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Searching for the Optimal CRC Surveillance Test
About a third of the US population are eligible for colorectal cancer screening but aren’t up to date on screening.
Many patients are reluctant to test for colon cancer for a variety of reasons, said Jeffrey K. Lee, MD, MPH, a research scientist at the Kaiser Permanente Northern California Division of Research and an attending gastroenterologist at Kaiser Permanente San Francisco Medical Center.
“As a gastroenterologist, I strongly believe we should emphasize the importance of colorectal cancer screening. And there’s many tests available, not just a colonoscopy, to help reduce your chances of developing colorectal cancer and even dying from colorectal cancer,” said Dr. Lee.
Many patients prefer a test that’s more convenient, that doesn’t require them to take time out of their busy schedules. “We must educate our patients that there are some noninvasive screening options that are helpful, and to be able to share with them some of the benefits, but also some of the drawbacks compared to colonoscopy and allow them to have a choice,” he advised.
He is a recipient of the AGA Research Scholar Award, and has in turn supported other researchers by contributing to the AGA Research Foundation. In 2012, Dr. Lee received a grant from the Sylvia Allison Kaplan Clinical Research Fund to fund a study on long-term colorectal cancer risk in patients with normal colonoscopy results.
The findings, published in JAMA Internal Medicine, determined that 10 years after a negative colonoscopy, Kaiser Permanente members had a 46% lower risk of being diagnosed with CRC and were 88% less likely to die from disease compared with patients who didn’t undergo screening.
“Furthermore, the reduced risk of developing colorectal cancer, even dying from it, persisted for more than 12 years after the examination compared with an unscreened population,” said Dr. Lee. “I firmly believe our study really supports the ten-year screening interval after a normal colonoscopy, as currently recommended by our guidelines.”
In an interview, he discussed his research efforts to find the best detection regimens for CRC, and the mentors who guided his career path as a GI scientist.
Q: Why did you choose GI?
During medical school I was fortunate to work in the lab of Dr. John M. Carethers at UC San Diego. He introduced me to GI and inspired me to choose GI as a career. His mentorship was invaluable because he not only solidified my interest in GI, but also inspired me to become a physician scientist, focusing on colorectal cancer prevention and control. His amazing mentorship drew me to this field.
Q: One of your clinical focus areas is hereditary gastrointestinal cancer syndromes. How did you become interested in this area of GI medicine?
My interest in hereditary GI cancer syndromes stemmed from my work as a medical student in Dr. Carethers’ lab. One of my research projects was looking at certain gene mutations among patients with hereditary GI cancer syndromes, specifically, familial hamartomatous polyposis syndrome. It was through these research projects and seeing how these genetic mutations impacted their risk of developing colorectal cancer, inspired me to care for patients with hereditary GI cancer syndromes.
Q: Have you been doing any research on the reasons why more young people are getting colon cancer?
We recently published work looking at the potential factors that may be driving the rising rates of early onset colorectal cancer. One hypothesis that’s been floating around is antibiotic exposure in early adulthood or childhood because of its effect on the microbiome. Using our large database at Kaiser Permanente Northern California, we did not find an association between oral antibiotic use during early adulthood and the risk of early-onset colorectal cancer.
You have the usual suspects like obesity and diabetes, but it’s not explaining all that risk. While familial colorectal cancer syndromes contribute to a small proportion of early-onset colorectal, these syndromes are not increasing across generations. I really do feel it’s something in the diet or how foods are processed and environmental factors that’s driving some of the risk of early onset colorectal cancer and this should be explored further.
Q: In 2018, you issued a landmark study which found an association between a 10-year follow-up after negative colonoscopy and reduced risk of disease and mortality. Has there been any updates to these findings over the last 6 years?
We recently saw a study in JAMA Oncology of a Swedish cohort that showed a negative colonoscopy result was associated with a reduced risk of developing and even dying from colorectal cancer 15 years from that examination, compared to the general population of Sweden. I think there’s some things that we need to be cautious about regarding that study. We have to think about the comparison group that they used and the lack of information regarding the indication of the colonoscopy and the quality of the examination. So, it remains uncertain whether future guidelines are going to stretch out that 10-year interval to 15 years.
Q: What other CRC studies are you working on now?
We have several studies that we are working on right now. One is called the PREVENT CRC study, which is looking at whether a polygenic risk score can improve risk stratification following adenoma removal for colorectal cancer prevention and tailoring post-polypectomy surveillance. This is a large observational cohort study that we have teamed up with the Fred Hutchinson Cancer Center, Erasmus University, and Kaiser Permanente Northwest to answer this important question that may have implications for personalized medicine.
Then there’s the COOP study, funded by the Patient-Centered Outcomes Research Institute. This is looking at the best surveillance test to use among older adults 65 years and older with a history of polyps. The trial is randomizing them to either getting a colonoscopy for surveillance or annual fecal immunochemical test (FIT) for surveillance. This is to see which test is best for detecting colorectal cancer among older adults with a history of polyps.
Q: Do you think FIT tests could eventually replace colonoscopy, given that it’s less invasive?
Although FIT and other stool-based tests are less invasive and have been shown to have high accuracy for detecting colorectal cancer, I personally do not think they are going to replace colonoscopy as the most popular screening modality in the United States. Colonoscopy remains the gold standard for detecting and removing precancerous polyps and has the highest accuracy for detecting colorectal cancer.
Q: Besides Dr. Carethers, what teacher or mentor had the greatest impact on you?
Clinically it’s been Dr. Jonathan Terdiman from UCSF, who taught me everything I know about clinical GI, and the art of colonoscopy. In addition, Douglas A. Corley, MD, PhD, the Permanente Medical Group’s chief research officer, has made the greatest impact on my research career. He’s really taught me how to rigorously design a research study to answer important clinically relevant questions, and has given me the skill set to write NIH grants. I would not be here without these mentors who are truly giants in the field of GI.
Q: When you’re not being a GI, how do you spend your free weekend afternoons? Are you still a “Cal Bears” fan at your alma mater, UC Berkeley?
I spend a lot of time taking my kids to their activities on the weekends. I just took my son to a Cal Bears Game Day, which was hosted by ESPN at Berkeley.
It was an incredible experience hearing sports analyst Pat McAfee lead all the Cal chants, seeing Nick Saban from the University of Alabama take off his red tie and replace it with a Cal Bears tie, and watching a Cal student win a hundred thousand dollars by kicking a football through the goal posts wearing checkered vans.
Lightning Round
Texting or talking?
Text
Favorite breakfast?
Taiwanese breakfast
Place you most want to travel to?
Japan
Favorite junk food?
Trader Joe’s chili lime chips
Favorite season?
Springtime, baseball season
Favorite ice cream flavor?
Mint chocolate chip
How many cups of coffee do you drink per day?
2-3
Last movie you watched?
Oppenheimer
Best place you ever went on vacation?
Hawaii
If you weren’t a gastroenterologist, what would you be?
Barber
Best Halloween costume you ever wore?
SpongeBob SquarePants
Favorite sport?
Tennis
What song do you have to sing along with when you hear it?
Any classic 80s song
Introvert or extrovert?
Introvert
About a third of the US population are eligible for colorectal cancer screening but aren’t up to date on screening.
Many patients are reluctant to test for colon cancer for a variety of reasons, said Jeffrey K. Lee, MD, MPH, a research scientist at the Kaiser Permanente Northern California Division of Research and an attending gastroenterologist at Kaiser Permanente San Francisco Medical Center.
“As a gastroenterologist, I strongly believe we should emphasize the importance of colorectal cancer screening. And there’s many tests available, not just a colonoscopy, to help reduce your chances of developing colorectal cancer and even dying from colorectal cancer,” said Dr. Lee.
Many patients prefer a test that’s more convenient, that doesn’t require them to take time out of their busy schedules. “We must educate our patients that there are some noninvasive screening options that are helpful, and to be able to share with them some of the benefits, but also some of the drawbacks compared to colonoscopy and allow them to have a choice,” he advised.
He is a recipient of the AGA Research Scholar Award, and has in turn supported other researchers by contributing to the AGA Research Foundation. In 2012, Dr. Lee received a grant from the Sylvia Allison Kaplan Clinical Research Fund to fund a study on long-term colorectal cancer risk in patients with normal colonoscopy results.
The findings, published in JAMA Internal Medicine, determined that 10 years after a negative colonoscopy, Kaiser Permanente members had a 46% lower risk of being diagnosed with CRC and were 88% less likely to die from disease compared with patients who didn’t undergo screening.
“Furthermore, the reduced risk of developing colorectal cancer, even dying from it, persisted for more than 12 years after the examination compared with an unscreened population,” said Dr. Lee. “I firmly believe our study really supports the ten-year screening interval after a normal colonoscopy, as currently recommended by our guidelines.”
In an interview, he discussed his research efforts to find the best detection regimens for CRC, and the mentors who guided his career path as a GI scientist.
Q: Why did you choose GI?
During medical school I was fortunate to work in the lab of Dr. John M. Carethers at UC San Diego. He introduced me to GI and inspired me to choose GI as a career. His mentorship was invaluable because he not only solidified my interest in GI, but also inspired me to become a physician scientist, focusing on colorectal cancer prevention and control. His amazing mentorship drew me to this field.
Q: One of your clinical focus areas is hereditary gastrointestinal cancer syndromes. How did you become interested in this area of GI medicine?
My interest in hereditary GI cancer syndromes stemmed from my work as a medical student in Dr. Carethers’ lab. One of my research projects was looking at certain gene mutations among patients with hereditary GI cancer syndromes, specifically, familial hamartomatous polyposis syndrome. It was through these research projects and seeing how these genetic mutations impacted their risk of developing colorectal cancer, inspired me to care for patients with hereditary GI cancer syndromes.
Q: Have you been doing any research on the reasons why more young people are getting colon cancer?
