Expert Interview

We know from the literature and in practice that type 2 diabetes (T2D) is one of the most common risk factors for developing chronic kidney disease (CKD). How prevalent is this overlap, and are certain patients more at risk than others?

Dr. McGill: That’s correct, in fact, 20% to 40% of people with T2D have identifiable CKD, and the rest are at risk for developing CKD in the future. All patients with T2D should recognize that risk and undergo annual screening for CKD. If an individual has prediabetes, then step up the screening to perhaps twice a year to see if the person has progressed. At that point, we can think about intervening with a medication to prevent the onset of diabetes, particularly if the patient is unable to adopt significant lifestyle changes.

In your day-to-day practice, what therapeutic approach do you take in managing patients with T2D and CKD?

Dr. McGill: The earliest and arguably the most important treatment for the care of CKD in T2D is glucose control. Establishing and maintaining blood glucose levels near the normal range is our strongest weapon for preventing CKD. Another treatment avenue is controlling blood pressure. The American Diabetes Association and other groups recommend that blood pressure be less than 130/80 mm Hg. It is critical that we treat hypertension effectively to achieve those numbers.

We also have therapies, such as the SGLT2 inhibitors, that offer protection from progression of CKD and from hospitalization for heart failure. Deployment of these newer agents is important for people who have more advanced diabetes or other serious health conditions.

What is the rate of disease progression, related complications, or even mortality for these patients?

Dr. McGill: People with CKD and T2D are at risk for many things. One risk is progression of kidney disease all the way to end-stage kidney disease, which requires dialysis or transplantation. Another huge risk is cardiovascular events such as myocardial infarction (MI) and stroke.

Persons with kidney disease, for reasons we don't understand, are at higher risk of MI and stroke than people who do not have kidney disease. Therefore, the risks of early mortality and events that adversely affect quality of life are greatly increased.

Can you please discuss the economic burdens associated with T2D and CKD, and whether any interventions are in place to help offset those costs?

Dr. McGill: Diabetes itself is wickedly expensive. We have excellent treatments for diabetes today, but they are very costly. The best approach for the prevention of diabetes is to be screened. When a patient presents with prediabetes, it’s important that they take important measures, such as weight loss, exercising 150 minutes per week, or reducing 500 calories a day from their diet, all of which have been shown to forestall the onset of diabetes.

Once diabetes develops, achieving near-normal glucose control can either be very inexpensive with one or more generic drugs, or it can be terribly expensive with the newer branded drugs. Both options can help with the achievement of near-normal glucose levels, but the newer drugs are better for weight loss and provide protection from heart and kidney disease.

It is important to consider where the patient is along the disease spectrum, and to educate them on the benefits of taking a proactive approach to their health. Don’t wait for diabetes to develop before doing something about it. We have to take action earlier, and more definitively.

We do everything we can to help patients with the high cost of diabetes medications. Pharma companies offer various coupons and patient assistance programs, but it's really important that we get people on the right therapy. In order for that to happen, they have to come to office visits and get lab tests done.

Is there anything else you would like to share on this topic?

Dr. McGill: Once a person has been diagnosed with diabetes, then excellent glucose control from the onset has been shown to prevent later complications, and early treatment is inexpensive. As people progress through their journey with diabetes and blood sugars go up, we have excellent therapies that help manage high glucose and help with weight loss.

We have to be realistic and rethink our approach in some ways, but as long as people develop good health care habits and visit the doctor once or twice a year specifically to address diabetes and blood pressure, we might be able to avoid long-term complications.

We know from the literature and in practice that type 2 diabetes (T2D) is one of the most common risk factors for developing chronic kidney disease (CKD). How prevalent is this overlap, and are certain patients more at risk than others?

Dr. McGill: That’s correct, in fact, 20% to 40% of people with T2D have identifiable CKD, and the rest are at risk for developing CKD in the future. All patients with T2D should recognize that risk and undergo annual screening for CKD. If an individual has prediabetes, then step up the screening to perhaps twice a year to see if the person has progressed. At that point, we can think about intervening with a medication to prevent the onset of diabetes, particularly if the patient is unable to adopt significant lifestyle changes.

In your day-to-day practice, what therapeutic approach do you take in managing patients with T2D and CKD?

Dr. McGill: The earliest and arguably the most important treatment for the care of CKD in T2D is glucose control. Establishing and maintaining blood glucose levels near the normal range is our strongest weapon for preventing CKD. Another treatment avenue is controlling blood pressure. The American Diabetes Association and other groups recommend that blood pressure be less than 130/80 mm Hg. It is critical that we treat hypertension effectively to achieve those numbers.

We also have therapies, such as the SGLT2 inhibitors, that offer protection from progression of CKD and from hospitalization for heart failure. Deployment of these newer agents is important for people who have more advanced diabetes or other serious health conditions.

What is the rate of disease progression, related complications, or even mortality for these patients?

Dr. McGill: People with CKD and T2D are at risk for many things. One risk is progression of kidney disease all the way to end-stage kidney disease, which requires dialysis or transplantation. Another huge risk is cardiovascular events such as myocardial infarction (MI) and stroke.

Persons with kidney disease, for reasons we don't understand, are at higher risk of MI and stroke than people who do not have kidney disease. Therefore, the risks of early mortality and events that adversely affect quality of life are greatly increased.

Can you please discuss the economic burdens associated with T2D and CKD, and whether any interventions are in place to help offset those costs?

Dr. McGill: Diabetes itself is wickedly expensive. We have excellent treatments for diabetes today, but they are very costly. The best approach for the prevention of diabetes is to be screened. When a patient presents with prediabetes, it’s important that they take important measures, such as weight loss, exercising 150 minutes per week, or reducing 500 calories a day from their diet, all of which have been shown to forestall the onset of diabetes.

Once diabetes develops, achieving near-normal glucose control can either be very inexpensive with one or more generic drugs, or it can be terribly expensive with the newer branded drugs. Both options can help with the achievement of near-normal glucose levels, but the newer drugs are better for weight loss and provide protection from heart and kidney disease.

It is important to consider where the patient is along the disease spectrum, and to educate them on the benefits of taking a proactive approach to their health. Don’t wait for diabetes to develop before doing something about it. We have to take action earlier, and more definitively.

We do everything we can to help patients with the high cost of diabetes medications. Pharma companies offer various coupons and patient assistance programs, but it's really important that we get people on the right therapy. In order for that to happen, they have to come to office visits and get lab tests done.

Is there anything else you would like to share on this topic?

Dr. McGill: Once a person has been diagnosed with diabetes, then excellent glucose control from the onset has been shown to prevent later complications, and early treatment is inexpensive. As people progress through their journey with diabetes and blood sugars go up, we have excellent therapies that help manage high glucose and help with weight loss.

We have to be realistic and rethink our approach in some ways, but as long as people develop good health care habits and visit the doctor once or twice a year specifically to address diabetes and blood pressure, we might be able to avoid long-term complications.

We know from the literature and in practice that type 2 diabetes (T2D) is one of the most common risk factors for developing chronic kidney disease (CKD). How prevalent is this overlap, and are certain patients more at risk than others?

Dr. McGill: That’s correct, in fact, 20% to 40% of people with T2D have identifiable CKD, and the rest are at risk for developing CKD in the future. All patients with T2D should recognize that risk and undergo annual screening for CKD. If an individual has prediabetes, then step up the screening to perhaps twice a year to see if the person has progressed. At that point, we can think about intervening with a medication to prevent the onset of diabetes, particularly if the patient is unable to adopt significant lifestyle changes.

In your day-to-day practice, what therapeutic approach do you take in managing patients with T2D and CKD?

Dr. McGill: The earliest and arguably the most important treatment for the care of CKD in T2D is glucose control. Establishing and maintaining blood glucose levels near the normal range is our strongest weapon for preventing CKD. Another treatment avenue is controlling blood pressure. The American Diabetes Association and other groups recommend that blood pressure be less than 130/80 mm Hg. It is critical that we treat hypertension effectively to achieve those numbers.

We also have therapies, such as the SGLT2 inhibitors, that offer protection from progression of CKD and from hospitalization for heart failure. Deployment of these newer agents is important for people who have more advanced diabetes or other serious health conditions.

What is the rate of disease progression, related complications, or even mortality for these patients?

Dr. McGill: People with CKD and T2D are at risk for many things. One risk is progression of kidney disease all the way to end-stage kidney disease, which requires dialysis or transplantation. Another huge risk is cardiovascular events such as myocardial infarction (MI) and stroke.

Persons with kidney disease, for reasons we don't understand, are at higher risk of MI and stroke than people who do not have kidney disease. Therefore, the risks of early mortality and events that adversely affect quality of life are greatly increased.

Can you please discuss the economic burdens associated with T2D and CKD, and whether any interventions are in place to help offset those costs?

Dr. McGill: Diabetes itself is wickedly expensive. We have excellent treatments for diabetes today, but they are very costly. The best approach for the prevention of diabetes is to be screened. When a patient presents with prediabetes, it’s important that they take important measures, such as weight loss, exercising 150 minutes per week, or reducing 500 calories a day from their diet, all of which have been shown to forestall the onset of diabetes.

Once diabetes develops, achieving near-normal glucose control can either be very inexpensive with one or more generic drugs, or it can be terribly expensive with the newer branded drugs. Both options can help with the achievement of near-normal glucose levels, but the newer drugs are better for weight loss and provide protection from heart and kidney disease.

It is important to consider where the patient is along the disease spectrum, and to educate them on the benefits of taking a proactive approach to their health. Don’t wait for diabetes to develop before doing something about it. We have to take action earlier, and more definitively.

We do everything we can to help patients with the high cost of diabetes medications. Pharma companies offer various coupons and patient assistance programs, but it's really important that we get people on the right therapy. In order for that to happen, they have to come to office visits and get lab tests done.

Is there anything else you would like to share on this topic?

Dr. McGill: Once a person has been diagnosed with diabetes, then excellent glucose control from the onset has been shown to prevent later complications, and early treatment is inexpensive. As people progress through their journey with diabetes and blood sugars go up, we have excellent therapies that help manage high glucose and help with weight loss.

We have to be realistic and rethink our approach in some ways, but as long as people develop good health care habits and visit the doctor once or twice a year specifically to address diabetes and blood pressure, we might be able to avoid long-term complications.

Early in 2020, Anne Peters, MD, caught COVID-19. The author of Medscape’s “Peters on Diabetes” column was sick in March 2020 before state-mandated lockdowns, and well before there were any vaccines.

She remembers sitting in a small exam room with two patients who had flown to her Los Angeles office from New York. The elderly couple had hearing difficulties, so Dr. Peters sat close to them, putting on a continuous glucose monitor. “At that time, we didn’t think of COVID-19 as being in L.A.,” Dr. Peters recalled, “so I think we were not terribly consistent at mask-wearing due to the need to educate.”

“Several days later, I got COVID, but I didn’t know I had COVID per se. I felt crappy, had a terrible sore throat, lost my sense of taste and smell [which was not yet described as a COVID symptom], was completely exhausted, but had no fever or cough, which were the only criteria for getting COVID tested at the time. I didn’t know I had been exposed until 2 weeks later, when the patient’s assistant returned the sensor warning us to ‘be careful’ with it because the patient and his wife were recovering from COVID.”

That early battle with COVID-19 was just the beginning of what would become a 2-year struggle, including familial loss amid her own health problems and concerns about the under-resourced patients she cares for. Here, she shares her journey through the pandemic with this news organization.
 

Question: Thanks for talking to us. Let’s discuss your journey over these past 2.5 years.

Answer: Everybody has their own COVID story because we all went through this together. Some of us have worse COVID stories, and some of us have better ones, but all have been impacted.

I’m not a sick person. I’m a very healthy person but COVID made me so unwell for 2 years. The brain fog and fatigue were nothing compared to the autonomic neuropathy that affected my heart. It was really limiting for me. And I still don’t know the long-term implications, looking 20-30 years from now.
 

Q: When you initially had COVID, what were your symptoms? What was the impact?

A: I had all the symptoms of COVID, except for a cough and fever. I lost my sense of taste and smell. I had a horrible headache, a sore throat, and I was exhausted. I couldn’t get tested because I didn’t have the right symptoms.

Despite being sick, I never stopped working but just switched to telemedicine. I also took my regular monthly trip to our cabin in Montana. I unknowingly flew on a plane with COVID. I wore a well-fitted N95 mask, so I don’t think I gave anybody COVID. I didn’t give COVID to my partner, Eric, which is hard to believe as – at 77 – he’s older than me. He has diabetes, heart disease, and every other high-risk characteristic. If he’d gotten COVID back then, it would have been terrible, as there were no treatments, but luckily he didn’t get it.
 

Q: When were you officially diagnosed?

A: Two or 3 months after I thought I might have had COVID, I checked my antibodies, which tested strongly positive for a prior COVID infection. That was when I knew all the symptoms I’d had were due to the disease.

Q: Not only were you dealing with your own illness, but also that of those close to you. Can you talk about that?

A: In April 2020, my mother who was in her 90s and otherwise healthy except for dementia, got COVID. She could have gotten it from me. I visited often but wore a mask. She had all the horrible pulmonary symptoms. In her advance directive, she didn’t want to be hospitalized so I kept her in her home. She died from COVID in her own bed. It was fairly brutal, but at least I kept her where she felt comforted.

My 91-year-old dad was living in a different residential facility. Throughout COVID he had become very depressed because his social patterns had changed. Prior to COVID, they all ate together, but during the pandemic they were unable to. He missed his social connections, disliked being isolated in his room, hated everyone in masks.

He was a bit demented, but not so much that he couldn’t communicate with me or remember where his grandson was going to law school. I wasn’t allowed inside the facility, which was hard on him. I hadn’t told him his wife died because the hospice social workers advised me that I shouldn’t give him news that he couldn’t process readily until I could spend time with him. Unfortunately, that time never came. In December 2020, he got COVID. One of the people in that facility had gone to the hospital, came back, and tested negative, but actually had COVID and gave it to my dad. The guy who gave it to my dad didn’t die but my dad was terribly ill. He died 2 weeks short of getting his vaccine. He was coherent enough to have a conversation. I asked him: ‘Do you want to go to the hospital?’ And he said: ‘No, because it would be too scary,’ since he couldn’t be with me. I put him on hospice and held his hand as he died from pulmonary COVID, which was awful. I couldn’t give him enough morphine or valium to ease his breathing. But his last words to me were “I love you,” and at the very end he seemed peaceful, which was a blessing.

I got an autopsy, because he wanted one. Nothing else was wrong with him other than COVID. It destroyed his lungs. The rest of him was fine – no heart disease, cancer, or anything else. He died of COVID-19, the same as my mother.

That same week, my aunt, my only surviving older relative, who was in Des Moines, Iowa, died of COVID-19. All three family members died before the vaccine came out.

It was hard to lose my parents. I’m the only surviving child because my sister died in her 20s. It’s not been an easy pandemic. But what pandemic is easy? I just happened to have lost more people than most. Ironically, my grandfather was one of the legionnaires at the Bellevue-Stratford Hotel in Philadelphia in 1976 and died of Legionnaire’s disease before we knew what was causing the outbreak.
 

Q: Were you still struggling with COVID?

A: COVID impacted my whole body. I lost a lot of weight. I didn’t want to eat, and my gastrointestinal system was not happy. It took a while for my sense of taste and smell to come back. Nothing tasted good. I’m not a foodie; I don’t really care about food. We could get takeout or whatever, but none of it appealed to me. I’m not so sure it was a taste thing, I just didn’t feel like eating.

I didn’t realize I had “brain fog” per se, because I felt stressed and overwhelmed by the pandemic and my patients’ concerns. But one day, about 3 months after I had developed COVID, I woke up without the fog. Which made me aware that I hadn’t been feeling right up until that point.

The worst symptoms, however, were cardiac. I noticed also immediately that my heart rate went up very quickly with minimal exertion. My pulse has always been in the 55-60 bpm range, and suddenly just walking across a room made it go up to over 140 bpm. If I did any aerobic activity, it went up over 160 and would be associated with dyspnea and chest pain. I believed these were all post-COVID symptoms and felt validated when reports of others having similar issues were published in the literature.

Q: Did you continue seeing patients?

A: Yes, of course. Patients never needed their doctors more. In East L.A., where patients don’t have easy access to telemedicine, I kept going into clinic throughout the pandemic. In the more affluent Westside of Los Angeles, we switched to telemedicine, which was quite effective for most. However, because diabetes was associated with an increased risk of hospitalization and death from COVID, my patients were understandably afraid. I’ve never been busier, but (like all health care providers), I became more of a COVID provider than a diabetologist.

Q: Do you feel your battle with COVID impacted your work?

A: It didn’t affect me at work. If I was sitting still, I was fine. Sitting at home at a desk, I didn’t notice any symptoms. But as a habitual stair-user, I would be gasping for breath in the stairwell because I couldn’t go up the stairs to my office as I once could.

I think you empathize more with people who had COVID (when you’ve had it yourself). There was such a huge patient burden. And I think that’s been the thing that’s affected health care providers the most – no matter what specialty we’re in – that nobody has answers.
 

Q: What happened after you had your vaccine?

A: The vaccine itself was fine. I didn’t have any reaction to the first two doses. But the first booster made my cardiac issues worse.

By this point, my cardiac problems stopped me from exercising. I even went to the ER with chest pain once because I was having palpitations and chest pressure caused by simply taking my morning shower. Fortunately, I wasn’t having an MI, but I certainly wasn’t “normal.”

My measure of my fitness is the cross-country skiing trail I use in Montana. I know exactly how far I can ski. Usually I can do the loop in 35 minutes. After COVID, I lasted 10 minutes. I would be tachycardic, short of breath with chest pain radiating down my left arm. I would rest and try to keep going. But with each rest period, I only got worse. I would be laying in the snow and strangers would ask if I needed help.
 

Q: What helped you?

A: I’ve read a lot about long COVID and have tried to learn from the experts. Of course, I never went to a doctor directly, although I did ask colleagues for advice. What I learned was to never push myself. I forced myself to create an exercise schedule where I only exercised three times a week with rest days in between. When exercising, the second my heart rate went above 140 bpm, I stopped until I could get it back down. I would push against this new limit, even though my limit was low.

Additionally, I worked on my breathing patterns and did meditative breathing for 10 minutes twice daily using a commercially available app.

Although progress was slow, I did improve, and by June 2022, I seemed back to normal. I was not as fit as I was prior to COVID and needed to improve, but the tachycardic response to exercise and cardiac symptoms were gone. I felt like my normal self. Normal enough to go on a spot packing trip in the Sierras in August. (Horses carried us and a mule carried the gear over the 12,000-foot pass into the mountains, and then left my friend and me high in the Sierras for a week.) We were camped above 10,000 feet and every day hiked up to another high mountain lake where we fly-fished for trout that we ate for dinner. The hikes were a challenge, but not abnormally so. Not as they would have been while I had long COVID.
 

Q: What is the current atmosphere in your clinic?

A: COVID is much milder now in my vaccinated patients, but I feel most health care providers are exhausted. Many of my staff left when COVID hit because they didn’t want to keep working. It made practicing medicine exhausting. There’s been a shortage of nurses, a shortage of everything. We’ve been required to do a whole lot more than we ever did before. It’s much harder to be a doctor. This pandemic is the first time I’ve ever thought of quitting. Granted, I lost my whole family, or at least the older generation, but it’s just been almost overwhelming.

On the plus side, almost every one of my patients has been vaccinated, because early on, people would ask: “Do you trust this vaccine?” I would reply: “I saw my parents die from COVID when they weren’t vaccinated, so you’re getting vaccinated. This is real and the vaccines help.” It made me very good at convincing people to get vaccines because I knew what it was like to see someone dying from COVID up close.
 

Q: What advice do you have for those struggling with the COVID pandemic?

A: People need to decide what their own risk is for getting sick and how many times they want to get COVID. At this point, I want people to go out, but safely. In the beginning, when my patients said, “can I go visit my granddaughter?” I said, “no,” but that was before we had the vaccine. Now I feel it is safe to go out using common sense. I still have my patients wear masks on planes. I still have patients try to eat outside as much as possible. And I tell people to take the precautions that make sense, but I tell them to go out and do things because life is short.

I had a patient in his 70s who has many risk factors like heart disease and diabetes. His granddaughter’s Bat Mitzvah in Florida was coming up. He asked: “Can I go?” I told him “Yes,” but to be safe – to wear an N95 mask on the plane and at the event, and stay in his own hotel room, rather than with the whole family. I said, “You need to do this.” Earlier in the pandemic, I saw people who literally died from loneliness and isolation.

He and his wife flew there. He sent me a picture of himself with his granddaughter. When he returned, he showed me a handwritten note from her that said, “I love you so much. Everyone else canceled, which made me cry. You’re the only one who came. You have no idea how much this meant to me.”

He’s back in L.A., and he didn’t get COVID. He said, “It was the best thing I’ve done in years.” That’s what I need to help people with, navigating this world with COVID and assessing risks and benefits. As with all of medicine, my advice is individualized. My advice changes based on the major circulating variant and the rates of the virus in the population, as well as the risk factors of the individual.
 

Q: What are you doing now?

A: I’m trying to avoid getting COVID again, or another booster. I could get pre-exposure monoclonal antibodies but am waiting to do anything further until I see what happens over the fall and winter. I still wear a mask inside but now do a mix of in-person and telemedicine visits. I still try to go to outdoor restaurants, which is easy in California. But I’m flying to see my son in New York and plan to go to Europe this fall for a meeting. I also go to my cabin in Montana every month to get my “dose” of the wilderness. Overall, I travel for conferences and speaking engagements much less because I have learned the joy of staying home.

Thinking back on my life as a doctor, my career began as an intern at Stanford rotating through Ward 5B, the AIDS unit at San Francisco General Hospital, and will likely end with COVID. In spite of all our medical advances, my generation of physicians, much as many generations before us, has a front-row seat to the vulnerability of humans to infectious diseases and how far we still need to go to protect our patients from communicable illness.

A version of this article first appeared on Medscape.com.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts; three books on diabetes; and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

Early in 2020, Anne Peters, MD, caught COVID-19. The author of Medscape’s “Peters on Diabetes” column was sick in March 2020 before state-mandated lockdowns, and well before there were any vaccines.

She remembers sitting in a small exam room with two patients who had flown to her Los Angeles office from New York. The elderly couple had hearing difficulties, so Dr. Peters sat close to them, putting on a continuous glucose monitor. “At that time, we didn’t think of COVID-19 as being in L.A.,” Dr. Peters recalled, “so I think we were not terribly consistent at mask-wearing due to the need to educate.”

“Several days later, I got COVID, but I didn’t know I had COVID per se. I felt crappy, had a terrible sore throat, lost my sense of taste and smell [which was not yet described as a COVID symptom], was completely exhausted, but had no fever or cough, which were the only criteria for getting COVID tested at the time. I didn’t know I had been exposed until 2 weeks later, when the patient’s assistant returned the sensor warning us to ‘be careful’ with it because the patient and his wife were recovering from COVID.”

That early battle with COVID-19 was just the beginning of what would become a 2-year struggle, including familial loss amid her own health problems and concerns about the under-resourced patients she cares for. Here, she shares her journey through the pandemic with this news organization.
 

Question: Thanks for talking to us. Let’s discuss your journey over these past 2.5 years.

Answer: Everybody has their own COVID story because we all went through this together. Some of us have worse COVID stories, and some of us have better ones, but all have been impacted.

I’m not a sick person. I’m a very healthy person but COVID made me so unwell for 2 years. The brain fog and fatigue were nothing compared to the autonomic neuropathy that affected my heart. It was really limiting for me. And I still don’t know the long-term implications, looking 20-30 years from now.
 

Q: When you initially had COVID, what were your symptoms? What was the impact?

A: I had all the symptoms of COVID, except for a cough and fever. I lost my sense of taste and smell. I had a horrible headache, a sore throat, and I was exhausted. I couldn’t get tested because I didn’t have the right symptoms.

Despite being sick, I never stopped working but just switched to telemedicine. I also took my regular monthly trip to our cabin in Montana. I unknowingly flew on a plane with COVID. I wore a well-fitted N95 mask, so I don’t think I gave anybody COVID. I didn’t give COVID to my partner, Eric, which is hard to believe as – at 77 – he’s older than me. He has diabetes, heart disease, and every other high-risk characteristic. If he’d gotten COVID back then, it would have been terrible, as there were no treatments, but luckily he didn’t get it.
 

Q: When were you officially diagnosed?

A: Two or 3 months after I thought I might have had COVID, I checked my antibodies, which tested strongly positive for a prior COVID infection. That was when I knew all the symptoms I’d had were due to the disease.

Q: Not only were you dealing with your own illness, but also that of those close to you. Can you talk about that?

A: In April 2020, my mother who was in her 90s and otherwise healthy except for dementia, got COVID. She could have gotten it from me. I visited often but wore a mask. She had all the horrible pulmonary symptoms. In her advance directive, she didn’t want to be hospitalized so I kept her in her home. She died from COVID in her own bed. It was fairly brutal, but at least I kept her where she felt comforted.

