Feature

In 1974, Tommy John of the Los Angeles Dodgers was 31 and a 12-year veteran of Major League Baseball when he became the unwitting vanguard of a revolution in baseball and orthopedics. Fifty years later, Mr. John might not be a candidate for the latest advances to a procedure that bears his name.

The southpaw pitcher had faced the abrupt end of his career when, after one fateful delivery, he found himself unable to throw to home. So he took a gamble on the surgical equivalent of a Hail Mary: the reconstruction of a torn ligament in his pitching elbow.

The experiment was a wild success. Mr. John pitched— and better than he had before — for another 14 seasons, retiring in 1989 at the age of 46. How much better? After the surgery, he tallied three 20-win seasons compared with none before the operation, and he finished among the top five vote-getters for the annual Cy Young Award three times. He was named an All-Star once before the surgery and three times after.

The triumph notwithstanding, Tommy John now cautions against Tommy John surgery. What’s given him and clinicians pause is a trend in recent years of ever-younger athletes who undergo the procedure.

Along with the surgical improvements in repairing a torn ulnar collateral ligament (UCL) is a demographic shift toward school-aged athletes who get it. By 2014, one study concluded that 67.4% of UCL reconstruction surgeries were performed on athletes between 16 and 20 years of age. Some patients are still in Little League when they undergo the procedure.

Experts say these athletes have weakened their UCLs through overuse. They disagree on whether to call it an “epidemic,” but if it is, “the vaccine is awareness” against throwing too hard and too often, said Eric Makhni, MD, an orthopedic surgeon at Henry Ford Health in Detroit.
 

From Career-Ending to Routine

Mr. John’s entry into baseball and orthopedic lore was initially slow, but the trickle turned into a tide. After Frank Jobe, MD, swapped a healthy tendon from John’s right wrist for his worn and torn left UCL on September 25, 1974, he didn’t perform his second surgery for another 1194 days. By the time “Tommy John surgery” became a recognized phrase, Mr. John was still active but only 14 professional baseball players had undergone the operation.

Prior to the start of spring training this year, an oft-cited database listed 366 pro players who’d undergone the operation. 

“Before Tommy John, that was a career-ending injury,” said Grant E. Garrigues, MD, an orthopedic surgeon at Midwest Orthopaedics at RUSH in Chicago, who called Mr. John “a pure revolutionary.”

Tommy John surgery is “the only one that I can think of that is named after the patient rather than the doctor who first did it,” said Patrick McCulloch, MD, an orthopedic surgeon in Houston and a team physician for the Astros.

Dr. McCulloch, who performs about 25 UCL repairs a year, said that by recent estimates, one-third of pro pitchers had had some sort of surgical repair. He hesitated to call the increasing number of operations an epidemic but acknowledged that the ingredients exist for more elbow trauma among baseball players.

“More people are playing more often, and people are bigger and stronger and throwing harder,” he said.

Either way, Dr. McCulloch said, “the procedure is a victim of its own success” because it is “just done phenomenally well.”

The surgery is now commonplace — perhaps too commonplace, said David W. Altchek, MD, attending surgeon and co-chief emeritus at Hospital for Special Surgery in New York City.

Dr. Altchek played a key role in the popularity of the operation. Twenty-two years after Mr. John’s surgery, he helped develop a variation of the procedure called the docking technique. 

Whereas Dr. Jobe sutured Mr. John’s replacement graft to itself, “we developed a different way of tying it over a bone bridge, which was more secure and more easy to tension,” Dr. Altchek explained.

The advance meant less drilling into bone and enabled surgeons to avoid moving a problem-free ulnar nerve or removing the flexor-pronator muscle that protects the elbow from stress. “The trauma of the surgery is significantly less,” he said. “We just made it a lot easier very quickly,” cutting the surgery time from 2 hours to 30-40 minutes.

Maybe the surgery became too easy, said Dr. Altchek, who estimates he has done 2000 of them over the past 30 years. “I don’t want to condemn my colleagues, but there are a lot of people doing the surgery,” he said. “And not a lot of people are doing a lot of them, and they don’t know the nuances of doing the surgery.”

The older procedures are known as the “full Tommy John”; each has a 12- to 18-month healing process, with a success rate of 80%-85%. Pitchers typically sit out a season while recovering.

Brandon Erickson, MD, an orthopedic surgeon at Rothman Orthopaedic Institute in New York City, said that in younger patients he has recently turned more often to the suture of the future: an internal brace that provides a repair rather than reconstruction.

The procedure, pioneered by Felix H. Savoie III, MD, the Ray J. Haddad Professor of Orthopaedics at Tulane University School of Medicine in New Orleans, and Jeffrey R. Dugas, MD, of Andrews Sports Medicine & Orthopaedic Center in Birmingham, Alabama, uses collagen-coated tape that looks like a shoelace and provides a scaffold that Dr. McCulloch said “is inductive to healing and growth of ligament tissue.”

The brace is intended for an “overhead” athlete (mostly baseball players but also javelin throwers and gymnasts) whose UCL is torn on only one side but is otherwise in good shape. In a pitcher the same age as Mr. John was when Dr. Jobe performed the first procedure, “that ligament may not be of very good quality,” Dr. McCulloch said. “It may have thickened. It may have calcifications.” But for a high-school junior with aspirations to pitch in college or beyond without “way too many miles on the elbow,” the approach is a good fit. The healing process is as little as 6 months.

“The ones who have a good ligament are very likely to do well,” said Dr. Erickson, an assistant team doctor for the Philadelphia Phillies.

“If the patient’s ligament is generally ‘good’ with only a tear, the InternalBrace procedure may be used to repair the native ligament. On the other end of the spectrum, if the patient’s ligament is torn and degenerative the surgeon may opt to do a UCL reconstruction using an auto or allograft — ie, Tommy John surgery,” Allen Holowecky, senior product manager of Arthrex of Naples, Florida, the maker of the InternalBrace, told this news organization. “Before UCL repair, Tommy John surgery was the only real treatment option. We tend to see repairs done on younger patients since their ligament hasn’t seen years of use-damage.”
 

Calls for Caution

Tommy John III wanted to play baseball like his dad until near-fatal complications from shoulder surgery altered his path. He was drawn to chiropractic and consults on injury prevention. “All surgeries and all medical interventions are cut first, ask questions later,” he said. “I was born with that.”

He saw his dad’s slow, heroic comeback from the surgery and described him as the perfect candidate for Dr. Jobe’s experiment. Tommy John spent his recovery time squeezing Silly Putty and throwing tennis balls. “He was willing to do anything necessary. He wanted to throw. That was his brush.” When the son was recovering from his own injury, “he said, ‘Learn the knuckleball.’ I said, ‘I don’t want to. I’ve reached my point.’ ”

He said he tells young patients with UCL injuries to rest. But instead “we have year-round sports with the promise that the more you play, the better,” he said. “They’re over-activitied.”

According to the American Academy of Orthopaedic Surgeons, 6.4 million children and adolescents in the United States played organized baseball in 2022, down from 11.5 million in 2014. Nearly half of pitchers played in a league with no maximum pitch counts, and 43.5% pitched on consecutive days, the group said.

How many UCL repair or reconstruction surgeries are performed on youth athletes each year is unclear. A 2019 study, however, found that although baseball injuries decreased between 2006 and 2016, the elbow was “the only location of injury that saw an increase.”

Dr. Garrigues said some parents of throwing athletes have asked about prophylactic Tommy John surgery for their children. He said it shouldn’t apply to pitchers.

“People have taken it a little too far,” he said. Dr. Garrigues and others argue against children throwing weighted balls when coming back from surgery. Instead, “we’re shutting them down,” he said.

Throwing any pitch is an act of violence on the body, Dr. Garrigues said, with the elbow taking the final brunt of the force. “These pitchers are functioning at the absolute limits of what the human body can take,” he said. “There’s only so many bullets in a gun,” which is why pitchers often feel the twinge of a torn UCL on a routine pitch.

Dr. Makhni suggested cross-training for pitchers in the off-season instead of playing baseball year-round. “If you play soccer, your footwork is going to be better,” he said.

“Kids shouldn’t be doing this all year round,” said Rebecca Carl, MD, associate professor of pediatrics at Northwestern University Feinberg School of Medicine in Chicago. “We are recommending that kids take 2 or 3 months off.” In the off-season, she urges them to strengthen their backs and cores. 

Such advice can “feel like a bombshell,” said Dr. Carl, who chairs the Council on Sports Medicine and Fitness for the American Academy of Pediatrics. ‘Some started at a very young age. They go to camps. If I say to a teenager, ‘If you do this, I can keep you from getting injured,’ they think, ‘I won’t be injured.’” Most parents, however, understand the risk of “doing too much, too soon.”

Justin Orenduff, a former pitching prospect until his arm blew out, has made a career teaching head-to-toe pitching mechanics. He founded DVS Baseball, which uses software to teach pitchers how to properly use every muscle, starting with the orientation of the back foot. He, too, argues against pitching year-round. “Everyone on that travel team expects to get their fair share of playing time,” he said. “It just never stops.”

Organized baseball is paying attention. It has come up with the Pitch Smart program that gives maximum pitch counts for young players, but experts said children often get around that by belonging to several leagues.

Dr. Altchek said some surgeons have added platelet-rich plasma, stem cells, and bone marrow during surgery to quicken the slow healing time from UCL replacement. But he said, “it has to heal. Can you speed up biology?”

Dr. McCulloch said that, all the advances in Tommy John surgery aside, “the next frontier is really trying to crack the code on prevention.”

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

In 1974, Tommy John of the Los Angeles Dodgers was 31 and a 12-year veteran of Major League Baseball when he became the unwitting vanguard of a revolution in baseball and orthopedics. Fifty years later, Mr. John might not be a candidate for the latest advances to a procedure that bears his name.

The southpaw pitcher had faced the abrupt end of his career when, after one fateful delivery, he found himself unable to throw to home. So he took a gamble on the surgical equivalent of a Hail Mary: the reconstruction of a torn ligament in his pitching elbow.

The experiment was a wild success. Mr. John pitched— and better than he had before — for another 14 seasons, retiring in 1989 at the age of 46. How much better? After the surgery, he tallied three 20-win seasons compared with none before the operation, and he finished among the top five vote-getters for the annual Cy Young Award three times. He was named an All-Star once before the surgery and three times after.

The triumph notwithstanding, Tommy John now cautions against Tommy John surgery. What’s given him and clinicians pause is a trend in recent years of ever-younger athletes who undergo the procedure.

Along with the surgical improvements in repairing a torn ulnar collateral ligament (UCL) is a demographic shift toward school-aged athletes who get it. By 2014, one study concluded that 67.4% of UCL reconstruction surgeries were performed on athletes between 16 and 20 years of age. Some patients are still in Little League when they undergo the procedure.

Experts say these athletes have weakened their UCLs through overuse. They disagree on whether to call it an “epidemic,” but if it is, “the vaccine is awareness” against throwing too hard and too often, said Eric Makhni, MD, an orthopedic surgeon at Henry Ford Health in Detroit.
 

From Career-Ending to Routine

Mr. John’s entry into baseball and orthopedic lore was initially slow, but the trickle turned into a tide. After Frank Jobe, MD, swapped a healthy tendon from John’s right wrist for his worn and torn left UCL on September 25, 1974, he didn’t perform his second surgery for another 1194 days. By the time “Tommy John surgery” became a recognized phrase, Mr. John was still active but only 14 professional baseball players had undergone the operation.

Prior to the start of spring training this year, an oft-cited database listed 366 pro players who’d undergone the operation. 

“Before Tommy John, that was a career-ending injury,” said Grant E. Garrigues, MD, an orthopedic surgeon at Midwest Orthopaedics at RUSH in Chicago, who called Mr. John “a pure revolutionary.”

Tommy John surgery is “the only one that I can think of that is named after the patient rather than the doctor who first did it,” said Patrick McCulloch, MD, an orthopedic surgeon in Houston and a team physician for the Astros.

Dr. McCulloch, who performs about 25 UCL repairs a year, said that by recent estimates, one-third of pro pitchers had had some sort of surgical repair. He hesitated to call the increasing number of operations an epidemic but acknowledged that the ingredients exist for more elbow trauma among baseball players.