We recently published work looking at the potential factors that may be driving the rising rates of early onset colorectal cancer. One hypothesis that’s been floating around is antibiotic exposure in early adulthood or childhood because of its effect on the microbiome. Using our large database at Kaiser Permanente Northern California, we did not find an association between oral antibiotic use during early adulthood and the risk of early-onset colorectal cancer.
You have the usual suspects like obesity and diabetes, but it’s not explaining all that risk. While familial colorectal cancer syndromes contribute to a small proportion of early-onset colorectal, these syndromes are not increasing across generations. I really do feel it’s something in the diet or how foods are processed and environmental factors that’s driving some of the risk of early onset colorectal cancer and this should be explored further.
Q: In 2018, you issued a landmark study which found an association between a 10-year follow-up after negative colonoscopy and reduced risk of disease and mortality. Has there been any updates to these findings over the last 6 years?
We recently saw a study in JAMA Oncology of a Swedish cohort that showed a negative colonoscopy result was associated with a reduced risk of developing and even dying from colorectal cancer 15 years from that examination, compared to the general population of Sweden. I think there’s some things that we need to be cautious about regarding that study. We have to think about the comparison group that they used and the lack of information regarding the indication of the colonoscopy and the quality of the examination. So, it remains uncertain whether future guidelines are going to stretch out that 10-year interval to 15 years.
Q: What other CRC studies are you working on now?
We have several studies that we are working on right now. One is called the PREVENT CRC study, which is looking at whether a polygenic risk score can improve risk stratification following adenoma removal for colorectal cancer prevention and tailoring post-polypectomy surveillance. This is a large observational cohort study that we have teamed up with the Fred Hutchinson Cancer Center, Erasmus University, and Kaiser Permanente Northwest to answer this important question that may have implications for personalized medicine.
Then there’s the COOP study, funded by the Patient-Centered Outcomes Research Institute. This is looking at the best surveillance test to use among older adults 65 years and older with a history of polyps. The trial is randomizing them to either getting a colonoscopy for surveillance or annual fecal immunochemical test (FIT) for surveillance. This is to see which test is best for detecting colorectal cancer among older adults with a history of polyps.
Q: Do you think FIT tests could eventually replace colonoscopy, given that it’s less invasive?
Although FIT and other stool-based tests are less invasive and have been shown to have high accuracy for detecting colorectal cancer, I personally do not think they are going to replace colonoscopy as the most popular screening modality in the United States. Colonoscopy remains the gold standard for detecting and removing precancerous polyps and has the highest accuracy for detecting colorectal cancer.
Q: Besides Dr. Carethers, what teacher or mentor had the greatest impact on you?
Clinically it’s been Dr. Jonathan Terdiman from UCSF, who taught me everything I know about clinical GI, and the art of colonoscopy. In addition, Douglas A. Corley, MD, PhD, the Permanente Medical Group’s chief research officer, has made the greatest impact on my research career. He’s really taught me how to rigorously design a research study to answer important clinically relevant questions, and has given me the skill set to write NIH grants. I would not be here without these mentors who are truly giants in the field of GI.
Q: When you’re not being a GI, how do you spend your free weekend afternoons? Are you still a “Cal Bears” fan at your alma mater, UC Berkeley?
I spend a lot of time taking my kids to their activities on the weekends. I just took my son to a Cal Bears Game Day, which was hosted by ESPN at Berkeley.
It was an incredible experience hearing sports analyst Pat McAfee lead all the Cal chants, seeing Nick Saban from the University of Alabama take off his red tie and replace it with a Cal Bears tie, and watching a Cal student win a hundred thousand dollars by kicking a football through the goal posts wearing checkered vans.
Lightning Round
Texting or talking?
Text
Favorite breakfast?
Taiwanese breakfast
Place you most want to travel to?
Japan
Favorite junk food?
Trader Joe’s chili lime chips
Favorite season?
Springtime, baseball season
Favorite ice cream flavor?
Mint chocolate chip
How many cups of coffee do you drink per day?
2-3
Last movie you watched?
Oppenheimer
Best place you ever went on vacation?
Hawaii
If you weren’t a gastroenterologist, what would you be?
Barber
Best Halloween costume you ever wore?
SpongeBob SquarePants
Favorite sport?
Tennis
What song do you have to sing along with when you hear it?
Any classic 80s song
Introvert or extrovert?
Introvert
About a third of the US population are eligible for colorectal cancer screening but aren’t up to date on screening.
Many patients are reluctant to test for colon cancer for a variety of reasons, said Jeffrey K. Lee, MD, MPH, a research scientist at the Kaiser Permanente Northern California Division of Research and an attending gastroenterologist at Kaiser Permanente San Francisco Medical Center.
“As a gastroenterologist, I strongly believe we should emphasize the importance of colorectal cancer screening. And there’s many tests available, not just a colonoscopy, to help reduce your chances of developing colorectal cancer and even dying from colorectal cancer,” said Dr. Lee.
Many patients prefer a test that’s more convenient, that doesn’t require them to take time out of their busy schedules. “We must educate our patients that there are some noninvasive screening options that are helpful, and to be able to share with them some of the benefits, but also some of the drawbacks compared to colonoscopy and allow them to have a choice,” he advised.
He is a recipient of the AGA Research Scholar Award, and has in turn supported other researchers by contributing to the AGA Research Foundation. In 2012, Dr. Lee received a grant from the Sylvia Allison Kaplan Clinical Research Fund to fund a study on long-term colorectal cancer risk in patients with normal colonoscopy results.
The findings, published in JAMA Internal Medicine, determined that 10 years after a negative colonoscopy, Kaiser Permanente members had a 46% lower risk of being diagnosed with CRC and were 88% less likely to die from disease compared with patients who didn’t undergo screening.
“Furthermore, the reduced risk of developing colorectal cancer, even dying from it, persisted for more than 12 years after the examination compared with an unscreened population,” said Dr. Lee. “I firmly believe our study really supports the ten-year screening interval after a normal colonoscopy, as currently recommended by our guidelines.”
In an interview, he discussed his research efforts to find the best detection regimens for CRC, and the mentors who guided his career path as a GI scientist.
Q: Why did you choose GI?
During medical school I was fortunate to work in the lab of Dr. John M. Carethers at UC San Diego. He introduced me to GI and inspired me to choose GI as a career. His mentorship was invaluable because he not only solidified my interest in GI, but also inspired me to become a physician scientist, focusing on colorectal cancer prevention and control. His amazing mentorship drew me to this field.
Q: One of your clinical focus areas is hereditary gastrointestinal cancer syndromes. How did you become interested in this area of GI medicine?
My interest in hereditary GI cancer syndromes stemmed from my work as a medical student in Dr. Carethers’ lab. One of my research projects was looking at certain gene mutations among patients with hereditary GI cancer syndromes, specifically, familial hamartomatous polyposis syndrome. It was through these research projects and seeing how these genetic mutations impacted their risk of developing colorectal cancer, inspired me to care for patients with hereditary GI cancer syndromes.
Q: Have you been doing any research on the reasons why more young people are getting colon cancer?
We recently published work looking at the potential factors that may be driving the rising rates of early onset colorectal cancer. One hypothesis that’s been floating around is antibiotic exposure in early adulthood or childhood because of its effect on the microbiome. Using our large database at Kaiser Permanente Northern California, we did not find an association between oral antibiotic use during early adulthood and the risk of early-onset colorectal cancer.
You have the usual suspects like obesity and diabetes, but it’s not explaining all that risk. While familial colorectal cancer syndromes contribute to a small proportion of early-onset colorectal, these syndromes are not increasing across generations. I really do feel it’s something in the diet or how foods are processed and environmental factors that’s driving some of the risk of early onset colorectal cancer and this should be explored further.
Q: In 2018, you issued a landmark study which found an association between a 10-year follow-up after negative colonoscopy and reduced risk of disease and mortality. Has there been any updates to these findings over the last 6 years?
We recently saw a study in JAMA Oncology of a Swedish cohort that showed a negative colonoscopy result was associated with a reduced risk of developing and even dying from colorectal cancer 15 years from that examination, compared to the general population of Sweden. I think there’s some things that we need to be cautious about regarding that study. We have to think about the comparison group that they used and the lack of information regarding the indication of the colonoscopy and the quality of the examination. So, it remains uncertain whether future guidelines are going to stretch out that 10-year interval to 15 years.
Q: What other CRC studies are you working on now?
We have several studies that we are working on right now. One is called the PREVENT CRC study, which is looking at whether a polygenic risk score can improve risk stratification following adenoma removal for colorectal cancer prevention and tailoring post-polypectomy surveillance. This is a large observational cohort study that we have teamed up with the Fred Hutchinson Cancer Center, Erasmus University, and Kaiser Permanente Northwest to answer this important question that may have implications for personalized medicine.
Then there’s the COOP study, funded by the Patient-Centered Outcomes Research Institute. This is looking at the best surveillance test to use among older adults 65 years and older with a history of polyps. The trial is randomizing them to either getting a colonoscopy for surveillance or annual fecal immunochemical test (FIT) for surveillance. This is to see which test is best for detecting colorectal cancer among older adults with a history of polyps.
Q: Do you think FIT tests could eventually replace colonoscopy, given that it’s less invasive?
Although FIT and other stool-based tests are less invasive and have been shown to have high accuracy for detecting colorectal cancer, I personally do not think they are going to replace colonoscopy as the most popular screening modality in the United States. Colonoscopy remains the gold standard for detecting and removing precancerous polyps and has the highest accuracy for detecting colorectal cancer.
Q: Besides Dr. Carethers, what teacher or mentor had the greatest impact on you?
Clinically it’s been Dr. Jonathan Terdiman from UCSF, who taught me everything I know about clinical GI, and the art of colonoscopy. In addition, Douglas A. Corley, MD, PhD, the Permanente Medical Group’s chief research officer, has made the greatest impact on my research career. He’s really taught me how to rigorously design a research study to answer important clinically relevant questions, and has given me the skill set to write NIH grants. I would not be here without these mentors who are truly giants in the field of GI.