My 91-year-old dad was living in a different residential facility. Throughout COVID he had become very depressed because his social patterns had changed. Prior to COVID, they all ate together, but during the pandemic they were unable to. He missed his social connections, disliked being isolated in his room, hated everyone in masks.

He was a bit demented, but not so much that he couldn’t communicate with me or remember where his grandson was going to law school. I wasn’t allowed inside the facility, which was hard on him. I hadn’t told him his wife died because the hospice social workers advised me that I shouldn’t give him news that he couldn’t process readily until I could spend time with him. Unfortunately, that time never came. In December 2020, he got COVID. One of the people in that facility had gone to the hospital, came back, and tested negative, but actually had COVID and gave it to my dad. The guy who gave it to my dad didn’t die but my dad was terribly ill. He died 2 weeks short of getting his vaccine. He was coherent enough to have a conversation. I asked him: ‘Do you want to go to the hospital?’ And he said: ‘No, because it would be too scary,’ since he couldn’t be with me. I put him on hospice and held his hand as he died from pulmonary COVID, which was awful. I couldn’t give him enough morphine or valium to ease his breathing. But his last words to me were “I love you,” and at the very end he seemed peaceful, which was a blessing.

I got an autopsy, because he wanted one. Nothing else was wrong with him other than COVID. It destroyed his lungs. The rest of him was fine – no heart disease, cancer, or anything else. He died of COVID-19, the same as my mother.

That same week, my aunt, my only surviving older relative, who was in Des Moines, Iowa, died of COVID-19. All three family members died before the vaccine came out.

It was hard to lose my parents. I’m the only surviving child because my sister died in her 20s. It’s not been an easy pandemic. But what pandemic is easy? I just happened to have lost more people than most. Ironically, my grandfather was one of the legionnaires at the Bellevue-Stratford Hotel in Philadelphia in 1976 and died of Legionnaire’s disease before we knew what was causing the outbreak.
 

Q: Were you still struggling with COVID?

A: COVID impacted my whole body. I lost a lot of weight. I didn’t want to eat, and my gastrointestinal system was not happy. It took a while for my sense of taste and smell to come back. Nothing tasted good. I’m not a foodie; I don’t really care about food. We could get takeout or whatever, but none of it appealed to me. I’m not so sure it was a taste thing, I just didn’t feel like eating.

I didn’t realize I had “brain fog” per se, because I felt stressed and overwhelmed by the pandemic and my patients’ concerns. But one day, about 3 months after I had developed COVID, I woke up without the fog. Which made me aware that I hadn’t been feeling right up until that point.

The worst symptoms, however, were cardiac. I noticed also immediately that my heart rate went up very quickly with minimal exertion. My pulse has always been in the 55-60 bpm range, and suddenly just walking across a room made it go up to over 140 bpm. If I did any aerobic activity, it went up over 160 and would be associated with dyspnea and chest pain. I believed these were all post-COVID symptoms and felt validated when reports of others having similar issues were published in the literature.

Q: Did you continue seeing patients?

A: Yes, of course. Patients never needed their doctors more. In East L.A., where patients don’t have easy access to telemedicine, I kept going into clinic throughout the pandemic. In the more affluent Westside of Los Angeles, we switched to telemedicine, which was quite effective for most. However, because diabetes was associated with an increased risk of hospitalization and death from COVID, my patients were understandably afraid. I’ve never been busier, but (like all health care providers), I became more of a COVID provider than a diabetologist.

Q: Do you feel your battle with COVID impacted your work?

A: It didn’t affect me at work. If I was sitting still, I was fine. Sitting at home at a desk, I didn’t notice any symptoms. But as a habitual stair-user, I would be gasping for breath in the stairwell because I couldn’t go up the stairs to my office as I once could.

I think you empathize more with people who had COVID (when you’ve had it yourself). There was such a huge patient burden. And I think that’s been the thing that’s affected health care providers the most – no matter what specialty we’re in – that nobody has answers.
 

Q: What happened after you had your vaccine?

A: The vaccine itself was fine. I didn’t have any reaction to the first two doses. But the first booster made my cardiac issues worse.

By this point, my cardiac problems stopped me from exercising. I even went to the ER with chest pain once because I was having palpitations and chest pressure caused by simply taking my morning shower. Fortunately, I wasn’t having an MI, but I certainly wasn’t “normal.”

My measure of my fitness is the cross-country skiing trail I use in Montana. I know exactly how far I can ski. Usually I can do the loop in 35 minutes. After COVID, I lasted 10 minutes. I would be tachycardic, short of breath with chest pain radiating down my left arm. I would rest and try to keep going. But with each rest period, I only got worse. I would be laying in the snow and strangers would ask if I needed help.
 

Q: What helped you?

A: I’ve read a lot about long COVID and have tried to learn from the experts. Of course, I never went to a doctor directly, although I did ask colleagues for advice. What I learned was to never push myself. I forced myself to create an exercise schedule where I only exercised three times a week with rest days in between. When exercising, the second my heart rate went above 140 bpm, I stopped until I could get it back down. I would push against this new limit, even though my limit was low.

Additionally, I worked on my breathing patterns and did meditative breathing for 10 minutes twice daily using a commercially available app.

Although progress was slow, I did improve, and by June 2022, I seemed back to normal. I was not as fit as I was prior to COVID and needed to improve, but the tachycardic response to exercise and cardiac symptoms were gone. I felt like my normal self. Normal enough to go on a spot packing trip in the Sierras in August. (Horses carried us and a mule carried the gear over the 12,000-foot pass into the mountains, and then left my friend and me high in the Sierras for a week.) We were camped above 10,000 feet and every day hiked up to another high mountain lake where we fly-fished for trout that we ate for dinner. The hikes were a challenge, but not abnormally so. Not as they would have been while I had long COVID.
 

Q: What is the current atmosphere in your clinic?

A: COVID is much milder now in my vaccinated patients, but I feel most health care providers are exhausted. Many of my staff left when COVID hit because they didn’t want to keep working. It made practicing medicine exhausting. There’s been a shortage of nurses, a shortage of everything. We’ve been required to do a whole lot more than we ever did before. It’s much harder to be a doctor. This pandemic is the first time I’ve ever thought of quitting. Granted, I lost my whole family, or at least the older generation, but it’s just been almost overwhelming.

On the plus side, almost every one of my patients has been vaccinated, because early on, people would ask: “Do you trust this vaccine?” I would reply: “I saw my parents die from COVID when they weren’t vaccinated, so you’re getting vaccinated. This is real and the vaccines help.” It made me very good at convincing people to get vaccines because I knew what it was like to see someone dying from COVID up close.
 

Q: What advice do you have for those struggling with the COVID pandemic?

A: People need to decide what their own risk is for getting sick and how many times they want to get COVID. At this point, I want people to go out, but safely. In the beginning, when my patients said, “can I go visit my granddaughter?” I said, “no,” but that was before we had the vaccine. Now I feel it is safe to go out using common sense. I still have my patients wear masks on planes. I still have patients try to eat outside as much as possible. And I tell people to take the precautions that make sense, but I tell them to go out and do things because life is short.

I had a patient in his 70s who has many risk factors like heart disease and diabetes. His granddaughter’s Bat Mitzvah in Florida was coming up. He asked: “Can I go?” I told him “Yes,” but to be safe – to wear an N95 mask on the plane and at the event, and stay in his own hotel room, rather than with the whole family. I said, “You need to do this.” Earlier in the pandemic, I saw people who literally died from loneliness and isolation.

He and his wife flew there. He sent me a picture of himself with his granddaughter. When he returned, he showed me a handwritten note from her that said, “I love you so much. Everyone else canceled, which made me cry. You’re the only one who came. You have no idea how much this meant to me.”

He’s back in L.A., and he didn’t get COVID. He said, “It was the best thing I’ve done in years.” That’s what I need to help people with, navigating this world with COVID and assessing risks and benefits. As with all of medicine, my advice is individualized. My advice changes based on the major circulating variant and the rates of the virus in the population, as well as the risk factors of the individual.
 

Q: What are you doing now?

A: I’m trying to avoid getting COVID again, or another booster. I could get pre-exposure monoclonal antibodies but am waiting to do anything further until I see what happens over the fall and winter. I still wear a mask inside but now do a mix of in-person and telemedicine visits. I still try to go to outdoor restaurants, which is easy in California. But I’m flying to see my son in New York and plan to go to Europe this fall for a meeting. I also go to my cabin in Montana every month to get my “dose” of the wilderness. Overall, I travel for conferences and speaking engagements much less because I have learned the joy of staying home.

Thinking back on my life as a doctor, my career began as an intern at Stanford rotating through Ward 5B, the AIDS unit at San Francisco General Hospital, and will likely end with COVID. In spite of all our medical advances, my generation of physicians, much as many generations before us, has a front-row seat to the vulnerability of humans to infectious diseases and how far we still need to go to protect our patients from communicable illness.

A version of this article first appeared on Medscape.com.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts; three books on diabetes; and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

Early in 2020, Anne Peters, MD, caught COVID-19. The author of Medscape’s “Peters on Diabetes” column was sick in March 2020 before state-mandated lockdowns, and well before there were any vaccines.

She remembers sitting in a small exam room with two patients who had flown to her Los Angeles office from New York. The elderly couple had hearing difficulties, so Dr. Peters sat close to them, putting on a continuous glucose monitor. “At that time, we didn’t think of COVID-19 as being in L.A.,” Dr. Peters recalled, “so I think we were not terribly consistent at mask-wearing due to the need to educate.”

“Several days later, I got COVID, but I didn’t know I had COVID per se. I felt crappy, had a terrible sore throat, lost my sense of taste and smell [which was not yet described as a COVID symptom], was completely exhausted, but had no fever or cough, which were the only criteria for getting COVID tested at the time. I didn’t know I had been exposed until 2 weeks later, when the patient’s assistant returned the sensor warning us to ‘be careful’ with it because the patient and his wife were recovering from COVID.”

That early battle with COVID-19 was just the beginning of what would become a 2-year struggle, including familial loss amid her own health problems and concerns about the under-resourced patients she cares for. Here, she shares her journey through the pandemic with this news organization.
 

Question: Thanks for talking to us. Let’s discuss your journey over these past 2.5 years.

Answer: Everybody has their own COVID story because we all went through this together. Some of us have worse COVID stories, and some of us have better ones, but all have been impacted.

I’m not a sick person. I’m a very healthy person but COVID made me so unwell for 2 years. The brain fog and fatigue were nothing compared to the autonomic neuropathy that affected my heart. It was really limiting for me. And I still don’t know the long-term implications, looking 20-30 years from now.
 

Q: When you initially had COVID, what were your symptoms? What was the impact?

A: I had all the symptoms of COVID, except for a cough and fever. I lost my sense of taste and smell. I had a horrible headache, a sore throat, and I was exhausted. I couldn’t get tested because I didn’t have the right symptoms.

Despite being sick, I never stopped working but just switched to telemedicine. I also took my regular monthly trip to our cabin in Montana. I unknowingly flew on a plane with COVID. I wore a well-fitted N95 mask, so I don’t think I gave anybody COVID. I didn’t give COVID to my partner, Eric, which is hard to believe as – at 77 – he’s older than me. He has diabetes, heart disease, and every other high-risk characteristic. If he’d gotten COVID back then, it would have been terrible, as there were no treatments, but luckily he didn’t get it.
 

Q: When were you officially diagnosed?

A: Two or 3 months after I thought I might have had COVID, I checked my antibodies, which tested strongly positive for a prior COVID infection. That was when I knew all the symptoms I’d had were due to the disease.

Q: Not only were you dealing with your own illness, but also that of those close to you. Can you talk about that?

A: In April 2020, my mother who was in her 90s and otherwise healthy except for dementia, got COVID. She could have gotten it from me. I visited often but wore a mask. She had all the horrible pulmonary symptoms. In her advance directive, she didn’t want to be hospitalized so I kept her in her home. She died from COVID in her own bed. It was fairly brutal, but at least I kept her where she felt comforted.

My 91-year-old dad was living in a different residential facility. Throughout COVID he had become very depressed because his social patterns had changed. Prior to COVID, they all ate together, but during the pandemic they were unable to. He missed his social connections, disliked being isolated in his room, hated everyone in masks.

He was a bit demented, but not so much that he couldn’t communicate with me or remember where his grandson was going to law school. I wasn’t allowed inside the facility, which was hard on him. I hadn’t told him his wife died because the hospice social workers advised me that I shouldn’t give him news that he couldn’t process readily until I could spend time with him. Unfortunately, that time never came. In December 2020, he got COVID. One of the people in that facility had gone to the hospital, came back, and tested negative, but actually had COVID and gave it to my dad. The guy who gave it to my dad didn’t die but my dad was terribly ill. He died 2 weeks short of getting his vaccine. He was coherent enough to have a conversation. I asked him: ‘Do you want to go to the hospital?’ And he said: ‘No, because it would be too scary,’ since he couldn’t be with me. I put him on hospice and held his hand as he died from pulmonary COVID, which was awful. I couldn’t give him enough morphine or valium to ease his breathing. But his last words to me were “I love you,” and at the very end he seemed peaceful, which was a blessing.

I got an autopsy, because he wanted one. Nothing else was wrong with him other than COVID. It destroyed his lungs. The rest of him was fine – no heart disease, cancer, or anything else. He died of COVID-19, the same as my mother.

That same week, my aunt, my only surviving older relative, who was in Des Moines, Iowa, died of COVID-19. All three family members died before the vaccine came out.

It was hard to lose my parents. I’m the only surviving child because my sister died in her 20s. It’s not been an easy pandemic. But what pandemic is easy? I just happened to have lost more people than most. Ironically, my grandfather was one of the legionnaires at the Bellevue-Stratford Hotel in Philadelphia in 1976 and died of Legionnaire’s disease before we knew what was causing the outbreak.
 

Q: Were you still struggling with COVID?

A: COVID impacted my whole body. I lost a lot of weight. I didn’t want to eat, and my gastrointestinal system was not happy. It took a while for my sense of taste and smell to come back. Nothing tasted good. I’m not a foodie; I don’t really care about food. We could get takeout or whatever, but none of it appealed to me. I’m not so sure it was a taste thing, I just didn’t feel like eating.

I didn’t realize I had “brain fog” per se, because I felt stressed and overwhelmed by the pandemic and my patients’ concerns. But one day, about 3 months after I had developed COVID, I woke up without the fog. Which made me aware that I hadn’t been feeling right up until that point.

The worst symptoms, however, were cardiac. I noticed also immediately that my heart rate went up very quickly with minimal exertion. My pulse has always been in the 55-60 bpm range, and suddenly just walking across a room made it go up to over 140 bpm. If I did any aerobic activity, it went up over 160 and would be associated with dyspnea and chest pain. I believed these were all post-COVID symptoms and felt validated when reports of others having similar issues were published in the literature.

Q: Did you continue seeing patients?

A: Yes, of course. Patients never needed their doctors more. In East L.A., where patients don’t have easy access to telemedicine, I kept going into clinic throughout the pandemic. In the more affluent Westside of Los Angeles, we switched to telemedicine, which was quite effective for most. However, because diabetes was associated with an increased risk of hospitalization and death from COVID, my patients were understandably afraid. I’ve never been busier, but (like all health care providers), I became more of a COVID provider than a diabetologist.

Q: Do you feel your battle with COVID impacted your work?

A: It didn’t affect me at work. If I was sitting still, I was fine. Sitting at home at a desk, I didn’t notice any symptoms. But as a habitual stair-user, I would be gasping for breath in the stairwell because I couldn’t go up the stairs to my office as I once could.

I think you empathize more with people who had COVID (when you’ve had it yourself). There was such a huge patient burden. And I think that’s been the thing that’s affected health care providers the most – no matter what specialty we’re in – that nobody has answers.
 

Q: What happened after you had your vaccine?

A: The vaccine itself was fine. I didn’t have any reaction to the first two doses. But the first booster made my cardiac issues worse.

By this point, my cardiac problems stopped me from exercising. I even went to the ER with chest pain once because I was having palpitations and chest pressure caused by simply taking my morning shower. Fortunately, I wasn’t having an MI, but I certainly wasn’t “normal.”

My measure of my fitness is the cross-country skiing trail I use in Montana. I know exactly how far I can ski. Usually I can do the loop in 35 minutes. After COVID, I lasted 10 minutes. I would be tachycardic, short of breath with chest pain radiating down my left arm. I would rest and try to keep going. But with each rest period, I only got worse. I would be laying in the snow and strangers would ask if I needed help.
 

Q: What helped you?

A: I’ve read a lot about long COVID and have tried to learn from the experts. Of course, I never went to a doctor directly, although I did ask colleagues for advice. What I learned was to never push myself. I forced myself to create an exercise schedule where I only exercised three times a week with rest days in between. When exercising, the second my heart rate went above 140 bpm, I stopped until I could get it back down. I would push against this new limit, even though my limit was low.

Additionally, I worked on my breathing patterns and did meditative breathing for 10 minutes twice daily using a commercially available app.

Although progress was slow, I did improve, and by June 2022, I seemed back to normal. I was not as fit as I was prior to COVID and needed to improve, but the tachycardic response to exercise and cardiac symptoms were gone. I felt like my normal self. Normal enough to go on a spot packing trip in the Sierras in August. (Horses carried us and a mule carried the gear over the 12,000-foot pass into the mountains, and then left my friend and me high in the Sierras for a week.) We were camped above 10,000 feet and every day hiked up to another high mountain lake where we fly-fished for trout that we ate for dinner. The hikes were a challenge, but not abnormally so. Not as they would have been while I had long COVID.
 

Q: What is the current atmosphere in your clinic?

A: COVID is much milder now in my vaccinated patients, but I feel most health care providers are exhausted. Many of my staff left when COVID hit because they didn’t want to keep working. It made practicing medicine exhausting. There’s been a shortage of nurses, a shortage of everything. We’ve been required to do a whole lot more than we ever did before. It’s much harder to be a doctor. This pandemic is the first time I’ve ever thought of quitting. Granted, I lost my whole family, or at least the older generation, but it’s just been almost overwhelming.

On the plus side, almost every one of my patients has been vaccinated, because early on, people would ask: “Do you trust this vaccine?” I would reply: “I saw my parents die from COVID when they weren’t vaccinated, so you’re getting vaccinated. This is real and the vaccines help.” It made me very good at convincing people to get vaccines because I knew what it was like to see someone dying from COVID up close.
 

Q: What advice do you have for those struggling with the COVID pandemic?

A: People need to decide what their own risk is for getting sick and how many times they want to get COVID. At this point, I want people to go out, but safely. In the beginning, when my patients said, “can I go visit my granddaughter?” I said, “no,” but that was before we had the vaccine. Now I feel it is safe to go out using common sense. I still have my patients wear masks on planes. I still have patients try to eat outside as much as possible. And I tell people to take the precautions that make sense, but I tell them to go out and do things because life is short.

I had a patient in his 70s who has many risk factors like heart disease and diabetes. His granddaughter’s Bat Mitzvah in Florida was coming up. He asked: “Can I go?” I told him “Yes,” but to be safe – to wear an N95 mask on the plane and at the event, and stay in his own hotel room, rather than with the whole family. I said, “You need to do this.” Earlier in the pandemic, I saw people who literally died from loneliness and isolation.

He and his wife flew there. He sent me a picture of himself with his granddaughter. When he returned, he showed me a handwritten note from her that said, “I love you so much. Everyone else canceled, which made me cry. You’re the only one who came. You have no idea how much this meant to me.”

He’s back in L.A., and he didn’t get COVID. He said, “It was the best thing I’ve done in years.” That’s what I need to help people with, navigating this world with COVID and assessing risks and benefits. As with all of medicine, my advice is individualized. My advice changes based on the major circulating variant and the rates of the virus in the population, as well as the risk factors of the individual.
 

Q: What are you doing now?

A: I’m trying to avoid getting COVID again, or another booster. I could get pre-exposure monoclonal antibodies but am waiting to do anything further until I see what happens over the fall and winter. I still wear a mask inside but now do a mix of in-person and telemedicine visits. I still try to go to outdoor restaurants, which is easy in California. But I’m flying to see my son in New York and plan to go to Europe this fall for a meeting. I also go to my cabin in Montana every month to get my “dose” of the wilderness. Overall, I travel for conferences and speaking engagements much less because I have learned the joy of staying home.

Thinking back on my life as a doctor, my career began as an intern at Stanford rotating through Ward 5B, the AIDS unit at San Francisco General Hospital, and will likely end with COVID. In spite of all our medical advances, my generation of physicians, much as many generations before us, has a front-row seat to the vulnerability of humans to infectious diseases and how far we still need to go to protect our patients from communicable illness.

A version of this article first appeared on Medscape.com.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts; three books on diabetes; and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

As both a clinician and investigator in the breast cancer space, how would you describe our current understanding of genomic assays in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease?

Dr. Kalinsky: There are a number of commercially-available assays for patients with early-stage HR-positive/HER2-negative breast cancer. We have seen the results of 3 large randomized phase 3 trials that have demonstrated and helped establish the clinical utility of assays, including the oncotype DX 21-gene recurrence score. This was evaluated in patients with node-negative breast cancer in the TAILORx trial and in patients with 1 to 3 nodes involved in the RxPONDER trial.

We also have data with the 70-gene MammaPrint assay from the MINDACT study, looking for patients who had a discordance between clinical and genomic risk. MINDACT has been published and was updated recently with data for 8-year distant metastasis-free survival. It is these studies that have helped establish what we do in the clinic and when we consider offering genomic assays in patients with this subtype of breast cancer.

How are you working to bring these genomic assays into practice?

Dr. Kalinsky: In 2020, we reported the initial results from the RxPonder study demonstrating that for patients with HR-positive HER2-negative breast cancer with 1 to 3 nodes involved, two-thirds of the patients were postmenopausal. For patients who had a recurrence score of 25 or less, we did not identify a subgroup of patients who benefited from chemotherapy.

For the premenopausal women, which was one-third of the patients, we saw that all those patients benefited from the addition of chemotherapy if the recurrence score was 25 or less. We did a number of subgroup analyses, which we reported on at the San Antonio Breast Cancer Symposium in 2021.

Several analyses are ongoing. These include some subgroup analyses looking at quality of life as well as a collection of circulating markers. In addition, there is ongoing biomarker work looking at tumor tissue to see if there are differences between the biology of premenopausal versus postmenopausal women.

What value does genomic testing bring to the treatment of HR-positive/HER2-negative breast cancer?

Dr. Kalinsky: These assays have achieved clinical utility, and this has been reflected in the recent update to the ASCO Guidelines for genomic assays. We have also learned that it is not just the assay by itself, but also the clinical features of a patient that help determine risk. In other words, it’s not just dependent on the score, but also involves the context of other important clinical features, including patient and tumor characteristics such as tumor size, patient age, and tumor grade. All of these add value and help us assess a patient’s individualized risk.

Is there a specific profile or qualifications candidates must meet for genomic testing to be done?

Dr. Kalinsky: We offer genomic tests for patients with HR-positive/HER2-negative breast cancer who are node-negative or have 1 to 3 nodes involved. There are other commercially-available tests such as the Breast Cancer Index, which assesses risk of recurrence in years 5 to 10 and looks at whether there is potential utility for continuing anti-estrogen therapy. That assay provides both prognostic and predictive information.

Is there any additional insight on genomic assays in HR-positive/HER2-negative breast cancer you would like to share?

Dr. Kalinsky: We’ve been talking about tumor-based assays. However, the question is, what’s going to be the role for circulating markers, such as circulating tumor DNA (ctDNA) or circulating tumor cells? There is a lot of information that we’re hoping to understand, not just regarding the prognostic significance but also the predictive utility. If you have a patient with a subtype of breast cancer and we know this subgroup can be at risk for late recurrence, if you identify said marker and you switch the therapy, do you see clearance of ctDNA? Does that lead to an improvement in outcome? That is an important question that is going to be answered in current and future trials.

As both a clinician and investigator in the breast cancer space, how would you describe our current understanding of genomic assays in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease?

Dr. Kalinsky: There are a number of commercially-available assays for patients with early-stage HR-positive/HER2-negative breast cancer. We have seen the results of 3 large randomized phase 3 trials that have demonstrated and helped establish the clinical utility of assays, including the oncotype DX 21-gene recurrence score. This was evaluated in patients with node-negative breast cancer in the TAILORx trial and in patients with 1 to 3 nodes involved in the RxPONDER trial.

We also have data with the 70-gene MammaPrint assay from the MINDACT study, looking for patients who had a discordance between clinical and genomic risk. MINDACT has been published and was updated recently with data for 8-year distant metastasis-free survival. It is these studies that have helped establish what we do in the clinic and when we consider offering genomic assays in patients with this subtype of breast cancer.

How are you working to bring these genomic assays into practice?

Dr. Kalinsky: In 2020, we reported the initial results from the RxPonder study demonstrating that for patients with HR-positive HER2-negative breast cancer with 1 to 3 nodes involved, two-thirds of the patients were postmenopausal. For patients who had a recurrence score of 25 or less, we did not identify a subgroup of patients who benefited from chemotherapy.