“More people are playing more often, and people are bigger and stronger and throwing harder,” he said.

Either way, Dr. McCulloch said, “the procedure is a victim of its own success” because it is “just done phenomenally well.”

The surgery is now commonplace — perhaps too commonplace, said David W. Altchek, MD, attending surgeon and co-chief emeritus at Hospital for Special Surgery in New York City.

Dr. Altchek played a key role in the popularity of the operation. Twenty-two years after Mr. John’s surgery, he helped develop a variation of the procedure called the docking technique. 

Whereas Dr. Jobe sutured Mr. John’s replacement graft to itself, “we developed a different way of tying it over a bone bridge, which was more secure and more easy to tension,” Dr. Altchek explained.

The advance meant less drilling into bone and enabled surgeons to avoid moving a problem-free ulnar nerve or removing the flexor-pronator muscle that protects the elbow from stress. “The trauma of the surgery is significantly less,” he said. “We just made it a lot easier very quickly,” cutting the surgery time from 2 hours to 30-40 minutes.

Maybe the surgery became too easy, said Dr. Altchek, who estimates he has done 2000 of them over the past 30 years. “I don’t want to condemn my colleagues, but there are a lot of people doing the surgery,” he said. “And not a lot of people are doing a lot of them, and they don’t know the nuances of doing the surgery.”

The older procedures are known as the “full Tommy John”; each has a 12- to 18-month healing process, with a success rate of 80%-85%. Pitchers typically sit out a season while recovering.

Brandon Erickson, MD, an orthopedic surgeon at Rothman Orthopaedic Institute in New York City, said that in younger patients he has recently turned more often to the suture of the future: an internal brace that provides a repair rather than reconstruction.

The procedure, pioneered by Felix H. Savoie III, MD, the Ray J. Haddad Professor of Orthopaedics at Tulane University School of Medicine in New Orleans, and Jeffrey R. Dugas, MD, of Andrews Sports Medicine & Orthopaedic Center in Birmingham, Alabama, uses collagen-coated tape that looks like a shoelace and provides a scaffold that Dr. McCulloch said “is inductive to healing and growth of ligament tissue.”

The brace is intended for an “overhead” athlete (mostly baseball players but also javelin throwers and gymnasts) whose UCL is torn on only one side but is otherwise in good shape. In a pitcher the same age as Mr. John was when Dr. Jobe performed the first procedure, “that ligament may not be of very good quality,” Dr. McCulloch said. “It may have thickened. It may have calcifications.” But for a high-school junior with aspirations to pitch in college or beyond without “way too many miles on the elbow,” the approach is a good fit. The healing process is as little as 6 months.

“The ones who have a good ligament are very likely to do well,” said Dr. Erickson, an assistant team doctor for the Philadelphia Phillies.

“If the patient’s ligament is generally ‘good’ with only a tear, the InternalBrace procedure may be used to repair the native ligament. On the other end of the spectrum, if the patient’s ligament is torn and degenerative the surgeon may opt to do a UCL reconstruction using an auto or allograft — ie, Tommy John surgery,” Allen Holowecky, senior product manager of Arthrex of Naples, Florida, the maker of the InternalBrace, told this news organization. “Before UCL repair, Tommy John surgery was the only real treatment option. We tend to see repairs done on younger patients since their ligament hasn’t seen years of use-damage.”
 

Calls for Caution

Tommy John III wanted to play baseball like his dad until near-fatal complications from shoulder surgery altered his path. He was drawn to chiropractic and consults on injury prevention. “All surgeries and all medical interventions are cut first, ask questions later,” he said. “I was born with that.”

He saw his dad’s slow, heroic comeback from the surgery and described him as the perfect candidate for Dr. Jobe’s experiment. Tommy John spent his recovery time squeezing Silly Putty and throwing tennis balls. “He was willing to do anything necessary. He wanted to throw. That was his brush.” When the son was recovering from his own injury, “he said, ‘Learn the knuckleball.’ I said, ‘I don’t want to. I’ve reached my point.’ ”

He said he tells young patients with UCL injuries to rest. But instead “we have year-round sports with the promise that the more you play, the better,” he said. “They’re over-activitied.”

According to the American Academy of Orthopaedic Surgeons, 6.4 million children and adolescents in the United States played organized baseball in 2022, down from 11.5 million in 2014. Nearly half of pitchers played in a league with no maximum pitch counts, and 43.5% pitched on consecutive days, the group said.

How many UCL repair or reconstruction surgeries are performed on youth athletes each year is unclear. A 2019 study, however, found that although baseball injuries decreased between 2006 and 2016, the elbow was “the only location of injury that saw an increase.”

Dr. Garrigues said some parents of throwing athletes have asked about prophylactic Tommy John surgery for their children. He said it shouldn’t apply to pitchers.

“People have taken it a little too far,” he said. Dr. Garrigues and others argue against children throwing weighted balls when coming back from surgery. Instead, “we’re shutting them down,” he said.

Throwing any pitch is an act of violence on the body, Dr. Garrigues said, with the elbow taking the final brunt of the force. “These pitchers are functioning at the absolute limits of what the human body can take,” he said. “There’s only so many bullets in a gun,” which is why pitchers often feel the twinge of a torn UCL on a routine pitch.

Dr. Makhni suggested cross-training for pitchers in the off-season instead of playing baseball year-round. “If you play soccer, your footwork is going to be better,” he said.

“Kids shouldn’t be doing this all year round,” said Rebecca Carl, MD, associate professor of pediatrics at Northwestern University Feinberg School of Medicine in Chicago. “We are recommending that kids take 2 or 3 months off.” In the off-season, she urges them to strengthen their backs and cores. 

Such advice can “feel like a bombshell,” said Dr. Carl, who chairs the Council on Sports Medicine and Fitness for the American Academy of Pediatrics. ‘Some started at a very young age. They go to camps. If I say to a teenager, ‘If you do this, I can keep you from getting injured,’ they think, ‘I won’t be injured.’” Most parents, however, understand the risk of “doing too much, too soon.”

Justin Orenduff, a former pitching prospect until his arm blew out, has made a career teaching head-to-toe pitching mechanics. He founded DVS Baseball, which uses software to teach pitchers how to properly use every muscle, starting with the orientation of the back foot. He, too, argues against pitching year-round. “Everyone on that travel team expects to get their fair share of playing time,” he said. “It just never stops.”

Organized baseball is paying attention. It has come up with the Pitch Smart program that gives maximum pitch counts for young players, but experts said children often get around that by belonging to several leagues.

Dr. Altchek said some surgeons have added platelet-rich plasma, stem cells, and bone marrow during surgery to quicken the slow healing time from UCL replacement. But he said, “it has to heal. Can you speed up biology?”

Dr. McCulloch said that, all the advances in Tommy John surgery aside, “the next frontier is really trying to crack the code on prevention.”

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

In 1974, Tommy John of the Los Angeles Dodgers was 31 and a 12-year veteran of Major League Baseball when he became the unwitting vanguard of a revolution in baseball and orthopedics. Fifty years later, Mr. John might not be a candidate for the latest advances to a procedure that bears his name.

The southpaw pitcher had faced the abrupt end of his career when, after one fateful delivery, he found himself unable to throw to home. So he took a gamble on the surgical equivalent of a Hail Mary: the reconstruction of a torn ligament in his pitching elbow.

The experiment was a wild success. Mr. John pitched— and better than he had before — for another 14 seasons, retiring in 1989 at the age of 46. How much better? After the surgery, he tallied three 20-win seasons compared with none before the operation, and he finished among the top five vote-getters for the annual Cy Young Award three times. He was named an All-Star once before the surgery and three times after.

The triumph notwithstanding, Tommy John now cautions against Tommy John surgery. What’s given him and clinicians pause is a trend in recent years of ever-younger athletes who undergo the procedure.

Along with the surgical improvements in repairing a torn ulnar collateral ligament (UCL) is a demographic shift toward school-aged athletes who get it. By 2014, one study concluded that 67.4% of UCL reconstruction surgeries were performed on athletes between 16 and 20 years of age. Some patients are still in Little League when they undergo the procedure.

Experts say these athletes have weakened their UCLs through overuse. They disagree on whether to call it an “epidemic,” but if it is, “the vaccine is awareness” against throwing too hard and too often, said Eric Makhni, MD, an orthopedic surgeon at Henry Ford Health in Detroit.
 

From Career-Ending to Routine

Mr. John’s entry into baseball and orthopedic lore was initially slow, but the trickle turned into a tide. After Frank Jobe, MD, swapped a healthy tendon from John’s right wrist for his worn and torn left UCL on September 25, 1974, he didn’t perform his second surgery for another 1194 days. By the time “Tommy John surgery” became a recognized phrase, Mr. John was still active but only 14 professional baseball players had undergone the operation.

Prior to the start of spring training this year, an oft-cited database listed 366 pro players who’d undergone the operation. 

“Before Tommy John, that was a career-ending injury,” said Grant E. Garrigues, MD, an orthopedic surgeon at Midwest Orthopaedics at RUSH in Chicago, who called Mr. John “a pure revolutionary.”

Tommy John surgery is “the only one that I can think of that is named after the patient rather than the doctor who first did it,” said Patrick McCulloch, MD, an orthopedic surgeon in Houston and a team physician for the Astros.

Dr. McCulloch, who performs about 25 UCL repairs a year, said that by recent estimates, one-third of pro pitchers had had some sort of surgical repair. He hesitated to call the increasing number of operations an epidemic but acknowledged that the ingredients exist for more elbow trauma among baseball players.

“More people are playing more often, and people are bigger and stronger and throwing harder,” he said.

Either way, Dr. McCulloch said, “the procedure is a victim of its own success” because it is “just done phenomenally well.”

The surgery is now commonplace — perhaps too commonplace, said David W. Altchek, MD, attending surgeon and co-chief emeritus at Hospital for Special Surgery in New York City.

Dr. Altchek played a key role in the popularity of the operation. Twenty-two years after Mr. John’s surgery, he helped develop a variation of the procedure called the docking technique. 

Whereas Dr. Jobe sutured Mr. John’s replacement graft to itself, “we developed a different way of tying it over a bone bridge, which was more secure and more easy to tension,” Dr. Altchek explained.

The advance meant less drilling into bone and enabled surgeons to avoid moving a problem-free ulnar nerve or removing the flexor-pronator muscle that protects the elbow from stress. “The trauma of the surgery is significantly less,” he said. “We just made it a lot easier very quickly,” cutting the surgery time from 2 hours to 30-40 minutes.

Maybe the surgery became too easy, said Dr. Altchek, who estimates he has done 2000 of them over the past 30 years. “I don’t want to condemn my colleagues, but there are a lot of people doing the surgery,” he said. “And not a lot of people are doing a lot of them, and they don’t know the nuances of doing the surgery.”

The older procedures are known as the “full Tommy John”; each has a 12- to 18-month healing process, with a success rate of 80%-85%. Pitchers typically sit out a season while recovering.

Brandon Erickson, MD, an orthopedic surgeon at Rothman Orthopaedic Institute in New York City, said that in younger patients he has recently turned more often to the suture of the future: an internal brace that provides a repair rather than reconstruction.

The procedure, pioneered by Felix H. Savoie III, MD, the Ray J. Haddad Professor of Orthopaedics at Tulane University School of Medicine in New Orleans, and Jeffrey R. Dugas, MD, of Andrews Sports Medicine & Orthopaedic Center in Birmingham, Alabama, uses collagen-coated tape that looks like a shoelace and provides a scaffold that Dr. McCulloch said “is inductive to healing and growth of ligament tissue.”

The brace is intended for an “overhead” athlete (mostly baseball players but also javelin throwers and gymnasts) whose UCL is torn on only one side but is otherwise in good shape. In a pitcher the same age as Mr. John was when Dr. Jobe performed the first procedure, “that ligament may not be of very good quality,” Dr. McCulloch said. “It may have thickened. It may have calcifications.” But for a high-school junior with aspirations to pitch in college or beyond without “way too many miles on the elbow,” the approach is a good fit. The healing process is as little as 6 months.