Q: When you’re not being a GI, how do you spend your free weekend afternoons? Are you still a “Cal Bears” fan at your alma mater, UC Berkeley?
I spend a lot of time taking my kids to their activities on the weekends. I just took my son to a Cal Bears Game Day, which was hosted by ESPN at Berkeley.
It was an incredible experience hearing sports analyst Pat McAfee lead all the Cal chants, seeing Nick Saban from the University of Alabama take off his red tie and replace it with a Cal Bears tie, and watching a Cal student win a hundred thousand dollars by kicking a football through the goal posts wearing checkered vans.
Lightning Round
Texting or talking?
Text
Favorite breakfast?
Taiwanese breakfast
Place you most want to travel to?
Japan
Favorite junk food?
Trader Joe’s chili lime chips
Favorite season?
Springtime, baseball season
Favorite ice cream flavor?
Mint chocolate chip
How many cups of coffee do you drink per day?
2-3
Last movie you watched?
Oppenheimer
Best place you ever went on vacation?
Hawaii
If you weren’t a gastroenterologist, what would you be?
Barber
Best Halloween costume you ever wore?
SpongeBob SquarePants
Favorite sport?
Tennis
What song do you have to sing along with when you hear it?
Any classic 80s song
Introvert or extrovert?
Introvert
Giving the Smallest GI Transplant Patients a New Lease On Life
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
In a Parallel Universe, “I’d Be a Concert Pianist” Says Tennessee GI
She also relishes opportunities to think, to analyze, and solve problems for her patients.
One of her chief interests is inflammatory bowel disease (IBD). It’s reassuring to focus on a field of work “where I know exactly what’s causing the issue, and I can select a therapeutic approach (medication and lifestyle changes) that help a patient achieve remission,” said Dr. Pointer, co-owner and managing partner of Digestive and Liver Health Specialists in Hendersonville, Tenn. She’s also the medical director and a principal investigator of Quality Medical Research in Nashville, and currently serves as chair of the AGA Trainee and Early Career Committee.
Starting her own practice has been just as challenging and rewarding as going through medical school. Medical training does not prepare you for starting your own practice, Dr. Pointer said, so she and her business partner have had to learn as they go. “But I think we’ve done very well. We’ve taken the ups and downs in stride.”
In an interview, Dr. Pointer spoke more about her work in IBD and the ways in which she’s given back to the community through music and mentoring.
Q: Why did you choose GI?
I knew from a very young age that I was going to be a physician. I had always been interested in science. When I got into medical school and became exposed to the different areas, I really liked the cognitive skills where you had to think through a problem or an issue. But I also liked the procedural things as well.
During my internal medicine residency training, I felt that I had a knack for it. As I was looking at different options, I decided on gastroenterology because it combined both cognitive thinking through issues, but also taking it to the next step and intervening through procedures.
Q: During fellowship, your focus was inflammatory bowel disease. What drew your interest to this condition?
There are a lot of different areas within gastroenterology that one can subspecialize in, as we see the full gamut of gastrointestinal and hepatic disorders. But treating some conditions, like functional disorders, means taking more of a ‘trial and error’ approach, and you may not always get the patient a hundred percent better. That’s not to say that we can’t improve a patient’s quality of life, but it’s not always a guarantee.
But inflammatory bowel disease is a little bit different. Because I can point to an exact spot in the intestines that’s causing the problem, it’s very fulfilling for me as a physician to take a patient who is having 10-12 bloody bowel movements a day, to normal form stools and no abdominal pain. They’re able to gain weight and go on about their lives and about their day. So that was why I picked inflammatory bowel disease as my subspecialty.
Q: Tell me about the gastroenterology elective you developed for family medicine residents and undergraduate students. What’s the status of the program now?
I’ve always been interested in teaching and giving back to the next generations. I feel like I had great mentor opportunities and people who helped me along the way. In my previous hospital position, I was able to work with the family medicine department and create an elective through which residents and even undergraduate students could come and shadow and work with me in the clinic and see me performing procedures.
That elective ended once I left that position, at least as far as I’m aware. But in the private practice that I co-own now, we have numerous shadowing opportunities. I was able to give a lecture at Middle Tennessee State University for some students. And through that lecture, many students have reached out to me to shadow. I have allowed them to come shadow and do clinic work as a medical assistant and watch me perform procedures. I have multiple students working with me weekly.
Q: Years ago, you founded the non-profit Enchanted Fingers Piano Lessons, which gave free piano lessons to underserved youth. What was that experience like?
Piano was one of my first loves. In some parallel universe, there’s a Dr. Pointer who is a classical, concert pianist. I started taking piano lessons when I was in early middle school, and I took to it very quickly. I was able to excel. I just loved it. I enjoyed practicing and I still play.
The impetus for starting Enchanted Fingers Piano lessons was because I wanted to give back again to the community. I came from an underserved community. Oftentimes children and young adults in those communities don’t get exposed to extracurricular activities and they don’t even know what they could potentially have a passion for. And I definitely had a passion for piano. I partnered with a church organization and they allowed me to use their church to host these piano lessons, and it was a phenomenal and rewarding experience. I would definitely like to start it up again one day in the future. It was an amazing experience.
It’s actually how I met my husband. He was one of the young adult students who signed up to take lessons. We both still enjoy playing the piano together.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
I’m a creative at heart. I really enjoy sewing and I’m working on a few sewing projects. I just got a serger. It is a machine that helps you finish a seam. It can also be used to sew entire garments. That has been fun, learning how to thread that machine. When I’m not doing that or just relaxing with my family, I do enjoy curling up with a good book. Stephen King is one of my favorite authors.
Lightning Round
Texting or talking?
Talking
Favorite junk food?
Chocolate chip cookies
Cat or dog person?
Cat
Favorite vacation?
Hawaii
How many cups of coffee do you drink per day?
I don’t drink coffee
Favorite ice cream?
Butter pecan
Favorite sport?
I don’t watch sports
Optimist or pessimist?
Optimist
She also relishes opportunities to think, to analyze, and solve problems for her patients.
One of her chief interests is inflammatory bowel disease (IBD). It’s reassuring to focus on a field of work “where I know exactly what’s causing the issue, and I can select a therapeutic approach (medication and lifestyle changes) that help a patient achieve remission,” said Dr. Pointer, co-owner and managing partner of Digestive and Liver Health Specialists in Hendersonville, Tenn. She’s also the medical director and a principal investigator of Quality Medical Research in Nashville, and currently serves as chair of the AGA Trainee and Early Career Committee.
Starting her own practice has been just as challenging and rewarding as going through medical school. Medical training does not prepare you for starting your own practice, Dr. Pointer said, so she and her business partner have had to learn as they go. “But I think we’ve done very well. We’ve taken the ups and downs in stride.”
In an interview, Dr. Pointer spoke more about her work in IBD and the ways in which she’s given back to the community through music and mentoring.
Q: Why did you choose GI?
I knew from a very young age that I was going to be a physician. I had always been interested in science. When I got into medical school and became exposed to the different areas, I really liked the cognitive skills where you had to think through a problem or an issue. But I also liked the procedural things as well.
During my internal medicine residency training, I felt that I had a knack for it. As I was looking at different options, I decided on gastroenterology because it combined both cognitive thinking through issues, but also taking it to the next step and intervening through procedures.
Q: During fellowship, your focus was inflammatory bowel disease. What drew your interest to this condition?
There are a lot of different areas within gastroenterology that one can subspecialize in, as we see the full gamut of gastrointestinal and hepatic disorders. But treating some conditions, like functional disorders, means taking more of a ‘trial and error’ approach, and you may not always get the patient a hundred percent better. That’s not to say that we can’t improve a patient’s quality of life, but it’s not always a guarantee.
But inflammatory bowel disease is a little bit different. Because I can point to an exact spot in the intestines that’s causing the problem, it’s very fulfilling for me as a physician to take a patient who is having 10-12 bloody bowel movements a day, to normal form stools and no abdominal pain. They’re able to gain weight and go on about their lives and about their day. So that was why I picked inflammatory bowel disease as my subspecialty.
Q: Tell me about the gastroenterology elective you developed for family medicine residents and undergraduate students. What’s the status of the program now?
I’ve always been interested in teaching and giving back to the next generations. I feel like I had great mentor opportunities and people who helped me along the way. In my previous hospital position, I was able to work with the family medicine department and create an elective through which residents and even undergraduate students could come and shadow and work with me in the clinic and see me performing procedures.
That elective ended once I left that position, at least as far as I’m aware. But in the private practice that I co-own now, we have numerous shadowing opportunities. I was able to give a lecture at Middle Tennessee State University for some students. And through that lecture, many students have reached out to me to shadow. I have allowed them to come shadow and do clinic work as a medical assistant and watch me perform procedures. I have multiple students working with me weekly.
Q: Years ago, you founded the non-profit Enchanted Fingers Piano Lessons, which gave free piano lessons to underserved youth. What was that experience like?
Piano was one of my first loves. In some parallel universe, there’s a Dr. Pointer who is a classical, concert pianist. I started taking piano lessons when I was in early middle school, and I took to it very quickly. I was able to excel. I just loved it. I enjoyed practicing and I still play.
The impetus for starting Enchanted Fingers Piano lessons was because I wanted to give back again to the community. I came from an underserved community. Oftentimes children and young adults in those communities don’t get exposed to extracurricular activities and they don’t even know what they could potentially have a passion for. And I definitely had a passion for piano. I partnered with a church organization and they allowed me to use their church to host these piano lessons, and it was a phenomenal and rewarding experience. I would definitely like to start it up again one day in the future. It was an amazing experience.
It’s actually how I met my husband. He was one of the young adult students who signed up to take lessons. We both still enjoy playing the piano together.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
I’m a creative at heart. I really enjoy sewing and I’m working on a few sewing projects. I just got a serger. It is a machine that helps you finish a seam. It can also be used to sew entire garments. That has been fun, learning how to thread that machine. When I’m not doing that or just relaxing with my family, I do enjoy curling up with a good book. Stephen King is one of my favorite authors.
