Ketamine used to treat severe depression in patients with a history of psychosis does not exacerbate psychosis risk, new research suggests.

A meta-analysis of nine studies, encompassing 41 patients with TRD and a history of psychosis, suggests ketamine is safe and effective and did not exacerbate psychotic symptoms in this patient population.

“We believe our findings could encourage clinicians and researchers to examine a broadened indication for ketamine treatment in individual patients with high levels of treatment resistance, carefully monitoring both clinical response and side effects, specifically looking at possible increases in psychotic symptoms,” study investigator Jolien K. E. Veraart, MD, University of Groningen, University Medical Center Groningen, the Netherlands, told this news organization.

The study was published online July 13 in the Journal of Clinical Psychiatry.
 

Rapid, robust effects

Ketamine has shown “rapid and robust antidepressant effects” in clinical studies. However, this research has not included patients with past or current psychosis, based on the assumption that psychosis will increase with ketamine administration, since side effects of ketamine can include transient “schizophrenia-like” psychotomimetic phenomena, including perceptual disorders and hallucinations in healthy individuals, the investigators note.

Dr. Veraart said psychotic symptoms are “common in people with severe depression,” and these patients have poorer outcomes with pharmacotherapy, psychotherapy, and electroconvulsive therapy.

Additionally, up to 60% of patients with schizophrenia experience negative symptomatology, including loss of motivation, affective blunting, and anhedonia, which “has a clear phenomenological overlap with depression,” the authors write. They also note anti-anhedonic effects of subanesthetic ketamine doses have been reported, without adversely impacting long-term psychotic symptoms in patients with schizophrenia.

“Positive results from carefully monitored trials with ketamine treatment in these patients have motivated us to summarize the currently available knowledge to inform our colleagues,” she said.

To investigate, the researchers conducted a literature search and selected 9 articles (N = 41 patients) that reported on ketamine treatment in patients with a history of psychosis or current psychotic symptoms.

All studies were either case reports or pilot studies, the authors report. Types of patients included those with bipolar or unipolar depression, or depression in schizoaffective disorder , or patients with schizophrenia and concurrent depression. Depressive symptomatology was the treatment target in eight studies, and one study targeted negative symptoms in patients with schizophrenia.

Dosing, frequency, and types of administration (ketamine IV, esketamine IV, or esketamine subcutaneous) varied from study to study.

In seven studies, ketamine was found to improve depressive symptoms, and in two studies, improvement in psychotic symptoms was also shown. Two studies revealed improvement in symptoms of suicidality. Results of the study that measured negative symptoms showed “significant improvement” in five of six patients, with a -37.3% decrease in mean Brief Negative Symptoms Scale (BNSS) from the baseline to the end of four infusions.

“Ketamine showed good antidepressant effects, and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Dr. Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added.

She also noted that ketamine administration did not negatively influence the course of psychotic illness or induce psychotic exacerbations in patients.

She pointed to one study limitation, which is that only small, uncontrolled trials were included and that there is a risk for publication bias.
 

Larger trials needed

Commenting on the study, Dan Iosifescu, MD, MSc, associate professor of psychiatry, New York University School of Medicine, said that if the finding “were based on a larger study it would be very important, as a theoretical risk of psychosis is preventing such patients from access to an otherwise beneficial treatment.”

However, “since the review is based on a small sample, a low risk of psychosis exacerbation after IV ketamine is still possible,” said Dr. Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved with the study.

Dr. Veraart agreed, adding that the “efficacy, safety, and tolerability of ketamine in depressed patients with a vulnerability to psychosis should be investigated in well-designed randomized controlled trials before application on a large scale is promoted.”

The study had no specific funding. Dr. Veraart has received speaker honoraria from Janssen outside of the submitted work. The other authors’ disclosures are listed in the original article. Dr. Iosifescu has been a consultant to the Centers of Psychiatric Excellence, advising clinics on the best methods of providing treatment with IV ketamine.

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

Ketamine used to treat severe depression in patients with a history of psychosis does not exacerbate psychosis risk, new research suggests.

A meta-analysis of nine studies, encompassing 41 patients with TRD and a history of psychosis, suggests ketamine is safe and effective and did not exacerbate psychotic symptoms in this patient population.

“We believe our findings could encourage clinicians and researchers to examine a broadened indication for ketamine treatment in individual patients with high levels of treatment resistance, carefully monitoring both clinical response and side effects, specifically looking at possible increases in psychotic symptoms,” study investigator Jolien K. E. Veraart, MD, University of Groningen, University Medical Center Groningen, the Netherlands, told this news organization.

The study was published online July 13 in the Journal of Clinical Psychiatry.
 

Rapid, robust effects

Ketamine has shown “rapid and robust antidepressant effects” in clinical studies. However, this research has not included patients with past or current psychosis, based on the assumption that psychosis will increase with ketamine administration, since side effects of ketamine can include transient “schizophrenia-like” psychotomimetic phenomena, including perceptual disorders and hallucinations in healthy individuals, the investigators note.

Dr. Veraart said psychotic symptoms are “common in people with severe depression,” and these patients have poorer outcomes with pharmacotherapy, psychotherapy, and electroconvulsive therapy.

Additionally, up to 60% of patients with schizophrenia experience negative symptomatology, including loss of motivation, affective blunting, and anhedonia, which “has a clear phenomenological overlap with depression,” the authors write. They also note anti-anhedonic effects of subanesthetic ketamine doses have been reported, without adversely impacting long-term psychotic symptoms in patients with schizophrenia.

“Positive results from carefully monitored trials with ketamine treatment in these patients have motivated us to summarize the currently available knowledge to inform our colleagues,” she said.

To investigate, the researchers conducted a literature search and selected 9 articles (N = 41 patients) that reported on ketamine treatment in patients with a history of psychosis or current psychotic symptoms.

All studies were either case reports or pilot studies, the authors report. Types of patients included those with bipolar or unipolar depression, or depression in schizoaffective disorder , or patients with schizophrenia and concurrent depression. Depressive symptomatology was the treatment target in eight studies, and one study targeted negative symptoms in patients with schizophrenia.

Dosing, frequency, and types of administration (ketamine IV, esketamine IV, or esketamine subcutaneous) varied from study to study.

In seven studies, ketamine was found to improve depressive symptoms, and in two studies, improvement in psychotic symptoms was also shown. Two studies revealed improvement in symptoms of suicidality. Results of the study that measured negative symptoms showed “significant improvement” in five of six patients, with a -37.3% decrease in mean Brief Negative Symptoms Scale (BNSS) from the baseline to the end of four infusions.

“Ketamine showed good antidepressant effects, and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Dr. Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added.

She also noted that ketamine administration did not negatively influence the course of psychotic illness or induce psychotic exacerbations in patients.

She pointed to one study limitation, which is that only small, uncontrolled trials were included and that there is a risk for publication bias.
 

Larger trials needed

Commenting on the study, Dan Iosifescu, MD, MSc, associate professor of psychiatry, New York University School of Medicine, said that if the finding “were based on a larger study it would be very important, as a theoretical risk of psychosis is preventing such patients from access to an otherwise beneficial treatment.”

However, “since the review is based on a small sample, a low risk of psychosis exacerbation after IV ketamine is still possible,” said Dr. Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved with the study.

Dr. Veraart agreed, adding that the “efficacy, safety, and tolerability of ketamine in depressed patients with a vulnerability to psychosis should be investigated in well-designed randomized controlled trials before application on a large scale is promoted.”

The study had no specific funding. Dr. Veraart has received speaker honoraria from Janssen outside of the submitted work. The other authors’ disclosures are listed in the original article. Dr. Iosifescu has been a consultant to the Centers of Psychiatric Excellence, advising clinics on the best methods of providing treatment with IV ketamine.

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

Ketamine used to treat severe depression in patients with a history of psychosis does not exacerbate psychosis risk, new research suggests.

A meta-analysis of nine studies, encompassing 41 patients with TRD and a history of psychosis, suggests ketamine is safe and effective and did not exacerbate psychotic symptoms in this patient population.

“We believe our findings could encourage clinicians and researchers to examine a broadened indication for ketamine treatment in individual patients with high levels of treatment resistance, carefully monitoring both clinical response and side effects, specifically looking at possible increases in psychotic symptoms,” study investigator Jolien K. E. Veraart, MD, University of Groningen, University Medical Center Groningen, the Netherlands, told this news organization.

The study was published online July 13 in the Journal of Clinical Psychiatry.
 

Rapid, robust effects

Ketamine has shown “rapid and robust antidepressant effects” in clinical studies. However, this research has not included patients with past or current psychosis, based on the assumption that psychosis will increase with ketamine administration, since side effects of ketamine can include transient “schizophrenia-like” psychotomimetic phenomena, including perceptual disorders and hallucinations in healthy individuals, the investigators note.

Dr. Veraart said psychotic symptoms are “common in people with severe depression,” and these patients have poorer outcomes with pharmacotherapy, psychotherapy, and electroconvulsive therapy.

Additionally, up to 60% of patients with schizophrenia experience negative symptomatology, including loss of motivation, affective blunting, and anhedonia, which “has a clear phenomenological overlap with depression,” the authors write. They also note anti-anhedonic effects of subanesthetic ketamine doses have been reported, without adversely impacting long-term psychotic symptoms in patients with schizophrenia.

“Positive results from carefully monitored trials with ketamine treatment in these patients have motivated us to summarize the currently available knowledge to inform our colleagues,” she said.

To investigate, the researchers conducted a literature search and selected 9 articles (N = 41 patients) that reported on ketamine treatment in patients with a history of psychosis or current psychotic symptoms.

All studies were either case reports or pilot studies, the authors report. Types of patients included those with bipolar or unipolar depression, or depression in schizoaffective disorder , or patients with schizophrenia and concurrent depression. Depressive symptomatology was the treatment target in eight studies, and one study targeted negative symptoms in patients with schizophrenia.

Dosing, frequency, and types of administration (ketamine IV, esketamine IV, or esketamine subcutaneous) varied from study to study.

In seven studies, ketamine was found to improve depressive symptoms, and in two studies, improvement in psychotic symptoms was also shown. Two studies revealed improvement in symptoms of suicidality. Results of the study that measured negative symptoms showed “significant improvement” in five of six patients, with a -37.3% decrease in mean Brief Negative Symptoms Scale (BNSS) from the baseline to the end of four infusions.

“Ketamine showed good antidepressant effects, and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Dr. Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added.

She also noted that ketamine administration did not negatively influence the course of psychotic illness or induce psychotic exacerbations in patients.

She pointed to one study limitation, which is that only small, uncontrolled trials were included and that there is a risk for publication bias.
 

Larger trials needed

Commenting on the study, Dan Iosifescu, MD, MSc, associate professor of psychiatry, New York University School of Medicine, said that if the finding “were based on a larger study it would be very important, as a theoretical risk of psychosis is preventing such patients from access to an otherwise beneficial treatment.”

However, “since the review is based on a small sample, a low risk of psychosis exacerbation after IV ketamine is still possible,” said Dr. Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved with the study.

Dr. Veraart agreed, adding that the “efficacy, safety, and tolerability of ketamine in depressed patients with a vulnerability to psychosis should be investigated in well-designed randomized controlled trials before application on a large scale is promoted.”

The study had no specific funding. Dr. Veraart has received speaker honoraria from Janssen outside of the submitted work. The other authors’ disclosures are listed in the original article. Dr. Iosifescu has been a consultant to the Centers of Psychiatric Excellence, advising clinics on the best methods of providing treatment with IV ketamine.

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

At a recent town hall meeting in Cincinnati, President Joe Biden was asked about COVID-19 cases, hospitalizations, and deaths rising in response to the Delta variant.

Touting the importance of vaccination, “We have a pandemic for those who haven’t gotten a vaccination. It’s that basic, that simple,” President Biden said at the event, which was broadcast live on CNN.

Andriy Onufriyenko

“If you’re vaccinated, you’re not going to be hospitalized, not going to the ICU unit, and not going to die,” he said, adding “you’re not going to get COVID if you have these vaccinations.”

Unfortunately, it’s not so simple. Fully vaccinated people continue to be well protected against severe disease and death, even with Delta, but so-called breakthrough cases, where a person gets infected despite being fully vaccinated, are on the rise. Because of that, many experts continue to advise caution, even if fully vaccinated.

“I was disappointed,” Leana Wen, MD, MSc, an emergency physician and visiting professor of health policy and management at George Washington University’s Milken School of Public Health in Washington, told CNN in response to the president’s statement.

“I actually thought he was answering questions as if it were a month ago. He’s not really meeting the realities of what’s happening on the ground,” she said. “I think he may have led people astray.”
 

Vaccines still work

Recent cases support Dr. Wen’s claim. Fully vaccinated Olympic athletes, wedding guests, healthcare workers, and even White House staff have recently tested positive. So what gives?

The vast majority of these illnesses are mild, and public health officials say they are to be expected. 

“The vaccines were designed to keep us out of the hospital and to keep us from dying. That was the whole purpose of the vaccine and they’re even more successful than we anticipated,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville.

As good as they are, these shots aren’t perfect. Their protection differs from person to person depending on age and underlying health. People with immune function that’s weakened because of age or a health condition can still become seriously ill, and, in very rare cases, die after vaccination.

When people are infected with Delta, they carry approximately 1,000 times more virus compared with previous versions of the virus, according to a recent study. All that virus can overwhelm even the strong protection from the vaccines.

“Three months ago, breakthroughs didn’t occur nearly at this rate because there was just so much less virus exposure in the community,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
 

Breakthroughs by the numbers

In Los Angeles County, where 69% of residents over age 12 have been fully vaccinated, COVID-19 cases are rising, and so, too, are cases that break through the protection of the vaccine.

In June, fully vaccinated people accounted for 20%, or 1 in 5, COVID cases in the county, which is the most populous in the United States. The increase mirrors Delta’s rise. The proportion of breakthrough cases is up from 11% in May, 5% in April, and 2% in March, according to the Los Angeles County Department of Public Health. 

In the United Kingdom, which is collecting the best information on infections caused by variants, the estimated effectiveness of the vaccines to prevent an illness that causes symptoms dropped by about 10 points against Delta compared with Alpha (or B.1.1.7). 

After two doses, vaccines prevent symptomatic infection about 79% of the time against Delta, according to data compiled by Public Health England. They are still highly effective at preventing hospitalization, 96% after two doses.

Out of 229,218 COVID infections in the United Kingdom between February and July 19, 28,773 — or 12.5% — were in fully vaccinated people. Of those breakthrough infections, 1,101, or 3.8%, required a visit to an emergency room, according to Public Health England. Just 474, or 2.9%, of fully vaccinated people required hospital admission, and 229, or less than 1%, died.
 

Unanswered questions

One of the biggest questions about breakthrough cases is how often people who have it may pass the virus to others.

“We know the vaccine reduces the likelihood of carrying the virus and the amount of virus you would carry,” Dr. Wen told CNN. But we don’t yet know whether a vaccinated person with a breakthrough infection may still be contagious to others.

For that reason, the Centers for Disease Control and Prevention says that fully vaccinated people still need to be tested if they have symptoms and shouldn’t be out in public for at least 10 days after a positive test. 

How should fully vaccinated people behave? That depends a lot on their underlying health and whether or not they have vulnerable people around them. 

If you’re older or immunocompromised, Dr. Schaffner recommends what he calls the “belt-and-suspenders approach,” in other words, do everything you can to stay safe.

“Get vaccinated for sure, but since we can’t be absolutely certain that the vaccines are going to be optimally protective and you are particularly susceptible to serious disease, you would be well advised to adopt at least one and perhaps more of the other mitigation measures,” he said.

These include wearing a mask, social distancing, making sure your spaces are well ventilated, and not spending prolonged periods of time indoors in crowded places.

Taking young children to visit vaccinated, elderly grandparents demands extra caution, again, with Delta circulating, particularly as they go back to school and start mixing with other kids.

Dr. Schaffner recommends explaining the ground rules before the visit: Hugs around the waist. No kissing. Wearing a mask while indoors with them.

Other important unanswered questions are whether breakthrough infections can lead to prolonged symptoms, or “long covid.” Most experts think that’s less likely in vaccinated people.

And Dr. Osterholm said it will be important to see whether there’s anything unusual about the breakthrough cases happening in the community.

“I think some of us have been challenged by the number of clusters that we’ve seen,” he said. “I think that really needs to be examined more.”

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

At a recent town hall meeting in Cincinnati, President Joe Biden was asked about COVID-19 cases, hospitalizations, and deaths rising in response to the Delta variant.

Touting the importance of vaccination, “We have a pandemic for those who haven’t gotten a vaccination. It’s that basic, that simple,” President Biden said at the event, which was broadcast live on CNN.

Andriy Onufriyenko

“If you’re vaccinated, you’re not going to be hospitalized, not going to the ICU unit, and not going to die,” he said, adding “you’re not going to get COVID if you have these vaccinations.”

Unfortunately, it’s not so simple. Fully vaccinated people continue to be well protected against severe disease and death, even with Delta, but so-called breakthrough cases, where a person gets infected despite being fully vaccinated, are on the rise. Because of that, many experts continue to advise caution, even if fully vaccinated.

“I was disappointed,” Leana Wen, MD, MSc, an emergency physician and visiting professor of health policy and management at George Washington University’s Milken School of Public Health in Washington, told CNN in response to the president’s statement.

“I actually thought he was answering questions as if it were a month ago. He’s not really meeting the realities of what’s happening on the ground,” she said. “I think he may have led people astray.”
 

Vaccines still work

Recent cases support Dr. Wen’s claim. Fully vaccinated Olympic athletes, wedding guests, healthcare workers, and even White House staff have recently tested positive. So what gives?

The vast majority of these illnesses are mild, and public health officials say they are to be expected. 

“The vaccines were designed to keep us out of the hospital and to keep us from dying. That was the whole purpose of the vaccine and they’re even more successful than we anticipated,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville.

As good as they are, these shots aren’t perfect. Their protection differs from person to person depending on age and underlying health. People with immune function that’s weakened because of age or a health condition can still become seriously ill, and, in very rare cases, die after vaccination.

When people are infected with Delta, they carry approximately 1,000 times more virus compared with previous versions of the virus, according to a recent study. All that virus can overwhelm even the strong protection from the vaccines.

“Three months ago, breakthroughs didn’t occur nearly at this rate because there was just so much less virus exposure in the community,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
 

Breakthroughs by the numbers

In Los Angeles County, where 69% of residents over age 12 have been fully vaccinated, COVID-19 cases are rising, and so, too, are cases that break through the protection of the vaccine.

In June, fully vaccinated people accounted for 20%, or 1 in 5, COVID cases in the county, which is the most populous in the United States. The increase mirrors Delta’s rise. The proportion of breakthrough cases is up from 11% in May, 5% in April, and 2% in March, according to the Los Angeles County Department of Public Health. 

In the United Kingdom, which is collecting the best information on infections caused by variants, the estimated effectiveness of the vaccines to prevent an illness that causes symptoms dropped by about 10 points against Delta compared with Alpha (or B.1.1.7). 

After two doses, vaccines prevent symptomatic infection about 79% of the time against Delta, according to data compiled by Public Health England. They are still highly effective at preventing hospitalization, 96% after two doses.

Out of 229,218 COVID infections in the United Kingdom between February and July 19, 28,773 — or 12.5% — were in fully vaccinated people. Of those breakthrough infections, 1,101, or 3.8%, required a visit to an emergency room, according to Public Health England. Just 474, or 2.9%, of fully vaccinated people required hospital admission, and 229, or less than 1%, died.
 

Unanswered questions

One of the biggest questions about breakthrough cases is how often people who have it may pass the virus to others.

“We know the vaccine reduces the likelihood of carrying the virus and the amount of virus you would carry,” Dr. Wen told CNN. But we don’t yet know whether a vaccinated person with a breakthrough infection may still be contagious to others.

For that reason, the Centers for Disease Control and Prevention says that fully vaccinated people still need to be tested if they have symptoms and shouldn’t be out in public for at least 10 days after a positive test. 

How should fully vaccinated people behave? That depends a lot on their underlying health and whether or not they have vulnerable people around them. 

If you’re older or immunocompromised, Dr. Schaffner recommends what he calls the “belt-and-suspenders approach,” in other words, do everything you can to stay safe.

“Get vaccinated for sure, but since we can’t be absolutely certain that the vaccines are going to be optimally protective and you are particularly susceptible to serious disease, you would be well advised to adopt at least one and perhaps more of the other mitigation measures,” he said.

These include wearing a mask, social distancing, making sure your spaces are well ventilated, and not spending prolonged periods of time indoors in crowded places.

Taking young children to visit vaccinated, elderly grandparents demands extra caution, again, with Delta circulating, particularly as they go back to school and start mixing with other kids.

Dr. Schaffner recommends explaining the ground rules before the visit: Hugs around the waist. No kissing. Wearing a mask while indoors with them.

Other important unanswered questions are whether breakthrough infections can lead to prolonged symptoms, or “long covid.” Most experts think that’s less likely in vaccinated people.

And Dr. Osterholm said it will be important to see whether there’s anything unusual about the breakthrough cases happening in the community.

“I think some of us have been challenged by the number of clusters that we’ve seen,” he said. “I think that really needs to be examined more.”

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

At a recent town hall meeting in Cincinnati, President Joe Biden was asked about COVID-19 cases, hospitalizations, and deaths rising in response to the Delta variant.

Touting the importance of vaccination, “We have a pandemic for those who haven’t gotten a vaccination. It’s that basic, that simple,” President Biden said at the event, which was broadcast live on CNN.

Andriy Onufriyenko

“If you’re vaccinated, you’re not going to be hospitalized, not going to the ICU unit, and not going to die,” he said, adding “you’re not going to get COVID if you have these vaccinations.”

Unfortunately, it’s not so simple. Fully vaccinated people continue to be well protected against severe disease and death, even with Delta, but so-called breakthrough cases, where a person gets infected despite being fully vaccinated, are on the rise. Because of that, many experts continue to advise caution, even if fully vaccinated.

“I was disappointed,” Leana Wen, MD, MSc, an emergency physician and visiting professor of health policy and management at George Washington University’s Milken School of Public Health in Washington, told CNN in response to the president’s statement.

“I actually thought he was answering questions as if it were a month ago. He’s not really meeting the realities of what’s happening on the ground,” she said. “I think he may have led people astray.”
 

Vaccines still work

Recent cases support Dr. Wen’s claim. Fully vaccinated Olympic athletes, wedding guests, healthcare workers, and even White House staff have recently tested positive. So what gives?

The vast majority of these illnesses are mild, and public health officials say they are to be expected. 

“The vaccines were designed to keep us out of the hospital and to keep us from dying. That was the whole purpose of the vaccine and they’re even more successful than we anticipated,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville.

As good as they are, these shots aren’t perfect. Their protection differs from person to person depending on age and underlying health. People with immune function that’s weakened because of age or a health condition can still become seriously ill, and, in very rare cases, die after vaccination.

When people are infected with Delta, they carry approximately 1,000 times more virus compared with previous versions of the virus, according to a recent study. All that virus can overwhelm even the strong protection from the vaccines.

“Three months ago, breakthroughs didn’t occur nearly at this rate because there was just so much less virus exposure in the community,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
 

Breakthroughs by the numbers

In Los Angeles County, where 69% of residents over age 12 have been fully vaccinated, COVID-19 cases are rising, and so, too, are cases that break through the protection of the vaccine.

In June, fully vaccinated people accounted for 20%, or 1 in 5, COVID cases in the county, which is the most populous in the United States. The increase mirrors Delta’s rise. The proportion of breakthrough cases is up from 11% in May, 5% in April, and 2% in March, according to the Los Angeles County Department of Public Health. 

In the United Kingdom, which is collecting the best information on infections caused by variants, the estimated effectiveness of the vaccines to prevent an illness that causes symptoms dropped by about 10 points against Delta compared with Alpha (or B.1.1.7). 

After two doses, vaccines prevent symptomatic infection about 79% of the time against Delta, according to data compiled by Public Health England. They are still highly effective at preventing hospitalization, 96% after two doses.

Out of 229,218 COVID infections in the United Kingdom between February and July 19, 28,773 — or 12.5% — were in fully vaccinated people. Of those breakthrough infections, 1,101, or 3.8%, required a visit to an emergency room, according to Public Health England. Just 474, or 2.9%, of fully vaccinated people required hospital admission, and 229, or less than 1%, died.
 

Unanswered questions

One of the biggest questions about breakthrough cases is how often people who have it may pass the virus to others.

“We know the vaccine reduces the likelihood of carrying the virus and the amount of virus you would carry,” Dr. Wen told CNN. But we don’t yet know whether a vaccinated person with a breakthrough infection may still be contagious to others.

For that reason, the Centers for Disease Control and Prevention says that fully vaccinated people still need to be tested if they have symptoms and shouldn’t be out in public for at least 10 days after a positive test. 

How should fully vaccinated people behave? That depends a lot on their underlying health and whether or not they have vulnerable people around them. 

If you’re older or immunocompromised, Dr. Schaffner recommends what he calls the “belt-and-suspenders approach,” in other words, do everything you can to stay safe.

“Get vaccinated for sure, but since we can’t be absolutely certain that the vaccines are going to be optimally protective and you are particularly susceptible to serious disease, you would be well advised to adopt at least one and perhaps more of the other mitigation measures,” he said.

These include wearing a mask, social distancing, making sure your spaces are well ventilated, and not spending prolonged periods of time indoors in crowded places.