“The ones who have a good ligament are very likely to do well,” said Dr. Erickson, an assistant team doctor for the Philadelphia Phillies.

“If the patient’s ligament is generally ‘good’ with only a tear, the InternalBrace procedure may be used to repair the native ligament. On the other end of the spectrum, if the patient’s ligament is torn and degenerative the surgeon may opt to do a UCL reconstruction using an auto or allograft — ie, Tommy John surgery,” Allen Holowecky, senior product manager of Arthrex of Naples, Florida, the maker of the InternalBrace, told this news organization. “Before UCL repair, Tommy John surgery was the only real treatment option. We tend to see repairs done on younger patients since their ligament hasn’t seen years of use-damage.”
 

Calls for Caution

Tommy John III wanted to play baseball like his dad until near-fatal complications from shoulder surgery altered his path. He was drawn to chiropractic and consults on injury prevention. “All surgeries and all medical interventions are cut first, ask questions later,” he said. “I was born with that.”

He saw his dad’s slow, heroic comeback from the surgery and described him as the perfect candidate for Dr. Jobe’s experiment. Tommy John spent his recovery time squeezing Silly Putty and throwing tennis balls. “He was willing to do anything necessary. He wanted to throw. That was his brush.” When the son was recovering from his own injury, “he said, ‘Learn the knuckleball.’ I said, ‘I don’t want to. I’ve reached my point.’ ”

He said he tells young patients with UCL injuries to rest. But instead “we have year-round sports with the promise that the more you play, the better,” he said. “They’re over-activitied.”

According to the American Academy of Orthopaedic Surgeons, 6.4 million children and adolescents in the United States played organized baseball in 2022, down from 11.5 million in 2014. Nearly half of pitchers played in a league with no maximum pitch counts, and 43.5% pitched on consecutive days, the group said.

How many UCL repair or reconstruction surgeries are performed on youth athletes each year is unclear. A 2019 study, however, found that although baseball injuries decreased between 2006 and 2016, the elbow was “the only location of injury that saw an increase.”

Dr. Garrigues said some parents of throwing athletes have asked about prophylactic Tommy John surgery for their children. He said it shouldn’t apply to pitchers.

“People have taken it a little too far,” he said. Dr. Garrigues and others argue against children throwing weighted balls when coming back from surgery. Instead, “we’re shutting them down,” he said.

Throwing any pitch is an act of violence on the body, Dr. Garrigues said, with the elbow taking the final brunt of the force. “These pitchers are functioning at the absolute limits of what the human body can take,” he said. “There’s only so many bullets in a gun,” which is why pitchers often feel the twinge of a torn UCL on a routine pitch.

Dr. Makhni suggested cross-training for pitchers in the off-season instead of playing baseball year-round. “If you play soccer, your footwork is going to be better,” he said.

“Kids shouldn’t be doing this all year round,” said Rebecca Carl, MD, associate professor of pediatrics at Northwestern University Feinberg School of Medicine in Chicago. “We are recommending that kids take 2 or 3 months off.” In the off-season, she urges them to strengthen their backs and cores. 

Such advice can “feel like a bombshell,” said Dr. Carl, who chairs the Council on Sports Medicine and Fitness for the American Academy of Pediatrics. ‘Some started at a very young age. They go to camps. If I say to a teenager, ‘If you do this, I can keep you from getting injured,’ they think, ‘I won’t be injured.’” Most parents, however, understand the risk of “doing too much, too soon.”

Justin Orenduff, a former pitching prospect until his arm blew out, has made a career teaching head-to-toe pitching mechanics. He founded DVS Baseball, which uses software to teach pitchers how to properly use every muscle, starting with the orientation of the back foot. He, too, argues against pitching year-round. “Everyone on that travel team expects to get their fair share of playing time,” he said. “It just never stops.”

Organized baseball is paying attention. It has come up with the Pitch Smart program that gives maximum pitch counts for young players, but experts said children often get around that by belonging to several leagues.

Dr. Altchek said some surgeons have added platelet-rich plasma, stem cells, and bone marrow during surgery to quicken the slow healing time from UCL replacement. But he said, “it has to heal. Can you speed up biology?”

Dr. McCulloch said that, all the advances in Tommy John surgery aside, “the next frontier is really trying to crack the code on prevention.”

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

Electronic health records (EHRs) make providing coordinated, efficient care easier and reduce medical errors and test duplications; research has also correlated EHR adoption with higher patient satisfaction and outcomes. However, for physicians, the benefits come at a cost.

Physicians spend significantly more time in healthcare portals, making notes, entering orders, reviewing clinical reports, and responding to patient messages.

“I spend at least the same amount of time in the portal that I do in scheduled clinical time with patients,” said Eve Rittenberg, MD, primary care physician at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, Boston. “So, if I have a 4-hour session of seeing patients, I spend at least another 4 or more hours in the patient portal.”

The latest data showed that primary care physicians logged a median of 36.2 minutes in the healthcare portal per patient visit, spending 58.9% more time on orders, 24.4% more time reading and responding to messages, and 13% more time on chart review compared with prepandemic portal use.

“EHRs can be very powerful tools,” said Ralph DeBiasi, MD, a clinical cardiac electrophysiologist at Yale New Haven Health in Connecticut. “We’re still working on how to best harness that power to make us better doctors and better care teams and to take better care of our patients because their use can take up a lot of time.”
 

Portal Time Isn’t Paid Time

Sharp increases in the amount of time spent in the EHR responding to messages or dispensing medical advice via the portal often aren’t linked to increases in compensation; most portal time is unpaid.

“There isn’t specific time allocated to working in the portal; it’s either done in the office while a patient is sitting in an exam room or in the mornings and evenings outside of traditional working hours,” Dr. DeBiasi told this news organization. “I think it’s reasonable to consider it being reimbursed because we’re taking our time and effort and making decisions to help the patient.”

Compensation for portal time affects all physicians, but the degree of impact depends on their specialties. Primary care physicians spent significantly more daily and after-hours time in the EHR, entering notes and orders, and doing clinical reviews compared to surgical and medical specialties.

In addition to the outsized impact on primary care, physician compensation for portal time is also an equity issue.

Dr. Rittenberg researched the issue and found a higher volume of communication from both patients and staff to female physicians than male physicians. As a result, female physicians spend 41.4 minutes more on the EHR than their male counterparts, which equates to more unpaid time. It’s likely no coincidence then that burnout rates are also higher among female physicians, who also leave the clinical workforce in higher numbers, especially in primary care.

“Finding ways to fairly compensate physicians for their work also will address some of the equity issues in workload and the consequences,” Dr. Rittenberg said.
 

Addressing the Issue

Some health systems have started charging patients who seek medical advice via patient portals, equating the communication to asynchronous acute care or an additional care touch point and billing based on the length and complexity of the messages. Patient fees for seeking medical advice via portals vary widely depending on their health system and insurance.

At University of California San Francisco Health, billing patients for EHR communication led to a sharp decrease in patient messages, which eased physician workload. At Cleveland Clinic, physicians receive “productivity credits” for the time spent in the EHR that can be used to reduce their clinic hours (but have no impact on their compensation).

Changes to the Medicare Physician Fee Schedule also allow physicians to bill for “digital evaluation and management” based on the time spent in an EHR responding to patient-initiated questions and requests.

However, more efforts are needed to ease burnout and reverse the number of physicians who are seeing fewer patients or leaving medical practice altogether as a direct result of spending increasing amounts of unpaid time in the EHR. Dr. Rittenberg, who spends an estimated 50% of her working hours in the portal, had to reduce her clinical workload by 25% due to such heavy portal requirements.

“The workload has become unsustainable,” she said. “The work has undergone a dramatic change over the past decade, and the compensation system has not kept up with that change.”
 

Prioritizing Patient and Physician Experiences

The ever-expanding use of EHRs is a result of their value as a healthcare tool. Data showed that the electronic exchange of information between patients and physicians improves diagnostics, reduces medical errors, enhances communication, and leads to more patient-centered care — and physicians want their patients to use the portal to maximize their healthcare.

“[The EHR] is good for patients,” said Dr. DeBiasi. “Sometimes, patients have access issues with healthcare, whether that’s not knowing what number to call or getting the right message to the right person at the right office. If [the portal] is good for them and helps them get access to care, we should embrace that and figure out a way to work it into our day-to-day schedules.”

But maximizing the patient experience shouldn’t come at the physicians’ expense. Dr. Rittenberg advocates a model that compensates physicians for the time spent in the EHR and prioritizes a team approach to rebalance the EHR workload to ensure that physicians aren’t devoting too much time to administrative tasks and can, instead, focus their time on clinical tasks.

“The way in which we provide healthcare has fundamentally shifted, and compensation models need to reflect that new reality,” Dr. Rittenberg added.

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

Electronic health records (EHRs) make providing coordinated, efficient care easier and reduce medical errors and test duplications; research has also correlated EHR adoption with higher patient satisfaction and outcomes. However, for physicians, the benefits come at a cost.

Physicians spend significantly more time in healthcare portals, making notes, entering orders, reviewing clinical reports, and responding to patient messages.

“I spend at least the same amount of time in the portal that I do in scheduled clinical time with patients,” said Eve Rittenberg, MD, primary care physician at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, Boston. “So, if I have a 4-hour session of seeing patients, I spend at least another 4 or more hours in the patient portal.”

The latest data showed that primary care physicians logged a median of 36.2 minutes in the healthcare portal per patient visit, spending 58.9% more time on orders, 24.4% more time reading and responding to messages, and 13% more time on chart review compared with prepandemic portal use.

“EHRs can be very powerful tools,” said Ralph DeBiasi, MD, a clinical cardiac electrophysiologist at Yale New Haven Health in Connecticut. “We’re still working on how to best harness that power to make us better doctors and better care teams and to take better care of our patients because their use can take up a lot of time.”
 

Portal Time Isn’t Paid Time

Sharp increases in the amount of time spent in the EHR responding to messages or dispensing medical advice via the portal often aren’t linked to increases in compensation; most portal time is unpaid.

“There isn’t specific time allocated to working in the portal; it’s either done in the office while a patient is sitting in an exam room or in the mornings and evenings outside of traditional working hours,” Dr. DeBiasi told this news organization. “I think it’s reasonable to consider it being reimbursed because we’re taking our time and effort and making decisions to help the patient.”

Compensation for portal time affects all physicians, but the degree of impact depends on their specialties. Primary care physicians spent significantly more daily and after-hours time in the EHR, entering notes and orders, and doing clinical reviews compared to surgical and medical specialties.

In addition to the outsized impact on primary care, physician compensation for portal time is also an equity issue.

Dr. Rittenberg researched the issue and found a higher volume of communication from both patients and staff to female physicians than male physicians. As a result, female physicians spend 41.4 minutes more on the EHR than their male counterparts, which equates to more unpaid time. It’s likely no coincidence then that burnout rates are also higher among female physicians, who also leave the clinical workforce in higher numbers, especially in primary care.

“Finding ways to fairly compensate physicians for their work also will address some of the equity issues in workload and the consequences,” Dr. Rittenberg said.
 

Addressing the Issue

Some health systems have started charging patients who seek medical advice via patient portals, equating the communication to asynchronous acute care or an additional care touch point and billing based on the length and complexity of the messages. Patient fees for seeking medical advice via portals vary widely depending on their health system and insurance.

At University of California San Francisco Health, billing patients for EHR communication led to a sharp decrease in patient messages, which eased physician workload. At Cleveland Clinic, physicians receive “productivity credits” for the time spent in the EHR that can be used to reduce their clinic hours (but have no impact on their compensation).

Changes to the Medicare Physician Fee Schedule also allow physicians to bill for “digital evaluation and management” based on the time spent in an EHR responding to patient-initiated questions and requests.

However, more efforts are needed to ease burnout and reverse the number of physicians who are seeing fewer patients or leaving medical practice altogether as a direct result of spending increasing amounts of unpaid time in the EHR. Dr. Rittenberg, who spends an estimated 50% of her working hours in the portal, had to reduce her clinical workload by 25% due to such heavy portal requirements.

“The workload has become unsustainable,” she said. “The work has undergone a dramatic change over the past decade, and the compensation system has not kept up with that change.”
 