For the premenopausal women, which was one-third of the patients, we saw that all those patients benefited from the addition of chemotherapy if the recurrence score was 25 or less. We did a number of subgroup analyses, which we reported on at the San Antonio Breast Cancer Symposium in 2021.

Several analyses are ongoing. These include some subgroup analyses looking at quality of life as well as a collection of circulating markers. In addition, there is ongoing biomarker work looking at tumor tissue to see if there are differences between the biology of premenopausal versus postmenopausal women.

What value does genomic testing bring to the treatment of HR-positive/HER2-negative breast cancer?

Dr. Kalinsky: These assays have achieved clinical utility, and this has been reflected in the recent update to the ASCO Guidelines for genomic assays. We have also learned that it is not just the assay by itself, but also the clinical features of a patient that help determine risk. In other words, it’s not just dependent on the score, but also involves the context of other important clinical features, including patient and tumor characteristics such as tumor size, patient age, and tumor grade. All of these add value and help us assess a patient’s individualized risk.

Is there a specific profile or qualifications candidates must meet for genomic testing to be done?

Dr. Kalinsky: We offer genomic tests for patients with HR-positive/HER2-negative breast cancer who are node-negative or have 1 to 3 nodes involved. There are other commercially-available tests such as the Breast Cancer Index, which assesses risk of recurrence in years 5 to 10 and looks at whether there is potential utility for continuing anti-estrogen therapy. That assay provides both prognostic and predictive information.

Is there any additional insight on genomic assays in HR-positive/HER2-negative breast cancer you would like to share?

Dr. Kalinsky: We’ve been talking about tumor-based assays. However, the question is, what’s going to be the role for circulating markers, such as circulating tumor DNA (ctDNA) or circulating tumor cells? There is a lot of information that we’re hoping to understand, not just regarding the prognostic significance but also the predictive utility. If you have a patient with a subtype of breast cancer and we know this subgroup can be at risk for late recurrence, if you identify said marker and you switch the therapy, do you see clearance of ctDNA? Does that lead to an improvement in outcome? That is an important question that is going to be answered in current and future trials.

As both a clinician and investigator in the breast cancer space, how would you describe our current understanding of genomic assays in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease?

Dr. Kalinsky: There are a number of commercially-available assays for patients with early-stage HR-positive/HER2-negative breast cancer. We have seen the results of 3 large randomized phase 3 trials that have demonstrated and helped establish the clinical utility of assays, including the oncotype DX 21-gene recurrence score. This was evaluated in patients with node-negative breast cancer in the TAILORx trial and in patients with 1 to 3 nodes involved in the RxPONDER trial.

We also have data with the 70-gene MammaPrint assay from the MINDACT study, looking for patients who had a discordance between clinical and genomic risk. MINDACT has been published and was updated recently with data for 8-year distant metastasis-free survival. It is these studies that have helped establish what we do in the clinic and when we consider offering genomic assays in patients with this subtype of breast cancer.

How are you working to bring these genomic assays into practice?

Dr. Kalinsky: In 2020, we reported the initial results from the RxPonder study demonstrating that for patients with HR-positive HER2-negative breast cancer with 1 to 3 nodes involved, two-thirds of the patients were postmenopausal. For patients who had a recurrence score of 25 or less, we did not identify a subgroup of patients who benefited from chemotherapy.

For the premenopausal women, which was one-third of the patients, we saw that all those patients benefited from the addition of chemotherapy if the recurrence score was 25 or less. We did a number of subgroup analyses, which we reported on at the San Antonio Breast Cancer Symposium in 2021.

Several analyses are ongoing. These include some subgroup analyses looking at quality of life as well as a collection of circulating markers. In addition, there is ongoing biomarker work looking at tumor tissue to see if there are differences between the biology of premenopausal versus postmenopausal women.

What value does genomic testing bring to the treatment of HR-positive/HER2-negative breast cancer?

Dr. Kalinsky: These assays have achieved clinical utility, and this has been reflected in the recent update to the ASCO Guidelines for genomic assays. We have also learned that it is not just the assay by itself, but also the clinical features of a patient that help determine risk. In other words, it’s not just dependent on the score, but also involves the context of other important clinical features, including patient and tumor characteristics such as tumor size, patient age, and tumor grade. All of these add value and help us assess a patient’s individualized risk.

Is there a specific profile or qualifications candidates must meet for genomic testing to be done?

Dr. Kalinsky: We offer genomic tests for patients with HR-positive/HER2-negative breast cancer who are node-negative or have 1 to 3 nodes involved. There are other commercially-available tests such as the Breast Cancer Index, which assesses risk of recurrence in years 5 to 10 and looks at whether there is potential utility for continuing anti-estrogen therapy. That assay provides both prognostic and predictive information.

Is there any additional insight on genomic assays in HR-positive/HER2-negative breast cancer you would like to share?

Dr. Kalinsky: We’ve been talking about tumor-based assays. However, the question is, what’s going to be the role for circulating markers, such as circulating tumor DNA (ctDNA) or circulating tumor cells? There is a lot of information that we’re hoping to understand, not just regarding the prognostic significance but also the predictive utility. If you have a patient with a subtype of breast cancer and we know this subgroup can be at risk for late recurrence, if you identify said marker and you switch the therapy, do you see clearance of ctDNA? Does that lead to an improvement in outcome? That is an important question that is going to be answered in current and future trials.

What characteristics or symptoms do you look for to identify patients who are at risk for exocrine pancreatic insufficiency (EPI)?

Dr. Barkin: The first thing we have to understand is which patient populations we should consider. EPI traditionally has been a disease associated with chronic pancreatitis, and that still makes up the majority of patients. But in addition to those with chronic pancreatitis, we have to think about patients who have had severe acute pancreatitis and who may have had loss of functional pancreatic parenchyma or pancreatic surgery, as well as patients with pancreatic cancer that may cause both ductal obstruction and parenchyma loss.

This might also include patients with foregut surgery who may develop postcibal dyskinesia, meaning they do not get appropriate mixing of the gastric chyme and food contents with the pancreatic enzymes and pancreatic juice in the duodenum. For example, this might be evident in patients who have had a Roux-en-Y gastric bypass, or in patients with untreated celiac disease, who do not get stimulation for pancreatic secretion based on the amount of small bowel mucosal damage.

A series of other conditions may present with EPI, such as inflammatory bowel disease, although these make up the minority of cases. When we think about symptoms, the end symptom of EPI from fat malabsorption is gross steatorrhea. Unfortunately, by the time the patient gets to that point, the cat is out of the bag—especially in patients with chronic pancreatitis. So, we want to try to identify these patients earlier.

Realistically, a series of symptoms can be seen far earlier than gross steatorrhea. In fact, most patients will present with symptoms like increased stool frequency or decreased stool consistency in their daily life. Some abdominal discomfort or bloating may be seen that is associated with maldigestion of  food, among other factors.

In some patients, night vision changes from fat-soluble vitamin deficiencies may be the first or an early presenting symptom if they have other conditions masking their diarrheal symptoms. Patients who do not feel well when they are eating or feel uncomfortable after they eat may avoid certain types of foods. You may see weight loss in these populations because they are avoiding foods, feeling sitophobia, or not appropriately digesting their food.

Unfortunately, even before we see clinically relevant symptoms, we may see micronutrient deficiencies and fat-soluble vitamin deficiencies. That is why it is so important, for example, in the chronic pancreatitis population, to screen these patients on a regular basis for the presence of EPI, whether with symptom questionnaires or by testing.

Can you expand on some of the risk factors and the importance of screening, particularly for malnutrition?

Dr. Barkin: The risk factors usually involve patients who have had some kind of damage to the gland. For example, many patients with cystic fibrosis are actually exocrine pancreatic insufficient from early in life to diagnosis. They have loss of the gland and loss of function at the gland.

Our patients with chronic pancreatitis, who may have had either recurrent acute pancreatitis or chronic pancreatitis for a variety of reasons, are screened for EPI on a regular basis. That may mean that you ask them a symptom questionnaire at each clinic visit and check a fecal elastase level on a regular basis. It is not just the symptoms that we have to worry about; we have to think about the effects of maldigestion on a patient’s weight and nutritional status and the impact of micronutrient deficiencies.

A series of new studies has looked at the impact of exocrine insufficiency. For example, a study from Spain found an increased risk of all-cause mortality with exocrine insufficiency. When we think about metabolic bone disease in this population with exocrine insufficiency, we see that there is decreased bone density and increased risk of pathologic low-trauma fractures. For example, the patient who has fallen from a standing position at home and suddenly has a hip fracture has substantial morbidity and mortality associated with that fracture. The decreases in bone density and increased risk of fracture are reversed when we identify EPI and treat it appropriately.

What is your approach to diagnosing EPI?

Dr. Barkin: For a patient who walks in the door with an obvious diagnosis or prior diagnosis of chronic pancreatitis, it is relatively easy to ask them a series of questions about whether they have symptoms that may be associated with EPI. So, first, I ask them about their bowel habits and stool frequency and consistency.

A couple of years ago, we showed that if you treat a patient with EPI using pancreatic enzyme replacement therapy, their stool consistency and frequency are the two reliable markers that get better. They not only get better, but these improvements directly correlate with objective stool markers of improvement in fat maldigestion.

Obviously, we want improvement in other symptoms—abdominal discomfort, bloating, etc.—but I have to set very realistic expectations for patients. Along with stool frequency and consistency, there should be subsequent improvement of steatorrhea. I talk to them about the importance of taking a multivitamin to prevent those micronutrient deficiencies. We check for micronutrient deficiencies and fat-soluble vitamin deficiencies routinely.

Patients who do not have obvious chronic pancreatitis who get diagnosed with EPI are a little bit harder to parse out. I want to make sure that they do not have celiac disease, or that they do not have a concomitant mimicking symptom that may result in, for example, a low fecal elastase level. I also check for small intestinal bacterial overgrowth (SIBO) as a mimicking condition.

Regarding fecal elastase testing, the gold standard for diagnosis of EPI was historically a 72-hour fecal fat collection on a standardized-fat-intake diet. That required patient confinement in the hospital. It is cumbersome, not widely available, and not realistic in practice.

In some centers, endoscopic pancreatic function testing, secretin-enhanced magnetic resonance cholangiopancreatography (MRCP), or breath testing, as is done in Europe, may be options to help diagnose EPI, but these tests are not widely available. Unfortunately, we do not have a great diagnostic test for exocrine insufficiency. As a result, we use fecal elastase level. If you have a patient who has a high pretest probability of having EPI, it is a relatively good test. If they have a low pretest probability, then a series of false-positive test results may occur in this patient population. That means they may not actually have exocrine insufficiency.

If a diarrheal stool is submitted for testing, a false-positive fecal elastase test may result. That is really key, because I see a number of patients with potentially functional diarrheal symptoms who also have low fecal elastase levels. As a result, they have been labeled as exocrine insufficient when, in fact, they may not actually have the disease, which is why it is so important to understand and think about that.

How do you choose the appropriate approach to managing EPI, and how do you consider the impact it has on the quality of life overall?

Dr. Barkin: There are two key points. The treatment for EPI is not to tell your patient to not eat fat and hope that it gets better. Rather, it is appropriate supplementation of pancreatic enzymes. This is done with pancreatic enzyme replacement therapy. A few FDA-approved medications are on the market. I recommend against the ones that have been labeled as pancreatic enzyme digestive aids that are available online. Those are not pancreatic enzymes; a regulatory push about 15 to 20 years ago got these digestive aids appropriately regulated.

The FDA-approved medications are dosed at approximately 40,000 to 50,000 lipase units per meal to start, according to the guidelines. Some of us may prescribe higher doses than that to start. These are taken with meals and about a half-dose with snacks.

If you have a patient who is taking, for example, two pills per meal or two capsules per meal, it is important that they take one at the very beginning of the meal and one about halfway through the meal. The pills should not be taken a half hour before or a half hour after the meal. The goal is to simulate normal pancreatic function as much as possible to get the food contents mixing.

The pancreatic enzymes come in a coated version that does not require coadministration with proton pump inhibitors or an uncoated version that does require coadministration of proton pump inhibitors to prevent degradation by gastric acid. Patients need to understand that, although they may take a large number of pills per day, adhering to this regimen is important, not only for treating their symptoms, but also for combating long-term morbidity and mortality.

I use the symptomatic response to assess response to therapy because, as discussed, there is a direct correlation between improvements in stool frequency and consistency and objective markers of response to therapy.

If a patient is not responding, we first check to make sure that there are no adherence issues and that they are able to access therapy, because sometimes there are issues with cost or insurance approvals. Second, I make sure that patients are taking it correctly, and that they understand the difference between a meal and a snack. For example, if somebody says, “Oh, I just had a small cheeseburger and that's my snack,” that is actually a meal and may require more enzymes. Once we ensure that those are not issues, I make sure again, as part of my approach, that there are no comorbid conditions that may be driving some of the symptoms, such as celiac disease or SIBO, with SIBO being very common in this population.

Then we have to decide whether we need to change the dose. Do we need to increase the dose? Some of us start a little bit higher than the 40,000 to 50,000 units of lipase per meal, as suggested in some of our national and international guidelines, and go from there.

What characteristics or symptoms do you look for to identify patients who are at risk for exocrine pancreatic insufficiency (EPI)?

Dr. Barkin: The first thing we have to understand is which patient populations we should consider. EPI traditionally has been a disease associated with chronic pancreatitis, and that still makes up the majority of patients. But in addition to those with chronic pancreatitis, we have to think about patients who have had severe acute pancreatitis and who may have had loss of functional pancreatic parenchyma or pancreatic surgery, as well as patients with pancreatic cancer that may cause both ductal obstruction and parenchyma loss.

This might also include patients with foregut surgery who may develop postcibal dyskinesia, meaning they do not get appropriate mixing of the gastric chyme and food contents with the pancreatic enzymes and pancreatic juice in the duodenum. For example, this might be evident in patients who have had a Roux-en-Y gastric bypass, or in patients with untreated celiac disease, who do not get stimulation for pancreatic secretion based on the amount of small bowel mucosal damage.

A series of other conditions may present with EPI, such as inflammatory bowel disease, although these make up the minority of cases. When we think about symptoms, the end symptom of EPI from fat malabsorption is gross steatorrhea. Unfortunately, by the time the patient gets to that point, the cat is out of the bag—especially in patients with chronic pancreatitis. So, we want to try to identify these patients earlier.

Realistically, a series of symptoms can be seen far earlier than gross steatorrhea. In fact, most patients will present with symptoms like increased stool frequency or decreased stool consistency in their daily life. Some abdominal discomfort or bloating may be seen that is associated with maldigestion of  food, among other factors.

In some patients, night vision changes from fat-soluble vitamin deficiencies may be the first or an early presenting symptom if they have other conditions masking their diarrheal symptoms. Patients who do not feel well when they are eating or feel uncomfortable after they eat may avoid certain types of foods. You may see weight loss in these populations because they are avoiding foods, feeling sitophobia, or not appropriately digesting their food.

Unfortunately, even before we see clinically relevant symptoms, we may see micronutrient deficiencies and fat-soluble vitamin deficiencies. That is why it is so important, for example, in the chronic pancreatitis population, to screen these patients on a regular basis for the presence of EPI, whether with symptom questionnaires or by testing.

Can you expand on some of the risk factors and the importance of screening, particularly for malnutrition?

Dr. Barkin: The risk factors usually involve patients who have had some kind of damage to the gland. For example, many patients with cystic fibrosis are actually exocrine pancreatic insufficient from early in life to diagnosis. They have loss of the gland and loss of function at the gland.

Our patients with chronic pancreatitis, who may have had either recurrent acute pancreatitis or chronic pancreatitis for a variety of reasons, are screened for EPI on a regular basis. That may mean that you ask them a symptom questionnaire at each clinic visit and check a fecal elastase level on a regular basis. It is not just the symptoms that we have to worry about; we have to think about the effects of maldigestion on a patient’s weight and nutritional status and the impact of micronutrient deficiencies.

A series of new studies has looked at the impact of exocrine insufficiency. For example, a study from Spain found an increased risk of all-cause mortality with exocrine insufficiency. When we think about metabolic bone disease in this population with exocrine insufficiency, we see that there is decreased bone density and increased risk of pathologic low-trauma fractures. For example, the patient who has fallen from a standing position at home and suddenly has a hip fracture has substantial morbidity and mortality associated with that fracture. The decreases in bone density and increased risk of fracture are reversed when we identify EPI and treat it appropriately.

What is your approach to diagnosing EPI?

Dr. Barkin: For a patient who walks in the door with an obvious diagnosis or prior diagnosis of chronic pancreatitis, it is relatively easy to ask them a series of questions about whether they have symptoms that may be associated with EPI. So, first, I ask them about their bowel habits and stool frequency and consistency.

A couple of years ago, we showed that if you treat a patient with EPI using pancreatic enzyme replacement therapy, their stool consistency and frequency are the two reliable markers that get better. They not only get better, but these improvements directly correlate with objective stool markers of improvement in fat maldigestion.

Obviously, we want improvement in other symptoms—abdominal discomfort, bloating, etc.—but I have to set very realistic expectations for patients. Along with stool frequency and consistency, there should be subsequent improvement of steatorrhea. I talk to them about the importance of taking a multivitamin to prevent those micronutrient deficiencies. We check for micronutrient deficiencies and fat-soluble vitamin deficiencies routinely.

Patients who do not have obvious chronic pancreatitis who get diagnosed with EPI are a little bit harder to parse out. I want to make sure that they do not have celiac disease, or that they do not have a concomitant mimicking symptom that may result in, for example, a low fecal elastase level. I also check for small intestinal bacterial overgrowth (SIBO) as a mimicking condition.

Regarding fecal elastase testing, the gold standard for diagnosis of EPI was historically a 72-hour fecal fat collection on a standardized-fat-intake diet. That required patient confinement in the hospital. It is cumbersome, not widely available, and not realistic in practice.

In some centers, endoscopic pancreatic function testing, secretin-enhanced magnetic resonance cholangiopancreatography (MRCP), or breath testing, as is done in Europe, may be options to help diagnose EPI, but these tests are not widely available. Unfortunately, we do not have a great diagnostic test for exocrine insufficiency. As a result, we use fecal elastase level. If you have a patient who has a high pretest probability of having EPI, it is a relatively good test. If they have a low pretest probability, then a series of false-positive test results may occur in this patient population. That means they may not actually have exocrine insufficiency.

If a diarrheal stool is submitted for testing, a false-positive fecal elastase test may result. That is really key, because I see a number of patients with potentially functional diarrheal symptoms who also have low fecal elastase levels. As a result, they have been labeled as exocrine insufficient when, in fact, they may not actually have the disease, which is why it is so important to understand and think about that.

How do you choose the appropriate approach to managing EPI, and how do you consider the impact it has on the quality of life overall?

Dr. Barkin: There are two key points. The treatment for EPI is not to tell your patient to not eat fat and hope that it gets better. Rather, it is appropriate supplementation of pancreatic enzymes. This is done with pancreatic enzyme replacement therapy. A few FDA-approved medications are on the market. I recommend against the ones that have been labeled as pancreatic enzyme digestive aids that are available online. Those are not pancreatic enzymes; a regulatory push about 15 to 20 years ago got these digestive aids appropriately regulated.

The FDA-approved medications are dosed at approximately 40,000 to 50,000 lipase units per meal to start, according to the guidelines. Some of us may prescribe higher doses than that to start. These are taken with meals and about a half-dose with snacks.

If you have a patient who is taking, for example, two pills per meal or two capsules per meal, it is important that they take one at the very beginning of the meal and one about halfway through the meal. The pills should not be taken a half hour before or a half hour after the meal. The goal is to simulate normal pancreatic function as much as possible to get the food contents mixing.

The pancreatic enzymes come in a coated version that does not require coadministration with proton pump inhibitors or an uncoated version that does require coadministration of proton pump inhibitors to prevent degradation by gastric acid. Patients need to understand that, although they may take a large number of pills per day, adhering to this regimen is important, not only for treating their symptoms, but also for combating long-term morbidity and mortality.

I use the symptomatic response to assess response to therapy because, as discussed, there is a direct correlation between improvements in stool frequency and consistency and objective markers of response to therapy.

If a patient is not responding, we first check to make sure that there are no adherence issues and that they are able to access therapy, because sometimes there are issues with cost or insurance approvals. Second, I make sure that patients are taking it correctly, and that they understand the difference between a meal and a snack. For example, if somebody says, “Oh, I just had a small cheeseburger and that's my snack,” that is actually a meal and may require more enzymes. Once we ensure that those are not issues, I make sure again, as part of my approach, that there are no comorbid conditions that may be driving some of the symptoms, such as celiac disease or SIBO, with SIBO being very common in this population.

Then we have to decide whether we need to change the dose. Do we need to increase the dose? Some of us start a little bit higher than the 40,000 to 50,000 units of lipase per meal, as suggested in some of our national and international guidelines, and go from there.

What characteristics or symptoms do you look for to identify patients who are at risk for exocrine pancreatic insufficiency (EPI)?

Dr. Barkin: The first thing we have to understand is which patient populations we should consider. EPI traditionally has been a disease associated with chronic pancreatitis, and that still makes up the majority of patients. But in addition to those with chronic pancreatitis, we have to think about patients who have had severe acute pancreatitis and who may have had loss of functional pancreatic parenchyma or pancreatic surgery, as well as patients with pancreatic cancer that may cause both ductal obstruction and parenchyma loss.

This might also include patients with foregut surgery who may develop postcibal dyskinesia, meaning they do not get appropriate mixing of the gastric chyme and food contents with the pancreatic enzymes and pancreatic juice in the duodenum. For example, this might be evident in patients who have had a Roux-en-Y gastric bypass, or in patients with untreated celiac disease, who do not get stimulation for pancreatic secretion based on the amount of small bowel mucosal damage.

A series of other conditions may present with EPI, such as inflammatory bowel disease, although these make up the minority of cases. When we think about symptoms, the end symptom of EPI from fat malabsorption is gross steatorrhea. Unfortunately, by the time the patient gets to that point, the cat is out of the bag—especially in patients with chronic pancreatitis. So, we want to try to identify these patients earlier.

Realistically, a series of symptoms can be seen far earlier than gross steatorrhea. In fact, most patients will present with symptoms like increased stool frequency or decreased stool consistency in their daily life. Some abdominal discomfort or bloating may be seen that is associated with maldigestion of  food, among other factors.

In some patients, night vision changes from fat-soluble vitamin deficiencies may be the first or an early presenting symptom if they have other conditions masking their diarrheal symptoms. Patients who do not feel well when they are eating or feel uncomfortable after they eat may avoid certain types of foods. You may see weight loss in these populations because they are avoiding foods, feeling sitophobia, or not appropriately digesting their food.

Unfortunately, even before we see clinically relevant symptoms, we may see micronutrient deficiencies and fat-soluble vitamin deficiencies. That is why it is so important, for example, in the chronic pancreatitis population, to screen these patients on a regular basis for the presence of EPI, whether with symptom questionnaires or by testing.

Can you expand on some of the risk factors and the importance of screening, particularly for malnutrition?

Dr. Barkin: The risk factors usually involve patients who have had some kind of damage to the gland. For example, many patients with cystic fibrosis are actually exocrine pancreatic insufficient from early in life to diagnosis. They have loss of the gland and loss of function at the gland.

Our patients with chronic pancreatitis, who may have had either recurrent acute pancreatitis or chronic pancreatitis for a variety of reasons, are screened for EPI on a regular basis. That may mean that you ask them a symptom questionnaire at each clinic visit and check a fecal elastase level on a regular basis. It is not just the symptoms that we have to worry about; we have to think about the effects of maldigestion on a patient’s weight and nutritional status and the impact of micronutrient deficiencies.

A series of new studies has looked at the impact of exocrine insufficiency. For example, a study from Spain found an increased risk of all-cause mortality with exocrine insufficiency. When we think about metabolic bone disease in this population with exocrine insufficiency, we see that there is decreased bone density and increased risk of pathologic low-trauma fractures. For example, the patient who has fallen from a standing position at home and suddenly has a hip fracture has substantial morbidity and mortality associated with that fracture. The decreases in bone density and increased risk of fracture are reversed when we identify EPI and treat it appropriately.

What is your approach to diagnosing EPI?

Dr. Barkin: For a patient who walks in the door with an obvious diagnosis or prior diagnosis of chronic pancreatitis, it is relatively easy to ask them a series of questions about whether they have symptoms that may be associated with EPI. So, first, I ask them about their bowel habits and stool frequency and consistency.

A couple of years ago, we showed that if you treat a patient with EPI using pancreatic enzyme replacement therapy, their stool consistency and frequency are the two reliable markers that get better. They not only get better, but these improvements directly correlate with objective stool markers of improvement in fat maldigestion.

Obviously, we want improvement in other symptoms—abdominal discomfort, bloating, etc.—but I have to set very realistic expectations for patients. Along with stool frequency and consistency, there should be subsequent improvement of steatorrhea. I talk to them about the importance of taking a multivitamin to prevent those micronutrient deficiencies. We check for micronutrient deficiencies and fat-soluble vitamin deficiencies routinely.