Taking young children to visit vaccinated, elderly grandparents demands extra caution, again, with Delta circulating, particularly as they go back to school and start mixing with other kids.

Dr. Schaffner recommends explaining the ground rules before the visit: Hugs around the waist. No kissing. Wearing a mask while indoors with them.

Other important unanswered questions are whether breakthrough infections can lead to prolonged symptoms, or “long covid.” Most experts think that’s less likely in vaccinated people.

And Dr. Osterholm said it will be important to see whether there’s anything unusual about the breakthrough cases happening in the community.

“I think some of us have been challenged by the number of clusters that we’ve seen,” he said. “I think that really needs to be examined more.”

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

Mohs micrographic surgery (MMS) is a unique dermatologic surgery technique that allows the dermatologist to fill the concomitant roles of surgeon and pathologist. It is utilized for the extirpation of skin malignancy, with an emphasis on tissue preservation and immediate surgical margin evaluation. In MMS, the Mohs surgeon acts as the surgeon for physical removal of the lesion and the pathologist during evaluation of frozen section margins.¹

Primary care providers (PCPs) are on the frontlines of management of cutaneous malignancy. Whether referring to Dermatology for biopsy or performing a biopsy themselves, PCPs can assure optimal treatment outcomes by guiding patients to ­evidence-based treatments, while still respecting the patient’s wishes. In this evidence-based review of the advantages, improved outcomes, and safety of Mohs surgery for the treatment of common and rare skin neoplasms, we provide our primary care colleagues with information on the indications, process (the order in which steps of the procedure are performed), and techniques used for treating cutaneous malignancies with Mohs surgery.

When is Mohs surgery appropriate?

MMS has typically been reserved for treatment of cutaneous malignancy in cosmetically sensitive areas where tissue preservation is key. In 2012, Connolly et al released appropriate use criteria (AUC) for MMS.² (See “An app that helps clinicians apply the criteria for Mohs surgery.”) Within the AUC, there are 4 major qualitative and quantitative categories when considering referral for MMS:

• area of the body in which the lesion manifests
• the patient’s medical characteristics
• tumor characteristics
• the size of the lesion to be treated.²

Areas of the body are divided into 3 categories by the AUC according to how challenging tumor extirpation is expected to be and how critical tissue preservation is. Areas termed “H” receive the highest score for appropriate Mohs usage, followed by areas “M” and “L.”

Patient medical characteristics that should be taken into account when referring for Mohs surgery are the patient’s immune status, genetic syndromes that may predispose the patient to cutaneous malignancies (eg, xeroderma pigmentosa), history of radiation to the area of involvement, and the patient’s history of aggressive cutaneous malignancies.

Tumor characteristics. The most common malignancies treated with MMS include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These malignancies are further delineated through histologic evaluation by a pathologist or dermatopathologist. Aggressive features of a BCC on any area of the body that warrant referral to a Mohs surgeon include morpheaform/fibrosing/sclerosing histologic findings, as well as micronodular architecture and perineural invasion. Concerning histologic SCC findings that warrant Mohs surgery through the AUC include sclerosing, basosquamous, and small cell histology, as well as poorly differentiated and/or undifferentiated SCC.

The procedure’s emphasis on evaluating 100% of tissue margins and tissue preservation give it many inherent advantages over wide local excisions.

Melanoma in situ and lentigo maligna, which are variants of melanoma limited to the epidermis without invasion into the underlying dermis, are included within the AUC for MMS. For invasive melanoma (melanoma that has invaded into the dermis or subcutaneous tissue), MMS has been shown to have marginal benefit but currently is not included within the AUC.³

Continue to: Due to excellent margin control...

Due to excellent margin control via immediate microscopic evaluation of surgical margins, MMS is an appropriate treatment choice and indicated for many more uncommon cutaneous malignancies, including sebaceous and mucinous carcinoma, microcystic adnexal carcinoma, Merkel cell carcinoma, leiomyosarcoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, angiosarcoma, and other more rarely encountered clinical malignancies.²

Tumor size. When considering a referral to MMS for cancer extirpation, the size of the tumor does play a role; however, size depends on the type of tumor as well as the location on the body. In general, most skin cancers of any size on the face, perianal area, genitalia, nipples, hands, feet and ankles, or pretibial surface are appropriate for Mohs surgery. Skin cancers on the trunk and extremities are also appropriate if they are above a certain size specified by the AUC. Tumor type and whether they are recurrences also factor into the equation.

Who will do the procedure?

A recent review showed that PCPs were more likely to refer patients to plastic surgery rather than Mohs surgery for skin cancer removal, especially among younger female patients.⁴ This is likely because of the perception that plastic surgeons do more complex closures and have more experience removing difficult cancers. Interestingly, this same study showed that Mohs surgeons may actually be doing several-fold more complex closures (flaps and grafts) on the nose and ears than plastic surgeons at similar practice settings.⁴

Aside from Mohs surgeons doing more closures, perhaps the biggest difference between Mohs surgeons and plastic surgeons is the pathology training of the Mohs surgeon. Mohs surgeons evaluate 100% of the tissue margins at the time of the procedure to both ensure complete tumor removal and to preserve as much tumor-free skin as possible, ultimately resulting in decreased recurrences and smaller scars. In contrast, the plastic surgeon’s rigorous training typically does not include extensive dermatopathology training, particularly the pathology of cutaneous neoplasms. Plastic surgeons will often send pathologic specimens for evaluation, meaning patients have to wait for outside histologic confirmation before their wounds can be closed. Additionally, the histologic evaluation is often not a full-margin assessment, as not all labs are equipped for this technique.

Consider early consultation with a Mohs surgeon for tumor extirpation to keep the defect size as small as possible, as MMS does not require taking margins of healthy surrounding tissue, in contrast to wide local excisions (WLEs; FIGURE 1). A smaller initial incision will result in a smaller scar, which is likely to have better cosmetic outcomes and decreased risk for wound infection.

Continue to: Before consultation...

Before consultation, include a picture of the surgical site with the patient’s referral documentation or have the patient present a photo from his or her phone to the Mohs surgeon. (If a camera or cell phone is not available, triangulation of the site’s location using cosmetic landmarks can be documented in the patient’s chart.)

What the patient can expect during preop visits

During an initial consultation, patients can expect an evaluation by the surgeon that will include more photo taking, a discussion of the surgery, and possibly, performance of an in-clinic biopsy of suspicious lesions. Many practices, including the authors’, use a photo capturing add-on for the EMR in the office.^5-7

During the consent process, MMS is described to the patient using lay language and, often, pictorial depictions of the procedure. While explaining that the procedure helps preserve healthy tissue and limit the size of the resulting scar, the surgeon will typically manage the expectations of the patient prior to the first incision. Many clinically small lesions can have significant subclinical extension adjacent to, or on top of, cosmetic landmarks, requiring a flap or graft to close the surgical defect with acceptable cosmetic outcomes.⁸

One more time. Immediately before surgery, the surgeon will again review the procedure with the patient, using photos of the biopsy site taken during the initial consult, in conjunction with patient verification of the biopsy site, to verify the surgical site and confirm that the patient understands and agrees to the surgery.

A look at how Mohs surgery is performed

MMS typically is performed in the outpatient setting but can also be performed in an operating room or outpatient surgical center. MMS can be performed in a nonsterile procedure room with surgeons and assistants typically utilizing clean, nonsterile gloves, although many Mohs surgeons prefer to perform part, or all, of the technique using sterile gloves.⁹ A recent systematic review and large meta-analysis showed no significant difference in postsurgical site infections when comparing the use of sterile vs nonsterile gloves.¹⁰

Continue to: Prior to initial incision...

Prior to initial incision, the site is marked with a surgical pen and given 1-mm margins around the clinically visualized lesion. The site is then cleansed with an antiseptic, typically a chlorhexidine solution. Local anesthesia is employed, most commonly with a 1:100,000 lidocaine and epinephrine injection. Marking of the tumor prior to numbing is imperative, as the boundaries of the tumor are typically obscured when the local cutaneous vasculature constricts and causes visualized blanching of adjacent skin. Many Mohs surgeons perform a brief curettage of the lesion with a nondisposable, dull curette to better define the tumor edges and to debulk any obvious exophytic tumor noted by the naked eye.

Prior to the first incision, the surgical site is scored in a variety of ways in order to properly orient the tissue after it has been removed from the patient. Mohs surgeons have differing opinions on how to score and/or mark the tissue, but a common practice is to make a nick at the 12 o’clock position. Following removal of the first stage, the nick will be visible on both the extirpated tissue and the tissue just above the surgical defect. This prevents potential confusion regarding orientation during tissue processing.

The majority of all WLEs are performed utilizing the scalpel blade at an angle 90° perpendicular to the plane of the skin. In MMS, a signature 45° angle with the tip of the scalpel pointing toward, and the handle pointing away from, the lesion is commonly used in order to bevel the tissue being excised (FIGURE 2). Once the tissue is excised, hemostasis is obtained using electrodessication/electrofulguration or electrocoagulation.

Tissue processing and microscopic evaluation

The technique of beveling allows the epidermis, dermis, and subcutaneous tissue to lie flat on the tissue block, so the Mohs surgeon can evaluate 100% of the excised tissue’s margins. The tissue is transported to a nearby lab for staining and processing. Even if near-perfect beveling is achieved, many stages will require bisecting, quadrissecting, or relaxing cuts in order to allow the margins to lie flat on the tissue block.

Using the scoring system made prior to incision, the tissue is oriented and stained with colored ink. Subsequently, a map is made with sections highlighting the colors used to stain designated areas of the tissue. This step is imperative for orientation during microscopic evaluation. Additionally, the map serves as a guide and log, should a section of the specimen have an involved margin and require another stage.

Continue to: Once fixed to the block...

Once fixed to the block, the tissue is engulfed in appropriate embedding medium and placed within the cryostat. The block is slowly cut to produce several micron-thin wafers of tissue that are then mounted on glass slides and processed with hematoxylin and eosin (H&E) or various stains. The first wafers of tissue that come from the tissue block are those that are closest to the margin that was excised. Thus, 100% of the epidermis and deep margin can be visualized. “Deeper sections” are those that come from deeper cuts within the tissue and are more likely to show the malignant neoplasm.

Mohs surgery is the standard of care for treating cutaneous malignancy in light of its high cure rates and maximal conservation of tissue in sensitive locations.

The evaluation of immediate margins at the very edge of the tissue is in contrast to the technique of “bread-loafing,” which is the standard of evaluating margins after a WLE.¹¹ With this process, the pathologist examines sections that are cut 2- to 4-mm apart. This process only allows the pathologist to examine roughly 1% of the total tissue that was excised, and large variability in cutaneous representation can occur depending on the individual who cuts and processes the tissue.¹¹

Closing the defect

Once the site is deemed clear of residual tumor, the Mohs surgeon approaches the defect and determines the most appropriate way to close the surgical wound. Mohs surgeons are trained to close wounds using a variety of methods, including complex linear closures, flaps, and full-thickness skin grafts. Thoughtful consideration of local anatomy, cosmetic landmarks that may be affected by the closure method, and local tissue laxity are evaluated.

Depending on the location, a secondary intention closure may prove to be just as effective and cosmetically satisfying as a primary intention closure. In light of the many methods of closure, a complex or large surface area defect may better be suited for evaluation and closure by another specialist such as an ENT physician, ophthalmologist, or plastic surgeon.¹²

Lower recurrence rates for patients who undergo Mohs surgery

As noted earlier, the cutaneous malignancies most commonly treated with MMS are BCCs, followed by SCCs.¹³ Comparison studies between WLE and MMS show clinically significant differences in terms of recurrence rates between the 2 procedures.

Continue to: For BCCs

For BCCs, recurrence rates for excisions vs MMS are 10% and 1%, respectively.^14-16 A randomized trial reviewing 10-year recurrence of primary BCCs on the face showed recurrence rates for MMS of 4.4% compared to 12.2% for WLE.¹⁷ This study also showed recurrence rates for recurrent facial BCCs treated with MMS to be 3.9% vs 13.5% for standard WLE.¹⁷

SCC. The evidence similarly supports the efficacy of MMS for SCCs. A recent study showed primary T2a tumors had a 1.2% local recurrence rate with Mohs vs a 4% recurrence rate with WLE at an average follow-up of 2.8 years.¹⁸ Another study showed that primary tumors that were < 2 cm in diameter had a 5-year cure rate of 99% with Mohs surgery.¹¹

Melanoma in situ. A few studies have shown no clinically significant benefit of MMS compared to WLE when it comes to melanoma in situ.^19,20 However, a more recent article by Etzkom et al noted the ability to potentially upstage melanoma in situ and invasive melanoma after reviewing peripheral and deep margins during MMS.²¹ In this study, the authors uniquely delayed wound closure if upstaging was established and the need for a sentinel lymph node biopsy was warranted. This approach to MMS with delayed closure ultimately paved the way for very low recurrence rates.

CORRESPONDENCE
Andres Garcia, MD, 2612 112th Street, Lubbock, TX 79423; [email protected]

Mohs micrographic surgery (MMS) is a unique dermatologic surgery technique that allows the dermatologist to fill the concomitant roles of surgeon and pathologist. It is utilized for the extirpation of skin malignancy, with an emphasis on tissue preservation and immediate surgical margin evaluation. In MMS, the Mohs surgeon acts as the surgeon for physical removal of the lesion and the pathologist during evaluation of frozen section margins.¹

Primary care providers (PCPs) are on the frontlines of management of cutaneous malignancy. Whether referring to Dermatology for biopsy or performing a biopsy themselves, PCPs can assure optimal treatment outcomes by guiding patients to ­evidence-based treatments, while still respecting the patient’s wishes. In this evidence-based review of the advantages, improved outcomes, and safety of Mohs surgery for the treatment of common and rare skin neoplasms, we provide our primary care colleagues with information on the indications, process (the order in which steps of the procedure are performed), and techniques used for treating cutaneous malignancies with Mohs surgery.

When is Mohs surgery appropriate?

MMS has typically been reserved for treatment of cutaneous malignancy in cosmetically sensitive areas where tissue preservation is key. In 2012, Connolly et al released appropriate use criteria (AUC) for MMS.² (See “An app that helps clinicians apply the criteria for Mohs surgery.”) Within the AUC, there are 4 major qualitative and quantitative categories when considering referral for MMS:

• area of the body in which the lesion manifests
• the patient’s medical characteristics
• tumor characteristics
• the size of the lesion to be treated.²

Areas of the body are divided into 3 categories by the AUC according to how challenging tumor extirpation is expected to be and how critical tissue preservation is. Areas termed “H” receive the highest score for appropriate Mohs usage, followed by areas “M” and “L.”

Patient medical characteristics that should be taken into account when referring for Mohs surgery are the patient’s immune status, genetic syndromes that may predispose the patient to cutaneous malignancies (eg, xeroderma pigmentosa), history of radiation to the area of involvement, and the patient’s history of aggressive cutaneous malignancies.

Tumor characteristics. The most common malignancies treated with MMS include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These malignancies are further delineated through histologic evaluation by a pathologist or dermatopathologist. Aggressive features of a BCC on any area of the body that warrant referral to a Mohs surgeon include morpheaform/fibrosing/sclerosing histologic findings, as well as micronodular architecture and perineural invasion. Concerning histologic SCC findings that warrant Mohs surgery through the AUC include sclerosing, basosquamous, and small cell histology, as well as poorly differentiated and/or undifferentiated SCC.

The procedure’s emphasis on evaluating 100% of tissue margins and tissue preservation give it many inherent advantages over wide local excisions.

Melanoma in situ and lentigo maligna, which are variants of melanoma limited to the epidermis without invasion into the underlying dermis, are included within the AUC for MMS. For invasive melanoma (melanoma that has invaded into the dermis or subcutaneous tissue), MMS has been shown to have marginal benefit but currently is not included within the AUC.³

Continue to: Due to excellent margin control...

Due to excellent margin control via immediate microscopic evaluation of surgical margins, MMS is an appropriate treatment choice and indicated for many more uncommon cutaneous malignancies, including sebaceous and mucinous carcinoma, microcystic adnexal carcinoma, Merkel cell carcinoma, leiomyosarcoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, angiosarcoma, and other more rarely encountered clinical malignancies.²

Tumor size. When considering a referral to MMS for cancer extirpation, the size of the tumor does play a role; however, size depends on the type of tumor as well as the location on the body. In general, most skin cancers of any size on the face, perianal area, genitalia, nipples, hands, feet and ankles, or pretibial surface are appropriate for Mohs surgery. Skin cancers on the trunk and extremities are also appropriate if they are above a certain size specified by the AUC. Tumor type and whether they are recurrences also factor into the equation.

Who will do the procedure?

A recent review showed that PCPs were more likely to refer patients to plastic surgery rather than Mohs surgery for skin cancer removal, especially among younger female patients.⁴ This is likely because of the perception that plastic surgeons do more complex closures and have more experience removing difficult cancers. Interestingly, this same study showed that Mohs surgeons may actually be doing several-fold more complex closures (flaps and grafts) on the nose and ears than plastic surgeons at similar practice settings.⁴

Aside from Mohs surgeons doing more closures, perhaps the biggest difference between Mohs surgeons and plastic surgeons is the pathology training of the Mohs surgeon. Mohs surgeons evaluate 100% of the tissue margins at the time of the procedure to both ensure complete tumor removal and to preserve as much tumor-free skin as possible, ultimately resulting in decreased recurrences and smaller scars. In contrast, the plastic surgeon’s rigorous training typically does not include extensive dermatopathology training, particularly the pathology of cutaneous neoplasms. Plastic surgeons will often send pathologic specimens for evaluation, meaning patients have to wait for outside histologic confirmation before their wounds can be closed. Additionally, the histologic evaluation is often not a full-margin assessment, as not all labs are equipped for this technique.

Consider early consultation with a Mohs surgeon for tumor extirpation to keep the defect size as small as possible, as MMS does not require taking margins of healthy surrounding tissue, in contrast to wide local excisions (WLEs; FIGURE 1). A smaller initial incision will result in a smaller scar, which is likely to have better cosmetic outcomes and decreased risk for wound infection.

Continue to: Before consultation...

Before consultation, include a picture of the surgical site with the patient’s referral documentation or have the patient present a photo from his or her phone to the Mohs surgeon. (If a camera or cell phone is not available, triangulation of the site’s location using cosmetic landmarks can be documented in the patient’s chart.)

What the patient can expect during preop visits

During an initial consultation, patients can expect an evaluation by the surgeon that will include more photo taking, a discussion of the surgery, and possibly, performance of an in-clinic biopsy of suspicious lesions. Many practices, including the authors’, use a photo capturing add-on for the EMR in the office.^5-7

During the consent process, MMS is described to the patient using lay language and, often, pictorial depictions of the procedure. While explaining that the procedure helps preserve healthy tissue and limit the size of the resulting scar, the surgeon will typically manage the expectations of the patient prior to the first incision. Many clinically small lesions can have significant subclinical extension adjacent to, or on top of, cosmetic landmarks, requiring a flap or graft to close the surgical defect with acceptable cosmetic outcomes.⁸

One more time. Immediately before surgery, the surgeon will again review the procedure with the patient, using photos of the biopsy site taken during the initial consult, in conjunction with patient verification of the biopsy site, to verify the surgical site and confirm that the patient understands and agrees to the surgery.

A look at how Mohs surgery is performed

MMS typically is performed in the outpatient setting but can also be performed in an operating room or outpatient surgical center. MMS can be performed in a nonsterile procedure room with surgeons and assistants typically utilizing clean, nonsterile gloves, although many Mohs surgeons prefer to perform part, or all, of the technique using sterile gloves.⁹ A recent systematic review and large meta-analysis showed no significant difference in postsurgical site infections when comparing the use of sterile vs nonsterile gloves.¹⁰

Continue to: Prior to initial incision...

Prior to initial incision, the site is marked with a surgical pen and given 1-mm margins around the clinically visualized lesion. The site is then cleansed with an antiseptic, typically a chlorhexidine solution. Local anesthesia is employed, most commonly with a 1:100,000 lidocaine and epinephrine injection. Marking of the tumor prior to numbing is imperative, as the boundaries of the tumor are typically obscured when the local cutaneous vasculature constricts and causes visualized blanching of adjacent skin. Many Mohs surgeons perform a brief curettage of the lesion with a nondisposable, dull curette to better define the tumor edges and to debulk any obvious exophytic tumor noted by the naked eye.

Prior to the first incision, the surgical site is scored in a variety of ways in order to properly orient the tissue after it has been removed from the patient. Mohs surgeons have differing opinions on how to score and/or mark the tissue, but a common practice is to make a nick at the 12 o’clock position. Following removal of the first stage, the nick will be visible on both the extirpated tissue and the tissue just above the surgical defect. This prevents potential confusion regarding orientation during tissue processing.

The majority of all WLEs are performed utilizing the scalpel blade at an angle 90° perpendicular to the plane of the skin. In MMS, a signature 45° angle with the tip of the scalpel pointing toward, and the handle pointing away from, the lesion is commonly used in order to bevel the tissue being excised (FIGURE 2). Once the tissue is excised, hemostasis is obtained using electrodessication/electrofulguration or electrocoagulation.

Tissue processing and microscopic evaluation

The technique of beveling allows the epidermis, dermis, and subcutaneous tissue to lie flat on the tissue block, so the Mohs surgeon can evaluate 100% of the excised tissue’s margins. The tissue is transported to a nearby lab for staining and processing. Even if near-perfect beveling is achieved, many stages will require bisecting, quadrissecting, or relaxing cuts in order to allow the margins to lie flat on the tissue block.

Using the scoring system made prior to incision, the tissue is oriented and stained with colored ink. Subsequently, a map is made with sections highlighting the colors used to stain designated areas of the tissue. This step is imperative for orientation during microscopic evaluation. Additionally, the map serves as a guide and log, should a section of the specimen have an involved margin and require another stage.

Continue to: Once fixed to the block...

Once fixed to the block, the tissue is engulfed in appropriate embedding medium and placed within the cryostat. The block is slowly cut to produce several micron-thin wafers of tissue that are then mounted on glass slides and processed with hematoxylin and eosin (H&E) or various stains. The first wafers of tissue that come from the tissue block are those that are closest to the margin that was excised. Thus, 100% of the epidermis and deep margin can be visualized. “Deeper sections” are those that come from deeper cuts within the tissue and are more likely to show the malignant neoplasm.

Mohs surgery is the standard of care for treating cutaneous malignancy in light of its high cure rates and maximal conservation of tissue in sensitive locations.

The evaluation of immediate margins at the very edge of the tissue is in contrast to the technique of “bread-loafing,” which is the standard of evaluating margins after a WLE.¹¹ With this process, the pathologist examines sections that are cut 2- to 4-mm apart. This process only allows the pathologist to examine roughly 1% of the total tissue that was excised, and large variability in cutaneous representation can occur depending on the individual who cuts and processes the tissue.¹¹

Closing the defect

Once the site is deemed clear of residual tumor, the Mohs surgeon approaches the defect and determines the most appropriate way to close the surgical wound. Mohs surgeons are trained to close wounds using a variety of methods, including complex linear closures, flaps, and full-thickness skin grafts. Thoughtful consideration of local anatomy, cosmetic landmarks that may be affected by the closure method, and local tissue laxity are evaluated.

Depending on the location, a secondary intention closure may prove to be just as effective and cosmetically satisfying as a primary intention closure. In light of the many methods of closure, a complex or large surface area defect may better be suited for evaluation and closure by another specialist such as an ENT physician, ophthalmologist, or plastic surgeon.¹²

Lower recurrence rates for patients who undergo Mohs surgery

As noted earlier, the cutaneous malignancies most commonly treated with MMS are BCCs, followed by SCCs.¹³ Comparison studies between WLE and MMS show clinically significant differences in terms of recurrence rates between the 2 procedures.

Continue to: For BCCs

For BCCs, recurrence rates for excisions vs MMS are 10% and 1%, respectively.^14-16 A randomized trial reviewing 10-year recurrence of primary BCCs on the face showed recurrence rates for MMS of 4.4% compared to 12.2% for WLE.¹⁷ This study also showed recurrence rates for recurrent facial BCCs treated with MMS to be 3.9% vs 13.5% for standard WLE.¹⁷

SCC. The evidence similarly supports the efficacy of MMS for SCCs. A recent study showed primary T2a tumors had a 1.2% local recurrence rate with Mohs vs a 4% recurrence rate with WLE at an average follow-up of 2.8 years.¹⁸ Another study showed that primary tumors that were < 2 cm in diameter had a 5-year cure rate of 99% with Mohs surgery.¹¹

Melanoma in situ. A few studies have shown no clinically significant benefit of MMS compared to WLE when it comes to melanoma in situ.^19,20 However, a more recent article by Etzkom et al noted the ability to potentially upstage melanoma in situ and invasive melanoma after reviewing peripheral and deep margins during MMS.²¹ In this study, the authors uniquely delayed wound closure if upstaging was established and the need for a sentinel lymph node biopsy was warranted. This approach to MMS with delayed closure ultimately paved the way for very low recurrence rates.