Prioritizing Patient and Physician Experiences

The ever-expanding use of EHRs is a result of their value as a healthcare tool. Data showed that the electronic exchange of information between patients and physicians improves diagnostics, reduces medical errors, enhances communication, and leads to more patient-centered care — and physicians want their patients to use the portal to maximize their healthcare.

“[The EHR] is good for patients,” said Dr. DeBiasi. “Sometimes, patients have access issues with healthcare, whether that’s not knowing what number to call or getting the right message to the right person at the right office. If [the portal] is good for them and helps them get access to care, we should embrace that and figure out a way to work it into our day-to-day schedules.”

But maximizing the patient experience shouldn’t come at the physicians’ expense. Dr. Rittenberg advocates a model that compensates physicians for the time spent in the EHR and prioritizes a team approach to rebalance the EHR workload to ensure that physicians aren’t devoting too much time to administrative tasks and can, instead, focus their time on clinical tasks.

“The way in which we provide healthcare has fundamentally shifted, and compensation models need to reflect that new reality,” Dr. Rittenberg added.

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

Electronic health records (EHRs) make providing coordinated, efficient care easier and reduce medical errors and test duplications; research has also correlated EHR adoption with higher patient satisfaction and outcomes. However, for physicians, the benefits come at a cost.

Physicians spend significantly more time in healthcare portals, making notes, entering orders, reviewing clinical reports, and responding to patient messages.

“I spend at least the same amount of time in the portal that I do in scheduled clinical time with patients,” said Eve Rittenberg, MD, primary care physician at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, Boston. “So, if I have a 4-hour session of seeing patients, I spend at least another 4 or more hours in the patient portal.”

The latest data showed that primary care physicians logged a median of 36.2 minutes in the healthcare portal per patient visit, spending 58.9% more time on orders, 24.4% more time reading and responding to messages, and 13% more time on chart review compared with prepandemic portal use.

“EHRs can be very powerful tools,” said Ralph DeBiasi, MD, a clinical cardiac electrophysiologist at Yale New Haven Health in Connecticut. “We’re still working on how to best harness that power to make us better doctors and better care teams and to take better care of our patients because their use can take up a lot of time.”
 

Portal Time Isn’t Paid Time

Sharp increases in the amount of time spent in the EHR responding to messages or dispensing medical advice via the portal often aren’t linked to increases in compensation; most portal time is unpaid.

“There isn’t specific time allocated to working in the portal; it’s either done in the office while a patient is sitting in an exam room or in the mornings and evenings outside of traditional working hours,” Dr. DeBiasi told this news organization. “I think it’s reasonable to consider it being reimbursed because we’re taking our time and effort and making decisions to help the patient.”

Compensation for portal time affects all physicians, but the degree of impact depends on their specialties. Primary care physicians spent significantly more daily and after-hours time in the EHR, entering notes and orders, and doing clinical reviews compared to surgical and medical specialties.

In addition to the outsized impact on primary care, physician compensation for portal time is also an equity issue.

Dr. Rittenberg researched the issue and found a higher volume of communication from both patients and staff to female physicians than male physicians. As a result, female physicians spend 41.4 minutes more on the EHR than their male counterparts, which equates to more unpaid time. It’s likely no coincidence then that burnout rates are also higher among female physicians, who also leave the clinical workforce in higher numbers, especially in primary care.

“Finding ways to fairly compensate physicians for their work also will address some of the equity issues in workload and the consequences,” Dr. Rittenberg said.
 

Addressing the Issue

Some health systems have started charging patients who seek medical advice via patient portals, equating the communication to asynchronous acute care or an additional care touch point and billing based on the length and complexity of the messages. Patient fees for seeking medical advice via portals vary widely depending on their health system and insurance.

At University of California San Francisco Health, billing patients for EHR communication led to a sharp decrease in patient messages, which eased physician workload. At Cleveland Clinic, physicians receive “productivity credits” for the time spent in the EHR that can be used to reduce their clinic hours (but have no impact on their compensation).

Changes to the Medicare Physician Fee Schedule also allow physicians to bill for “digital evaluation and management” based on the time spent in an EHR responding to patient-initiated questions and requests.

However, more efforts are needed to ease burnout and reverse the number of physicians who are seeing fewer patients or leaving medical practice altogether as a direct result of spending increasing amounts of unpaid time in the EHR. Dr. Rittenberg, who spends an estimated 50% of her working hours in the portal, had to reduce her clinical workload by 25% due to such heavy portal requirements.

“The workload has become unsustainable,” she said. “The work has undergone a dramatic change over the past decade, and the compensation system has not kept up with that change.”
 

Prioritizing Patient and Physician Experiences

The ever-expanding use of EHRs is a result of their value as a healthcare tool. Data showed that the electronic exchange of information between patients and physicians improves diagnostics, reduces medical errors, enhances communication, and leads to more patient-centered care — and physicians want their patients to use the portal to maximize their healthcare.

“[The EHR] is good for patients,” said Dr. DeBiasi. “Sometimes, patients have access issues with healthcare, whether that’s not knowing what number to call or getting the right message to the right person at the right office. If [the portal] is good for them and helps them get access to care, we should embrace that and figure out a way to work it into our day-to-day schedules.”

But maximizing the patient experience shouldn’t come at the physicians’ expense. Dr. Rittenberg advocates a model that compensates physicians for the time spent in the EHR and prioritizes a team approach to rebalance the EHR workload to ensure that physicians aren’t devoting too much time to administrative tasks and can, instead, focus their time on clinical tasks.

“The way in which we provide healthcare has fundamentally shifted, and compensation models need to reflect that new reality,” Dr. Rittenberg added.

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

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.

Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.

Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.

Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.

“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.

He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.

In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.

Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.

Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).

The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.

The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.

“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
 

Common Complaints and Causes

In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.

“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.

Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.

Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”

Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.

“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.

The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
 

Taking Sex Seriously

Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.

Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).

“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.

Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.

In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.

Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).

A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.

“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.

Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.

Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.

“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
 

Barriers and Solutions

Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.

Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.

“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.

Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.

Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.

Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.

Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.

Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.

For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.

Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.

Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.

“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.

Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.

Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.

Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.

Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.

“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.

He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.

In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.

Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.

Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).

The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.

The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.

“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
 

Common Complaints and Causes

In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.

“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.

Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.

Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”

Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.

“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.

The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
 

Taking Sex Seriously

Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.

Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).

“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.

Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.

In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.

Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).

A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.

“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.

Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.

Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.

“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
 

Barriers and Solutions

Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.

Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.

“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.

Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.

Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.

Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.

Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.

Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.

For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.

Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.

Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.

“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.

Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.

Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.

Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.

Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.

“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.

He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.

In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.

Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.

Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).

The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.

The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.

“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
 

Common Complaints and Causes

In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.

“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.

Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.

Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”

Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.

“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.

The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
 

Taking Sex Seriously

Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.

Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).

“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.

Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.

In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.

Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).

A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.

“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.

Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.

Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.

“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
 

Barriers and Solutions

Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.

Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.

“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.

Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.

Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.

Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.

Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.

Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.

For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.

Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.

Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.

“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.

Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.

In most Western countries, professional standards dictate that physicians should practice medicine with compassion. Patients also expect compassionate care from physicians because it represents a model capable of providing greater patient satisfaction, fostering better doctor-patient relationships, and enabling better psychological states among patients.

The etymology of the term “compassion” derives from the Latin roots “com,” meaning “together with,” and “pati,” meaning “to endure or suffer.” When discussing compassion, it is necessary to distinguish it from empathy, a term generally used to refer to cognitive or emotional processes in which the perspective of the other (in this case, the patient) is taken. Compassion implies or requires empathy and includes the desire to help or alleviate the suffering of others. Compassion in the medical context is likely a specific instance of a more complex adaptive system that has evolved, not only among humans, to motivate recognition and assistance when others suffer.
 

Compassion Fatigue

Physicians’ compassion is expected by patients and the profession. It is fundamental for effective clinical practice. Although compassion is central to medical practice, most research related to the topic has focused on “compassion fatigue,” which is understood as a specific type of professional burnout, as if physicians had a limited reserve of compassion that dwindles or becomes exhausted with use or overuse. This is one aspect of a much more complex problem, in which compassion represents the endpoint of a dynamic process that encompasses the influences of the physician, the patient, the clinic, and the institution.

Compassion Capacity: Conditioning Factors

Chronic exposure of physicians to conflicting work demands may be associated with the depletion of their psychological resources and, consequently, emotional and cognitive fatigue that can contribute to poorer work outcomes, including the ability to express compassion.

Rates of professional burnout in medicine are increasing. The driving factors of this phenomenon are largely rooted in organizations and healthcare systems and include excessive workloads, inefficient work processes, administrative burdens, and lack of input or control by physicians regarding issues concerning their work life. The outcome often is early retirement of physicians, a current, increasingly widespread phenomenon and a critical issue not only for the Italian National Health Service but also for other healthcare systems worldwide.
 

Organizational and Personal Values

There is no clear empirical evidence supporting the hypothesis that working in healthcare environments experienced as discrepant with one’s own values has negative effects on key professional outcomes. However, a study published in the Journal of Internal Medicine highlighted the overall negative effect of misalignment between system values and physicians’ personal values, including impaired ability to provide compassionate care, as well as reduced job satisfaction, burnout, absenteeism, and considering the possibility of early retirement. Results from 1000 surveyed professionals indicate that physicians’ subjective competence in providing compassionate care may remain high, but their ability to express it is compromised. From data analysis, the authors hypothesize that when working in environments with discrepant values, occupational contingencies may repeatedly require physicians to set aside their personal values, which can lead them to refrain from using available skills to keep their performance in line with organizational requirements.

These results and hypotheses are not consistent with the notion of compassion fatigue as a reflection of the cost of care resulting from exposure to repeated suffering. Previous evidence shows that expressing compassion in healthcare facilitates greater understanding, suggesting that providing compassion does not impoverish physicians but rather supports them in the effectiveness of interventions and in their satisfaction.

In summary, this study suggests that what prevents compassion is the inability to provide it when hindered by factors related to the situation in which the physician operates. Improving compassion does not simply depend on motivating individual professionals to be more compassionate or on promoting fundamental skills, but probably on the creation of organizational and clinical conditions in which physician compassion can thrive.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

In most Western countries, professional standards dictate that physicians should practice medicine with compassion. Patients also expect compassionate care from physicians because it represents a model capable of providing greater patient satisfaction, fostering better doctor-patient relationships, and enabling better psychological states among patients.

The etymology of the term “compassion” derives from the Latin roots “com,” meaning “together with,” and “pati,” meaning “to endure or suffer.” When discussing compassion, it is necessary to distinguish it from empathy, a term generally used to refer to cognitive or emotional processes in which the perspective of the other (in this case, the patient) is taken. Compassion implies or requires empathy and includes the desire to help or alleviate the suffering of others. Compassion in the medical context is likely a specific instance of a more complex adaptive system that has evolved, not only among humans, to motivate recognition and assistance when others suffer.
 

Compassion Fatigue

Physicians’ compassion is expected by patients and the profession. It is fundamental for effective clinical practice. Although compassion is central to medical practice, most research related to the topic has focused on “compassion fatigue,” which is understood as a specific type of professional burnout, as if physicians had a limited reserve of compassion that dwindles or becomes exhausted with use or overuse. This is one aspect of a much more complex problem, in which compassion represents the endpoint of a dynamic process that encompasses the influences of the physician, the patient, the clinic, and the institution.

Compassion Capacity: Conditioning Factors

Chronic exposure of physicians to conflicting work demands may be associated with the depletion of their psychological resources and, consequently, emotional and cognitive fatigue that can contribute to poorer work outcomes, including the ability to express compassion.

Rates of professional burnout in medicine are increasing. The driving factors of this phenomenon are largely rooted in organizations and healthcare systems and include excessive workloads, inefficient work processes, administrative burdens, and lack of input or control by physicians regarding issues concerning their work life. The outcome often is early retirement of physicians, a current, increasingly widespread phenomenon and a critical issue not only for the Italian National Health Service but also for other healthcare systems worldwide.
 