Lightning Round
Texting or talking?
Talking
Favorite junk food?
Chocolate chip cookies
Cat or dog person?
Cat
Favorite vacation?
Hawaii
How many cups of coffee do you drink per day?
I don’t drink coffee
Favorite ice cream?
Butter pecan
Favorite sport?
I don’t watch sports
Optimist or pessimist?
Optimist
She also relishes opportunities to think, to analyze, and solve problems for her patients.
One of her chief interests is inflammatory bowel disease (IBD). It’s reassuring to focus on a field of work “where I know exactly what’s causing the issue, and I can select a therapeutic approach (medication and lifestyle changes) that help a patient achieve remission,” said Dr. Pointer, co-owner and managing partner of Digestive and Liver Health Specialists in Hendersonville, Tenn. She’s also the medical director and a principal investigator of Quality Medical Research in Nashville, and currently serves as chair of the AGA Trainee and Early Career Committee.
Starting her own practice has been just as challenging and rewarding as going through medical school. Medical training does not prepare you for starting your own practice, Dr. Pointer said, so she and her business partner have had to learn as they go. “But I think we’ve done very well. We’ve taken the ups and downs in stride.”
In an interview, Dr. Pointer spoke more about her work in IBD and the ways in which she’s given back to the community through music and mentoring.
Q: Why did you choose GI?
I knew from a very young age that I was going to be a physician. I had always been interested in science. When I got into medical school and became exposed to the different areas, I really liked the cognitive skills where you had to think through a problem or an issue. But I also liked the procedural things as well.
During my internal medicine residency training, I felt that I had a knack for it. As I was looking at different options, I decided on gastroenterology because it combined both cognitive thinking through issues, but also taking it to the next step and intervening through procedures.
Q: During fellowship, your focus was inflammatory bowel disease. What drew your interest to this condition?
There are a lot of different areas within gastroenterology that one can subspecialize in, as we see the full gamut of gastrointestinal and hepatic disorders. But treating some conditions, like functional disorders, means taking more of a ‘trial and error’ approach, and you may not always get the patient a hundred percent better. That’s not to say that we can’t improve a patient’s quality of life, but it’s not always a guarantee.
But inflammatory bowel disease is a little bit different. Because I can point to an exact spot in the intestines that’s causing the problem, it’s very fulfilling for me as a physician to take a patient who is having 10-12 bloody bowel movements a day, to normal form stools and no abdominal pain. They’re able to gain weight and go on about their lives and about their day. So that was why I picked inflammatory bowel disease as my subspecialty.
Q: Tell me about the gastroenterology elective you developed for family medicine residents and undergraduate students. What’s the status of the program now?
I’ve always been interested in teaching and giving back to the next generations. I feel like I had great mentor opportunities and people who helped me along the way. In my previous hospital position, I was able to work with the family medicine department and create an elective through which residents and even undergraduate students could come and shadow and work with me in the clinic and see me performing procedures.
That elective ended once I left that position, at least as far as I’m aware. But in the private practice that I co-own now, we have numerous shadowing opportunities. I was able to give a lecture at Middle Tennessee State University for some students. And through that lecture, many students have reached out to me to shadow. I have allowed them to come shadow and do clinic work as a medical assistant and watch me perform procedures. I have multiple students working with me weekly.
Q: Years ago, you founded the non-profit Enchanted Fingers Piano Lessons, which gave free piano lessons to underserved youth. What was that experience like?
Piano was one of my first loves. In some parallel universe, there’s a Dr. Pointer who is a classical, concert pianist. I started taking piano lessons when I was in early middle school, and I took to it very quickly. I was able to excel. I just loved it. I enjoyed practicing and I still play.
The impetus for starting Enchanted Fingers Piano lessons was because I wanted to give back again to the community. I came from an underserved community. Oftentimes children and young adults in those communities don’t get exposed to extracurricular activities and they don’t even know what they could potentially have a passion for. And I definitely had a passion for piano. I partnered with a church organization and they allowed me to use their church to host these piano lessons, and it was a phenomenal and rewarding experience. I would definitely like to start it up again one day in the future. It was an amazing experience.
It’s actually how I met my husband. He was one of the young adult students who signed up to take lessons. We both still enjoy playing the piano together.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
I’m a creative at heart. I really enjoy sewing and I’m working on a few sewing projects. I just got a serger. It is a machine that helps you finish a seam. It can also be used to sew entire garments. That has been fun, learning how to thread that machine. When I’m not doing that or just relaxing with my family, I do enjoy curling up with a good book. Stephen King is one of my favorite authors.
Lightning Round
Texting or talking?
Talking
Favorite junk food?
Chocolate chip cookies
Cat or dog person?
Cat
Favorite vacation?
Hawaii
How many cups of coffee do you drink per day?
I don’t drink coffee
Favorite ice cream?
Butter pecan
Favorite sport?
I don’t watch sports
Optimist or pessimist?
Optimist
Patient Navigators for Serious Illnesses Can Now Bill Under New Medicare Codes
In a move that acknowledges the gauntlet the US health system poses for people facing serious and fatal illnesses, Medicare will pay for a new class of workers to help patients manage treatments for conditions like cancer and heart failure.
The 2024 Medicare physician fee schedule includes new billing codes, including G0023, to pay for 60 minutes a month of care coordination by certified or trained auxiliary personnel working under the direction of a clinician.
A diagnosis of cancer or another serious illness takes a toll beyond the physical effects of the disease. Patients often scramble to make adjustments in family and work schedules to manage treatment, said Samyukta Mullangi, MD, MBA, medical director of oncology at Thyme Care, a Nashville, Tennessee–based firm that provides navigation and coordination services to oncology practices and insurers.
“It just really does create a bit of a pressure cooker for patients,” Dr. Mullangi told this news organization.
Medicare has for many years paid for medical professionals to help patients cope with the complexities of disease, such as chronic care management (CCM) provided by physicians, nurses, and physician assistants.
The new principal illness navigation (PIN) payments are intended to pay for work that to date typically has been done by people without medical degrees, including those involved in peer support networks and community health programs. The US Centers for Medicare and Medicaid Services(CMS) expects these navigators will undergo training and work under the supervision of clinicians.
The new navigators may coordinate care transitions between medical settings, follow up with patients after emergency department (ED) visits, or communicate with skilled nursing facilities regarding the psychosocial needs and functional deficits of a patient, among other functions.
CMS expects the new navigators may:
- Conduct assessments to understand a patient’s life story, strengths, needs, goals, preferences, and desired outcomes, including understanding cultural and linguistic factors.
- Provide support to accomplish the clinician’s treatment plan.
- Coordinate the receipt of needed services from healthcare facilities, home- and community-based service providers, and caregivers.
Peers as Navigators
The new navigators can be former patients who have undergone similar treatments for serious diseases, CMS said. This approach sets the new program apart from other care management services Medicare already covers, program officials wrote in the 2024 physician fee schedule.
“For some conditions, patients are best able to engage with the healthcare system and access care if they have assistance from a single, dedicated individual who has ‘lived experience,’ ” according to the rule.
The agency has taken a broad initial approach in defining what kinds of illnesses a patient may have to qualify for services. Patients must have a serious condition that is expected to last at least 3 months, such as cancer, heart failure, or substance use disorder.
But those without a definitive diagnosis may also qualify to receive navigator services.
In the rule, CMS cited a case in which a CT scan identified a suspicious mass in a patient’s colon. A clinician might decide this person would benefit from navigation services due to the potential risks for an undiagnosed illness.
“Regardless of the definitive diagnosis of the mass, presence of a colonic mass for that patient may be a serious high-risk condition that could, for example, cause obstruction and lead the patient to present to the emergency department, as well as be potentially indicative of an underlying life-threatening illness such as colon cancer,” CMS wrote in the rule.
Navigators often start their work when cancer patients are screened and guide them through initial diagnosis, potential surgery, radiation, or chemotherapy, said Sharon Gentry, MSN, RN, a former nurse navigator who is now the editor in chief of the Journal of the Academy of Oncology Nurse & Patient Navigators.
The navigators are meant to be a trusted and continual presence for patients, who otherwise might be left to start anew in finding help at each phase of care.
The navigators “see the whole picture. They see the whole journey the patient takes, from pre-diagnosis all the way through diagnosis care out through survival,” Ms. Gentry said.
Gaining a special Medicare payment for these kinds of services will elevate this work, she said.
Many newer drugs can target specific mechanisms and proteins of cancer. Often, oncology treatment involves testing to find out if mutations are allowing the cancer cells to evade a patient’s immune system.
Checking these biomarkers takes time, however. Patients sometimes become frustrated because they are anxious to begin treatment. Patients may receive inaccurate information from friends or family who went through treatment previously. Navigators can provide knowledge on the current state of care for a patient’s disease, helping them better manage anxieties.
“You have to explain to them that things have changed since the guy you drink coffee with was diagnosed with cancer, and there may be a drug that could target that,” Ms. Gentry said.
Potential Challenges
Initial uptake of the new PIN codes may be slow going, however, as clinicians and health systems may already use well-established codes. These include CCM and principal care management services, which may pay higher rates, Mullangi said.
“There might be sensitivity around not wanting to cannibalize existing programs with a new program,” Dr. Mullangi said.
In addition, many patients will have a copay for the services of principal illness navigators, Dr. Mullangi said.
While many patients have additional insurance that would cover the service, not all do. People with traditional Medicare coverage can sometimes pay 20% of the cost of some medical services.
“I think that may give patients pause, particularly if they’re already feeling the financial burden of a cancer treatment journey,” Dr. Mullangi said.
Pay rates for PIN services involve calculations of regional price differences, which are posted publicly by CMS, and potential added fees for services provided by hospital-affiliated organizations.
Consider payments for code G0023, covering 60 minutes of principal navigation services provided in a single month.
