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How will SNF readmissions penalties affect hospitalists?
Starting in 2018, skilled nursing facilities (SNFs), like acute care hospitals before them, will be subject to a penalty of up to 2% of their Medicare reimbursement for posting higher-than-average rates of hospital readmissions.
The Protecting Access to Medicare Act of 2014 established a value-based purchasing component for SNFs, including incentives for high-performing facilities and a measure for all-cause, all-condition readmissions to any hospital from the SNF within 30 days following hospital discharge – designed to recognize and reward, or punish, facilities’ performance on preventing unnecessary readmissions. Public reporting of SNF quality data, including readmission rates, started in October 2017. Penalties follow a year later. Some patients’ readmissions could trigger penalties for both the hospital and the SNF.
According to 2010 data, 23.5% of patients discharged from acute care hospitals to SNFs were readmitted to the hospital within 30 days, at a financial cost of $10,362 per readmission or $4.34 billion per year.1 Seventy eight percent of these readmissions were labeled avoidable. More recent evidence suggests that hospitalization rates for dual-eligible patients living in long-term care facilities decreased by 31% between 2010 and 2015.2As increasing numbers of hospitalists spend some or all of their work week in post-acute care settings, how will the SNF readmission penalty affect their relationships with post-acute facilities?
Experts say SNFs – as with hospitals before them – lack the ability to allocate rewards or penalties for readmission rate performance to individual doctors. But increasingly close collaborative relationships between post-acute facilities and the hospitalists who work in post-acute care mean that the hospitalist has an important role in helping the SNF to manage its readmissions exposure.
“Hospitals and hospitalists want to keep good relationships with the SNFs they partner with, for a variety of reasons,” Dr. Frizner said. “We believe that the best way to reduce readmissions and unplanned transfers from the SNF is for the doctor to know the patient. We need dedicated doctors in the facility. We want hospitalists who already know the patient to come to the facility and see the patient there.”
The hospitalist’s role in post-acute care
Hospitalists who work in post-acute care typically make scheduled, billable medical visits to patients in long-term care facilities, and may also take on roles such as facility medical director or contribute to quality improvement. Relationships may be initiated by a facility seeking more medical coverage, by a hospitalist group seeking additional work or an ability to impact on the post-acute care delivered to hospital patients discharged to the facility, or by health systems, health plans, or accountable care organizations seeking to better manage the quality of care transitions for their beneficiaries.
“What I’m seeing is that with opportunities for bundled payments, we all have new incentives for moving patients along and reducing waste,” Dr. Boutwell said. “For hospitalists practicing in SNFs, it’s going to be a much bigger phenomenon. They’ll be called to reevaluate patients and make more visits than they have been accustomed to.” She hopes SNFs are studying what happened with hospitals’ readmission penalties, and will respond more quickly and effectively to their own penalty exposure.
“What we are seeing is an effort to shift folks to lower cost – but still clinically appropriate – levels of care,” he said. “These dynamics will force SNFs to reevaluate and improve their clinical competencies, to accept patients and then treat them in place. It’s no longer acceptable for the medical director to make rounds in person twice a month and do the rest by telephone.”
Instead, someone needs to be on site several times a week, working with nursing staff and developing protocols and pathways to control variability, Dr. Harrington said. “And in many cases that will be a hospitalist. Hospitalists are finding ways to partner and provide that level of care. I believe good hospitalist groups can change the facility for the better, and fairly quickly.”
What happens in post-acute care
Cari Levy, MD, PhD, who does hospital coverage and post-acute care for a number of facilities and home health agencies in the Denver area, calls the changes coming to SNFs a thrilling time for post-acute care.
“Suddenly medical professionals care about what happens in the post-acute world,” she said. “Everyone is now looking at the same measures. If this works the way it should, there would be a lot more mutual respect between providers.”
SNFs that are concerned about their readmissions rates will want to do root cause analysis to figure out what’s going on, Dr. Levy said. “Maybe the doctor didn’t do a good assessment. Maybe it was just a tough case. Once you start talking, you’ll develop systems to help everyone responsible. Hospitalists can be part of that conversation,” she said.
“You can have a good outcome at Shady Oaks and a terrible outcome at Whispering Pines, for all sorts of reasons. The hospital wants to make sure we’re sending patients to facilities that produce good outcomes,” he explained. “But there has to be communication between providers – the SNF medical director, the hospitalists, and the emergency department.”
A TeamHealth doctor in Phoenix has convened a consortium of providers from different care settings to meet and talk about cases and how they could have gone better. “The reality is, these conversations are going on all over,” Dr. Wilborn said. “What’s driving them is the realization of what we all need to do in this new environment.”
Opportunities from reforms
Robert Burke, MD, FHM, assistant chief of Hospital Medicine at the Denver VA Medical Center, is lead author of a study in the Journal of Hospital Medicine highlighting implications and opportunities from reforms in post-acute care.3 Hospitalists may not appreciate that post-acute care is poised to undergo transformative change from the recently legislated reforms, opening opportunities for hospitalists to improve health care value by improving transitions of care, he noted.
“My sense is that payment reform will put pressure on physicians to use home health care more often than institutional care, because of the cost pressures. We know that hospitalists choose long-term care facility placements less often when participating in bundled payment,” Dr. Burke said. “I think few hospitalists really know what happens on a day-to-day basis in SNFs – or in patients’ homes, for that matter.”
According to Dr. Burke, there’s just not enough data currently to guide these decisions. He said that, based on his research, the best thing hospitalists can do is try to understand what’s available in post-acute spaces, and build relationships with post-acute facilities.
“Find ways to get feedback on your discharge decisions,” he said. “Here in Colorado, we met recently with the local chapter of the Society for Post-Acute and Long-Term Care Medicine, also known as AMDA. It’s been revealing for everyone involved.”
He recommends AMDA’s learning modules – which are designed for doctors who are new to long-term care – to any hospitalist who is entering the post-acute world.
References
1. Mor V et al. The revolving door of rehospitalization from skilled nursing facilities. Health Aff (Millwood). 2010 Jan-Feb;29(1):57-64.
2. Brennan N et al. Data Brief: Sharp reduction in avoidable hospitalizations among long-term care facility residents. The CMS Blog, 2017 Jan 17.
3. Burke RE et al. Post-acute care reform: Implications and opportunities for hospitalists. J Hosp Med. 2017 Jan;12(1);46-51.
Starting in 2018, skilled nursing facilities (SNFs), like acute care hospitals before them, will be subject to a penalty of up to 2% of their Medicare reimbursement for posting higher-than-average rates of hospital readmissions.
The Protecting Access to Medicare Act of 2014 established a value-based purchasing component for SNFs, including incentives for high-performing facilities and a measure for all-cause, all-condition readmissions to any hospital from the SNF within 30 days following hospital discharge – designed to recognize and reward, or punish, facilities’ performance on preventing unnecessary readmissions. Public reporting of SNF quality data, including readmission rates, started in October 2017. Penalties follow a year later. Some patients’ readmissions could trigger penalties for both the hospital and the SNF.
According to 2010 data, 23.5% of patients discharged from acute care hospitals to SNFs were readmitted to the hospital within 30 days, at a financial cost of $10,362 per readmission or $4.34 billion per year.1 Seventy eight percent of these readmissions were labeled avoidable. More recent evidence suggests that hospitalization rates for dual-eligible patients living in long-term care facilities decreased by 31% between 2010 and 2015.2As increasing numbers of hospitalists spend some or all of their work week in post-acute care settings, how will the SNF readmission penalty affect their relationships with post-acute facilities?
Experts say SNFs – as with hospitals before them – lack the ability to allocate rewards or penalties for readmission rate performance to individual doctors. But increasingly close collaborative relationships between post-acute facilities and the hospitalists who work in post-acute care mean that the hospitalist has an important role in helping the SNF to manage its readmissions exposure.
“Hospitals and hospitalists want to keep good relationships with the SNFs they partner with, for a variety of reasons,” Dr. Frizner said. “We believe that the best way to reduce readmissions and unplanned transfers from the SNF is for the doctor to know the patient. We need dedicated doctors in the facility. We want hospitalists who already know the patient to come to the facility and see the patient there.”
The hospitalist’s role in post-acute care
Hospitalists who work in post-acute care typically make scheduled, billable medical visits to patients in long-term care facilities, and may also take on roles such as facility medical director or contribute to quality improvement. Relationships may be initiated by a facility seeking more medical coverage, by a hospitalist group seeking additional work or an ability to impact on the post-acute care delivered to hospital patients discharged to the facility, or by health systems, health plans, or accountable care organizations seeking to better manage the quality of care transitions for their beneficiaries.
“What I’m seeing is that with opportunities for bundled payments, we all have new incentives for moving patients along and reducing waste,” Dr. Boutwell said. “For hospitalists practicing in SNFs, it’s going to be a much bigger phenomenon. They’ll be called to reevaluate patients and make more visits than they have been accustomed to.” She hopes SNFs are studying what happened with hospitals’ readmission penalties, and will respond more quickly and effectively to their own penalty exposure.
“What we are seeing is an effort to shift folks to lower cost – but still clinically appropriate – levels of care,” he said. “These dynamics will force SNFs to reevaluate and improve their clinical competencies, to accept patients and then treat them in place. It’s no longer acceptable for the medical director to make rounds in person twice a month and do the rest by telephone.”
Instead, someone needs to be on site several times a week, working with nursing staff and developing protocols and pathways to control variability, Dr. Harrington said. “And in many cases that will be a hospitalist. Hospitalists are finding ways to partner and provide that level of care. I believe good hospitalist groups can change the facility for the better, and fairly quickly.”
What happens in post-acute care
Cari Levy, MD, PhD, who does hospital coverage and post-acute care for a number of facilities and home health agencies in the Denver area, calls the changes coming to SNFs a thrilling time for post-acute care.
“Suddenly medical professionals care about what happens in the post-acute world,” she said. “Everyone is now looking at the same measures. If this works the way it should, there would be a lot more mutual respect between providers.”
SNFs that are concerned about their readmissions rates will want to do root cause analysis to figure out what’s going on, Dr. Levy said. “Maybe the doctor didn’t do a good assessment. Maybe it was just a tough case. Once you start talking, you’ll develop systems to help everyone responsible. Hospitalists can be part of that conversation,” she said.
“You can have a good outcome at Shady Oaks and a terrible outcome at Whispering Pines, for all sorts of reasons. The hospital wants to make sure we’re sending patients to facilities that produce good outcomes,” he explained. “But there has to be communication between providers – the SNF medical director, the hospitalists, and the emergency department.”
A TeamHealth doctor in Phoenix has convened a consortium of providers from different care settings to meet and talk about cases and how they could have gone better. “The reality is, these conversations are going on all over,” Dr. Wilborn said. “What’s driving them is the realization of what we all need to do in this new environment.”
Opportunities from reforms
Robert Burke, MD, FHM, assistant chief of Hospital Medicine at the Denver VA Medical Center, is lead author of a study in the Journal of Hospital Medicine highlighting implications and opportunities from reforms in post-acute care.3 Hospitalists may not appreciate that post-acute care is poised to undergo transformative change from the recently legislated reforms, opening opportunities for hospitalists to improve health care value by improving transitions of care, he noted.
“My sense is that payment reform will put pressure on physicians to use home health care more often than institutional care, because of the cost pressures. We know that hospitalists choose long-term care facility placements less often when participating in bundled payment,” Dr. Burke said. “I think few hospitalists really know what happens on a day-to-day basis in SNFs – or in patients’ homes, for that matter.”
According to Dr. Burke, there’s just not enough data currently to guide these decisions. He said that, based on his research, the best thing hospitalists can do is try to understand what’s available in post-acute spaces, and build relationships with post-acute facilities.
“Find ways to get feedback on your discharge decisions,” he said. “Here in Colorado, we met recently with the local chapter of the Society for Post-Acute and Long-Term Care Medicine, also known as AMDA. It’s been revealing for everyone involved.”
He recommends AMDA’s learning modules – which are designed for doctors who are new to long-term care – to any hospitalist who is entering the post-acute world.
References
1. Mor V et al. The revolving door of rehospitalization from skilled nursing facilities. Health Aff (Millwood). 2010 Jan-Feb;29(1):57-64.
2. Brennan N et al. Data Brief: Sharp reduction in avoidable hospitalizations among long-term care facility residents. The CMS Blog, 2017 Jan 17.
3. Burke RE et al. Post-acute care reform: Implications and opportunities for hospitalists. J Hosp Med. 2017 Jan;12(1);46-51.
Starting in 2018, skilled nursing facilities (SNFs), like acute care hospitals before them, will be subject to a penalty of up to 2% of their Medicare reimbursement for posting higher-than-average rates of hospital readmissions.
The Protecting Access to Medicare Act of 2014 established a value-based purchasing component for SNFs, including incentives for high-performing facilities and a measure for all-cause, all-condition readmissions to any hospital from the SNF within 30 days following hospital discharge – designed to recognize and reward, or punish, facilities’ performance on preventing unnecessary readmissions. Public reporting of SNF quality data, including readmission rates, started in October 2017. Penalties follow a year later. Some patients’ readmissions could trigger penalties for both the hospital and the SNF.
According to 2010 data, 23.5% of patients discharged from acute care hospitals to SNFs were readmitted to the hospital within 30 days, at a financial cost of $10,362 per readmission or $4.34 billion per year.1 Seventy eight percent of these readmissions were labeled avoidable. More recent evidence suggests that hospitalization rates for dual-eligible patients living in long-term care facilities decreased by 31% between 2010 and 2015.2As increasing numbers of hospitalists spend some or all of their work week in post-acute care settings, how will the SNF readmission penalty affect their relationships with post-acute facilities?
Experts say SNFs – as with hospitals before them – lack the ability to allocate rewards or penalties for readmission rate performance to individual doctors. But increasingly close collaborative relationships between post-acute facilities and the hospitalists who work in post-acute care mean that the hospitalist has an important role in helping the SNF to manage its readmissions exposure.
“Hospitals and hospitalists want to keep good relationships with the SNFs they partner with, for a variety of reasons,” Dr. Frizner said. “We believe that the best way to reduce readmissions and unplanned transfers from the SNF is for the doctor to know the patient. We need dedicated doctors in the facility. We want hospitalists who already know the patient to come to the facility and see the patient there.”
The hospitalist’s role in post-acute care
Hospitalists who work in post-acute care typically make scheduled, billable medical visits to patients in long-term care facilities, and may also take on roles such as facility medical director or contribute to quality improvement. Relationships may be initiated by a facility seeking more medical coverage, by a hospitalist group seeking additional work or an ability to impact on the post-acute care delivered to hospital patients discharged to the facility, or by health systems, health plans, or accountable care organizations seeking to better manage the quality of care transitions for their beneficiaries.
“What I’m seeing is that with opportunities for bundled payments, we all have new incentives for moving patients along and reducing waste,” Dr. Boutwell said. “For hospitalists practicing in SNFs, it’s going to be a much bigger phenomenon. They’ll be called to reevaluate patients and make more visits than they have been accustomed to.” She hopes SNFs are studying what happened with hospitals’ readmission penalties, and will respond more quickly and effectively to their own penalty exposure.
“What we are seeing is an effort to shift folks to lower cost – but still clinically appropriate – levels of care,” he said. “These dynamics will force SNFs to reevaluate and improve their clinical competencies, to accept patients and then treat them in place. It’s no longer acceptable for the medical director to make rounds in person twice a month and do the rest by telephone.”
Instead, someone needs to be on site several times a week, working with nursing staff and developing protocols and pathways to control variability, Dr. Harrington said. “And in many cases that will be a hospitalist. Hospitalists are finding ways to partner and provide that level of care. I believe good hospitalist groups can change the facility for the better, and fairly quickly.”
What happens in post-acute care
Cari Levy, MD, PhD, who does hospital coverage and post-acute care for a number of facilities and home health agencies in the Denver area, calls the changes coming to SNFs a thrilling time for post-acute care.
“Suddenly medical professionals care about what happens in the post-acute world,” she said. “Everyone is now looking at the same measures. If this works the way it should, there would be a lot more mutual respect between providers.”
SNFs that are concerned about their readmissions rates will want to do root cause analysis to figure out what’s going on, Dr. Levy said. “Maybe the doctor didn’t do a good assessment. Maybe it was just a tough case. Once you start talking, you’ll develop systems to help everyone responsible. Hospitalists can be part of that conversation,” she said.
“You can have a good outcome at Shady Oaks and a terrible outcome at Whispering Pines, for all sorts of reasons. The hospital wants to make sure we’re sending patients to facilities that produce good outcomes,” he explained. “But there has to be communication between providers – the SNF medical director, the hospitalists, and the emergency department.”
A TeamHealth doctor in Phoenix has convened a consortium of providers from different care settings to meet and talk about cases and how they could have gone better. “The reality is, these conversations are going on all over,” Dr. Wilborn said. “What’s driving them is the realization of what we all need to do in this new environment.”
Opportunities from reforms
Robert Burke, MD, FHM, assistant chief of Hospital Medicine at the Denver VA Medical Center, is lead author of a study in the Journal of Hospital Medicine highlighting implications and opportunities from reforms in post-acute care.3 Hospitalists may not appreciate that post-acute care is poised to undergo transformative change from the recently legislated reforms, opening opportunities for hospitalists to improve health care value by improving transitions of care, he noted.
“My sense is that payment reform will put pressure on physicians to use home health care more often than institutional care, because of the cost pressures. We know that hospitalists choose long-term care facility placements less often when participating in bundled payment,” Dr. Burke said. “I think few hospitalists really know what happens on a day-to-day basis in SNFs – or in patients’ homes, for that matter.”
According to Dr. Burke, there’s just not enough data currently to guide these decisions. He said that, based on his research, the best thing hospitalists can do is try to understand what’s available in post-acute spaces, and build relationships with post-acute facilities.
“Find ways to get feedback on your discharge decisions,” he said. “Here in Colorado, we met recently with the local chapter of the Society for Post-Acute and Long-Term Care Medicine, also known as AMDA. It’s been revealing for everyone involved.”
He recommends AMDA’s learning modules – which are designed for doctors who are new to long-term care – to any hospitalist who is entering the post-acute world.
References
1. Mor V et al. The revolving door of rehospitalization from skilled nursing facilities. Health Aff (Millwood). 2010 Jan-Feb;29(1):57-64.
2. Brennan N et al. Data Brief: Sharp reduction in avoidable hospitalizations among long-term care facility residents. The CMS Blog, 2017 Jan 17.
3. Burke RE et al. Post-acute care reform: Implications and opportunities for hospitalists. J Hosp Med. 2017 Jan;12(1);46-51.
Corynebacterium in the gut can trigger Parkinson’s disease
SAN DIEGO – The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.
If the finding is replicated, it means that Corynebacterium is the trigger for Parkinson’s disease (PD) in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for PD identified to date, but it’s not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there’s a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, professor of neurology and genomics at the University of Alabama, Birmingham.
Her team genotyped SNCA rs356219 from blood samples in 197 middle-aged PD patients and 115 age-matched controls. They also extracted DNA from stool samples to see what bacteria were in their gut and then looked for interactions between rs356219 genotype, gut microbiome, and PD risk.
The medical literature has been full of hints for a while now that PD might be set off by something going wrong in the gastrointestinal tract. Colonic inflammation, alpha-synuclein pathology in the gut, and dysbiosis of the gut microbiome in PD are among the many clues. The goal of the work was to find the link between PD and its GI aberrations.
Ninety genera were identified in the stool samples, but “no matter how you looked at the data, whichever method you used, one [genus] kept coming up” for interaction with the rs356219 genotype, “and that was Corynebacterium,” Dr. Payami said.
As in past studies, the rs356219 AA genotype did not increase the odds of PD, and there was no difference in microbiome abundance between PD patients and controls. The GA genotype increased the odds slightly without Corynebacterium, but it increased the odds more than fivefold when Corynebacterium was in the gut (odds ratio, 5.9; P = .04). If people had GG plus Corynebacterium, however, “you nailed it,” Dr. Payami said: The odds of developing PD were infinite (P = .0003).
Corynebacterium was more abundant in GA subjects with PD than GA subjects without PD, but it was by far the most abundant in GG subjects, and every person who had the GG genotype and gut Corynebacterium also had PD.
Corynebacterium are gram-positive, aerobic bacilli commonly found on the skin. Some members of the genus are opportunistic pathogens. It’s not clear how they get incorporated into the gut microbiome, or if they can be wiped out selectively in the gut with antibiotics or probiotics.
Perhaps Corynebacterium in the GI tract induces expression of alpha-synuclein protein, a major component of PD Lewy bodies that’s known to travel from the gut to the brain. Maybe the amount expressed depends on how many Gs people have in rs356219. Perhaps “if you have two Gs, you get so much alpha-synuclein that’s there’s no turning back, and it’s enough to cause PD,” Dr. Payami said.
The study was led by Zachary Wallen, a PhD candidate in Dr. Payami’s lab, and presented by him at the annual meeting of the American Neurological Association. The work was supported by the National Institutes of Health. Dr. Payami and Mr. Wallen had no industry disclosures.
SOURCE: Wallen Z et al. ANA 2017 abstract number S268
SAN DIEGO – The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.
If the finding is replicated, it means that Corynebacterium is the trigger for Parkinson’s disease (PD) in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for PD identified to date, but it’s not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there’s a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, professor of neurology and genomics at the University of Alabama, Birmingham.
Her team genotyped SNCA rs356219 from blood samples in 197 middle-aged PD patients and 115 age-matched controls. They also extracted DNA from stool samples to see what bacteria were in their gut and then looked for interactions between rs356219 genotype, gut microbiome, and PD risk.
The medical literature has been full of hints for a while now that PD might be set off by something going wrong in the gastrointestinal tract. Colonic inflammation, alpha-synuclein pathology in the gut, and dysbiosis of the gut microbiome in PD are among the many clues. The goal of the work was to find the link between PD and its GI aberrations.
Ninety genera were identified in the stool samples, but “no matter how you looked at the data, whichever method you used, one [genus] kept coming up” for interaction with the rs356219 genotype, “and that was Corynebacterium,” Dr. Payami said.
As in past studies, the rs356219 AA genotype did not increase the odds of PD, and there was no difference in microbiome abundance between PD patients and controls. The GA genotype increased the odds slightly without Corynebacterium, but it increased the odds more than fivefold when Corynebacterium was in the gut (odds ratio, 5.9; P = .04). If people had GG plus Corynebacterium, however, “you nailed it,” Dr. Payami said: The odds of developing PD were infinite (P = .0003).
Corynebacterium was more abundant in GA subjects with PD than GA subjects without PD, but it was by far the most abundant in GG subjects, and every person who had the GG genotype and gut Corynebacterium also had PD.
Corynebacterium are gram-positive, aerobic bacilli commonly found on the skin. Some members of the genus are opportunistic pathogens. It’s not clear how they get incorporated into the gut microbiome, or if they can be wiped out selectively in the gut with antibiotics or probiotics.
Perhaps Corynebacterium in the GI tract induces expression of alpha-synuclein protein, a major component of PD Lewy bodies that’s known to travel from the gut to the brain. Maybe the amount expressed depends on how many Gs people have in rs356219. Perhaps “if you have two Gs, you get so much alpha-synuclein that’s there’s no turning back, and it’s enough to cause PD,” Dr. Payami said.
The study was led by Zachary Wallen, a PhD candidate in Dr. Payami’s lab, and presented by him at the annual meeting of the American Neurological Association. The work was supported by the National Institutes of Health. Dr. Payami and Mr. Wallen had no industry disclosures.
SOURCE: Wallen Z et al. ANA 2017 abstract number S268
SAN DIEGO – The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.
If the finding is replicated, it means that Corynebacterium is the trigger for Parkinson’s disease (PD) in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for PD identified to date, but it’s not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there’s a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, professor of neurology and genomics at the University of Alabama, Birmingham.
Her team genotyped SNCA rs356219 from blood samples in 197 middle-aged PD patients and 115 age-matched controls. They also extracted DNA from stool samples to see what bacteria were in their gut and then looked for interactions between rs356219 genotype, gut microbiome, and PD risk.
The medical literature has been full of hints for a while now that PD might be set off by something going wrong in the gastrointestinal tract. Colonic inflammation, alpha-synuclein pathology in the gut, and dysbiosis of the gut microbiome in PD are among the many clues. The goal of the work was to find the link between PD and its GI aberrations.
Ninety genera were identified in the stool samples, but “no matter how you looked at the data, whichever method you used, one [genus] kept coming up” for interaction with the rs356219 genotype, “and that was Corynebacterium,” Dr. Payami said.
As in past studies, the rs356219 AA genotype did not increase the odds of PD, and there was no difference in microbiome abundance between PD patients and controls. The GA genotype increased the odds slightly without Corynebacterium, but it increased the odds more than fivefold when Corynebacterium was in the gut (odds ratio, 5.9; P = .04). If people had GG plus Corynebacterium, however, “you nailed it,” Dr. Payami said: The odds of developing PD were infinite (P = .0003).
Corynebacterium was more abundant in GA subjects with PD than GA subjects without PD, but it was by far the most abundant in GG subjects, and every person who had the GG genotype and gut Corynebacterium also had PD.
Corynebacterium are gram-positive, aerobic bacilli commonly found on the skin. Some members of the genus are opportunistic pathogens. It’s not clear how they get incorporated into the gut microbiome, or if they can be wiped out selectively in the gut with antibiotics or probiotics.
Perhaps Corynebacterium in the GI tract induces expression of alpha-synuclein protein, a major component of PD Lewy bodies that’s known to travel from the gut to the brain. Maybe the amount expressed depends on how many Gs people have in rs356219. Perhaps “if you have two Gs, you get so much alpha-synuclein that’s there’s no turning back, and it’s enough to cause PD,” Dr. Payami said.
The study was led by Zachary Wallen, a PhD candidate in Dr. Payami’s lab, and presented by him at the annual meeting of the American Neurological Association. The work was supported by the National Institutes of Health. Dr. Payami and Mr. Wallen had no industry disclosures.
SOURCE: Wallen Z et al. ANA 2017 abstract number S268
REPORTING FROM ANA 2017
Key clinical point: in genetically susceptible people.
Major finding: Those who have Corynebacterium in their gut microbiome plus two G alleles at the rs356219 locus of the alpha-synuclein gene have infinite odds of developing PD (P = .0003).
Study details: A case-control study involving 197 middle-aged PD patients and 115 age-matched controls.
Disclosures: The work was supported by the National Institutes of Health. The lead and senior investigators had no industry disclosures.
Source: Wallen Z et al. ANA 2017 abstract number S268
FDA: Laparoscopic power morcellators can spread malignant cells when used in women with occult uterine cancers*
Laparoscopic power morcellation appears capable of spreading fulminant uterine malignancies when used to remove uterine fibroids from women who have unsuspected uterine cancers.
A new Food and Drug Administration literature review of 23 studies found consistent evidence that women who undergo surgery using laparoscopic power morcellators (LPMs) for fibroids that were assumed to be benign may have an occult uterine sarcoma or leiomyosarcoma. In the FDA’s literature review of 12 studies from 2014 to 2016, women who received power morcellation were at a significantly increased risk of death, compared with those whose fibroids were removed by other methods.
The findings reaffirm the agency’s 2014 warnings about LPMs:
• LPMs are contraindicated in gynecologic surgery in which the tissue to be morcellated is known or suspected to contain malignancy.
• LPMs are contraindicated for removal of uterine tissue containing suspected fibroids in patients who are peri- or postmenopausal, or in candidates for en bloc tissue removal.
• Boxed warning: Uterine tissue may contain unsuspected cancer. The use of LPMs during fibroid surgery may spread cancer and decrease long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.
“We recognize that some health organizations have reported a lower estimate of risk and that some groups continue to request that we scale back our recommendations. However, after looking at all the relevant data, we believe our estimates remain accurate, and our recommendation against the use of this device to remove fibroids in the vast majority of women is appropriate and critical to better protecting these women. We are committed to continuing to review new relevant data to assure patient safety.”
The review determined that 1 in 350 women undergoing hysterectomy or myomectomy for fibroids may have an occult uterine sarcoma, and that 1 in about 500 have an unsuspected leiomyosarcoma. The literature review clearly identified increased risk of uterine cancers and decreased survival when these women are treated with an LPM, as opposed to manual morcellation or en bloc removal.
Twelve studies of women with uterine cancers examined this outcome in comparison groups. LPMs were associated with a 2- to 3-times increased risk of disease recurrence, compared with manual morcellation or other fibroid removal methods. In some studies, disease-free survival was significantly shorter among those who had undergone an LPM procedure; others found a higher risk of death – including, in one study, almost a quintupling of mortality risk by 1 year (crude risk ratio, 4.75).
Device-related malignancies began appearing in 2013; since then, 262 cases have been reported. But after the 2014 warning, use of LPMs in this application has decreased sharply. Two studies examined this, one finding that LPM use in fibroid surgery dropped from 14% to 3% and the other, that it dropped from 11% to 0.02%.
“The agency also continues to recommend that the advantages and risks of using LPMs during fibroid surgery be thoroughly discussed between the patient and physician before surgery,” the paper concluded. “FDA continues to actively encourage and engage in research to evaluate outcomes for a range of treatment options for fibroids and support the development of safer alternatives for providing a minimally invasive approach.”
[email protected]
Laparoscopic power morcellation appears capable of spreading fulminant uterine malignancies when used to remove uterine fibroids from women who have unsuspected uterine cancers.
A new Food and Drug Administration literature review of 23 studies found consistent evidence that women who undergo surgery using laparoscopic power morcellators (LPMs) for fibroids that were assumed to be benign may have an occult uterine sarcoma or leiomyosarcoma. In the FDA’s literature review of 12 studies from 2014 to 2016, women who received power morcellation were at a significantly increased risk of death, compared with those whose fibroids were removed by other methods.
The findings reaffirm the agency’s 2014 warnings about LPMs:
• LPMs are contraindicated in gynecologic surgery in which the tissue to be morcellated is known or suspected to contain malignancy.
• LPMs are contraindicated for removal of uterine tissue containing suspected fibroids in patients who are peri- or postmenopausal, or in candidates for en bloc tissue removal.
• Boxed warning: Uterine tissue may contain unsuspected cancer. The use of LPMs during fibroid surgery may spread cancer and decrease long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.
“We recognize that some health organizations have reported a lower estimate of risk and that some groups continue to request that we scale back our recommendations. However, after looking at all the relevant data, we believe our estimates remain accurate, and our recommendation against the use of this device to remove fibroids in the vast majority of women is appropriate and critical to better protecting these women. We are committed to continuing to review new relevant data to assure patient safety.”
The review determined that 1 in 350 women undergoing hysterectomy or myomectomy for fibroids may have an occult uterine sarcoma, and that 1 in about 500 have an unsuspected leiomyosarcoma. The literature review clearly identified increased risk of uterine cancers and decreased survival when these women are treated with an LPM, as opposed to manual morcellation or en bloc removal.
Twelve studies of women with uterine cancers examined this outcome in comparison groups. LPMs were associated with a 2- to 3-times increased risk of disease recurrence, compared with manual morcellation or other fibroid removal methods. In some studies, disease-free survival was significantly shorter among those who had undergone an LPM procedure; others found a higher risk of death – including, in one study, almost a quintupling of mortality risk by 1 year (crude risk ratio, 4.75).
Device-related malignancies began appearing in 2013; since then, 262 cases have been reported. But after the 2014 warning, use of LPMs in this application has decreased sharply. Two studies examined this, one finding that LPM use in fibroid surgery dropped from 14% to 3% and the other, that it dropped from 11% to 0.02%.
“The agency also continues to recommend that the advantages and risks of using LPMs during fibroid surgery be thoroughly discussed between the patient and physician before surgery,” the paper concluded. “FDA continues to actively encourage and engage in research to evaluate outcomes for a range of treatment options for fibroids and support the development of safer alternatives for providing a minimally invasive approach.”
[email protected]
Laparoscopic power morcellation appears capable of spreading fulminant uterine malignancies when used to remove uterine fibroids from women who have unsuspected uterine cancers.
A new Food and Drug Administration literature review of 23 studies found consistent evidence that women who undergo surgery using laparoscopic power morcellators (LPMs) for fibroids that were assumed to be benign may have an occult uterine sarcoma or leiomyosarcoma. In the FDA’s literature review of 12 studies from 2014 to 2016, women who received power morcellation were at a significantly increased risk of death, compared with those whose fibroids were removed by other methods.
The findings reaffirm the agency’s 2014 warnings about LPMs:
• LPMs are contraindicated in gynecologic surgery in which the tissue to be morcellated is known or suspected to contain malignancy.
• LPMs are contraindicated for removal of uterine tissue containing suspected fibroids in patients who are peri- or postmenopausal, or in candidates for en bloc tissue removal.
• Boxed warning: Uterine tissue may contain unsuspected cancer. The use of LPMs during fibroid surgery may spread cancer and decrease long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.
“We recognize that some health organizations have reported a lower estimate of risk and that some groups continue to request that we scale back our recommendations. However, after looking at all the relevant data, we believe our estimates remain accurate, and our recommendation against the use of this device to remove fibroids in the vast majority of women is appropriate and critical to better protecting these women. We are committed to continuing to review new relevant data to assure patient safety.”
The review determined that 1 in 350 women undergoing hysterectomy or myomectomy for fibroids may have an occult uterine sarcoma, and that 1 in about 500 have an unsuspected leiomyosarcoma. The literature review clearly identified increased risk of uterine cancers and decreased survival when these women are treated with an LPM, as opposed to manual morcellation or en bloc removal.
Twelve studies of women with uterine cancers examined this outcome in comparison groups. LPMs were associated with a 2- to 3-times increased risk of disease recurrence, compared with manual morcellation or other fibroid removal methods. In some studies, disease-free survival was significantly shorter among those who had undergone an LPM procedure; others found a higher risk of death – including, in one study, almost a quintupling of mortality risk by 1 year (crude risk ratio, 4.75).
Device-related malignancies began appearing in 2013; since then, 262 cases have been reported. But after the 2014 warning, use of LPMs in this application has decreased sharply. Two studies examined this, one finding that LPM use in fibroid surgery dropped from 14% to 3% and the other, that it dropped from 11% to 0.02%.
“The agency also continues to recommend that the advantages and risks of using LPMs during fibroid surgery be thoroughly discussed between the patient and physician before surgery,” the paper concluded. “FDA continues to actively encourage and engage in research to evaluate outcomes for a range of treatment options for fibroids and support the development of safer alternatives for providing a minimally invasive approach.”
[email protected]
AHA: Childhood adversity strongly linked to poorer health outcomes
Research suggests an association between adverse childhood events and poorer cardiometabolic health across the lifespan, a new scientific statement from the American Heart Association declares, although it acknowledges various limitations in understanding the connection.
Studies haven’t confirmed a cause-and-effect relationship or the full extent of excess risk, and it’s not clear why some people who experience childhood trauma are more resilient than others. There’s also scant information about any link to higher cardiometabolic death rates.
For the new statement, which appears in Circulation, researchers reviewed recent systematic reviews into the links between childhood adversity – including events like violence and abuse – and cardiometabolic outcome.
By one estimate, nearly 60% of adults in the United States experienced at least one adverse childhood event. According to the statement, reviews have linked childhood adversity to higher risks of cardiac death and outcomes like heart attack and stroke. They’ve also linked adversity to risk factors like high blood pressure, obesity, and type 2 diabetes.
the statement said. However, Dr. Suglia noted that research into mortality is limited.
The level of higher risk varies by study and outcome, and no one knows if there’s a cause-and-effect link. “As you can imagine, child adversity is not an exposure that lends itself to randomized trials,” she said. “On top of that, we are talking about health effects that take many years to manifest so we rely on observational studies.”
However, “while there is a possibility that there is an alternate factor that is responsible for these associations, the evidence is consistent across different populations,” said Dr. Suglia of Emory University in Atlanta. “And in general, studies do consider alternative factors that may be associated with both child adversity and cardiovascular health, further strengthening inferences we can make from the observational studies.”
Why might the association exist? “The mechanisms that drive these associations are still not fully elucidated but we hypothesize three pathways that may mediate these associations: behavioral factors (diet, sleep, physical activity, smoking), biological (hypothalamic-pituitary-adrenal axis dysregulation, epigenetic, chronic inflammation), and mental health (posttraumatic stress disorder and depression),” she said.
The statement notes that research is limited into why some people thrive on the cardiometabolic front despite childhood adversity. “One of the recommendations is that we need to focus more on factors that could inform prevention and intervention efforts so that those that are affected by adversity in childhood are not also affected by adverse cardiovascular events,” Dr. Suglia said.
The statement also notes that there’s been only limited research into modifiers of vulnerability to the effects of childhood adversity, such as gender, race/ethnicity, genetics, and community characteristics. And it says there’s been little study of how early interventions may affect cardiometabolic outcomes: “Additional research, including longitudinal prospective studies, designed to guide and inform effective and timely individual/clinical and population-level preventive interventions is required.”
Dr. Suglia reports a research grant from the National Heart, Lung, and Blood Institute. Most of the other statement coauthors report no disclosures outside of government funding.
SOURCE: Suglia S et al. Circulation. 2017 Dec 18. doi: 10.1161/CIR.0000000000000536
Research suggests an association between adverse childhood events and poorer cardiometabolic health across the lifespan, a new scientific statement from the American Heart Association declares, although it acknowledges various limitations in understanding the connection.
Studies haven’t confirmed a cause-and-effect relationship or the full extent of excess risk, and it’s not clear why some people who experience childhood trauma are more resilient than others. There’s also scant information about any link to higher cardiometabolic death rates.
For the new statement, which appears in Circulation, researchers reviewed recent systematic reviews into the links between childhood adversity – including events like violence and abuse – and cardiometabolic outcome.
By one estimate, nearly 60% of adults in the United States experienced at least one adverse childhood event. According to the statement, reviews have linked childhood adversity to higher risks of cardiac death and outcomes like heart attack and stroke. They’ve also linked adversity to risk factors like high blood pressure, obesity, and type 2 diabetes.
the statement said. However, Dr. Suglia noted that research into mortality is limited.
The level of higher risk varies by study and outcome, and no one knows if there’s a cause-and-effect link. “As you can imagine, child adversity is not an exposure that lends itself to randomized trials,” she said. “On top of that, we are talking about health effects that take many years to manifest so we rely on observational studies.”
However, “while there is a possibility that there is an alternate factor that is responsible for these associations, the evidence is consistent across different populations,” said Dr. Suglia of Emory University in Atlanta. “And in general, studies do consider alternative factors that may be associated with both child adversity and cardiovascular health, further strengthening inferences we can make from the observational studies.”
Why might the association exist? “The mechanisms that drive these associations are still not fully elucidated but we hypothesize three pathways that may mediate these associations: behavioral factors (diet, sleep, physical activity, smoking), biological (hypothalamic-pituitary-adrenal axis dysregulation, epigenetic, chronic inflammation), and mental health (posttraumatic stress disorder and depression),” she said.
The statement notes that research is limited into why some people thrive on the cardiometabolic front despite childhood adversity. “One of the recommendations is that we need to focus more on factors that could inform prevention and intervention efforts so that those that are affected by adversity in childhood are not also affected by adverse cardiovascular events,” Dr. Suglia said.
The statement also notes that there’s been only limited research into modifiers of vulnerability to the effects of childhood adversity, such as gender, race/ethnicity, genetics, and community characteristics. And it says there’s been little study of how early interventions may affect cardiometabolic outcomes: “Additional research, including longitudinal prospective studies, designed to guide and inform effective and timely individual/clinical and population-level preventive interventions is required.”
Dr. Suglia reports a research grant from the National Heart, Lung, and Blood Institute. Most of the other statement coauthors report no disclosures outside of government funding.
SOURCE: Suglia S et al. Circulation. 2017 Dec 18. doi: 10.1161/CIR.0000000000000536
Research suggests an association between adverse childhood events and poorer cardiometabolic health across the lifespan, a new scientific statement from the American Heart Association declares, although it acknowledges various limitations in understanding the connection.
Studies haven’t confirmed a cause-and-effect relationship or the full extent of excess risk, and it’s not clear why some people who experience childhood trauma are more resilient than others. There’s also scant information about any link to higher cardiometabolic death rates.
For the new statement, which appears in Circulation, researchers reviewed recent systematic reviews into the links between childhood adversity – including events like violence and abuse – and cardiometabolic outcome.
By one estimate, nearly 60% of adults in the United States experienced at least one adverse childhood event. According to the statement, reviews have linked childhood adversity to higher risks of cardiac death and outcomes like heart attack and stroke. They’ve also linked adversity to risk factors like high blood pressure, obesity, and type 2 diabetes.
the statement said. However, Dr. Suglia noted that research into mortality is limited.
The level of higher risk varies by study and outcome, and no one knows if there’s a cause-and-effect link. “As you can imagine, child adversity is not an exposure that lends itself to randomized trials,” she said. “On top of that, we are talking about health effects that take many years to manifest so we rely on observational studies.”
However, “while there is a possibility that there is an alternate factor that is responsible for these associations, the evidence is consistent across different populations,” said Dr. Suglia of Emory University in Atlanta. “And in general, studies do consider alternative factors that may be associated with both child adversity and cardiovascular health, further strengthening inferences we can make from the observational studies.”
Why might the association exist? “The mechanisms that drive these associations are still not fully elucidated but we hypothesize three pathways that may mediate these associations: behavioral factors (diet, sleep, physical activity, smoking), biological (hypothalamic-pituitary-adrenal axis dysregulation, epigenetic, chronic inflammation), and mental health (posttraumatic stress disorder and depression),” she said.
The statement notes that research is limited into why some people thrive on the cardiometabolic front despite childhood adversity. “One of the recommendations is that we need to focus more on factors that could inform prevention and intervention efforts so that those that are affected by adversity in childhood are not also affected by adverse cardiovascular events,” Dr. Suglia said.
The statement also notes that there’s been only limited research into modifiers of vulnerability to the effects of childhood adversity, such as gender, race/ethnicity, genetics, and community characteristics. And it says there’s been little study of how early interventions may affect cardiometabolic outcomes: “Additional research, including longitudinal prospective studies, designed to guide and inform effective and timely individual/clinical and population-level preventive interventions is required.”
Dr. Suglia reports a research grant from the National Heart, Lung, and Blood Institute. Most of the other statement coauthors report no disclosures outside of government funding.
SOURCE: Suglia S et al. Circulation. 2017 Dec 18. doi: 10.1161/CIR.0000000000000536
FROM CIRCULATION
Self-administered subcutaneous Depo-Provera ‘feasible and acceptable’
Self-administration of subcutaneous depot medroxyprogesterone acetate contraceptive is a “feasible and acceptable” alternative to clinic-based administration, according to a study published online Dec. 12 in Contraception.
Researchers randomized 401 women aged 15-44 years – who had requested depot medroxyprogesterone acetate – to four injections over the year, administered by clinic staff at one of three Planned Parenthood health centers or self-administered at home.
The self-administered group performed the first injection at the clinic under supervision, then received instructions and three doses for home use.
At the 12-month follow-up, the rates of continuous use of the contraceptive – defined as reporting two additional doses on the 6-month survey and at least one additional dose on the 12-month survey – were 69% in the self-administration group and 54% in the clinic group (P = .005).
A significantly greater proportion of women in the self-administration group reported receiving at least four shots over the study period, compared with the clinic administration group (78% vs. 64%; P = .008). The authors also noted that 64% of the self-administration group reported receiving five doses – an additional poststudy shot – compared with 52% of the clinic group.
The self-administered injection was well received by women in that group, with 97% saying it was very or somewhat easy to administer, and 87% saying they would recommend self-injection to a friend.
Around half of the participants in the clinic group said they would be interested in self-administration in the future, but both groups reported similar levels of satisfaction with the injectable contraceptive overall.
“A survey study found that women who had difficulty obtaining or refilling a prescription in the past year were almost twice as likely to be interested in self-administration compared to those without such difficulty, suggesting that self-administration has potential to reduce barriers and disparities in access to effective contraception,” wrote Julia E. Kohn, PhD, MPA, and her colleagues at Planned Parenthood. “It is important to note, however, that potential barriers related to insurance coverage and reimbursement will need to be identified and addressed for self-administration to be successfully put into practice.”
There were three pregnancies. They were in the clinic group in women who had discontinued the contraceptive, and one was a planned pregnancy. There were two reports of pain and two reports of bruising at the injection site, but no serious adverse events were reported.
While the study relied on self-report of successful injections, the authors pointed to a recent study in which all women who reported self-injections had therapeutic levels of depot medroxyprogesterone acetate confirmed by blood testing.
Tara Health Foundation supported the study. Pfizer provided the study drug through an investigator-initiated research grant. No disclosures were made.
SOURCE: Kohn JE et al. Contraception. 2017 Dec 7. doi: 10.1016/j.contraception.2017.11.009
Self-administration of subcutaneous depot medroxyprogesterone acetate contraceptive is a “feasible and acceptable” alternative to clinic-based administration, according to a study published online Dec. 12 in Contraception.
Researchers randomized 401 women aged 15-44 years – who had requested depot medroxyprogesterone acetate – to four injections over the year, administered by clinic staff at one of three Planned Parenthood health centers or self-administered at home.
The self-administered group performed the first injection at the clinic under supervision, then received instructions and three doses for home use.
At the 12-month follow-up, the rates of continuous use of the contraceptive – defined as reporting two additional doses on the 6-month survey and at least one additional dose on the 12-month survey – were 69% in the self-administration group and 54% in the clinic group (P = .005).
A significantly greater proportion of women in the self-administration group reported receiving at least four shots over the study period, compared with the clinic administration group (78% vs. 64%; P = .008). The authors also noted that 64% of the self-administration group reported receiving five doses – an additional poststudy shot – compared with 52% of the clinic group.
The self-administered injection was well received by women in that group, with 97% saying it was very or somewhat easy to administer, and 87% saying they would recommend self-injection to a friend.
Around half of the participants in the clinic group said they would be interested in self-administration in the future, but both groups reported similar levels of satisfaction with the injectable contraceptive overall.
“A survey study found that women who had difficulty obtaining or refilling a prescription in the past year were almost twice as likely to be interested in self-administration compared to those without such difficulty, suggesting that self-administration has potential to reduce barriers and disparities in access to effective contraception,” wrote Julia E. Kohn, PhD, MPA, and her colleagues at Planned Parenthood. “It is important to note, however, that potential barriers related to insurance coverage and reimbursement will need to be identified and addressed for self-administration to be successfully put into practice.”
There were three pregnancies. They were in the clinic group in women who had discontinued the contraceptive, and one was a planned pregnancy. There were two reports of pain and two reports of bruising at the injection site, but no serious adverse events were reported.
While the study relied on self-report of successful injections, the authors pointed to a recent study in which all women who reported self-injections had therapeutic levels of depot medroxyprogesterone acetate confirmed by blood testing.
Tara Health Foundation supported the study. Pfizer provided the study drug through an investigator-initiated research grant. No disclosures were made.
SOURCE: Kohn JE et al. Contraception. 2017 Dec 7. doi: 10.1016/j.contraception.2017.11.009
Self-administration of subcutaneous depot medroxyprogesterone acetate contraceptive is a “feasible and acceptable” alternative to clinic-based administration, according to a study published online Dec. 12 in Contraception.
Researchers randomized 401 women aged 15-44 years – who had requested depot medroxyprogesterone acetate – to four injections over the year, administered by clinic staff at one of three Planned Parenthood health centers or self-administered at home.
The self-administered group performed the first injection at the clinic under supervision, then received instructions and three doses for home use.
At the 12-month follow-up, the rates of continuous use of the contraceptive – defined as reporting two additional doses on the 6-month survey and at least one additional dose on the 12-month survey – were 69% in the self-administration group and 54% in the clinic group (P = .005).
A significantly greater proportion of women in the self-administration group reported receiving at least four shots over the study period, compared with the clinic administration group (78% vs. 64%; P = .008). The authors also noted that 64% of the self-administration group reported receiving five doses – an additional poststudy shot – compared with 52% of the clinic group.
The self-administered injection was well received by women in that group, with 97% saying it was very or somewhat easy to administer, and 87% saying they would recommend self-injection to a friend.
Around half of the participants in the clinic group said they would be interested in self-administration in the future, but both groups reported similar levels of satisfaction with the injectable contraceptive overall.
“A survey study found that women who had difficulty obtaining or refilling a prescription in the past year were almost twice as likely to be interested in self-administration compared to those without such difficulty, suggesting that self-administration has potential to reduce barriers and disparities in access to effective contraception,” wrote Julia E. Kohn, PhD, MPA, and her colleagues at Planned Parenthood. “It is important to note, however, that potential barriers related to insurance coverage and reimbursement will need to be identified and addressed for self-administration to be successfully put into practice.”
There were three pregnancies. They were in the clinic group in women who had discontinued the contraceptive, and one was a planned pregnancy. There were two reports of pain and two reports of bruising at the injection site, but no serious adverse events were reported.
While the study relied on self-report of successful injections, the authors pointed to a recent study in which all women who reported self-injections had therapeutic levels of depot medroxyprogesterone acetate confirmed by blood testing.
Tara Health Foundation supported the study. Pfizer provided the study drug through an investigator-initiated research grant. No disclosures were made.
SOURCE: Kohn JE et al. Contraception. 2017 Dec 7. doi: 10.1016/j.contraception.2017.11.009
FROM CONTRACEPTION
Key clinical point: Self-administration of subcutaneous depot medroxyprogesterone acetate contraceptive is a “feasible and acceptable” alternative to administration in a clinic.
Major finding: The rates of continuous use of subcutaneous depot medroxyprogesterone acetate were 69% in the self-administration group and 54% in the clinic group.
Data source: Randomized controlled trial of 401 women.
Disclosures: Tara Health Foundation supported the study. Pfizer provided the study drug through an investigator-initiated research grant. No disclosures were made.
Source: Kohn JE et al. Contraception. 2017 Dec 7. doi: 10.1016/j.contraception.2017.11.009.
Pseudomyogenic Hemangioendothelioma
Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,1 is a rare soft tissue tumor that was described in 1992 by Mirra et al2 as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.
Case Report
A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.
After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.
Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.
Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.
Comment
Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.3 It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.4 The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.5
Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al2 as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al6 under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.
Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al7 (N=8) in 2017 and Hornick and Fletcher4 (N=50) in 2011. Hornick and Fletcher4 reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al7 also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher4 and 0.3 to 6.0 com in the series by Pradhan et al.7 Hornick and Fletcher4 reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,7 with 2 cases occurring on the arm. In the series by Hornick and Fletcher,4 the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.4 Pradhan et al7 also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.5-10
Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.4 The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.4,11
Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.
Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.12 Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.16
Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,4 adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.5 In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.13
Conclusion
In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.
- Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma (pseudomyogenic hemangioendothelioma). Am J Surg Pathol. 2011;35:1088; author reply 1088-1089.
- Mirra JM, Kessler S, Bhuta S, et al. The fibroma-like variant of epithelioid sarcoma. a fibrohistiocytic/myoid cell lesion often confused with benign and malignant spindle cell tumors. Cancer. 1992;69:1382-1395.
- Jo VY, Fletcher CD. WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology. 2014;46:95-104.
- Hornick JL, Fletcher CD. Pseudomyogenic hemangioendothelioma: a distinctive, often multicentric tumor with indolent behavior. Am J Surg Pathol. 2011;35:190-201.
- Sheng W, Pan Y, Wang J. Pseudomyogenic hemangioendothelioma: report of an additional case with aggressive clinical course. Am J Dermatopathol. 2013;35:597-600.
- Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma. Am J Surg Pathol. 2003;27:48-57.
- Pradhan D, Schoedel K, McGough RL, et al. Pseudomyogenic hemangioendothelioma of skin, bone and soft tissue—a clinicopathological, immunohistochemical and fluorescence in situ hybridization study [published online November 2, 2017]. Hum Pathol. 2017. doi:0.1016/j.humpath.2017.10.023.
- Requena L, Santonja C, Martinez-Amo JL, et al. Cutaneous epithelioid sarcoma like (pseudomyogenic) hemangioendothelioma: a little-known low-grade cutaneous vascular neoplasm. JAMA Dermatol. 2013;149:459-465.
- McGinity M, Bartanusz V, Dengler B, et al. Pseudomyogenic hemangioendothelioma (epithelioid sarcoma-like hemangioendothelioma, fibroma-like variant of epithelioid sarcoma) of the thoracic spine. Eur Spine J. 2013;22(suppl 3):S506-S511.
- Stuart LN, Gardner JM, Lauer SR, et al. Epithelioid sarcoma-like (pseudomyogenic) hemangioendothelioma, clinically mimicking dermatofibroma, diagnosed by skin biopsy in a 30-year-old man. J Cutan Pathol. 2013;40:909-913.
- Amary MF, O’Donnell P, Berisha F, et al. Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma: characterization of five cases. Skeletal Radiol. 2013;42:947-957.
- Hornick JL, Dal Cin P, Fletcher CD. Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol. 2009;33:542-550.
- Chbani L, Guillou L, Terrier P, et al. Epithelioid sarcoma: a clinicopathologic and immunohistochemical analysis of 106 cases from the French Sarcoma Group. Am J Clin Pathol. 2009;131:222-227.
- Fisher C. Epithelioid sarcoma of Enzinger. Adv Anat Pathol. 2006;13:114-121.
- Requena L, Santonja C, Martinez-Amo JL, et al. Cutaneous epithelioid sarcoma like (pseudomyogenic) hemangioendothelioma: a little-known low-grade cutaneous vascular neoplasm. JAMA Dermatol. 2013;149:459-465.
- Trombetta D, Magnusson L, von Steyern FV, et al. Translocation t(7;19)(q22;q13)—a recurrent chromosome aberration in pseudomyogenic hemangioendothelioma? Cancer Genet. 2011;204:211-215.
Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,1 is a rare soft tissue tumor that was described in 1992 by Mirra et al2 as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.
Case Report
A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.
After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.
Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.
Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.
Comment
Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.3 It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.4 The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.5
Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al2 as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al6 under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.
Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al7 (N=8) in 2017 and Hornick and Fletcher4 (N=50) in 2011. Hornick and Fletcher4 reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al7 also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher4 and 0.3 to 6.0 com in the series by Pradhan et al.7 Hornick and Fletcher4 reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,7 with 2 cases occurring on the arm. In the series by Hornick and Fletcher,4 the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.4 Pradhan et al7 also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.5-10
Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.4 The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.4,11
Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.
Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.12 Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.16
Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,4 adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.5 In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.13
Conclusion
In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.
Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,1 is a rare soft tissue tumor that was described in 1992 by Mirra et al2 as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.
Case Report
A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.
After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.
Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.
Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.
Comment
Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.3 It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.4 The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.5
Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al2 as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al6 under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.
Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al7 (N=8) in 2017 and Hornick and Fletcher4 (N=50) in 2011. Hornick and Fletcher4 reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al7 also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher4 and 0.3 to 6.0 com in the series by Pradhan et al.7 Hornick and Fletcher4 reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,7 with 2 cases occurring on the arm. In the series by Hornick and Fletcher,4 the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.4 Pradhan et al7 also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.5-10
Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.4 The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.4,11
Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.
Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.12 Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.16
Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,4 adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.5 In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.13
Conclusion
In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.
- Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma (pseudomyogenic hemangioendothelioma). Am J Surg Pathol. 2011;35:1088; author reply 1088-1089.
- Mirra JM, Kessler S, Bhuta S, et al. The fibroma-like variant of epithelioid sarcoma. a fibrohistiocytic/myoid cell lesion often confused with benign and malignant spindle cell tumors. Cancer. 1992;69:1382-1395.
- Jo VY, Fletcher CD. WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology. 2014;46:95-104.
- Hornick JL, Fletcher CD. Pseudomyogenic hemangioendothelioma: a distinctive, often multicentric tumor with indolent behavior. Am J Surg Pathol. 2011;35:190-201.
- Sheng W, Pan Y, Wang J. Pseudomyogenic hemangioendothelioma: report of an additional case with aggressive clinical course. Am J Dermatopathol. 2013;35:597-600.
- Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma. Am J Surg Pathol. 2003;27:48-57.
- Pradhan D, Schoedel K, McGough RL, et al. Pseudomyogenic hemangioendothelioma of skin, bone and soft tissue—a clinicopathological, immunohistochemical and fluorescence in situ hybridization study [published online November 2, 2017]. Hum Pathol. 2017. doi:0.1016/j.humpath.2017.10.023.
- Requena L, Santonja C, Martinez-Amo JL, et al. Cutaneous epithelioid sarcoma like (pseudomyogenic) hemangioendothelioma: a little-known low-grade cutaneous vascular neoplasm. JAMA Dermatol. 2013;149:459-465.
- McGinity M, Bartanusz V, Dengler B, et al. Pseudomyogenic hemangioendothelioma (epithelioid sarcoma-like hemangioendothelioma, fibroma-like variant of epithelioid sarcoma) of the thoracic spine. Eur Spine J. 2013;22(suppl 3):S506-S511.
- Stuart LN, Gardner JM, Lauer SR, et al. Epithelioid sarcoma-like (pseudomyogenic) hemangioendothelioma, clinically mimicking dermatofibroma, diagnosed by skin biopsy in a 30-year-old man. J Cutan Pathol. 2013;40:909-913.
- Amary MF, O’Donnell P, Berisha F, et al. Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma: characterization of five cases. Skeletal Radiol. 2013;42:947-957.
- Hornick JL, Dal Cin P, Fletcher CD. Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol. 2009;33:542-550.
- Chbani L, Guillou L, Terrier P, et al. Epithelioid sarcoma: a clinicopathologic and immunohistochemical analysis of 106 cases from the French Sarcoma Group. Am J Clin Pathol. 2009;131:222-227.
- Fisher C. Epithelioid sarcoma of Enzinger. Adv Anat Pathol. 2006;13:114-121.
- Requena L, Santonja C, Martinez-Amo JL, et al. Cutaneous epithelioid sarcoma like (pseudomyogenic) hemangioendothelioma: a little-known low-grade cutaneous vascular neoplasm. JAMA Dermatol. 2013;149:459-465.
- Trombetta D, Magnusson L, von Steyern FV, et al. Translocation t(7;19)(q22;q13)—a recurrent chromosome aberration in pseudomyogenic hemangioendothelioma? Cancer Genet. 2011;204:211-215.
- Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma (pseudomyogenic hemangioendothelioma). Am J Surg Pathol. 2011;35:1088; author reply 1088-1089.
- Mirra JM, Kessler S, Bhuta S, et al. The fibroma-like variant of epithelioid sarcoma. a fibrohistiocytic/myoid cell lesion often confused with benign and malignant spindle cell tumors. Cancer. 1992;69:1382-1395.
- Jo VY, Fletcher CD. WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology. 2014;46:95-104.
- Hornick JL, Fletcher CD. Pseudomyogenic hemangioendothelioma: a distinctive, often multicentric tumor with indolent behavior. Am J Surg Pathol. 2011;35:190-201.
- Sheng W, Pan Y, Wang J. Pseudomyogenic hemangioendothelioma: report of an additional case with aggressive clinical course. Am J Dermatopathol. 2013;35:597-600.
- Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma. Am J Surg Pathol. 2003;27:48-57.
- Pradhan D, Schoedel K, McGough RL, et al. Pseudomyogenic hemangioendothelioma of skin, bone and soft tissue—a clinicopathological, immunohistochemical and fluorescence in situ hybridization study [published online November 2, 2017]. Hum Pathol. 2017. doi:0.1016/j.humpath.2017.10.023.
- Requena L, Santonja C, Martinez-Amo JL, et al. Cutaneous epithelioid sarcoma like (pseudomyogenic) hemangioendothelioma: a little-known low-grade cutaneous vascular neoplasm. JAMA Dermatol. 2013;149:459-465.
- McGinity M, Bartanusz V, Dengler B, et al. Pseudomyogenic hemangioendothelioma (epithelioid sarcoma-like hemangioendothelioma, fibroma-like variant of epithelioid sarcoma) of the thoracic spine. Eur Spine J. 2013;22(suppl 3):S506-S511.
- Stuart LN, Gardner JM, Lauer SR, et al. Epithelioid sarcoma-like (pseudomyogenic) hemangioendothelioma, clinically mimicking dermatofibroma, diagnosed by skin biopsy in a 30-year-old man. J Cutan Pathol. 2013;40:909-913.
- Amary MF, O’Donnell P, Berisha F, et al. Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma: characterization of five cases. Skeletal Radiol. 2013;42:947-957.
- Hornick JL, Dal Cin P, Fletcher CD. Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol. 2009;33:542-550.
- Chbani L, Guillou L, Terrier P, et al. Epithelioid sarcoma: a clinicopathologic and immunohistochemical analysis of 106 cases from the French Sarcoma Group. Am J Clin Pathol. 2009;131:222-227.
- Fisher C. Epithelioid sarcoma of Enzinger. Adv Anat Pathol. 2006;13:114-121.
- Requena L, Santonja C, Martinez-Amo JL, et al. Cutaneous epithelioid sarcoma like (pseudomyogenic) hemangioendothelioma: a little-known low-grade cutaneous vascular neoplasm. JAMA Dermatol. 2013;149:459-465.
- Trombetta D, Magnusson L, von Steyern FV, et al. Translocation t(7;19)(q22;q13)—a recurrent chromosome aberration in pseudomyogenic hemangioendothelioma? Cancer Genet. 2011;204:211-215.
Practice Points
- Pseudomyogenic hemangioendothelioma (PMHE) is an uncommon vascular tumor that most often presents as multiple distinct nodules on the legs in young men.
- Pseudomyogenic hemangioendothelioma has an unusual immunohistochemistry staining pattern, with positive staining for cytokeratin AE1/AE3, CD31, and ERG but negative for CD34.
- Although local reoccurrence is common, PMHE metastasis is very uncommon.
Sequential chemotherapy and radiotherapy may be best in locally advanced NSCLC with negative margins
Chemotherapy followed by radiation resulted in superior outcomes compared with concurrent chemoradiotherapy in patients with non–small-cell lung cancer (NSCLC) who had negative margins after surgery and pN2 disease, according to results of a retrospective analysis.
“We also found that sequential therapy is becoming the more frequent practice pattern over time for patients with R0 pN2 disease, and our results support this practice,” wrote Samual Francis, MD, of the University of Utah Huntsman Cancer Institute, Salt Lake City, and his coauthors.
By contrast, there was no clear association between treatment sequence and survival among patients who had positive margins after surgery in this analysis, authors of the study reported (J Clin Oncol. 2017 Dec 13. doi: 10.1200/JCO.2017.74.4771).
The study included 1,024 patients in National Cancer Database who received a diagnosis of nonmetastatic NSCLC and received chemotherapy and radiation concurrently or sequentially after surgery. Of those patients, 747 had R0 resections and pN2 nodal status, and the remainder had R1 or R2 resections and pN0-N2 disease.
For patients with R0 pN2 NSCLC, median overall survival was 58.8 months for sequential chemotherapy followed by radiation, versus 40.4 months for concurrent chemoradiotherapy (log-rank P less than .001), data show.
That association between sequential treatment and improved overall survival remained significant even after propensity score matching (hazard ratio [HR], 1.35; P = .019), investigators reported.
However, for the remaining cohort of patients with positive margins regardless of nodal status, there was no significant difference in overall survival favoring either approach (42.6 months for sequential versus 38.5 months for concurrent; log-rank P = .42), they added, and no clear association between treatment approaches (HR 1.35; P = .19).
The analysis covered patients diagnosed between 2006 and 2012, the most recent data period available.
Investigators were also able to identify changes in practice patterns over time using this data set. Between 2006 and 2012, there was an increase in the use of sequential chemotherapy and radiotherapy for patients with R0 resection and pN2 disease, and a decrease in the use of concurrent chemoradiotherapy.
Conversely, they found that for patients with positive margins, there was an increase over time in use of the concurrent approach and decrease in the sequential approach.
“These findings suggest practice patterns have shifted toward concordance with consensus guideline recommendations over time,” Dr. Francis and his colleagues said in their report.
Current guidelines advocate for chemotherapy followed by postoperative radiotherapy for patients with negative margins and pN2 disease, but suggest concurrent chemoradiotherapy for patients with positive margins, they added.
Dr. Francis had no relationships to disclose. Study coauthors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.
Chemotherapy followed by radiation resulted in superior outcomes compared with concurrent chemoradiotherapy in patients with non–small-cell lung cancer (NSCLC) who had negative margins after surgery and pN2 disease, according to results of a retrospective analysis.
“We also found that sequential therapy is becoming the more frequent practice pattern over time for patients with R0 pN2 disease, and our results support this practice,” wrote Samual Francis, MD, of the University of Utah Huntsman Cancer Institute, Salt Lake City, and his coauthors.
By contrast, there was no clear association between treatment sequence and survival among patients who had positive margins after surgery in this analysis, authors of the study reported (J Clin Oncol. 2017 Dec 13. doi: 10.1200/JCO.2017.74.4771).
The study included 1,024 patients in National Cancer Database who received a diagnosis of nonmetastatic NSCLC and received chemotherapy and radiation concurrently or sequentially after surgery. Of those patients, 747 had R0 resections and pN2 nodal status, and the remainder had R1 or R2 resections and pN0-N2 disease.
For patients with R0 pN2 NSCLC, median overall survival was 58.8 months for sequential chemotherapy followed by radiation, versus 40.4 months for concurrent chemoradiotherapy (log-rank P less than .001), data show.
That association between sequential treatment and improved overall survival remained significant even after propensity score matching (hazard ratio [HR], 1.35; P = .019), investigators reported.
However, for the remaining cohort of patients with positive margins regardless of nodal status, there was no significant difference in overall survival favoring either approach (42.6 months for sequential versus 38.5 months for concurrent; log-rank P = .42), they added, and no clear association between treatment approaches (HR 1.35; P = .19).
The analysis covered patients diagnosed between 2006 and 2012, the most recent data period available.
Investigators were also able to identify changes in practice patterns over time using this data set. Between 2006 and 2012, there was an increase in the use of sequential chemotherapy and radiotherapy for patients with R0 resection and pN2 disease, and a decrease in the use of concurrent chemoradiotherapy.
Conversely, they found that for patients with positive margins, there was an increase over time in use of the concurrent approach and decrease in the sequential approach.
“These findings suggest practice patterns have shifted toward concordance with consensus guideline recommendations over time,” Dr. Francis and his colleagues said in their report.
Current guidelines advocate for chemotherapy followed by postoperative radiotherapy for patients with negative margins and pN2 disease, but suggest concurrent chemoradiotherapy for patients with positive margins, they added.
Dr. Francis had no relationships to disclose. Study coauthors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.
Chemotherapy followed by radiation resulted in superior outcomes compared with concurrent chemoradiotherapy in patients with non–small-cell lung cancer (NSCLC) who had negative margins after surgery and pN2 disease, according to results of a retrospective analysis.
“We also found that sequential therapy is becoming the more frequent practice pattern over time for patients with R0 pN2 disease, and our results support this practice,” wrote Samual Francis, MD, of the University of Utah Huntsman Cancer Institute, Salt Lake City, and his coauthors.
By contrast, there was no clear association between treatment sequence and survival among patients who had positive margins after surgery in this analysis, authors of the study reported (J Clin Oncol. 2017 Dec 13. doi: 10.1200/JCO.2017.74.4771).
The study included 1,024 patients in National Cancer Database who received a diagnosis of nonmetastatic NSCLC and received chemotherapy and radiation concurrently or sequentially after surgery. Of those patients, 747 had R0 resections and pN2 nodal status, and the remainder had R1 or R2 resections and pN0-N2 disease.
For patients with R0 pN2 NSCLC, median overall survival was 58.8 months for sequential chemotherapy followed by radiation, versus 40.4 months for concurrent chemoradiotherapy (log-rank P less than .001), data show.
That association between sequential treatment and improved overall survival remained significant even after propensity score matching (hazard ratio [HR], 1.35; P = .019), investigators reported.
However, for the remaining cohort of patients with positive margins regardless of nodal status, there was no significant difference in overall survival favoring either approach (42.6 months for sequential versus 38.5 months for concurrent; log-rank P = .42), they added, and no clear association between treatment approaches (HR 1.35; P = .19).
The analysis covered patients diagnosed between 2006 and 2012, the most recent data period available.
Investigators were also able to identify changes in practice patterns over time using this data set. Between 2006 and 2012, there was an increase in the use of sequential chemotherapy and radiotherapy for patients with R0 resection and pN2 disease, and a decrease in the use of concurrent chemoradiotherapy.
Conversely, they found that for patients with positive margins, there was an increase over time in use of the concurrent approach and decrease in the sequential approach.
“These findings suggest practice patterns have shifted toward concordance with consensus guideline recommendations over time,” Dr. Francis and his colleagues said in their report.
Current guidelines advocate for chemotherapy followed by postoperative radiotherapy for patients with negative margins and pN2 disease, but suggest concurrent chemoradiotherapy for patients with positive margins, they added.
Dr. Francis had no relationships to disclose. Study coauthors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: In patients with pN2 non–small-cell lung cancer who have negative margins after surgery, sequential chemotherapy and radiotherapy provided superior outcomes compared with concurrent chemoradiotherapy.
Major finding: Median overall survival was 58.8 months for the sequential approach and 40.4 months for concurrent (log-rank P less than .001).
Data source: A retrospective analysis including 1,024 patients with nonmetastatic NSCLC who received chemotherapy and radiation concurrently or sequentially after surgery.
Disclosures: Study authors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.
Sleepless in adolescence
One thing that constantly surprises me about adolescent sleep is that neither the teen nor the parent is as concerned about it as I am. Instead, they complain about irritability, dropping grades, anxiety, depression, obesity, oppositionality, fatigue, and even substance use – all documented effects of sleep debt.
Inadequate sleep changes the brain, resulting in thinner gray matter, less neuroplasticity, poorer higher-level cognitive abilities (attention, working memory, inhibition, judgment, decision-making), lower motivation, and poorer academic functioning. None of these are losses teens can afford!
While sleep problems are more common in those with mental health disorders, poor sleep precedes anxiety and depression more than the reverse. Sleep problems increase the risk of depression, and depression relapses. Insomnia predicts risk behaviors – drinking and driving, smoking, delinquency. Getting less than 8 hours of sleep is associated with a threefold higher risk of suicide attempts.
Despite these pervasive threats to health and development, instead of concern, I find a lot of resistance in families and teens to taking action to improve sleep.
Teens don’t believe in problems from inadequate sleep. After all, they say, their peers are “all” getting the same amount of sleep. And they are largely correct – 75% of U.S. 12th graders get less than 8 hours of sleep. But the data are clear that children aged 12-18 years need 8.25-9.25 hours of sleep.
Parents generally are not aware of how little sleep their teens are getting because they go to bed on their own. If parents do check, any teenagers worth the label can growl their way out of supervision, “promise” to shut off the lights, or feign sleep. Having the house, pantry, and electronics to themselves at night is worth the risk of a consequence, especially for those who would rather avoid interacting.
The social forces keeping teens up at night are their “life”: the hours required for homework can be the reason for inadequate sleep. In subgroups of teens, sports practices, employment, or family responsibilities may extend the day past a bedtime needed for optimal sleep.
But use of electronics – the lifeline of adolescents – is responsible for much of their sleep debt. Electronic devices both delay sleep onset and reduce sleep duration. After 9:00 p.m., 34% of children aged older than 12 years are text messaging, 44% are talking, 55% are online, and 24% are playing computer games. Use of a TV or tablet at bedtime results in reduced sleep, and increased poor quality of sleep. Three or more hours of TV result not only in difficulty falling asleep and frequent awakenings, but also sleep issues later as adults. Shooter video games result in lower sleepiness, longer sleep latency, and shorter REM sleep. Even the low level light from electronic devices alters circadian rhythm and suppresses nocturnal melatonin secretion.
Keep in mind the biological reasons teens go to bed later. One is the typical emotional hyperarousal of being a teen. But other biological forces are at work in adolescence, such as reduction in the accumulation of sleep pressure during wakefulness and delaying the melatonin release that produces sleepiness. Teens (and parents) think sleeping in on weekends takes care of inadequate weekday sleep, but this so-called “recovery sleep” tends to occur at an inappropriate time in the circadian phase and further delays melatonin production, as well as reducing sleep pressure, making it even harder to fall asleep.
In some cases, medications we prescribe – such as stimulants, theophylline, antihistamines, or anticonvulsants – are at fault for delaying or disturbing sleep. But more often it is self-administered substances that are part of the teen’s attempt to stay awake – including nicotine, alcohol, and caffeine – that produce shorter sleep duration, increased latency to sleep, more wake time during sleep, and increased daytime sleepiness; it results in a vicious cycle. Sleep disruption may explain the association of these substances with less memory consolidation, poorer academic performance, and higher rates of risk behaviors.
We adults also are a cause of teen sleep debt. We are the ones allowing the early school start times for teens, primarily to allow for after school sports programs that glorify the school and bring kudos to some at the expense of all the students. A 65-minute earlier start in 10th grade resulted in less than half of students getting 7 hours of sleep or more. The level of resulting sleepiness is equal to that of narcolepsy.
As primary care clinicians, we can and need to detect, educate about, and treat sleep debt and sleep disorders. Sleep questionnaires can help. Treatment of sleep includes coaching for: having a cool, dark room used mainly for sleep; a regular schedule 7 days per week; avoiding exercise within 2 hours of bedtime; avoiding stimulants such as caffeine, tea, nicotine, and medications at least 3 hours before bedtime; keeping to a routine with no daytime naps; and especially no media in the bedroom! For teens already not able to sleep until early morning, you can recommend that they work bedtime back or forward by 1 hour per day until hitting a time that will allow 9 hours of sleep. Alternatively, have them stay up all night to reset their biological clock. Subsequently, the sleep schedule has to stay within 1 hour for sleep and waking 7 days per week. Anxious teens, besides needing therapy, may need a soothing routine, no visible clock, and a plan to get back up for 1 hour every time it takes longer than 10 minutes to fall asleep.
If sleepy teens report adequate time in bed, then we need to understand pathologies such as obstructive sleep apnea, restless legs syndrome, menstruation-related or primary hypersomnias, and narcolepsy to diagnose and resolve the problem.
Parents may have given up protecting their teens from inadequate sleep so we as health providers need to do so.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. E-mail her at [email protected].
One thing that constantly surprises me about adolescent sleep is that neither the teen nor the parent is as concerned about it as I am. Instead, they complain about irritability, dropping grades, anxiety, depression, obesity, oppositionality, fatigue, and even substance use – all documented effects of sleep debt.
Inadequate sleep changes the brain, resulting in thinner gray matter, less neuroplasticity, poorer higher-level cognitive abilities (attention, working memory, inhibition, judgment, decision-making), lower motivation, and poorer academic functioning. None of these are losses teens can afford!
While sleep problems are more common in those with mental health disorders, poor sleep precedes anxiety and depression more than the reverse. Sleep problems increase the risk of depression, and depression relapses. Insomnia predicts risk behaviors – drinking and driving, smoking, delinquency. Getting less than 8 hours of sleep is associated with a threefold higher risk of suicide attempts.
Despite these pervasive threats to health and development, instead of concern, I find a lot of resistance in families and teens to taking action to improve sleep.
Teens don’t believe in problems from inadequate sleep. After all, they say, their peers are “all” getting the same amount of sleep. And they are largely correct – 75% of U.S. 12th graders get less than 8 hours of sleep. But the data are clear that children aged 12-18 years need 8.25-9.25 hours of sleep.
Parents generally are not aware of how little sleep their teens are getting because they go to bed on their own. If parents do check, any teenagers worth the label can growl their way out of supervision, “promise” to shut off the lights, or feign sleep. Having the house, pantry, and electronics to themselves at night is worth the risk of a consequence, especially for those who would rather avoid interacting.
The social forces keeping teens up at night are their “life”: the hours required for homework can be the reason for inadequate sleep. In subgroups of teens, sports practices, employment, or family responsibilities may extend the day past a bedtime needed for optimal sleep.
But use of electronics – the lifeline of adolescents – is responsible for much of their sleep debt. Electronic devices both delay sleep onset and reduce sleep duration. After 9:00 p.m., 34% of children aged older than 12 years are text messaging, 44% are talking, 55% are online, and 24% are playing computer games. Use of a TV or tablet at bedtime results in reduced sleep, and increased poor quality of sleep. Three or more hours of TV result not only in difficulty falling asleep and frequent awakenings, but also sleep issues later as adults. Shooter video games result in lower sleepiness, longer sleep latency, and shorter REM sleep. Even the low level light from electronic devices alters circadian rhythm and suppresses nocturnal melatonin secretion.
Keep in mind the biological reasons teens go to bed later. One is the typical emotional hyperarousal of being a teen. But other biological forces are at work in adolescence, such as reduction in the accumulation of sleep pressure during wakefulness and delaying the melatonin release that produces sleepiness. Teens (and parents) think sleeping in on weekends takes care of inadequate weekday sleep, but this so-called “recovery sleep” tends to occur at an inappropriate time in the circadian phase and further delays melatonin production, as well as reducing sleep pressure, making it even harder to fall asleep.
In some cases, medications we prescribe – such as stimulants, theophylline, antihistamines, or anticonvulsants – are at fault for delaying or disturbing sleep. But more often it is self-administered substances that are part of the teen’s attempt to stay awake – including nicotine, alcohol, and caffeine – that produce shorter sleep duration, increased latency to sleep, more wake time during sleep, and increased daytime sleepiness; it results in a vicious cycle. Sleep disruption may explain the association of these substances with less memory consolidation, poorer academic performance, and higher rates of risk behaviors.
We adults also are a cause of teen sleep debt. We are the ones allowing the early school start times for teens, primarily to allow for after school sports programs that glorify the school and bring kudos to some at the expense of all the students. A 65-minute earlier start in 10th grade resulted in less than half of students getting 7 hours of sleep or more. The level of resulting sleepiness is equal to that of narcolepsy.
As primary care clinicians, we can and need to detect, educate about, and treat sleep debt and sleep disorders. Sleep questionnaires can help. Treatment of sleep includes coaching for: having a cool, dark room used mainly for sleep; a regular schedule 7 days per week; avoiding exercise within 2 hours of bedtime; avoiding stimulants such as caffeine, tea, nicotine, and medications at least 3 hours before bedtime; keeping to a routine with no daytime naps; and especially no media in the bedroom! For teens already not able to sleep until early morning, you can recommend that they work bedtime back or forward by 1 hour per day until hitting a time that will allow 9 hours of sleep. Alternatively, have them stay up all night to reset their biological clock. Subsequently, the sleep schedule has to stay within 1 hour for sleep and waking 7 days per week. Anxious teens, besides needing therapy, may need a soothing routine, no visible clock, and a plan to get back up for 1 hour every time it takes longer than 10 minutes to fall asleep.
If sleepy teens report adequate time in bed, then we need to understand pathologies such as obstructive sleep apnea, restless legs syndrome, menstruation-related or primary hypersomnias, and narcolepsy to diagnose and resolve the problem.
Parents may have given up protecting their teens from inadequate sleep so we as health providers need to do so.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. E-mail her at [email protected].
One thing that constantly surprises me about adolescent sleep is that neither the teen nor the parent is as concerned about it as I am. Instead, they complain about irritability, dropping grades, anxiety, depression, obesity, oppositionality, fatigue, and even substance use – all documented effects of sleep debt.
Inadequate sleep changes the brain, resulting in thinner gray matter, less neuroplasticity, poorer higher-level cognitive abilities (attention, working memory, inhibition, judgment, decision-making), lower motivation, and poorer academic functioning. None of these are losses teens can afford!
While sleep problems are more common in those with mental health disorders, poor sleep precedes anxiety and depression more than the reverse. Sleep problems increase the risk of depression, and depression relapses. Insomnia predicts risk behaviors – drinking and driving, smoking, delinquency. Getting less than 8 hours of sleep is associated with a threefold higher risk of suicide attempts.
Despite these pervasive threats to health and development, instead of concern, I find a lot of resistance in families and teens to taking action to improve sleep.
Teens don’t believe in problems from inadequate sleep. After all, they say, their peers are “all” getting the same amount of sleep. And they are largely correct – 75% of U.S. 12th graders get less than 8 hours of sleep. But the data are clear that children aged 12-18 years need 8.25-9.25 hours of sleep.
Parents generally are not aware of how little sleep their teens are getting because they go to bed on their own. If parents do check, any teenagers worth the label can growl their way out of supervision, “promise” to shut off the lights, or feign sleep. Having the house, pantry, and electronics to themselves at night is worth the risk of a consequence, especially for those who would rather avoid interacting.
The social forces keeping teens up at night are their “life”: the hours required for homework can be the reason for inadequate sleep. In subgroups of teens, sports practices, employment, or family responsibilities may extend the day past a bedtime needed for optimal sleep.
But use of electronics – the lifeline of adolescents – is responsible for much of their sleep debt. Electronic devices both delay sleep onset and reduce sleep duration. After 9:00 p.m., 34% of children aged older than 12 years are text messaging, 44% are talking, 55% are online, and 24% are playing computer games. Use of a TV or tablet at bedtime results in reduced sleep, and increased poor quality of sleep. Three or more hours of TV result not only in difficulty falling asleep and frequent awakenings, but also sleep issues later as adults. Shooter video games result in lower sleepiness, longer sleep latency, and shorter REM sleep. Even the low level light from electronic devices alters circadian rhythm and suppresses nocturnal melatonin secretion.
Keep in mind the biological reasons teens go to bed later. One is the typical emotional hyperarousal of being a teen. But other biological forces are at work in adolescence, such as reduction in the accumulation of sleep pressure during wakefulness and delaying the melatonin release that produces sleepiness. Teens (and parents) think sleeping in on weekends takes care of inadequate weekday sleep, but this so-called “recovery sleep” tends to occur at an inappropriate time in the circadian phase and further delays melatonin production, as well as reducing sleep pressure, making it even harder to fall asleep.
In some cases, medications we prescribe – such as stimulants, theophylline, antihistamines, or anticonvulsants – are at fault for delaying or disturbing sleep. But more often it is self-administered substances that are part of the teen’s attempt to stay awake – including nicotine, alcohol, and caffeine – that produce shorter sleep duration, increased latency to sleep, more wake time during sleep, and increased daytime sleepiness; it results in a vicious cycle. Sleep disruption may explain the association of these substances with less memory consolidation, poorer academic performance, and higher rates of risk behaviors.
We adults also are a cause of teen sleep debt. We are the ones allowing the early school start times for teens, primarily to allow for after school sports programs that glorify the school and bring kudos to some at the expense of all the students. A 65-minute earlier start in 10th grade resulted in less than half of students getting 7 hours of sleep or more. The level of resulting sleepiness is equal to that of narcolepsy.
As primary care clinicians, we can and need to detect, educate about, and treat sleep debt and sleep disorders. Sleep questionnaires can help. Treatment of sleep includes coaching for: having a cool, dark room used mainly for sleep; a regular schedule 7 days per week; avoiding exercise within 2 hours of bedtime; avoiding stimulants such as caffeine, tea, nicotine, and medications at least 3 hours before bedtime; keeping to a routine with no daytime naps; and especially no media in the bedroom! For teens already not able to sleep until early morning, you can recommend that they work bedtime back or forward by 1 hour per day until hitting a time that will allow 9 hours of sleep. Alternatively, have them stay up all night to reset their biological clock. Subsequently, the sleep schedule has to stay within 1 hour for sleep and waking 7 days per week. Anxious teens, besides needing therapy, may need a soothing routine, no visible clock, and a plan to get back up for 1 hour every time it takes longer than 10 minutes to fall asleep.
If sleepy teens report adequate time in bed, then we need to understand pathologies such as obstructive sleep apnea, restless legs syndrome, menstruation-related or primary hypersomnias, and narcolepsy to diagnose and resolve the problem.
Parents may have given up protecting their teens from inadequate sleep so we as health providers need to do so.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. E-mail her at [email protected].