Organizational and Personal Values

There is no clear empirical evidence supporting the hypothesis that working in healthcare environments experienced as discrepant with one’s own values has negative effects on key professional outcomes. However, a study published in the Journal of Internal Medicine highlighted the overall negative effect of misalignment between system values and physicians’ personal values, including impaired ability to provide compassionate care, as well as reduced job satisfaction, burnout, absenteeism, and considering the possibility of early retirement. Results from 1000 surveyed professionals indicate that physicians’ subjective competence in providing compassionate care may remain high, but their ability to express it is compromised. From data analysis, the authors hypothesize that when working in environments with discrepant values, occupational contingencies may repeatedly require physicians to set aside their personal values, which can lead them to refrain from using available skills to keep their performance in line with organizational requirements.

These results and hypotheses are not consistent with the notion of compassion fatigue as a reflection of the cost of care resulting from exposure to repeated suffering. Previous evidence shows that expressing compassion in healthcare facilitates greater understanding, suggesting that providing compassion does not impoverish physicians but rather supports them in the effectiveness of interventions and in their satisfaction.

In summary, this study suggests that what prevents compassion is the inability to provide it when hindered by factors related to the situation in which the physician operates. Improving compassion does not simply depend on motivating individual professionals to be more compassionate or on promoting fundamental skills, but probably on the creation of organizational and clinical conditions in which physician compassion can thrive.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

In most Western countries, professional standards dictate that physicians should practice medicine with compassion. Patients also expect compassionate care from physicians because it represents a model capable of providing greater patient satisfaction, fostering better doctor-patient relationships, and enabling better psychological states among patients.

The etymology of the term “compassion” derives from the Latin roots “com,” meaning “together with,” and “pati,” meaning “to endure or suffer.” When discussing compassion, it is necessary to distinguish it from empathy, a term generally used to refer to cognitive or emotional processes in which the perspective of the other (in this case, the patient) is taken. Compassion implies or requires empathy and includes the desire to help or alleviate the suffering of others. Compassion in the medical context is likely a specific instance of a more complex adaptive system that has evolved, not only among humans, to motivate recognition and assistance when others suffer.
 

Compassion Fatigue

Physicians’ compassion is expected by patients and the profession. It is fundamental for effective clinical practice. Although compassion is central to medical practice, most research related to the topic has focused on “compassion fatigue,” which is understood as a specific type of professional burnout, as if physicians had a limited reserve of compassion that dwindles or becomes exhausted with use or overuse. This is one aspect of a much more complex problem, in which compassion represents the endpoint of a dynamic process that encompasses the influences of the physician, the patient, the clinic, and the institution.

Compassion Capacity: Conditioning Factors

Chronic exposure of physicians to conflicting work demands may be associated with the depletion of their psychological resources and, consequently, emotional and cognitive fatigue that can contribute to poorer work outcomes, including the ability to express compassion.

Rates of professional burnout in medicine are increasing. The driving factors of this phenomenon are largely rooted in organizations and healthcare systems and include excessive workloads, inefficient work processes, administrative burdens, and lack of input or control by physicians regarding issues concerning their work life. The outcome often is early retirement of physicians, a current, increasingly widespread phenomenon and a critical issue not only for the Italian National Health Service but also for other healthcare systems worldwide.
 

Organizational and Personal Values

There is no clear empirical evidence supporting the hypothesis that working in healthcare environments experienced as discrepant with one’s own values has negative effects on key professional outcomes. However, a study published in the Journal of Internal Medicine highlighted the overall negative effect of misalignment between system values and physicians’ personal values, including impaired ability to provide compassionate care, as well as reduced job satisfaction, burnout, absenteeism, and considering the possibility of early retirement. Results from 1000 surveyed professionals indicate that physicians’ subjective competence in providing compassionate care may remain high, but their ability to express it is compromised. From data analysis, the authors hypothesize that when working in environments with discrepant values, occupational contingencies may repeatedly require physicians to set aside their personal values, which can lead them to refrain from using available skills to keep their performance in line with organizational requirements.

These results and hypotheses are not consistent with the notion of compassion fatigue as a reflection of the cost of care resulting from exposure to repeated suffering. Previous evidence shows that expressing compassion in healthcare facilitates greater understanding, suggesting that providing compassion does not impoverish physicians but rather supports them in the effectiveness of interventions and in their satisfaction.

In summary, this study suggests that what prevents compassion is the inability to provide it when hindered by factors related to the situation in which the physician operates. Improving compassion does not simply depend on motivating individual professionals to be more compassionate or on promoting fundamental skills, but probably on the creation of organizational and clinical conditions in which physician compassion can thrive.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Amid rising concern about the potential long-term costs of using glucagon-like peptide 1 (GLP-1) agonists to treat obesity, some insurers are making access to bariatric surgery easier.

While the relationship may not be entirely causal, data do suggest that at least for now, these new agents for treating obesity including semaglutide (Wegovy) and tirzepatide (Zepbound) are not cost-effective, whereas the surgery is.

According to GoodRx, Wegovy (semaglutide) has a list price of about $1350 for a 28-day supply. And the American Society for Metabolic and Bariatric Surgery (ASMBS) said that the average cost of bariatric surgery ranges between $17,000 and $26,000. But ASMBS added that third-party payers will recover those costs within 2-4 years due to reduction or elimination of obesity-related conditions and associated treatment costs, with an approximate 29% healthcare cost reduction at 5 years.

Recently, for example, Geisinger Health of Pennsylvania and Blue Cross/Blue Shield of Massachusetts expanded body mass index (BMI) eligibility for bariatric surgery procedures, while Blue Cross Blue Shield of Michigan dropped prior authorization requirements for several services, including bariatric surgery.

While most major health insurers cover Wegovy for obesity treatment, they typically require prior authorization and/or trials of other therapies first. Recently, some employers have denied coverage for the medications for treating obesity. Medicare does not cover these drugs. Coverage varies across state Medicaid plans.

“For years, insurers…have played games with the surgery, making people jump through hoops, hoping that they would just give up and go away. And now that health plans are getting concerned about [the cost of] drugs for obesity, and they’re getting so much attention, they’re thinking oh, maybe we shouldn’t be playing these games anymore,” obesity policy expert Ted Kyle, RPh, founder of ConscienHealth, told this news organization.

However, Christopher Doubet Still, DO, director of Nutrition and Weight Management at Geisinger Medical Center, Danville, Pennsylvania, told this news organization that Geisinger Health Plan’s change in May 2023 to lower the BMI surgery eligibility cutoff from 35 kg/m2 to 30 kg/m2 for people with comorbidities was not related to the cost of GLP-1 drugs.

“To date, bariatric surgery remains the most effective, enduring treatment of obesity, and most importantly, its comorbid medical problems. So that was really the reasoning. The weight loss is secondary to the profound medical benefits of bariatric surgery. I think that was the impetus of that change, not having really anything to do at the time with GLP-1s,” Dr. Still said.

The Geisinger Health Plan does not currently cover antiobesity medications, although Geisinger Health Plan Family, a state Medicaid plan, does because Pennsylvania is now one of a handful of states that cover the medications through Medicaid.
 

The Equation Keeps Changing

Health economist James Chambers, PhD, of Tufts University, Boston, Massachusetts, told this news organizations, “when you think about the value of a treatment, you don’t look at it in isolation. You’re looking at the difference in cost and benefits. So now that you have these expensive drugs, it’s not that surgeries become less expensive, but it does make you interpret the cost differently. When diet and exercise and counseling were the only real options, surgeries seemed like a much more expensive intervention. But with the advent of the GLP-1s, then, maybe plans consider the costs of surgery a little bit differently.”

And that equation is likely to change further, Dr. Still noted.

“I just think we’re dealing with a short-term financial problem because there’s basically only two main medications so the prices are high, but as more medications come on the market, the prices will come down,” he said.

Cristy Ms. Gallagher, MPAff, research project director of the STOP Obesity Alliance at the Milken Institute School of Public Health at George Washington University, Washington, DC, agreed.

“We have a lot of data on obesity treatment coverage from before 2023. But then this [GLP-1] explosion happened in 2023…The health payers are out there trying to figure out coverage, and they’re trying to figure out what this is going to look like for them,” Ms. Gallagher said.

However, she pointed out, “there is no treatment that fits everyone. The GLP-1s won’t work for every person because of the different stages of obesity, the side effects, and then because of the coverage. I think that you will not see a decrease in bariatric surgery in the near term, by any means.”

Ms. Gallagher also noted that although the data now suggest people will have to keep taking the drugs for life, there may be other future approaches.

“Once a person hits their goal weight, maybe then they could be transferred to a different pill form that might be cheaper, something that’s sort of more of a maintenance drug. I think that is a huge unknown right now,” she said.

And Mr. Kyle said that while bariatric surgery does provide the most durable benefit, “weight regain after surgery is a fact of life. People are still healthier 5 years later, but they do have some weight regain. And in those cases, you might want to follow-up with medicines…It’s not necessarily an either/or proposition any more than surgical treatment of cancer, surgical oncology is an either/or with medical oncology.”
 

A New View of Obesity

According to Mr. Kyle, all this attention on the new medications “is prompting people to rethink or think differently about obesity and consider it more carefully as a chronic medical condition and not a condition of appearance and behavior. And that’s all good, whether you’re thinking about it from the standpoint of bariatric surgery or from the standpoint of medical treatment of obesity because then people start considering options more rationally.”

This shifting view of obesity has meant that bariatric surgeons and medical obesity specialists are starting to work more collaboratively, he said.

“There is a trend that I detect toward more integrated approaches to obesity,” Mr. Kyle said.

He added, “We now have more tools. And we’re in the messy middle of figuring out how, as a practical matter, to use them.”

And as far as insurance coverage, “people are going to make mistakes. They are making mistakes. But I have been the eternal optimist, and I have faith that people are also figuring it out. It would be hard to do worse.”

For now, any initiatives to increase bariatric surgery rates in the GLP-1 era haven’t yet had an impact, American Society for Metabolic and Bariatric Surgery President Marina S. Kurian, MD, told this news organization in a statement.

“While we have heard of some insurers possibly changing their requirements for bariatric surgery, we have not seen a significant rise in procedures related to changes in insurance coverage for either antiobesity medications or metabolic and bariatric surgery,” Dr. Kurian said.

Mr. Kyle had accepted speaking or professional fees from Novo Nordisk, Behringer Ingelheim, Nutrisystem, Roman Health, and Emerald Lake Safety. Dr. Still was on the speaker’s bureau and did clinical trials for Eli Lilly and Novo Nordisk. Dr. Chambers and Gallagher had no disclosures.

A version of this article appeared on Medscape.com.

Amid rising concern about the potential long-term costs of using glucagon-like peptide 1 (GLP-1) agonists to treat obesity, some insurers are making access to bariatric surgery easier.

While the relationship may not be entirely causal, data do suggest that at least for now, these new agents for treating obesity including semaglutide (Wegovy) and tirzepatide (Zepbound) are not cost-effective, whereas the surgery is.

According to GoodRx, Wegovy (semaglutide) has a list price of about $1350 for a 28-day supply. And the American Society for Metabolic and Bariatric Surgery (ASMBS) said that the average cost of bariatric surgery ranges between $17,000 and $26,000. But ASMBS added that third-party payers will recover those costs within 2-4 years due to reduction or elimination of obesity-related conditions and associated treatment costs, with an approximate 29% healthcare cost reduction at 5 years.

Recently, for example, Geisinger Health of Pennsylvania and Blue Cross/Blue Shield of Massachusetts expanded body mass index (BMI) eligibility for bariatric surgery procedures, while Blue Cross Blue Shield of Michigan dropped prior authorization requirements for several services, including bariatric surgery.

While most major health insurers cover Wegovy for obesity treatment, they typically require prior authorization and/or trials of other therapies first. Recently, some employers have denied coverage for the medications for treating obesity. Medicare does not cover these drugs. Coverage varies across state Medicaid plans.

“For years, insurers…have played games with the surgery, making people jump through hoops, hoping that they would just give up and go away. And now that health plans are getting concerned about [the cost of] drugs for obesity, and they’re getting so much attention, they’re thinking oh, maybe we shouldn’t be playing these games anymore,” obesity policy expert Ted Kyle, RPh, founder of ConscienHealth, told this news organization.