CORRESPONDENCE
Andres Garcia, MD, 2612 112th Street, Lubbock, TX 79423; [email protected]

Mohs micrographic surgery (MMS) is a unique dermatologic surgery technique that allows the dermatologist to fill the concomitant roles of surgeon and pathologist. It is utilized for the extirpation of skin malignancy, with an emphasis on tissue preservation and immediate surgical margin evaluation. In MMS, the Mohs surgeon acts as the surgeon for physical removal of the lesion and the pathologist during evaluation of frozen section margins.¹

Primary care providers (PCPs) are on the frontlines of management of cutaneous malignancy. Whether referring to Dermatology for biopsy or performing a biopsy themselves, PCPs can assure optimal treatment outcomes by guiding patients to ­evidence-based treatments, while still respecting the patient’s wishes. In this evidence-based review of the advantages, improved outcomes, and safety of Mohs surgery for the treatment of common and rare skin neoplasms, we provide our primary care colleagues with information on the indications, process (the order in which steps of the procedure are performed), and techniques used for treating cutaneous malignancies with Mohs surgery.

When is Mohs surgery appropriate?

MMS has typically been reserved for treatment of cutaneous malignancy in cosmetically sensitive areas where tissue preservation is key. In 2012, Connolly et al released appropriate use criteria (AUC) for MMS.² (See “An app that helps clinicians apply the criteria for Mohs surgery.”) Within the AUC, there are 4 major qualitative and quantitative categories when considering referral for MMS:

• area of the body in which the lesion manifests
• the patient’s medical characteristics
• tumor characteristics
• the size of the lesion to be treated.²

Areas of the body are divided into 3 categories by the AUC according to how challenging tumor extirpation is expected to be and how critical tissue preservation is. Areas termed “H” receive the highest score for appropriate Mohs usage, followed by areas “M” and “L.”

Patient medical characteristics that should be taken into account when referring for Mohs surgery are the patient’s immune status, genetic syndromes that may predispose the patient to cutaneous malignancies (eg, xeroderma pigmentosa), history of radiation to the area of involvement, and the patient’s history of aggressive cutaneous malignancies.

Tumor characteristics. The most common malignancies treated with MMS include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These malignancies are further delineated through histologic evaluation by a pathologist or dermatopathologist. Aggressive features of a BCC on any area of the body that warrant referral to a Mohs surgeon include morpheaform/fibrosing/sclerosing histologic findings, as well as micronodular architecture and perineural invasion. Concerning histologic SCC findings that warrant Mohs surgery through the AUC include sclerosing, basosquamous, and small cell histology, as well as poorly differentiated and/or undifferentiated SCC.

The procedure’s emphasis on evaluating 100% of tissue margins and tissue preservation give it many inherent advantages over wide local excisions.

Melanoma in situ and lentigo maligna, which are variants of melanoma limited to the epidermis without invasion into the underlying dermis, are included within the AUC for MMS. For invasive melanoma (melanoma that has invaded into the dermis or subcutaneous tissue), MMS has been shown to have marginal benefit but currently is not included within the AUC.³

Continue to: Due to excellent margin control...

Due to excellent margin control via immediate microscopic evaluation of surgical margins, MMS is an appropriate treatment choice and indicated for many more uncommon cutaneous malignancies, including sebaceous and mucinous carcinoma, microcystic adnexal carcinoma, Merkel cell carcinoma, leiomyosarcoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, angiosarcoma, and other more rarely encountered clinical malignancies.²

Tumor size. When considering a referral to MMS for cancer extirpation, the size of the tumor does play a role; however, size depends on the type of tumor as well as the location on the body. In general, most skin cancers of any size on the face, perianal area, genitalia, nipples, hands, feet and ankles, or pretibial surface are appropriate for Mohs surgery. Skin cancers on the trunk and extremities are also appropriate if they are above a certain size specified by the AUC. Tumor type and whether they are recurrences also factor into the equation.

Who will do the procedure?

A recent review showed that PCPs were more likely to refer patients to plastic surgery rather than Mohs surgery for skin cancer removal, especially among younger female patients.⁴ This is likely because of the perception that plastic surgeons do more complex closures and have more experience removing difficult cancers. Interestingly, this same study showed that Mohs surgeons may actually be doing several-fold more complex closures (flaps and grafts) on the nose and ears than plastic surgeons at similar practice settings.⁴

Aside from Mohs surgeons doing more closures, perhaps the biggest difference between Mohs surgeons and plastic surgeons is the pathology training of the Mohs surgeon. Mohs surgeons evaluate 100% of the tissue margins at the time of the procedure to both ensure complete tumor removal and to preserve as much tumor-free skin as possible, ultimately resulting in decreased recurrences and smaller scars. In contrast, the plastic surgeon’s rigorous training typically does not include extensive dermatopathology training, particularly the pathology of cutaneous neoplasms. Plastic surgeons will often send pathologic specimens for evaluation, meaning patients have to wait for outside histologic confirmation before their wounds can be closed. Additionally, the histologic evaluation is often not a full-margin assessment, as not all labs are equipped for this technique.

Consider early consultation with a Mohs surgeon for tumor extirpation to keep the defect size as small as possible, as MMS does not require taking margins of healthy surrounding tissue, in contrast to wide local excisions (WLEs; FIGURE 1). A smaller initial incision will result in a smaller scar, which is likely to have better cosmetic outcomes and decreased risk for wound infection.

Continue to: Before consultation...

Before consultation, include a picture of the surgical site with the patient’s referral documentation or have the patient present a photo from his or her phone to the Mohs surgeon. (If a camera or cell phone is not available, triangulation of the site’s location using cosmetic landmarks can be documented in the patient’s chart.)

What the patient can expect during preop visits

During an initial consultation, patients can expect an evaluation by the surgeon that will include more photo taking, a discussion of the surgery, and possibly, performance of an in-clinic biopsy of suspicious lesions. Many practices, including the authors’, use a photo capturing add-on for the EMR in the office.^5-7

During the consent process, MMS is described to the patient using lay language and, often, pictorial depictions of the procedure. While explaining that the procedure helps preserve healthy tissue and limit the size of the resulting scar, the surgeon will typically manage the expectations of the patient prior to the first incision. Many clinically small lesions can have significant subclinical extension adjacent to, or on top of, cosmetic landmarks, requiring a flap or graft to close the surgical defect with acceptable cosmetic outcomes.⁸

One more time. Immediately before surgery, the surgeon will again review the procedure with the patient, using photos of the biopsy site taken during the initial consult, in conjunction with patient verification of the biopsy site, to verify the surgical site and confirm that the patient understands and agrees to the surgery.

A look at how Mohs surgery is performed

MMS typically is performed in the outpatient setting but can also be performed in an operating room or outpatient surgical center. MMS can be performed in a nonsterile procedure room with surgeons and assistants typically utilizing clean, nonsterile gloves, although many Mohs surgeons prefer to perform part, or all, of the technique using sterile gloves.⁹ A recent systematic review and large meta-analysis showed no significant difference in postsurgical site infections when comparing the use of sterile vs nonsterile gloves.¹⁰

Continue to: Prior to initial incision...

Prior to initial incision, the site is marked with a surgical pen and given 1-mm margins around the clinically visualized lesion. The site is then cleansed with an antiseptic, typically a chlorhexidine solution. Local anesthesia is employed, most commonly with a 1:100,000 lidocaine and epinephrine injection. Marking of the tumor prior to numbing is imperative, as the boundaries of the tumor are typically obscured when the local cutaneous vasculature constricts and causes visualized blanching of adjacent skin. Many Mohs surgeons perform a brief curettage of the lesion with a nondisposable, dull curette to better define the tumor edges and to debulk any obvious exophytic tumor noted by the naked eye.

Prior to the first incision, the surgical site is scored in a variety of ways in order to properly orient the tissue after it has been removed from the patient. Mohs surgeons have differing opinions on how to score and/or mark the tissue, but a common practice is to make a nick at the 12 o’clock position. Following removal of the first stage, the nick will be visible on both the extirpated tissue and the tissue just above the surgical defect. This prevents potential confusion regarding orientation during tissue processing.

The majority of all WLEs are performed utilizing the scalpel blade at an angle 90° perpendicular to the plane of the skin. In MMS, a signature 45° angle with the tip of the scalpel pointing toward, and the handle pointing away from, the lesion is commonly used in order to bevel the tissue being excised (FIGURE 2). Once the tissue is excised, hemostasis is obtained using electrodessication/electrofulguration or electrocoagulation.

Tissue processing and microscopic evaluation

The technique of beveling allows the epidermis, dermis, and subcutaneous tissue to lie flat on the tissue block, so the Mohs surgeon can evaluate 100% of the excised tissue’s margins. The tissue is transported to a nearby lab for staining and processing. Even if near-perfect beveling is achieved, many stages will require bisecting, quadrissecting, or relaxing cuts in order to allow the margins to lie flat on the tissue block.

Using the scoring system made prior to incision, the tissue is oriented and stained with colored ink. Subsequently, a map is made with sections highlighting the colors used to stain designated areas of the tissue. This step is imperative for orientation during microscopic evaluation. Additionally, the map serves as a guide and log, should a section of the specimen have an involved margin and require another stage.

Continue to: Once fixed to the block...

Once fixed to the block, the tissue is engulfed in appropriate embedding medium and placed within the cryostat. The block is slowly cut to produce several micron-thin wafers of tissue that are then mounted on glass slides and processed with hematoxylin and eosin (H&E) or various stains. The first wafers of tissue that come from the tissue block are those that are closest to the margin that was excised. Thus, 100% of the epidermis and deep margin can be visualized. “Deeper sections” are those that come from deeper cuts within the tissue and are more likely to show the malignant neoplasm.

Mohs surgery is the standard of care for treating cutaneous malignancy in light of its high cure rates and maximal conservation of tissue in sensitive locations.

The evaluation of immediate margins at the very edge of the tissue is in contrast to the technique of “bread-loafing,” which is the standard of evaluating margins after a WLE.¹¹ With this process, the pathologist examines sections that are cut 2- to 4-mm apart. This process only allows the pathologist to examine roughly 1% of the total tissue that was excised, and large variability in cutaneous representation can occur depending on the individual who cuts and processes the tissue.¹¹

Closing the defect

Once the site is deemed clear of residual tumor, the Mohs surgeon approaches the defect and determines the most appropriate way to close the surgical wound. Mohs surgeons are trained to close wounds using a variety of methods, including complex linear closures, flaps, and full-thickness skin grafts. Thoughtful consideration of local anatomy, cosmetic landmarks that may be affected by the closure method, and local tissue laxity are evaluated.

Depending on the location, a secondary intention closure may prove to be just as effective and cosmetically satisfying as a primary intention closure. In light of the many methods of closure, a complex or large surface area defect may better be suited for evaluation and closure by another specialist such as an ENT physician, ophthalmologist, or plastic surgeon.¹²

Lower recurrence rates for patients who undergo Mohs surgery

As noted earlier, the cutaneous malignancies most commonly treated with MMS are BCCs, followed by SCCs.¹³ Comparison studies between WLE and MMS show clinically significant differences in terms of recurrence rates between the 2 procedures.

Continue to: For BCCs

For BCCs, recurrence rates for excisions vs MMS are 10% and 1%, respectively.^14-16 A randomized trial reviewing 10-year recurrence of primary BCCs on the face showed recurrence rates for MMS of 4.4% compared to 12.2% for WLE.¹⁷ This study also showed recurrence rates for recurrent facial BCCs treated with MMS to be 3.9% vs 13.5% for standard WLE.¹⁷

SCC. The evidence similarly supports the efficacy of MMS for SCCs. A recent study showed primary T2a tumors had a 1.2% local recurrence rate with Mohs vs a 4% recurrence rate with WLE at an average follow-up of 2.8 years.¹⁸ Another study showed that primary tumors that were < 2 cm in diameter had a 5-year cure rate of 99% with Mohs surgery.¹¹

Melanoma in situ. A few studies have shown no clinically significant benefit of MMS compared to WLE when it comes to melanoma in situ.^19,20 However, a more recent article by Etzkom et al noted the ability to potentially upstage melanoma in situ and invasive melanoma after reviewing peripheral and deep margins during MMS.²¹ In this study, the authors uniquely delayed wound closure if upstaging was established and the need for a sentinel lymph node biopsy was warranted. This approach to MMS with delayed closure ultimately paved the way for very low recurrence rates.

CORRESPONDENCE
Andres Garcia, MD, 2612 112th Street, Lubbock, TX 79423; [email protected]

Key clinical point: HCC patients with hepatitis B/C coinfection had worse long-term outcomes after liver resection than patients with hepatitis B infection only.

Major finding: In the propensity score matched cohort, 3-year and 5-year recurrence-free survival rates were significantly worse in HCC patients with hepatitis B/C coinfection (48.3% and 38.9%) than in those with hepatitis B only (61.8% and 49.2%, P = 0.037).

Study details: The data come from a multicenter, observational study of 2,467 adults with HCC who underwent curative-intent liver resection. Of these, 93 also had concurrent hepatitis B/C coinfection and 2,374 had hepatitis B. Propensity score matching paired patients with hepatitis B and hepatitis B/C co-infection.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Jia H-D et al. Ann Hepatobiliary Pancreat Surg. 2021 Jun 30. doi: 10.14701/ahbps.EP-44.

Key clinical point: HCC patients with hepatitis B/C coinfection had worse long-term outcomes after liver resection than patients with hepatitis B infection only.

Major finding: In the propensity score matched cohort, 3-year and 5-year recurrence-free survival rates were significantly worse in HCC patients with hepatitis B/C coinfection (48.3% and 38.9%) than in those with hepatitis B only (61.8% and 49.2%, P = 0.037).

Study details: The data come from a multicenter, observational study of 2,467 adults with HCC who underwent curative-intent liver resection. Of these, 93 also had concurrent hepatitis B/C coinfection and 2,374 had hepatitis B. Propensity score matching paired patients with hepatitis B and hepatitis B/C co-infection.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Jia H-D et al. Ann Hepatobiliary Pancreat Surg. 2021 Jun 30. doi: 10.14701/ahbps.EP-44.

Key clinical point: HCC patients with hepatitis B/C coinfection had worse long-term outcomes after liver resection than patients with hepatitis B infection only.

Major finding: In the propensity score matched cohort, 3-year and 5-year recurrence-free survival rates were significantly worse in HCC patients with hepatitis B/C coinfection (48.3% and 38.9%) than in those with hepatitis B only (61.8% and 49.2%, P = 0.037).

Study details: The data come from a multicenter, observational study of 2,467 adults with HCC who underwent curative-intent liver resection. Of these, 93 also had concurrent hepatitis B/C coinfection and 2,374 had hepatitis B. Propensity score matching paired patients with hepatitis B and hepatitis B/C co-infection.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Jia H-D et al. Ann Hepatobiliary Pancreat Surg. 2021 Jun 30. doi: 10.14701/ahbps.EP-44.

Key clinical point: Perioperative outcomes were significantly better in recurrent HCC patients who underwent laparoscopic repeat liver resection (LRLR) compared to those who had open laparoscopic repeat liver resection (ORLR).

Major finding: Patients with recurrent hepatocellular carcinoma who underwent LRLR had shorter operative times (mean 159.74 minutes vs 250.19 minutes), less intraoperative blood loss (mean 185.65 mL vs 385.56 mL), lower morbidity (8.6% vs 62.9%), and shorter hospital stays (mean 5.83 days vs 9.26 days) compared to patients who had ORLR.

Study details: The data come from a review of 50 cases of repeat liver resections performed at a single center between January 2009 and November 2020; 23 patients had laparoscopic procedures and 27 had open procedures.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Tagaytay TG et al. Ann Hepatobiliary Pancreat Surg. 2021 Jun 30. doi: 10.14701/ahbps.LV-PP-4-1.

Key clinical point: Perioperative outcomes were significantly better in recurrent HCC patients who underwent laparoscopic repeat liver resection (LRLR) compared to those who had open laparoscopic repeat liver resection (ORLR).

Major finding: Patients with recurrent hepatocellular carcinoma who underwent LRLR had shorter operative times (mean 159.74 minutes vs 250.19 minutes), less intraoperative blood loss (mean 185.65 mL vs 385.56 mL), lower morbidity (8.6% vs 62.9%), and shorter hospital stays (mean 5.83 days vs 9.26 days) compared to patients who had ORLR.

Study details: The data come from a review of 50 cases of repeat liver resections performed at a single center between January 2009 and November 2020; 23 patients had laparoscopic procedures and 27 had open procedures.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Tagaytay TG et al. Ann Hepatobiliary Pancreat Surg. 2021 Jun 30. doi: 10.14701/ahbps.LV-PP-4-1.

Key clinical point: Perioperative outcomes were significantly better in recurrent HCC patients who underwent laparoscopic repeat liver resection (LRLR) compared to those who had open laparoscopic repeat liver resection (ORLR).

Major finding: Patients with recurrent hepatocellular carcinoma who underwent LRLR had shorter operative times (mean 159.74 minutes vs 250.19 minutes), less intraoperative blood loss (mean 185.65 mL vs 385.56 mL), lower morbidity (8.6% vs 62.9%), and shorter hospital stays (mean 5.83 days vs 9.26 days) compared to patients who had ORLR.

Study details: The data come from a review of 50 cases of repeat liver resections performed at a single center between January 2009 and November 2020; 23 patients had laparoscopic procedures and 27 had open procedures.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Tagaytay TG et al. Ann Hepatobiliary Pancreat Surg. 2021 Jun 30. doi: 10.14701/ahbps.LV-PP-4-1.

Key clinical point: Overall survival at 3 and 5 years was significantly greater in HCC patients who underwent anatomical liver resection compared to those who had nonanatomical liver resection (hazard ratios 0.79 and 0.83, respectively).

Major finding: Patients who underwent anatomical liver resection showed significantly better recurrence-free survival at 1, 3, and 5 years compared to those who underwent nonanatomical liver resection (HR 0.79, 0.81, and 0.82, respectively); anatomical liver resection patients also showed improved recurrence-free survival in a subgroup analysis of tumors less than 5 cm in diameter.

Study details: The data come from a meta-analysis of 19 propensity score matching studies of hepatocellular carcinoma patients who underwent anatomical or nonanatomical liver resection.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Shin S and Kim T-S. Ann Hepatobiliary Pancreat Surg. 2021 Jun 30. doi: 10.14701/ahbps.EP-37.

Key clinical point: Overall survival at 3 and 5 years was significantly greater in HCC patients who underwent anatomical liver resection compared to those who had nonanatomical liver resection (hazard ratios 0.79 and 0.83, respectively).

Major finding: Patients who underwent anatomical liver resection showed significantly better recurrence-free survival at 1, 3, and 5 years compared to those who underwent nonanatomical liver resection (HR 0.79, 0.81, and 0.82, respectively); anatomical liver resection patients also showed improved recurrence-free survival in a subgroup analysis of tumors less than 5 cm in diameter.

Study details: The data come from a meta-analysis of 19 propensity score matching studies of hepatocellular carcinoma patients who underwent anatomical or nonanatomical liver resection.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Shin S and Kim T-S. Ann Hepatobiliary Pancreat Surg. 2021 Jun 30. doi: 10.14701/ahbps.EP-37.

Key clinical point: Overall survival at 3 and 5 years was significantly greater in HCC patients who underwent anatomical liver resection compared to those who had nonanatomical liver resection (hazard ratios 0.79 and 0.83, respectively).

Major finding: Patients who underwent anatomical liver resection showed significantly better recurrence-free survival at 1, 3, and 5 years compared to those who underwent nonanatomical liver resection (HR 0.79, 0.81, and 0.82, respectively); anatomical liver resection patients also showed improved recurrence-free survival in a subgroup analysis of tumors less than 5 cm in diameter.

Study details: The data come from a meta-analysis of 19 propensity score matching studies of hepatocellular carcinoma patients who underwent anatomical or nonanatomical liver resection.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Shin S and Kim T-S. Ann Hepatobiliary Pancreat Surg. 2021 Jun 30. doi: 10.14701/ahbps.EP-37.

Key clinical point: Hepatocellular carcinoma patients with PVTT who received lenvatinib had a significantly longer time to progression compared to those treated with sorafenib.

Major finding: The median time to progression was 4.7 months for HCC patients with PVTT who received lenvatinib, compared to 3.1 months for those treated with sorafenib (hazard ratio 0.55, P = .029). In addition, objective response rates were significantly higher in the lenvatinib group vs the sorafenib group (53.1% vs 25.0%).

Study details: The data come from an open-label, single-center, randomized trial of 64 adults with previous untreated hepatocellular carcinoma and portal vein tumor thrombus (PVTT). Patients received TACE plus lenvatinib or sorafenib.

Disclosures: The study was supported by the Beijing Municipal Hospital Management Center Young Talent Training program. The researchers had no financial conflicts to disclose.

Source: Ding X et al. Cancer. 2021 Jul 8. doi: 10.1002/cncr.33677. 

Key clinical point: Hepatocellular carcinoma patients with PVTT who received lenvatinib had a significantly longer time to progression compared to those treated with sorafenib.

Major finding: The median time to progression was 4.7 months for HCC patients with PVTT who received lenvatinib, compared to 3.1 months for those treated with sorafenib (hazard ratio 0.55, P = .029). In addition, objective response rates were significantly higher in the lenvatinib group vs the sorafenib group (53.1% vs 25.0%).

Study details: The data come from an open-label, single-center, randomized trial of 64 adults with previous untreated hepatocellular carcinoma and portal vein tumor thrombus (PVTT). Patients received TACE plus lenvatinib or sorafenib.

Disclosures: The study was supported by the Beijing Municipal Hospital Management Center Young Talent Training program. The researchers had no financial conflicts to disclose.

Source: Ding X et al. Cancer. 2021 Jul 8. doi: 10.1002/cncr.33677. 

Key clinical point: Hepatocellular carcinoma patients with PVTT who received lenvatinib had a significantly longer time to progression compared to those treated with sorafenib.

Major finding: The median time to progression was 4.7 months for HCC patients with PVTT who received lenvatinib, compared to 3.1 months for those treated with sorafenib (hazard ratio 0.55, P = .029). In addition, objective response rates were significantly higher in the lenvatinib group vs the sorafenib group (53.1% vs 25.0%).

Study details: The data come from an open-label, single-center, randomized trial of 64 adults with previous untreated hepatocellular carcinoma and portal vein tumor thrombus (PVTT). Patients received TACE plus lenvatinib or sorafenib.

Disclosures: The study was supported by the Beijing Municipal Hospital Management Center Young Talent Training program. The researchers had no financial conflicts to disclose.

Source: Ding X et al. Cancer. 2021 Jul 8. doi: 10.1002/cncr.33677. 

Mark Nelson, PharmD, recalls the anguish when a major pharmacy benefit manager (PBM) moved all veteran patients with prostate cancer at his facility from an effective medication to a pricier alternative therapy. “All of these patients were stable on their therapy and were extremely distraught about their medications being changed,” said Dr. Nelson, CEO of Northwest Medical Specialties in Washington State. While there was no clinical reason to change the medication, “our oncologists had no choice other than to comply,” he said.

Niyazz/ThinkStock

It’s unclear why a PBM would switch to a more expensive medication that has no additional clinical benefit, he continued. “Why upset so many veterans? For what reason? We were not given a reason despite our very vocal protest.”

Angus B. Worthing, MD, sees these scenarios unfold every day in his rheumatology practice in the Washington, D.C., area. “In my clinic with 25 doctors, we have three full-time people that only handle PBMs,” he said in an interview. He and others in the medical community, as well as many states, have been pushing back on what they see as efforts by PBMs to raise drug prices and collect the profits at the expense of patients.

PCMA’s challenges against PBM law

The Pharmaceutical Care Management Association (PCMA), a trade group that represents PBMs, has sued at least a half dozen states on their ability to regulate PBMs. However, a landmark case in late 2020 (Pharmaceutical Care Management Association v. Rutledge) set a new precedent. Reversing a lower appeals court decision, the Supreme Court unanimously ruled in favor of allowing states to put in place fair regulation of these entities.

Dr. Worthing and others hope that the medical community and states can leverage this ruling in another lawsuit PCMA brought against North Dakota (PCMA v. Wehbi). PCMA filed this lawsuit in 2017, which challenges two statutes on PBM regulation. The group has issued similar legal challenges in Maine, the District of Columbia, Iowa, Oklahoma, and Arkansas with the Rutledge case.

“PBMs have become massive profit centers while (ironically) increasing patients’ out-of-pocket costs, interfering with doctor-patient relationships, and impairing patient access to appropriate treatment,” according to an amicus brief filed by The Alliance for Transparent & Affordable Prescriptions (ATAP), the Community Oncology Alliance (COA), and American Pharmacies, supporting North Dakota in the Wehbi case.

This is to ensure the case represents the voices of physicians, patients, nurses, and other stakeholders, and underscores PBM abuses, said Dr. Worthing, vice president of ATAP. He also serves as the American College of Rheumatology’s representative on ATAP’s Executive Committee.

PCMA did not respond to requests for comment. Its CEO and president, J.C. Scott, emphasizes that PBMs have a long track record of reducing drug costs for patients and plan sponsors. In 2021, PCMA released 21 policy solutions, a set of industry principles and a three-part policy platform, all with an aim to bring down costs and increase access to pharmaceutical care, according to the organization.

PCMA estimates that the strategies in its platform (updating Medicare Part D, accelerating value-based care, and eliminating anticompetitive ‘pay for delay’ agreements) would save the federal government a maximum of $398.7 billion over 10 years.

According to Wendy Hemmen, senior director with Texas Oncology in Dallas, PBMs do their own unique calculations to arrive at their cost reductions. “Essentially in a PBM, they use things that make their story. Numbers reported to plan sponsors and to the public are not audited and are usually in terms of percentages or a per member per month. Data points are moved around, dropped, or reclassified to make the story that the PBM needs to tell,” Ms. Hemmen said.


 

Amicus briefs dispute ERISA connection

North Dakota legislation prohibits PBMs from charging copays to patients that exceed the cost of a drug. It also prohibits gag clause provisions that restrict what pharmacists may discuss with patients. PBMs may charge fees based on performance metrics, but they must use nationally recognized metrics. Fees must be disclosed at the point of sale.

In its legal challenges, PCMA has asserted that state laws violate the preemption clause in the Employee Retirement Income Security Act (ERISA). “Federal preemption allows employers flexibility to administer innovative benefit plans in an environment of increasing health care costs. The court’s decision in Rutledge v. PCMA will either uphold or threaten these federal protections,” PCMA asserted in a statement issued in March 2020.

ATAP’s amicus brief, and another one filed by 34 attorneys general that supports the North Dakota statute to regulate PBMs, counter that this isn’t the case.

“First, PBM regulation (in its common and standard form) does not reference ERISA itself. These laws leave all plans on equal footing; they do not single out ERISA plans for preferred or disfavored coverage, and they do not change the playing field for ERISA plans alone ... Second, PBM regulation does not have any prohibited connection with ERISA plans,” noted authors in the ATAP brief.

PCMA has also included Medicare preemption in its arguments against PBM regulation. This is meritless, wrote the state attorneys general. “Medicare preempts state laws only if a Medicare ‘standard’ particularly addresses the subject of state regulation. Because the challenged North Dakota laws do not dictate plan benefits or conflict with a Medicare standard, they are not preempted.”

The auctioning of medications

PBMs in theory could use their market power to drive down costs by extracting discounts from drug makers and pharmacies. In reality, they retain any price concessions and discounts for themselves, ATAP’s brief continued.

A system that PBMs have put into place, called step therapy, is essentially an auction for the preferred spot that will be authorized and covered, Dr. Worthing explained.

PBMs create formularies through this auction. The highest rebate to the PBM earns the top spot in the auction and becomes the preferred drug. “That highest bid gets paid for by passing the cost along to patients and insurance plans, and PBMs pocket the profits. This provides an incentive for pharmaceutical manufacturers to raise prices,” he said.

Dr. Worthing has seen these practices trickle down and affect his patients. “Frequently, the medication I prescribe based on what’s best for the patient based on their disease activity, values, and medical history is often not covered because a different drug or portfolio of drugs has earned the top spot in step therapy. This is an extremely frustrating and cumbersome process that not only delays access to treatments but also provides an incentive for higher drug prices,” he said.

There are other ways in which PBMs get in the way of care, said Ms. Hemmen, whose facility serves complex-care oncology patients.

“PBMs force scripts out of higher-quality pharmacies that preserve unfragmented care. They incentivize plan sponsors to put programs into place that take away patient choice, fragment care, and drive scripts to their own owned pharmacies,” she said.
 

Rutledge case sets precedent

In the Rutledge case, PCMA had challenged an Arkansas law that forbid PBMs from paying local pharmacies at a lower rate than what the pharmacies were reimbursed to fill prescriptions. Although the 8th Circuit Court of Appeals agreed with PCMA, the Supreme Court ruled in favor of Arkansas in late 2020.

The appeals court also backed PCMA in PCMA v. Wehbi. However, the Supreme Court vacated this decision and remanded it back to the appeals court, asking for a reconsideration in wake of the outcome in Rutledge v. PCMA.

PCMA has argued that Rutledge was a narrow decision, limited to state laws that regulate PBM reimbursements, and that Rutledge has no bearing on North Dakota law.

While it’s unfortunate that PCMA is trying to delay implementation of sensible regulations, “a lot of us are happy that this issue is coming to light,” Dr. Worthing said. “As a rheumatologist and health policy advocate, exposing drug middlemen is the most important bipartisan issue in the country today because it gets at the core of making sure that sick people get access to the medications they need and reducing the budget of insurance carriers, hospitals, and the federal budget.”

The ATAP brief noted that 28 state attorneys general have filed suit against PBMs, “securing settlements compelling PBMs to correct deceptive trade practices.”

Many people at the state and local level were waiting for the Supreme Court to decide on Rutledge before enacting legislation and sensible regulations, and now they can go ahead and do it, said Dr. Worthing. “I expect to see this across the country as states look at budgets, and as patients bring personal stories to light. We look forward to states passing these kinds of laws to regulate PBMs.”

The ACR doesn’t anticipate a ruling in the Wehbi case until the spring of 2022.

Recent laws passed around PBMs and the pharmacy benefit are a good first step in holding PBMs accountable for quality of care and honoring patient choice, Ms. Hemmen said. The laws also begin to address the fiscal manipulations PBMs use to gain advantage and direct scripts to their own coffers, she added. However, this may not have enough teeth. “These state laws are coming from a provider perspective, and they don’t anticipate what PBMs will do in response. The PBMs are going to work around it.”

Mark Nelson, PharmD, recalls the anguish when a major pharmacy benefit manager (PBM) moved all veteran patients with prostate cancer at his facility from an effective medication to a pricier alternative therapy. “All of these patients were stable on their therapy and were extremely distraught about their medications being changed,” said Dr. Nelson, CEO of Northwest Medical Specialties in Washington State. While there was no clinical reason to change the medication, “our oncologists had no choice other than to comply,” he said.

Niyazz/ThinkStock

It’s unclear why a PBM would switch to a more expensive medication that has no additional clinical benefit, he continued. “Why upset so many veterans? For what reason? We were not given a reason despite our very vocal protest.”

Angus B. Worthing, MD, sees these scenarios unfold every day in his rheumatology practice in the Washington, D.C., area. “In my clinic with 25 doctors, we have three full-time people that only handle PBMs,” he said in an interview. He and others in the medical community, as well as many states, have been pushing back on what they see as efforts by PBMs to raise drug prices and collect the profits at the expense of patients.

PCMA’s challenges against PBM law

The Pharmaceutical Care Management Association (PCMA), a trade group that represents PBMs, has sued at least a half dozen states on their ability to regulate PBMs. However, a landmark case in late 2020 (Pharmaceutical Care Management Association v. Rutledge) set a new precedent. Reversing a lower appeals court decision, the Supreme Court unanimously ruled in favor of allowing states to put in place fair regulation of these entities.

Dr. Worthing and others hope that the medical community and states can leverage this ruling in another lawsuit PCMA brought against North Dakota (PCMA v. Wehbi). PCMA filed this lawsuit in 2017, which challenges two statutes on PBM regulation. The group has issued similar legal challenges in Maine, the District of Columbia, Iowa, Oklahoma, and Arkansas with the Rutledge case.

“PBMs have become massive profit centers while (ironically) increasing patients’ out-of-pocket costs, interfering with doctor-patient relationships, and impairing patient access to appropriate treatment,” according to an amicus brief filed by The Alliance for Transparent & Affordable Prescriptions (ATAP), the Community Oncology Alliance (COA), and American Pharmacies, supporting North Dakota in the Wehbi case.

This is to ensure the case represents the voices of physicians, patients, nurses, and other stakeholders, and underscores PBM abuses, said Dr. Worthing, vice president of ATAP. He also serves as the American College of Rheumatology’s representative on ATAP’s Executive Committee.

PCMA did not respond to requests for comment. Its CEO and president, J.C. Scott, emphasizes that PBMs have a long track record of reducing drug costs for patients and plan sponsors. In 2021, PCMA released 21 policy solutions, a set of industry principles and a three-part policy platform, all with an aim to bring down costs and increase access to pharmaceutical care, according to the organization.

PCMA estimates that the strategies in its platform (updating Medicare Part D, accelerating value-based care, and eliminating anticompetitive ‘pay for delay’ agreements) would save the federal government a maximum of $398.7 billion over 10 years.

According to Wendy Hemmen, senior director with Texas Oncology in Dallas, PBMs do their own unique calculations to arrive at their cost reductions. “Essentially in a PBM, they use things that make their story. Numbers reported to plan sponsors and to the public are not audited and are usually in terms of percentages or a per member per month. Data points are moved around, dropped, or reclassified to make the story that the PBM needs to tell,” Ms. Hemmen said.


 

Amicus briefs dispute ERISA connection

North Dakota legislation prohibits PBMs from charging copays to patients that exceed the cost of a drug. It also prohibits gag clause provisions that restrict what pharmacists may discuss with patients. PBMs may charge fees based on performance metrics, but they must use nationally recognized metrics. Fees must be disclosed at the point of sale.

In its legal challenges, PCMA has asserted that state laws violate the preemption clause in the Employee Retirement Income Security Act (ERISA). “Federal preemption allows employers flexibility to administer innovative benefit plans in an environment of increasing health care costs. The court’s decision in Rutledge v. PCMA will either uphold or threaten these federal protections,” PCMA asserted in a statement issued in March 2020.

ATAP’s amicus brief, and another one filed by 34 attorneys general that supports the North Dakota statute to regulate PBMs, counter that this isn’t the case.

“First, PBM regulation (in its common and standard form) does not reference ERISA itself. These laws leave all plans on equal footing; they do not single out ERISA plans for preferred or disfavored coverage, and they do not change the playing field for ERISA plans alone ... Second, PBM regulation does not have any prohibited connection with ERISA plans,” noted authors in the ATAP brief.

PCMA has also included Medicare preemption in its arguments against PBM regulation. This is meritless, wrote the state attorneys general. “Medicare preempts state laws only if a Medicare ‘standard’ particularly addresses the subject of state regulation. Because the challenged North Dakota laws do not dictate plan benefits or conflict with a Medicare standard, they are not preempted.”

The auctioning of medications

PBMs in theory could use their market power to drive down costs by extracting discounts from drug makers and pharmacies. In reality, they retain any price concessions and discounts for themselves, ATAP’s brief continued.

A system that PBMs have put into place, called step therapy, is essentially an auction for the preferred spot that will be authorized and covered, Dr. Worthing explained.

PBMs create formularies through this auction. The highest rebate to the PBM earns the top spot in the auction and becomes the preferred drug. “That highest bid gets paid for by passing the cost along to patients and insurance plans, and PBMs pocket the profits. This provides an incentive for pharmaceutical manufacturers to raise prices,” he said.

Dr. Worthing has seen these practices trickle down and affect his patients. “Frequently, the medication I prescribe based on what’s best for the patient based on their disease activity, values, and medical history is often not covered because a different drug or portfolio of drugs has earned the top spot in step therapy. This is an extremely frustrating and cumbersome process that not only delays access to treatments but also provides an incentive for higher drug prices,” he said.

There are other ways in which PBMs get in the way of care, said Ms. Hemmen, whose facility serves complex-care oncology patients.

“PBMs force scripts out of higher-quality pharmacies that preserve unfragmented care. They incentivize plan sponsors to put programs into place that take away patient choice, fragment care, and drive scripts to their own owned pharmacies,” she said.
 

Rutledge case sets precedent

In the Rutledge case, PCMA had challenged an Arkansas law that forbid PBMs from paying local pharmacies at a lower rate than what the pharmacies were reimbursed to fill prescriptions. Although the 8th Circuit Court of Appeals agreed with PCMA, the Supreme Court ruled in favor of Arkansas in late 2020.

The appeals court also backed PCMA in PCMA v. Wehbi. However, the Supreme Court vacated this decision and remanded it back to the appeals court, asking for a reconsideration in wake of the outcome in Rutledge v. PCMA.

PCMA has argued that Rutledge was a narrow decision, limited to state laws that regulate PBM reimbursements, and that Rutledge has no bearing on North Dakota law.

While it’s unfortunate that PCMA is trying to delay implementation of sensible regulations, “a lot of us are happy that this issue is coming to light,” Dr. Worthing said. “As a rheumatologist and health policy advocate, exposing drug middlemen is the most important bipartisan issue in the country today because it gets at the core of making sure that sick people get access to the medications they need and reducing the budget of insurance carriers, hospitals, and the federal budget.”

The ATAP brief noted that 28 state attorneys general have filed suit against PBMs, “securing settlements compelling PBMs to correct deceptive trade practices.”

Many people at the state and local level were waiting for the Supreme Court to decide on Rutledge before enacting legislation and sensible regulations, and now they can go ahead and do it, said Dr. Worthing. “I expect to see this across the country as states look at budgets, and as patients bring personal stories to light. We look forward to states passing these kinds of laws to regulate PBMs.”

The ACR doesn’t anticipate a ruling in the Wehbi case until the spring of 2022.

Recent laws passed around PBMs and the pharmacy benefit are a good first step in holding PBMs accountable for quality of care and honoring patient choice, Ms. Hemmen said. The laws also begin to address the fiscal manipulations PBMs use to gain advantage and direct scripts to their own coffers, she added. However, this may not have enough teeth. “These state laws are coming from a provider perspective, and they don’t anticipate what PBMs will do in response. The PBMs are going to work around it.”

Mark Nelson, PharmD, recalls the anguish when a major pharmacy benefit manager (PBM) moved all veteran patients with prostate cancer at his facility from an effective medication to a pricier alternative therapy. “All of these patients were stable on their therapy and were extremely distraught about their medications being changed,” said Dr. Nelson, CEO of Northwest Medical Specialties in Washington State. While there was no clinical reason to change the medication, “our oncologists had no choice other than to comply,” he said.

Niyazz/ThinkStock

It’s unclear why a PBM would switch to a more expensive medication that has no additional clinical benefit, he continued. “Why upset so many veterans? For what reason? We were not given a reason despite our very vocal protest.”

Angus B. Worthing, MD, sees these scenarios unfold every day in his rheumatology practice in the Washington, D.C., area. “In my clinic with 25 doctors, we have three full-time people that only handle PBMs,” he said in an interview. He and others in the medical community, as well as many states, have been pushing back on what they see as efforts by PBMs to raise drug prices and collect the profits at the expense of patients.

PCMA’s challenges against PBM law

The Pharmaceutical Care Management Association (PCMA), a trade group that represents PBMs, has sued at least a half dozen states on their ability to regulate PBMs. However, a landmark case in late 2020 (Pharmaceutical Care Management Association v. Rutledge) set a new precedent. Reversing a lower appeals court decision, the Supreme Court unanimously ruled in favor of allowing states to put in place fair regulation of these entities.

Dr. Worthing and others hope that the medical community and states can leverage this ruling in another lawsuit PCMA brought against North Dakota (PCMA v. Wehbi). PCMA filed this lawsuit in 2017, which challenges two statutes on PBM regulation. The group has issued similar legal challenges in Maine, the District of Columbia, Iowa, Oklahoma, and Arkansas with the Rutledge case.

“PBMs have become massive profit centers while (ironically) increasing patients’ out-of-pocket costs, interfering with doctor-patient relationships, and impairing patient access to appropriate treatment,” according to an amicus brief filed by The Alliance for Transparent & Affordable Prescriptions (ATAP), the Community Oncology Alliance (COA), and American Pharmacies, supporting North Dakota in the Wehbi case.

This is to ensure the case represents the voices of physicians, patients, nurses, and other stakeholders, and underscores PBM abuses, said Dr. Worthing, vice president of ATAP. He also serves as the American College of Rheumatology’s representative on ATAP’s Executive Committee.

PCMA did not respond to requests for comment. Its CEO and president, J.C. Scott, emphasizes that PBMs have a long track record of reducing drug costs for patients and plan sponsors. In 2021, PCMA released 21 policy solutions, a set of industry principles and a three-part policy platform, all with an aim to bring down costs and increase access to pharmaceutical care, according to the organization.

PCMA estimates that the strategies in its platform (updating Medicare Part D, accelerating value-based care, and eliminating anticompetitive ‘pay for delay’ agreements) would save the federal government a maximum of $398.7 billion over 10 years.

According to Wendy Hemmen, senior director with Texas Oncology in Dallas, PBMs do their own unique calculations to arrive at their cost reductions. “Essentially in a PBM, they use things that make their story. Numbers reported to plan sponsors and to the public are not audited and are usually in terms of percentages or a per member per month. Data points are moved around, dropped, or reclassified to make the story that the PBM needs to tell,” Ms. Hemmen said.


 

Amicus briefs dispute ERISA connection

North Dakota legislation prohibits PBMs from charging copays to patients that exceed the cost of a drug. It also prohibits gag clause provisions that restrict what pharmacists may discuss with patients. PBMs may charge fees based on performance metrics, but they must use nationally recognized metrics. Fees must be disclosed at the point of sale.

In its legal challenges, PCMA has asserted that state laws violate the preemption clause in the Employee Retirement Income Security Act (ERISA). “Federal preemption allows employers flexibility to administer innovative benefit plans in an environment of increasing health care costs. The court’s decision in Rutledge v. PCMA will either uphold or threaten these federal protections,” PCMA asserted in a statement issued in March 2020.

ATAP’s amicus brief, and another one filed by 34 attorneys general that supports the North Dakota statute to regulate PBMs, counter that this isn’t the case.

“First, PBM regulation (in its common and standard form) does not reference ERISA itself. These laws leave all plans on equal footing; they do not single out ERISA plans for preferred or disfavored coverage, and they do not change the playing field for ERISA plans alone ... Second, PBM regulation does not have any prohibited connection with ERISA plans,” noted authors in the ATAP brief.

PCMA has also included Medicare preemption in its arguments against PBM regulation. This is meritless, wrote the state attorneys general. “Medicare preempts state laws only if a Medicare ‘standard’ particularly addresses the subject of state regulation. Because the challenged North Dakota laws do not dictate plan benefits or conflict with a Medicare standard, they are not preempted.”

The auctioning of medications

PBMs in theory could use their market power to drive down costs by extracting discounts from drug makers and pharmacies. In reality, they retain any price concessions and discounts for themselves, ATAP’s brief continued.

A system that PBMs have put into place, called step therapy, is essentially an auction for the preferred spot that will be authorized and covered, Dr. Worthing explained.

PBMs create formularies through this auction. The highest rebate to the PBM earns the top spot in the auction and becomes the preferred drug. “That highest bid gets paid for by passing the cost along to patients and insurance plans, and PBMs pocket the profits. This provides an incentive for pharmaceutical manufacturers to raise prices,” he said.

Dr. Worthing has seen these practices trickle down and affect his patients. “Frequently, the medication I prescribe based on what’s best for the patient based on their disease activity, values, and medical history is often not covered because a different drug or portfolio of drugs has earned the top spot in step therapy. This is an extremely frustrating and cumbersome process that not only delays access to treatments but also provides an incentive for higher drug prices,” he said.

There are other ways in which PBMs get in the way of care, said Ms. Hemmen, whose facility serves complex-care oncology patients.

“PBMs force scripts out of higher-quality pharmacies that preserve unfragmented care. They incentivize plan sponsors to put programs into place that take away patient choice, fragment care, and drive scripts to their own owned pharmacies,” she said.
 

Rutledge case sets precedent

In the Rutledge case, PCMA had challenged an Arkansas law that forbid PBMs from paying local pharmacies at a lower rate than what the pharmacies were reimbursed to fill prescriptions. Although the 8th Circuit Court of Appeals agreed with PCMA, the Supreme Court ruled in favor of Arkansas in late 2020.

The appeals court also backed PCMA in PCMA v. Wehbi. However, the Supreme Court vacated this decision and remanded it back to the appeals court, asking for a reconsideration in wake of the outcome in Rutledge v. PCMA.

PCMA has argued that Rutledge was a narrow decision, limited to state laws that regulate PBM reimbursements, and that Rutledge has no bearing on North Dakota law.

While it’s unfortunate that PCMA is trying to delay implementation of sensible regulations, “a lot of us are happy that this issue is coming to light,” Dr. Worthing said. “As a rheumatologist and health policy advocate, exposing drug middlemen is the most important bipartisan issue in the country today because it gets at the core of making sure that sick people get access to the medications they need and reducing the budget of insurance carriers, hospitals, and the federal budget.”

The ATAP brief noted that 28 state attorneys general have filed suit against PBMs, “securing settlements compelling PBMs to correct deceptive trade practices.”

Many people at the state and local level were waiting for the Supreme Court to decide on Rutledge before enacting legislation and sensible regulations, and now they can go ahead and do it, said Dr. Worthing. “I expect to see this across the country as states look at budgets, and as patients bring personal stories to light. We look forward to states passing these kinds of laws to regulate PBMs.”

The ACR doesn’t anticipate a ruling in the Wehbi case until the spring of 2022.

Recent laws passed around PBMs and the pharmacy benefit are a good first step in holding PBMs accountable for quality of care and honoring patient choice, Ms. Hemmen said. The laws also begin to address the fiscal manipulations PBMs use to gain advantage and direct scripts to their own coffers, she added. However, this may not have enough teeth. “These state laws are coming from a provider perspective, and they don’t anticipate what PBMs will do in response. The PBMs are going to work around it.”

Key clinical point: Statin users had a consistent, significant, dose-dependent reduction in the risk of hepatocellular carcinoma in a nested case-control study. Aspirin users showed some reduction in risk, but it was not dose dependent.

Major finding: In the nested case-control study, both statin use, and aspirin use were significantly associated with reduced HCC risk (odds ratio 0.34 and 0.92, respectively), but only statins showed a dose-dependent risk reduction.

Study details: The data come from a nationwide, nested case-control study with a cohort of 538 135 treatment-naïve, non-cirrhotic adults with chronic hepatitis B. The participants were identified from data gathered between 2005 and 2015 through the National Health Insurance Service in Korea. From this group, 6,539 HCC cases were matched to 26,156 controls.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Choi W-M et al. Liver Int. 2021. doi: 10.1111/liv.15011. 

Key clinical point: Statin users had a consistent, significant, dose-dependent reduction in the risk of hepatocellular carcinoma in a nested case-control study. Aspirin users showed some reduction in risk, but it was not dose dependent.

Major finding: In the nested case-control study, both statin use, and aspirin use were significantly associated with reduced HCC risk (odds ratio 0.34 and 0.92, respectively), but only statins showed a dose-dependent risk reduction.

Study details: The data come from a nationwide, nested case-control study with a cohort of 538 135 treatment-naïve, non-cirrhotic adults with chronic hepatitis B. The participants were identified from data gathered between 2005 and 2015 through the National Health Insurance Service in Korea. From this group, 6,539 HCC cases were matched to 26,156 controls.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Choi W-M et al. Liver Int. 2021. doi: 10.1111/liv.15011. 

Key clinical point: Statin users had a consistent, significant, dose-dependent reduction in the risk of hepatocellular carcinoma in a nested case-control study. Aspirin users showed some reduction in risk, but it was not dose dependent.

Major finding: In the nested case-control study, both statin use, and aspirin use were significantly associated with reduced HCC risk (odds ratio 0.34 and 0.92, respectively), but only statins showed a dose-dependent risk reduction.

Study details: The data come from a nationwide, nested case-control study with a cohort of 538 135 treatment-naïve, non-cirrhotic adults with chronic hepatitis B. The participants were identified from data gathered between 2005 and 2015 through the National Health Insurance Service in Korea. From this group, 6,539 HCC cases were matched to 26,156 controls.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Choi W-M et al. Liver Int. 2021. doi: 10.1111/liv.15011. 

Key clinical point: Transarterial radioembolization (TARE) was associated with a significantly higher overall survival compared to systemic therapy in patients with hepatocellular carcinoma with major vascular invasion (HCC-MVI).

Major finding: In a propensity-score matched and landmark-time adjusted analysis, the median overall survival for HCC-MVI patients treated with TARE was 7.1 months, compared to 4.9 months for patients treated with systemic therapy. Target trial emulation of an additional 236 patients with HCC-MVI showed a similar advantage with TARE.

Study details: The data come from 1,514 patients with hepatocellular carcinoma with major vascular invasion (HCC-MVI) identified from the National Cancer Database for the period between 2010 and 2015.

Disclosures: The study was supported by the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. The researchers had no financial conflicts to disclose.

Source: Kwee SA et al. J Vasc Interv Radiol. 2021 Jul 6. doi: 10.1016/j.jvir.2021.07.001.

Key clinical point: Transarterial radioembolization (TARE) was associated with a significantly higher overall survival compared to systemic therapy in patients with hepatocellular carcinoma with major vascular invasion (HCC-MVI).

Major finding: In a propensity-score matched and landmark-time adjusted analysis, the median overall survival for HCC-MVI patients treated with TARE was 7.1 months, compared to 4.9 months for patients treated with systemic therapy. Target trial emulation of an additional 236 patients with HCC-MVI showed a similar advantage with TARE.

Study details: The data come from 1,514 patients with hepatocellular carcinoma with major vascular invasion (HCC-MVI) identified from the National Cancer Database for the period between 2010 and 2015.

Disclosures: The study was supported by the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. The researchers had no financial conflicts to disclose.

Source: Kwee SA et al. J Vasc Interv Radiol. 2021 Jul 6. doi: 10.1016/j.jvir.2021.07.001.

Key clinical point: Transarterial radioembolization (TARE) was associated with a significantly higher overall survival compared to systemic therapy in patients with hepatocellular carcinoma with major vascular invasion (HCC-MVI).

Major finding: In a propensity-score matched and landmark-time adjusted analysis, the median overall survival for HCC-MVI patients treated with TARE was 7.1 months, compared to 4.9 months for patients treated with systemic therapy. Target trial emulation of an additional 236 patients with HCC-MVI showed a similar advantage with TARE.

Study details: The data come from 1,514 patients with hepatocellular carcinoma with major vascular invasion (HCC-MVI) identified from the National Cancer Database for the period between 2010 and 2015.

Disclosures: The study was supported by the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. The researchers had no financial conflicts to disclose.

Source: Kwee SA et al. J Vasc Interv Radiol. 2021 Jul 6. doi: 10.1016/j.jvir.2021.07.001.