A set reimbursement for patients cared for in independent medical practices exists, with variation for local costs. Medicare’s non-facility price for G0023 would be $102.41 in some parts of Silicon Valley in California, including San Jose. In Arkansas, where costs are lower, reimbursement would be $73.14 for this same service.
Patients who get services covered by code G0023 in independent medical practices would have monthly copays of about $15-$20, depending on where they live.
The tab for patients tends to be higher for these same services if delivered through a medical practice owned by a hospital, as this would trigger the addition of facility fees to the payments made to cover the services. Facility fees are difficult for the public to ascertain before getting a treatment or service.
Dr. Mullangi and Ms. Gentry reported no relevant financial disclosures outside of their employers.
A version of this article first appeared on Medscape.com.
In a move that acknowledges the gauntlet the US health system poses for people facing serious and fatal illnesses, Medicare will pay for a new class of workers to help patients manage treatments for conditions like cancer and heart failure.
The 2024 Medicare physician fee schedule includes new billing codes, including G0023, to pay for 60 minutes a month of care coordination by certified or trained auxiliary personnel working under the direction of a clinician.
A diagnosis of cancer or another serious illness takes a toll beyond the physical effects of the disease. Patients often scramble to make adjustments in family and work schedules to manage treatment, said Samyukta Mullangi, MD, MBA, medical director of oncology at Thyme Care, a Nashville, Tennessee–based firm that provides navigation and coordination services to oncology practices and insurers.
“It just really does create a bit of a pressure cooker for patients,” Dr. Mullangi told this news organization.
Medicare has for many years paid for medical professionals to help patients cope with the complexities of disease, such as chronic care management (CCM) provided by physicians, nurses, and physician assistants.
The new principal illness navigation (PIN) payments are intended to pay for work that to date typically has been done by people without medical degrees, including those involved in peer support networks and community health programs. The US Centers for Medicare and Medicaid Services(CMS) expects these navigators will undergo training and work under the supervision of clinicians.
The new navigators may coordinate care transitions between medical settings, follow up with patients after emergency department (ED) visits, or communicate with skilled nursing facilities regarding the psychosocial needs and functional deficits of a patient, among other functions.
CMS expects the new navigators may:
- Conduct assessments to understand a patient’s life story, strengths, needs, goals, preferences, and desired outcomes, including understanding cultural and linguistic factors.
- Provide support to accomplish the clinician’s treatment plan.
- Coordinate the receipt of needed services from healthcare facilities, home- and community-based service providers, and caregivers.
Peers as Navigators
The new navigators can be former patients who have undergone similar treatments for serious diseases, CMS said. This approach sets the new program apart from other care management services Medicare already covers, program officials wrote in the 2024 physician fee schedule.
“For some conditions, patients are best able to engage with the healthcare system and access care if they have assistance from a single, dedicated individual who has ‘lived experience,’ ” according to the rule.
The agency has taken a broad initial approach in defining what kinds of illnesses a patient may have to qualify for services. Patients must have a serious condition that is expected to last at least 3 months, such as cancer, heart failure, or substance use disorder.
But those without a definitive diagnosis may also qualify to receive navigator services.
In the rule, CMS cited a case in which a CT scan identified a suspicious mass in a patient’s colon. A clinician might decide this person would benefit from navigation services due to the potential risks for an undiagnosed illness.
“Regardless of the definitive diagnosis of the mass, presence of a colonic mass for that patient may be a serious high-risk condition that could, for example, cause obstruction and lead the patient to present to the emergency department, as well as be potentially indicative of an underlying life-threatening illness such as colon cancer,” CMS wrote in the rule.
Navigators often start their work when cancer patients are screened and guide them through initial diagnosis, potential surgery, radiation, or chemotherapy, said Sharon Gentry, MSN, RN, a former nurse navigator who is now the editor in chief of the Journal of the Academy of Oncology Nurse & Patient Navigators.
The navigators are meant to be a trusted and continual presence for patients, who otherwise might be left to start anew in finding help at each phase of care.
The navigators “see the whole picture. They see the whole journey the patient takes, from pre-diagnosis all the way through diagnosis care out through survival,” Ms. Gentry said.
Gaining a special Medicare payment for these kinds of services will elevate this work, she said.
Many newer drugs can target specific mechanisms and proteins of cancer. Often, oncology treatment involves testing to find out if mutations are allowing the cancer cells to evade a patient’s immune system.
Checking these biomarkers takes time, however. Patients sometimes become frustrated because they are anxious to begin treatment. Patients may receive inaccurate information from friends or family who went through treatment previously. Navigators can provide knowledge on the current state of care for a patient’s disease, helping them better manage anxieties.
“You have to explain to them that things have changed since the guy you drink coffee with was diagnosed with cancer, and there may be a drug that could target that,” Ms. Gentry said.
Potential Challenges
Initial uptake of the new PIN codes may be slow going, however, as clinicians and health systems may already use well-established codes. These include CCM and principal care management services, which may pay higher rates, Mullangi said.
“There might be sensitivity around not wanting to cannibalize existing programs with a new program,” Dr. Mullangi said.
In addition, many patients will have a copay for the services of principal illness navigators, Dr. Mullangi said.
While many patients have additional insurance that would cover the service, not all do. People with traditional Medicare coverage can sometimes pay 20% of the cost of some medical services.
“I think that may give patients pause, particularly if they’re already feeling the financial burden of a cancer treatment journey,” Dr. Mullangi said.
Pay rates for PIN services involve calculations of regional price differences, which are posted publicly by CMS, and potential added fees for services provided by hospital-affiliated organizations.
Consider payments for code G0023, covering 60 minutes of principal navigation services provided in a single month.
A set reimbursement for patients cared for in independent medical practices exists, with variation for local costs. Medicare’s non-facility price for G0023 would be $102.41 in some parts of Silicon Valley in California, including San Jose. In Arkansas, where costs are lower, reimbursement would be $73.14 for this same service.
Patients who get services covered by code G0023 in independent medical practices would have monthly copays of about $15-$20, depending on where they live.
The tab for patients tends to be higher for these same services if delivered through a medical practice owned by a hospital, as this would trigger the addition of facility fees to the payments made to cover the services. Facility fees are difficult for the public to ascertain before getting a treatment or service.
Dr. Mullangi and Ms. Gentry reported no relevant financial disclosures outside of their employers.
A version of this article first appeared on Medscape.com.
In a move that acknowledges the gauntlet the US health system poses for people facing serious and fatal illnesses, Medicare will pay for a new class of workers to help patients manage treatments for conditions like cancer and heart failure.
The 2024 Medicare physician fee schedule includes new billing codes, including G0023, to pay for 60 minutes a month of care coordination by certified or trained auxiliary personnel working under the direction of a clinician.
A diagnosis of cancer or another serious illness takes a toll beyond the physical effects of the disease. Patients often scramble to make adjustments in family and work schedules to manage treatment, said Samyukta Mullangi, MD, MBA, medical director of oncology at Thyme Care, a Nashville, Tennessee–based firm that provides navigation and coordination services to oncology practices and insurers.
“It just really does create a bit of a pressure cooker for patients,” Dr. Mullangi told this news organization.
Medicare has for many years paid for medical professionals to help patients cope with the complexities of disease, such as chronic care management (CCM) provided by physicians, nurses, and physician assistants.
The new principal illness navigation (PIN) payments are intended to pay for work that to date typically has been done by people without medical degrees, including those involved in peer support networks and community health programs. The US Centers for Medicare and Medicaid Services(CMS) expects these navigators will undergo training and work under the supervision of clinicians.
The new navigators may coordinate care transitions between medical settings, follow up with patients after emergency department (ED) visits, or communicate with skilled nursing facilities regarding the psychosocial needs and functional deficits of a patient, among other functions.
CMS expects the new navigators may:
- Conduct assessments to understand a patient’s life story, strengths, needs, goals, preferences, and desired outcomes, including understanding cultural and linguistic factors.
- Provide support to accomplish the clinician’s treatment plan.
- Coordinate the receipt of needed services from healthcare facilities, home- and community-based service providers, and caregivers.
Peers as Navigators
The new navigators can be former patients who have undergone similar treatments for serious diseases, CMS said. This approach sets the new program apart from other care management services Medicare already covers, program officials wrote in the 2024 physician fee schedule.
“For some conditions, patients are best able to engage with the healthcare system and access care if they have assistance from a single, dedicated individual who has ‘lived experience,’ ” according to the rule.
The agency has taken a broad initial approach in defining what kinds of illnesses a patient may have to qualify for services. Patients must have a serious condition that is expected to last at least 3 months, such as cancer, heart failure, or substance use disorder.
But those without a definitive diagnosis may also qualify to receive navigator services.
In the rule, CMS cited a case in which a CT scan identified a suspicious mass in a patient’s colon. A clinician might decide this person would benefit from navigation services due to the potential risks for an undiagnosed illness.
“Regardless of the definitive diagnosis of the mass, presence of a colonic mass for that patient may be a serious high-risk condition that could, for example, cause obstruction and lead the patient to present to the emergency department, as well as be potentially indicative of an underlying life-threatening illness such as colon cancer,” CMS wrote in the rule.
Navigators often start their work when cancer patients are screened and guide them through initial diagnosis, potential surgery, radiation, or chemotherapy, said Sharon Gentry, MSN, RN, a former nurse navigator who is now the editor in chief of the Journal of the Academy of Oncology Nurse & Patient Navigators.
The navigators are meant to be a trusted and continual presence for patients, who otherwise might be left to start anew in finding help at each phase of care.
The navigators “see the whole picture. They see the whole journey the patient takes, from pre-diagnosis all the way through diagnosis care out through survival,” Ms. Gentry said.
Gaining a special Medicare payment for these kinds of services will elevate this work, she said.
Many newer drugs can target specific mechanisms and proteins of cancer. Often, oncology treatment involves testing to find out if mutations are allowing the cancer cells to evade a patient’s immune system.