However, Christopher Doubet Still, DO, director of Nutrition and Weight Management at Geisinger Medical Center, Danville, Pennsylvania, told this news organization that Geisinger Health Plan’s change in May 2023 to lower the BMI surgery eligibility cutoff from 35 kg/m2 to 30 kg/m2 for people with comorbidities was not related to the cost of GLP-1 drugs.

“To date, bariatric surgery remains the most effective, enduring treatment of obesity, and most importantly, its comorbid medical problems. So that was really the reasoning. The weight loss is secondary to the profound medical benefits of bariatric surgery. I think that was the impetus of that change, not having really anything to do at the time with GLP-1s,” Dr. Still said.

The Geisinger Health Plan does not currently cover antiobesity medications, although Geisinger Health Plan Family, a state Medicaid plan, does because Pennsylvania is now one of a handful of states that cover the medications through Medicaid.
 

The Equation Keeps Changing

Health economist James Chambers, PhD, of Tufts University, Boston, Massachusetts, told this news organizations, “when you think about the value of a treatment, you don’t look at it in isolation. You’re looking at the difference in cost and benefits. So now that you have these expensive drugs, it’s not that surgeries become less expensive, but it does make you interpret the cost differently. When diet and exercise and counseling were the only real options, surgeries seemed like a much more expensive intervention. But with the advent of the GLP-1s, then, maybe plans consider the costs of surgery a little bit differently.”

And that equation is likely to change further, Dr. Still noted.

“I just think we’re dealing with a short-term financial problem because there’s basically only two main medications so the prices are high, but as more medications come on the market, the prices will come down,” he said.

Cristy Ms. Gallagher, MPAff, research project director of the STOP Obesity Alliance at the Milken Institute School of Public Health at George Washington University, Washington, DC, agreed.

“We have a lot of data on obesity treatment coverage from before 2023. But then this [GLP-1] explosion happened in 2023…The health payers are out there trying to figure out coverage, and they’re trying to figure out what this is going to look like for them,” Ms. Gallagher said.

However, she pointed out, “there is no treatment that fits everyone. The GLP-1s won’t work for every person because of the different stages of obesity, the side effects, and then because of the coverage. I think that you will not see a decrease in bariatric surgery in the near term, by any means.”

Ms. Gallagher also noted that although the data now suggest people will have to keep taking the drugs for life, there may be other future approaches.

“Once a person hits their goal weight, maybe then they could be transferred to a different pill form that might be cheaper, something that’s sort of more of a maintenance drug. I think that is a huge unknown right now,” she said.

And Mr. Kyle said that while bariatric surgery does provide the most durable benefit, “weight regain after surgery is a fact of life. People are still healthier 5 years later, but they do have some weight regain. And in those cases, you might want to follow-up with medicines…It’s not necessarily an either/or proposition any more than surgical treatment of cancer, surgical oncology is an either/or with medical oncology.”
 

A New View of Obesity

According to Mr. Kyle, all this attention on the new medications “is prompting people to rethink or think differently about obesity and consider it more carefully as a chronic medical condition and not a condition of appearance and behavior. And that’s all good, whether you’re thinking about it from the standpoint of bariatric surgery or from the standpoint of medical treatment of obesity because then people start considering options more rationally.”

This shifting view of obesity has meant that bariatric surgeons and medical obesity specialists are starting to work more collaboratively, he said.

“There is a trend that I detect toward more integrated approaches to obesity,” Mr. Kyle said.

He added, “We now have more tools. And we’re in the messy middle of figuring out how, as a practical matter, to use them.”

And as far as insurance coverage, “people are going to make mistakes. They are making mistakes. But I have been the eternal optimist, and I have faith that people are also figuring it out. It would be hard to do worse.”

For now, any initiatives to increase bariatric surgery rates in the GLP-1 era haven’t yet had an impact, American Society for Metabolic and Bariatric Surgery President Marina S. Kurian, MD, told this news organization in a statement.

“While we have heard of some insurers possibly changing their requirements for bariatric surgery, we have not seen a significant rise in procedures related to changes in insurance coverage for either antiobesity medications or metabolic and bariatric surgery,” Dr. Kurian said.

Mr. Kyle had accepted speaking or professional fees from Novo Nordisk, Behringer Ingelheim, Nutrisystem, Roman Health, and Emerald Lake Safety. Dr. Still was on the speaker’s bureau and did clinical trials for Eli Lilly and Novo Nordisk. Dr. Chambers and Gallagher had no disclosures.

A version of this article appeared on Medscape.com.

Amid rising concern about the potential long-term costs of using glucagon-like peptide 1 (GLP-1) agonists to treat obesity, some insurers are making access to bariatric surgery easier.

While the relationship may not be entirely causal, data do suggest that at least for now, these new agents for treating obesity including semaglutide (Wegovy) and tirzepatide (Zepbound) are not cost-effective, whereas the surgery is.

According to GoodRx, Wegovy (semaglutide) has a list price of about $1350 for a 28-day supply. And the American Society for Metabolic and Bariatric Surgery (ASMBS) said that the average cost of bariatric surgery ranges between $17,000 and $26,000. But ASMBS added that third-party payers will recover those costs within 2-4 years due to reduction or elimination of obesity-related conditions and associated treatment costs, with an approximate 29% healthcare cost reduction at 5 years.

Recently, for example, Geisinger Health of Pennsylvania and Blue Cross/Blue Shield of Massachusetts expanded body mass index (BMI) eligibility for bariatric surgery procedures, while Blue Cross Blue Shield of Michigan dropped prior authorization requirements for several services, including bariatric surgery.

While most major health insurers cover Wegovy for obesity treatment, they typically require prior authorization and/or trials of other therapies first. Recently, some employers have denied coverage for the medications for treating obesity. Medicare does not cover these drugs. Coverage varies across state Medicaid plans.

“For years, insurers…have played games with the surgery, making people jump through hoops, hoping that they would just give up and go away. And now that health plans are getting concerned about [the cost of] drugs for obesity, and they’re getting so much attention, they’re thinking oh, maybe we shouldn’t be playing these games anymore,” obesity policy expert Ted Kyle, RPh, founder of ConscienHealth, told this news organization.

However, Christopher Doubet Still, DO, director of Nutrition and Weight Management at Geisinger Medical Center, Danville, Pennsylvania, told this news organization that Geisinger Health Plan’s change in May 2023 to lower the BMI surgery eligibility cutoff from 35 kg/m2 to 30 kg/m2 for people with comorbidities was not related to the cost of GLP-1 drugs.

“To date, bariatric surgery remains the most effective, enduring treatment of obesity, and most importantly, its comorbid medical problems. So that was really the reasoning. The weight loss is secondary to the profound medical benefits of bariatric surgery. I think that was the impetus of that change, not having really anything to do at the time with GLP-1s,” Dr. Still said.

The Geisinger Health Plan does not currently cover antiobesity medications, although Geisinger Health Plan Family, a state Medicaid plan, does because Pennsylvania is now one of a handful of states that cover the medications through Medicaid.
 

The Equation Keeps Changing

Health economist James Chambers, PhD, of Tufts University, Boston, Massachusetts, told this news organizations, “when you think about the value of a treatment, you don’t look at it in isolation. You’re looking at the difference in cost and benefits. So now that you have these expensive drugs, it’s not that surgeries become less expensive, but it does make you interpret the cost differently. When diet and exercise and counseling were the only real options, surgeries seemed like a much more expensive intervention. But with the advent of the GLP-1s, then, maybe plans consider the costs of surgery a little bit differently.”

And that equation is likely to change further, Dr. Still noted.

“I just think we’re dealing with a short-term financial problem because there’s basically only two main medications so the prices are high, but as more medications come on the market, the prices will come down,” he said.

Cristy Ms. Gallagher, MPAff, research project director of the STOP Obesity Alliance at the Milken Institute School of Public Health at George Washington University, Washington, DC, agreed.

“We have a lot of data on obesity treatment coverage from before 2023. But then this [GLP-1] explosion happened in 2023…The health payers are out there trying to figure out coverage, and they’re trying to figure out what this is going to look like for them,” Ms. Gallagher said.

However, she pointed out, “there is no treatment that fits everyone. The GLP-1s won’t work for every person because of the different stages of obesity, the side effects, and then because of the coverage. I think that you will not see a decrease in bariatric surgery in the near term, by any means.”

Ms. Gallagher also noted that although the data now suggest people will have to keep taking the drugs for life, there may be other future approaches.

“Once a person hits their goal weight, maybe then they could be transferred to a different pill form that might be cheaper, something that’s sort of more of a maintenance drug. I think that is a huge unknown right now,” she said.

And Mr. Kyle said that while bariatric surgery does provide the most durable benefit, “weight regain after surgery is a fact of life. People are still healthier 5 years later, but they do have some weight regain. And in those cases, you might want to follow-up with medicines…It’s not necessarily an either/or proposition any more than surgical treatment of cancer, surgical oncology is an either/or with medical oncology.”
 

A New View of Obesity

According to Mr. Kyle, all this attention on the new medications “is prompting people to rethink or think differently about obesity and consider it more carefully as a chronic medical condition and not a condition of appearance and behavior. And that’s all good, whether you’re thinking about it from the standpoint of bariatric surgery or from the standpoint of medical treatment of obesity because then people start considering options more rationally.”

This shifting view of obesity has meant that bariatric surgeons and medical obesity specialists are starting to work more collaboratively, he said.

“There is a trend that I detect toward more integrated approaches to obesity,” Mr. Kyle said.

He added, “We now have more tools. And we’re in the messy middle of figuring out how, as a practical matter, to use them.”

And as far as insurance coverage, “people are going to make mistakes. They are making mistakes. But I have been the eternal optimist, and I have faith that people are also figuring it out. It would be hard to do worse.”

For now, any initiatives to increase bariatric surgery rates in the GLP-1 era haven’t yet had an impact, American Society for Metabolic and Bariatric Surgery President Marina S. Kurian, MD, told this news organization in a statement.

“While we have heard of some insurers possibly changing their requirements for bariatric surgery, we have not seen a significant rise in procedures related to changes in insurance coverage for either antiobesity medications or metabolic and bariatric surgery,” Dr. Kurian said.

Mr. Kyle had accepted speaking or professional fees from Novo Nordisk, Behringer Ingelheim, Nutrisystem, Roman Health, and Emerald Lake Safety. Dr. Still was on the speaker’s bureau and did clinical trials for Eli Lilly and Novo Nordisk. Dr. Chambers and Gallagher had no disclosures.

A version of this article appeared on Medscape.com.

The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.

Where do the ABC International Consensus Guidelines come from?

The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
 

How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?

These guidelines have some characteristics that are different from the NCCN guidelines. One of the major differences is that the ABC guidelines are developed together with patients and patient advocates. Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
 

Can you tell me about the other issues discussed in the guidelines besides drugs?

For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
 

What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?

The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.

Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.

We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.

We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
 

The ABC Guidelines discuss tough clinical situations. Can you explain?

The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.

It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
 

What other tough clinical situations do you discuss in the new guidelines?

We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.

It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.

Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.

We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
 

Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?

A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.

It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.

Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.

We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.

Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.

Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
 

Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?

In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.

Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.

The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.

Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.

Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.

A version of this article appeared on Medscape.com.

The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.

Where do the ABC International Consensus Guidelines come from?

The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
 

How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?

These guidelines have some characteristics that are different from the NCCN guidelines. One of the major differences is that the ABC guidelines are developed together with patients and patient advocates. Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
 

Can you tell me about the other issues discussed in the guidelines besides drugs?

For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
 

What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?

The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.

Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.

We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.

We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
 

The ABC Guidelines discuss tough clinical situations. Can you explain?

The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.

It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
 

What other tough clinical situations do you discuss in the new guidelines?

We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.

It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.

Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.

We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
 

Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?

A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.

It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.

Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.

We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.

Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.

Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
 

Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?

In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.

Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.

The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.

Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.

Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.

A version of this article appeared on Medscape.com.

The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.

Where do the ABC International Consensus Guidelines come from?

The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
 

How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?

These guidelines have some characteristics that are different from the NCCN guidelines. One of the major differences is that the ABC guidelines are developed together with patients and patient advocates. Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
 

Can you tell me about the other issues discussed in the guidelines besides drugs?

For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
 

What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?

The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.

Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.

We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.

We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
 

The ABC Guidelines discuss tough clinical situations. Can you explain?

The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.

It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
 

What other tough clinical situations do you discuss in the new guidelines?

We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.

It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.

Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.

We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
 

Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?

A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.

It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.

Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.

We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.

Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.

Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
 

Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?

In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.

Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.

The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.

Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.

Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.

A version of this article appeared on Medscape.com.

Minimally invasive cytoreductive surgery for epithelial ovarian cancer appears to be safe and does not compromise survival, compared with open surgery, when patients have completely resected tumors.

This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.

Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.

“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.

The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
 

Growing Use of MIS

Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).

Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
 

Outcomes Compared

Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.

As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.

Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.

Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.

Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.

As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).

There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.

The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
 

MIS Use Debatable: CON

Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.

In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.

“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.

Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.

Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.

In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.

Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.

She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.

MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
 

Debate: PRO

Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”

He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.

In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.

Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.

To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.

The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.

Minimally invasive cytoreductive surgery for epithelial ovarian cancer appears to be safe and does not compromise survival, compared with open surgery, when patients have completely resected tumors.

This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.

Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.

“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.

The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
 

Growing Use of MIS

Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).

Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
 

Outcomes Compared

Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.

As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.

Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.

Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.

Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.

As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).

There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.

The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
 

MIS Use Debatable: CON

Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.

In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.

“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.

Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.

Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.

In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.

Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.

She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.

MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
 

Debate: PRO

Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”

He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.

In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.

Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.

To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.

The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.

Minimally invasive cytoreductive surgery for epithelial ovarian cancer appears to be safe and does not compromise survival, compared with open surgery, when patients have completely resected tumors.

This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.

Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.

“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.

The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
 

Growing Use of MIS

Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).

Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
 

Outcomes Compared

Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.

As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.

Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.

Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.

Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.

As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).

There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.

The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
 

MIS Use Debatable: CON

Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.

In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.

“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.

Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.

Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.

In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.

Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.

She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.

MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
 

Debate: PRO

Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”

He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.

In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.

Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.

To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.

The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

A recent study linking a niacin derivative to an increased risk for cardiovascular events has raised questions about the safety of this B vitamin, which is added to many food staples in the Western diet and taken in the form of supplements.

The findings, which were published in Nature Medicine, may also help explain why taking niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events in major clinical trials.

But could this essential micronutrient really have an adverse effect on cardiovascular risk, and what are the implications for niacin intake?

Senior author of the new study Stanley Hazen, MD, believes some prudence on excessive niacin intake may be justified.

“I’m not suggesting we should completely avoid niacin — it is an essential nutrient, but our results suggest that too much may be harmful,” Dr. Hazen said.

Niacin supplements are also sold with claims of antiaging effects, arthritis relief, and boosting brain function, although none of these claims have been proven. And the related compound, nicotinamide, is recommended to prevent skin cancer in high-risk patients; however, a recent study questioned that guidance.

“I would say to the general public that avoiding supplements containing niacin or related compounds could be a sensible approach at present, while these findings are investigated further.”

Other experts are unsure if such action is justified on the basis of this single study.
 

Residual Cardiovascular Risk

Dr. Hazen, who is chair of the Department of Cardiovascular & Metabolic Sciences, at the Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, explained to this news organization that they did not set out to study niacin.

“It began as a study to look for novel pathways involved in residual cardiovascular disease risk — the risk for cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

The researchers began looking for compounds in plasma that predicted future adverse cardiovascular events in individuals undergoing elective diagnostic cardiac evaluation. Two of the leading candidates identified were niacin derivatives — 2PY and 4PY — that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts — 2331 US individuals and a European cohort of 832 individuals. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling in cardiovascular risk seen in those with levels in the highest vs the lowest quartile.

To move beyond these observational studies and to explore a potentially causal relationship, Dr. Hazen’s team went on to perform genome-wide association studies and found that genetic variants that tracked with higher levels of 4PY also linked to levels of the inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1).

And in cell culture and animal studies, they found that 4PY was a driver of inflammation, upregulating VCAM-1 and eliciting vascular inflammation responses.

“So, we have shown in several different ways that the niacin derivative, 4PY, is linked to increased cardiovascular risk,” Dr. Hazen commented.
 

Significant Health Implications?

Dr. Hazen believed these findings could have significant health implications.

He noted that Western populations have been consuming large amounts of niacin ever since World War 2 when we began to fortify many foods with essential vitamins to avoid diseases caused by deficiencies. Niacin was added to foods to prevent pellagra — a disease characterized by inflamed skin, diarrhea, and dementia, that was often fatal.

“While we may have eliminated pellagra, have we, as a consequence, increased the prevalence of cardiovascular disease many years later?” Dr. Hazen asked.

This may be a clue to why niacin does not lower cardiovascular risk as much as would be expected from the degree of cholesterol lowering it brings about. “This is the niacin paradox and has led to the thought that there could be some kind of adverse effect that niacin is promoting. I think we may have found something that contributes to the niacin paradox,” he said.

However, the niacin pathway is complicated. Niacin is the major source of nicotinamide adenine dinucleotide (NAD), an integral molecule that allows cells to create energy. “Because it is so important, our bodies are designed to salvage and retain NADs, but once storage capacity is exceeded, then these 4PY and 2PY derivatives are generated,” Dr. Hazen explained. “But you have to really eat a lot of niacin-rich foods for this to happen.”

He is not claiming that niacin causes cardiovascular disease. “It is 4PY that appears to be the driver of vascular inflammation. And 4PY is a breakdown product of niacin. But there is more than one pathway that could lead to 4PY generation. There is a whole interconnecting network of compounds that interchange with each other — known as the niacin pool — any one or more of these compounds can be ingested and raise pool levels and ultimately 4PY levels. However, by far and away, niacin is one of the major sources,” Dr. Hazen commented.
 

Are High-Protein Diets Also Implicated?

Other sources of NADs include tryptophan, present in protein. And one of the genetic variants linked to changes in 4PY levels is connected to how dietary protein is directed into the niacin pool, raising the possibility that a high-protein diet may also raise cardiovascular risk in some people, Dr. Hazen noted.

Dr. Hazen estimated that about 3% of the niacin pool in a normal diet comes from protein intake, but that the percentage could increase substantially in very high–protein diets.

“Our data support the concept that if we lower our 4PY level long-term, then that would result in a reduction in cardiovascular disease. But this is still just a hypothesis. If we lower niacin intake, we will lower 4PY,” Dr. Hazen stated.

He said that this research is at too early a stage to give firm recommendations in what this means for the consumer.

“Based on these findings, I would advise people to avoid taking niacin or nicotinic acid or nicotinamide supplements and to eat a sensible balanced diet — maybe not to overdo the high protein–type diets. That’s all we can really say at the moment.”

Noting that niacin can also be one of the major components in energy drinks, he suggested it may be prudent to limit consumption of these products.
 

What Is the Optimum Niacin Intake?

Dr. Hazen noted that the recommended dietary allowance (RDA) for niacin is well known — between 14 and 18 mg, but he said the average American ingests four times that amount, and some people have substantially higher intakes — up to 50 times the RDA if taking supplements.

While food fortification with niacin may have been useful in the past, Dr. Hazen questioned whether it should still be mandated.

“In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin has led to an increase in cardiovascular disease?”

He does not propose stopping all niacin fortification, “but maybe, we could have the choice of selecting an unfortified option,” he said.
 

Causal Link Not Proven

Commenting for this news organization, John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed “interesting and important results,” but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.

“These findings need to be investigated further, and more studies are certainly justified, but I don’t think that this study alone makes an adequate case for restricting niacin intake, or thinking about stopping niacin fortification of foodstuffs,” Dr. Guyton said.

Noting that niacin is present in large quantities in many fast foods, he suggested the researchers may have just picked up the consequences of eating an unhealthy diet.

“If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet,” he commented.

Dr. Guyton also pointed out that major clinical trials with niacin have shown mixed results, and its effect on cardiovascular risk is still not completely understood. While the HPS2-THRIVE and AIM-HIGH trials did not show benefits in reducing cardiovascular events, an earlier study, the Coronary Drug Project in which the agent was given with food, did show some positive effects with substantial reductions in myocardial infarction and stroke, and there was the suggestion of a reduction in long-term mortality in the niacin group several years after the trial had ended.
 

Nicotinamide in Skin Cancer Prevention

What about the use of nicotinamide in skin cancer prevention?

Addressing this question, Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, pointed out that nicotinamide, although closely related to niacin, may have different effects. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, professor of dermatology at the University of Sydney, Camperdown, Australia, told this news organization that it was hard to extrapolate these findings on basal levels of niacin in a cardiac cohort to the administration of supra-physiological doses of nicotinamide for skin cancer prevention.

There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin, Dr. Damian said, adding that it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.

She pointed out that high vs low levels of nicotinamide supplementation can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. At high doses, nicotinamide is anti-inflammatory in skin.

Dr. Damian noted that two phase 3 studies (ONTRAC and ONTRANS) of nicotinamide 500 mg twice daily for skin cancer prevention did not find a significant increase in cardiovascular events compared to placebo over 12 months.

“Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,” she commented.

“For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,” she added.

Meanwhile, Dr. Hazen said the most exciting part of this new research is the discovery of a new pathway that contributes to cardiovascular disease and potentially a new target to treat residual cardiovascular risk.

“I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk.”

The next step will be to confirm these results in other populations and then to develop a diagnostic test to identify people with a high 4PY level, he said.

A version of this article appeared on Medscape.com.

A recent study linking a niacin derivative to an increased risk for cardiovascular events has raised questions about the safety of this B vitamin, which is added to many food staples in the Western diet and taken in the form of supplements.

The findings, which were published in Nature Medicine, may also help explain why taking niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events in major clinical trials.

But could this essential micronutrient really have an adverse effect on cardiovascular risk, and what are the implications for niacin intake?

Senior author of the new study Stanley Hazen, MD, believes some prudence on excessive niacin intake may be justified.

“I’m not suggesting we should completely avoid niacin — it is an essential nutrient, but our results suggest that too much may be harmful,” Dr. Hazen said.

Niacin supplements are also sold with claims of antiaging effects, arthritis relief, and boosting brain function, although none of these claims have been proven. And the related compound, nicotinamide, is recommended to prevent skin cancer in high-risk patients; however, a recent study questioned that guidance.

“I would say to the general public that avoiding supplements containing niacin or related compounds could be a sensible approach at present, while these findings are investigated further.”

Other experts are unsure if such action is justified on the basis of this single study.
 

Residual Cardiovascular Risk

Dr. Hazen, who is chair of the Department of Cardiovascular & Metabolic Sciences, at the Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, explained to this news organization that they did not set out to study niacin.

“It began as a study to look for novel pathways involved in residual cardiovascular disease risk — the risk for cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

The researchers began looking for compounds in plasma that predicted future adverse cardiovascular events in individuals undergoing elective diagnostic cardiac evaluation. Two of the leading candidates identified were niacin derivatives — 2PY and 4PY — that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts — 2331 US individuals and a European cohort of 832 individuals. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling in cardiovascular risk seen in those with levels in the highest vs the lowest quartile.

To move beyond these observational studies and to explore a potentially causal relationship, Dr. Hazen’s team went on to perform genome-wide association studies and found that genetic variants that tracked with higher levels of 4PY also linked to levels of the inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1).

And in cell culture and animal studies, they found that 4PY was a driver of inflammation, upregulating VCAM-1 and eliciting vascular inflammation responses.

“So, we have shown in several different ways that the niacin derivative, 4PY, is linked to increased cardiovascular risk,” Dr. Hazen commented.
 

Significant Health Implications?

Dr. Hazen believed these findings could have significant health implications.

He noted that Western populations have been consuming large amounts of niacin ever since World War 2 when we began to fortify many foods with essential vitamins to avoid diseases caused by deficiencies. Niacin was added to foods to prevent pellagra — a disease characterized by inflamed skin, diarrhea, and dementia, that was often fatal.

“While we may have eliminated pellagra, have we, as a consequence, increased the prevalence of cardiovascular disease many years later?” Dr. Hazen asked.

