab and all of that, we help these patients achieve that goal. And from pulmonary standpoint, if they need any long-term treatment, like some inhaler therapy or management of their volume status to diagnose, if they have like a new pulmonary embolism or pulmonary hypertension, we still see them in our clinic and deal with these long-term complications as well.
Host: Well, thank you for that. So, I'd like to give you each a chance for some final thoughts. So Dr. Alzghoul, can you tell us a little bit how Tele-health has augmented your ability to care for COVID patients after discharge? What's involved? We've talked a little bit about follow-up. Can you tell us a little bit about the difference in care for patients that are discharged home versus patients that are discharged to a supervised residential care for recovery and available resources for longterm management of post COVID fibrosis, including lung transplant.
Dr. Alzghoul: Yeah. So even the patients that go home from the hospital, even the patients that have mild to moderate disease, there was some studies out there. So just think that maybe 10 to 20% of these patients after a month of discharge, they are still, they still have some degree of disability.
They still cannot do their, what they used to do before hospitalization. I'm not talking about the sickest patients that were in the ICU. I'm talking about, patients who just went to the hospital with COVID, where on couple of liters oxygen and then were discharged. They still suffer from some long-term symptoms.
So that's why during the pandemic, we managed, you know, we increased the number of the patients that we see in our clinic, by utilizing the Telehealth service, you know, we are able to reach those patients at home and have some you know, a long distance encounters with them to see how they are doing.
And without having them come to the healthcare system and being exposed to catching an infection or especially if they're not able to drive themselves. And so, so Telehealth has extended our abilities to, to reach these patients. Now as for, for the patients that go to rehab facilities or long-term care facilities you know, as I said, we do have a rehab, like a rehab facility associated with our hospital and as well as a long-term facility that we have here, and our group also continues to see these patients while they are there.
And we help them achieve their goals. We help them go through the physical therapy to gain their strength and build up their muscles. And we follow them until they get decannulated while they are over there or until they get discharged from those facilities. And then we hook them up with our, our clinic as outpatients.
Host: What amazing and wonderful work you both are doing and thank you so much. Dr. Mehta, last word to you. Are there any drugs or investigational therapies that you find exciting right now for COVID? What can you share about what you're doing at UF Health Shands Hospital? Wrap this all up for us with anything exciting that you can share with other providers about where you see this going or what you hope to see happen.
Dr. Mehta: So that's a bit, a big question, Melanie, because as you know that despite of all the research and all the efforts that have been focused on COVID for the last two years, we still struggle. We still struggled with surge. We had a lot of mortality and we had a lot of morbidity with this.
So, I mean, when you asked me this question, there's two parts to it. One is what's actually happening and what I hope that would happen. So what's actually happening is that the medical community and the scientific community in general has made COVID its priority over the last two years. Never, ever in the history of medicine have we seen a vaccine for a viral illness being so effective and rolled out at a pace that we saw for COVID. So, so that just tells you the pace at which the research is going on in the field. And the research is focusing on everything from preventing COVID, which includes vaccination, to targeting COVID early on in the disease so that we can prevent these patients from getting admitted in the hospital and being as sick as they are.
And that includes monoclonal antibody. And recently there's another medication, which is hopefully going to get approval soon, which is going to be a pill. It's an antiviral medication, which is going to prevent patients from, once the patients are diagnosed with COVID from having severe illness. So the research is focusing on that part. The research is focusing currently on aspects that include, once these patients are hospitalized, how can we best help them to get better quicker and not end up in the intensive care unit?
And that is everything from steroids to antivirals, to anticoagulation and different types of anticoagulation modality to prevent this patient from getting critically ill. And once they do get critically ill, there has been a lot of research focusing on how quickly to get them better without causing significant damage to their lungs.
And again, that we talked about tocilizumab and IL6 inhibitors for that, so on and so forth. When it comes to UF Health, UF Health from the beginning of the pandemic has been very active in clinical trials for COVID. We have so far had at least 10 active trials that we have enrolled COVID-19 patients for.
And that included patients from, included patients who are in the intensive care unit, not in the intensive care unit, on the regular floors. These include multinational studies. Multi-institutional studies and investigator initiative projects locally. So UF Health has been very active when it comes to research, on this front as well.
What I really hope is that we find that and I think the prevention is the going to be the biggest deterrent and the vaccines are so far proven, very effective. And as any virus, I think this virus is going to continue to mutate. And I hope that we continue to find effective prevention for ever mutating coronavirus. And we don't have to deal with the surges in 21st century where we can prevent it.
Host: I just didn't know if Dr. Alzghoul, did you have any little final thoughts? Cause I kind of asked you a lamer little question then Dr. Mehta, who got to really get into the meat of it. Do you have anything you want to add before I wrap it up?
Dr. Alzghoul: Yeah, absolutely. So it's two things. So as Dr. Mehta said, prevention, I hope everyone would get vaccinated. I got a, in my vaccine, all of, all of the people in our division got vaccinated. I hope everyone in the community will get vaccinated. So that as Dr. Mehta said we won't have to deal with some of those surges and with the winter and early spring.
And the other thing, what I found is it's the little things, just be patient. What these patients need is time. And what we need to do as healthcare providers is to provide evidence based medicine to help them recover in this long journey of recovery. They need time. We just need to follow the guidelines and we need to be patient with them.
And as I said, I've seen a patient, many patients actually, who were extremely sick on ECMO, got tracheostomy, where paralyzed, where proned; I've seen them recover. I've seen them go home and see their family. I've seen them watch a soccer game after three months of being ill. So we just need time and need to provide evidence-based medicine during that time.
Host: What an amazing episode and so informative. Really, really great information you shared today. And thank you so much for coming on with us and sharing your incredible expertise the both of you. Thank you again. To refer your patient or to listen to more podcasts from our experts, you can always visit ufhealth.org/medmatters.
That concludes today's episode of UF Health Med Ed Cast with UF Health Shands Hospital. Please remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
Additional Info
- Audio Fileuf_health_shands/ufhs055.mp3
- DoctorsBrisbane, Wayne
- Featured SpeakerWayne Brisbane, M.D.
- Guest BioWayne Brisbane, MD, is an assistant professor of medicine in the Department of Urology at the University of Florida College of Medicine. Dr. Brisbane received his undergraduate degree in Biology, cum laude, from Seattle Pacific University and his medical degree from Loma Linda University School of Medicine.
Learn more about Wayne Brisbane, M.D. - TranscriptionMelanie Cole (Host): Welcome to UF Health Med Ed Cast with UF Health Shands Hospital. I'm Melanie Cole and today we're talking about prostate cancer focal therapy. Joining me is Dr. Wayne Brisbane. He's an Assistant Professor in the Department of Urology at the University of Florida College of Medicine. Dr. Brisbane, it's a pleasure to have you join us today. Before we get into prostate cancer focal therapy, can you tell us a little bit about your background and expertise in focal therapy and how this hasppened?
Wayne Brisbane, M.D. (Guest): I am a Prostate Cancer Specialist. That's pretty much all I do and see, and treat. I did my residency at the University of Washington and did a lot of surgery for prostate cancer. And then I went and did a fellowship, at UCLA and in the second year of that fellowship, found focal therapy through my mentor, who's Leonard Marks and does a lot of focal therapy out in California. And he showed me a lot about prostate cancer and focal therapy. And I really found it to be a very compelling treatment option for some men. And so, I did about 150 focal therapies with a variety of different energies, including cryotherapy, high intensity focused ultrasound or HIFU, and laser ablation of the prostate.
We also published a bunch of papers on focal therapy. Who's a good candidate, how we do focal therapy better. And then when I was looking for positions was very interested in coming out to Florida under our chairman, Dr. Su, and he felt like this was an area that we could expand for our patients.
Host: Well, thank you for sharing that with us. So, give us an overview of prostate cancer focal therapy, and really talk about its role as a middle ground, as it were, to the treatment of prostate cancer as a means of bridging the gap between a radical prostatectomy and active surveillance, all the different treatment modalities out there.
Dr. Brisbane: Prostate cancer focal therapy, the main idea behind it is that you're treating just the cancer and you're trying to spare critical structures that surround the prostate. And the prostate's kind of in a confluence of many different organ systems. The prostate is responsible as far as mother nature is concerned, for reproduction. So it produces the thing like proteins and sugars that help the sperm survive. The urine, as it exits, the bladder goes through the prostate. It sits right next to the rectum. It also sits right on top of a couple of nerve bundles that are responsible kind of for the hydraulics of erections.
So it's in the confluence of a lot of different things. And prostate cancer is really common. The prostate is working hard all the time, under the influence of testosterone and there's a bunch of brake pedals that kind of have the prostate stop its growth and start working on function. If any of those brake pedals malfunction, you can get cancer and over the course of a man's life, he has a 12.5% risk. And so that translates into about one in nine men getting prostate cancer at some point and it causes about a little over 33,000 deaths per year. So prostate cancer is very prevalent.
So the really big, important thing for prostate cancer is you have to risk stratify it. There's basically three main buckets. Low risk, intermediate risk and high risk. And that's very important for prostate cancer because it tends to be in the family of all cancers, a slower growing cancer. So it's not like treating pancreas or brain or lung cancer. And so it's really important once somebody gets a diagnosis of prostate cancer to put it in one of those risk buckets. And so there's, the Gleason score is the grade. And so the Gleason score is how it looks under the microscope, obviously.
And if it's in the 3+3 category and the PSA is less than 10 where the provider feels like they can't feel it, all those are going to be in the low risk bucket or category. Those patients are often able to be treated with nothing, just active surveillance.
And that's been a paradigm shift as things have gone through the last 10 years. High risk cancers are kind of Gleason scores greater than 4+4, PSA is greater than 20, T3 disease, things that feel like they're kind of trying to extend into the neurovascular bundle or the seminal vesicles.
And oftentimes those are best treated with surgery or radiation, but then you have this big family and which is going to be your Gleason 3+4 and 4+3, where they can probably be treated with a lot of different options. So, some men with low volume, 3+3 or 3+4 can be watched. There's some active surveillance going on there. Men with high volume 4+3, probably need some surgery or radiation, but there's an option to provide these men focal therapy and what we're doing with focal therapy is we are trying to identify the tumor. So that's the first step with focal therapy is some kind of imaging.
And then second, ablate the tumor, which would be trying to ablate just the tumor and leave everything else around spared and then surveilling the patient, over years because these tumors can pop up other places or they can recur at the margins.
Host: Well, then differentiate for us between this focal therapy and whole gland therapy and help us to understand the limitations to this type of focal therapy.
Dr. Brisbane: When I was a kid, I was one of four kids and we were responsible for cleaning our bathrooms and so, we had this little spot of mold that kind of popped up in the corner of the bathroom. We scrubbed it and didn't pay attention to it for a while. And finally let my mom know about it. And she came down and it turned into a huge deal where we actually had to take out the dry wall and it was much more aggressive on the other side of the drywall than it initially had been presenting. If you were to equate this mold with prostate cancer, it's got a lot of similarities.
And so if you have mold in your bathroom, and you want to take care of it, a whole gland therapy, as far as surgery would be just removing the entire bathroom. A whole gland therapy, as far as radiation would be kind of taking some kind of ablation, like a flame thrower or something silly, but basically ablating the entire bathroom.
And the problem with that is it causes a lot of collateral damage. You have to find a new place to urinate or all the kinds of tissue is no longer functional. But with focal therapy, what you're trying to do is you're going in and you're just removing the mold and leaving everything else there.
So the bathroom is still functional. What that equates to for patients is they're going to have many fewer side effects as far as erectile dysfunction, or leakage or urinary urgency. But they'll have treatment of their cancer. The careful thing is you have to monitor these patients. And so that's a really big differentiation between a full whole gland therapy and focal therapy. You're going to have to continue to monitor patients long-term because the mold can come back or the prostate cancer can come back at different locations. And you have to be able to monitor them continually in order to kind of mop up when that happens.
Host: Well, then as you're telling us about some of the limitations and what a great educator you are, that was an excellent explanation; can you characterize for us the ideal patients? Speak about patient selection for this type of therapy?
Dr. Brisbane: So, your ideal patient is going to be not your low risk and not your high risk, it's that big group in the middle. So, it's going to be intermediate risk patients. So Gleason 3+4 or 4+3 easy way to remember it is just Gleason 7 cancer. They're going to need to have some kind of imaging and MRI is the best kind of imaging.
There's also PSMA PET scans and micro ultrasound, which we're doing at University of Florida, quite a bit. The imaging is all in effort to localize the tumor. So, we're really make sure that we're adequately treating, A, that we're establishing a good margin. So treating up to the extent of where the tumor is, and then also, you know, it doesn't really work to treat invisible disease because if I can't see it on an MRI, it's hard for me to go through and actually do a good job of putting needles in and ablating the tissue.
So you're going to have intermediate risk disease. It has to be visible on an imaging modality, and then you don't want the tumors to be too big. So, at times people will say it needs to be less than T2C, which the technical term for that is just needs to be on one side of the prostate.
There's some nuances there, but really big tumors are probably not the best candidates for this kind of treatment. And then you also, probably want patients who can benefit from this longterm. So prostate cancer treatment, you're not talking about benefiting patients within a year or two years. It's oftentimes over five to 10, even 15 years. And so you really need to look at the patients and say, are they healthy? Are we expecting them to live a ten-year lifespan?
Host: So interesting. So then tell us a little bit about the outcomes that you've seen or the efficacy of focal therapy and really what you would like to see happen in the future with this technology.
Dr. Brisbane: Yeah, so the outcomes are trally the carrot. That's what's really nice about this is so far, when patients get focal therapy, they tend to have very limited side effects. And that's where, you know, it's very appealing to patients. And so we will have a lot of your patients coming in to talk to you about focal therapy will say, oh, this is really what I want. What they're saying is I really don't want bad side effects. I really would like to get rid of my cancer and not have side effects, which is definitely the carrot. So, because we're trying to not damage any adjacent critical structures, mainly the nerves, and the bladder, the urethra to some extent and the external sphincters that control continence. Patients tend to do great as far as urinary side effects. They, you know, they oftentimes actually urinate better after these procedures than when they started. As far as erectile function, that's a little bit more complicated. I tell my patients that about 50% of patients are going to have the same erectile function after their procedure, as they came coming in, about 25% are going to be a little bit worse and unexplainably within our data about 25% get a little bit better. What I tell people is it's going to be kind of variable what your erectile function is coming out of the procedure, but it's a lot gentler than radiation or surgery.
Host: Wow. What an informative episode this was. Dr. Brisbane, as we wrap up with your incredible expertise in this area, what projects are you working on or what will you be working on at UF Health Shands? And what would you like urologists and other providers to know about prostate cancer focal therapy?
Dr. Brisbane: Yeah. So a lot of the things that we're doing within our research is really using the imaging to its fullest extent. So we're using, at least bi-modal imaging and occasionally trimodal imaging to inform exactly where the margins need to be and so we're using micro ultrasound, MRI, and occasionally PSMA PET scans to kind of really localize where the tumor is and get our margins, right. There's a lot of ways to kill the cancer. But there's only one margin. And so when you see patients coming in and saying, oh, you know, I want Tulsa Pro or I want HIFU, or I want a focal laser ablation or cryo or a photodynamic therapy, NanoKnife these are all technologies that kind of do a good job of treating the tumor, but really what we're working on is making sure that the margins for treatment are perfect. And then, the other thing is we're trying to figure out kind of a bunch of trials to see how should this be done correctly with neoadjuvant therapies? How can this be done in order to kind of do a nerve sparing focal therapy. So can we warm the nerves? Can we cool the nerves? What are the ways that we can really optimize our outcomes while still taking care of patient's tumors? And then, you know, we're also trying to run some trials where we compare outcomes in regular therapy versus focal therapy. So, there's a lot of work in this space that needs to be done. And it's really an exciting space to work in.
Host: Certainly an exciting time to be in your field. Thank you so much, Dr. Brisbane for joining us today. To refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. That concludes today's episode of UF Health Med Ed Cast with UF Health Shands Hospital.
Please also remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
Additional Info
- Audio Fileuf_health_shands/ufhs054.mp3
- DoctorsZarrinpar, Ali;Ramnaraign, Brian;Hughes, Steven;Hitchcock, Kathryn
- Featured SpeakerAli Zarrinpar, M.D | Brian Ramnaraign, M.D | Steven Hughes, M.D | Kathryn Hitchcock, M.D
- Guest BioAli Zarrinpar, MD, PhD, is an associate professor in the Division of Transplantation and Hepatobiliary Surgery at the University of Florida College of Medicine. n
Learn more about Ali Zarrinpar, MD, PhD
Brian Ramnaraign, MD is an assistant professor of medicine in the division of hematology and oncology at the University of Florida College of Medicine.
Learn more about Brian Ramnaraign, MD
Steven J. Hughes, MD, is a professor and chief of surgical oncology at the UF College of Medicine. He also serves as vice chair for the department of surgery.
Learn more about Steven J. Hughes, MD
Kathryn Hitchcock, MD, PhD, is an assistant professor in the UF Health department of radiation oncology.
Learn more about Kathryn Hitchcock, MD, PhD - TranscriptionMelanie: Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole. And today, in this round table panel, we have a thought leader conversation as we discuss neuroendocrine tumor management, the state-of-the-art in 2021, including PRRT.
Joining me in this panel is Dr. Ali Zarrinpar, he's an Associate Professor in the Division of Transplantation and Hepatobiliary Surgery; Dr. Brian Ramnaraign, he's an Assistant Professor in Hematology and Oncology; Dr. Steven Hughes is the Chief of Surgical Oncology; and Dr. Kathryn Hitchcock, she's an Assistant Professor in the Department of Radiation Oncology, and they're all at the University of Florida College of Medicine. Thank you, doctors, for taking part in this today and for joining us.
Dr. Hughes, I'd like to start with you. Can you tell us a little bit about the incidence and prevalence of neuroendocrine neoplasms and what you're seeing in the trends?
Dr. Steven Hughes: Good morning. It's my pleasure to be with everybody today. These are actually very rare tumors affecting far less than 1% of the overall population. They are fairly common for us at the University of Florida as a tertiary referral center. Majority of them are incidentally noted and found because of other reasons, rather than actually causing symptoms. And if one actually performs autopsies, the number of patients that have microscopic neuroendocrine tumors is actually greater than 10%. So the majority of these tumors are silent, small, and very slow-growing.
Melanie: Dr. Ramnaraign, can you please give us an overview of the current management of neuroendocrine tumors if they're found whether incidentally or not? And how has treatment evolved over the years?
Dr. Brian Ramnaraign: Certainly, Melanie. The treatment of neuroendocrine tumors really should involve a multidisciplinary approach with radiation-oncology, medical-oncology and surgical-oncology. And the most important question to ask is the extent of the patient's disease. Is there a single lesion? Are there a few lesions or is it metastatic cancer?
A patient with a single neuroendocrine tumor or what we would call as oligometastatic, few metastatic lesions, may actually have a potentially curable disease. And that would usually involve a combination of a surgery, medical oncology, and radiation oncology, a patient with diffusely metastatic disease that's found later on in their disease course, we only have palliative options for. And that would involve systemic therapy options, including somatostatin analogs or even localized radiation therapy with a treatment called PRRT.
Melanie: So Dr. Hitchcock, on to you, how have advances in radiologic imaging significantly augmented your diagnostic and therapeutic capabilities? Can you speak about any that have really changed the landscape of treatment for you that helped to ensure superior staging and prognostication of neuroendocrine neoplasms?
Dr. Kathryn Hitchcock: Absolutely. This is an exciting topic where a lot has changed just in the time that I've been involved in medicine. Just like all cancers, imaging of this type of tumor has improved a lot since the late 1980s. We've got CT scan, MRI and PET now, all of which work for these tumors. But in addition to that, for these low-grade neuroendocrine tumors, we have a molecule called Dotatate that really likes to stick to this somatostatin receptor, which is very common on cells of these tumors. We're able to attach to that atom of gallium and then do a PET-type scan in order to see where the tumor is. The advantage of that over a regular PET scan is it's more specific to these types of cells so that you get a lot less confusing highlighting of things like inflamed hair follicles, for example.
Melanie: Dr. Zarrinpar, this one is for you. Do you have any specific recommendations for other providers as to if their patients are presenting with a neuroendocrine tumor? What should they be scrutinizing that could impair survival, might require dedicated therapy or help their mortality rate?
Dr. Ali Zarrinpar: So neuroendocrine tumors are rare. of that, partly because of that, the systemic therapies for neuroendocrine tumors are not really well established. So what providers need to know and what patients need to know is that for this kind of rare disease, they need to go to centers, regional centers, that are specialized in this kind of care.
These centers will be able to provide the latest in systemic therapy, physicians that have more experience than the local area physicians just because they see more of these patients. And they'll be able to provide more options like PRRT for example. And this multidisciplinary care that these regional specialized centers can provide are really absolutely necessary for these rare tumors.
Dr. Steven Hughes: Yeah. It's Dr. Hughes here. I was going to add to what Dr. Zarrinpar said, which is that, you know, one of the things that our center has value to add is that a number of these tumors actually can be safely followed by serial imaging over time. They don't all necessarily have to be removed at the time that they're identified. Some of these, the surgical treatment is more dangerous than observation is what I'm trying to say. But understanding which ones can be safely observed versus which ones need to be removed or treated more aggressively in a multidisciplinary care fashion really requires a high volume of these very rare tumors and that's the benefit we have at the tertiary referral center.
Melanie: Dr. Hughes, following up on what you just said, what are some of the considerations that go into knowing whether these cancers are resectable?
Dr. Steven Hughes: That's a great question. And to be honest with you, there's a variety of factors. Size of the lesion is one of the most important features, the location and where it arose. The biology of neuroendocrine tumors is actually dependent on the organ in which it arose. And so these tumors can arise in the stomach, in the small intestine, in the pancreas, in the colon, even in the esophagus. So anywhere in the gastrointestinal tract, one can develop a neuroendocrine tumor. And so the location of where it arose sometimes leads to just safely knowing that it can be observed for a period of time, sometimes leads to a recommendation for a biopsy to get an understanding of what's called the grade of the tumor, which is basically a measurement of how fast it's growing.
And then finally, of course, like what Dr. Hitchcock mentioned, some advanced imaging may give us some insight into whether the tumor has the capacity to break free of words started in spread to lymph nodes or the liver or even other areas. And so all of those things can come together to put together a comprehensive plan for a patient. Oftentimes this can mean let's just look at it again in six months.
Melanie: And we're going to get to PRRT, which is really what our topic is centered around. However, Dr. Zarrinpar, before we get to that, is liver transplant ever used to cure these patients? And when liver resection is used? Is it appropriate to remove a small area? Do you have to take out an entire lobe of the liver?
Dr. Ali Zarrinpar: So for patients with liver metastases and the very, very rare patient with a liver primary neuroendocrine tumor, when the tumors are well-differentiated, low grades and there is not diffused liver involvement or compromised liver function or really disease outside of the liver, resection or transplantation is a great option.
And the reason for that is that these tumors are generally indolent and systemic therapies are limited. And so if we can remove all the tumor or, you know, the vast majority of the tumor to get the patients either disease-free or deal with a lot of the side effects or the results of the tumor being there, then resection or transplantation would be an option.
Now, this is going to come back for the vast majority of the time. The question is, how do we decide which of these tumors is least likely to come back. For transplantation, there are a number of factors that patients will need to meet before being eligible for transplantation. And these are set out by the National Review Board.
Generally, you know, the tumors need to be just in the liver. They need to have scans that demonstrate the lack of metastasis outside of the liver. This needs to happen every three months. There needs to be a biopsy that shows lower grades. And they can't ever have any solid organ metastases outside of the liver. Those are the reasons for these things coming back very quickly. And the immunosuppression that liver transplantation needs makes these tumors actually grow faster. And so that's why patient selection is a big deal.
For liver resection, and I'd like to include local regional therapy like arterial embolization or ablation as a part of that liver resection modality. You know, that depends on how many tumors there are, whether there are tumors outside of the liver or not. And whether these tumors can be removed without really affecting liver function. And patients with liver tumors, I think surgery should be part of the armamentarium.
Melanie: Well, thank you so much, Dr. Zarrinpar, for discussing patient selection and considerations for surgical treatments. So Dr. Hitchcock, onto you, describe for the listeners the use of peptide receptor radionuclide therapy or PRRT for treatment of neuroendocrine tumors. Explain when in the course of the disease PRRT is best given.
Dr. Kathryn Hitchcock: That is a really important point because I think that as a community, we're not very good at getting these patients into PRRT at the right time quite yet. It's a very new technology and we're all learning. If there's one thing that I would like our listeners to remember today, it's that it's never too early to refer one of these patients to come just to have a discussion about PRRT. It may not necessarily be time to give it yet when the patient first comes to us, but just to talk about it upfront.
I would guess that 70% of my new consults for this disease end up in me saying, you know, "You, the patient, of course, are in charge of deciding what happens, but I would recommend that we wait on giving you PRRT for right now. In the meantime, let's talk about what that experience will be like when it comes down the road."
Unfortunately, another 15% or 20% of my new consults end up in me saying, "I think this treatment would probably hurt you more than help you. Let's instead talk to your medical oncologist about what we can do instead." And of course, what I'm not saying to those patients is that PRRT probably would have helped them if they had just come to me sooner. But now, that opportunity is lost, which is a terrible feeling.
So as far as optimal timing, there's a lot of complicated things that go into that, just like everything in cancer. But the best answer is that it's time to use PRRT when the neuroendocrine cancer is metastatic and showing signs that it's going to grow out of control despite the use of octreotide. But there's not yet such a huge volume of the tumor that if I use the PRRT, it will end up damaging the patient's normal organ. So, fairly early in the course of the disease, and there's a lot of research that is being proposed right now to use it even earlier before the disease gets very widespread, but the jury is still out as to whether that's a good idea.
Melanie: Dr. Ramnaraig, can you expand on Dr. Hitchcock's answer then for us? When you treat patients with octreotide, do you give it forever or is it a finite course? Are there situations where it can't be used?
Dr. Brian Ramnaraign: Yeah, I think that's a great question. when we start off octreotide or lanreotide, and those are the two somatostatin analogs which are our typical first-line treatment for someone with an unresectable or metastatic neuroendocrine tumor that's well-differentiated. It's usually lifelong and we sometimes can take treatment holidays or treatment breaks. But this somatostatin analog class of treatment was the first treatment that really was shown to slow the growth of the tumor as well as improve the symptoms of the carcinoid tumor, symptoms such as diarrhea, flushing, and palpitations.
And to pick up on where Dr. Hitchcock led off, the Lutathera PRRT treatment is a really effective treatment. And typically, we have given that as a second-line treatment after patients have progressed on a somatostatin analog. And that's based on the FDA approval, which was of course based on the large phase III trial called the NETTER-1 study, where patients after progressing on octreotide at 30 milligrams given every four weeks, they were either randomized to PRRT or to doubling of the dose of octreotide. And then what we've seen is that patients who received PRRT actually lived longer. So, I agree. We want to get these patients into PRRT as soon as we can, but patients just on octreotide or lanreotide can do very well for a long time.
Melanie: And I'd like to give you all an opportunity for a final thought. So, Dr. Hughes, starting with you, as we've discussed that this is a second line therapy. Tell us about any other analogs that might be widely used to treat metastatic neuroendocrine tumors that have been shown to slow progression. Do you have any other therapies that you'd like to discuss?
Dr. Steven Hughes: Well, I think as far as second line therapy, Dr. Ramnaraign is probably in a better position to talk about what's coming down the investigational pipeline, so to speak. I think a combination of systemic therapy, whether it's something like Lutathera that Dr. Hitchcock provides or a more conventional chemotherapy that Dr. Ramnaraign provides, typically what we see are certain spots of tumor that are not responding to those treatments and that's where Dr. Zarrinpar and I can kind of still fit in. And those smaller areas that are not responding to systemic therapy can be surgically removed and we can literally keep these patients disease under control for a long time. And so it's a nice notion that your disease is under control and you're going to have a long life. And that's very typical for many patients with neuroendocrine tumors. And surgery plays a role for those certain areas that systemic therapies are not keeping under control. I think that answers your question.
Melanie: Well then, Dr. Ramnaraign, would you like to respond to Dr. Hughes?
Dr. Brian Ramnaraign: Absolutely. Just to pick up where doctors use left off, I think we still have a long way to go in neuroendocrine tumors. You know, there's two factors that we still need to improve on. And one is reducing the chance of the neuroendocrine tumor coming back for patients with early stage who have had it resected.
You know, last week in clinic, I saw a woman who had a pancreatic neuroendocrine tumor diagnosed 15 years ago, had it resected and was doing well for those 15 years and, you know, all of a sudden it came back. So I think we need better treatments to reduce the risk and cure these patients and to prevent the cancer from coming back. And there are studies, you know, looking at giving a treatment after surgery, it's called adjuvant chemotherapy. There is a large phase III trial. coming out through the national cooperative groups. So I'm looking at giving these patients adjuvant chemotherapy. And, you know, we'll see if that pans out. And if that is actually going to work. But currently, that's not part of the standard of care.
And then the second point is with our metastatic cancers, we want our patients to live longer and healthier and have more fruitful lives. We need better treatments and PRRT definitely has allowed us to help our patients live longer. And I think a couple of questions that we need to answer are, can we make PRRT a first-line therapy now? Which, you know, it's not currently, it's a second line treatment. But maybe patients will do better if we give it first-line and there are trials looking at that. And there also are trials looking at combining PRRT with immunotherapy and other treatments and other chemotherapies. And, you know, in general, you know, we need better treatments and we've come a long way, but there's still a long ways to go.
Melanie: Dr. Zarrinpar, next word to you. We mentioned a few times, but can you expand for referring physicians that the program has this focus in engaging multidisciplinary teams to best treat patients. Can you tell us how you all work together and how you communicate with the referring physicians?
Dr. Ali Zarrinpar: So we're really a team and not just we have regular meetings. We have a regular, very organized meeting where we present patients. Radiologists are there. The medical oncologists are there. The surgical oncologists are there. The interventional radiologists and the transplant surgeons are there. The research folks are there. You know, this is something where every patient goes through that discussion with everyone present.
But also we work next to each other. We run into each other in the hospital and in the hallways between our offices and we talk about patients and we call each other regularly. So if there's a question or if there's a quick update or we're in the operating room and we find something either pleasantly or unpleasantly surprising, we'll call each other and ask each other their opinions. And so this really allows us to come together and provide what, you know, the best options are for each patient. I think it's really important to not just have one mind looking at a problem, but multiple ones from different angles with different set of tools and different viewpoints.
Melanie: And Dr. Hitchcock, last word to you. Can you tell referring physicians when and reiterate for us when to refer patients to UF Health Shands Hospital for PRRT? Can you wrap it up for us as to when and what you'd like the takeaway message to be for other providers on this topic?
Dr. Kathryn Hitchcock: Sure. So I think that, because this is a rare cancer, it's never a bad idea to get patients in contact with a group of people who, as Dr. Hughes described at the beginning of the program, see a lot of this particular disease in order to understand what the best program is going to be for that patient.
Of course, if every patient and every neuroendocrine tumor were the same, it would be a lot simpler and that wouldn't be necessary. But the number of variables here is huge. And so getting these patients in to see a group of people who, as Dr. Zarrinpar described, talk frequently, have formal meetings where we all review the data together, but also we're in constant contact with one another is so important in these complex cancer situations.
And although referring oncologists might want to continue the care of that patient at home, it doesn't hurt to very early on have a consultation at a tertiary care center like ours in order to help sort of lay out a plan for when something like PRRT or when a surgery is going to come into play for that patient. So early referral is really the answer.
Melanie: Thank you all so much for taking part in this panel today. What a fascinating topic. And to refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. Please remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. Thanks so much for listening. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
Additional Info
- Audio Fileuf_health_shands/ufhs053.mp3
- DoctorsOkun, Michael;Foote, Kelly
- Featured SpeakerMichael Okun, MD | Kelly Foote, MD
- Guest BioMichael S. Okun, MD, received his B.A. in History from Florida State University, and his M.D. from the University of Florida where he graduated with Honors. Dr. Okun completed an internship and Neurology residency at the University of Florida. Following residency he was trained at Emory University, one of the world’s leading centers for movement disorders research, in both general movement disorders and in microelectrode recording/surgical treatments.
He is currently Administrative Director and Co-director of the Center for Movement Disorders and Neurorestoration which is part of the Center for Translational Research in Neurodegenerative Diseases, the McKnight Brain Institute, and the University of Florida College of Medicine. The center is unique in that it is comprised of over 45 interdisciplinary faculty members from diverse areas of campus, all of whom are dedicated to care, outreach, education and research. Dr. Okun has been dedicated to this interdisciplinary care concept, and since his appointment as the National Medical Director for the National Parkinson Foundation in 2006, he has worked with the 43 international NPF centers of excellence to help foster the best possible environments for care, research and outreach in Parkinson disease, dystonia, Tourette, and movement disorders.
Dr. Okun was one of the driving forces behind the creation of the Center for Movement Disorders and Neurorestoration and its completely patient-centric approach to care. He and his wife support many charities and he is currently the Medical Advisor for Tyler’s Hope for a Dystonia Cure, and also the Co-Medical Director for the Tourette Syndrome Association (TSA).
Dr. Okun has been supported by grants from the National Parkinson Foundation, the National Institutes of Health, the Parkinson Alliance, and the Michael J. Fox Foundation for Parkinson’s Disease Research, and he currently runs the online international “Ask The Expert” forums, on the National Parkinson Foundation website. The forum is a free service that answers questions from every continent (except Antarctica) and has over 10,000 postings in the last 3 years.
Dr. Okun has dedicated much of his career to the development of care centers for people suffering with movement disorders, but has also has enjoyed a prolific research career exploring non-motor basal ganglia brain features and he has participated in pioneering studies exploring the cognitive, behavioral, and mood effects of deep brain stimulation (DBS). Dr. Okun holds the Adelaide Lackner Associate Professorship in Neurology, has published over 200 peer-reviewed articles, is a published poet (Lessons From the Bedside, 1995), and has served as a reviewer for more than 25 major medical journals including JAMA and the New England Journal of Medicine. He has been invited to speak about Parkinson disease and movement disorders all over the world.
Kelly D. Foote, MD, is a graduate of the University of Utah, where he completed a BS degree in Materials Engineering as well as his Doctorate of Medicine. The U of U School of Medicine honored him with the Florence M. Strong Award in recognition of his outstanding qualities as a physician dedicated to patients. He did his general surgery internship at the University of Florida, where he also completed his residency in Neurological Surgery, including one year of dedicated training in Stereotactic and Functional Neurosurgery under the mentorship of Dr. William Friedman.
In 2002, he completed additional specialized training in Movement Disorder Neurosurgery and Deep Brain Stimulation (DBS) at the Universite Joseph Fourier in Grenoble France, and Emory University in Atlanta two of the world’s leading centers for such studies. Dr. Foote is the Co-Director of the University of Florida Movement Disorders Center and has strong clinical and research interests in the application of computers and high technology to neurosurgical problems. His areas of expertise include deep brain stimulation for Parkinson’s disease and other disorders, stereotactic and functional neurosurgery, radiosurgery and brain tumors. His research investigating novel applications of deep brain stimulation is sponsored by the National Institutes of Health and his work in the fields of DBS and radiosurgery has been extensively published.
Dr. Foote is sought after as a teacher and a dynamic public speaker. He moderates a nationwide on-line forum for the National Parkinson Foundation called “ask the surgeon”, in which he responds to patients’ questions regarding DBS and the surgical treatment of Parkinson’s disease. As a consultant for Medtronic, Inc. (the manufacturer of DBS devices) he teaches courses for physicians on how to perform DBS surgery, and he earns consistently stellar reviews from medical students and residents as a neurosurgery professor at the University of Florida College of Medicine.
He is the recipient of numerous awards and prizes including the Congress of Neurological Surgeons annual resident award and the Charles Chuck Shank Award for Excellence in Neurosurgery at the University of Florida. Dr. Foote is an avid sportsman who enjoys basketball, scuba diving, volleyball and snowboarding. He also speaks French fluently and enjoys travel and cinema. He welcomes your comments or questions, and can be reached by email. - TranscriptionMelanie Cole (Host): Welcome to UF Health Med Ed Cast with UF Health Shands Hospital. I'm Melanie Cole and today we're offering an update on new applications for DBS and Parkinson's treatments. Joining me in this panel are Dr. Michael Okun. He's a University of Florida Chair of Neurology, Executive Director of the Norman Fixel Institute for Neurological Diseases at UF Health and a Professor at the University of Florida. And Dr. Kelly Foote. He's the Co-Director at the Norman Fixel Institute for Neurological Diseases and a Professor at the University of Florida College of Medicine in the Department of Neurosurgery at UF Health. Gentlemen, I'm so glad to have you join us again today. Dr. Okun, as we're giving this update, and it's such an interesting topic, I'd like you to set the stage for us on the first-line treatment for tremors resulting from movement disorders, such as Parkinson's and for patients that haven't seen positive effects from medication. Give us a little update and some of the history on the clinical indications for use of DBS for referring physicians.
Michael Okun, MD (Guest): Yeah. So, it is a very interesting field and one that is evolving quickly and something that I think is important for physicians that see people with movement disorders within their clinics to pay attention to, because it turns out, that there are a lot of folks with diseases like Parkinson's and essential tremor, and even some others that have these extra movements, we call hyperkinetic movements that might be associated with their particular disorder. So, with Parkinson's disease, it might be shaking or tremor, or it might be something like dyskinesia, which are extra dance like movements. And so we think of these extra movements as hyperkinetic movements.
And of course we do address them first with medications. And so there are over a dozen different medicines that we use to treat Parkinson's disease. And there's three or four first-line medicines that we think about for diseases like essential tremor when people have tremors. And then of course, if you have movements that have been precipitated or caused by the medicines or the progression of a disease, like Parkinson's, those are those dance like movements like dyskinesias we then begin to shift our thinking if we've tried medicines. And of course we try not only a cocktail of all of those different medicines together, but we also think about how we give them.
So, timing of the medications is super important in the management, but if you've done everything that you can do and you're still getting or resulting in a case where you just can't get a hold of the symptoms, these extra movements, then we begin to think about deep brain stimulation therapy.
Host: Dr Foote, can you speak about the clinical criteria and patient selection for DBS? Has anything changed? Is there anyone who this is contraindicated for? Tell us a little bit about the inclusion and exclusion criteria for DBS.
Kelly Foote, MD (Guest): Sure. Sure. I would say that as the safety profile and the efficacy of deep brain stimulation over the last 30 years or so has improved, the indications for DBS surgery have increased. We're less nervous about this procedure than we were in the beginning. And you know, Michael mentioned hyperkinetic movement disorders, but the truth is it's not just the hyperkinetic movement disorders, it's hypokinetic as well. You know, a large percentage of patients with Parkinson's disease don't have tremor. So, I would say the primary indication is a patient who, who has known Parkinson's disease and who suffers from debilitating motor fluctuations. What I mean by that is they spend their day going back and forth between states of hyperkinetic dyskinesias when their medications wear off. When they're on their medications, they have side effects that make them move more than they want to. And when their medications wear off, they may have the tremor, but that they may not, but they may also be stiff and slow.
You know, they have brief episodes during each dose of their medication where they function reasonably well, but as the disease progresses over the years, the efficacy of the medications wanes, you have to take more and more medication as your native dopamine production diminishes, and interestingly, the threshold for stimulation induced side effects like dyskinesia and hallucinations actually decreases as well.
So, the therapeutic window for dopamine in the human brain, in someone with Parkinson's disease, gradually narrows to the point where even a very good movement disorders neurologist is going to really struggle to keep the dopamine levels at a good point with various manipulations of the patient's dopaminergic medications. So, the patients who are struggling to function and variable ability to function throughout the day, tend to be the ones who get the most benefit from deep brain stimulation therapy.
Host: Now Dr. Okun, I'd like you to tell us about the UF research study about home management of DBS settings. Please tell us about your recent trials. I find this so interesting and I imagine for the patients and their families, this is preferable.
Dr. Okun: Yes. So, we have been quite interested over the years in not only the development of the technology. So, our laboratories have been working on what we call neuromodulation. So, you know, we try to change those conversations that are going on in the brain to improve symptoms, but we realize that it is really important to try to address these public health issues in a way in which people can actually get access to the devices. And so, we know that practitioners that are out there in various clinics all over the United States and frankly all over the world, you know, are going to have to manage this generation of people who are bionic.
And we know that they're over 200,000 folks now that are walking the planet that have these types of devices. And so, we've been interested in the development of technologies to help nurses and other practitioners and the individual patients themselves to be able to manage their diseases within their home. And we talk about this in the context of bringing the disease to the home, to the patient. And many of these patients have difficulties traveling. They have dysfunctions that make their lives difficult to get in the car, and it might be difficult to get to the offices. And so having the technologies for people to be able to reach out and either manage from the office to the home or alternatively to have people that go out to the home to help folks to manage these these deep brain stimulation devices, which can have thousands of settings, is really important.
And so we published a study in JAMA Neurology just here in June of 2021. And the way it worked was we randomized people to two groups. Those folks that came to the clinic for all their adjustments, and then we had a group where they were visited a few times by a home health nurse, and then the home health nurse checked in with them by telephone. And we looked at the results and provided this really cool, easy to use tablet to help to manage these folks. And we found out that we could manage them in their homes just as well as we manage them within the clinic setting, meaning that all of the outcomes were the same when we compared those groups. And so figuring practical ways for folks to be able to have really complicated devices implanted and managed and have them stay in the home settings is going to be important.
And then on top of that, our group is also working a lot on the ways in which we can help the practitioners. So, the people that are in the clinic. So, the docs and the nurses and the nurse practitioners and the physician assistants, they need to be able to be equipped with the tools so that they don't have to spend hours and hours adjusting these really complicated devices. And so we work a lot on trying to develop the technology to make it easier to manage people and to make sure that their outcomes stay the same or potentially in the future could even get better.
Dr. Foote: Yeah. I think I can add something interesting to that from a surgeon's perspective. You know, I think many people think of deep brain stimulation as surgical treatment, which of course it is. But the implantation of the deep brain stimulation lead into the appropriate place in the brain and getting the patient through that process and getting the system implanted, I would say is, you know, only half the battle. And of course, you know, we have a bunch of research that's focused on improving our ability to do that well which improves the outcomes. But what a lot of people don't realize isthat the management of the patients after the surgical procedure is done is a huge determinant of the success or failure of that intervention.
So, so, a program like this, you know, a lot of our research goes into how do we optimize these systems once they're implanted? And if you can figure out a way to have this done at home, develop tools that help people do it more effectively and more efficiently, that's really helpful. You know, the other exciting thing that we're working on is trying to teach these systems to program themselves, which I guess would be opening another discussion of closed loop deep brain stimulation that we ultimately hope to be able to do.
Host: Well, that was a perfect segue, Dr. Foote and I find that home adaptation so interesting to make treatment far more accessible really, to people who have difficulty traveling or in remote areas. Tell us a little bit about adaptive DBS, targeting the different regions and modifying this in real time. I find this absolutely fascinating.
Dr. Foote: Well, adaptive DBS or closed loop DBS is something that we think ultimately all DBS will exploit. It just sort of makes intuitive sense. You know, the brain is not a static organ. You know, I mentioned that patients' symptomatic states fluctuate throughout the day. And a treatment that continuously delivers the same therapy is not going to match that dynamic environment in the brain. But if we can find neurophysiologic biomarkers in the signals that we record from the brain, that correlate with the patient's pathology. For example, just to simplify it, let's say, you know, I have a patient who has tremor that is debilitating and that tremor fluctuates throughout the day. Or that tremor is only present when the patient is doing certain things. If I can continuously record the electrical activity from that patient's brain, and I can identify in those signals from the brain a biomarker that says when this signal appears, this patient is about to have a tremor that's debilitating.
We also have an effector loop in that system that says, whenever this appears, deliver stimulation to this area of the brain, which will prevent the tremor then you have a system that continuously monitors the state of the patient's brain and responds appropriately when needed, but when not needed, doesn't stimulate.
And one of the important notions about deep brain stimulation that people don't focus on is, you know, we're excited about disrupting pathologic signals in the brain that are causing problems, but there's always collateral damage, if you will, when you stimulate the brain. If you're really good and you put the electrode in just the right spot, you can disrupt some pathological signal that results in alleviating the patient's symptoms, but there will always be some disruption of normal information flow in the brain say in surrounding circuits. And you know, we focus a lot of energy on trying to minimize stimulation induced side effects and in theory, this adaptive simulation, because it would only be on when the patient needs it would minimize that disruption of normal information flow in the brain and minimize side effects of DBS.
Host: This is such an interesting topic and these updates are so important, really, very innovative. So, Dr. Okun, do you have any updates on non-surgical DBS techniques?
Dr. Okun: Yeah. So, there are a number of really interesting what we call surgical approaches to various movement disorders, including Parkinson's disease that have really reached, you know, the field. And if you're a practitioner in your office, you should always be aware of all of the alternatives from medicines to surgeries to the various different things that we would think about.
And so there are a number of categories that when you're talking to patients it's important to, to not forget. One is a group of therapies that we would think of as pump therapies that have been evolving. And so there's a dopamine pump called a Duopa pump that can provide continuous stimulation. It's kind of a tube that goes into the first section of the intestine into the duodenum and can provide continuous stimulation with sort of a cartridge that you put into a belt and set a flow rate on. There's a pump that's been approved in Europe and in other locales, but not yet, at least that we've seen. And we're following with the FDA on this story called an apomorphine pump. And so that actually goes underneath the skin, it's subcutaneous and provides a drug called a dopamine agonist continuously for the treatment of what we call these off symptoms of Parkinson.
And so when you get tremor, stiffness or slowness, you can get some improvement and both of these therapies can help with the symptoms of Parkinson disease, both the Duopa pump and the apomorphine pump. Now of course, the Duopa is a available in the United States and the therapy's not quite as good as deep brain stimulation and does require management of that tube. And that's where we've seen the most complications there. Remember it's not completely internalized. And so when you have a deep brain stimulator implanted by an experienced neurosurgeon like Kelly Foote, it's completely internalized, meaning it's inside the skin. You can swim, you can do anything that you want.
And these other therapies are sort of from the outside in. And the third therapy that we think about is one called focused ultrasound. And this has been around since the 1950s. And it's where you point sound waves from the outside to the inside of the body. And you can do this, actually, not just in the brain, but in all areas of the body. And it can allow you to destroy tissue. And I say, oh my gosh, well, why would I want to do that? Well, it turns out there's a long history in movement disorder surgery for tremors and Parkinson's especially, but also for other disorders that if you actually ablate or destroy the tissue in the right area of the brain, it changes those conversations, just like the stimulators that Dr. Foote implants called deep brain stimulators. You can change that conversation by actually destroying the tissue. The advantage to the focused ultrasound is you can do it from outside the brain and outside to inside. So, you don't need that surgical incision. The disadvantages are that you can only do it on one side of the brain and the accuracy is not as good coming from outside the brain than when you go in and actually record and listen and map out that region, because millimeters are like miles in the brain. And so this is another option that, that we think about. It was first approved for tremor in essential tremor, but also the tremor of Parkinson's can be treated. But again, only one side of the brain. And we might even think about this therapy in some folks maybe have some things that might make them at higher risk for conventional or regular deep brain stimulation therapy. So, maybe they're on blood thinners or maybe their age is older. They're have fragile skin. And so we think about these as other options that might be on the table.
Dr. Foote: Yeah I'll add to that as well. You know, I think that MR guided focused ultrasound is actually a very exciting therapy and it has the obvious advantage of not having to have an incision. It's you're not going to get an infection. You're not going to have adverse effects of bleeding and things like that. But you know, the interesting perspective that a lot of people miss is that the origin of deep brain stimulation was actually looking for a way. It was one of my mentors Professor Benabid in Grenoble, France in the late 1980s. At the time neurosurgeons were quite good at doing lesion therapy, doing what are called thalamotomys, which is a treatment actually that Michael J. Fox got at one point to suppress tremor. And thalamotomys, were very effective. But the, as I mentioned before, they're all, there's always a little bit of collateral damage and the circuitry that controls speech and walking is closely intertwined with that circuitry through the cerebellum that causes the tremor.
So, Professor Benabid and others at the time were very good at basically burning a hole in the thalamus by implanting a heat probe, an electrode into the thalamus and burning a hole in the thalamus, which would stop the tremor. And occasionally have some side effects that adversely affected speech and walking. And Professor Benabid, at the time, you know, the technique for doing that was you would put the electrode in and before you would heat it up to burn a hole, you would deliver electrical stimulation. And he, of course, like everyone noticed that you know, during the electrical stimulation, that tremor would also abate.
And you could also test for side effects during electrical stimulation to see if the patient's speech or or their movement was affected. And, at the time they determined that making a lesion on both sides of the brain just had an unacceptably high rate of adverse effects on speech and walking. So, he had this idea, well, what if we instead burning a hole on the second side of the brain, let's just implant an electrode and continuously stimulate to have similar effects with controllable side effects. And that was the actually the origin of modern deep brain stimulation. I feel like now we've come full circle and we're going back to burning holes in the brain strategically. But you know, that's a perspective that I think a lot of people miss. I do think MR guided focused ultrasound lesioning is the most elegant and probably the safest way of creating a lesion in the brain, but it's still burning a hole in the brain.
Host: Wow. This is such an interesting and informative episode. And I'd like to give you each a chance for a brief, final thought for referring physicians. So, Dr. Foote, any new therapies such as immunotherapies, cell based gene therapies. Tell us a little bit about anything that you think is exciting coming in the future.
Dr. Foote: Well, I will say I'm very excited about the potential for gene therapy for treatment of Parkinson's disease and the potential for stem cell therapy as well. I do want to temper that excitement and make one important public service announcement, which is there is to date, no evidence that stem cell therapy affects the progression of Parkinson's disease. There are however, many stem cell clinics that are charging high prices to patients who sometimes can't afford it, for stem cell treatment for their Parkinson's disease. And I just sort of want to caution people, that right now, stem cell therapy is not ready for prime time and they should not pay for stem cell therapy for Parkinson's disease.
That's not to say that there aren't some very exciting, there are several exciting trials ongoing for both stem cell therapy and gene therapy for Parkinson's disease that we think may end up being you know, hopefully putting us out of business in the deep brain stimulation world if we can find a therapy that actually cures or stops the progression of Parkinson's disease using some of these other more exciting cellular techniques.
Host: Dr. Okun, last word to you. What would you like referring physicians to know about this update we're giving and your UF research study on home management of DBS settings.
Dr. Okun: I really would like to emphasize that it's an exciting time. And it's really important that we share with our patients, you know, all of the medical therapies and there's nuance too. And so making sure that we are not only using the right drugs, but we're using them in the right way. So, make sure you ask lots of questions and work with some folks that maybe have some experience in that area so they can help to manage your patients.
But if you get to the point where you're having difficulty managing them with medicines, then we would refer them for deep brain stimulation to center that's very experienced, that has a lot of folks that get together and evaluate the people in an interdisciplinary fashion and decide the risk benefit ratio as to moving forward with one of those therapies. I would make sure to, you know, always broaden your discussions to include pump therapies, you know, like the Duopa pump, like the apomorphine pump that's coming, the focused ultrasound and just discuss in a very honest and open way, the risks and benefits of each and what might fit an individual person. And then finally, you know, I always tell folks, ask your doc what's new. And it's, you know, one of the most important questions that you can explore when you're at an appointment.
And so I would just say to the practitioners, be ready for that question. And it's important to be able to help folks to find the information on clinicaltrials.gov, where all of the research trials are listed and to make sure that people know as Dr. Foote talks about, that none of the stem cell therapies have really advanced past research and there's thousands of clinics offering fee for service. And we should be really careful and make sure that we're counseling people to be very careful with that particular therapy. So, that our patients don't get sold down the road of something that they might regret or might cause some harm to them. But we're also moving to a personalized era of medicine and we see this happening in cancer, and we're going to see more and more of this in Parkinson's and movement disorders.
Getting people's genes and their genetics and seeing if they have genetic abnormalities, and for those folks, developing more personalized therapies. And then for others, you know, developing the right way to manage them and to try to manage them at home is going to be important. And so there's a lot of really cool things coming with neuroimmunology and diets and surgeries. And so just keep an open mind and make sure when you're talking to your patients, that you have a complete discussion. And even when you're talking about new things, make sure that, that you can help them to be safe when they're choosing what's right for them.
Host: What an exciting time to be in your field. Thank you gentlemen, for joining us today and giving us this update. To learn more about Parkinson's disease and the Norman Fixel Institute of Neurological Disease, please visit fixel.UFhealth.org. Or to refer your patient or to listen to more podcasts from our experts, you can always visit ufhealth.org/medmatters.
That concludes today's episode of UF Health Med Ed Cast with UF Health Shands Hospital. I'm Melanie Cole. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
Additional Info
- Audio Fileuf_health_shands/ufhs051.mp3
- DoctorsCampbell, Kevin
- Featured SpeakerKevin Campbell, MD
- Guest BioKevin Campbell, MD is an Assistant Professor, Department of Urology University of Florida College of Medicine.
- TranscriptionMelanie Cole: Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole. And today, we're discussing hypogonadism and the management of testosterone therapy. Joining me is Dr. Kevin Campbell. He's an assistant professor in the Department of Urology at the University of Florida College of Medicine.
Dr. Campbell, it's a pleasure to have you join us again today. Can you tell us a little bit about hypogonadism and how prevalent it is?
Dr. Kevin Campbell: Sure. Well, thanks Melanie. I first want to thank you for having me on the podcast. Again, I'm glad to have the opportunity to be here and discuss this aspect of men's health that I really find interesting and important in today's medical world. So a little bit of background on male hypogonadism, which is also to say low testosterone.
So the prevalence of hypogonadism or low testosterone, you can describe them interchangeably in the American male population, it really ranges widely. There are some reports that have it as low as 2% and some that have it as high as almost 77%, depending on what you read. So expectedly, you have testosterone testing and prescriptions nearly tripling in the recent years.
And you can also look back from a really historical perspective and see that this has been going on for a long time. So even Aristotle was right about castration and the effects of the lack of testosterone in the 4th century, BC, and then all the way up to the early 1900s, even have vocalists who were being castrated to avoid the masculinizing effects of puberty and they were called castrato.
So we first testosterone being synthesized in 1935 and those folks even won a Nobel Prize for it. So if we fast forward to today, we see testosterone therapy is a common therapy in the aging male, who is known to be hypogonadal
Melanie Cole: Well, so then let's talk about some of the complications of it. And you mentioned some things from long ago. Do we know what causes it?
Dr. Kevin Campbell: So we know that it's a natural phenomenon as the body in the male gets older, you produce less testosterone. There's also a lot of comorbidities like obesity., Hyperlipidemia, these things can cause decreases in testosterone production. And also you have decreases in the available testosterone because there's other proteins in your body that can bind to your testosterone and make it less available.
And so if we were to really look at what a normal testosterone range is, it's going to vary from reference range to reference range or whichever lab you look at. But in general, it's between 300 and 800 or even 300 and 1000 nanograms per deciliter. And that's just if you took a hundred people off the street and you measured their levels and they weren't having any signs or symptoms, or you wouldn't say that they were hypogonadal.
Now, there's other levels and other periphery values that can influence that decision to go on testosterone therapy, such as the free testosterone, as well as some other hormones like a sex hormone binding globulin. But the testosterone itself, if you look at it, about half of it is bound to a protein called albumin. The other half or just under it is bound to that SHBG which we just talked about. And then another 2% is free.
So you can hear someone talk about bioavailable testosterone, and that's that free testosterone, and also the loosely bound testosterone. However, when we look at diagnosis, the total testosterone is the most important. So because these values can really vary widely, depending on what time of day you take it, you know, if a person has a viral illness, if you've have a high cortisol response, like you just get sick or you haven't gotten much sleep, it can really change.
So going back to your point, your environment is certainly something that can affect your testosterone production. It can be genetics. There's a whole lot of things. So we really have to take that into consideration. And so we recommend getting two measurements or two blood values on separate occasions. Both in the early morning fashion when your testosterone generally is at its highest, so low value is truly indicative of a deficiency. And then also we have to pair that with your symptoms and your signs. So all those together lead to a diagnosis of hypogonadism or low testosterone that we see in today's population.
Melanie Cole: Well, thank you for that. And as we're talking about diagnostic criteria and that evaluation, as you say morning and evening, tell us a little bit about those symptoms, if you would expand. Why is somebody going to be telling this to a urologist, if a male is seeing their urologist or is this something a primary care provider would notice? Tell us a little bit why and expand on that evaluation for us.
Dr. Kevin Campbell: Now, certainly a primary care physician or urologist, or really any provider who's taking care of a patient should have this in the back of their mindset. So signs and symptoms of low testosterone can include a combination of physical, cognitive or even sexual symptoms. Those being reduced energy, decreased sex drive, decrease in erections, diminished work performance, increased fatigue, the inability to maintain lean muscle mass or an increase in fat content. Additionally, low testosterone can also manifest in depressive symptoms or persistent mental fog. So that's why you have to kind of keep a keen eye because these are very generalizable symptoms.
But who should be tested? Well, I really go by the AUA guidelines. I'll reference them probably throughout the talk here as we get more in depth here. But they recommend screening people with unexplained anemia, bone density loss, diabetes, if you have a history of chemotherapy or radiation to the genitals, those with HIV or AIDS, chronic narcotic use or opioid use, which is very important in today's culture, male infertility, pituitary dysfunction, and chronic steroid use. So these are the patients who in addition to the previously described symptomatic patients should be screened in the absence of symptoms.
Melanie Cole: Does it often go undiagnosed for a while, doctor?
Dr. Kevin Campbell: Yes, it can go undiagnosed for a long time. In fact, the average person may see anywhere between three to seven physicians before they're diagnosed with hypogonadism because the symptoms will lead you down other workup paths, those for depression, for low blood sugar, lots of different things can be thought to be coincidental with low testosterone. So that's why we really do a workup looking for the signs and symptoms and serum levels too.
So once you have the signs, it's really important to do blood work. We measure morning testosterone as we talked about. And if that's low, then we repeat the testosterone to get a second value and also some other labs including what's called a luteinizing hormone and a hermatocrit.
So luteinizing hormone is a gonadotropin, which is a signal to the testes from the pituitary in the brain. And that can be suppressed by another hormone called prolactin. So we get this hormone as well in the blood value. And if you have a testosterone out of range, this will confirm the deficiency and leads us into discussion for the aspects of treatment.
So you can do also additional testing that can be considered in select circumstances. So we do a DEXA scan, which can be performed to evaluate bone strength in patients who have a history of unlikely bone fractures, such as those with low volume trauma. If you have an elevated gonadotropin level, so like the luteinizing hormone I talked about, that with a low testosterone can be suggestive of a genetic cause of hypogonadism and warrants a karyotype or genetic workup. And also patients over the age of 40 should obtain a PSA prior to starting therapy, because we're also screening for prostate cancer in those patients.
And lastly, as with any good medical workup, a physical exam is included to evaluate for general body habitus, BMI, body hair patterns, and a genital exam, including testicular evaluation.
Melanie Cole: So then speak to us about management, risks and benefits. You mentioned testosterone therapy. Tell us about the standard treatment options and what UF Health Shands Hospital is doing differently. Tell us a little bit for other providers about this type of treatment and how it's working for you.
Dr. Kevin Campbell: Sure. I'd be happy to. So with medical options or medication options, there's tons of them out there. There's about 1,001 different formulations of testosterone nowadays. There's testosterone gels. There's creams. There's patches. Oral formulations for daily use and all these maintain a more even serum level. These are good for those patients who wish to avoid needles and want to maintain a daily administration regimen. They also have to consider taking into the risk of transference of these topicals for people you come into contact with such as children and loved ones.
Additionally, there's oral formulations, such as pills that had previously fallen out of favor because their compounds were alkylated and they put stress on the liver whenever you're taking these on a daily fashion. But they do have newer formulations that are absorbed into the lymphatics, which avoid this concern and make these oral pills a good option or alternative.
There's also a weekly or biweekly injections. These can be performed and are titrated up in order to maintain a trough above the symptomatic level, without an exceptionally high peak and injections can be performed either intramuscularly to directly get the medication into the bloodstream or even subcutaneously. There are even auto-injectors which disperse the medication over the course of about a 10-second period with little or no discomfort to the patient.
There's also longer-acting formulations. They're present in the form of testosterone pellets, which are roughly the size of a grain of rice and are implanted under the skin of the buttock and dissolve over the time, giving an even serum level for several months before having to go back in and have a second pellet placement. And there's a longer acting testosterone injection that can be performed in the office, which needs to be repeated every 10 months.
So these are all formulations of exogenous testosterone replacement. But in consideration of patients who mainly do not want to go on exogenous testosterone or who want to maintain fertility potential, then stimulation of a patient's own hypothalamic-pituitary-testicular axis can be performed to increase production of testosterone from a patient's own Leydig cells in the testicle. This also supports a Sertoli cell function, which are responsible for sperm production in the testicle as well. And we have a couple of options.
First, there's clomiphene. This is commonly used to inhibit the negative feedback of estrogen on the brain. And this in turn can lead to an increase in those gonadotropins, which leads to an increase in testicular testosterone production. This is a medication that's commonly used in the male infertility world to assist with sperm production. And if you want to look further, that clomiphene molecule can be broken down into two different isomers or two different components, zuclomiphene and enclomiphene. And enclomiphene has been manufactured to be a standalone pill. And it's got fewer estrogenic side effects, which has been shown in studies to have similar raises in testosterone to the 1% testosterone gels that are out there and also maintains a patient's sperm production. So this is a very favorable alternative to exogenous testosterone.
There's also recent and ongoing studies, which is focused on the use of intra-nasal testosterone gel. And the dose isn't as high as the other formulations, and it's roughly 11 milligrams and it's taken over three times daily. So that level of testosterone doesn't meet the threshold for suppression of that HBG access. And it hasn't been shown to significantly lower gonadotropins and thus sperm production. So this is also good for maintaining sperm production while also fighting those hypogonadal symptoms.
Let's talk a little bit about supplemental roles. So there's supplemental regimens to these other testosterone therapies in the form of hCG and anastrazole. And hCG is also a gonadotropin as we talked about. It's called human chorionic gonadotropin. It's an analog of luteinizing hormone, which is that same hormone that promotes the production of intratesticular testosterone. And so all men who are looking to have children or are children-bearing age and haven't made up their mind, if they want to maintain their fertility, should consider also being on an hCG supplementation regimen in addition to their testosterone. And this is in the form of a subcutaneous injection one to three times weekly.
And lastly, I want to talk about the body's conversion to estrogen. So your body's naturally going to try and convert your testosterone to estrogen with an enzyme called aromatase. It's found in your liver and your fat tissue all throughout the body. And so in an effort to maintain higher levels of testosterone, this enzyme can be blocked and it's done by an aromatase inhibitor, such as aanastrazole, and this is weekly pill.
So during routine serum hormone evaluation and medical checkups, estrogen levels can dictate the need for increasing or decreasing estrogen blockade. So these are some of the things that we will consider whenever we're talking to someone about their testosterone management and what they're looking to achieve and what sort of side effect profile we should talk about.
Melanie Cole: That's so interesting. Dr. Campbell. Wow. So many available therapies in your armamentarium. As you wrap up for us, what would you like other physicians to know about hypogonadism in males and the management with testosterone therapy and some of these other therapies that you've mentioned here today?
Dr. Kevin Campbell: So there's a couple of things that go with testosterone management that I think are important for all providers. And that's knowing the side effect profiles, and also some of the things to monitor. So, in all patients who are on an exogenous testosterone regimen, you got to make sure that you're looking at their hermatocrit or their blood density since testosterone can cause an increase in the production of red blood cells. If that density gets too high, side effects can include fatigue, sluggishness, headaches, and more seriously blood clots can also be possible. So if a patient's coming to you and saying that, you know, "I've still got more fatigue and sluggishness," despite having appropriate serum levels of testosterone, it could be indicative that they have too high of a hermatocrit and they need to undergo a therapeutic phlebotomy to attain a lower hermatocrit
Also, prostate cancer. So it should be pointed out to patients with testosterone deficiency and a history of prostate cancer should be informed that according to those American Urological Association guidelines we talked about, there's an absence of evidence linking testosterone therapy to the development of prostate cancer. And so that's very important because there's a lot of controversy surrounding testosterone therapy and prostate cancer. And so now What that means is that the decision to initiate testosterone therapy in men with previously treated prostate cancer orwhere those who are on active surveillance should discuss the risk and benefits of testosterone therapy prior to starting that therapy.
So if you have undergone a radical prostatectomy or you have a patient who has, and you have a subsequent undetectable PSA on followup, those patients can be considered for therapy as the studies, though limited, have not demonstrated a significant increase in prostate cancer recurrence.
Additionally, if a patient's prostate cancer was treated with radiation, studies have shown that these patients do not experience increased risks of recurrences or progression of that prostate cancer once starting testosterone therapy. So similar results have also been shown in men who initiated that testosterone therapy while on active surveillance for low-risk prostate cancer. Now, this is different from those patients with metastatic prostate cancer, who are being treated with androgen deprivation therapy, who should not be considered for testosterone therapy
Lastly, I'd also like to talk about cardiovascular disease. So there's conflicting information out there regarding the use of testosterone therapy in the setting of cardiovascular disease. And it should be noted that low testosterone is an independent risk factor for cardiovascular disease, not high testosterone.
So our literature has consistently shown that low testosterone levels are associated with an increased incidence of major cardiac events, such as myocardial infarctions, strokes, possible cardiovascular-related mortality as well. And it's because of this, that testosterone deficient patients should also be assessed for modifiable risk factors like smoking, high blood pressure, diabetes, dyslipidemia, for instance.
So now, in these patients who have had a recent cardiovascular event, such as a heart attack or a stroke, testosterone therapy should be withheld for at least three to six months before resuming therapy with close monitoring. And we previously talked about blood clots. Patients should be notified that there's no definitive evidence linking testosterone therapy to a higher incidence of these venous thromboembolic events, which are blood clots.
The FDA requires pharmaceutical companies to add a warning label of concern about possible association between testosterone therapy and these events. And the AUA or those American Urological Association guidelines note that in testosterone deficiency, this decision was based on anecdotal cases and not peer reviewed literature. So since this warning came out in 2014 by the FDA, close followup observational studies have not shown an association between testosterone therapy and an increased risk in these events. So these are some things that I think should be known for anyone who's talking about testosterone therapy, that being prostate cancer or cardiovascular disease.
And also briefly we touched on fertility, which should also enter the discussion whenever we're talking about initiating exogenous testosterone or not, because elevated testosterone levels or exogenous testosterone levels can shut down a person's own production of testosterone and thus sperm production, so we have to really keep these in mind whenever we're talking to a patient about what their goals are.
Melanie Cole: What an informative episode, Dr. Campbell. And what a great guest you are. Thank you so much for such an educational episode today.
To refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital.
Please remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
Additional Info
- Audio Fileuf_health_shands/ufhs052.mp3
- DoctorsO’Malley, Padraic
- Featured SpeakerPadraic O’Malley, MSc, MD, FRCSC
- Guest BioPadraic O’Malley, MSc, MD, FRCSC is an Assistant Professor, Department of Urology University of Florida College of Medicine.
Learn more about Padraic O’Malley, MSc, MD, FRCSC - TranscriptionHost: Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole. And today, we're discussing advanced kidney cancer management. Joining me is Dr. Padraic O'Malley. He's an assistant professor in the Department of Urology at the University of Florida College of Medicine.
Dr. O'Malley, it's a pleasure to have you join us today. Before we get into some of the treatment options, tell us a little bit about the prevalence of kidney cancer. What have you been seeing in the trends lately?
Dr. Padraic O’Malley: Kidney cancer is a very common type of cancer. It's in both men and women. It's one of the top 10 most common malignancies. And interestingly is that the incidence of kidney cancer has continued to rise over time. A large bit of that was because we are imaging people a lot more often now for other reasons. But even when you control for that, the incidence of kidney cancer continued to rise. And we're not sure why that is yet, but it is a very common type of cancer that we encounter.
Host: So then let's talk about advanced kidney cancer management. How do you utilize various modalities, surgery, radiation, medical oncology therapies in this type of advanced kidney cancer care?
Dr. Padraic O’Malley: This is one area I'm very interested in. And I think part of my interest, not only clinically, but just as far as how we approach it comes from my interest outside of medicine and sports. I've always been an avid sports fan and sport require you, many of them, to be part of a team and be a team member and play different roles.
Traditionally in medicine, patients with localized disease, as long as they didn't have spread elsewhere, were treated primarily with surgery alone. And then those patients who had spread that were outside, say the kidney to other areas of the body were treated primarily by medical oncologists with systemic drugs. And so they were treated by independent silos of physicians. It wasn't really a very team-oriented approach to cancer care and patient care. And what we've come to realize in the last few years in the last 5 to 10 to 15 years, is that having a team-based approach where we use multiple modalities of treatment in combination or in sequence actually is the better outcomes amongst patients with not just advanced kidney cancer, but many other malignancies as well.
Host: So then let's talk about that. Given the complexity and with increasingly complex treatment algorithms that are adding new options to your armamentarium of available therapies, expand a little bit more on that multidisciplinary approach. How do you all work together? And really, who's in charge of guiding patient care?
Dr. Padraic O’Malley: So we use a sort of standardized approach for many of these patients. It's a combination of using the sort of best practice, which is mainly based on national and international guidelines, particularly those provided by the NCCN or national cancer groups. And then we also use clinical trials. The only way we know the answers to many of our clinical questions is if we test those hypotheses. And the best way to do that, generally speaking, is through clinical trials. That allows us to know how to treat patients with advanced disease better in the future. So we use a combination of clinical trials, a combination of standard guidelines to make sure we're doing the best treatment for patients.
And then in order to put that sort of into effect or an action, we often use a number of different strategies. We have a group meeting every week or two weeks, which is our genitourinary tumor board, which is a group meeting with several surgeons, several medical oncologists, our radiation oncologist, our pathologists and our radiologists.
So it's a real group of experts who sit down and review each individual patient's case, blood work, pathology, imaging as well as the sort of overall health status of those patients. And by doing so, we have the input from not just one physician, but a group of physicians, all of whom have a particular area of expertise. And that gives us a more balanced approach to these patients. .
The second strategy is using clinical trials which operate on a very rigorous background rationale behind their design. So these studies are not just fancifully thought up. They are all predicated on our previous history and knowledge.
And so when they're set up, they are set up, they're more likely to succeed than not because they've been well thought out. By enrolling patients, we actually have a group meeting every week, which involves several physicians from medical oncology and urological oncology where we meet and look at potential candidates for each trial to try and optimize our patient care.
So by using those combination of strategies, we find we can really tailor care to patients individually, but also optimize the sort of multimodal treatment of these patients.
Host: So then how do you envision your research and these clinical trials you're discussing, translating to patient care? What do you see happening?
Dr. Padraic O’Malley: Yeah. So, one of the most exciting things that's happened in oncology as a whole has been the advent of immunotherapy. Immunotherapy is a form of systemic therapy. The most common type of systemic therapy many people are familiar with of course is chemo, but chemo was like a nuclear bomb. It destroys everything, including the healthy cells and the immunotherapy obviously has a more specific or targeted approach where it harnesses your body's immune system to attack these cancer cells. We've seen with the use of these in a number of malignancies a more durable and impressive response than we have with some traditional agents.
And we started using these a lot more in kidney cancer. We know from several studies that have been done, that these drugs work better than the previous standard of care, which what we'll call tyrosine kinase inhibitor. And with this group of drugs, these tyrosine kinase inhibitors, for instance, we used to see patients who had larger more advanced malignancies that had not spread elsewhere, but we knew were at high risk for having a recurrence, anywhere from 30% to 65% chance of having a recurrence. We knew many of these patients it was only a matter of time.
In these patients, we tried using these drugs after surgery to see if we could prolong their survival. And unfortunately, despite several studies, there's about five studies done, none of these showed an overall survival benefit. And only one of them actually showed an improvement as far as how long it took before patients' disease recurred.
We know the immunotherapy drugs work better in the metastatic setting. And we're currently doing trials now in the field to determine can these immunotherapy drugs, which we know work better, maybe work better in this setting where patients have large volume disease that hasn't spread elsewhere. Can we prevent them from having recurrence? And so those are the trials that are undergoing. And actually all of those trials have finished accruing within the last year because there was such a popularity with them, because we really feel like these are likely to change management for our patients on the trial as well as for our future patients.
Host: It's such a fascinating and exciting time to be in this field, Dr. O'Malley. And as you've been telling us about immunology, what about some of the most exciting advanced surgical technologies? Is there anything, whether it's intraoperative, radiologic imaging or anything exciting you'd like other providers to know about?
Dr. Padraic O’Malley: Yeah, I think one of the biggest changes in surgical management in all fields has been the advent of minimally invasive surgery. It first began with laparoscopic surgery and now with robotic surgery. Certainly, there were some patients we were able to do laparoscopic surgery on before, but the advent of robotic surgery has really allowed us to do more complex cases. So in patients who have smaller lesions, we can preserve their kidney function by only doing a partial nephrectomy, only taking part of a kidney. And the nice thing about doing that robotically is we can do more complex lesions this way. And patient's recovery time is much quicker. So that's always a benefit for patients and their ongoing day-to-day care.
In the advanced kidney cancer setting, what we're starting to see is a greater utilization of robotic techniques in advanced cases. So one thing we started doing a lot more at the University of Florida is some patients with these advanced types of cancers in the kidney, the tumor will actually start growing along the vein of the kidney and will eventually grow into what's called the inferior vena cava, which is the largest vein that drains the majority of the blood from your lower body and some abdominal organs.
And traditionally, when this happens, this is a big open operation, which requires five to seven-day hospital stay and a fairly large incision most often times. We've actually started doing these robotically. And what we found is that most patients are ready to go home either the day after or the next day and the recovery time is much quicker. So it allows patients not only to get back to what they liked doing quicker, it leads to less of a disruption to quality of life. And it allows them to potentially go on to other therapies should they require them quicker. So we've seen a big change in how long a patient would need to recover with using this technology.
Host: As we wrap up, and again, this is so interesting, do you have anything else you would like to inform other providers about when we're talking about advanced kidney cancer management?
Dr. Padraic O’Malley: Yeah. I think whether you're a primary care physician, a urologist or someone who's incidentally seen someone with a larger renal mass or potentially spread to other organs or to the lymph nodes or to the chest, I think those are the type of patients that we are best managed by providers at high-volume centers who have I'd say more than the expertise of resources.
There are excellent surgeons in many hospitals. But what allows us, I think, to optimize care for these patients is the resource that exists in academic or tertiary care centers, where we can pull in the expertise from medical oncology and radiology. And so many providers out in community care setting may not have access to those resources readily. Their system's not set up for that. They're fine surgeons. It's just that the focus of what they do is not this.
And so I think if you're looking at these patients and you want to optimize their care, I think these patients are best seen at these centers that you do offer clinical trials and do have a multidisciplinary approach to these patients. And I think your patients will thank you for it. And I think you'll be happier with how they do long-term as well.
Host: That's great information, Dr. O'Malley. Thank you so much for joining us today. And to refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters.
That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. Please remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole. - HostsMelanie Cole, MS
- Post Test URLhttps://cme.ufl.edu/mededcast/
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