Checking these biomarkers takes time, however. Patients sometimes become frustrated because they are anxious to begin treatment. Patients may receive inaccurate information from friends or family who went through treatment previously. Navigators can provide knowledge on the current state of care for a patient’s disease, helping them better manage anxieties.
“You have to explain to them that things have changed since the guy you drink coffee with was diagnosed with cancer, and there may be a drug that could target that,” Ms. Gentry said.
Potential Challenges
Initial uptake of the new PIN codes may be slow going, however, as clinicians and health systems may already use well-established codes. These include CCM and principal care management services, which may pay higher rates, Mullangi said.
“There might be sensitivity around not wanting to cannibalize existing programs with a new program,” Dr. Mullangi said.
In addition, many patients will have a copay for the services of principal illness navigators, Dr. Mullangi said.
While many patients have additional insurance that would cover the service, not all do. People with traditional Medicare coverage can sometimes pay 20% of the cost of some medical services.
“I think that may give patients pause, particularly if they’re already feeling the financial burden of a cancer treatment journey,” Dr. Mullangi said.
Pay rates for PIN services involve calculations of regional price differences, which are posted publicly by CMS, and potential added fees for services provided by hospital-affiliated organizations.
Consider payments for code G0023, covering 60 minutes of principal navigation services provided in a single month.
A set reimbursement for patients cared for in independent medical practices exists, with variation for local costs. Medicare’s non-facility price for G0023 would be $102.41 in some parts of Silicon Valley in California, including San Jose. In Arkansas, where costs are lower, reimbursement would be $73.14 for this same service.
Patients who get services covered by code G0023 in independent medical practices would have monthly copays of about $15-$20, depending on where they live.
The tab for patients tends to be higher for these same services if delivered through a medical practice owned by a hospital, as this would trigger the addition of facility fees to the payments made to cover the services. Facility fees are difficult for the public to ascertain before getting a treatment or service.
Dr. Mullangi and Ms. Gentry reported no relevant financial disclosures outside of their employers.
A version of this article first appeared on Medscape.com.
SVS Now Accepting Abstracts for VAM 2017
Abstracts for the 2017 Vascular Annual Meeting are now being accepted. The submission site opened Monday, Nov. 14 for the meeting, to be held May 31 to June 3, 2017, in San Diego. Plenary sessions and exhibits will be June 1 to 3.
Participants may submit abstracts into any of 14 categories and a number of presentation types, including videos. In 2016, organizers selected approximately two-thirds of the submitted abstracts, and this year the VAM Program Committee is seeking additional venues for people to present their work in, including more sessions and other presentation formats.
Click here for abstract guidelines and more information. Abstracts themselves may be submitted here.
Abstracts for the 2017 Vascular Annual Meeting are now being accepted. The submission site opened Monday, Nov. 14 for the meeting, to be held May 31 to June 3, 2017, in San Diego. Plenary sessions and exhibits will be June 1 to 3.
Participants may submit abstracts into any of 14 categories and a number of presentation types, including videos. In 2016, organizers selected approximately two-thirds of the submitted abstracts, and this year the VAM Program Committee is seeking additional venues for people to present their work in, including more sessions and other presentation formats.
Click here for abstract guidelines and more information. Abstracts themselves may be submitted here.
Abstracts for the 2017 Vascular Annual Meeting are now being accepted. The submission site opened Monday, Nov. 14 for the meeting, to be held May 31 to June 3, 2017, in San Diego. Plenary sessions and exhibits will be June 1 to 3.
Participants may submit abstracts into any of 14 categories and a number of presentation types, including videos. In 2016, organizers selected approximately two-thirds of the submitted abstracts, and this year the VAM Program Committee is seeking additional venues for people to present their work in, including more sessions and other presentation formats.
Click here for abstract guidelines and more information. Abstracts themselves may be submitted here.
Atypical Antipsychotics Tied to Adrenal Issues
NEW ORLEANS — It is important to recognize the potential for atypical antipsychotics to cause adrenal insufficiency to ensure that the condition is managed appropriately, according to Dr. Violeta Tan and Dr. Natalie Rasgon.
They described the case of a 54-year-old man with a history of depression and posttraumatic stress disorder who was admitted to the hospital after complaining of malaise 9 days after a previous admission for a urinary tract infection that had been treated with ciprofloxacin.
At the first admission, the patient was restarted on 225 mg/day of bupropion and 300 mg/day of quetiapine (Seroquel), both of which he had discontinued 6–8 months prior, said Dr. Tan and Dr. Rasgon, who presented the case in a poster session at the American Psychiatric Association's Institute of Psychiatric Services.
Symptoms at the time of the second admission included fatigue, warmth, chills, loose stools, mild headache, and reproducible chest wall pain. Laboratory findings showed that previously normal eosinophil levels were elevated (6.5%–8.3%), reported Dr. Tan and Dr. Rasgon, both of Stanford (Calif.) University.
A work-up for infection, malignancy, and rheumatologic conditions was negative, and primary adrenal insufficiency was ruled out based on the findings of a cosyntropin stimulation test. However, adrenocorticotropic hormone (ACTH) levels (less than 5 pg/mL) indicated secondary or tertiary adrenal insufficiency, and a review of the patient's medications alerted the authors to the possibility of quetiapine-associated ACTH and cortisol reductions.
Atypical antipsychotics such as quetiapine can reduce cortisol levels—often in association with improved psychopathology. Thus, although the cortisol-lowering effects of such drugs may ameliorate negative symptomatology, the reduction could be detrimental, they wrote.
However, adrenal insufficiency caused by such agents has not been specifically studied, and although it might seem appropriate to discontinue the “offending agent,” the risks of discontinuing antipsychotics should be weighed against the benefits of preventing adrenal insufficiency sequelae, they added.
In the current case, which also demonstrated that quetiapine administration, particularly under precipitating circumstances such as an infection or stress, can contribute to reductions in ACTH and cortisol secretion, the patient's condition improved after quetiapine, a standard treatment for adrenal insufficiency, was administered at 20 mg every morning and at 10 mg at bedtime.
Atypical antipsychotics can cause adrenal insufficiency, which presents ambiguously, and awareness of this can be key in preventing false diagnoses, they said.
Adrenal insufficiency can present ambiguously, which can lead to false diagnoses. DR. RASGON
Spotting Adrenal Insufficiency
Dr. Tan and Dr. Rasgon say determining whether a patient has developed adrenal insufficiency requires an investigation into four areas:
▸ Symptoms. Look for weakness and fatigue, abdominal distress, anorexia, nausea, vomiting, myalgia or arthralgia, postural dizziness, salt craving, headache, impaired memory, and depression.
▸ Physical findings. Some factors to look out for are increased pigmentation, postural hypotension, tachycardia, fever, decreased body hair, vitiligo, amenorrhea, and cold intolerance.
▸ Laboratory findings. Red flags include hyponatremia, hyperkalemia, hypoglycemia, eosinophilia, and elevated thyroid stimulating hormone.
▸ Clinical problems. Watch for hemodynamic instability, ongoing inflammation, multiple-organ dysfunction, and hypoglycemia.
NEW ORLEANS — It is important to recognize the potential for atypical antipsychotics to cause adrenal insufficiency to ensure that the condition is managed appropriately, according to Dr. Violeta Tan and Dr. Natalie Rasgon.
They described the case of a 54-year-old man with a history of depression and posttraumatic stress disorder who was admitted to the hospital after complaining of malaise 9 days after a previous admission for a urinary tract infection that had been treated with ciprofloxacin.
At the first admission, the patient was restarted on 225 mg/day of bupropion and 300 mg/day of quetiapine (Seroquel), both of which he had discontinued 6–8 months prior, said Dr. Tan and Dr. Rasgon, who presented the case in a poster session at the American Psychiatric Association's Institute of Psychiatric Services.
Symptoms at the time of the second admission included fatigue, warmth, chills, loose stools, mild headache, and reproducible chest wall pain. Laboratory findings showed that previously normal eosinophil levels were elevated (6.5%–8.3%), reported Dr. Tan and Dr. Rasgon, both of Stanford (Calif.) University.
A work-up for infection, malignancy, and rheumatologic conditions was negative, and primary adrenal insufficiency was ruled out based on the findings of a cosyntropin stimulation test. However, adrenocorticotropic hormone (ACTH) levels (less than 5 pg/mL) indicated secondary or tertiary adrenal insufficiency, and a review of the patient's medications alerted the authors to the possibility of quetiapine-associated ACTH and cortisol reductions.
Atypical antipsychotics such as quetiapine can reduce cortisol levels—often in association with improved psychopathology. Thus, although the cortisol-lowering effects of such drugs may ameliorate negative symptomatology, the reduction could be detrimental, they wrote.
However, adrenal insufficiency caused by such agents has not been specifically studied, and although it might seem appropriate to discontinue the “offending agent,” the risks of discontinuing antipsychotics should be weighed against the benefits of preventing adrenal insufficiency sequelae, they added.
In the current case, which also demonstrated that quetiapine administration, particularly under precipitating circumstances such as an infection or stress, can contribute to reductions in ACTH and cortisol secretion, the patient's condition improved after quetiapine, a standard treatment for adrenal insufficiency, was administered at 20 mg every morning and at 10 mg at bedtime.
Atypical antipsychotics can cause adrenal insufficiency, which presents ambiguously, and awareness of this can be key in preventing false diagnoses, they said.
Adrenal insufficiency can present ambiguously, which can lead to false diagnoses. DR. RASGON
Spotting Adrenal Insufficiency
Dr. Tan and Dr. Rasgon say determining whether a patient has developed adrenal insufficiency requires an investigation into four areas:
▸ Symptoms. Look for weakness and fatigue, abdominal distress, anorexia, nausea, vomiting, myalgia or arthralgia, postural dizziness, salt craving, headache, impaired memory, and depression.
▸ Physical findings. Some factors to look out for are increased pigmentation, postural hypotension, tachycardia, fever, decreased body hair, vitiligo, amenorrhea, and cold intolerance.