Patients who do not have obvious chronic pancreatitis who get diagnosed with EPI are a little bit harder to parse out. I want to make sure that they do not have celiac disease, or that they do not have a concomitant mimicking symptom that may result in, for example, a low fecal elastase level. I also check for small intestinal bacterial overgrowth (SIBO) as a mimicking condition.

Regarding fecal elastase testing, the gold standard for diagnosis of EPI was historically a 72-hour fecal fat collection on a standardized-fat-intake diet. That required patient confinement in the hospital. It is cumbersome, not widely available, and not realistic in practice.

In some centers, endoscopic pancreatic function testing, secretin-enhanced magnetic resonance cholangiopancreatography (MRCP), or breath testing, as is done in Europe, may be options to help diagnose EPI, but these tests are not widely available. Unfortunately, we do not have a great diagnostic test for exocrine insufficiency. As a result, we use fecal elastase level. If you have a patient who has a high pretest probability of having EPI, it is a relatively good test. If they have a low pretest probability, then a series of false-positive test results may occur in this patient population. That means they may not actually have exocrine insufficiency.

If a diarrheal stool is submitted for testing, a false-positive fecal elastase test may result. That is really key, because I see a number of patients with potentially functional diarrheal symptoms who also have low fecal elastase levels. As a result, they have been labeled as exocrine insufficient when, in fact, they may not actually have the disease, which is why it is so important to understand and think about that.

How do you choose the appropriate approach to managing EPI, and how do you consider the impact it has on the quality of life overall?

Dr. Barkin: There are two key points. The treatment for EPI is not to tell your patient to not eat fat and hope that it gets better. Rather, it is appropriate supplementation of pancreatic enzymes. This is done with pancreatic enzyme replacement therapy. A few FDA-approved medications are on the market. I recommend against the ones that have been labeled as pancreatic enzyme digestive aids that are available online. Those are not pancreatic enzymes; a regulatory push about 15 to 20 years ago got these digestive aids appropriately regulated.

The FDA-approved medications are dosed at approximately 40,000 to 50,000 lipase units per meal to start, according to the guidelines. Some of us may prescribe higher doses than that to start. These are taken with meals and about a half-dose with snacks.

If you have a patient who is taking, for example, two pills per meal or two capsules per meal, it is important that they take one at the very beginning of the meal and one about halfway through the meal. The pills should not be taken a half hour before or a half hour after the meal. The goal is to simulate normal pancreatic function as much as possible to get the food contents mixing.

The pancreatic enzymes come in a coated version that does not require coadministration with proton pump inhibitors or an uncoated version that does require coadministration of proton pump inhibitors to prevent degradation by gastric acid. Patients need to understand that, although they may take a large number of pills per day, adhering to this regimen is important, not only for treating their symptoms, but also for combating long-term morbidity and mortality.

I use the symptomatic response to assess response to therapy because, as discussed, there is a direct correlation between improvements in stool frequency and consistency and objective markers of response to therapy.

If a patient is not responding, we first check to make sure that there are no adherence issues and that they are able to access therapy, because sometimes there are issues with cost or insurance approvals. Second, I make sure that patients are taking it correctly, and that they understand the difference between a meal and a snack. For example, if somebody says, “Oh, I just had a small cheeseburger and that's my snack,” that is actually a meal and may require more enzymes. Once we ensure that those are not issues, I make sure again, as part of my approach, that there are no comorbid conditions that may be driving some of the symptoms, such as celiac disease or SIBO, with SIBO being very common in this population.

Then we have to decide whether we need to change the dose. Do we need to increase the dose? Some of us start a little bit higher than the 40,000 to 50,000 units of lipase per meal, as suggested in some of our national and international guidelines, and go from there.

How much does the risk of new-onset type 2 diabetes (T2D) increase in patients who have had a mild SARS-CoV-2 (COVID-19) infection?

Dr. Jain: We are now finding many associations between COVID-19 and T2D. Recently, there have been studies, especially from the United States and Germany, showing that even after mild COVID-19, the occurrence of new onset T2D is greater than what we thought previously. For instance, we are now seeing that the rate of new-onset T2D in adults who have had mild COVID-19 is about 18 additional adults per 1000 people. These people have about a 46% higher risk of developing T2D compared to those who did not have COVID-19. This is something we must keep in mind moving forward when it comes to screening for diabetes.

How have you navigated through the diagnostic components of T2D and COVID-19?

Dr. Jain: When people were exclusively doing virtual appointments during the COVID-19 lockdowns, there wasn't enough screening for retinopathy, worsening blood pressure, or even basic lab testing, for instance. We could not perform electrocardiography screenings for our patients with diabetes; we had to defer it unless people were symptomatic. This was not the ideal situation, as many people with diabetes may have “silent” coronary artery disease, making screening crucial even in those patients who are not symptomatic. The impact of this is anyone’s guess at this time. Unfortunately, there is no literature that has looked at the impact of deferred screenings during the pandemic.

However, in my own practice, we are now transitioning back to in-person appointments and making sure that all of these screening visits are being conducted in a timely manner so that we can catch the micro- and macrovascular complications of diabetes sooner.

Although data on the long-term impact are not available, what studies have been done regarding the treatment of T2D during the pandemic?

Dr. Jain: There are some observational studies. There was a claims database analysis that looked at patient visits, screening tests, filling of medications, and glycated hemoglobin (A1C) levels in 2020 vs 2019 in the United States. There was no significant difference between the A1C levels and medication fills. I think one reason for this is that we all were able to adapt to the changes required from us, and we were able to incorporate the virtual appointments. That's reassuring. I think we still need some more data to make any definitive assumptions about what the overall care of diabetes has been as we are coming out of the pandemic.

Have you seen any particular characteristics or disparities in those patients who have been impacted by T2D and COVID-19?

Dr. Jain: With the mask mandate, physical distancing requirements, and differing vaccination rates across parts of the world, we have seen disparities in the impact of COVID-19, especially for those that are the most vulnerable. This includes people with multiple comorbidities.

We also know that, even at baseline, patients with T2D are often prone to multiple cardiovascular issues and dialysis requirements. These individuals still have to be extremely cautious. I have seen that those patients who actually need the most attention are still not able to go out and get the care. It is important that we are inclusive in our understanding of the requirements of people at high risk for T2D and other comorbidities. Necessary requirements to reduce infection risk include following physical distancing and masking requirements as appropriate and ensuring timely screening for retinopathy, nephropathy, and coronary artery disease as well as getting foot exams.

We have to give them all the care and access to healthcare that they need. Expert consensus suggests that we ensure optimization of vaccination status, glycemic control, cardiovascular risk, and weight control. We also need to ensure that these high-risk individuals have not slipped through the cracks and have appropriate appointment follow-ups, labs, etc. booked in a timely manner.

What guidelines and standards do you rely upon to ensure that patients are getting the most out of their treatment?

Dr. Jain: COVID-19 aside, we still want to make sure that the management of T2D is not glucose-centric. We now understand that diabetes requires 360-degree care, and that involves not only controlling the blood sugars but also making sure that we are mitigating risk factors for vascular complications. That includes ensuring blood pressure is well controlled and that cholesterol levels are in target range for patients who either have history of heart attacks, strokes, heart failure, kidney disease, or who are at future risk for these events.

We are using medications that can help protect the heart and the kidneys. Considering that T2D and obesity are so closely interlinked, we are using medications that help with overcoming the weight aspect as well. I think that a patient-centric, multidisciplinary approach is the most crucial and the most reliable way of getting that 360-degree comprehensive care for patients with diabetes.

Is there anything else you would like to share with your colleagues or peers?

Dr. Jain: As we are coming out of the pandemic, we still we need to realize that the repercussions of COVID-19 will still stay with us for a long, long time. We do know that COVID-19 infection leads to a tsunami of inflammation in the body. This can have long-lasting effects, including chronic conditions.

It is important that we continue to screen for diabetes given that there is a higher incidence of T2D in those with even mild COVID-19, and especially those at highest risk, such as people with obesity. We need to make sure that we are not missing any pieces of the puzzle there, especially because diabetes is a silent disease. We should not rely on symptoms to determine when we should screen; instead, we must be proactive about screening and management.

How much does the risk of new-onset type 2 diabetes (T2D) increase in patients who have had a mild SARS-CoV-2 (COVID-19) infection?

Dr. Jain: We are now finding many associations between COVID-19 and T2D. Recently, there have been studies, especially from the United States and Germany, showing that even after mild COVID-19, the occurrence of new onset T2D is greater than what we thought previously. For instance, we are now seeing that the rate of new-onset T2D in adults who have had mild COVID-19 is about 18 additional adults per 1000 people. These people have about a 46% higher risk of developing T2D compared to those who did not have COVID-19. This is something we must keep in mind moving forward when it comes to screening for diabetes.

How have you navigated through the diagnostic components of T2D and COVID-19?

Dr. Jain: When people were exclusively doing virtual appointments during the COVID-19 lockdowns, there wasn't enough screening for retinopathy, worsening blood pressure, or even basic lab testing, for instance. We could not perform electrocardiography screenings for our patients with diabetes; we had to defer it unless people were symptomatic. This was not the ideal situation, as many people with diabetes may have “silent” coronary artery disease, making screening crucial even in those patients who are not symptomatic. The impact of this is anyone’s guess at this time. Unfortunately, there is no literature that has looked at the impact of deferred screenings during the pandemic.

However, in my own practice, we are now transitioning back to in-person appointments and making sure that all of these screening visits are being conducted in a timely manner so that we can catch the micro- and macrovascular complications of diabetes sooner.

Although data on the long-term impact are not available, what studies have been done regarding the treatment of T2D during the pandemic?

Dr. Jain: There are some observational studies. There was a claims database analysis that looked at patient visits, screening tests, filling of medications, and glycated hemoglobin (A1C) levels in 2020 vs 2019 in the United States. There was no significant difference between the A1C levels and medication fills. I think one reason for this is that we all were able to adapt to the changes required from us, and we were able to incorporate the virtual appointments. That's reassuring. I think we still need some more data to make any definitive assumptions about what the overall care of diabetes has been as we are coming out of the pandemic.

Have you seen any particular characteristics or disparities in those patients who have been impacted by T2D and COVID-19?

Dr. Jain: With the mask mandate, physical distancing requirements, and differing vaccination rates across parts of the world, we have seen disparities in the impact of COVID-19, especially for those that are the most vulnerable. This includes people with multiple comorbidities.

We also know that, even at baseline, patients with T2D are often prone to multiple cardiovascular issues and dialysis requirements. These individuals still have to be extremely cautious. I have seen that those patients who actually need the most attention are still not able to go out and get the care. It is important that we are inclusive in our understanding of the requirements of people at high risk for T2D and other comorbidities. Necessary requirements to reduce infection risk include following physical distancing and masking requirements as appropriate and ensuring timely screening for retinopathy, nephropathy, and coronary artery disease as well as getting foot exams.

We have to give them all the care and access to healthcare that they need. Expert consensus suggests that we ensure optimization of vaccination status, glycemic control, cardiovascular risk, and weight control. We also need to ensure that these high-risk individuals have not slipped through the cracks and have appropriate appointment follow-ups, labs, etc. booked in a timely manner.

What guidelines and standards do you rely upon to ensure that patients are getting the most out of their treatment?

Dr. Jain: COVID-19 aside, we still want to make sure that the management of T2D is not glucose-centric. We now understand that diabetes requires 360-degree care, and that involves not only controlling the blood sugars but also making sure that we are mitigating risk factors for vascular complications. That includes ensuring blood pressure is well controlled and that cholesterol levels are in target range for patients who either have history of heart attacks, strokes, heart failure, kidney disease, or who are at future risk for these events.

We are using medications that can help protect the heart and the kidneys. Considering that T2D and obesity are so closely interlinked, we are using medications that help with overcoming the weight aspect as well. I think that a patient-centric, multidisciplinary approach is the most crucial and the most reliable way of getting that 360-degree comprehensive care for patients with diabetes.

Is there anything else you would like to share with your colleagues or peers?

Dr. Jain: As we are coming out of the pandemic, we still we need to realize that the repercussions of COVID-19 will still stay with us for a long, long time. We do know that COVID-19 infection leads to a tsunami of inflammation in the body. This can have long-lasting effects, including chronic conditions.

It is important that we continue to screen for diabetes given that there is a higher incidence of T2D in those with even mild COVID-19, and especially those at highest risk, such as people with obesity. We need to make sure that we are not missing any pieces of the puzzle there, especially because diabetes is a silent disease. We should not rely on symptoms to determine when we should screen; instead, we must be proactive about screening and management.

How much does the risk of new-onset type 2 diabetes (T2D) increase in patients who have had a mild SARS-CoV-2 (COVID-19) infection?

Dr. Jain: We are now finding many associations between COVID-19 and T2D. Recently, there have been studies, especially from the United States and Germany, showing that even after mild COVID-19, the occurrence of new onset T2D is greater than what we thought previously. For instance, we are now seeing that the rate of new-onset T2D in adults who have had mild COVID-19 is about 18 additional adults per 1000 people. These people have about a 46% higher risk of developing T2D compared to those who did not have COVID-19. This is something we must keep in mind moving forward when it comes to screening for diabetes.

How have you navigated through the diagnostic components of T2D and COVID-19?

Dr. Jain: When people were exclusively doing virtual appointments during the COVID-19 lockdowns, there wasn't enough screening for retinopathy, worsening blood pressure, or even basic lab testing, for instance. We could not perform electrocardiography screenings for our patients with diabetes; we had to defer it unless people were symptomatic. This was not the ideal situation, as many people with diabetes may have “silent” coronary artery disease, making screening crucial even in those patients who are not symptomatic. The impact of this is anyone’s guess at this time. Unfortunately, there is no literature that has looked at the impact of deferred screenings during the pandemic.

However, in my own practice, we are now transitioning back to in-person appointments and making sure that all of these screening visits are being conducted in a timely manner so that we can catch the micro- and macrovascular complications of diabetes sooner.

Although data on the long-term impact are not available, what studies have been done regarding the treatment of T2D during the pandemic?

Dr. Jain: There are some observational studies. There was a claims database analysis that looked at patient visits, screening tests, filling of medications, and glycated hemoglobin (A1C) levels in 2020 vs 2019 in the United States. There was no significant difference between the A1C levels and medication fills. I think one reason for this is that we all were able to adapt to the changes required from us, and we were able to incorporate the virtual appointments. That's reassuring. I think we still need some more data to make any definitive assumptions about what the overall care of diabetes has been as we are coming out of the pandemic.

Have you seen any particular characteristics or disparities in those patients who have been impacted by T2D and COVID-19?

Dr. Jain: With the mask mandate, physical distancing requirements, and differing vaccination rates across parts of the world, we have seen disparities in the impact of COVID-19, especially for those that are the most vulnerable. This includes people with multiple comorbidities.

We also know that, even at baseline, patients with T2D are often prone to multiple cardiovascular issues and dialysis requirements. These individuals still have to be extremely cautious. I have seen that those patients who actually need the most attention are still not able to go out and get the care. It is important that we are inclusive in our understanding of the requirements of people at high risk for T2D and other comorbidities. Necessary requirements to reduce infection risk include following physical distancing and masking requirements as appropriate and ensuring timely screening for retinopathy, nephropathy, and coronary artery disease as well as getting foot exams.

We have to give them all the care and access to healthcare that they need. Expert consensus suggests that we ensure optimization of vaccination status, glycemic control, cardiovascular risk, and weight control. We also need to ensure that these high-risk individuals have not slipped through the cracks and have appropriate appointment follow-ups, labs, etc. booked in a timely manner.

What guidelines and standards do you rely upon to ensure that patients are getting the most out of their treatment?

Dr. Jain: COVID-19 aside, we still want to make sure that the management of T2D is not glucose-centric. We now understand that diabetes requires 360-degree care, and that involves not only controlling the blood sugars but also making sure that we are mitigating risk factors for vascular complications. That includes ensuring blood pressure is well controlled and that cholesterol levels are in target range for patients who either have history of heart attacks, strokes, heart failure, kidney disease, or who are at future risk for these events.

We are using medications that can help protect the heart and the kidneys. Considering that T2D and obesity are so closely interlinked, we are using medications that help with overcoming the weight aspect as well. I think that a patient-centric, multidisciplinary approach is the most crucial and the most reliable way of getting that 360-degree comprehensive care for patients with diabetes.

Is there anything else you would like to share with your colleagues or peers?

Dr. Jain: As we are coming out of the pandemic, we still we need to realize that the repercussions of COVID-19 will still stay with us for a long, long time. We do know that COVID-19 infection leads to a tsunami of inflammation in the body. This can have long-lasting effects, including chronic conditions.

It is important that we continue to screen for diabetes given that there is a higher incidence of T2D in those with even mild COVID-19, and especially those at highest risk, such as people with obesity. We need to make sure that we are not missing any pieces of the puzzle there, especially because diabetes is a silent disease. We should not rely on symptoms to determine when we should screen; instead, we must be proactive about screening and management.

Interventional approaches are being used as a standard of care more and more to provide image-guided techniques to perform minimally invasive procedures. With this being said, what are some indications and best practices used with interventional radiology for the treatment of uterine fibroids?

Dr. Boone:  Interventional radiologists offer minimally invasive non-surgical treatment options for the management of symptomatic uterine fibroids. These approaches include uterine artery embolization or UAE. It may also be called uterine fibroid embolization or UFE.  In this procedure, the uterine arteries are embolized with permanent embolic particles to block blood flow to the fibroids.

The goal of this treatment is to shrink the fibroids. It usually leads to a gradual shrinkage of fibroids and can also be particularly effective for reducing bleeding from fibroids. This procedure has been around for more than 20 years and has a lot of data describing its safety and efficacy.

Another treatment, which is non-invasive, but some interventional radiologists offer, is magnetic resonance-guided focused ultrasound. This might also be called high intensity focused ultrasound or HIFU. In this treatment, MRI is used to direct high intensity ultrasound waves onto the fibroid. This focused application of these high intensity ultrasound waves generates heat and leads to coagulative necrosis of the fibroid.

This procedure is newer than uterine artery embolization, but it has some benefits of avoiding ionizing radiation. Although, it can have longer procedure times. For both procedures, the indications are symptomatic uterine fibroids.

The symptoms we're concerned about include menorrhagia, which can result in anemia. There are also “bulk” symptoms, related to the actual bulk of the fibroids, which can cause bladder or bowel dysfunction. Some patients also have protrusion of their abdomen, dysmenorrhea, and infertility.

The goal is to help reduce those symptoms. The Society for Interventional Radiology has published best practices. For expected outcomes, with the uterine artery embolization, it is 50% to 60% reduction in the size of fibroid of the fibroids themselves, 40% to 50% reduction in the size of the uterus, 88% to 92% of reduction of the bulk symptoms.

Every consultation should discuss the range of treatment options—the medical, surgical, and non-surgical or interventional. I wanted to point out that there is a real need for this. The Society for Interventional Radiology commissioned a poll in 2017 of patients–women  who had been diagnosed with uterine fibroids—and found that 44% of patients noted never hearing of uterine artery embolization. Eleven percent of these patients believed that hysterectomy was their only treatment option. Further, a recent article from NPR noted concerns about disparities in which women of color, particularly Black women, were not offered or made aware of more minimally invasive options during consultations. Very broad patient education about the range of treatment options is important.

In addition, we want to consider other differential diagnoses that patients may have, such as adenomyosis or rare malignancies. Leiomyosarcoma can present with similar symptoms to uterine fibroids or can even coexist with uterine fibroids. In the case of leiomyosarcoma, the treatment pathway may be completely different, and we don't want to undertreat or delay diagnosis. Other considerations that can have bearing on the selection of treatment can be the number and the size of the fibroids.

To help with the decision-making process, these patients need a complete workup. We want to get lab tests. We want to also make sure they have a complete gynecologic evaluation, which includes an ultrasound and an MRI. Particularly, contrast-enhanced MRI has great accuracy for evaluating fibroid location because we’re imaging the entire pelvis. We can see where everything is and map out our target fibroids.

We can also see the enhancement characteristics of the fibroids. Some fibroids are not just supplied by uterine arteries but ovarian arteries, which can affect the efficacy of the treatment and even some of the risks of the treatment.

What is your role and particularly what is the role of the Nurse Practitioner when thinking about diagnosis and treatment and how do you and the nurse practitioner work together?

Dr. Boone: I would say the specific roles for the physicians and nurse practitioners on an interventional radiology team can vary with a lot of different factors. It could depend on the practice setting, such as, whether you're in a busy academic center or in a small private practice. It can depend on the types of cases we're doing. Even some of the local regulations of the institution and state can come into play. The roles tend to be laid out and specified by the supervising physician based on this context.

For example, ideally, all of that work up and planning is happening in that clinic setting before the patient even comes down to the suite for the procedure. In this setting, nurse practitioners can provide a significant role in obtaining the data that we need. They'll perform the history and physical exam, which helps the team learn about the patients. It helps answer relevant questions: What symptoms is the patient having? What are their wishes for the procedure? What are the things they're hoping to avoid or hoping to get from having the procedure done? They review for those relevant labs and imaging, and in order to recognize the information we don’t have.

The next step is developing the assessment and plan which is usually done in conjunction with the interventional radiologist. This is especially important with new patients. Once that assessment and plan are determined, the nurse practitioner can be helpful in explaining the process in depth to the patient and their family or caregivers while they're in the clinic.

Another important role for nurse practitioners in this setting is the consent. I can talk a little bit more about that later, but informed consent is critical. It can be a pretty extensive discussion, especially if we want to talk about this wide range of treatment options. So that is substantial value added by the nurse practitioner.

The other important role is the follow up visits, which may be almost completely independently by a nurse practitioner. They see patients post-procedure, evaluating how they’re doing and what's changed. This is critical because we need to determine: 1. Have we gotten the result that we want? 2. Do we want to give more time to see changes? and;  3. Do we need to do another procedure? We also want to follow these patients and their response to treatment to look out for something concerning that might raise concern for malignancy, such as the fibroid continuing to grow rapidly. Those follow up visits are also a critical role for NPs.

In the inpatient setting, the attending and senior interventional radiology residents may actually determine the roles and tasks the other team members are going to perform to help the IR service run smoothly. And typically, nurse practitioners and also physician assistants will share many of those responsibilities of running that interventional radiology service outside of the procedure room.

There are also cases where nurse practitioners and physician assistants can have a dedicated role in performing certain procedures. Personally, I've seen physician assistants in these cases, where they were our dedicated bone marrow biopsy providers. Throughout the day, they would do all the bone marrow biopsy cases. Another example I saw was placement of vascular access catheters, whether for ports or dialysis. NPs see many patients throughout the day and perform these procedures. This is helpful because these are very popular procedures and are needed. While those are being done, it frees up time for the other members of the team to do other, more time-consuming, procedures as well.

In all cases, we work closely together. We're sharing this responsibility of patient care. We communicate frequently and it's a valuable team dynamic. NPs are fantastic team members

Dr. Boone, you talked about the treatments and how you work together with NPs. Can you touch on the interventional procedures and the value or benefit over conservative treatments and drugs, particularly, where you receive support or recommendations from nurse practitioners at this stage?

Dr. Boone: Regarding more conservative treatment,  there’s expectant management where the patients may not want to undergo an intervention at that time. You’re following the patient and watching for possible worsening of symptoms that may lead to a change in management.

There’s also medical management, which generally gets broken down into hormonal or non-hormonal medications. Among these, there's a lot of different drugs that are available. Among the more frequently used hormonal therapies would be gonadotropin-releasing hormone agonists.

The non-hormonal therapies such as, NSAIDs, or procoagulation medications, like tranexamic acid, are more targeted at symptom control. Particularly, these target the abnormal uterine bleeding and the pain.

For these therapies, the limitations can be side-effect profiles. Sometimes these side effects are just not acceptable to patients. Hormonal therapies like the gonadotropin-releasing hormone agonists create this hypoestrogenic state. Patients may not like having the menopause-like symptoms.

Additionally, medications are more short-term in their benefit. For example, with the cessation of gonadotropin-releasing hormone agonists, the fibroids actually can show rapid rebound growth. Some of the non-surgical interventions can provide longer term benefit, even if they may require re-intervention more frequently compared to surgical interventions.

For interventional radiology, we primarily focus on the procedures. We don't typically manage the medical therapy. These treatment approaches are cultivated more by gynecology or other clinicians.

When it comes to interventional radiology treatment for uterine fibroids in your day-to-day practices, which you've talked a lot about today, what has been your experience in working with Nurse Practitioners overall and where do they, should they or could they potentially add even more value?

Dr. Boone: Nurse practitioners play an integral role on the team and, I think, they provide a lot of value. They have an important role in teaching settings, were they provide continuity of care. They can also greatly impact with teaching of trainees.

In teaching settings, there's a substantial turnover of trainees because -- and this includes residents, medical students, in some cases fellows -- they're  rotating between different hospitals every few weeks. Even at the end of the year, the most senior residents, the most experience trainees, leave to go to new jobs. Nurse practitioners on the IR team are a critical source of continuity and consistency for patients and for the rest of the team because they spend the most time on the service and they know the team members well. They also know how to get things done efficiently and really know the system.

They've also honed the skills that trainees, particularly junior residents, are learning. In my experience, I first learned to place and remove tunneled catheters and bone marrow biopsies by spending the day with a physician assistant and a nurse practitioner. Both from the educational standpoint and also consistent, efficient care standpoint, having NPs and PAs on our team is hugely valuable.

Emphasizing that role in teaching is highly valuable. I would encourage nurse practitioners on an IR team with trainees to take ownership of teaching a particular skill or a certain topic, because they're going to bring a different perspective and that's extremely valuable.

Another arena where there's a lot of value, is  in the informed consent and patient education portion of patient care. Interventional radiology is not the most familiar medical field for a lot of people. Interventional radiologists also perform a wide array of procedures and they can be very different. Even treatments for the same problem, uterine artery embolization and MRI-guided focused ultrasound, are very different procedures in terms of how they're actually performed.

For example, if you mentioned surgery to most people, there is some idea of what that entails and who performs it. But if you say embolization to most people, they may not entirely understand all those components. For a patient to sufficiently be informed and able to consent, they do need to understand not only their disease and the treatment being offered, but also the risks, the benefits, and the alternatives. They need to understand what to expect from the procedure.

Doing this well can take a substantial amount of time, but it is important. From a physician standpoint, that entails balancing. Along with performing the procedures and reviewing patient imaging as well as other clinical duties this is very  challenging. Nurse practitioners can really leverage their expertise in patient communication and education to fill in those knowledge gaps and best serve the patient while also helping the IR service. These are just two of many areas in which NPs can be highly valuable to an IR practice.

Interventional approaches are being used as a standard of care more and more to provide image-guided techniques to perform minimally invasive procedures. With this being said, what are some indications and best practices used with interventional radiology for the treatment of uterine fibroids?

Dr. Boone:  Interventional radiologists offer minimally invasive non-surgical treatment options for the management of symptomatic uterine fibroids. These approaches include uterine artery embolization or UAE. It may also be called uterine fibroid embolization or UFE.  In this procedure, the uterine arteries are embolized with permanent embolic particles to block blood flow to the fibroids.

The goal of this treatment is to shrink the fibroids. It usually leads to a gradual shrinkage of fibroids and can also be particularly effective for reducing bleeding from fibroids. This procedure has been around for more than 20 years and has a lot of data describing its safety and efficacy.

Another treatment, which is non-invasive, but some interventional radiologists offer, is magnetic resonance-guided focused ultrasound. This might also be called high intensity focused ultrasound or HIFU. In this treatment, MRI is used to direct high intensity ultrasound waves onto the fibroid. This focused application of these high intensity ultrasound waves generates heat and leads to coagulative necrosis of the fibroid.

This procedure is newer than uterine artery embolization, but it has some benefits of avoiding ionizing radiation. Although, it can have longer procedure times. For both procedures, the indications are symptomatic uterine fibroids.

The symptoms we're concerned about include menorrhagia, which can result in anemia. There are also “bulk” symptoms, related to the actual bulk of the fibroids, which can cause bladder or bowel dysfunction. Some patients also have protrusion of their abdomen, dysmenorrhea, and infertility.

The goal is to help reduce those symptoms. The Society for Interventional Radiology has published best practices. For expected outcomes, with the uterine artery embolization, it is 50% to 60% reduction in the size of fibroid of the fibroids themselves, 40% to 50% reduction in the size of the uterus, 88% to 92% of reduction of the bulk symptoms.

Every consultation should discuss the range of treatment options—the medical, surgical, and non-surgical or interventional. I wanted to point out that there is a real need for this. The Society for Interventional Radiology commissioned a poll in 2017 of patients–women  who had been diagnosed with uterine fibroids—and found that 44% of patients noted never hearing of uterine artery embolization. Eleven percent of these patients believed that hysterectomy was their only treatment option. Further, a recent article from NPR noted concerns about disparities in which women of color, particularly Black women, were not offered or made aware of more minimally invasive options during consultations. Very broad patient education about the range of treatment options is important.

In addition, we want to consider other differential diagnoses that patients may have, such as adenomyosis or rare malignancies. Leiomyosarcoma can present with similar symptoms to uterine fibroids or can even coexist with uterine fibroids. In the case of leiomyosarcoma, the treatment pathway may be completely different, and we don't want to undertreat or delay diagnosis. Other considerations that can have bearing on the selection of treatment can be the number and the size of the fibroids.

To help with the decision-making process, these patients need a complete workup. We want to get lab tests. We want to also make sure they have a complete gynecologic evaluation, which includes an ultrasound and an MRI. Particularly, contrast-enhanced MRI has great accuracy for evaluating fibroid location because we’re imaging the entire pelvis. We can see where everything is and map out our target fibroids.

We can also see the enhancement characteristics of the fibroids. Some fibroids are not just supplied by uterine arteries but ovarian arteries, which can affect the efficacy of the treatment and even some of the risks of the treatment.

What is your role and particularly what is the role of the Nurse Practitioner when thinking about diagnosis and treatment and how do you and the nurse practitioner work together?

Dr. Boone: I would say the specific roles for the physicians and nurse practitioners on an interventional radiology team can vary with a lot of different factors. It could depend on the practice setting, such as, whether you're in a busy academic center or in a small private practice. It can depend on the types of cases we're doing. Even some of the local regulations of the institution and state can come into play. The roles tend to be laid out and specified by the supervising physician based on this context.

For example, ideally, all of that work up and planning is happening in that clinic setting before the patient even comes down to the suite for the procedure. In this setting, nurse practitioners can provide a significant role in obtaining the data that we need. They'll perform the history and physical exam, which helps the team learn about the patients. It helps answer relevant questions: What symptoms is the patient having? What are their wishes for the procedure? What are the things they're hoping to avoid or hoping to get from having the procedure done? They review for those relevant labs and imaging, and in order to recognize the information we don’t have.

The next step is developing the assessment and plan which is usually done in conjunction with the interventional radiologist. This is especially important with new patients. Once that assessment and plan are determined, the nurse practitioner can be helpful in explaining the process in depth to the patient and their family or caregivers while they're in the clinic.

Another important role for nurse practitioners in this setting is the consent. I can talk a little bit more about that later, but informed consent is critical. It can be a pretty extensive discussion, especially if we want to talk about this wide range of treatment options. So that is substantial value added by the nurse practitioner.

The other important role is the follow up visits, which may be almost completely independently by a nurse practitioner. They see patients post-procedure, evaluating how they’re doing and what's changed. This is critical because we need to determine: 1. Have we gotten the result that we want? 2. Do we want to give more time to see changes? and;  3. Do we need to do another procedure? We also want to follow these patients and their response to treatment to look out for something concerning that might raise concern for malignancy, such as the fibroid continuing to grow rapidly. Those follow up visits are also a critical role for NPs.

In the inpatient setting, the attending and senior interventional radiology residents may actually determine the roles and tasks the other team members are going to perform to help the IR service run smoothly. And typically, nurse practitioners and also physician assistants will share many of those responsibilities of running that interventional radiology service outside of the procedure room.

There are also cases where nurse practitioners and physician assistants can have a dedicated role in performing certain procedures. Personally, I've seen physician assistants in these cases, where they were our dedicated bone marrow biopsy providers. Throughout the day, they would do all the bone marrow biopsy cases. Another example I saw was placement of vascular access catheters, whether for ports or dialysis. NPs see many patients throughout the day and perform these procedures. This is helpful because these are very popular procedures and are needed. While those are being done, it frees up time for the other members of the team to do other, more time-consuming, procedures as well.

In all cases, we work closely together. We're sharing this responsibility of patient care. We communicate frequently and it's a valuable team dynamic. NPs are fantastic team members

Dr. Boone, you talked about the treatments and how you work together with NPs. Can you touch on the interventional procedures and the value or benefit over conservative treatments and drugs, particularly, where you receive support or recommendations from nurse practitioners at this stage?

Dr. Boone: Regarding more conservative treatment,  there’s expectant management where the patients may not want to undergo an intervention at that time. You’re following the patient and watching for possible worsening of symptoms that may lead to a change in management.

There’s also medical management, which generally gets broken down into hormonal or non-hormonal medications. Among these, there's a lot of different drugs that are available. Among the more frequently used hormonal therapies would be gonadotropin-releasing hormone agonists.

The non-hormonal therapies such as, NSAIDs, or procoagulation medications, like tranexamic acid, are more targeted at symptom control. Particularly, these target the abnormal uterine bleeding and the pain.

For these therapies, the limitations can be side-effect profiles. Sometimes these side effects are just not acceptable to patients. Hormonal therapies like the gonadotropin-releasing hormone agonists create this hypoestrogenic state. Patients may not like having the menopause-like symptoms.

Additionally, medications are more short-term in their benefit. For example, with the cessation of gonadotropin-releasing hormone agonists, the fibroids actually can show rapid rebound growth. Some of the non-surgical interventions can provide longer term benefit, even if they may require re-intervention more frequently compared to surgical interventions.

For interventional radiology, we primarily focus on the procedures. We don't typically manage the medical therapy. These treatment approaches are cultivated more by gynecology or other clinicians.

When it comes to interventional radiology treatment for uterine fibroids in your day-to-day practices, which you've talked a lot about today, what has been your experience in working with Nurse Practitioners overall and where do they, should they or could they potentially add even more value?

Dr. Boone: Nurse practitioners play an integral role on the team and, I think, they provide a lot of value. They have an important role in teaching settings, were they provide continuity of care. They can also greatly impact with teaching of trainees.

In teaching settings, there's a substantial turnover of trainees because -- and this includes residents, medical students, in some cases fellows -- they're  rotating between different hospitals every few weeks. Even at the end of the year, the most senior residents, the most experience trainees, leave to go to new jobs. Nurse practitioners on the IR team are a critical source of continuity and consistency for patients and for the rest of the team because they spend the most time on the service and they know the team members well. They also know how to get things done efficiently and really know the system.

They've also honed the skills that trainees, particularly junior residents, are learning. In my experience, I first learned to place and remove tunneled catheters and bone marrow biopsies by spending the day with a physician assistant and a nurse practitioner. Both from the educational standpoint and also consistent, efficient care standpoint, having NPs and PAs on our team is hugely valuable.

Emphasizing that role in teaching is highly valuable. I would encourage nurse practitioners on an IR team with trainees to take ownership of teaching a particular skill or a certain topic, because they're going to bring a different perspective and that's extremely valuable.

Another arena where there's a lot of value, is  in the informed consent and patient education portion of patient care. Interventional radiology is not the most familiar medical field for a lot of people. Interventional radiologists also perform a wide array of procedures and they can be very different. Even treatments for the same problem, uterine artery embolization and MRI-guided focused ultrasound, are very different procedures in terms of how they're actually performed.

For example, if you mentioned surgery to most people, there is some idea of what that entails and who performs it. But if you say embolization to most people, they may not entirely understand all those components. For a patient to sufficiently be informed and able to consent, they do need to understand not only their disease and the treatment being offered, but also the risks, the benefits, and the alternatives. They need to understand what to expect from the procedure.

Doing this well can take a substantial amount of time, but it is important. From a physician standpoint, that entails balancing. Along with performing the procedures and reviewing patient imaging as well as other clinical duties this is very  challenging. Nurse practitioners can really leverage their expertise in patient communication and education to fill in those knowledge gaps and best serve the patient while also helping the IR service. These are just two of many areas in which NPs can be highly valuable to an IR practice.

Interventional approaches are being used as a standard of care more and more to provide image-guided techniques to perform minimally invasive procedures. With this being said, what are some indications and best practices used with interventional radiology for the treatment of uterine fibroids?

Dr. Boone:  Interventional radiologists offer minimally invasive non-surgical treatment options for the management of symptomatic uterine fibroids. These approaches include uterine artery embolization or UAE. It may also be called uterine fibroid embolization or UFE.  In this procedure, the uterine arteries are embolized with permanent embolic particles to block blood flow to the fibroids.

The goal of this treatment is to shrink the fibroids. It usually leads to a gradual shrinkage of fibroids and can also be particularly effective for reducing bleeding from fibroids. This procedure has been around for more than 20 years and has a lot of data describing its safety and efficacy.

Another treatment, which is non-invasive, but some interventional radiologists offer, is magnetic resonance-guided focused ultrasound. This might also be called high intensity focused ultrasound or HIFU. In this treatment, MRI is used to direct high intensity ultrasound waves onto the fibroid. This focused application of these high intensity ultrasound waves generates heat and leads to coagulative necrosis of the fibroid.

This procedure is newer than uterine artery embolization, but it has some benefits of avoiding ionizing radiation. Although, it can have longer procedure times. For both procedures, the indications are symptomatic uterine fibroids.

The symptoms we're concerned about include menorrhagia, which can result in anemia. There are also “bulk” symptoms, related to the actual bulk of the fibroids, which can cause bladder or bowel dysfunction. Some patients also have protrusion of their abdomen, dysmenorrhea, and infertility.

The goal is to help reduce those symptoms. The Society for Interventional Radiology has published best practices. For expected outcomes, with the uterine artery embolization, it is 50% to 60% reduction in the size of fibroid of the fibroids themselves, 40% to 50% reduction in the size of the uterus, 88% to 92% of reduction of the bulk symptoms.

Every consultation should discuss the range of treatment options—the medical, surgical, and non-surgical or interventional. I wanted to point out that there is a real need for this. The Society for Interventional Radiology commissioned a poll in 2017 of patients–women  who had been diagnosed with uterine fibroids—and found that 44% of patients noted never hearing of uterine artery embolization. Eleven percent of these patients believed that hysterectomy was their only treatment option. Further, a recent article from NPR noted concerns about disparities in which women of color, particularly Black women, were not offered or made aware of more minimally invasive options during consultations. Very broad patient education about the range of treatment options is important.

In addition, we want to consider other differential diagnoses that patients may have, such as adenomyosis or rare malignancies. Leiomyosarcoma can present with similar symptoms to uterine fibroids or can even coexist with uterine fibroids. In the case of leiomyosarcoma, the treatment pathway may be completely different, and we don't want to undertreat or delay diagnosis. Other considerations that can have bearing on the selection of treatment can be the number and the size of the fibroids.

To help with the decision-making process, these patients need a complete workup. We want to get lab tests. We want to also make sure they have a complete gynecologic evaluation, which includes an ultrasound and an MRI. Particularly, contrast-enhanced MRI has great accuracy for evaluating fibroid location because we’re imaging the entire pelvis. We can see where everything is and map out our target fibroids.

We can also see the enhancement characteristics of the fibroids. Some fibroids are not just supplied by uterine arteries but ovarian arteries, which can affect the efficacy of the treatment and even some of the risks of the treatment.

What is your role and particularly what is the role of the Nurse Practitioner when thinking about diagnosis and treatment and how do you and the nurse practitioner work together?

Dr. Boone: I would say the specific roles for the physicians and nurse practitioners on an interventional radiology team can vary with a lot of different factors. It could depend on the practice setting, such as, whether you're in a busy academic center or in a small private practice. It can depend on the types of cases we're doing. Even some of the local regulations of the institution and state can come into play. The roles tend to be laid out and specified by the supervising physician based on this context.

For example, ideally, all of that work up and planning is happening in that clinic setting before the patient even comes down to the suite for the procedure. In this setting, nurse practitioners can provide a significant role in obtaining the data that we need. They'll perform the history and physical exam, which helps the team learn about the patients. It helps answer relevant questions: What symptoms is the patient having? What are their wishes for the procedure? What are the things they're hoping to avoid or hoping to get from having the procedure done? They review for those relevant labs and imaging, and in order to recognize the information we don’t have.

The next step is developing the assessment and plan which is usually done in conjunction with the interventional radiologist. This is especially important with new patients. Once that assessment and plan are determined, the nurse practitioner can be helpful in explaining the process in depth to the patient and their family or caregivers while they're in the clinic.

Another important role for nurse practitioners in this setting is the consent. I can talk a little bit more about that later, but informed consent is critical. It can be a pretty extensive discussion, especially if we want to talk about this wide range of treatment options. So that is substantial value added by the nurse practitioner.

The other important role is the follow up visits, which may be almost completely independently by a nurse practitioner. They see patients post-procedure, evaluating how they’re doing and what's changed. This is critical because we need to determine: 1. Have we gotten the result that we want? 2. Do we want to give more time to see changes? and;  3. Do we need to do another procedure? We also want to follow these patients and their response to treatment to look out for something concerning that might raise concern for malignancy, such as the fibroid continuing to grow rapidly. Those follow up visits are also a critical role for NPs.

In the inpatient setting, the attending and senior interventional radiology residents may actually determine the roles and tasks the other team members are going to perform to help the IR service run smoothly. And typically, nurse practitioners and also physician assistants will share many of those responsibilities of running that interventional radiology service outside of the procedure room.

There are also cases where nurse practitioners and physician assistants can have a dedicated role in performing certain procedures. Personally, I've seen physician assistants in these cases, where they were our dedicated bone marrow biopsy providers. Throughout the day, they would do all the bone marrow biopsy cases. Another example I saw was placement of vascular access catheters, whether for ports or dialysis. NPs see many patients throughout the day and perform these procedures. This is helpful because these are very popular procedures and are needed. While those are being done, it frees up time for the other members of the team to do other, more time-consuming, procedures as well.

In all cases, we work closely together. We're sharing this responsibility of patient care. We communicate frequently and it's a valuable team dynamic. NPs are fantastic team members

Dr. Boone, you talked about the treatments and how you work together with NPs. Can you touch on the interventional procedures and the value or benefit over conservative treatments and drugs, particularly, where you receive support or recommendations from nurse practitioners at this stage?

Dr. Boone: Regarding more conservative treatment,  there’s expectant management where the patients may not want to undergo an intervention at that time. You’re following the patient and watching for possible worsening of symptoms that may lead to a change in management.

There’s also medical management, which generally gets broken down into hormonal or non-hormonal medications. Among these, there's a lot of different drugs that are available. Among the more frequently used hormonal therapies would be gonadotropin-releasing hormone agonists.

The non-hormonal therapies such as, NSAIDs, or procoagulation medications, like tranexamic acid, are more targeted at symptom control. Particularly, these target the abnormal uterine bleeding and the pain.

For these therapies, the limitations can be side-effect profiles. Sometimes these side effects are just not acceptable to patients. Hormonal therapies like the gonadotropin-releasing hormone agonists create this hypoestrogenic state. Patients may not like having the menopause-like symptoms.

Additionally, medications are more short-term in their benefit. For example, with the cessation of gonadotropin-releasing hormone agonists, the fibroids actually can show rapid rebound growth. Some of the non-surgical interventions can provide longer term benefit, even if they may require re-intervention more frequently compared to surgical interventions.

For interventional radiology, we primarily focus on the procedures. We don't typically manage the medical therapy. These treatment approaches are cultivated more by gynecology or other clinicians.

When it comes to interventional radiology treatment for uterine fibroids in your day-to-day practices, which you've talked a lot about today, what has been your experience in working with Nurse Practitioners overall and where do they, should they or could they potentially add even more value?

Dr. Boone: Nurse practitioners play an integral role on the team and, I think, they provide a lot of value. They have an important role in teaching settings, were they provide continuity of care. They can also greatly impact with teaching of trainees.

In teaching settings, there's a substantial turnover of trainees because -- and this includes residents, medical students, in some cases fellows -- they're  rotating between different hospitals every few weeks. Even at the end of the year, the most senior residents, the most experience trainees, leave to go to new jobs. Nurse practitioners on the IR team are a critical source of continuity and consistency for patients and for the rest of the team because they spend the most time on the service and they know the team members well. They also know how to get things done efficiently and really know the system.

They've also honed the skills that trainees, particularly junior residents, are learning. In my experience, I first learned to place and remove tunneled catheters and bone marrow biopsies by spending the day with a physician assistant and a nurse practitioner. Both from the educational standpoint and also consistent, efficient care standpoint, having NPs and PAs on our team is hugely valuable.

Emphasizing that role in teaching is highly valuable. I would encourage nurse practitioners on an IR team with trainees to take ownership of teaching a particular skill or a certain topic, because they're going to bring a different perspective and that's extremely valuable.

Another arena where there's a lot of value, is  in the informed consent and patient education portion of patient care. Interventional radiology is not the most familiar medical field for a lot of people. Interventional radiologists also perform a wide array of procedures and they can be very different. Even treatments for the same problem, uterine artery embolization and MRI-guided focused ultrasound, are very different procedures in terms of how they're actually performed.

For example, if you mentioned surgery to most people, there is some idea of what that entails and who performs it. But if you say embolization to most people, they may not entirely understand all those components. For a patient to sufficiently be informed and able to consent, they do need to understand not only their disease and the treatment being offered, but also the risks, the benefits, and the alternatives. They need to understand what to expect from the procedure.

Doing this well can take a substantial amount of time, but it is important. From a physician standpoint, that entails balancing. Along with performing the procedures and reviewing patient imaging as well as other clinical duties this is very  challenging. Nurse practitioners can really leverage their expertise in patient communication and education to fill in those knowledge gaps and best serve the patient while also helping the IR service. These are just two of many areas in which NPs can be highly valuable to an IR practice.

As a gynecologist specializing in minimally invasive surgical techniques, what is your involvement in the process for diagnosing endometriosis?

Dr. Lager: At our multidisciplinary endometriosis center, we receive a range of referrals from excellent providers near San Francisco and beyond. As a result, patients will often have had extensive evaluations and multiple treatments. Nonetheless, it is important to take a thorough history, to gain an understanding of the progress of their disease, treatments they have taken and the results or side effects of those treatments, and the goals of the patient in order to guide next steps.

Reviewing previous operative reports, pathology, and surgical photos can also be helpful to guide next steps. Commonly, patients will present with dysmenorrhea, and depending on the severity of associated symptoms, such as dysuria, dyschezia, hematuria, or hematochezia, I may refer patients to our colleagues in urology or GI for further evaluation. 

Patients will often have previous imaging such as an ultrasound or CT to evaluate anatomic etiology of the pain, but those studies are often negative. Depending on their history, I may order additional imaging, such as an MRI pelvis, and consideration of vaginal or rectal gel. We have worked closely with our radiologists who have developed a specific endometriosis protocol for deeply infiltrative endometriosis and have a multidisciplinary review committee to discuss complex cases.

Although the gold standard for diagnosis of endometriosis is surgical, this leads to a delay in treatment of 7 to 12 years.[1] So, if a patient presents with symptoms of endometriosis, I will discuss the likely diagnosis and start treatment.

Are there specific techniques that you prefer in your standard practice once a clear diagnosis is determined?

Dr. Lager: As I mentioned, although endometriosis is a surgical diagnosis, there may be findings on imaging which will lead to a diagnosis of endometriosis, including endometriomas, uterosacral thickening, a “kissing ovary” appearance, or hematosalpinx for example.

I discuss a broad range of treatment options based on the patient’s goals, from least invasive treatments to definitive surgery. I discuss dietary changes, integrative medicine (we are fortunate to have an integrative medicine gynecologist here at UCSF Osher Center), and pain psychology.  Additionally, I review first-line hormonal management options such as: birth control pills, progestin-only pills, levenogestrol IUD, etonogestrel implant, and medroxyprogesterone acetate injection. In my practice, most patients have already tried initial treatment options, and are most interested in other options. I then review second-line options such as GnRH agonists, antagonists, danazol, and aromatase inhibitors. For patients that have had chronic pelvic pain, I also discuss peripheral and central sensitization, and overlapping diagnoses. Surgical management includes diagnostic laparoscopy and excision or ablation of endometriosis, hysterectomy, and oophorectomy.

Are there specific factors that you look for to help you decide whether surgical management is necessary?

Dr. Lager: There are several reasons why patients decide to proceed with surgical management.  First, some patients are reticent to start treatment, particularly if they have had negative experiences with hormonal medications and desire a definitive diagnosis. Other patients choose to proceed with surgery for fertility reasons, and others have severe symptoms that are not managed by medications.

The goal of surgery is to remove all visible endometriotic lesions, restore normal anatomy and for pathologic diagnosis if there is atypical characteristics of an endometrial mass. The pelvic exam and imaging can often be helpful surgical planning. If there is a deeply infiltrative lesion in the bowel or bladder, I consult my urology and colorectal colleagues for surgical planning.

Endometriotic lesions are heterogenous, and can include superficial peritoneal lesions, clear vesicular lesions, “powder burn lesions”, endometriomas, and deep infiltrative lesions. 

Additionally, I counsel patients on surgical options depending on the fertility desires. For patients with infertility and symptoms of endometriosis, primary surgery with excision or ablation increases pregnancy rates. One meta-analysis showed that operative laparoscopy improved live births and ongoing pregnancy rates.[2] This was found for the first laparoscopic surgery and not repeat surgery.

Can you talk a little bit more about some of the advancements and the controversies in surgical management, and how that impacts your practice or your treatment?

Dr. Lager: Controversy in surgical management includes excision versus ablation in surgical management of endometriosis. One randomized controlled trial showed an improvement with dyspareunia with excision versus ablation after 5 year follow up.[3] However, a recent meta-analysis from 2021 showed no difference in dysmenorrhea between excision and ablation.[4] I generally perform excision of endometriosis as it can provide a tissue for diagnosis and may allow for complete excision of a lesion that may have an underlying component not easily seen.

We also discussed some of the controversy related to fertility and endometriosis. Management of endometriomas in the face of desired fertility is unclear. Endometriomas that are >3 cm in diameter are associated with decreased anti-Mullerian hormone (AMH) levels, but ovarian cystectomy for endometriomas is also associated with decreased AMH levels. I will counsel patients regarding the risks and benefits of ovarian cystectomy and discuss with the reproductive endocrinologists if they recommend removal to improve oocyte retrieval.

Lastly, conservative versus definitive treatment is an important issue to discuss. Depending on a patient’s goals, conservative surgical management of endometriosis may be the most appropriate procedure. However, if a patient has multiple surgeries, does not desire to have children or has completed childbearing regardless of age and wants to decrease the risk of need for repeat surgery, I will discuss with patients that the risk of reoperation after hysterectomy versus conservative surgery is 8% vs 21% in 2 years and 59% vs 22% after 7 years, respectively.[5]  Additionally, the patient may have an overlapping gynecological condition, such as adenomyosis or fibroids, and desire surgical management for those conditions as well. Management ultimately will depend on shared decision making,

You mentioned overlapping diagnosis. What are the impacts and barriers related to misdiagnosis or overlapping diagnosis, and what is your approach to recognizing those signs and symptoms?

Dr. Lager: The classic symptoms of endometriosis can overlap with several medical conditions. In addition to gynecologic issues such as adenomyosis and fibroids that I mentioned previously, symptoms such as pelvic pain, bloating, and dysuria can be associated with gastrointestinal conditions, painful bladder syndrome, neurologic, and musculoskeletal pain conditions. This is complex because the overlapping diagnoses can lead to misdiagnosis, and delay in diagnosis and missing an associated diagnosis can lead to inadequate treatment.

I approach the possibility of overlapping diagnoses in consultation with my colleagues who may recommend further testing, such as endoscopy and colonoscopy. Depending on the diagnoses, several treatments can be started concomitantly to address the multifactorial components of pain.  For example, pelvic floor dysfunction related to pelvic pain can affect bowel habits, even without a diagnosis of IBS. Pelvic floor physical therapy can address one component of this. Similarly, even if we surgically or medically manage symptoms of endometriosis, the musculoskeletal pain can lead to persistent or worsening pain. The same goes for pain medicine and peripheral or central pain sensitization or neurological pain.

Was there anything else you’d like to share with your colleagues?

Dr. Lager: Endometriosis is a complex condition that requires a multifactorial approach that takes into consideration a patient’s goals. There is not a one-size fit for all patients with endometriosis due to all the issues we discussed. It will take time to address the varied components of pain and is an iterative process. Minimally invasive surgery has an important role in diagnosis and management of endometriosis but is one of several approaches to treat this complex condition. Thanks for taking the time to discuss this important condition that affects at least 10% of gynecological patients, and potentially more due to delayed and undiagnosed disease.

As a gynecologist specializing in minimally invasive surgical techniques, what is your involvement in the process for diagnosing endometriosis?

Dr. Lager: At our multidisciplinary endometriosis center, we receive a range of referrals from excellent providers near San Francisco and beyond. As a result, patients will often have had extensive evaluations and multiple treatments. Nonetheless, it is important to take a thorough history, to gain an understanding of the progress of their disease, treatments they have taken and the results or side effects of those treatments, and the goals of the patient in order to guide next steps.

Reviewing previous operative reports, pathology, and surgical photos can also be helpful to guide next steps. Commonly, patients will present with dysmenorrhea, and depending on the severity of associated symptoms, such as dysuria, dyschezia, hematuria, or hematochezia, I may refer patients to our colleagues in urology or GI for further evaluation. 

Patients will often have previous imaging such as an ultrasound or CT to evaluate anatomic etiology of the pain, but those studies are often negative. Depending on their history, I may order additional imaging, such as an MRI pelvis, and consideration of vaginal or rectal gel. We have worked closely with our radiologists who have developed a specific endometriosis protocol for deeply infiltrative endometriosis and have a multidisciplinary review committee to discuss complex cases.

Although the gold standard for diagnosis of endometriosis is surgical, this leads to a delay in treatment of 7 to 12 years.[1] So, if a patient presents with symptoms of endometriosis, I will discuss the likely diagnosis and start treatment.

Are there specific techniques that you prefer in your standard practice once a clear diagnosis is determined?

Dr. Lager: As I mentioned, although endometriosis is a surgical diagnosis, there may be findings on imaging which will lead to a diagnosis of endometriosis, including endometriomas, uterosacral thickening, a “kissing ovary” appearance, or hematosalpinx for example.

I discuss a broad range of treatment options based on the patient’s goals, from least invasive treatments to definitive surgery. I discuss dietary changes, integrative medicine (we are fortunate to have an integrative medicine gynecologist here at UCSF Osher Center), and pain psychology.  Additionally, I review first-line hormonal management options such as: birth control pills, progestin-only pills, levenogestrol IUD, etonogestrel implant, and medroxyprogesterone acetate injection. In my practice, most patients have already tried initial treatment options, and are most interested in other options. I then review second-line options such as GnRH agonists, antagonists, danazol, and aromatase inhibitors. For patients that have had chronic pelvic pain, I also discuss peripheral and central sensitization, and overlapping diagnoses. Surgical management includes diagnostic laparoscopy and excision or ablation of endometriosis, hysterectomy, and oophorectomy.

Are there specific factors that you look for to help you decide whether surgical management is necessary?

Dr. Lager: There are several reasons why patients decide to proceed with surgical management.  First, some patients are reticent to start treatment, particularly if they have had negative experiences with hormonal medications and desire a definitive diagnosis. Other patients choose to proceed with surgery for fertility reasons, and others have severe symptoms that are not managed by medications.

The goal of surgery is to remove all visible endometriotic lesions, restore normal anatomy and for pathologic diagnosis if there is atypical characteristics of an endometrial mass. The pelvic exam and imaging can often be helpful surgical planning. If there is a deeply infiltrative lesion in the bowel or bladder, I consult my urology and colorectal colleagues for surgical planning.

Endometriotic lesions are heterogenous, and can include superficial peritoneal lesions, clear vesicular lesions, “powder burn lesions”, endometriomas, and deep infiltrative lesions. 

Additionally, I counsel patients on surgical options depending on the fertility desires. For patients with infertility and symptoms of endometriosis, primary surgery with excision or ablation increases pregnancy rates. One meta-analysis showed that operative laparoscopy improved live births and ongoing pregnancy rates.[2] This was found for the first laparoscopic surgery and not repeat surgery.

Can you talk a little bit more about some of the advancements and the controversies in surgical management, and how that impacts your practice or your treatment?

Dr. Lager: Controversy in surgical management includes excision versus ablation in surgical management of endometriosis. One randomized controlled trial showed an improvement with dyspareunia with excision versus ablation after 5 year follow up.[3] However, a recent meta-analysis from 2021 showed no difference in dysmenorrhea between excision and ablation.[4] I generally perform excision of endometriosis as it can provide a tissue for diagnosis and may allow for complete excision of a lesion that may have an underlying component not easily seen.

We also discussed some of the controversy related to fertility and endometriosis. Management of endometriomas in the face of desired fertility is unclear. Endometriomas that are >3 cm in diameter are associated with decreased anti-Mullerian hormone (AMH) levels, but ovarian cystectomy for endometriomas is also associated with decreased AMH levels. I will counsel patients regarding the risks and benefits of ovarian cystectomy and discuss with the reproductive endocrinologists if they recommend removal to improve oocyte retrieval.

Lastly, conservative versus definitive treatment is an important issue to discuss. Depending on a patient’s goals, conservative surgical management of endometriosis may be the most appropriate procedure. However, if a patient has multiple surgeries, does not desire to have children or has completed childbearing regardless of age and wants to decrease the risk of need for repeat surgery, I will discuss with patients that the risk of reoperation after hysterectomy versus conservative surgery is 8% vs 21% in 2 years and 59% vs 22% after 7 years, respectively.[5]  Additionally, the patient may have an overlapping gynecological condition, such as adenomyosis or fibroids, and desire surgical management for those conditions as well. Management ultimately will depend on shared decision making,

You mentioned overlapping diagnosis. What are the impacts and barriers related to misdiagnosis or overlapping diagnosis, and what is your approach to recognizing those signs and symptoms?

Dr. Lager: The classic symptoms of endometriosis can overlap with several medical conditions. In addition to gynecologic issues such as adenomyosis and fibroids that I mentioned previously, symptoms such as pelvic pain, bloating, and dysuria can be associated with gastrointestinal conditions, painful bladder syndrome, neurologic, and musculoskeletal pain conditions. This is complex because the overlapping diagnoses can lead to misdiagnosis, and delay in diagnosis and missing an associated diagnosis can lead to inadequate treatment.

I approach the possibility of overlapping diagnoses in consultation with my colleagues who may recommend further testing, such as endoscopy and colonoscopy. Depending on the diagnoses, several treatments can be started concomitantly to address the multifactorial components of pain.  For example, pelvic floor dysfunction related to pelvic pain can affect bowel habits, even without a diagnosis of IBS. Pelvic floor physical therapy can address one component of this. Similarly, even if we surgically or medically manage symptoms of endometriosis, the musculoskeletal pain can lead to persistent or worsening pain. The same goes for pain medicine and peripheral or central pain sensitization or neurological pain.

Was there anything else you’d like to share with your colleagues?

Dr. Lager: Endometriosis is a complex condition that requires a multifactorial approach that takes into consideration a patient’s goals. There is not a one-size fit for all patients with endometriosis due to all the issues we discussed. It will take time to address the varied components of pain and is an iterative process. Minimally invasive surgery has an important role in diagnosis and management of endometriosis but is one of several approaches to treat this complex condition. Thanks for taking the time to discuss this important condition that affects at least 10% of gynecological patients, and potentially more due to delayed and undiagnosed disease.

As a gynecologist specializing in minimally invasive surgical techniques, what is your involvement in the process for diagnosing endometriosis?

Dr. Lager: At our multidisciplinary endometriosis center, we receive a range of referrals from excellent providers near San Francisco and beyond. As a result, patients will often have had extensive evaluations and multiple treatments. Nonetheless, it is important to take a thorough history, to gain an understanding of the progress of their disease, treatments they have taken and the results or side effects of those treatments, and the goals of the patient in order to guide next steps.

Reviewing previous operative reports, pathology, and surgical photos can also be helpful to guide next steps. Commonly, patients will present with dysmenorrhea, and depending on the severity of associated symptoms, such as dysuria, dyschezia, hematuria, or hematochezia, I may refer patients to our colleagues in urology or GI for further evaluation. 

Patients will often have previous imaging such as an ultrasound or CT to evaluate anatomic etiology of the pain, but those studies are often negative. Depending on their history, I may order additional imaging, such as an MRI pelvis, and consideration of vaginal or rectal gel. We have worked closely with our radiologists who have developed a specific endometriosis protocol for deeply infiltrative endometriosis and have a multidisciplinary review committee to discuss complex cases.

Although the gold standard for diagnosis of endometriosis is surgical, this leads to a delay in treatment of 7 to 12 years.[1] So, if a patient presents with symptoms of endometriosis, I will discuss the likely diagnosis and start treatment.

Are there specific techniques that you prefer in your standard practice once a clear diagnosis is determined?

Dr. Lager: As I mentioned, although endometriosis is a surgical diagnosis, there may be findings on imaging which will lead to a diagnosis of endometriosis, including endometriomas, uterosacral thickening, a “kissing ovary” appearance, or hematosalpinx for example.

I discuss a broad range of treatment options based on the patient’s goals, from least invasive treatments to definitive surgery. I discuss dietary changes, integrative medicine (we are fortunate to have an integrative medicine gynecologist here at UCSF Osher Center), and pain psychology.  Additionally, I review first-line hormonal management options such as: birth control pills, progestin-only pills, levenogestrol IUD, etonogestrel implant, and medroxyprogesterone acetate injection. In my practice, most patients have already tried initial treatment options, and are most interested in other options. I then review second-line options such as GnRH agonists, antagonists, danazol, and aromatase inhibitors. For patients that have had chronic pelvic pain, I also discuss peripheral and central sensitization, and overlapping diagnoses. Surgical management includes diagnostic laparoscopy and excision or ablation of endometriosis, hysterectomy, and oophorectomy.

Are there specific factors that you look for to help you decide whether surgical management is necessary?

Dr. Lager: There are several reasons why patients decide to proceed with surgical management.  First, some patients are reticent to start treatment, particularly if they have had negative experiences with hormonal medications and desire a definitive diagnosis. Other patients choose to proceed with surgery for fertility reasons, and others have severe symptoms that are not managed by medications.

The goal of surgery is to remove all visible endometriotic lesions, restore normal anatomy and for pathologic diagnosis if there is atypical characteristics of an endometrial mass. The pelvic exam and imaging can often be helpful surgical planning. If there is a deeply infiltrative lesion in the bowel or bladder, I consult my urology and colorectal colleagues for surgical planning.

Endometriotic lesions are heterogenous, and can include superficial peritoneal lesions, clear vesicular lesions, “powder burn lesions”, endometriomas, and deep infiltrative lesions. 

Additionally, I counsel patients on surgical options depending on the fertility desires. For patients with infertility and symptoms of endometriosis, primary surgery with excision or ablation increases pregnancy rates. One meta-analysis showed that operative laparoscopy improved live births and ongoing pregnancy rates.[2] This was found for the first laparoscopic surgery and not repeat surgery.

Can you talk a little bit more about some of the advancements and the controversies in surgical management, and how that impacts your practice or your treatment?

Dr. Lager: Controversy in surgical management includes excision versus ablation in surgical management of endometriosis. One randomized controlled trial showed an improvement with dyspareunia with excision versus ablation after 5 year follow up.[3] However, a recent meta-analysis from 2021 showed no difference in dysmenorrhea between excision and ablation.[4] I generally perform excision of endometriosis as it can provide a tissue for diagnosis and may allow for complete excision of a lesion that may have an underlying component not easily seen.

We also discussed some of the controversy related to fertility and endometriosis. Management of endometriomas in the face of desired fertility is unclear. Endometriomas that are >3 cm in diameter are associated with decreased anti-Mullerian hormone (AMH) levels, but ovarian cystectomy for endometriomas is also associated with decreased AMH levels. I will counsel patients regarding the risks and benefits of ovarian cystectomy and discuss with the reproductive endocrinologists if they recommend removal to improve oocyte retrieval.

Lastly, conservative versus definitive treatment is an important issue to discuss. Depending on a patient’s goals, conservative surgical management of endometriosis may be the most appropriate procedure. However, if a patient has multiple surgeries, does not desire to have children or has completed childbearing regardless of age and wants to decrease the risk of need for repeat surgery, I will discuss with patients that the risk of reoperation after hysterectomy versus conservative surgery is 8% vs 21% in 2 years and 59% vs 22% after 7 years, respectively.[5]  Additionally, the patient may have an overlapping gynecological condition, such as adenomyosis or fibroids, and desire surgical management for those conditions as well. Management ultimately will depend on shared decision making,

You mentioned overlapping diagnosis. What are the impacts and barriers related to misdiagnosis or overlapping diagnosis, and what is your approach to recognizing those signs and symptoms?

Dr. Lager: The classic symptoms of endometriosis can overlap with several medical conditions. In addition to gynecologic issues such as adenomyosis and fibroids that I mentioned previously, symptoms such as pelvic pain, bloating, and dysuria can be associated with gastrointestinal conditions, painful bladder syndrome, neurologic, and musculoskeletal pain conditions. This is complex because the overlapping diagnoses can lead to misdiagnosis, and delay in diagnosis and missing an associated diagnosis can lead to inadequate treatment.

I approach the possibility of overlapping diagnoses in consultation with my colleagues who may recommend further testing, such as endoscopy and colonoscopy. Depending on the diagnoses, several treatments can be started concomitantly to address the multifactorial components of pain.  For example, pelvic floor dysfunction related to pelvic pain can affect bowel habits, even without a diagnosis of IBS. Pelvic floor physical therapy can address one component of this. Similarly, even if we surgically or medically manage symptoms of endometriosis, the musculoskeletal pain can lead to persistent or worsening pain. The same goes for pain medicine and peripheral or central pain sensitization or neurological pain.

Was there anything else you’d like to share with your colleagues?

Dr. Lager: Endometriosis is a complex condition that requires a multifactorial approach that takes into consideration a patient’s goals. There is not a one-size fit for all patients with endometriosis due to all the issues we discussed. It will take time to address the varied components of pain and is an iterative process. Minimally invasive surgery has an important role in diagnosis and management of endometriosis but is one of several approaches to treat this complex condition. Thanks for taking the time to discuss this important condition that affects at least 10% of gynecological patients, and potentially more due to delayed and undiagnosed disease.

Approximately 20% of the population is affected by IBS. When looking at IBS with constipation specifically, how important is diet in relieving symptoms? Is there a specific type of diet recommended for patients to consider?

Dr. Menees: Dietary therapy can be really important for patients with IBS. It’s something they can control, and it can be empowering to them. When I first meet a patient with IBS, I always take a diet history. I want to know what they're putting in their mouth including the beverages that they are drinking.

When it comes to IBS, for a long time, fiber has been first-line treatment, particularly when constipation is the predominant complaint. As you know, fiber is classified into 2 different categories: soluble and insoluble. The soluble fiber is found in psyllium, oat bran, barley, and beans, whereas the insoluble fiber is found in wheat bran, some vegetables, and whole grains.

Soluble fiber exerts its laxative effect as it is hydrophilic, so it brings the water to the stool and increases the stool water content. It also resists colonic fermentation. Insoluble fiber is fermentable and loses its water holding capacity, produces gas that aggravates patients with bloating and flatulence. I always recommend soluble fiber.

When we're thinking about those properties that I just described, the ability to improve stool viscosity and frequency argues for the use of fiber in patients with IBS-C, although there are few studies to support this. There have been a lot of trials, but only a few that have been done within  IBS-C patients. The most recent meta-analysis was done by Moayyedi and colleagues. Here they looked at 15 RCTs of which only 6 had sub-typed the different types of IBS that were in the trials. Only 2 were IBS-C. So, the key takeaway for this meta-analysis was that-- and per the ACG guidelines-- the use of soluble, viscous, nonfermentable fiber provides benefits for global IBS symptoms.

There's also a general lack of side effects with this intervention. It’s important to instruct patients to titrate up on the soluble fiber slowly. Soluble fiber is a very reasonable first-line therapy for patients with IBS.

There are other dietary interventions that we can talk about. In 2015, the National Institute for Health Care Excellence issued their own IBS guideline recommendations. These are common sense things that I discuss with my patients, such as moderation in their diet: don't drink too much alcohol or don't drink too much caffeine. I go over these with patients as the guidelines specifically talk about soluble fiber. It can be helpful for patients to look at what they're doing on a daily basis.

The other important dietary intervention that we have utilized in IBS is the low-FODMAP diet.  This diet is based on restricting fermentable carbohydrates that bacteria work on, producing short chain fatty acids which cause an osmotic shift, bringing water into the colon, producing gases that lead to luminal dissension, and triggering meal-related symptoms in patients with IBS.

A recent meta-analysis of 7 randomized clinical trials looked at low FODMAP diet versus several different comparators. The low-FODMAP diet was associated with a significant reduction in global IBS symptoms compared with the different comparators. However, there are no data on a low-FODMAP diet strictly in IBS-C patients. So, stay tuned on that. We are doing a trial in IBS-C only.

If you are planning on using the low-FODMAP diet in your IBS patients, it's also important to utilize a GI trained dietician, because it can be overwhelming for patients to figure out what's an oligosaccharides, disaccharide, monosaccharides, and polyols. Having a wealth of knowledge available to these patients is critical.

Are there recent studies that show the effectiveness of diet as an approach to managing patients with IBS/CIC and what has been your in-practice experience?

Dr. Menees: Yes.  For IBS and CIC, the initial approach, which is soluble fiber, is what I use in practice for both disorders. However, that response can vary between the 2 conditions, and the next step you chose varies by the disorder.

As far as for my patients, soluble fiber is well accepted, but I do make sure that they are adequately hydrated. Hydration alone doesn't seem to change the incidence of constipation for patients, although there is some evidence for mineral water. Believe it or not, there are 3 randomized controlled trials showing the efficacy of mineral water in patients with CIC. However, it's also important in the chronic constipation patients that you find out how often they're having a bowel movement. If they are having a bm every 7 to 10 days, I'm afraid that fiber will actually worsen their symptoms. In those patients, fiber will not be my first-line treatment.

As far as other dietary options that I use specifically in patients with CIC, we now have data for fruit fibers. Specifically, we have data for prunes and kiwifruit, both green and golden kiwifruit. Chey and colleagues compared the efficacy of psyllium, 2 green kiwi per day, and prunes, 6 twice-daily in patients with CIC.  All 3 arms - kiwifruit (45%), psyllium (64%) and prunes (67%)- were found to be effective. Despite the primary endpoint results, patients randomized to the kiwi arm were most likely to be satisfied with treatment compared to the other arms. There was another trial performed in 32 patients, comparing the gold kiwifruit to psyllium. The kiwifruit resulted in significant improvement in BM frequency and GI discomfort as compared to psyllium. I use all of these as tools for my patients in clinical practice. 

We talked about symptoms, but how important is diet in preventing other diseases or conditions in patients with IBS-C?

Dr. Menees: For diet management, since soluble fibers are the gold standard and our first-line treatment, I discuss the general health benefits of fiber. Fiber is associated with reduced cardiovascular mortality, stroke, diabetes, and colorectal cancer. So that's important.

Being on a high fiber diet can improve the patient's overall general health. It is also helpful for other GI diseases. It helps reduce the risk of diverticulitis and diverticular bleeding. People who are on a high fiber diet are the least likely to have fecal incontinence. These are all excellent benefits of one of our first-line treatments.

Are there first-line therapies you recommend in conjunction with diet to help?

Dr. Menees: When it comes to chronic intermittent constipation, I certainly use osmotic laxatives after at least a 6- to 8-week trial of fiber. When you're adding fiber to your diet, its important to add slowly, about 5 grams per week.

I also tell the patient that it's not going to be quick. It takes at least 6 to 8 weeks for it to kick in. I will use osmotics, PEG 3350 and milk of magnesia which are very cheap and over the counter if they're not reaching the stool consistency and frequency. I also use stimulant and laxatives in my chronic intermittent constipation.

Now, for IBS, PEG 3350 osmotic laxatives are not recommended as it only changes stool frequency, but it has no impact on abdominal discomfort or abdominal pain. For IBS patients, I will utilize the secretagogues, the chloride channel activator, such as lubiprostone or guanylate cyclase activator, such as linaclotide or plecanatide.

Are there specific demographics more susceptible to constipation? What are your standards for dietary considerations for these populations? 

Dr. Menees: There are specific demographics that are susceptible to constipation. Women are more likely than men to have constipation. Women have a longer colon due to reproductive organs. This increases the surface area for absorption of water, which can predispose women to constipation.

In the US and UK, self-reported constipation is definitely more prevalent in women and those over age 60. When you adjust for those factors, you'll see it in patients who have low income, poor education, and little physical activity.

We also know that the prevalence of chronic constipation rises with age, and most dramatically in patients who are 65 and older. Over a quarter of males and almost a third of females will complain of constipation. Now, this age factor can be  compounded by other medical problems, such as hypertension. Additionally, in those over 65, there seems to be a correlation with decreased calories, but not with fluid or fiber.

Other populations that one must consider include any neurologic diseases, such as Parkinson Disease. We have to think of patients with chronic pain as they can be on opioids. But even those with chronic pain who are not on opioids will be on NSAIDs, which can also cause constipation. There are many different factors that make patients susceptible to constipation.

Approximately 20% of the population is affected by IBS. When looking at IBS with constipation specifically, how important is diet in relieving symptoms? Is there a specific type of diet recommended for patients to consider?

Dr. Menees: Dietary therapy can be really important for patients with IBS. It’s something they can control, and it can be empowering to them. When I first meet a patient with IBS, I always take a diet history. I want to know what they're putting in their mouth including the beverages that they are drinking.

When it comes to IBS, for a long time, fiber has been first-line treatment, particularly when constipation is the predominant complaint. As you know, fiber is classified into 2 different categories: soluble and insoluble. The soluble fiber is found in psyllium, oat bran, barley, and beans, whereas the insoluble fiber is found in wheat bran, some vegetables, and whole grains.

Soluble fiber exerts its laxative effect as it is hydrophilic, so it brings the water to the stool and increases the stool water content. It also resists colonic fermentation. Insoluble fiber is fermentable and loses its water holding capacity, produces gas that aggravates patients with bloating and flatulence. I always recommend soluble fiber.

When we're thinking about those properties that I just described, the ability to improve stool viscosity and frequency argues for the use of fiber in patients with IBS-C, although there are few studies to support this. There have been a lot of trials, but only a few that have been done within  IBS-C patients. The most recent meta-analysis was done by Moayyedi and colleagues. Here they looked at 15 RCTs of which only 6 had sub-typed the different types of IBS that were in the trials. Only 2 were IBS-C. So, the key takeaway for this meta-analysis was that-- and per the ACG guidelines-- the use of soluble, viscous, nonfermentable fiber provides benefits for global IBS symptoms.

There's also a general lack of side effects with this intervention. It’s important to instruct patients to titrate up on the soluble fiber slowly. Soluble fiber is a very reasonable first-line therapy for patients with IBS.

There are other dietary interventions that we can talk about. In 2015, the National Institute for Health Care Excellence issued their own IBS guideline recommendations. These are common sense things that I discuss with my patients, such as moderation in their diet: don't drink too much alcohol or don't drink too much caffeine. I go over these with patients as the guidelines specifically talk about soluble fiber. It can be helpful for patients to look at what they're doing on a daily basis.

The other important dietary intervention that we have utilized in IBS is the low-FODMAP diet.  This diet is based on restricting fermentable carbohydrates that bacteria work on, producing short chain fatty acids which cause an osmotic shift, bringing water into the colon, producing gases that lead to luminal dissension, and triggering meal-related symptoms in patients with IBS.

A recent meta-analysis of 7 randomized clinical trials looked at low FODMAP diet versus several different comparators. The low-FODMAP diet was associated with a significant reduction in global IBS symptoms compared with the different comparators. However, there are no data on a low-FODMAP diet strictly in IBS-C patients. So, stay tuned on that. We are doing a trial in IBS-C only.

If you are planning on using the low-FODMAP diet in your IBS patients, it's also important to utilize a GI trained dietician, because it can be overwhelming for patients to figure out what's an oligosaccharides, disaccharide, monosaccharides, and polyols. Having a wealth of knowledge available to these patients is critical.

Are there recent studies that show the effectiveness of diet as an approach to managing patients with IBS/CIC and what has been your in-practice experience?

Dr. Menees: Yes.  For IBS and CIC, the initial approach, which is soluble fiber, is what I use in practice for both disorders. However, that response can vary between the 2 conditions, and the next step you chose varies by the disorder.

As far as for my patients, soluble fiber is well accepted, but I do make sure that they are adequately hydrated. Hydration alone doesn't seem to change the incidence of constipation for patients, although there is some evidence for mineral water. Believe it or not, there are 3 randomized controlled trials showing the efficacy of mineral water in patients with CIC. However, it's also important in the chronic constipation patients that you find out how often they're having a bowel movement. If they are having a bm every 7 to 10 days, I'm afraid that fiber will actually worsen their symptoms. In those patients, fiber will not be my first-line treatment.

As far as other dietary options that I use specifically in patients with CIC, we now have data for fruit fibers. Specifically, we have data for prunes and kiwifruit, both green and golden kiwifruit. Chey and colleagues compared the efficacy of psyllium, 2 green kiwi per day, and prunes, 6 twice-daily in patients with CIC.  All 3 arms - kiwifruit (45%), psyllium (64%) and prunes (67%)- were found to be effective. Despite the primary endpoint results, patients randomized to the kiwi arm were most likely to be satisfied with treatment compared to the other arms. There was another trial performed in 32 patients, comparing the gold kiwifruit to psyllium. The kiwifruit resulted in significant improvement in BM frequency and GI discomfort as compared to psyllium. I use all of these as tools for my patients in clinical practice. 

We talked about symptoms, but how important is diet in preventing other diseases or conditions in patients with IBS-C?

Dr. Menees: For diet management, since soluble fibers are the gold standard and our first-line treatment, I discuss the general health benefits of fiber. Fiber is associated with reduced cardiovascular mortality, stroke, diabetes, and colorectal cancer. So that's important.

Being on a high fiber diet can improve the patient's overall general health. It is also helpful for other GI diseases. It helps reduce the risk of diverticulitis and diverticular bleeding. People who are on a high fiber diet are the least likely to have fecal incontinence. These are all excellent benefits of one of our first-line treatments.

Are there first-line therapies you recommend in conjunction with diet to help?

Dr. Menees: When it comes to chronic intermittent constipation, I certainly use osmotic laxatives after at least a 6- to 8-week trial of fiber. When you're adding fiber to your diet, its important to add slowly, about 5 grams per week.

I also tell the patient that it's not going to be quick. It takes at least 6 to 8 weeks for it to kick in. I will use osmotics, PEG 3350 and milk of magnesia which are very cheap and over the counter if they're not reaching the stool consistency and frequency. I also use stimulant and laxatives in my chronic intermittent constipation.

Now, for IBS, PEG 3350 osmotic laxatives are not recommended as it only changes stool frequency, but it has no impact on abdominal discomfort or abdominal pain. For IBS patients, I will utilize the secretagogues, the chloride channel activator, such as lubiprostone or guanylate cyclase activator, such as linaclotide or plecanatide.

Are there specific demographics more susceptible to constipation? What are your standards for dietary considerations for these populations? 

Dr. Menees: There are specific demographics that are susceptible to constipation. Women are more likely than men to have constipation. Women have a longer colon due to reproductive organs. This increases the surface area for absorption of water, which can predispose women to constipation.

In the US and UK, self-reported constipation is definitely more prevalent in women and those over age 60. When you adjust for those factors, you'll see it in patients who have low income, poor education, and little physical activity.

We also know that the prevalence of chronic constipation rises with age, and most dramatically in patients who are 65 and older. Over a quarter of males and almost a third of females will complain of constipation. Now, this age factor can be  compounded by other medical problems, such as hypertension. Additionally, in those over 65, there seems to be a correlation with decreased calories, but not with fluid or fiber.

Other populations that one must consider include any neurologic diseases, such as Parkinson Disease. We have to think of patients with chronic pain as they can be on opioids. But even those with chronic pain who are not on opioids will be on NSAIDs, which can also cause constipation. There are many different factors that make patients susceptible to constipation.

Approximately 20% of the population is affected by IBS. When looking at IBS with constipation specifically, how important is diet in relieving symptoms? Is there a specific type of diet recommended for patients to consider?

Dr. Menees: Dietary therapy can be really important for patients with IBS. It’s something they can control, and it can be empowering to them. When I first meet a patient with IBS, I always take a diet history. I want to know what they're putting in their mouth including the beverages that they are drinking.

When it comes to IBS, for a long time, fiber has been first-line treatment, particularly when constipation is the predominant complaint. As you know, fiber is classified into 2 different categories: soluble and insoluble. The soluble fiber is found in psyllium, oat bran, barley, and beans, whereas the insoluble fiber is found in wheat bran, some vegetables, and whole grains.

Soluble fiber exerts its laxative effect as it is hydrophilic, so it brings the water to the stool and increases the stool water content. It also resists colonic fermentation. Insoluble fiber is fermentable and loses its water holding capacity, produces gas that aggravates patients with bloating and flatulence. I always recommend soluble fiber.

When we're thinking about those properties that I just described, the ability to improve stool viscosity and frequency argues for the use of fiber in patients with IBS-C, although there are few studies to support this. There have been a lot of trials, but only a few that have been done within  IBS-C patients. The most recent meta-analysis was done by Moayyedi and colleagues. Here they looked at 15 RCTs of which only 6 had sub-typed the different types of IBS that were in the trials. Only 2 were IBS-C. So, the key takeaway for this meta-analysis was that-- and per the ACG guidelines-- the use of soluble, viscous, nonfermentable fiber provides benefits for global IBS symptoms.

There's also a general lack of side effects with this intervention. It’s important to instruct patients to titrate up on the soluble fiber slowly. Soluble fiber is a very reasonable first-line therapy for patients with IBS.

There are other dietary interventions that we can talk about. In 2015, the National Institute for Health Care Excellence issued their own IBS guideline recommendations. These are common sense things that I discuss with my patients, such as moderation in their diet: don't drink too much alcohol or don't drink too much caffeine. I go over these with patients as the guidelines specifically talk about soluble fiber. It can be helpful for patients to look at what they're doing on a daily basis.

The other important dietary intervention that we have utilized in IBS is the low-FODMAP diet.  This diet is based on restricting fermentable carbohydrates that bacteria work on, producing short chain fatty acids which cause an osmotic shift, bringing water into the colon, producing gases that lead to luminal dissension, and triggering meal-related symptoms in patients with IBS.

A recent meta-analysis of 7 randomized clinical trials looked at low FODMAP diet versus several different comparators. The low-FODMAP diet was associated with a significant reduction in global IBS symptoms compared with the different comparators. However, there are no data on a low-FODMAP diet strictly in IBS-C patients. So, stay tuned on that. We are doing a trial in IBS-C only.

If you are planning on using the low-FODMAP diet in your IBS patients, it's also important to utilize a GI trained dietician, because it can be overwhelming for patients to figure out what's an oligosaccharides, disaccharide, monosaccharides, and polyols. Having a wealth of knowledge available to these patients is critical.

Are there recent studies that show the effectiveness of diet as an approach to managing patients with IBS/CIC and what has been your in-practice experience?

Dr. Menees: Yes.  For IBS and CIC, the initial approach, which is soluble fiber, is what I use in practice for both disorders. However, that response can vary between the 2 conditions, and the next step you chose varies by the disorder.

As far as for my patients, soluble fiber is well accepted, but I do make sure that they are adequately hydrated. Hydration alone doesn't seem to change the incidence of constipation for patients, although there is some evidence for mineral water. Believe it or not, there are 3 randomized controlled trials showing the efficacy of mineral water in patients with CIC. However, it's also important in the chronic constipation patients that you find out how often they're having a bowel movement. If they are having a bm every 7 to 10 days, I'm afraid that fiber will actually worsen their symptoms. In those patients, fiber will not be my first-line treatment.

As far as other dietary options that I use specifically in patients with CIC, we now have data for fruit fibers. Specifically, we have data for prunes and kiwifruit, both green and golden kiwifruit. Chey and colleagues compared the efficacy of psyllium, 2 green kiwi per day, and prunes, 6 twice-daily in patients with CIC.  All 3 arms - kiwifruit (45%), psyllium (64%) and prunes (67%)- were found to be effective. Despite the primary endpoint results, patients randomized to the kiwi arm were most likely to be satisfied with treatment compared to the other arms. There was another trial performed in 32 patients, comparing the gold kiwifruit to psyllium. The kiwifruit resulted in significant improvement in BM frequency and GI discomfort as compared to psyllium. I use all of these as tools for my patients in clinical practice. 

We talked about symptoms, but how important is diet in preventing other diseases or conditions in patients with IBS-C?

Dr. Menees: For diet management, since soluble fibers are the gold standard and our first-line treatment, I discuss the general health benefits of fiber. Fiber is associated with reduced cardiovascular mortality, stroke, diabetes, and colorectal cancer. So that's important.

Being on a high fiber diet can improve the patient's overall general health. It is also helpful for other GI diseases. It helps reduce the risk of diverticulitis and diverticular bleeding. People who are on a high fiber diet are the least likely to have fecal incontinence. These are all excellent benefits of one of our first-line treatments.

Are there first-line therapies you recommend in conjunction with diet to help?

Dr. Menees: When it comes to chronic intermittent constipation, I certainly use osmotic laxatives after at least a 6- to 8-week trial of fiber. When you're adding fiber to your diet, its important to add slowly, about 5 grams per week.

I also tell the patient that it's not going to be quick. It takes at least 6 to 8 weeks for it to kick in. I will use osmotics, PEG 3350 and milk of magnesia which are very cheap and over the counter if they're not reaching the stool consistency and frequency. I also use stimulant and laxatives in my chronic intermittent constipation.

Now, for IBS, PEG 3350 osmotic laxatives are not recommended as it only changes stool frequency, but it has no impact on abdominal discomfort or abdominal pain. For IBS patients, I will utilize the secretagogues, the chloride channel activator, such as lubiprostone or guanylate cyclase activator, such as linaclotide or plecanatide.

Are there specific demographics more susceptible to constipation? What are your standards for dietary considerations for these populations? 

Dr. Menees: There are specific demographics that are susceptible to constipation. Women are more likely than men to have constipation. Women have a longer colon due to reproductive organs. This increases the surface area for absorption of water, which can predispose women to constipation.

In the US and UK, self-reported constipation is definitely more prevalent in women and those over age 60. When you adjust for those factors, you'll see it in patients who have low income, poor education, and little physical activity.

We also know that the prevalence of chronic constipation rises with age, and most dramatically in patients who are 65 and older. Over a quarter of males and almost a third of females will complain of constipation. Now, this age factor can be  compounded by other medical problems, such as hypertension. Additionally, in those over 65, there seems to be a correlation with decreased calories, but not with fluid or fiber.

Other populations that one must consider include any neurologic diseases, such as Parkinson Disease. We have to think of patients with chronic pain as they can be on opioids. But even those with chronic pain who are not on opioids will be on NSAIDs, which can also cause constipation. There are many different factors that make patients susceptible to constipation.

Based on the work you do at the Cleveland Clinic Taussig Cancer Institute, what is your standard approach to managing  early stage cancer patients?

Dr. Roesch: The approach to managing patients with early stage breast cancer very much depends on the subtype of breast cancer. Clinical stage at presentation and patient factors are considered here. For example, patients with small hormone receptor-positive tumors will often have surgery first, while patients with triple-negative or HER2-positive tumors will often receive preoperative or neoadjuvant chemotherapy.

In situations where there is a need or a desire for downstaging or shrinking of the primary tumor or lymph nodes in the axilla, we will also discuss neoadjuvant systemic therapy. For hormone receptor-positive tumors, endocrine or anti-estrogen therapy will be incorporated into their treatment regimen at some point in the future.

The role of chemotherapy for hormone receptor-positive breast cancer depends on a variety of factors, including pathologic staging, which we obtain at the time of surgery. Exceptions may include very small tumors or patients who have medical comorbidities that affect their candidacy for chemotherapy where the risk may outweigh the benefit.

Are there specific steps you take in managing and treating early stage triple-negative breast cancer?

Dr. Roesch: Most patients with early stage triple-negative breast cancer receive neoadjuvant or preoperative chemotherapy. As I mentioned above, this has the benefits of downstaging the primary tumor itself and the lymph nodes in the axilla as well as providing prognostic information. This approach can also help guide adjuvant therapy recommendations. Additionally, we often discuss the role of genetic counseling for these patients.

Are there targeted therapies you rely upon?

Dr. Roesch: This has been an evolving field with dramatic advances in the past couple of years. One is immunotherapy. There was a phase III study called the KEYONTE-522 trial, which demonstrated improvements in pathologic response rate and event-free survival with a regimen of neoadjuvant pembrolizumab plus chemotherapy followed by the pembrolizumab given in the adjuvant setting, compared to chemotherapy approach alone (1).

For patients who meet criteria for this study, which is essentially stage II/III triple-negative breast cancer, we have adopted this regimen in the neoadjuvant setting. Additionally, we consider adjuvant capecitabine for patients who have received neoadjuvant chemotherapy with an anthracycline, taxane or both and who have residual disease at the time of surgery. This is based on the CREATE-X trial, which showed a survival benefit for patients with triple-negative breast cancer in this situation (2).

Lastly, the PARP inhibitor, olaparib, was recently approved by the FDA in the adjuvant setting for BRCA mutation carriers diagnosed with HER-2-negative high-risk early breast cancer who have received neoadjuvant or adjuvant chemotherapy. This treatment also demonstrated survival benefit and is an exciting new option for these patients (3).

A critical question in my mind that has arisen out of these new developments is sequencing of these therapies. For example, if I have a patient who received the KEYNOTE-522 regimen with the immunotherapy agent, pembrolizumab, and has residual disease after surgery, how do we administer the capecitabine with the pembrolizumab? And what about radiation? What if a patient is a BRCA mutation carrier? These are all very relevant questions, which we are encountering every day, and the approach we take is often individualized.

This sounds very exciting. Can you talk about the research on managing early triple-negative breast cancer and what the future might hold?

Dr. Roesch: This is a very exciting time for both us as oncologists and our patients as there is a very rapid pace of new therapies being explored in the context of clinical trials. First, I'd like to mention the adjuvant vaccine trial we have at Cleveland Clinic for patients diagnosed with early stage triple-negative breast cancer at high risk of recurrence. This trial is investigating an alpha lactalbumin vaccine, which has been selected as a vaccine target because it is a breast-specific differentiation protein expressed at high levels in many human breast cancers, particularly in triple-negative breast cancer. The current trial's main objective is to determine the maximum tolerated dose of the vaccine, and other endpoints include looking at biomarkers of immune responses (4).

The I-SPY2 trial is another very exciting study we have open at Cleveland Clinic. This is a multicenter phase II trial using response adaptive randomization within molecular subtypes, which is defined by the receptor status and MammaPrint risk, which is a genomic assay, to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Patients undergo serial MRIs and biopsies with information on the likelihood of them achieving a pathologic complete response (pCR) provided back in real time, which will then allow for therapy escalation or de-escalation. The goal here is individualized precision therapy based on the specific intrinsic subtype of the tumor itself and response with the ultimate goal being to achieve a pCR (5).

Again, this is a very exciting time for us as medical providers and our patients because new therapies are being developed and studied in clinical trials every day.

Based on the work you do at the Cleveland Clinic Taussig Cancer Institute, what is your standard approach to managing  early stage cancer patients?

Dr. Roesch: The approach to managing patients with early stage breast cancer very much depends on the subtype of breast cancer. Clinical stage at presentation and patient factors are considered here. For example, patients with small hormone receptor-positive tumors will often have surgery first, while patients with triple-negative or HER2-positive tumors will often receive preoperative or neoadjuvant chemotherapy.

In situations where there is a need or a desire for downstaging or shrinking of the primary tumor or lymph nodes in the axilla, we will also discuss neoadjuvant systemic therapy. For hormone receptor-positive tumors, endocrine or anti-estrogen therapy will be incorporated into their treatment regimen at some point in the future.

The role of chemotherapy for hormone receptor-positive breast cancer depends on a variety of factors, including pathologic staging, which we obtain at the time of surgery. Exceptions may include very small tumors or patients who have medical comorbidities that affect their candidacy for chemotherapy where the risk may outweigh the benefit.

Are there specific steps you take in managing and treating early stage triple-negative breast cancer?

Dr. Roesch: Most patients with early stage triple-negative breast cancer receive neoadjuvant or preoperative chemotherapy. As I mentioned above, this has the benefits of downstaging the primary tumor itself and the lymph nodes in the axilla as well as providing prognostic information. This approach can also help guide adjuvant therapy recommendations. Additionally, we often discuss the role of genetic counseling for these patients.

Are there targeted therapies you rely upon?

Dr. Roesch: This has been an evolving field with dramatic advances in the past couple of years. One is immunotherapy. There was a phase III study called the KEYONTE-522 trial, which demonstrated improvements in pathologic response rate and event-free survival with a regimen of neoadjuvant pembrolizumab plus chemotherapy followed by the pembrolizumab given in the adjuvant setting, compared to chemotherapy approach alone (1).

For patients who meet criteria for this study, which is essentially stage II/III triple-negative breast cancer, we have adopted this regimen in the neoadjuvant setting. Additionally, we consider adjuvant capecitabine for patients who have received neoadjuvant chemotherapy with an anthracycline, taxane or both and who have residual disease at the time of surgery. This is based on the CREATE-X trial, which showed a survival benefit for patients with triple-negative breast cancer in this situation (2).

Lastly, the PARP inhibitor, olaparib, was recently approved by the FDA in the adjuvant setting for BRCA mutation carriers diagnosed with HER-2-negative high-risk early breast cancer who have received neoadjuvant or adjuvant chemotherapy. This treatment also demonstrated survival benefit and is an exciting new option for these patients (3).

A critical question in my mind that has arisen out of these new developments is sequencing of these therapies. For example, if I have a patient who received the KEYNOTE-522 regimen with the immunotherapy agent, pembrolizumab, and has residual disease after surgery, how do we administer the capecitabine with the pembrolizumab? And what about radiation? What if a patient is a BRCA mutation carrier? These are all very relevant questions, which we are encountering every day, and the approach we take is often individualized.

This sounds very exciting. Can you talk about the research on managing early triple-negative breast cancer and what the future might hold?

Dr. Roesch: This is a very exciting time for both us as oncologists and our patients as there is a very rapid pace of new therapies being explored in the context of clinical trials. First, I'd like to mention the adjuvant vaccine trial we have at Cleveland Clinic for patients diagnosed with early stage triple-negative breast cancer at high risk of recurrence. This trial is investigating an alpha lactalbumin vaccine, which has been selected as a vaccine target because it is a breast-specific differentiation protein expressed at high levels in many human breast cancers, particularly in triple-negative breast cancer. The current trial's main objective is to determine the maximum tolerated dose of the vaccine, and other endpoints include looking at biomarkers of immune responses (4).

The I-SPY2 trial is another very exciting study we have open at Cleveland Clinic. This is a multicenter phase II trial using response adaptive randomization within molecular subtypes, which is defined by the receptor status and MammaPrint risk, which is a genomic assay, to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Patients undergo serial MRIs and biopsies with information on the likelihood of them achieving a pathologic complete response (pCR) provided back in real time, which will then allow for therapy escalation or de-escalation. The goal here is individualized precision therapy based on the specific intrinsic subtype of the tumor itself and response with the ultimate goal being to achieve a pCR (5).

Again, this is a very exciting time for us as medical providers and our patients because new therapies are being developed and studied in clinical trials every day.

Based on the work you do at the Cleveland Clinic Taussig Cancer Institute, what is your standard approach to managing  early stage cancer patients?

Dr. Roesch: The approach to managing patients with early stage breast cancer very much depends on the subtype of breast cancer. Clinical stage at presentation and patient factors are considered here. For example, patients with small hormone receptor-positive tumors will often have surgery first, while patients with triple-negative or HER2-positive tumors will often receive preoperative or neoadjuvant chemotherapy.

In situations where there is a need or a desire for downstaging or shrinking of the primary tumor or lymph nodes in the axilla, we will also discuss neoadjuvant systemic therapy. For hormone receptor-positive tumors, endocrine or anti-estrogen therapy will be incorporated into their treatment regimen at some point in the future.

The role of chemotherapy for hormone receptor-positive breast cancer depends on a variety of factors, including pathologic staging, which we obtain at the time of surgery. Exceptions may include very small tumors or patients who have medical comorbidities that affect their candidacy for chemotherapy where the risk may outweigh the benefit.

Are there specific steps you take in managing and treating early stage triple-negative breast cancer?

Dr. Roesch: Most patients with early stage triple-negative breast cancer receive neoadjuvant or preoperative chemotherapy. As I mentioned above, this has the benefits of downstaging the primary tumor itself and the lymph nodes in the axilla as well as providing prognostic information. This approach can also help guide adjuvant therapy recommendations. Additionally, we often discuss the role of genetic counseling for these patients.

Are there targeted therapies you rely upon?

Dr. Roesch: This has been an evolving field with dramatic advances in the past couple of years. One is immunotherapy. There was a phase III study called the KEYONTE-522 trial, which demonstrated improvements in pathologic response rate and event-free survival with a regimen of neoadjuvant pembrolizumab plus chemotherapy followed by the pembrolizumab given in the adjuvant setting, compared to chemotherapy approach alone (1).

For patients who meet criteria for this study, which is essentially stage II/III triple-negative breast cancer, we have adopted this regimen in the neoadjuvant setting. Additionally, we consider adjuvant capecitabine for patients who have received neoadjuvant chemotherapy with an anthracycline, taxane or both and who have residual disease at the time of surgery. This is based on the CREATE-X trial, which showed a survival benefit for patients with triple-negative breast cancer in this situation (2).

Lastly, the PARP inhibitor, olaparib, was recently approved by the FDA in the adjuvant setting for BRCA mutation carriers diagnosed with HER-2-negative high-risk early breast cancer who have received neoadjuvant or adjuvant chemotherapy. This treatment also demonstrated survival benefit and is an exciting new option for these patients (3).

A critical question in my mind that has arisen out of these new developments is sequencing of these therapies. For example, if I have a patient who received the KEYNOTE-522 regimen with the immunotherapy agent, pembrolizumab, and has residual disease after surgery, how do we administer the capecitabine with the pembrolizumab? And what about radiation? What if a patient is a BRCA mutation carrier? These are all very relevant questions, which we are encountering every day, and the approach we take is often individualized.

This sounds very exciting. Can you talk about the research on managing early triple-negative breast cancer and what the future might hold?

Dr. Roesch: This is a very exciting time for both us as oncologists and our patients as there is a very rapid pace of new therapies being explored in the context of clinical trials. First, I'd like to mention the adjuvant vaccine trial we have at Cleveland Clinic for patients diagnosed with early stage triple-negative breast cancer at high risk of recurrence. This trial is investigating an alpha lactalbumin vaccine, which has been selected as a vaccine target because it is a breast-specific differentiation protein expressed at high levels in many human breast cancers, particularly in triple-negative breast cancer. The current trial's main objective is to determine the maximum tolerated dose of the vaccine, and other endpoints include looking at biomarkers of immune responses (4).