This may be a clue to why niacin does not lower cardiovascular risk as much as would be expected from the degree of cholesterol lowering it brings about. “This is the niacin paradox and has led to the thought that there could be some kind of adverse effect that niacin is promoting. I think we may have found something that contributes to the niacin paradox,” he said.

However, the niacin pathway is complicated. Niacin is the major source of nicotinamide adenine dinucleotide (NAD), an integral molecule that allows cells to create energy. “Because it is so important, our bodies are designed to salvage and retain NADs, but once storage capacity is exceeded, then these 4PY and 2PY derivatives are generated,” Dr. Hazen explained. “But you have to really eat a lot of niacin-rich foods for this to happen.”

He is not claiming that niacin causes cardiovascular disease. “It is 4PY that appears to be the driver of vascular inflammation. And 4PY is a breakdown product of niacin. But there is more than one pathway that could lead to 4PY generation. There is a whole interconnecting network of compounds that interchange with each other — known as the niacin pool — any one or more of these compounds can be ingested and raise pool levels and ultimately 4PY levels. However, by far and away, niacin is one of the major sources,” Dr. Hazen commented.
 

Are High-Protein Diets Also Implicated?

Other sources of NADs include tryptophan, present in protein. And one of the genetic variants linked to changes in 4PY levels is connected to how dietary protein is directed into the niacin pool, raising the possibility that a high-protein diet may also raise cardiovascular risk in some people, Dr. Hazen noted.

Dr. Hazen estimated that about 3% of the niacin pool in a normal diet comes from protein intake, but that the percentage could increase substantially in very high–protein diets.

“Our data support the concept that if we lower our 4PY level long-term, then that would result in a reduction in cardiovascular disease. But this is still just a hypothesis. If we lower niacin intake, we will lower 4PY,” Dr. Hazen stated.

He said that this research is at too early a stage to give firm recommendations in what this means for the consumer.

“Based on these findings, I would advise people to avoid taking niacin or nicotinic acid or nicotinamide supplements and to eat a sensible balanced diet — maybe not to overdo the high protein–type diets. That’s all we can really say at the moment.”

Noting that niacin can also be one of the major components in energy drinks, he suggested it may be prudent to limit consumption of these products.
 

What Is the Optimum Niacin Intake?

Dr. Hazen noted that the recommended dietary allowance (RDA) for niacin is well known — between 14 and 18 mg, but he said the average American ingests four times that amount, and some people have substantially higher intakes — up to 50 times the RDA if taking supplements.

While food fortification with niacin may have been useful in the past, Dr. Hazen questioned whether it should still be mandated.

“In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin has led to an increase in cardiovascular disease?”

He does not propose stopping all niacin fortification, “but maybe, we could have the choice of selecting an unfortified option,” he said.
 

Causal Link Not Proven

Commenting for this news organization, John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed “interesting and important results,” but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.

“These findings need to be investigated further, and more studies are certainly justified, but I don’t think that this study alone makes an adequate case for restricting niacin intake, or thinking about stopping niacin fortification of foodstuffs,” Dr. Guyton said.

Noting that niacin is present in large quantities in many fast foods, he suggested the researchers may have just picked up the consequences of eating an unhealthy diet.

“If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet,” he commented.

Dr. Guyton also pointed out that major clinical trials with niacin have shown mixed results, and its effect on cardiovascular risk is still not completely understood. While the HPS2-THRIVE and AIM-HIGH trials did not show benefits in reducing cardiovascular events, an earlier study, the Coronary Drug Project in which the agent was given with food, did show some positive effects with substantial reductions in myocardial infarction and stroke, and there was the suggestion of a reduction in long-term mortality in the niacin group several years after the trial had ended.
 

Nicotinamide in Skin Cancer Prevention

What about the use of nicotinamide in skin cancer prevention?

Addressing this question, Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, pointed out that nicotinamide, although closely related to niacin, may have different effects. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, professor of dermatology at the University of Sydney, Camperdown, Australia, told this news organization that it was hard to extrapolate these findings on basal levels of niacin in a cardiac cohort to the administration of supra-physiological doses of nicotinamide for skin cancer prevention.

There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin, Dr. Damian said, adding that it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.

She pointed out that high vs low levels of nicotinamide supplementation can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. At high doses, nicotinamide is anti-inflammatory in skin.

Dr. Damian noted that two phase 3 studies (ONTRAC and ONTRANS) of nicotinamide 500 mg twice daily for skin cancer prevention did not find a significant increase in cardiovascular events compared to placebo over 12 months.

“Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,” she commented.

“For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,” she added.

Meanwhile, Dr. Hazen said the most exciting part of this new research is the discovery of a new pathway that contributes to cardiovascular disease and potentially a new target to treat residual cardiovascular risk.

“I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk.”

The next step will be to confirm these results in other populations and then to develop a diagnostic test to identify people with a high 4PY level, he said.

A version of this article appeared on Medscape.com.

A recent study linking a niacin derivative to an increased risk for cardiovascular events has raised questions about the safety of this B vitamin, which is added to many food staples in the Western diet and taken in the form of supplements.

The findings, which were published in Nature Medicine, may also help explain why taking niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events in major clinical trials.

But could this essential micronutrient really have an adverse effect on cardiovascular risk, and what are the implications for niacin intake?

Senior author of the new study Stanley Hazen, MD, believes some prudence on excessive niacin intake may be justified.

“I’m not suggesting we should completely avoid niacin — it is an essential nutrient, but our results suggest that too much may be harmful,” Dr. Hazen said.

Niacin supplements are also sold with claims of antiaging effects, arthritis relief, and boosting brain function, although none of these claims have been proven. And the related compound, nicotinamide, is recommended to prevent skin cancer in high-risk patients; however, a recent study questioned that guidance.

“I would say to the general public that avoiding supplements containing niacin or related compounds could be a sensible approach at present, while these findings are investigated further.”

Other experts are unsure if such action is justified on the basis of this single study.
 

Residual Cardiovascular Risk

Dr. Hazen, who is chair of the Department of Cardiovascular & Metabolic Sciences, at the Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, explained to this news organization that they did not set out to study niacin.

“It began as a study to look for novel pathways involved in residual cardiovascular disease risk — the risk for cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

The researchers began looking for compounds in plasma that predicted future adverse cardiovascular events in individuals undergoing elective diagnostic cardiac evaluation. Two of the leading candidates identified were niacin derivatives — 2PY and 4PY — that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts — 2331 US individuals and a European cohort of 832 individuals. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling in cardiovascular risk seen in those with levels in the highest vs the lowest quartile.

To move beyond these observational studies and to explore a potentially causal relationship, Dr. Hazen’s team went on to perform genome-wide association studies and found that genetic variants that tracked with higher levels of 4PY also linked to levels of the inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1).

And in cell culture and animal studies, they found that 4PY was a driver of inflammation, upregulating VCAM-1 and eliciting vascular inflammation responses.

“So, we have shown in several different ways that the niacin derivative, 4PY, is linked to increased cardiovascular risk,” Dr. Hazen commented.
 

Significant Health Implications?

Dr. Hazen believed these findings could have significant health implications.

He noted that Western populations have been consuming large amounts of niacin ever since World War 2 when we began to fortify many foods with essential vitamins to avoid diseases caused by deficiencies. Niacin was added to foods to prevent pellagra — a disease characterized by inflamed skin, diarrhea, and dementia, that was often fatal.

“While we may have eliminated pellagra, have we, as a consequence, increased the prevalence of cardiovascular disease many years later?” Dr. Hazen asked.

This may be a clue to why niacin does not lower cardiovascular risk as much as would be expected from the degree of cholesterol lowering it brings about. “This is the niacin paradox and has led to the thought that there could be some kind of adverse effect that niacin is promoting. I think we may have found something that contributes to the niacin paradox,” he said.

However, the niacin pathway is complicated. Niacin is the major source of nicotinamide adenine dinucleotide (NAD), an integral molecule that allows cells to create energy. “Because it is so important, our bodies are designed to salvage and retain NADs, but once storage capacity is exceeded, then these 4PY and 2PY derivatives are generated,” Dr. Hazen explained. “But you have to really eat a lot of niacin-rich foods for this to happen.”

He is not claiming that niacin causes cardiovascular disease. “It is 4PY that appears to be the driver of vascular inflammation. And 4PY is a breakdown product of niacin. But there is more than one pathway that could lead to 4PY generation. There is a whole interconnecting network of compounds that interchange with each other — known as the niacin pool — any one or more of these compounds can be ingested and raise pool levels and ultimately 4PY levels. However, by far and away, niacin is one of the major sources,” Dr. Hazen commented.
 

Are High-Protein Diets Also Implicated?

Other sources of NADs include tryptophan, present in protein. And one of the genetic variants linked to changes in 4PY levels is connected to how dietary protein is directed into the niacin pool, raising the possibility that a high-protein diet may also raise cardiovascular risk in some people, Dr. Hazen noted.

Dr. Hazen estimated that about 3% of the niacin pool in a normal diet comes from protein intake, but that the percentage could increase substantially in very high–protein diets.

“Our data support the concept that if we lower our 4PY level long-term, then that would result in a reduction in cardiovascular disease. But this is still just a hypothesis. If we lower niacin intake, we will lower 4PY,” Dr. Hazen stated.

He said that this research is at too early a stage to give firm recommendations in what this means for the consumer.

“Based on these findings, I would advise people to avoid taking niacin or nicotinic acid or nicotinamide supplements and to eat a sensible balanced diet — maybe not to overdo the high protein–type diets. That’s all we can really say at the moment.”

Noting that niacin can also be one of the major components in energy drinks, he suggested it may be prudent to limit consumption of these products.
 

What Is the Optimum Niacin Intake?

Dr. Hazen noted that the recommended dietary allowance (RDA) for niacin is well known — between 14 and 18 mg, but he said the average American ingests four times that amount, and some people have substantially higher intakes — up to 50 times the RDA if taking supplements.

While food fortification with niacin may have been useful in the past, Dr. Hazen questioned whether it should still be mandated.

“In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin has led to an increase in cardiovascular disease?”

He does not propose stopping all niacin fortification, “but maybe, we could have the choice of selecting an unfortified option,” he said.
 

Causal Link Not Proven

Commenting for this news organization, John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed “interesting and important results,” but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.

“These findings need to be investigated further, and more studies are certainly justified, but I don’t think that this study alone makes an adequate case for restricting niacin intake, or thinking about stopping niacin fortification of foodstuffs,” Dr. Guyton said.

Noting that niacin is present in large quantities in many fast foods, he suggested the researchers may have just picked up the consequences of eating an unhealthy diet.

“If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet,” he commented.

Dr. Guyton also pointed out that major clinical trials with niacin have shown mixed results, and its effect on cardiovascular risk is still not completely understood. While the HPS2-THRIVE and AIM-HIGH trials did not show benefits in reducing cardiovascular events, an earlier study, the Coronary Drug Project in which the agent was given with food, did show some positive effects with substantial reductions in myocardial infarction and stroke, and there was the suggestion of a reduction in long-term mortality in the niacin group several years after the trial had ended.
 

Nicotinamide in Skin Cancer Prevention

What about the use of nicotinamide in skin cancer prevention?

Addressing this question, Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, pointed out that nicotinamide, although closely related to niacin, may have different effects. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, professor of dermatology at the University of Sydney, Camperdown, Australia, told this news organization that it was hard to extrapolate these findings on basal levels of niacin in a cardiac cohort to the administration of supra-physiological doses of nicotinamide for skin cancer prevention.

There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin, Dr. Damian said, adding that it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.

She pointed out that high vs low levels of nicotinamide supplementation can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. At high doses, nicotinamide is anti-inflammatory in skin.

Dr. Damian noted that two phase 3 studies (ONTRAC and ONTRANS) of nicotinamide 500 mg twice daily for skin cancer prevention did not find a significant increase in cardiovascular events compared to placebo over 12 months.

“Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,” she commented.

“For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,” she added.

Meanwhile, Dr. Hazen said the most exciting part of this new research is the discovery of a new pathway that contributes to cardiovascular disease and potentially a new target to treat residual cardiovascular risk.

“I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk.”

The next step will be to confirm these results in other populations and then to develop a diagnostic test to identify people with a high 4PY level, he said.

A version of this article appeared on Medscape.com.