▸ Laboratory findings. Red flags include hyponatremia, hyperkalemia, hypoglycemia, eosinophilia, and elevated thyroid stimulating hormone.
▸ Clinical problems. Watch for hemodynamic instability, ongoing inflammation, multiple-organ dysfunction, and hypoglycemia.
NEW ORLEANS — It is important to recognize the potential for atypical antipsychotics to cause adrenal insufficiency to ensure that the condition is managed appropriately, according to Dr. Violeta Tan and Dr. Natalie Rasgon.
They described the case of a 54-year-old man with a history of depression and posttraumatic stress disorder who was admitted to the hospital after complaining of malaise 9 days after a previous admission for a urinary tract infection that had been treated with ciprofloxacin.
At the first admission, the patient was restarted on 225 mg/day of bupropion and 300 mg/day of quetiapine (Seroquel), both of which he had discontinued 6–8 months prior, said Dr. Tan and Dr. Rasgon, who presented the case in a poster session at the American Psychiatric Association's Institute of Psychiatric Services.
Symptoms at the time of the second admission included fatigue, warmth, chills, loose stools, mild headache, and reproducible chest wall pain. Laboratory findings showed that previously normal eosinophil levels were elevated (6.5%–8.3%), reported Dr. Tan and Dr. Rasgon, both of Stanford (Calif.) University.
A work-up for infection, malignancy, and rheumatologic conditions was negative, and primary adrenal insufficiency was ruled out based on the findings of a cosyntropin stimulation test. However, adrenocorticotropic hormone (ACTH) levels (less than 5 pg/mL) indicated secondary or tertiary adrenal insufficiency, and a review of the patient's medications alerted the authors to the possibility of quetiapine-associated ACTH and cortisol reductions.
Atypical antipsychotics such as quetiapine can reduce cortisol levels—often in association with improved psychopathology. Thus, although the cortisol-lowering effects of such drugs may ameliorate negative symptomatology, the reduction could be detrimental, they wrote.
However, adrenal insufficiency caused by such agents has not been specifically studied, and although it might seem appropriate to discontinue the “offending agent,” the risks of discontinuing antipsychotics should be weighed against the benefits of preventing adrenal insufficiency sequelae, they added.
In the current case, which also demonstrated that quetiapine administration, particularly under precipitating circumstances such as an infection or stress, can contribute to reductions in ACTH and cortisol secretion, the patient's condition improved after quetiapine, a standard treatment for adrenal insufficiency, was administered at 20 mg every morning and at 10 mg at bedtime.
Atypical antipsychotics can cause adrenal insufficiency, which presents ambiguously, and awareness of this can be key in preventing false diagnoses, they said.
Adrenal insufficiency can present ambiguously, which can lead to false diagnoses. DR. RASGON
Spotting Adrenal Insufficiency
Dr. Tan and Dr. Rasgon say determining whether a patient has developed adrenal insufficiency requires an investigation into four areas:
▸ Symptoms. Look for weakness and fatigue, abdominal distress, anorexia, nausea, vomiting, myalgia or arthralgia, postural dizziness, salt craving, headache, impaired memory, and depression.
▸ Physical findings. Some factors to look out for are increased pigmentation, postural hypotension, tachycardia, fever, decreased body hair, vitiligo, amenorrhea, and cold intolerance.
▸ Laboratory findings. Red flags include hyponatremia, hyperkalemia, hypoglycemia, eosinophilia, and elevated thyroid stimulating hormone.
▸ Clinical problems. Watch for hemodynamic instability, ongoing inflammation, multiple-organ dysfunction, and hypoglycemia.
GI Disorders Linked With Sleep Problems
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
Support GI Research Through a Named Research Award
Did you know you can honor a family member, friend, or colleague whose life has been touched by GI research through a gift to the AGA Research Foundation? Your gift will honor a loved one or yourself and support the AGA Research Awards Program, while giving you a tax benefit.
Named award. An AGA pilot award can be renamed after you or a loved one, and targeted for a specific gastrointestinal research area. A new pilot research award can be established with a pledge of $40,000+ or through an estate gift. Gifts of cash or appreciated securities may be used to establish a named award.
Your next step. A named award gift is a wonderful way to acknowledge a loved one’s vision for the future. To learn more about ways to recognize your honoree, contact us at [email protected].
A lack of funding can prevent talented individuals from pursuing a research career, thereby denying them the opportunity to conduct work that will ultimately benefit patients with critical needs.
Did you know you can honor a family member, friend, or colleague whose life has been touched by GI research through a gift to the AGA Research Foundation? Your gift will honor a loved one or yourself and support the AGA Research Awards Program, while giving you a tax benefit.
Named award. An AGA pilot award can be renamed after you or a loved one, and targeted for a specific gastrointestinal research area. A new pilot research award can be established with a pledge of $40,000+ or through an estate gift. Gifts of cash or appreciated securities may be used to establish a named award.
Your next step. A named award gift is a wonderful way to acknowledge a loved one’s vision for the future. To learn more about ways to recognize your honoree, contact us at [email protected].
A lack of funding can prevent talented individuals from pursuing a research career, thereby denying them the opportunity to conduct work that will ultimately benefit patients with critical needs.
Did you know you can honor a family member, friend, or colleague whose life has been touched by GI research through a gift to the AGA Research Foundation? Your gift will honor a loved one or yourself and support the AGA Research Awards Program, while giving you a tax benefit.
Named award. An AGA pilot award can be renamed after you or a loved one, and targeted for a specific gastrointestinal research area. A new pilot research award can be established with a pledge of $40,000+ or through an estate gift. Gifts of cash or appreciated securities may be used to establish a named award.
Your next step. A named award gift is a wonderful way to acknowledge a loved one’s vision for the future. To learn more about ways to recognize your honoree, contact us at [email protected].
A lack of funding can prevent talented individuals from pursuing a research career, thereby denying them the opportunity to conduct work that will ultimately benefit patients with critical needs.
From Neglect to Novelty: Emerging Treatment Strategies in Papillary Renal Cell Carcinoma
This transcript has been edited for clarity.
Hi, I’m Doctor Monty Pal, and I’m a medical oncologist at City of Hope Comprehensive Cancer Center.
I run the kidney cancer program there, and it’s really been amazing to see the tidal wave of new therapies that we’ve developed for kidney cancer over the years.
What I will say is that most of the treatments that we have, the doublet therapies and adjuvant treatments, really pertain to the most dominant subset of kidney cancer, and that’s clear cell; that really represents about 75%-80% of all cases of kidney cancer.
Having said that, I’d like to focus on perhaps a less dominant subset of kidney cancer known as papillary. This represents about 15%-20% of cases.
To be fair, there are other rare subtypes and those certainly warrant focus as well: Chromophobe represents about 5% of all diseases; translocation, unclassified, a percentage point or 2.
But papillary really is a setting in which we can do — and as I’ll demonstrate, have done — clinical trials.
Now papillary kidney cancer is similar in terms of its demographics to clear cell renal cell carcinoma (RCC). There still tends to be a male predominance. It may have a slightly lower age of initial presentation, but otherwise there’s many commonalities.
I do think one of the areas where it differs, and this is critical, is in the context of biology: We think that papillary RCC is really driven by the MET proto-oncogene amongst other things. With that in mind, there have been a whole host of therapies directed at the MET proto-oncogene, and we’ll discuss that in just a moment.
I wanted to first talk about management of localized papillary kidney cancer. This management doesn’t differ significantly from what we would perhaps consider in the context of localized clear cell kidney cancer. For stage 1 through 3 disease, patients still receive surgery as the mainstay, and I would argue that, in the context of stage 4 disease, we should still really consider aggressive local definitive therapies if at all possible.
Having said that, the role of adjuvant therapy is a bit unclear in this context. I would suggest that in the context of adjuvant therapy for papillary kidney cancer, it’s a bit of a no go until we have greater data in this setting. Therapies like pembrolizumab and sunitinib really were only tested in the context of clear cell disease.
And with that background, I wanted to move into metastatic disease. For patients with stage 4 papillary kidney cancer, therapy may or may not resemble the treatments that we use for clear cell kidney cancer.
There have been trials in yesteryear with really creative names, ASPEN and ESPN for instance, that actually juxtaposed older therapies against one another. Sunitinib against everolimus, for instance, was common to both of those studies. And it really suggested perhaps that sunitinib was the preferred choice between those two targeted therapies. Sunitinib then became a bit of a standard when it came to randomized trials, and in fact, it still remains something that’s incorporated as a base regimen at phase 3 clinical trials.
I’ll show you that in the PAPMET clinical trial, which was a randomized phase 2 experience, we were able to compare sunitinib to cabozantinib, crizotinib, and savolitinib. The latter three drugs are all so-called MET inhibitors. And what’s quite interesting about this study is that cabozantinib, the dual VEGF/MET inhibitor, really is the one that seemed to win out.
When you look at median progression-free survival (PFS), in sunitinib in that study was around 6 months. When you look at cabozantinib, it was around 9 months.
Having said that, with cabozantinib, there was no overall survival advantage, and I will say that the PFS benefit is modest. So, we still need more in the way of clinical trials.
To that end, there’s a number of single arm studies supporting cabozantinib-based regimens, cabozantinib/atezolizumab and cabozantinib/nivolumab, with healthy response rates. For papillary kidney cancer, the response rate with those regimens is around 43%-47%.
In the context of lenvatinib and pembrolizumab, we actually see the response rate augmented to approximately 53%.
So, with those numbers in mind, I definitely think that doublet therapy is promising, but as we always tell our fellows in the clinic, randomization is really king.
So, we do have two phase 3 clinical trials, STELLAR-304, which is a study that I’m running, and the second study is known as SAMETA. Both evaluate papillary patients, but in very different ways.
STELLAR-304 includes patients with papillary, translocation, and unclassified kidney cancer and randomizes to sunitinib vs zanzalintinib, a novel TKI, with nivolumab.