The I-SPY2 trial is another very exciting study we have open at Cleveland Clinic. This is a multicenter phase II trial using response adaptive randomization within molecular subtypes, which is defined by the receptor status and MammaPrint risk, which is a genomic assay, to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Patients undergo serial MRIs and biopsies with information on the likelihood of them achieving a pathologic complete response (pCR) provided back in real time, which will then allow for therapy escalation or de-escalation. The goal here is individualized precision therapy based on the specific intrinsic subtype of the tumor itself and response with the ultimate goal being to achieve a pCR (5).

Again, this is a very exciting time for us as medical providers and our patients because new therapies are being developed and studied in clinical trials every day.

Kelsey Kennedy is a Family Nurse Practitioner (FNP) and has been working as a nurse practitioner in the Women's Health Institute at the Cleveland Clinic in General Gynecology for the past three years. She has her undergraduate degree from Saint Louis University and completed her graduate studies at Walsh University. She works with patients providing annual/wellness care, contraceptive counseling, abnormal bleeding evaluation and addresses many other non-OB gynecologic issues. The best part about her job is connecting with women and empowering the women she serves to be in control of their reproductive health and wellness.

As a nurse practitioner focused on benign gynecological treatment, what is your role as it relates to uterine fibroids, which are benign non-cancerous tumors?

Ms. Kennedy: As Nurse Practitioner (NP) working in GYN, I see both common and complex gynecologic, sexual, reproductive, menopausal issues. We really do it all. The NP collaborates with the entire medical health care team, including physicians, medical assistants, nursing, and administrators.

In the outpatient office practice with the Cleveland Clinic, I provide mostly benign or general GYN care, which means I see a lot of annual wellness exams, infection checks, birth control consults, and abnormal bleeding. I see patients that may have complaints of heavy periods, pelvic pain, pressure, but they might not have a formal diagnosis or know exactly why they have such heavy periods. Sometimes I see patients that have never even heard of fibroids. It’s my job to take a thorough history, perform a physical exam, and order any additional testing indicated to get the workup started to figure out exactly what's going on.

Abnormal uterine bleeding is defined as a change in the frequency, duration, or amount of menstrual bleeding. It's a common GYN complaint that affects anywhere from 10% to 30% of reproductive age women. In fact, abnormal bleeding is the reason for 1/3 of all outpatient GYN visits and a common cause of abnormal uterine bleeding is fibroids.

So just to review, fibroids are those benign, meaning non-cancerous, tumors made of smooth muscle tissue. Fibroids affect up to 40% of women of reproductive age. And by age 50, up to 70% of women have at least one fibroid. Fibroids are very common. It is important to know that only about 25% of fibroids are clinically significant or problematic enough to require intervention. With that being said, we know that fibroids can be asymptomatic, but often, they can cause pain and bleeding.

Some situations that occur that might make me suspect fibroids include a history of periods that are regular, once monthly, but progressively becoming heavier and heavier over time; periods that last longer than seven days; menstrual bleeding so heavy patients soak through overnight pads or their clothes during the day or overnight; menstrual bleeding with large clots; pelvic pain; pressure; urinary frequency, which could be related to fibroids pressing on the bladder; or constipation, which we know has many causes but can sometimes be related to fibroids pressing on the rectum. That’s it.

What impact does Long-Acting Reversible Contraception, or LARC, have on the uterus?

Ms. Kennedy: Generally speaking, Long-Acting Reversible Contraception, or LARC, is a broad category of birth control methods that provide contraception for an extended period of time-- anywhere from 3 to 10 years, depending on the type you choose. The best part about LARC options is they do not require user action. It's 99% effective in preventing unwanted pregnancy. I like to call it set-it-and-forget-it birth control.

The LARC options we have included are all the IUDs, which consists of the Paragard or copper IUD, and the three different hormonal IUDs-- the Mirena, Kyleena, and the Skyla. That also includes the Nexplanon arm implant. Out of all these LARC options, the Mirena IUD is the only one that’s FDA approved to treat heavy menstrual bleeding which can include heavy menstrual bleeding related to fibroids. The Mirena is FDA approved right now for seven years of use, which is a nice long time to get a lot of good benefit.

The Mirena IUD, specifically, is a T-shaped device that's placed in the uterus. It releases a steady local, meaning the hormone is released pretty much just in the uterus, amount of levonorgestrel, which is a second-generation synthetic progesterone. Basically, it's a hormone. The Mirena releases 20 micrograms of levonorgestrel into the uterus every day. What this hormone does is cause a dramatic reduction of blood flow by changing the endometrium, or the lining of the uterus.

The Mirena IUD was found to reduce blood loss by 86% after three months of use and by up to 97% after 12 months of use. This big reduction in bleeding subsequently leads to an increase in iron and hemoglobin levels in women with heavy bleeding and fibroids.

Hysterectomy has long been the definitive solution for abnormal bleeding that doesn't respond to our usual treatments. But since the Mirena was developed in the 1990s, more and more evidence has come to light that the Mirena can be a safe and effective medical alternative to hysterectomy. Many women benefit from and seek other management options for bleeding and heavy bleeding relating to fibroids other than hysterectomy because they might desire future childbearing, or they just might want to retain their uterus.

In addition, we also know that fibroids typically regress in menopause. Using the Mirena IUD is a great solution to control heavy bleeding that a woman can use until they're in menopause and no longer having periods. The Mirena IUD is much less invasive than a hysterectomy and has lower risk for complications.

What steps do you take to identify encounters that might impose challenges as it relates to the uterine structure?

Ms. Kennedy: One thing that may impose a challenge in using the Mirena IUD to manage heavy bleeding related to fibroids is the specific size and location of the fibroids. Submucosal fibroids, also called intracavitary fibroids, grow into the uterus. These submucosal fibroids grow just below the inner lining of the uterus. They often cause more bleeding and problems than other types of fibroids because they crowd the uterine space. If the submucosal fibroid is too big or filling up too much of the uterine cavity, there may not be enough room for us to place a Mirena IUD.

The rates of IUD expulsion are increased in patients with fibroids that distort the uterine cavity. That's one thing we definitely want to consider. I typically refer these patients to one of my GYN surgeon colleagues to determine if the submucosal fibroid should be removed hysteroscopically in the OR. Sometimes after removing these submucosal fibroids via hysteroscopy in the OR, the surgeons will place the Mirena IUD at the end of the case.

I think you touched on this a little bit, but are there methods, in addition to IUDs, that would assist in managing heavy menstrual bleeding associated with uterine fibroids?

Ms. Kennedy: Yes. We have several current methods to manage heavy menstrual bleeding associated with uterine fibroids. One method is simply expectant management or watchful waiting. This means that the amount of bleeding or pain a woman is having related to fibroids is neither severe nor debilitating for her, but we continue to monitor them closely. We usually review what criteria the patient should look out for that may indicate she needs to follow up on, for us to take a closer look at her fibroids. Typically, that would be worsening bleeding or worsening pain.

Some oral medication options are hormonal methods which can include combined oral birth control pills, oral progesterone pills, and sometimes we use injections such as Depo-Provera, which is typically used for birth control. Oral contraceptives can reduce bleeding associated with fibroids by about 40% to 50%.

We also have non-hormonal medications like tranexamic acid, or Lysteda, which is an antifibrinolytic agent that women take only during their monthly periods for up to five days. Women who have a history of clots cannot take this drug. However, for women who can safely use this medication, on average, Lysteda has been shown to reduce the amount of blood loss during monthly periods by about 40%. There are other medication options, including GnRH antagonists that I don't prescribe as often.

The Mirena IUD, as we've discussed, is also such a great option to reduce heavy menstrual bleeding in women which can reduce menstrual bleeding by 86% to 97%. That’s a big jump. For patients that might need procedural interventions or surgical approaches, that may be most appropriate if they are having bulk symptoms associated with their fibroids like pelvic pain, pelvic pressure, urinary, or frequency. These kinds of symptoms are caused by the sheer size of the fibroids or from the fibroids pressing on surrounding structures. Bulk symptoms often do not improve much with medications or the IUDs. Those options address bleeding associated with fibroids much better.

How likely are women to stay on these medications that have contraceptive benefits based on the impact it may have in relation to uterine fibroids?

Ms. Kennedy: In one study that examined the effectiveness of the Mirena IUD versus other medications, including oral progesterone therapy to manage heavy bleeding, 76% of women using the Mirena IUD wished to continue the treatment compared to 22% of women that wished to continue the oral progestin therapy.

In another prospective observational clinical study, 82.5% of women had improvement of heavy menstrual bleeding with the Mirena. They continued to use the Mirena after 12 months. The Mirena IUD is effective in controlling heavy menstrual bleeding related to fibroids in about 77% of cases. The most common side effect is menstrual spotting for a few months after insertion. But overall, we do see a pretty high user satisfaction rate.

Kelsey Kennedy is a Family Nurse Practitioner (FNP) and has been working as a nurse practitioner in the Women's Health Institute at the Cleveland Clinic in General Gynecology for the past three years. She has her undergraduate degree from Saint Louis University and completed her graduate studies at Walsh University. She works with patients providing annual/wellness care, contraceptive counseling, abnormal bleeding evaluation and addresses many other non-OB gynecologic issues. The best part about her job is connecting with women and empowering the women she serves to be in control of their reproductive health and wellness.

As a nurse practitioner focused on benign gynecological treatment, what is your role as it relates to uterine fibroids, which are benign non-cancerous tumors?

Ms. Kennedy: As Nurse Practitioner (NP) working in GYN, I see both common and complex gynecologic, sexual, reproductive, menopausal issues. We really do it all. The NP collaborates with the entire medical health care team, including physicians, medical assistants, nursing, and administrators.

In the outpatient office practice with the Cleveland Clinic, I provide mostly benign or general GYN care, which means I see a lot of annual wellness exams, infection checks, birth control consults, and abnormal bleeding. I see patients that may have complaints of heavy periods, pelvic pain, pressure, but they might not have a formal diagnosis or know exactly why they have such heavy periods. Sometimes I see patients that have never even heard of fibroids. It’s my job to take a thorough history, perform a physical exam, and order any additional testing indicated to get the workup started to figure out exactly what's going on.

Abnormal uterine bleeding is defined as a change in the frequency, duration, or amount of menstrual bleeding. It's a common GYN complaint that affects anywhere from 10% to 30% of reproductive age women. In fact, abnormal bleeding is the reason for 1/3 of all outpatient GYN visits and a common cause of abnormal uterine bleeding is fibroids.

So just to review, fibroids are those benign, meaning non-cancerous, tumors made of smooth muscle tissue. Fibroids affect up to 40% of women of reproductive age. And by age 50, up to 70% of women have at least one fibroid. Fibroids are very common. It is important to know that only about 25% of fibroids are clinically significant or problematic enough to require intervention. With that being said, we know that fibroids can be asymptomatic, but often, they can cause pain and bleeding.

Some situations that occur that might make me suspect fibroids include a history of periods that are regular, once monthly, but progressively becoming heavier and heavier over time; periods that last longer than seven days; menstrual bleeding so heavy patients soak through overnight pads or their clothes during the day or overnight; menstrual bleeding with large clots; pelvic pain; pressure; urinary frequency, which could be related to fibroids pressing on the bladder; or constipation, which we know has many causes but can sometimes be related to fibroids pressing on the rectum. That’s it.

What impact does Long-Acting Reversible Contraception, or LARC, have on the uterus?

Ms. Kennedy: Generally speaking, Long-Acting Reversible Contraception, or LARC, is a broad category of birth control methods that provide contraception for an extended period of time-- anywhere from 3 to 10 years, depending on the type you choose. The best part about LARC options is they do not require user action. It's 99% effective in preventing unwanted pregnancy. I like to call it set-it-and-forget-it birth control.

The LARC options we have included are all the IUDs, which consists of the Paragard or copper IUD, and the three different hormonal IUDs-- the Mirena, Kyleena, and the Skyla. That also includes the Nexplanon arm implant. Out of all these LARC options, the Mirena IUD is the only one that’s FDA approved to treat heavy menstrual bleeding which can include heavy menstrual bleeding related to fibroids. The Mirena is FDA approved right now for seven years of use, which is a nice long time to get a lot of good benefit.

The Mirena IUD, specifically, is a T-shaped device that's placed in the uterus. It releases a steady local, meaning the hormone is released pretty much just in the uterus, amount of levonorgestrel, which is a second-generation synthetic progesterone. Basically, it's a hormone. The Mirena releases 20 micrograms of levonorgestrel into the uterus every day. What this hormone does is cause a dramatic reduction of blood flow by changing the endometrium, or the lining of the uterus.

The Mirena IUD was found to reduce blood loss by 86% after three months of use and by up to 97% after 12 months of use. This big reduction in bleeding subsequently leads to an increase in iron and hemoglobin levels in women with heavy bleeding and fibroids.

Hysterectomy has long been the definitive solution for abnormal bleeding that doesn't respond to our usual treatments. But since the Mirena was developed in the 1990s, more and more evidence has come to light that the Mirena can be a safe and effective medical alternative to hysterectomy. Many women benefit from and seek other management options for bleeding and heavy bleeding relating to fibroids other than hysterectomy because they might desire future childbearing, or they just might want to retain their uterus.

In addition, we also know that fibroids typically regress in menopause. Using the Mirena IUD is a great solution to control heavy bleeding that a woman can use until they're in menopause and no longer having periods. The Mirena IUD is much less invasive than a hysterectomy and has lower risk for complications.

What steps do you take to identify encounters that might impose challenges as it relates to the uterine structure?

Ms. Kennedy: One thing that may impose a challenge in using the Mirena IUD to manage heavy bleeding related to fibroids is the specific size and location of the fibroids. Submucosal fibroids, also called intracavitary fibroids, grow into the uterus. These submucosal fibroids grow just below the inner lining of the uterus. They often cause more bleeding and problems than other types of fibroids because they crowd the uterine space. If the submucosal fibroid is too big or filling up too much of the uterine cavity, there may not be enough room for us to place a Mirena IUD.

The rates of IUD expulsion are increased in patients with fibroids that distort the uterine cavity. That's one thing we definitely want to consider. I typically refer these patients to one of my GYN surgeon colleagues to determine if the submucosal fibroid should be removed hysteroscopically in the OR. Sometimes after removing these submucosal fibroids via hysteroscopy in the OR, the surgeons will place the Mirena IUD at the end of the case.

I think you touched on this a little bit, but are there methods, in addition to IUDs, that would assist in managing heavy menstrual bleeding associated with uterine fibroids?

Ms. Kennedy: Yes. We have several current methods to manage heavy menstrual bleeding associated with uterine fibroids. One method is simply expectant management or watchful waiting. This means that the amount of bleeding or pain a woman is having related to fibroids is neither severe nor debilitating for her, but we continue to monitor them closely. We usually review what criteria the patient should look out for that may indicate she needs to follow up on, for us to take a closer look at her fibroids. Typically, that would be worsening bleeding or worsening pain.

Some oral medication options are hormonal methods which can include combined oral birth control pills, oral progesterone pills, and sometimes we use injections such as Depo-Provera, which is typically used for birth control. Oral contraceptives can reduce bleeding associated with fibroids by about 40% to 50%.

We also have non-hormonal medications like tranexamic acid, or Lysteda, which is an antifibrinolytic agent that women take only during their monthly periods for up to five days. Women who have a history of clots cannot take this drug. However, for women who can safely use this medication, on average, Lysteda has been shown to reduce the amount of blood loss during monthly periods by about 40%. There are other medication options, including GnRH antagonists that I don't prescribe as often.

The Mirena IUD, as we've discussed, is also such a great option to reduce heavy menstrual bleeding in women which can reduce menstrual bleeding by 86% to 97%. That’s a big jump. For patients that might need procedural interventions or surgical approaches, that may be most appropriate if they are having bulk symptoms associated with their fibroids like pelvic pain, pelvic pressure, urinary, or frequency. These kinds of symptoms are caused by the sheer size of the fibroids or from the fibroids pressing on surrounding structures. Bulk symptoms often do not improve much with medications or the IUDs. Those options address bleeding associated with fibroids much better.

How likely are women to stay on these medications that have contraceptive benefits based on the impact it may have in relation to uterine fibroids?

Ms. Kennedy: In one study that examined the effectiveness of the Mirena IUD versus other medications, including oral progesterone therapy to manage heavy bleeding, 76% of women using the Mirena IUD wished to continue the treatment compared to 22% of women that wished to continue the oral progestin therapy.

In another prospective observational clinical study, 82.5% of women had improvement of heavy menstrual bleeding with the Mirena. They continued to use the Mirena after 12 months. The Mirena IUD is effective in controlling heavy menstrual bleeding related to fibroids in about 77% of cases. The most common side effect is menstrual spotting for a few months after insertion. But overall, we do see a pretty high user satisfaction rate.

Kelsey Kennedy is a Family Nurse Practitioner (FNP) and has been working as a nurse practitioner in the Women's Health Institute at the Cleveland Clinic in General Gynecology for the past three years. She has her undergraduate degree from Saint Louis University and completed her graduate studies at Walsh University. She works with patients providing annual/wellness care, contraceptive counseling, abnormal bleeding evaluation and addresses many other non-OB gynecologic issues. The best part about her job is connecting with women and empowering the women she serves to be in control of their reproductive health and wellness.

As a nurse practitioner focused on benign gynecological treatment, what is your role as it relates to uterine fibroids, which are benign non-cancerous tumors?

Ms. Kennedy: As Nurse Practitioner (NP) working in GYN, I see both common and complex gynecologic, sexual, reproductive, menopausal issues. We really do it all. The NP collaborates with the entire medical health care team, including physicians, medical assistants, nursing, and administrators.

In the outpatient office practice with the Cleveland Clinic, I provide mostly benign or general GYN care, which means I see a lot of annual wellness exams, infection checks, birth control consults, and abnormal bleeding. I see patients that may have complaints of heavy periods, pelvic pain, pressure, but they might not have a formal diagnosis or know exactly why they have such heavy periods. Sometimes I see patients that have never even heard of fibroids. It’s my job to take a thorough history, perform a physical exam, and order any additional testing indicated to get the workup started to figure out exactly what's going on.

Abnormal uterine bleeding is defined as a change in the frequency, duration, or amount of menstrual bleeding. It's a common GYN complaint that affects anywhere from 10% to 30% of reproductive age women. In fact, abnormal bleeding is the reason for 1/3 of all outpatient GYN visits and a common cause of abnormal uterine bleeding is fibroids.

So just to review, fibroids are those benign, meaning non-cancerous, tumors made of smooth muscle tissue. Fibroids affect up to 40% of women of reproductive age. And by age 50, up to 70% of women have at least one fibroid. Fibroids are very common. It is important to know that only about 25% of fibroids are clinically significant or problematic enough to require intervention. With that being said, we know that fibroids can be asymptomatic, but often, they can cause pain and bleeding.

Some situations that occur that might make me suspect fibroids include a history of periods that are regular, once monthly, but progressively becoming heavier and heavier over time; periods that last longer than seven days; menstrual bleeding so heavy patients soak through overnight pads or their clothes during the day or overnight; menstrual bleeding with large clots; pelvic pain; pressure; urinary frequency, which could be related to fibroids pressing on the bladder; or constipation, which we know has many causes but can sometimes be related to fibroids pressing on the rectum. That’s it.

What impact does Long-Acting Reversible Contraception, or LARC, have on the uterus?

Ms. Kennedy: Generally speaking, Long-Acting Reversible Contraception, or LARC, is a broad category of birth control methods that provide contraception for an extended period of time-- anywhere from 3 to 10 years, depending on the type you choose. The best part about LARC options is they do not require user action. It's 99% effective in preventing unwanted pregnancy. I like to call it set-it-and-forget-it birth control.

The LARC options we have included are all the IUDs, which consists of the Paragard or copper IUD, and the three different hormonal IUDs-- the Mirena, Kyleena, and the Skyla. That also includes the Nexplanon arm implant. Out of all these LARC options, the Mirena IUD is the only one that’s FDA approved to treat heavy menstrual bleeding which can include heavy menstrual bleeding related to fibroids. The Mirena is FDA approved right now for seven years of use, which is a nice long time to get a lot of good benefit.

The Mirena IUD, specifically, is a T-shaped device that's placed in the uterus. It releases a steady local, meaning the hormone is released pretty much just in the uterus, amount of levonorgestrel, which is a second-generation synthetic progesterone. Basically, it's a hormone. The Mirena releases 20 micrograms of levonorgestrel into the uterus every day. What this hormone does is cause a dramatic reduction of blood flow by changing the endometrium, or the lining of the uterus.

The Mirena IUD was found to reduce blood loss by 86% after three months of use and by up to 97% after 12 months of use. This big reduction in bleeding subsequently leads to an increase in iron and hemoglobin levels in women with heavy bleeding and fibroids.

Hysterectomy has long been the definitive solution for abnormal bleeding that doesn't respond to our usual treatments. But since the Mirena was developed in the 1990s, more and more evidence has come to light that the Mirena can be a safe and effective medical alternative to hysterectomy. Many women benefit from and seek other management options for bleeding and heavy bleeding relating to fibroids other than hysterectomy because they might desire future childbearing, or they just might want to retain their uterus.

In addition, we also know that fibroids typically regress in menopause. Using the Mirena IUD is a great solution to control heavy bleeding that a woman can use until they're in menopause and no longer having periods. The Mirena IUD is much less invasive than a hysterectomy and has lower risk for complications.

What steps do you take to identify encounters that might impose challenges as it relates to the uterine structure?

Ms. Kennedy: One thing that may impose a challenge in using the Mirena IUD to manage heavy bleeding related to fibroids is the specific size and location of the fibroids. Submucosal fibroids, also called intracavitary fibroids, grow into the uterus. These submucosal fibroids grow just below the inner lining of the uterus. They often cause more bleeding and problems than other types of fibroids because they crowd the uterine space. If the submucosal fibroid is too big or filling up too much of the uterine cavity, there may not be enough room for us to place a Mirena IUD.

The rates of IUD expulsion are increased in patients with fibroids that distort the uterine cavity. That's one thing we definitely want to consider. I typically refer these patients to one of my GYN surgeon colleagues to determine if the submucosal fibroid should be removed hysteroscopically in the OR. Sometimes after removing these submucosal fibroids via hysteroscopy in the OR, the surgeons will place the Mirena IUD at the end of the case.

I think you touched on this a little bit, but are there methods, in addition to IUDs, that would assist in managing heavy menstrual bleeding associated with uterine fibroids?

Ms. Kennedy: Yes. We have several current methods to manage heavy menstrual bleeding associated with uterine fibroids. One method is simply expectant management or watchful waiting. This means that the amount of bleeding or pain a woman is having related to fibroids is neither severe nor debilitating for her, but we continue to monitor them closely. We usually review what criteria the patient should look out for that may indicate she needs to follow up on, for us to take a closer look at her fibroids. Typically, that would be worsening bleeding or worsening pain.

Some oral medication options are hormonal methods which can include combined oral birth control pills, oral progesterone pills, and sometimes we use injections such as Depo-Provera, which is typically used for birth control. Oral contraceptives can reduce bleeding associated with fibroids by about 40% to 50%.

We also have non-hormonal medications like tranexamic acid, or Lysteda, which is an antifibrinolytic agent that women take only during their monthly periods for up to five days. Women who have a history of clots cannot take this drug. However, for women who can safely use this medication, on average, Lysteda has been shown to reduce the amount of blood loss during monthly periods by about 40%. There are other medication options, including GnRH antagonists that I don't prescribe as often.

The Mirena IUD, as we've discussed, is also such a great option to reduce heavy menstrual bleeding in women which can reduce menstrual bleeding by 86% to 97%. That’s a big jump. For patients that might need procedural interventions or surgical approaches, that may be most appropriate if they are having bulk symptoms associated with their fibroids like pelvic pain, pelvic pressure, urinary, or frequency. These kinds of symptoms are caused by the sheer size of the fibroids or from the fibroids pressing on surrounding structures. Bulk symptoms often do not improve much with medications or the IUDs. Those options address bleeding associated with fibroids much better.

How likely are women to stay on these medications that have contraceptive benefits based on the impact it may have in relation to uterine fibroids?

Ms. Kennedy: In one study that examined the effectiveness of the Mirena IUD versus other medications, including oral progesterone therapy to manage heavy bleeding, 76% of women using the Mirena IUD wished to continue the treatment compared to 22% of women that wished to continue the oral progestin therapy.

In another prospective observational clinical study, 82.5% of women had improvement of heavy menstrual bleeding with the Mirena. They continued to use the Mirena after 12 months. The Mirena IUD is effective in controlling heavy menstrual bleeding related to fibroids in about 77% of cases. The most common side effect is menstrual spotting for a few months after insertion. But overall, we do see a pretty high user satisfaction rate.