In contrast, SAMETA takes the very interesting approach of actually selecting out patients with MET abnormalities and randomizing them to sunitinib vs savolitinib.
There are other approaches. For instance, the SUNNIFORECAST study recently assessed nivolumab and ipilimumab. There are randomized phase 2 studies looking at axitinib and pembrolizumab or perhaps axitinib and, sorry, cabozantinib with atezolizumab.
But I do think these phase 3 studies, SAMETA and STELLAR-304, are the ones that are really poised to change the landscape of therapy for papillary kidney cancer.
Sumanta K. Pal, MD, Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, has disclosed the following relevant financial relationships: Received travel from: CRISPR; Ipsen. A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hi, I’m Doctor Monty Pal, and I’m a medical oncologist at City of Hope Comprehensive Cancer Center.
I run the kidney cancer program there, and it’s really been amazing to see the tidal wave of new therapies that we’ve developed for kidney cancer over the years.
What I will say is that most of the treatments that we have, the doublet therapies and adjuvant treatments, really pertain to the most dominant subset of kidney cancer, and that’s clear cell; that really represents about 75%-80% of all cases of kidney cancer.
Having said that, I’d like to focus on perhaps a less dominant subset of kidney cancer known as papillary. This represents about 15%-20% of cases.
To be fair, there are other rare subtypes and those certainly warrant focus as well: Chromophobe represents about 5% of all diseases; translocation, unclassified, a percentage point or 2.
But papillary really is a setting in which we can do — and as I’ll demonstrate, have done — clinical trials.
Now papillary kidney cancer is similar in terms of its demographics to clear cell renal cell carcinoma (RCC). There still tends to be a male predominance. It may have a slightly lower age of initial presentation, but otherwise there’s many commonalities.
I do think one of the areas where it differs, and this is critical, is in the context of biology: We think that papillary RCC is really driven by the MET proto-oncogene amongst other things. With that in mind, there have been a whole host of therapies directed at the MET proto-oncogene, and we’ll discuss that in just a moment.
I wanted to first talk about management of localized papillary kidney cancer. This management doesn’t differ significantly from what we would perhaps consider in the context of localized clear cell kidney cancer. For stage 1 through 3 disease, patients still receive surgery as the mainstay, and I would argue that, in the context of stage 4 disease, we should still really consider aggressive local definitive therapies if at all possible.
Having said that, the role of adjuvant therapy is a bit unclear in this context. I would suggest that in the context of adjuvant therapy for papillary kidney cancer, it’s a bit of a no go until we have greater data in this setting. Therapies like pembrolizumab and sunitinib really were only tested in the context of clear cell disease.
And with that background, I wanted to move into metastatic disease. For patients with stage 4 papillary kidney cancer, therapy may or may not resemble the treatments that we use for clear cell kidney cancer.
There have been trials in yesteryear with really creative names, ASPEN and ESPN for instance, that actually juxtaposed older therapies against one another. Sunitinib against everolimus, for instance, was common to both of those studies. And it really suggested perhaps that sunitinib was the preferred choice between those two targeted therapies. Sunitinib then became a bit of a standard when it came to randomized trials, and in fact, it still remains something that’s incorporated as a base regimen at phase 3 clinical trials.
I’ll show you that in the PAPMET clinical trial, which was a randomized phase 2 experience, we were able to compare sunitinib to cabozantinib, crizotinib, and savolitinib. The latter three drugs are all so-called MET inhibitors. And what’s quite interesting about this study is that cabozantinib, the dual VEGF/MET inhibitor, really is the one that seemed to win out.
When you look at median progression-free survival (PFS), in sunitinib in that study was around 6 months. When you look at cabozantinib, it was around 9 months.
Having said that, with cabozantinib, there was no overall survival advantage, and I will say that the PFS benefit is modest. So, we still need more in the way of clinical trials.
To that end, there’s a number of single arm studies supporting cabozantinib-based regimens, cabozantinib/atezolizumab and cabozantinib/nivolumab, with healthy response rates. For papillary kidney cancer, the response rate with those regimens is around 43%-47%.
In the context of lenvatinib and pembrolizumab, we actually see the response rate augmented to approximately 53%.
So, with those numbers in mind, I definitely think that doublet therapy is promising, but as we always tell our fellows in the clinic, randomization is really king.
So, we do have two phase 3 clinical trials, STELLAR-304, which is a study that I’m running, and the second study is known as SAMETA. Both evaluate papillary patients, but in very different ways.
STELLAR-304 includes patients with papillary, translocation, and unclassified kidney cancer and randomizes to sunitinib vs zanzalintinib, a novel TKI, with nivolumab.
In contrast, SAMETA takes the very interesting approach of actually selecting out patients with MET abnormalities and randomizing them to sunitinib vs savolitinib.
There are other approaches. For instance, the SUNNIFORECAST study recently assessed nivolumab and ipilimumab. There are randomized phase 2 studies looking at axitinib and pembrolizumab or perhaps axitinib and, sorry, cabozantinib with atezolizumab.
But I do think these phase 3 studies, SAMETA and STELLAR-304, are the ones that are really poised to change the landscape of therapy for papillary kidney cancer.
Sumanta K. Pal, MD, Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, has disclosed the following relevant financial relationships: Received travel from: CRISPR; Ipsen. A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hi, I’m Doctor Monty Pal, and I’m a medical oncologist at City of Hope Comprehensive Cancer Center.
I run the kidney cancer program there, and it’s really been amazing to see the tidal wave of new therapies that we’ve developed for kidney cancer over the years.
What I will say is that most of the treatments that we have, the doublet therapies and adjuvant treatments, really pertain to the most dominant subset of kidney cancer, and that’s clear cell; that really represents about 75%-80% of all cases of kidney cancer.
Having said that, I’d like to focus on perhaps a less dominant subset of kidney cancer known as papillary. This represents about 15%-20% of cases.
To be fair, there are other rare subtypes and those certainly warrant focus as well: Chromophobe represents about 5% of all diseases; translocation, unclassified, a percentage point or 2.
But papillary really is a setting in which we can do — and as I’ll demonstrate, have done — clinical trials.
Now papillary kidney cancer is similar in terms of its demographics to clear cell renal cell carcinoma (RCC). There still tends to be a male predominance. It may have a slightly lower age of initial presentation, but otherwise there’s many commonalities.
I do think one of the areas where it differs, and this is critical, is in the context of biology: We think that papillary RCC is really driven by the MET proto-oncogene amongst other things. With that in mind, there have been a whole host of therapies directed at the MET proto-oncogene, and we’ll discuss that in just a moment.
I wanted to first talk about management of localized papillary kidney cancer. This management doesn’t differ significantly from what we would perhaps consider in the context of localized clear cell kidney cancer. For stage 1 through 3 disease, patients still receive surgery as the mainstay, and I would argue that, in the context of stage 4 disease, we should still really consider aggressive local definitive therapies if at all possible.
Having said that, the role of adjuvant therapy is a bit unclear in this context. I would suggest that in the context of adjuvant therapy for papillary kidney cancer, it’s a bit of a no go until we have greater data in this setting. Therapies like pembrolizumab and sunitinib really were only tested in the context of clear cell disease.
And with that background, I wanted to move into metastatic disease. For patients with stage 4 papillary kidney cancer, therapy may or may not resemble the treatments that we use for clear cell kidney cancer.
There have been trials in yesteryear with really creative names, ASPEN and ESPN for instance, that actually juxtaposed older therapies against one another. Sunitinib against everolimus, for instance, was common to both of those studies. And it really suggested perhaps that sunitinib was the preferred choice between those two targeted therapies. Sunitinib then became a bit of a standard when it came to randomized trials, and in fact, it still remains something that’s incorporated as a base regimen at phase 3 clinical trials.
I’ll show you that in the PAPMET clinical trial, which was a randomized phase 2 experience, we were able to compare sunitinib to cabozantinib, crizotinib, and savolitinib. The latter three drugs are all so-called MET inhibitors. And what’s quite interesting about this study is that cabozantinib, the dual VEGF/MET inhibitor, really is the one that seemed to win out.
When you look at median progression-free survival (PFS), in sunitinib in that study was around 6 months. When you look at cabozantinib, it was around 9 months.
Having said that, with cabozantinib, there was no overall survival advantage, and I will say that the PFS benefit is modest. So, we still need more in the way of clinical trials.
To that end, there’s a number of single arm studies supporting cabozantinib-based regimens, cabozantinib/atezolizumab and cabozantinib/nivolumab, with healthy response rates. For papillary kidney cancer, the response rate with those regimens is around 43%-47%.
In the context of lenvatinib and pembrolizumab, we actually see the response rate augmented to approximately 53%.
So, with those numbers in mind, I definitely think that doublet therapy is promising, but as we always tell our fellows in the clinic, randomization is really king.
So, we do have two phase 3 clinical trials, STELLAR-304, which is a study that I’m running, and the second study is known as SAMETA. Both evaluate papillary patients, but in very different ways.
STELLAR-304 includes patients with papillary, translocation, and unclassified kidney cancer and randomizes to sunitinib vs zanzalintinib, a novel TKI, with nivolumab.
In contrast, SAMETA takes the very interesting approach of actually selecting out patients with MET abnormalities and randomizing them to sunitinib vs savolitinib.
There are other approaches. For instance, the SUNNIFORECAST study recently assessed nivolumab and ipilimumab. There are randomized phase 2 studies looking at axitinib and pembrolizumab or perhaps axitinib and, sorry, cabozantinib with atezolizumab.
But I do think these phase 3 studies, SAMETA and STELLAR-304, are the ones that are really poised to change the landscape of therapy for papillary kidney cancer.
Sumanta K. Pal, MD, Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, has disclosed the following relevant financial relationships: Received travel from: CRISPR; Ipsen. A version of this article appeared on Medscape.com.
Intestinal Methanogen Overgrowth Fosters More Constipation, Less Diarrhea
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY