PHOENIX — The use of radiotherapy has been steadily increasing by dermatologists, according to new findings from a study analyzing trends in Medicare claims from 2016 to 2021. More specifically, the persistent growth in the use of superficial radiotherapy (SRT) devices and electronic brachytherapy (eBT) to treat nonmelanoma skin cancer (NMSC) has exceeded that of traditional procedures among dermatologists using these modalities, according to Christian Gronbeck, MD, a resident in dermatology at the University of Connecticut Health Center, Farmington.

“These services increased substantially over the study period,” Dr. Gronbeck said at the annual meeting of the American College of Mohs Surgery, where he presented the results of the study. “Our findings suggest that those using eBT/SRT were frequently general dermatologists and non-fellowship–trained Mohs surgeons who have less formalized surgical training.”

He also noted that billing for these services also rose substantially, which is being driven by growing utilization and an increased SRT payment rate.

Surgical approaches are standard for most NMSC cases, but some patients are not good surgical candidates because of medical comorbidities and/or other factors, and radiotherapy is emerging as a potential treatment option for those patients. Traditionally, radiotherapy was administered by radiation oncologists, but with the growing availability of SRT devices and the introduction of eBT, dermatologists are now treating patients with these modalities.

“It is a potential treatment option for nonmelanoma skin cancer and keloids, and these lower energy devices can be used in the outpatient setting,” said Dr. Gronbeck. “Treatment typically involves a series of fractions over a period of several weeks. There has been recent growth in the use of radiotherapy despite this being a secondary option in skin cancer, primarily when surgery is contraindicated.”

Steady Expansion of Use

Dr. Gronbeck and colleagues sought to gain a better understanding of the use of SRT and eBT for NMSC among dermatologists, as well as trends in cost. Data were obtained from the 2016-2021 Medicare Public Use Files to evaluate the trend in the volume of Medicare Part B claims for eBT (CPT 0394T) and SRT (CPT 77401) by dermatologists, and they also looked at related billable services for radiotherapy.

Of 12,050 dermatologists, 293 (2.4%) were identified as utilizing eBT or SRT in 2021, representing a 75.4% increase from 2016. The usage of both eBT and SRT increased by 59.6% and 148.4%, respectively, from 2016 to 2021.

There were notable geographic differences in the utilization of radiotherapy. “Florida, California, Texas, and Arizona had the highest utilization,” Dr. Gronbeck said, although during the study period, utilization increased in other states, including North Carolina and Alabama.

When looking at geographic regions as a whole, the highest number of dermatologists using radiotherapy were located in the South (n = 143, 50.9%), followed by the West (n = 69, 23.6%). Utilization was more common in metro areas than in nonmetro/rural areas (86% vs 14%).

Differences were also noted among dermatologists. Those who performed eBT/SRT than those who did not were significantly more likely to have had 15 or more years of independent practice (70.1% vs 48.6%), be in a small private dermatology practice (62.7% vs 47.5%), and be non–fellowship-trained Mohs surgeons (33.5% vs 10.2%). Dermatologists utilizing radiotherapy were also more likely to treat Medicare beneficiaries who were older, with a mean age over 75 years (39.3% vs 31.1%) and a mean hierarchical condition category (HCC) score, above the national average (55.2% vs 44.6%).

Dr. Gronbeck and colleagues also looked at cost. The number of direct payments for eBT/SRT payments increased throughout the study period, from 3,678,224 in 2016 to 11,680,925 in 2021, nearly a 218% increase. The change in payments for services related to eBT/SRT, such as radiotherapy simulation, radiotherapy dosing, and ultrasound guidance, increased by 621.4% during this same timeframe.

Radiotherapy in dermatology has primarily been assessed through retrospective studies. “Our findings suggest that eBT and SRT are more frequently utilized by dermatologists managing older and sicker patients, but further studies are needed to identify whether these interventions are truly addressing poor surgical candidates,” Dr. Gronbeck said.

The Centers for Medicare & Medicaid Services (CMS) has recently proposed changes in Medicare coverage in seven states for Image-Guided Superficial Radiation Therapy (image-guided SRT or IGSRT) for the treatment of NMSC. The proposed local coverage determination, or LCD, if finalized in its current form, would affect residents in North Carolina, South Carolina, Virginia, West Virginia, Alabama, Georgia, and Tennessee.

“These changes would mean more restrictive coverage,” said Dr. Gronbeck, and further support the need for “improved clinical data and development of guidelines to support evidence-based utilization.”

Surgical Management Standard, but SRT Has a Role

Asked to comment on the findings, Seemal R. Desai, MD, president of the American Academy of Dermatology (AAD), who was not involved with the study, reiterated that according to this abstract, efficacy has mainly been assessed through retrospective studies, and results are likely inferior to Mohs surgery, require multiple treatment visits, and are associated with significant costs. More study is needed for the use of radiation therapy in dermatology, he told this news organization.

A version of this article appeared on Medscape.com.

PHOENIX — The use of radiotherapy has been steadily increasing by dermatologists, according to new findings from a study analyzing trends in Medicare claims from 2016 to 2021. More specifically, the persistent growth in the use of superficial radiotherapy (SRT) devices and electronic brachytherapy (eBT) to treat nonmelanoma skin cancer (NMSC) has exceeded that of traditional procedures among dermatologists using these modalities, according to Christian Gronbeck, MD, a resident in dermatology at the University of Connecticut Health Center, Farmington.

“These services increased substantially over the study period,” Dr. Gronbeck said at the annual meeting of the American College of Mohs Surgery, where he presented the results of the study. “Our findings suggest that those using eBT/SRT were frequently general dermatologists and non-fellowship–trained Mohs surgeons who have less formalized surgical training.”

He also noted that billing for these services also rose substantially, which is being driven by growing utilization and an increased SRT payment rate.

Surgical approaches are standard for most NMSC cases, but some patients are not good surgical candidates because of medical comorbidities and/or other factors, and radiotherapy is emerging as a potential treatment option for those patients. Traditionally, radiotherapy was administered by radiation oncologists, but with the growing availability of SRT devices and the introduction of eBT, dermatologists are now treating patients with these modalities.

“It is a potential treatment option for nonmelanoma skin cancer and keloids, and these lower energy devices can be used in the outpatient setting,” said Dr. Gronbeck. “Treatment typically involves a series of fractions over a period of several weeks. There has been recent growth in the use of radiotherapy despite this being a secondary option in skin cancer, primarily when surgery is contraindicated.”

Steady Expansion of Use

Dr. Gronbeck and colleagues sought to gain a better understanding of the use of SRT and eBT for NMSC among dermatologists, as well as trends in cost. Data were obtained from the 2016-2021 Medicare Public Use Files to evaluate the trend in the volume of Medicare Part B claims for eBT (CPT 0394T) and SRT (CPT 77401) by dermatologists, and they also looked at related billable services for radiotherapy.

Of 12,050 dermatologists, 293 (2.4%) were identified as utilizing eBT or SRT in 2021, representing a 75.4% increase from 2016. The usage of both eBT and SRT increased by 59.6% and 148.4%, respectively, from 2016 to 2021.

There were notable geographic differences in the utilization of radiotherapy. “Florida, California, Texas, and Arizona had the highest utilization,” Dr. Gronbeck said, although during the study period, utilization increased in other states, including North Carolina and Alabama.

When looking at geographic regions as a whole, the highest number of dermatologists using radiotherapy were located in the South (n = 143, 50.9%), followed by the West (n = 69, 23.6%). Utilization was more common in metro areas than in nonmetro/rural areas (86% vs 14%).

Differences were also noted among dermatologists. Those who performed eBT/SRT than those who did not were significantly more likely to have had 15 or more years of independent practice (70.1% vs 48.6%), be in a small private dermatology practice (62.7% vs 47.5%), and be non–fellowship-trained Mohs surgeons (33.5% vs 10.2%). Dermatologists utilizing radiotherapy were also more likely to treat Medicare beneficiaries who were older, with a mean age over 75 years (39.3% vs 31.1%) and a mean hierarchical condition category (HCC) score, above the national average (55.2% vs 44.6%).

Dr. Gronbeck and colleagues also looked at cost. The number of direct payments for eBT/SRT payments increased throughout the study period, from 3,678,224 in 2016 to 11,680,925 in 2021, nearly a 218% increase. The change in payments for services related to eBT/SRT, such as radiotherapy simulation, radiotherapy dosing, and ultrasound guidance, increased by 621.4% during this same timeframe.

Radiotherapy in dermatology has primarily been assessed through retrospective studies. “Our findings suggest that eBT and SRT are more frequently utilized by dermatologists managing older and sicker patients, but further studies are needed to identify whether these interventions are truly addressing poor surgical candidates,” Dr. Gronbeck said.

The Centers for Medicare & Medicaid Services (CMS) has recently proposed changes in Medicare coverage in seven states for Image-Guided Superficial Radiation Therapy (image-guided SRT or IGSRT) for the treatment of NMSC. The proposed local coverage determination, or LCD, if finalized in its current form, would affect residents in North Carolina, South Carolina, Virginia, West Virginia, Alabama, Georgia, and Tennessee.

“These changes would mean more restrictive coverage,” said Dr. Gronbeck, and further support the need for “improved clinical data and development of guidelines to support evidence-based utilization.”

Surgical Management Standard, but SRT Has a Role

Asked to comment on the findings, Seemal R. Desai, MD, president of the American Academy of Dermatology (AAD), who was not involved with the study, reiterated that according to this abstract, efficacy has mainly been assessed through retrospective studies, and results are likely inferior to Mohs surgery, require multiple treatment visits, and are associated with significant costs. More study is needed for the use of radiation therapy in dermatology, he told this news organization.

A version of this article appeared on Medscape.com.

PHOENIX — The use of radiotherapy has been steadily increasing by dermatologists, according to new findings from a study analyzing trends in Medicare claims from 2016 to 2021. More specifically, the persistent growth in the use of superficial radiotherapy (SRT) devices and electronic brachytherapy (eBT) to treat nonmelanoma skin cancer (NMSC) has exceeded that of traditional procedures among dermatologists using these modalities, according to Christian Gronbeck, MD, a resident in dermatology at the University of Connecticut Health Center, Farmington.

“These services increased substantially over the study period,” Dr. Gronbeck said at the annual meeting of the American College of Mohs Surgery, where he presented the results of the study. “Our findings suggest that those using eBT/SRT were frequently general dermatologists and non-fellowship–trained Mohs surgeons who have less formalized surgical training.”

He also noted that billing for these services also rose substantially, which is being driven by growing utilization and an increased SRT payment rate.

Surgical approaches are standard for most NMSC cases, but some patients are not good surgical candidates because of medical comorbidities and/or other factors, and radiotherapy is emerging as a potential treatment option for those patients. Traditionally, radiotherapy was administered by radiation oncologists, but with the growing availability of SRT devices and the introduction of eBT, dermatologists are now treating patients with these modalities.

“It is a potential treatment option for nonmelanoma skin cancer and keloids, and these lower energy devices can be used in the outpatient setting,” said Dr. Gronbeck. “Treatment typically involves a series of fractions over a period of several weeks. There has been recent growth in the use of radiotherapy despite this being a secondary option in skin cancer, primarily when surgery is contraindicated.”

Steady Expansion of Use

Dr. Gronbeck and colleagues sought to gain a better understanding of the use of SRT and eBT for NMSC among dermatologists, as well as trends in cost. Data were obtained from the 2016-2021 Medicare Public Use Files to evaluate the trend in the volume of Medicare Part B claims for eBT (CPT 0394T) and SRT (CPT 77401) by dermatologists, and they also looked at related billable services for radiotherapy.

Of 12,050 dermatologists, 293 (2.4%) were identified as utilizing eBT or SRT in 2021, representing a 75.4% increase from 2016. The usage of both eBT and SRT increased by 59.6% and 148.4%, respectively, from 2016 to 2021.

There were notable geographic differences in the utilization of radiotherapy. “Florida, California, Texas, and Arizona had the highest utilization,” Dr. Gronbeck said, although during the study period, utilization increased in other states, including North Carolina and Alabama.

When looking at geographic regions as a whole, the highest number of dermatologists using radiotherapy were located in the South (n = 143, 50.9%), followed by the West (n = 69, 23.6%). Utilization was more common in metro areas than in nonmetro/rural areas (86% vs 14%).

Differences were also noted among dermatologists. Those who performed eBT/SRT than those who did not were significantly more likely to have had 15 or more years of independent practice (70.1% vs 48.6%), be in a small private dermatology practice (62.7% vs 47.5%), and be non–fellowship-trained Mohs surgeons (33.5% vs 10.2%). Dermatologists utilizing radiotherapy were also more likely to treat Medicare beneficiaries who were older, with a mean age over 75 years (39.3% vs 31.1%) and a mean hierarchical condition category (HCC) score, above the national average (55.2% vs 44.6%).

Dr. Gronbeck and colleagues also looked at cost. The number of direct payments for eBT/SRT payments increased throughout the study period, from 3,678,224 in 2016 to 11,680,925 in 2021, nearly a 218% increase. The change in payments for services related to eBT/SRT, such as radiotherapy simulation, radiotherapy dosing, and ultrasound guidance, increased by 621.4% during this same timeframe.

Radiotherapy in dermatology has primarily been assessed through retrospective studies. “Our findings suggest that eBT and SRT are more frequently utilized by dermatologists managing older and sicker patients, but further studies are needed to identify whether these interventions are truly addressing poor surgical candidates,” Dr. Gronbeck said.

The Centers for Medicare & Medicaid Services (CMS) has recently proposed changes in Medicare coverage in seven states for Image-Guided Superficial Radiation Therapy (image-guided SRT or IGSRT) for the treatment of NMSC. The proposed local coverage determination, or LCD, if finalized in its current form, would affect residents in North Carolina, South Carolina, Virginia, West Virginia, Alabama, Georgia, and Tennessee.

“These changes would mean more restrictive coverage,” said Dr. Gronbeck, and further support the need for “improved clinical data and development of guidelines to support evidence-based utilization.”

Surgical Management Standard, but SRT Has a Role

Asked to comment on the findings, Seemal R. Desai, MD, president of the American Academy of Dermatology (AAD), who was not involved with the study, reiterated that according to this abstract, efficacy has mainly been assessed through retrospective studies, and results are likely inferior to Mohs surgery, require multiple treatment visits, and are associated with significant costs. More study is needed for the use of radiation therapy in dermatology, he told this news organization.

A version of this article appeared on Medscape.com.

PHOENIX — Certain minority populations may be at a higher absolute risk of being prescribed opioids after undergoing dermatologic surgery, according to a new study. The study also found that patients who do receive opioids postoperatively are at an increased risk for chronic opioid use and complications.

This report represents the largest analysis to date of opioid prescribing after dermatologic surgery, said lead author Kyle C. Lauck, MD, a dermatology resident at Baylor University Medical Center, Dallas, Texas. “Females, African Americans, and Latino patients may be at a higher risk of opioid prescription after dermatologic surgery. Surgeons should be aware of these populations and the risks they face when determining candidacy for postsurgical opioid analgesia.”

He presented the results at the annual meeting of the American College of Mohs Surgery.

The opioid epidemic is a concern across all areas of medicine, and the majority of opioid prescriptions in dermatology are given following surgery. Dr. Lauck noted that even though guidelines delegate opioids as second line for pain control, the existing data on opioid prescribing in dermatologic surgery is mixed. For example, some reports have shown that up to 58% of patients receive opioids postoperatively. “No consensus exists when we should routinely give opioids to these patients,” he said.

Even though most surgeons prescribe short courses of opioids, even brief regimens are associated with increased risks for overuse and substance abuse. Population-level data are limited concerning opioid prescriptions in dermatologic surgery, and in particular, there is an absence of data on the risk for long-term complications associated with use.

Certain Populations at Risk

To evaluate opioid prescription rates in dermatologic surgery, focusing on disparities between demographic populations, as well as the risk for long-term complications of postoperative opioid prescriptions, Dr. Lauck and colleagues conducted a retrospective study that included 914,721 dermatologic surgery patients, with billing codes for Mohs micrographic surgery. Patient data were obtained from TriNetX, a federated health research network.

The mean age of patients in this cohort was 54 years, and 124,494 (13.6%) were prescribed postsurgical oral opioids. The most common was oxycodone, prescribed to 43% of patients. Dr. Lauck noted that, according to their data, certain groups appeared more likely to receive a prescription for opioids following surgery. These included Black or African American patients (23.75% vs 12.86% for White patients), females (13.73% vs 13.16% for males), and Latino or Hispanic patients (17.02% vs 13.61% non-Latino/Hispanic patients).

Patients with a history of prior oral opioid prescription, prior opioid abuse or dependence, and any type of substance abuse had a significant increase in absolute risk of being prescribed postsurgical opioids (P < .0001). 

The type of surgery also was associated with prescribed postop opioids. For a malignant excision, 18.29% of patients were prescribed postop opioids compared with 14.9% for a benign excision. About a third of patients (34.9%) undergoing a graft repair received opioids.

There was an elevated rate of postop opioid prescribing that was specific to the site of surgery, with the highest rates observed with eyelids, scalp and neck, trunk, and genital sites. The highest overall rates of opioid prescriptions were for patients who underwent excisions in the genital area (54.5%).
 

Long-Term Consequences

The authors also looked at the longer-term consequences of postop opioid use. “Nearly one in three patients who were prescribed opioids needed subsequent prescriptions down the line,” said Dr. Lauck. 

From 3 months to 5 years after surgery, patients who received postsurgical opioids were at significantly higher risk for not only subsequent oral opioid prescription but also opiate abuse, any substance abuse, overdose by opioid narcotics, constipation, and chronic pain. “An opioid prescription may confer further risks of longitudinal complications of chronic opioid use,” he concluded.

Commenting on the study, Jesse M. Lewin, MD, chief of Mohs micrographic and dermatologic surgery at Icahn School of Medicine at Mount Sinai, New York City, noted an important finding of this study was the long-term sequelae of patients who did receive postop opioids.

“This is striking given that postsurgical opiate prescriptions are for short durations and limited number of pills,” he told this news organization. “This study highlights the potential danger of even short course of opiates and should serve as a reminder to dermatologic surgeons to be judicious about opiate prescribing.”

Dr. Lauck and Dr. Lewin had no disclosures. 
 

A version of this article appeared on Medscape.com.

PHOENIX — Certain minority populations may be at a higher absolute risk of being prescribed opioids after undergoing dermatologic surgery, according to a new study. The study also found that patients who do receive opioids postoperatively are at an increased risk for chronic opioid use and complications.

This report represents the largest analysis to date of opioid prescribing after dermatologic surgery, said lead author Kyle C. Lauck, MD, a dermatology resident at Baylor University Medical Center, Dallas, Texas. “Females, African Americans, and Latino patients may be at a higher risk of opioid prescription after dermatologic surgery. Surgeons should be aware of these populations and the risks they face when determining candidacy for postsurgical opioid analgesia.”

He presented the results at the annual meeting of the American College of Mohs Surgery.

The opioid epidemic is a concern across all areas of medicine, and the majority of opioid prescriptions in dermatology are given following surgery. Dr. Lauck noted that even though guidelines delegate opioids as second line for pain control, the existing data on opioid prescribing in dermatologic surgery is mixed. For example, some reports have shown that up to 58% of patients receive opioids postoperatively. “No consensus exists when we should routinely give opioids to these patients,” he said.

Even though most surgeons prescribe short courses of opioids, even brief regimens are associated with increased risks for overuse and substance abuse. Population-level data are limited concerning opioid prescriptions in dermatologic surgery, and in particular, there is an absence of data on the risk for long-term complications associated with use.

Certain Populations at Risk

To evaluate opioid prescription rates in dermatologic surgery, focusing on disparities between demographic populations, as well as the risk for long-term complications of postoperative opioid prescriptions, Dr. Lauck and colleagues conducted a retrospective study that included 914,721 dermatologic surgery patients, with billing codes for Mohs micrographic surgery. Patient data were obtained from TriNetX, a federated health research network.

The mean age of patients in this cohort was 54 years, and 124,494 (13.6%) were prescribed postsurgical oral opioids. The most common was oxycodone, prescribed to 43% of patients. Dr. Lauck noted that, according to their data, certain groups appeared more likely to receive a prescription for opioids following surgery. These included Black or African American patients (23.75% vs 12.86% for White patients), females (13.73% vs 13.16% for males), and Latino or Hispanic patients (17.02% vs 13.61% non-Latino/Hispanic patients).

Patients with a history of prior oral opioid prescription, prior opioid abuse or dependence, and any type of substance abuse had a significant increase in absolute risk of being prescribed postsurgical opioids (P < .0001). 

The type of surgery also was associated with prescribed postop opioids. For a malignant excision, 18.29% of patients were prescribed postop opioids compared with 14.9% for a benign excision. About a third of patients (34.9%) undergoing a graft repair received opioids.

There was an elevated rate of postop opioid prescribing that was specific to the site of surgery, with the highest rates observed with eyelids, scalp and neck, trunk, and genital sites. The highest overall rates of opioid prescriptions were for patients who underwent excisions in the genital area (54.5%).
 

Long-Term Consequences

The authors also looked at the longer-term consequences of postop opioid use. “Nearly one in three patients who were prescribed opioids needed subsequent prescriptions down the line,” said Dr. Lauck. 

From 3 months to 5 years after surgery, patients who received postsurgical opioids were at significantly higher risk for not only subsequent oral opioid prescription but also opiate abuse, any substance abuse, overdose by opioid narcotics, constipation, and chronic pain. “An opioid prescription may confer further risks of longitudinal complications of chronic opioid use,” he concluded.

Commenting on the study, Jesse M. Lewin, MD, chief of Mohs micrographic and dermatologic surgery at Icahn School of Medicine at Mount Sinai, New York City, noted an important finding of this study was the long-term sequelae of patients who did receive postop opioids.

“This is striking given that postsurgical opiate prescriptions are for short durations and limited number of pills,” he told this news organization. “This study highlights the potential danger of even short course of opiates and should serve as a reminder to dermatologic surgeons to be judicious about opiate prescribing.”

Dr. Lauck and Dr. Lewin had no disclosures. 
 

A version of this article appeared on Medscape.com.

PHOENIX — Certain minority populations may be at a higher absolute risk of being prescribed opioids after undergoing dermatologic surgery, according to a new study. The study also found that patients who do receive opioids postoperatively are at an increased risk for chronic opioid use and complications.

This report represents the largest analysis to date of opioid prescribing after dermatologic surgery, said lead author Kyle C. Lauck, MD, a dermatology resident at Baylor University Medical Center, Dallas, Texas. “Females, African Americans, and Latino patients may be at a higher risk of opioid prescription after dermatologic surgery. Surgeons should be aware of these populations and the risks they face when determining candidacy for postsurgical opioid analgesia.”

He presented the results at the annual meeting of the American College of Mohs Surgery.

The opioid epidemic is a concern across all areas of medicine, and the majority of opioid prescriptions in dermatology are given following surgery. Dr. Lauck noted that even though guidelines delegate opioids as second line for pain control, the existing data on opioid prescribing in dermatologic surgery is mixed. For example, some reports have shown that up to 58% of patients receive opioids postoperatively. “No consensus exists when we should routinely give opioids to these patients,” he said.

Even though most surgeons prescribe short courses of opioids, even brief regimens are associated with increased risks for overuse and substance abuse. Population-level data are limited concerning opioid prescriptions in dermatologic surgery, and in particular, there is an absence of data on the risk for long-term complications associated with use.

Certain Populations at Risk

To evaluate opioid prescription rates in dermatologic surgery, focusing on disparities between demographic populations, as well as the risk for long-term complications of postoperative opioid prescriptions, Dr. Lauck and colleagues conducted a retrospective study that included 914,721 dermatologic surgery patients, with billing codes for Mohs micrographic surgery. Patient data were obtained from TriNetX, a federated health research network.

The mean age of patients in this cohort was 54 years, and 124,494 (13.6%) were prescribed postsurgical oral opioids. The most common was oxycodone, prescribed to 43% of patients. Dr. Lauck noted that, according to their data, certain groups appeared more likely to receive a prescription for opioids following surgery. These included Black or African American patients (23.75% vs 12.86% for White patients), females (13.73% vs 13.16% for males), and Latino or Hispanic patients (17.02% vs 13.61% non-Latino/Hispanic patients).

Patients with a history of prior oral opioid prescription, prior opioid abuse or dependence, and any type of substance abuse had a significant increase in absolute risk of being prescribed postsurgical opioids (P < .0001). 

The type of surgery also was associated with prescribed postop opioids. For a malignant excision, 18.29% of patients were prescribed postop opioids compared with 14.9% for a benign excision. About a third of patients (34.9%) undergoing a graft repair received opioids.

There was an elevated rate of postop opioid prescribing that was specific to the site of surgery, with the highest rates observed with eyelids, scalp and neck, trunk, and genital sites. The highest overall rates of opioid prescriptions were for patients who underwent excisions in the genital area (54.5%).
 

Long-Term Consequences

The authors also looked at the longer-term consequences of postop opioid use. “Nearly one in three patients who were prescribed opioids needed subsequent prescriptions down the line,” said Dr. Lauck. 

From 3 months to 5 years after surgery, patients who received postsurgical opioids were at significantly higher risk for not only subsequent oral opioid prescription but also opiate abuse, any substance abuse, overdose by opioid narcotics, constipation, and chronic pain. “An opioid prescription may confer further risks of longitudinal complications of chronic opioid use,” he concluded.

Commenting on the study, Jesse M. Lewin, MD, chief of Mohs micrographic and dermatologic surgery at Icahn School of Medicine at Mount Sinai, New York City, noted an important finding of this study was the long-term sequelae of patients who did receive postop opioids.

“This is striking given that postsurgical opiate prescriptions are for short durations and limited number of pills,” he told this news organization. “This study highlights the potential danger of even short course of opiates and should serve as a reminder to dermatologic surgeons to be judicious about opiate prescribing.”

Dr. Lauck and Dr. Lewin had no disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — The selective interleukin (IL)–23p29 monoclonal antibody mirikizumab demonstrated safety and efficacy in people with moderate to severe Crohn’s disease compared with placebo up to 52 weeks, according to results of the phase 3 randomized, double blind, treat-through VIVID-1 study. 

Bruce E. Sands, MD, AGAF, chief of gastroenterology at the Icahn School of Medicine at Mount Sinai in New York, reported the findings in a poster (Abstract Su1801) at the annual Digestive Disease Week^® (DDW).

The FDA approved mirikizumab (Omvoh, Eli Lilly) to treat moderate to severe ulcerative colitis in October 2023. 

Dr. Sands and a team of US and international collaborators studied 1065 adults with Crohn’s disease or fistulizing Crohn’s disease for 3 months or more, with a mean duration of more than 7 years. At baseline, participants had a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 7 or more and reported an inadequate response, lost response, or intolerance to other therapy.

A total of 579 people were randomly assigned to mirikizumab and another 199 to placebo. Another 287 patients received ustekinumab; though they were not included in this current analysis, the findings were presented separately at DDW 2024. 

Mean age of study participants was 30 years, and men comprised 57%-59% of the groups. Nearly half (49%) of each group previously failed biologic therapy. 

A primary composite endpoint was clinical response at 12 weeks according to patient reported outcome and endoscopic response at 52 weeks measured with the SES-CD. A second primary endpoint was clinical response at 12 weeks by patient reported outcome combined with clinical remission on Crohn’s Disease Activity Index (CDAI) at 52 weeks.

Researchers also tracked 12 major secondary endpoints for mirikizumab vs placebo, including clinical response, endoscopic response, and clinical remission at week 12 and week 52. 
 

Efficacy Findings

A higher percentage of participants in the mirikizumab group achieved 12-week secondary endpoints compared with placebo. In the treatment group, 32.5% reached endoscopic response vs 12.6% in the placebo group, a statistically significant difference (P < .000001). In addition, 17.6% achieved endoscopic remission in the treatment group vs 7.0% in the placebo group at 12 weeks (P < .000213).

The “treat-through” results at 52 weeks revealed that a higher proportion of the group taking mirikizumab met the co-primary endpoints compared with placebo. A total of 48.4% in the mirikizumab group vs 9.0% in the placebo group achieved endoscopic response (P < .000001). Similarly, a higher proportion met clinical remission on the CDAI, 54.1% in the treatment group vs 19.6% in the placebo group (P < .000001).

Overall, 38% of mirikizumab-treated patients vs 9% of the placebo group reached a composite endpoint of patient reported clinical response at week 12 and endoscopic response by SES-CD at week 52 (P < .000001).

Dr. Sands and colleagues also combined clinical response reported by patients at 12 weeks with CDAI findings for clinical remission at week 52. A total of 45.4% in the treatment group met the combined endpoint compared with 19.6% of the placebo group (P < .000001). 

In an additional analysis, the researchers looked at this composite endpoint in patients in both groups who had failed or not failed a prior biologic for a total of 43.4% vs 12.4%, and 47.3% vs 26.5%, respectively.

“Mirikizumab demonstrated statistically significant and clinically meaningful improvements” in the study co-primary endpoints and secondary endpoints compared with placebo, the researchers concluded. 
 

Safety Findings

Safety outcomes during the 52-week study were “consistent with the known safety profile” of mirikizumab, the researchers noted. 

Treatment-emergent adverse events occurred in 78.6% of mirikizumab participants vs 73.0% of the placebo group. The most common were COVID-19, anemia, and arthralgia. Serious adverse events were reported in 10.3% of the mirikizumab group vs 17.1% of the placebo group. There were seven opportunistic infections in the treatment group, including herpes zoster and Candida, compared with none in the placebo group. 

One person in the placebo cohort died of a pulmonary embolism; there were no deaths in the mirikizumab group. 

People randomly assigned to placebo without a response at 12 weeks were switched over to mirikizumab. However, the findings from this group between 12 and 52 weeks were excluded from the 1-year data presented at DDW 2024, including one death from worsening Crohn’s disease during that time.

Mirikizumab looked particularly robust in this study, and it may turn out to be a critically important option for our patients, said Jordan Axelrad, MD, MPH, co-director of the Inflammatory Bowel Disease Center at NYU Langone Health in New York City. Dr. Axelrad was not involved in this study. 

Of importance, effect sizes were similar for “bio-naive and previously biologic-exposed patients,” he added. 

These data “really underscore that therapies targeting IL-23 may be clinically useful for Crohn’s disease patients with prior biologic failure, representing a significant departure from our previous experience with other biologic classes,” Dr. Axelrad said.

The study was funded by Eli Lilly and Company. Dr. Sands is a consultant and receives grant funding from Lilly. Dr. Axelrad had no relevant disclosures. 

A version of this article appeared on Medscape.com.

WASHINGTON — The selective interleukin (IL)–23p29 monoclonal antibody mirikizumab demonstrated safety and efficacy in people with moderate to severe Crohn’s disease compared with placebo up to 52 weeks, according to results of the phase 3 randomized, double blind, treat-through VIVID-1 study. 

Bruce E. Sands, MD, AGAF, chief of gastroenterology at the Icahn School of Medicine at Mount Sinai in New York, reported the findings in a poster (Abstract Su1801) at the annual Digestive Disease Week^® (DDW).

The FDA approved mirikizumab (Omvoh, Eli Lilly) to treat moderate to severe ulcerative colitis in October 2023. 

Dr. Sands and a team of US and international collaborators studied 1065 adults with Crohn’s disease or fistulizing Crohn’s disease for 3 months or more, with a mean duration of more than 7 years. At baseline, participants had a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 7 or more and reported an inadequate response, lost response, or intolerance to other therapy.

A total of 579 people were randomly assigned to mirikizumab and another 199 to placebo. Another 287 patients received ustekinumab; though they were not included in this current analysis, the findings were presented separately at DDW 2024. 

Mean age of study participants was 30 years, and men comprised 57%-59% of the groups. Nearly half (49%) of each group previously failed biologic therapy. 

A primary composite endpoint was clinical response at 12 weeks according to patient reported outcome and endoscopic response at 52 weeks measured with the SES-CD. A second primary endpoint was clinical response at 12 weeks by patient reported outcome combined with clinical remission on Crohn’s Disease Activity Index (CDAI) at 52 weeks.

Researchers also tracked 12 major secondary endpoints for mirikizumab vs placebo, including clinical response, endoscopic response, and clinical remission at week 12 and week 52. 
 

Efficacy Findings

A higher percentage of participants in the mirikizumab group achieved 12-week secondary endpoints compared with placebo. In the treatment group, 32.5% reached endoscopic response vs 12.6% in the placebo group, a statistically significant difference (P < .000001). In addition, 17.6% achieved endoscopic remission in the treatment group vs 7.0% in the placebo group at 12 weeks (P < .000213).

The “treat-through” results at 52 weeks revealed that a higher proportion of the group taking mirikizumab met the co-primary endpoints compared with placebo. A total of 48.4% in the mirikizumab group vs 9.0% in the placebo group achieved endoscopic response (P < .000001). Similarly, a higher proportion met clinical remission on the CDAI, 54.1% in the treatment group vs 19.6% in the placebo group (P < .000001).

Overall, 38% of mirikizumab-treated patients vs 9% of the placebo group reached a composite endpoint of patient reported clinical response at week 12 and endoscopic response by SES-CD at week 52 (P < .000001).

Dr. Sands and colleagues also combined clinical response reported by patients at 12 weeks with CDAI findings for clinical remission at week 52. A total of 45.4% in the treatment group met the combined endpoint compared with 19.6% of the placebo group (P < .000001). 

In an additional analysis, the researchers looked at this composite endpoint in patients in both groups who had failed or not failed a prior biologic for a total of 43.4% vs 12.4%, and 47.3% vs 26.5%, respectively.

“Mirikizumab demonstrated statistically significant and clinically meaningful improvements” in the study co-primary endpoints and secondary endpoints compared with placebo, the researchers concluded. 
 

Safety Findings

Safety outcomes during the 52-week study were “consistent with the known safety profile” of mirikizumab, the researchers noted. 

Treatment-emergent adverse events occurred in 78.6% of mirikizumab participants vs 73.0% of the placebo group. The most common were COVID-19, anemia, and arthralgia. Serious adverse events were reported in 10.3% of the mirikizumab group vs 17.1% of the placebo group. There were seven opportunistic infections in the treatment group, including herpes zoster and Candida, compared with none in the placebo group. 

One person in the placebo cohort died of a pulmonary embolism; there were no deaths in the mirikizumab group. 

People randomly assigned to placebo without a response at 12 weeks were switched over to mirikizumab. However, the findings from this group between 12 and 52 weeks were excluded from the 1-year data presented at DDW 2024, including one death from worsening Crohn’s disease during that time.

Mirikizumab looked particularly robust in this study, and it may turn out to be a critically important option for our patients, said Jordan Axelrad, MD, MPH, co-director of the Inflammatory Bowel Disease Center at NYU Langone Health in New York City. Dr. Axelrad was not involved in this study. 

Of importance, effect sizes were similar for “bio-naive and previously biologic-exposed patients,” he added. 

These data “really underscore that therapies targeting IL-23 may be clinically useful for Crohn’s disease patients with prior biologic failure, representing a significant departure from our previous experience with other biologic classes,” Dr. Axelrad said.

The study was funded by Eli Lilly and Company. Dr. Sands is a consultant and receives grant funding from Lilly. Dr. Axelrad had no relevant disclosures. 

A version of this article appeared on Medscape.com.

WASHINGTON — The selective interleukin (IL)–23p29 monoclonal antibody mirikizumab demonstrated safety and efficacy in people with moderate to severe Crohn’s disease compared with placebo up to 52 weeks, according to results of the phase 3 randomized, double blind, treat-through VIVID-1 study. 

Bruce E. Sands, MD, AGAF, chief of gastroenterology at the Icahn School of Medicine at Mount Sinai in New York, reported the findings in a poster (Abstract Su1801) at the annual Digestive Disease Week^® (DDW).

The FDA approved mirikizumab (Omvoh, Eli Lilly) to treat moderate to severe ulcerative colitis in October 2023. 

Dr. Sands and a team of US and international collaborators studied 1065 adults with Crohn’s disease or fistulizing Crohn’s disease for 3 months or more, with a mean duration of more than 7 years. At baseline, participants had a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 7 or more and reported an inadequate response, lost response, or intolerance to other therapy.

A total of 579 people were randomly assigned to mirikizumab and another 199 to placebo. Another 287 patients received ustekinumab; though they were not included in this current analysis, the findings were presented separately at DDW 2024. 

Mean age of study participants was 30 years, and men comprised 57%-59% of the groups. Nearly half (49%) of each group previously failed biologic therapy. 

A primary composite endpoint was clinical response at 12 weeks according to patient reported outcome and endoscopic response at 52 weeks measured with the SES-CD. A second primary endpoint was clinical response at 12 weeks by patient reported outcome combined with clinical remission on Crohn’s Disease Activity Index (CDAI) at 52 weeks.

Researchers also tracked 12 major secondary endpoints for mirikizumab vs placebo, including clinical response, endoscopic response, and clinical remission at week 12 and week 52. 
 

Efficacy Findings

A higher percentage of participants in the mirikizumab group achieved 12-week secondary endpoints compared with placebo. In the treatment group, 32.5% reached endoscopic response vs 12.6% in the placebo group, a statistically significant difference (P < .000001). In addition, 17.6% achieved endoscopic remission in the treatment group vs 7.0% in the placebo group at 12 weeks (P < .000213).

The “treat-through” results at 52 weeks revealed that a higher proportion of the group taking mirikizumab met the co-primary endpoints compared with placebo. A total of 48.4% in the mirikizumab group vs 9.0% in the placebo group achieved endoscopic response (P < .000001). Similarly, a higher proportion met clinical remission on the CDAI, 54.1% in the treatment group vs 19.6% in the placebo group (P < .000001).

Overall, 38% of mirikizumab-treated patients vs 9% of the placebo group reached a composite endpoint of patient reported clinical response at week 12 and endoscopic response by SES-CD at week 52 (P < .000001).

Dr. Sands and colleagues also combined clinical response reported by patients at 12 weeks with CDAI findings for clinical remission at week 52. A total of 45.4% in the treatment group met the combined endpoint compared with 19.6% of the placebo group (P < .000001). 

In an additional analysis, the researchers looked at this composite endpoint in patients in both groups who had failed or not failed a prior biologic for a total of 43.4% vs 12.4%, and 47.3% vs 26.5%, respectively.

“Mirikizumab demonstrated statistically significant and clinically meaningful improvements” in the study co-primary endpoints and secondary endpoints compared with placebo, the researchers concluded. 
 

Safety Findings

Safety outcomes during the 52-week study were “consistent with the known safety profile” of mirikizumab, the researchers noted. 

Treatment-emergent adverse events occurred in 78.6% of mirikizumab participants vs 73.0% of the placebo group. The most common were COVID-19, anemia, and arthralgia. Serious adverse events were reported in 10.3% of the mirikizumab group vs 17.1% of the placebo group. There were seven opportunistic infections in the treatment group, including herpes zoster and Candida, compared with none in the placebo group. 

One person in the placebo cohort died of a pulmonary embolism; there were no deaths in the mirikizumab group. 

People randomly assigned to placebo without a response at 12 weeks were switched over to mirikizumab. However, the findings from this group between 12 and 52 weeks were excluded from the 1-year data presented at DDW 2024, including one death from worsening Crohn’s disease during that time.

Mirikizumab looked particularly robust in this study, and it may turn out to be a critically important option for our patients, said Jordan Axelrad, MD, MPH, co-director of the Inflammatory Bowel Disease Center at NYU Langone Health in New York City. Dr. Axelrad was not involved in this study. 

Of importance, effect sizes were similar for “bio-naive and previously biologic-exposed patients,” he added. 

These data “really underscore that therapies targeting IL-23 may be clinically useful for Crohn’s disease patients with prior biologic failure, representing a significant departure from our previous experience with other biologic classes,” Dr. Axelrad said.

The study was funded by Eli Lilly and Company. Dr. Sands is a consultant and receives grant funding from Lilly. Dr. Axelrad had no relevant disclosures. 

A version of this article appeared on Medscape.com.

In February, the US Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) as part of a new regimen for first-line metastatic pancreatic adenocarcinoma called NALIRIFOX.

The main difference between NALIRIFOX and a standard go-to regimen for the indication, modified FOLFIRINOX, is that liposomal irinotecan — irinotecan encased in a lipid nanoparticle — is used instead of free irinotecan.

Trial data suggested a better overall response rate, a slight progression-free survival advantage, and potentially fewer adverse events with the liposomal formulation.

The substitution, however, raises the cost of treatment substantially. According to one estimate, a single cycle of FOLFIRINOX costs about $500 at a body surface area of 2 m², while the equivalent single cycle of NALIRIFOX costs $7800 — over 15-fold more expensive.

While some oncologists have called the NALIRIFOX regimen a potential new standard first-line treatment for metastatic pancreatic adenocarcinoma, others have expressed serious doubts about whether the potential benefits are worth the extra cost.

“I can’t really see a single scenario where I would recommend NALIRIFOX over FOLFIRINOX” Ignacio Garrido-Laguna, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher at the University of Utah, Salt Lake City, told this news organization. “Most of us in the academic setting have the same take on this.”
 

No Head-to-Head Comparison

Uncertainty surrounding the benefits of NALIRIFOX is largely driven by the fact that NALIRIFOX wasn’t compared with FOLFIRINOX in the phase 3 trial that won liposomal irinotecan approval.

Instead, the 770-patient NAPOLI 3 trial compared NALIRIFOX — which also includes oxaliplatin, fluorouracil, and leucovorin — with a two-drug regimen, nab-paclitaxel and gemcitabine. In the trial, overall survival and other outcomes were moderately better with NALIRIFOX.

Oncologists have said that the true value of the trial is that it conclusively demonstrates that a four-drug regimen is superior to a two-drug regimen for patients who can tolerate the more intensive therapy.

Eileen M. O’Reilly, MD, the senior investigator on NAPOLI 3, made this point when she presented the phase 3 results at the 2023 ASCO annual meeting.

The trial “answers the question of four drugs versus two” for first-line metastatic pancreatic cancer but “does not address the question of NALIRIFOX versus FOLFIRINOX,” said Dr. O’Reilly, a pancreatic and hepatobiliary oncologist and researcher at Memorial Sloan Kettering Cancer Center in New York City.

Comparing them directly in the study “probably wouldn’t have been in the interest of the sponsor,” said Dr. O’Reilly.

With no head-to-head comparison, oncologists have been comparing NAPOLI 3 results with those from PRODIGE 4, the 2011 trial that won FOLFIRINOX its place as a first-line regimen.

When comparing the trials, median overall survival was exactly the same for the two regimens — 11.1 months. FOLFIRINOX was associated with a slightly higher 1-year survival rate — 48.4% with FOLFIRINOX vs 45.6% with NALIRIFOX.

However, Dr. O’Reilly and her colleagues also highlighted comparisons between the two trials that favored NAPOLI 3.

NAPOLI 3 had no age limit, while PRODIGE subjects were no older than 75 years. Median progression-free survival was 1 month longer among patients receiving NALIRIFOX — 7.4 months vs 6.4 months in PRODIGE — and overall response rates were higher as well — 41.8% in NAPOLI 3 vs 31.6%. Patients receiving NALIRIFOX also had lower rates of grade 3/4 neutropenia (23.8% vs 45.7%, respectively) and peripheral sensory neuropathy (3.5% vs 9.0%, respectively).

The authors explained that the lower rate of neuropathy could be because NALIRIFOX uses a lower dose of oxaliplatin (FOLFIRINOX), at 60 mg/m² instead of 85 mg/m².
 

Is It Worth It?

During a presentation of the phase 3 findings last year, study author Zev A. Wainberg, MD, of the University of California, Los Angeles, said the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma.

The study discussant, Laura Goff, MD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, agreed that the results support the NALIRIFOX regimen as “the new standard for fit patients.”

However, other oncologists remain skeptical about the benefits of the new regimen over FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma.

In a recent editorial, Dr. Garrido-Laguna and University of Utah gastrointestinal oncologist Christopher Nevala-Plagemann, MD, compared the evidence for both regimens.

The experts pointed out that overall response rates were assessed by investigators in NAPOLI 3 and not by an independent review committee, as in PRODIGE 4, and might have been overestimated.

Although the lack of an age limit was touted as a benefit of NAPOLI 3, Dr. Garrido-Laguna and Dr. Nevala-Plagemann doubt whether enough patients over 75 years old participated to draw any meaningful conclusions about using NALIRIFOX in older, frailer patients. If anything, patients in PRODIGE 4 might have been less fit because, among other things, the trial allowed patients with serum albumins < 3 g/dL.

On the adverse event front, the authors highlighted the higher incidences of grade 3 or worse diarrhea with NALIRIFOX (20% vs 12.7%) and questioned if there truly is less neutropenia with NALIRIFOX because high-risk patients in NAPOLI 3 were treated with granulocyte colony-stimulating factor to prevent it. The pair also questioned whether the differences in neuropathy rates between the two trials were big enough to be clinically meaningful.

Insights from a recent meta-analysis may further clarify some of the lingering questions about the efficacy of NALIRIFOX vs FOLFIRINOX.

In the analysis, the team found no meaningful difference in overall and progression-free survival between the two regimens. Differences in rates of peripheral neuropathy and diarrhea were not statistically significant, but NALIRIFOX did carry a statistically significant advantage in lower rates of febrile neutropenia, thrombocytopenia, and vomiting.

The team concluded that “NALIRIFOX and FOLFIRINOX may provide equal efficacy as first-line treatment of metastatic pancreatic cancer, but with different toxicity profiles,” and called for careful patient selection when choosing between the two regimens as well as consideration of financial toxicity.

Dr. Garrido-Laguna had a different take. With the current data, NALIRIFOX does not seem to “add anything substantially different to what we already” have with FOLFIRINOX, he told this news organization. Given that, “we can’t really justify NALIRIFOX over FOLFIRINOX without more of a head-to-head comparison.”

The higher cost of NALIRIFOX, in particular, remains a major drawback.

“We think it would be an economic disservice to our healthcare systems if we used NALIRIFOX instead of FOLFIRINOX for these patients on the basis of [NAPOLI 3] data,” Bishal Gyawali, MD, PhD, and Christopher Booth, MD, gastrointestinal oncologists at Queen’s University in Kingston, Ontario, Canada, said in a recent essay.

Dr. Garrido-Laguna and Dr. Nevala-Plagemann reiterated this concern.

Overall, “NALIRIFOX does not seem to raise the bar but rather exposes patients and healthcare systems to financial toxicities,” Dr. Garrido-Laguna and Dr. Nevala-Plagemann wrote in their review.

NAPOLI 3 was funded by Ipsen and PRODIGE 4 was funded by the government of France. No funding source was reported for the meta-analysis. NAPOLI 3 investigators included Ipsen employees. Dr. O’Reilly disclosed grants or contracts from Ipsen and many other companies. Dr. Garrido-Laguna reported institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and other companies, but not Ipsen. Dr. Nevala-Plagemann is an advisor for Seagen and reported institutional research funding from Theriva. Dr. Gyawali is a consultant for Vivio Health; Dr. Booth had no disclosures. Two meta-analysis authors reported grants or personal fees from Ipsen as well as ties to other companies.

A version of this article appeared on Medscape.com.

In February, the US Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) as part of a new regimen for first-line metastatic pancreatic adenocarcinoma called NALIRIFOX.

The main difference between NALIRIFOX and a standard go-to regimen for the indication, modified FOLFIRINOX, is that liposomal irinotecan — irinotecan encased in a lipid nanoparticle — is used instead of free irinotecan.

Trial data suggested a better overall response rate, a slight progression-free survival advantage, and potentially fewer adverse events with the liposomal formulation.

The substitution, however, raises the cost of treatment substantially. According to one estimate, a single cycle of FOLFIRINOX costs about $500 at a body surface area of 2 m², while the equivalent single cycle of NALIRIFOX costs $7800 — over 15-fold more expensive.

While some oncologists have called the NALIRIFOX regimen a potential new standard first-line treatment for metastatic pancreatic adenocarcinoma, others have expressed serious doubts about whether the potential benefits are worth the extra cost.

“I can’t really see a single scenario where I would recommend NALIRIFOX over FOLFIRINOX” Ignacio Garrido-Laguna, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher at the University of Utah, Salt Lake City, told this news organization. “Most of us in the academic setting have the same take on this.”
 

No Head-to-Head Comparison

Uncertainty surrounding the benefits of NALIRIFOX is largely driven by the fact that NALIRIFOX wasn’t compared with FOLFIRINOX in the phase 3 trial that won liposomal irinotecan approval.

Instead, the 770-patient NAPOLI 3 trial compared NALIRIFOX — which also includes oxaliplatin, fluorouracil, and leucovorin — with a two-drug regimen, nab-paclitaxel and gemcitabine. In the trial, overall survival and other outcomes were moderately better with NALIRIFOX.

Oncologists have said that the true value of the trial is that it conclusively demonstrates that a four-drug regimen is superior to a two-drug regimen for patients who can tolerate the more intensive therapy.

Eileen M. O’Reilly, MD, the senior investigator on NAPOLI 3, made this point when she presented the phase 3 results at the 2023 ASCO annual meeting.

The trial “answers the question of four drugs versus two” for first-line metastatic pancreatic cancer but “does not address the question of NALIRIFOX versus FOLFIRINOX,” said Dr. O’Reilly, a pancreatic and hepatobiliary oncologist and researcher at Memorial Sloan Kettering Cancer Center in New York City.

Comparing them directly in the study “probably wouldn’t have been in the interest of the sponsor,” said Dr. O’Reilly.

With no head-to-head comparison, oncologists have been comparing NAPOLI 3 results with those from PRODIGE 4, the 2011 trial that won FOLFIRINOX its place as a first-line regimen.

When comparing the trials, median overall survival was exactly the same for the two regimens — 11.1 months. FOLFIRINOX was associated with a slightly higher 1-year survival rate — 48.4% with FOLFIRINOX vs 45.6% with NALIRIFOX.

However, Dr. O’Reilly and her colleagues also highlighted comparisons between the two trials that favored NAPOLI 3.

NAPOLI 3 had no age limit, while PRODIGE subjects were no older than 75 years. Median progression-free survival was 1 month longer among patients receiving NALIRIFOX — 7.4 months vs 6.4 months in PRODIGE — and overall response rates were higher as well — 41.8% in NAPOLI 3 vs 31.6%. Patients receiving NALIRIFOX also had lower rates of grade 3/4 neutropenia (23.8% vs 45.7%, respectively) and peripheral sensory neuropathy (3.5% vs 9.0%, respectively).

The authors explained that the lower rate of neuropathy could be because NALIRIFOX uses a lower dose of oxaliplatin (FOLFIRINOX), at 60 mg/m² instead of 85 mg/m².
 

Is It Worth It?

During a presentation of the phase 3 findings last year, study author Zev A. Wainberg, MD, of the University of California, Los Angeles, said the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma.

The study discussant, Laura Goff, MD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, agreed that the results support the NALIRIFOX regimen as “the new standard for fit patients.”

However, other oncologists remain skeptical about the benefits of the new regimen over FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma.

In a recent editorial, Dr. Garrido-Laguna and University of Utah gastrointestinal oncologist Christopher Nevala-Plagemann, MD, compared the evidence for both regimens.

The experts pointed out that overall response rates were assessed by investigators in NAPOLI 3 and not by an independent review committee, as in PRODIGE 4, and might have been overestimated.

Although the lack of an age limit was touted as a benefit of NAPOLI 3, Dr. Garrido-Laguna and Dr. Nevala-Plagemann doubt whether enough patients over 75 years old participated to draw any meaningful conclusions about using NALIRIFOX in older, frailer patients. If anything, patients in PRODIGE 4 might have been less fit because, among other things, the trial allowed patients with serum albumins < 3 g/dL.

On the adverse event front, the authors highlighted the higher incidences of grade 3 or worse diarrhea with NALIRIFOX (20% vs 12.7%) and questioned if there truly is less neutropenia with NALIRIFOX because high-risk patients in NAPOLI 3 were treated with granulocyte colony-stimulating factor to prevent it. The pair also questioned whether the differences in neuropathy rates between the two trials were big enough to be clinically meaningful.

Insights from a recent meta-analysis may further clarify some of the lingering questions about the efficacy of NALIRIFOX vs FOLFIRINOX.

In the analysis, the team found no meaningful difference in overall and progression-free survival between the two regimens. Differences in rates of peripheral neuropathy and diarrhea were not statistically significant, but NALIRIFOX did carry a statistically significant advantage in lower rates of febrile neutropenia, thrombocytopenia, and vomiting.

The team concluded that “NALIRIFOX and FOLFIRINOX may provide equal efficacy as first-line treatment of metastatic pancreatic cancer, but with different toxicity profiles,” and called for careful patient selection when choosing between the two regimens as well as consideration of financial toxicity.

Dr. Garrido-Laguna had a different take. With the current data, NALIRIFOX does not seem to “add anything substantially different to what we already” have with FOLFIRINOX, he told this news organization. Given that, “we can’t really justify NALIRIFOX over FOLFIRINOX without more of a head-to-head comparison.”

The higher cost of NALIRIFOX, in particular, remains a major drawback.

“We think it would be an economic disservice to our healthcare systems if we used NALIRIFOX instead of FOLFIRINOX for these patients on the basis of [NAPOLI 3] data,” Bishal Gyawali, MD, PhD, and Christopher Booth, MD, gastrointestinal oncologists at Queen’s University in Kingston, Ontario, Canada, said in a recent essay.

Dr. Garrido-Laguna and Dr. Nevala-Plagemann reiterated this concern.

Overall, “NALIRIFOX does not seem to raise the bar but rather exposes patients and healthcare systems to financial toxicities,” Dr. Garrido-Laguna and Dr. Nevala-Plagemann wrote in their review.

NAPOLI 3 was funded by Ipsen and PRODIGE 4 was funded by the government of France. No funding source was reported for the meta-analysis. NAPOLI 3 investigators included Ipsen employees. Dr. O’Reilly disclosed grants or contracts from Ipsen and many other companies. Dr. Garrido-Laguna reported institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and other companies, but not Ipsen. Dr. Nevala-Plagemann is an advisor for Seagen and reported institutional research funding from Theriva. Dr. Gyawali is a consultant for Vivio Health; Dr. Booth had no disclosures. Two meta-analysis authors reported grants or personal fees from Ipsen as well as ties to other companies.

A version of this article appeared on Medscape.com.

In February, the US Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) as part of a new regimen for first-line metastatic pancreatic adenocarcinoma called NALIRIFOX.

The main difference between NALIRIFOX and a standard go-to regimen for the indication, modified FOLFIRINOX, is that liposomal irinotecan — irinotecan encased in a lipid nanoparticle — is used instead of free irinotecan.

Trial data suggested a better overall response rate, a slight progression-free survival advantage, and potentially fewer adverse events with the liposomal formulation.

The substitution, however, raises the cost of treatment substantially. According to one estimate, a single cycle of FOLFIRINOX costs about $500 at a body surface area of 2 m², while the equivalent single cycle of NALIRIFOX costs $7800 — over 15-fold more expensive.

While some oncologists have called the NALIRIFOX regimen a potential new standard first-line treatment for metastatic pancreatic adenocarcinoma, others have expressed serious doubts about whether the potential benefits are worth the extra cost.

“I can’t really see a single scenario where I would recommend NALIRIFOX over FOLFIRINOX” Ignacio Garrido-Laguna, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher at the University of Utah, Salt Lake City, told this news organization. “Most of us in the academic setting have the same take on this.”
 

No Head-to-Head Comparison

Uncertainty surrounding the benefits of NALIRIFOX is largely driven by the fact that NALIRIFOX wasn’t compared with FOLFIRINOX in the phase 3 trial that won liposomal irinotecan approval.

Instead, the 770-patient NAPOLI 3 trial compared NALIRIFOX — which also includes oxaliplatin, fluorouracil, and leucovorin — with a two-drug regimen, nab-paclitaxel and gemcitabine. In the trial, overall survival and other outcomes were moderately better with NALIRIFOX.

Oncologists have said that the true value of the trial is that it conclusively demonstrates that a four-drug regimen is superior to a two-drug regimen for patients who can tolerate the more intensive therapy.

Eileen M. O’Reilly, MD, the senior investigator on NAPOLI 3, made this point when she presented the phase 3 results at the 2023 ASCO annual meeting.

The trial “answers the question of four drugs versus two” for first-line metastatic pancreatic cancer but “does not address the question of NALIRIFOX versus FOLFIRINOX,” said Dr. O’Reilly, a pancreatic and hepatobiliary oncologist and researcher at Memorial Sloan Kettering Cancer Center in New York City.

Comparing them directly in the study “probably wouldn’t have been in the interest of the sponsor,” said Dr. O’Reilly.

With no head-to-head comparison, oncologists have been comparing NAPOLI 3 results with those from PRODIGE 4, the 2011 trial that won FOLFIRINOX its place as a first-line regimen.

When comparing the trials, median overall survival was exactly the same for the two regimens — 11.1 months. FOLFIRINOX was associated with a slightly higher 1-year survival rate — 48.4% with FOLFIRINOX vs 45.6% with NALIRIFOX.

However, Dr. O’Reilly and her colleagues also highlighted comparisons between the two trials that favored NAPOLI 3.

NAPOLI 3 had no age limit, while PRODIGE subjects were no older than 75 years. Median progression-free survival was 1 month longer among patients receiving NALIRIFOX — 7.4 months vs 6.4 months in PRODIGE — and overall response rates were higher as well — 41.8% in NAPOLI 3 vs 31.6%. Patients receiving NALIRIFOX also had lower rates of grade 3/4 neutropenia (23.8% vs 45.7%, respectively) and peripheral sensory neuropathy (3.5% vs 9.0%, respectively).

The authors explained that the lower rate of neuropathy could be because NALIRIFOX uses a lower dose of oxaliplatin (FOLFIRINOX), at 60 mg/m² instead of 85 mg/m².
 

Is It Worth It?

During a presentation of the phase 3 findings last year, study author Zev A. Wainberg, MD, of the University of California, Los Angeles, said the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma.

The study discussant, Laura Goff, MD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, agreed that the results support the NALIRIFOX regimen as “the new standard for fit patients.”

However, other oncologists remain skeptical about the benefits of the new regimen over FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma.

In a recent editorial, Dr. Garrido-Laguna and University of Utah gastrointestinal oncologist Christopher Nevala-Plagemann, MD, compared the evidence for both regimens.

The experts pointed out that overall response rates were assessed by investigators in NAPOLI 3 and not by an independent review committee, as in PRODIGE 4, and might have been overestimated.

Although the lack of an age limit was touted as a benefit of NAPOLI 3, Dr. Garrido-Laguna and Dr. Nevala-Plagemann doubt whether enough patients over 75 years old participated to draw any meaningful conclusions about using NALIRIFOX in older, frailer patients. If anything, patients in PRODIGE 4 might have been less fit because, among other things, the trial allowed patients with serum albumins < 3 g/dL.

On the adverse event front, the authors highlighted the higher incidences of grade 3 or worse diarrhea with NALIRIFOX (20% vs 12.7%) and questioned if there truly is less neutropenia with NALIRIFOX because high-risk patients in NAPOLI 3 were treated with granulocyte colony-stimulating factor to prevent it. The pair also questioned whether the differences in neuropathy rates between the two trials were big enough to be clinically meaningful.

Insights from a recent meta-analysis may further clarify some of the lingering questions about the efficacy of NALIRIFOX vs FOLFIRINOX.

In the analysis, the team found no meaningful difference in overall and progression-free survival between the two regimens. Differences in rates of peripheral neuropathy and diarrhea were not statistically significant, but NALIRIFOX did carry a statistically significant advantage in lower rates of febrile neutropenia, thrombocytopenia, and vomiting.

The team concluded that “NALIRIFOX and FOLFIRINOX may provide equal efficacy as first-line treatment of metastatic pancreatic cancer, but with different toxicity profiles,” and called for careful patient selection when choosing between the two regimens as well as consideration of financial toxicity.

Dr. Garrido-Laguna had a different take. With the current data, NALIRIFOX does not seem to “add anything substantially different to what we already” have with FOLFIRINOX, he told this news organization. Given that, “we can’t really justify NALIRIFOX over FOLFIRINOX without more of a head-to-head comparison.”

The higher cost of NALIRIFOX, in particular, remains a major drawback.

“We think it would be an economic disservice to our healthcare systems if we used NALIRIFOX instead of FOLFIRINOX for these patients on the basis of [NAPOLI 3] data,” Bishal Gyawali, MD, PhD, and Christopher Booth, MD, gastrointestinal oncologists at Queen’s University in Kingston, Ontario, Canada, said in a recent essay.

Dr. Garrido-Laguna and Dr. Nevala-Plagemann reiterated this concern.

Overall, “NALIRIFOX does not seem to raise the bar but rather exposes patients and healthcare systems to financial toxicities,” Dr. Garrido-Laguna and Dr. Nevala-Plagemann wrote in their review.

NAPOLI 3 was funded by Ipsen and PRODIGE 4 was funded by the government of France. No funding source was reported for the meta-analysis. NAPOLI 3 investigators included Ipsen employees. Dr. O’Reilly disclosed grants or contracts from Ipsen and many other companies. Dr. Garrido-Laguna reported institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and other companies, but not Ipsen. Dr. Nevala-Plagemann is an advisor for Seagen and reported institutional research funding from Theriva. Dr. Gyawali is a consultant for Vivio Health; Dr. Booth had no disclosures. Two meta-analysis authors reported grants or personal fees from Ipsen as well as ties to other companies.

A version of this article appeared on Medscape.com.

Atopic dermatitis (AD) among older individuals presented most frequently on the extensor surfaces and trunk, with lichenification and nummular lesions being the most frequent rash characteristics, in a retrospective study of almost 800 patients aged 60 years and older.

The researchers reviewed charts of patients aged 60 years and older who were seen at either a private or county dermatology clinic in Houston between 2009 and 2020 and had been diagnosed with AD by a dermatologist. The findings of their cross-sectional study further supports that AD in this age group “presents as a unique phenotype compared to AD in younger ages, which may inform dermatologists’ diagnosis of AD in these patients” they wrote.

The 791 patients in the study had an average age of 69.3 years, were predominantly women (60.1%), and were racially diverse, with almost 40% being non-Hispanic White individuals. Others were non-Hispanic Black individuals (21.8%), Hispanics (20.4%), and non-Hispanic Asian/Pacific Islanders (11.7%).

Use of topicals, mainly topical corticosteroids (92.2%), was the most frequent treatment prescribed. Oral corticosteroids and antihistamines were “frequent systemic treatments” in this population, prescribed to 10.4% and 12.1%, respectively, “likely due to management prior to a diagnosis of AD by a dermatologist,” wrote first author Hannah Y. Wang, Baylor College of Medicine, Houston, and her coauthors, including Soo Jung Kim, MD, PhD, of the department of dermatology at Baylor.

Other treatments included dupilumab in 5.4%, systemic immunosuppressants (including methotrexate, cyclosporine, and mycophenolate) in 5.4%, and UVB-phototherapy in 2.7%.

Approximately 40% of the patients had a history of allergic rhinitis, while 20% had a history of asthma. Lichenification was noted in 14.5% of patients and nummular lesions in almost 13%. Other rash characteristics — ichthyosis and hyperpigmented patches — were less frequent, seen in 9.7% and 9.1%, respectively.

AD in this older population was most commonly documented on the extensors (49.9%) and the trunk (46%) and less commonly on the hands (19.8%) and feet (9%) — a distribution that is similar to past reports, the authors wrote.

Asked to comment on the findings, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization that the data relating to clinical morphology are consistent with past reports and with his own experiences. Lichenification is a “tell-tale sign of chronic disease” and may indicate undertreatment, and the frequency of nummular plaques is unsurprising because “nummular dermatitis as an independent eczema tends to occur more so in the elderly.”

A version of this article appeared on Medscape.com.

Atopic dermatitis (AD) among older individuals presented most frequently on the extensor surfaces and trunk, with lichenification and nummular lesions being the most frequent rash characteristics, in a retrospective study of almost 800 patients aged 60 years and older.

The researchers reviewed charts of patients aged 60 years and older who were seen at either a private or county dermatology clinic in Houston between 2009 and 2020 and had been diagnosed with AD by a dermatologist. The findings of their cross-sectional study further supports that AD in this age group “presents as a unique phenotype compared to AD in younger ages, which may inform dermatologists’ diagnosis of AD in these patients” they wrote.

The 791 patients in the study had an average age of 69.3 years, were predominantly women (60.1%), and were racially diverse, with almost 40% being non-Hispanic White individuals. Others were non-Hispanic Black individuals (21.8%), Hispanics (20.4%), and non-Hispanic Asian/Pacific Islanders (11.7%).

Use of topicals, mainly topical corticosteroids (92.2%), was the most frequent treatment prescribed. Oral corticosteroids and antihistamines were “frequent systemic treatments” in this population, prescribed to 10.4% and 12.1%, respectively, “likely due to management prior to a diagnosis of AD by a dermatologist,” wrote first author Hannah Y. Wang, Baylor College of Medicine, Houston, and her coauthors, including Soo Jung Kim, MD, PhD, of the department of dermatology at Baylor.

Other treatments included dupilumab in 5.4%, systemic immunosuppressants (including methotrexate, cyclosporine, and mycophenolate) in 5.4%, and UVB-phototherapy in 2.7%.

Approximately 40% of the patients had a history of allergic rhinitis, while 20% had a history of asthma. Lichenification was noted in 14.5% of patients and nummular lesions in almost 13%. Other rash characteristics — ichthyosis and hyperpigmented patches — were less frequent, seen in 9.7% and 9.1%, respectively.

AD in this older population was most commonly documented on the extensors (49.9%) and the trunk (46%) and less commonly on the hands (19.8%) and feet (9%) — a distribution that is similar to past reports, the authors wrote.

Asked to comment on the findings, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization that the data relating to clinical morphology are consistent with past reports and with his own experiences. Lichenification is a “tell-tale sign of chronic disease” and may indicate undertreatment, and the frequency of nummular plaques is unsurprising because “nummular dermatitis as an independent eczema tends to occur more so in the elderly.”

A version of this article appeared on Medscape.com.

Atopic dermatitis (AD) among older individuals presented most frequently on the extensor surfaces and trunk, with lichenification and nummular lesions being the most frequent rash characteristics, in a retrospective study of almost 800 patients aged 60 years and older.

The researchers reviewed charts of patients aged 60 years and older who were seen at either a private or county dermatology clinic in Houston between 2009 and 2020 and had been diagnosed with AD by a dermatologist. The findings of their cross-sectional study further supports that AD in this age group “presents as a unique phenotype compared to AD in younger ages, which may inform dermatologists’ diagnosis of AD in these patients” they wrote.

The 791 patients in the study had an average age of 69.3 years, were predominantly women (60.1%), and were racially diverse, with almost 40% being non-Hispanic White individuals. Others were non-Hispanic Black individuals (21.8%), Hispanics (20.4%), and non-Hispanic Asian/Pacific Islanders (11.7%).

Use of topicals, mainly topical corticosteroids (92.2%), was the most frequent treatment prescribed. Oral corticosteroids and antihistamines were “frequent systemic treatments” in this population, prescribed to 10.4% and 12.1%, respectively, “likely due to management prior to a diagnosis of AD by a dermatologist,” wrote first author Hannah Y. Wang, Baylor College of Medicine, Houston, and her coauthors, including Soo Jung Kim, MD, PhD, of the department of dermatology at Baylor.

Other treatments included dupilumab in 5.4%, systemic immunosuppressants (including methotrexate, cyclosporine, and mycophenolate) in 5.4%, and UVB-phototherapy in 2.7%.

Approximately 40% of the patients had a history of allergic rhinitis, while 20% had a history of asthma. Lichenification was noted in 14.5% of patients and nummular lesions in almost 13%. Other rash characteristics — ichthyosis and hyperpigmented patches — were less frequent, seen in 9.7% and 9.1%, respectively.

AD in this older population was most commonly documented on the extensors (49.9%) and the trunk (46%) and less commonly on the hands (19.8%) and feet (9%) — a distribution that is similar to past reports, the authors wrote.

Asked to comment on the findings, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization that the data relating to clinical morphology are consistent with past reports and with his own experiences. Lichenification is a “tell-tale sign of chronic disease” and may indicate undertreatment, and the frequency of nummular plaques is unsurprising because “nummular dermatitis as an independent eczema tends to occur more so in the elderly.”

A version of this article appeared on Medscape.com.

Local injection of tranexamic acid (TXA) effectively reduced the risk for clinically significant bleeding following Mohs micrographic surgery (MMS), results from a single-center cohort study showed.

“Though Mohs micrographic surgery is associated with low bleeding complication rates, around 1% of patients in the literature report postoperative bleeding,” corresponding author Abigail H. Waldman, MD, director of the Mohs and Dermatologic Surgery Center, at Brigham and Women’s Hospital, Boston, and colleagues wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Intravenous tranexamic acid has been used across surgical specialties to reduce perioperative blood loss. Prior studies have shown topical TXA, an antifibrinolytic agent, following MMS may be effective in reducing postoperative bleeding complications, but there are no large cohort studies on injectable TXA utilization in all patients undergoing MMS.”

To improve the understanding of this intervention, the researchers examined the impact of off-label, locally injected TXA on postoperative bleeding outcomes following MMS conducted at Brigham and Women’s Hospital. They evaluated two cohorts: 1843 patients who underwent MMS from January 1, 2019, to December 31, 2019 (the pre-TXA cohort), and 2101 patients who underwent MMS from July 1, 2022, to June 30, 2023 (the TXA cohort), and extracted data, including patient and tumor characteristics, MMS procedure details, antithrombotic medication use, systemic conditions that predispose to bleeding, encounters reporting postoperative bleeding, and interventions required for postoperative bleeding, from electronic medical records. Patients reconstructed by a non-MMS surgeon were excluded from the analysis.

Overall, 2509 cases among 1843 patients and 2818 cases among 2101 were included in the pre-TXA and TXA cohorts, respectively. The researchers found that local subcutaneous injection of TXA reduced the risk for postoperative phone calls or visits for bleeding by 25% (RR [risk ratio], 0.75; 0.57-0.99) and risk for bleeding necessitating a medical visit by 51% (RR, 0.49; 0.32-0.77).

The use of preoperative TXA in several subgroups of patients also was also associated with a reduction in visits for bleeding, including those using alcohol (52% reduction; RR, 0.47; 0.26-0.85), cigarettes (57% reduction; RR, 0.43; 0.23-0.82), oral anticoagulants (61% reduction; RR, 0.39; 0.20-0.77), or antiplatelets (60% reduction; RR, 0.40; 0.20-0.79). The use of TXA was also associated with reduced visits for bleeding in tumors of the head and neck (RR, 0.45; 0.26-0.77) and tumors with a preoperative diameter > 2 cm (RR, 0.37; 0.15-0.90).

Impact of Surgical Repair Type

In other findings, the type of surgical repair was a potential confounder, the authors reported. Grafts and flaps were associated with an increased risk for bleeding across both cohorts (RR, 2.36 [1.5-3.6] and 1.7 [1.1-2.6], respectively) and together comprised 15% of all procedures in the pre-TXA cohort compared with 11.1% in TXA cohort. Two patients in the TXA cohort (0.11%) developed deep vein thrombosis (DVT) 10- and 20-days postoperation, a rate that the authors said is comparable to that of the general population. The two patients had risk factors for hypercoagulability, including advanced cancer and recurrent DVT.

“Overall, local injection of TXA was an effective method for reducing the risk of clinically significant bleeding following MMS,” the researchers concluded. “Perioperative TXA may help to limit the risk of bleeding overall, as well as in populations predisposed to bleeding.” Adverse events with TXA use were rare “and delayed beyond the activity of TXA, indicating a low likelihood of being due to TXA,” they wrote.

“Dermatologists performing MMS may consider incorporating local TXA injection into their regular practice,” they noted, adding that “legal counsel on adverse effects in the setting of off-label pharmaceutical usage may be advised.”

In an interview, Patricia M. Richey, MD, director of Mohs surgery at Boston Medical Center, who was asked to comment on the study, said that postoperative bleeding is one of the most commonly encountered Mohs surgery complications. “Because of increased clinic visits and phone calls, it can also often result in decreased patient satisfaction,” she said.

“This study is particularly notable in that we see that local subcutaneous TXA injection decreased visits for bleeding even in those using oral anticoagulants, antiplatelets, alcohol, and cigarettes. Dermatologic surgery has a very low complication rate, even in patients on anticoagulant and antiplatelet medications, but this study shows that TXA is a fantastic option for Mohs surgeons and patients.”

Neither the study authors nor Dr. Richey reported having financial disclosures.

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

Local injection of tranexamic acid (TXA) effectively reduced the risk for clinically significant bleeding following Mohs micrographic surgery (MMS), results from a single-center cohort study showed.

“Though Mohs micrographic surgery is associated with low bleeding complication rates, around 1% of patients in the literature report postoperative bleeding,” corresponding author Abigail H. Waldman, MD, director of the Mohs and Dermatologic Surgery Center, at Brigham and Women’s Hospital, Boston, and colleagues wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Intravenous tranexamic acid has been used across surgical specialties to reduce perioperative blood loss. Prior studies have shown topical TXA, an antifibrinolytic agent, following MMS may be effective in reducing postoperative bleeding complications, but there are no large cohort studies on injectable TXA utilization in all patients undergoing MMS.”

To improve the understanding of this intervention, the researchers examined the impact of off-label, locally injected TXA on postoperative bleeding outcomes following MMS conducted at Brigham and Women’s Hospital. They evaluated two cohorts: 1843 patients who underwent MMS from January 1, 2019, to December 31, 2019 (the pre-TXA cohort), and 2101 patients who underwent MMS from July 1, 2022, to June 30, 2023 (the TXA cohort), and extracted data, including patient and tumor characteristics, MMS procedure details, antithrombotic medication use, systemic conditions that predispose to bleeding, encounters reporting postoperative bleeding, and interventions required for postoperative bleeding, from electronic medical records. Patients reconstructed by a non-MMS surgeon were excluded from the analysis.

Overall, 2509 cases among 1843 patients and 2818 cases among 2101 were included in the pre-TXA and TXA cohorts, respectively. The researchers found that local subcutaneous injection of TXA reduced the risk for postoperative phone calls or visits for bleeding by 25% (RR [risk ratio], 0.75; 0.57-0.99) and risk for bleeding necessitating a medical visit by 51% (RR, 0.49; 0.32-0.77).

The use of preoperative TXA in several subgroups of patients also was also associated with a reduction in visits for bleeding, including those using alcohol (52% reduction; RR, 0.47; 0.26-0.85), cigarettes (57% reduction; RR, 0.43; 0.23-0.82), oral anticoagulants (61% reduction; RR, 0.39; 0.20-0.77), or antiplatelets (60% reduction; RR, 0.40; 0.20-0.79). The use of TXA was also associated with reduced visits for bleeding in tumors of the head and neck (RR, 0.45; 0.26-0.77) and tumors with a preoperative diameter > 2 cm (RR, 0.37; 0.15-0.90).

Impact of Surgical Repair Type

In other findings, the type of surgical repair was a potential confounder, the authors reported. Grafts and flaps were associated with an increased risk for bleeding across both cohorts (RR, 2.36 [1.5-3.6] and 1.7 [1.1-2.6], respectively) and together comprised 15% of all procedures in the pre-TXA cohort compared with 11.1% in TXA cohort. Two patients in the TXA cohort (0.11%) developed deep vein thrombosis (DVT) 10- and 20-days postoperation, a rate that the authors said is comparable to that of the general population. The two patients had risk factors for hypercoagulability, including advanced cancer and recurrent DVT.

“Overall, local injection of TXA was an effective method for reducing the risk of clinically significant bleeding following MMS,” the researchers concluded. “Perioperative TXA may help to limit the risk of bleeding overall, as well as in populations predisposed to bleeding.” Adverse events with TXA use were rare “and delayed beyond the activity of TXA, indicating a low likelihood of being due to TXA,” they wrote.

“Dermatologists performing MMS may consider incorporating local TXA injection into their regular practice,” they noted, adding that “legal counsel on adverse effects in the setting of off-label pharmaceutical usage may be advised.”

In an interview, Patricia M. Richey, MD, director of Mohs surgery at Boston Medical Center, who was asked to comment on the study, said that postoperative bleeding is one of the most commonly encountered Mohs surgery complications. “Because of increased clinic visits and phone calls, it can also often result in decreased patient satisfaction,” she said.

“This study is particularly notable in that we see that local subcutaneous TXA injection decreased visits for bleeding even in those using oral anticoagulants, antiplatelets, alcohol, and cigarettes. Dermatologic surgery has a very low complication rate, even in patients on anticoagulant and antiplatelet medications, but this study shows that TXA is a fantastic option for Mohs surgeons and patients.”

Neither the study authors nor Dr. Richey reported having financial disclosures.

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

Local injection of tranexamic acid (TXA) effectively reduced the risk for clinically significant bleeding following Mohs micrographic surgery (MMS), results from a single-center cohort study showed.

“Though Mohs micrographic surgery is associated with low bleeding complication rates, around 1% of patients in the literature report postoperative bleeding,” corresponding author Abigail H. Waldman, MD, director of the Mohs and Dermatologic Surgery Center, at Brigham and Women’s Hospital, Boston, and colleagues wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Intravenous tranexamic acid has been used across surgical specialties to reduce perioperative blood loss. Prior studies have shown topical TXA, an antifibrinolytic agent, following MMS may be effective in reducing postoperative bleeding complications, but there are no large cohort studies on injectable TXA utilization in all patients undergoing MMS.”

To improve the understanding of this intervention, the researchers examined the impact of off-label, locally injected TXA on postoperative bleeding outcomes following MMS conducted at Brigham and Women’s Hospital. They evaluated two cohorts: 1843 patients who underwent MMS from January 1, 2019, to December 31, 2019 (the pre-TXA cohort), and 2101 patients who underwent MMS from July 1, 2022, to June 30, 2023 (the TXA cohort), and extracted data, including patient and tumor characteristics, MMS procedure details, antithrombotic medication use, systemic conditions that predispose to bleeding, encounters reporting postoperative bleeding, and interventions required for postoperative bleeding, from electronic medical records. Patients reconstructed by a non-MMS surgeon were excluded from the analysis.

Overall, 2509 cases among 1843 patients and 2818 cases among 2101 were included in the pre-TXA and TXA cohorts, respectively. The researchers found that local subcutaneous injection of TXA reduced the risk for postoperative phone calls or visits for bleeding by 25% (RR [risk ratio], 0.75; 0.57-0.99) and risk for bleeding necessitating a medical visit by 51% (RR, 0.49; 0.32-0.77).

The use of preoperative TXA in several subgroups of patients also was also associated with a reduction in visits for bleeding, including those using alcohol (52% reduction; RR, 0.47; 0.26-0.85), cigarettes (57% reduction; RR, 0.43; 0.23-0.82), oral anticoagulants (61% reduction; RR, 0.39; 0.20-0.77), or antiplatelets (60% reduction; RR, 0.40; 0.20-0.79). The use of TXA was also associated with reduced visits for bleeding in tumors of the head and neck (RR, 0.45; 0.26-0.77) and tumors with a preoperative diameter > 2 cm (RR, 0.37; 0.15-0.90).

Impact of Surgical Repair Type

In other findings, the type of surgical repair was a potential confounder, the authors reported. Grafts and flaps were associated with an increased risk for bleeding across both cohorts (RR, 2.36 [1.5-3.6] and 1.7 [1.1-2.6], respectively) and together comprised 15% of all procedures in the pre-TXA cohort compared with 11.1% in TXA cohort. Two patients in the TXA cohort (0.11%) developed deep vein thrombosis (DVT) 10- and 20-days postoperation, a rate that the authors said is comparable to that of the general population. The two patients had risk factors for hypercoagulability, including advanced cancer and recurrent DVT.

“Overall, local injection of TXA was an effective method for reducing the risk of clinically significant bleeding following MMS,” the researchers concluded. “Perioperative TXA may help to limit the risk of bleeding overall, as well as in populations predisposed to bleeding.” Adverse events with TXA use were rare “and delayed beyond the activity of TXA, indicating a low likelihood of being due to TXA,” they wrote.

“Dermatologists performing MMS may consider incorporating local TXA injection into their regular practice,” they noted, adding that “legal counsel on adverse effects in the setting of off-label pharmaceutical usage may be advised.”

In an interview, Patricia M. Richey, MD, director of Mohs surgery at Boston Medical Center, who was asked to comment on the study, said that postoperative bleeding is one of the most commonly encountered Mohs surgery complications. “Because of increased clinic visits and phone calls, it can also often result in decreased patient satisfaction,” she said.

“This study is particularly notable in that we see that local subcutaneous TXA injection decreased visits for bleeding even in those using oral anticoagulants, antiplatelets, alcohol, and cigarettes. Dermatologic surgery has a very low complication rate, even in patients on anticoagulant and antiplatelet medications, but this study shows that TXA is a fantastic option for Mohs surgeons and patients.”

Neither the study authors nor Dr. Richey reported having financial disclosures.

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

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

Presentation

A 24-year-old man with no significant past medical history presents to urgent care with a 1-week history of sudden-onset dark urine, leg swelling, and unusually high blood pressure readings, with recent values around 160/100 mm Hg. Physical examination reveals pitting edema up to the mid-shins and mild periorbital edema, with an elevated blood pressure of 158/98 mm Hg. Past medical history was significant for frequent upper respiratory tract infections over the past year. Laboratory findings include hematuria, proteinuria, and a raised serum creatinine level at 1.8 mg/dL, indicating a reduced estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m². Other tests such as a complete blood count and comprehensive metabolic panel (except for creatinine and albumin) are within normal limits. Given these findings, the patient is referred to nephrology for further evaluation to determine the underlying cause of his renal symptoms.

Differential Diagnosis

A glomerular disease can be assumed to be present if the patient manifests glomerular hematuria, glomerular proteinuria, or both, such as in this patient.

Glomerulonephritis occurs due to inflammation in the glomeruli, which leads to blood in urine, variable degrees of protein in urine (sometimes in the nephrotic range), and white blood cells in urine without any urinary tract infection. Patients may also experience hypertension and kidney function impairment. Diagnoses to consider include:

• Postinfectious glomerulonephritis
• Crescentic glomerulonephritis
• Diffuse proliferative glomerulonephritis
• Glomerulonephritis associated with nonstreptococcal infection
• Membranoproliferative glomerulonephritis
• Membranous glomerulonephritis
• Poststreptococcal glomerulonephritis
• Rapidly Progressive glomerulonephritis

All patients presenting with proteinuria and hematuria should undergo a thorough evaluation for glomerular disease, which generally involves laboratory testing and, in most patients, a kidney biopsy to obtain a definitive diagnosis.
 

Diagnosis

This patient underwent a renal biopsy, which showed C3-dominant deposition by immunofluorescence; electron microscopy (EM) showed discontinuous, ill-defined intramembranous deposits; and mass spectrometry showed terminal complement components in C3 deposits. The patient was diagnosed with C3 glomerulonephritis (C3G).

The diagnosis of C3G is established by kidney biopsy demonstrating the characteristic findings on immunofluorescence microscopy or EM in a patient with suspected glomerulonephritis. In patients with biopsy-confirmed C3G, additional testing should be performed to help identify the underlying etiology of the glomerulopathy to help determine therapy.

For all patients diagnosed with C3G, especially those who are older than 50 years, it is important to rule out monoclonal gammopathy which can be done through various tests such as serum protein electrophoresis and immunofixation, serum free light chains, and urine protein electrophoresis and immunofixation. The presence of a paraprotein, including a monoclonal light chain, can activate the alternative complement cascade and may be responsible for the condition.

Expert opinion recommends a comprehensive complement evaluation for all C3 glomerulopathy patients, including overall complement activity assessment, serum levels measurement of complement proteins and their split products, and autoantibodies screening.

Complement evaluation may include:

• Serum C3 and C4
• Soluble C5b-9 (soluble membrane attack complex)
• Serum factor H
• Serum factor B, factor I, and membrane cofactor protein (MCP; CD46)

All patients with C3G should also undergo screening for autoantibodies:

• C3 nephritic factor (C3NeF)
• C5 nephritic factor (C5NeF)
• C4 nephritic factor (C4NeF)
• Other autoantibodies against factor H, factor B, and/or C3b

It is recommended that genetic testing be considered for patients with C3 glomerulopathy to screen for complement genes including C3, CFB, CFH, CFHR5, and CFI and copy number variations and rearrangements of the CFH-CFHR gene cluster. The value of genetic testing in the clinical setting is still being defined; however, it has been observed that patients with mutations in complement genes generally respond less favorably to mycophenolate mofetil (MMF) compared with those who are positive for nephritic factors.
 

Management

The patient was managed with an angiotensin-converting enzyme (ACE) inhibitor to treat proteinuria and hypertension and MMF for immunosuppression. Enrollment in a clinical trial of an investigational complement inhibitor was discussed with the patient.

Currently, there are no therapeutic agents specifically designed to target the underlying complement dysregulation that occurs in individuals with C3G, and an optimal treatment for C3 glomerulopathy has not been established.

Various nonspecific therapies have been used to treat C3G, including plasmapheresis, steroids, rituximab, cyclophosphamide, and MMF and have shown positive results. For patients with C3G who have a known genetic variant (eg, CFH mutation) or who have acute kidney injury, plasmapheresis and plasma exchange may be helpful. Using these agents judiciously and in conjunction with optimal blood pressure control is important for maximum benefit in treating C3G. When someone with end-stage renal disease (ESRD) caused by C3G chooses to have a kidney transplant, it is important to know that C3G is likely to return in almost all cases and is the leading cause of transplant failure in 50%-90% of recipients.
 

Prognosis

The prognosis of C3G varies and is affected by various clinical and histological factors. While some patients may have consistently low levels of protein in their urine and maintain stable kidney function over time, others may experience severe nephrotic syndrome or rapidly progressive glomerulonephritis, which often leads to a poor prognosis.

Progression to ESRD is a major complication of C3G, with approximately 70% of affected children and 30%-50% of adults reaching this stage. In addition, disease recurrence is common after kidney transplantation, with about 50% of patients experiencing allograft loss within 10 years. Predictive factors for disease progression, although not robustly established, include initial eGFR at diagnosis, percentage of tubular atrophy, and extent of interstitial fibrosis in the cortical area as observed on kidney biopsies.
 

Clinical Takeaways

For patients exhibiting symptoms like proteinuria and hematuria indicative of glomerulonephritis, a comprehensive evaluation including laboratory tests and a kidney biopsy is essential to confirm a C3G diagnosis through characteristic findings on immunofluorescence microscopy or electron microscopy.

Additional tests to rule out associated conditions like monoclonal gammopathy and comprehensive complement evaluation are also recommended to understand the underlying etiology and guide therapy.

Though there are no treatments specifically targeting the underlying complement dysregulation unique to C3G, nonspecific therapies like ACE inhibitors, immunosuppressants (eg, MMF), and plasmapheresis are commonly used.

Some anticomplement therapies are available or under investigation, which might offer more targeted intervention options.

The prognosis for patients with C3G can vary widely and factors such as initial eGFR, the extent of tubular atrophy, and interstitial fibrosis are important predictors of disease progression.

Dr. Alper is an associate professor, Nephrology, Tulane University School of Medicine, New Orleans, Louisiana. He has disclosed no relevant financial relationships.

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

Presentation

A 24-year-old man with no significant past medical history presents to urgent care with a 1-week history of sudden-onset dark urine, leg swelling, and unusually high blood pressure readings, with recent values around 160/100 mm Hg. Physical examination reveals pitting edema up to the mid-shins and mild periorbital edema, with an elevated blood pressure of 158/98 mm Hg. Past medical history was significant for frequent upper respiratory tract infections over the past year. Laboratory findings include hematuria, proteinuria, and a raised serum creatinine level at 1.8 mg/dL, indicating a reduced estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m². Other tests such as a complete blood count and comprehensive metabolic panel (except for creatinine and albumin) are within normal limits. Given these findings, the patient is referred to nephrology for further evaluation to determine the underlying cause of his renal symptoms.

Differential Diagnosis

A glomerular disease can be assumed to be present if the patient manifests glomerular hematuria, glomerular proteinuria, or both, such as in this patient.

Glomerulonephritis occurs due to inflammation in the glomeruli, which leads to blood in urine, variable degrees of protein in urine (sometimes in the nephrotic range), and white blood cells in urine without any urinary tract infection. Patients may also experience hypertension and kidney function impairment. Diagnoses to consider include:

• Postinfectious glomerulonephritis
• Crescentic glomerulonephritis
• Diffuse proliferative glomerulonephritis
• Glomerulonephritis associated with nonstreptococcal infection
• Membranoproliferative glomerulonephritis
• Membranous glomerulonephritis
• Poststreptococcal glomerulonephritis
• Rapidly Progressive glomerulonephritis

All patients presenting with proteinuria and hematuria should undergo a thorough evaluation for glomerular disease, which generally involves laboratory testing and, in most patients, a kidney biopsy to obtain a definitive diagnosis.
 

Diagnosis

This patient underwent a renal biopsy, which showed C3-dominant deposition by immunofluorescence; electron microscopy (EM) showed discontinuous, ill-defined intramembranous deposits; and mass spectrometry showed terminal complement components in C3 deposits. The patient was diagnosed with C3 glomerulonephritis (C3G).

The diagnosis of C3G is established by kidney biopsy demonstrating the characteristic findings on immunofluorescence microscopy or EM in a patient with suspected glomerulonephritis. In patients with biopsy-confirmed C3G, additional testing should be performed to help identify the underlying etiology of the glomerulopathy to help determine therapy.

For all patients diagnosed with C3G, especially those who are older than 50 years, it is important to rule out monoclonal gammopathy which can be done through various tests such as serum protein electrophoresis and immunofixation, serum free light chains, and urine protein electrophoresis and immunofixation. The presence of a paraprotein, including a monoclonal light chain, can activate the alternative complement cascade and may be responsible for the condition.

Expert opinion recommends a comprehensive complement evaluation for all C3 glomerulopathy patients, including overall complement activity assessment, serum levels measurement of complement proteins and their split products, and autoantibodies screening.

Complement evaluation may include:

• Serum C3 and C4
• Soluble C5b-9 (soluble membrane attack complex)
• Serum factor H
• Serum factor B, factor I, and membrane cofactor protein (MCP; CD46)

All patients with C3G should also undergo screening for autoantibodies:

• C3 nephritic factor (C3NeF)
• C5 nephritic factor (C5NeF)
• C4 nephritic factor (C4NeF)
• Other autoantibodies against factor H, factor B, and/or C3b

It is recommended that genetic testing be considered for patients with C3 glomerulopathy to screen for complement genes including C3, CFB, CFH, CFHR5, and CFI and copy number variations and rearrangements of the CFH-CFHR gene cluster. The value of genetic testing in the clinical setting is still being defined; however, it has been observed that patients with mutations in complement genes generally respond less favorably to mycophenolate mofetil (MMF) compared with those who are positive for nephritic factors.
 

Management

The patient was managed with an angiotensin-converting enzyme (ACE) inhibitor to treat proteinuria and hypertension and MMF for immunosuppression. Enrollment in a clinical trial of an investigational complement inhibitor was discussed with the patient.

Currently, there are no therapeutic agents specifically designed to target the underlying complement dysregulation that occurs in individuals with C3G, and an optimal treatment for C3 glomerulopathy has not been established.

Various nonspecific therapies have been used to treat C3G, including plasmapheresis, steroids, rituximab, cyclophosphamide, and MMF and have shown positive results. For patients with C3G who have a known genetic variant (eg, CFH mutation) or who have acute kidney injury, plasmapheresis and plasma exchange may be helpful. Using these agents judiciously and in conjunction with optimal blood pressure control is important for maximum benefit in treating C3G. When someone with end-stage renal disease (ESRD) caused by C3G chooses to have a kidney transplant, it is important to know that C3G is likely to return in almost all cases and is the leading cause of transplant failure in 50%-90% of recipients.
 

Prognosis

The prognosis of C3G varies and is affected by various clinical and histological factors. While some patients may have consistently low levels of protein in their urine and maintain stable kidney function over time, others may experience severe nephrotic syndrome or rapidly progressive glomerulonephritis, which often leads to a poor prognosis.

Progression to ESRD is a major complication of C3G, with approximately 70% of affected children and 30%-50% of adults reaching this stage. In addition, disease recurrence is common after kidney transplantation, with about 50% of patients experiencing allograft loss within 10 years. Predictive factors for disease progression, although not robustly established, include initial eGFR at diagnosis, percentage of tubular atrophy, and extent of interstitial fibrosis in the cortical area as observed on kidney biopsies.
 

Clinical Takeaways

For patients exhibiting symptoms like proteinuria and hematuria indicative of glomerulonephritis, a comprehensive evaluation including laboratory tests and a kidney biopsy is essential to confirm a C3G diagnosis through characteristic findings on immunofluorescence microscopy or electron microscopy.

Additional tests to rule out associated conditions like monoclonal gammopathy and comprehensive complement evaluation are also recommended to understand the underlying etiology and guide therapy.

Though there are no treatments specifically targeting the underlying complement dysregulation unique to C3G, nonspecific therapies like ACE inhibitors, immunosuppressants (eg, MMF), and plasmapheresis are commonly used.

Some anticomplement therapies are available or under investigation, which might offer more targeted intervention options.

The prognosis for patients with C3G can vary widely and factors such as initial eGFR, the extent of tubular atrophy, and interstitial fibrosis are important predictors of disease progression.

Dr. Alper is an associate professor, Nephrology, Tulane University School of Medicine, New Orleans, Louisiana. He has disclosed no relevant financial relationships.

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

Presentation

A 24-year-old man with no significant past medical history presents to urgent care with a 1-week history of sudden-onset dark urine, leg swelling, and unusually high blood pressure readings, with recent values around 160/100 mm Hg. Physical examination reveals pitting edema up to the mid-shins and mild periorbital edema, with an elevated blood pressure of 158/98 mm Hg. Past medical history was significant for frequent upper respiratory tract infections over the past year. Laboratory findings include hematuria, proteinuria, and a raised serum creatinine level at 1.8 mg/dL, indicating a reduced estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m². Other tests such as a complete blood count and comprehensive metabolic panel (except for creatinine and albumin) are within normal limits. Given these findings, the patient is referred to nephrology for further evaluation to determine the underlying cause of his renal symptoms.

Differential Diagnosis

A glomerular disease can be assumed to be present if the patient manifests glomerular hematuria, glomerular proteinuria, or both, such as in this patient.

Glomerulonephritis occurs due to inflammation in the glomeruli, which leads to blood in urine, variable degrees of protein in urine (sometimes in the nephrotic range), and white blood cells in urine without any urinary tract infection. Patients may also experience hypertension and kidney function impairment. Diagnoses to consider include:

• Postinfectious glomerulonephritis
• Crescentic glomerulonephritis
• Diffuse proliferative glomerulonephritis
• Glomerulonephritis associated with nonstreptococcal infection
• Membranoproliferative glomerulonephritis
• Membranous glomerulonephritis
• Poststreptococcal glomerulonephritis
• Rapidly Progressive glomerulonephritis

All patients presenting with proteinuria and hematuria should undergo a thorough evaluation for glomerular disease, which generally involves laboratory testing and, in most patients, a kidney biopsy to obtain a definitive diagnosis.
 

Diagnosis

This patient underwent a renal biopsy, which showed C3-dominant deposition by immunofluorescence; electron microscopy (EM) showed discontinuous, ill-defined intramembranous deposits; and mass spectrometry showed terminal complement components in C3 deposits. The patient was diagnosed with C3 glomerulonephritis (C3G).

The diagnosis of C3G is established by kidney biopsy demonstrating the characteristic findings on immunofluorescence microscopy or EM in a patient with suspected glomerulonephritis. In patients with biopsy-confirmed C3G, additional testing should be performed to help identify the underlying etiology of the glomerulopathy to help determine therapy.

For all patients diagnosed with C3G, especially those who are older than 50 years, it is important to rule out monoclonal gammopathy which can be done through various tests such as serum protein electrophoresis and immunofixation, serum free light chains, and urine protein electrophoresis and immunofixation. The presence of a paraprotein, including a monoclonal light chain, can activate the alternative complement cascade and may be responsible for the condition.

Expert opinion recommends a comprehensive complement evaluation for all C3 glomerulopathy patients, including overall complement activity assessment, serum levels measurement of complement proteins and their split products, and autoantibodies screening.

Complement evaluation may include:

• Serum C3 and C4
• Soluble C5b-9 (soluble membrane attack complex)
• Serum factor H
• Serum factor B, factor I, and membrane cofactor protein (MCP; CD46)

All patients with C3G should also undergo screening for autoantibodies:

• C3 nephritic factor (C3NeF)
• C5 nephritic factor (C5NeF)
• C4 nephritic factor (C4NeF)
• Other autoantibodies against factor H, factor B, and/or C3b

It is recommended that genetic testing be considered for patients with C3 glomerulopathy to screen for complement genes including C3, CFB, CFH, CFHR5, and CFI and copy number variations and rearrangements of the CFH-CFHR gene cluster. The value of genetic testing in the clinical setting is still being defined; however, it has been observed that patients with mutations in complement genes generally respond less favorably to mycophenolate mofetil (MMF) compared with those who are positive for nephritic factors.
 

Management

The patient was managed with an angiotensin-converting enzyme (ACE) inhibitor to treat proteinuria and hypertension and MMF for immunosuppression. Enrollment in a clinical trial of an investigational complement inhibitor was discussed with the patient.

Currently, there are no therapeutic agents specifically designed to target the underlying complement dysregulation that occurs in individuals with C3G, and an optimal treatment for C3 glomerulopathy has not been established.

Various nonspecific therapies have been used to treat C3G, including plasmapheresis, steroids, rituximab, cyclophosphamide, and MMF and have shown positive results. For patients with C3G who have a known genetic variant (eg, CFH mutation) or who have acute kidney injury, plasmapheresis and plasma exchange may be helpful. Using these agents judiciously and in conjunction with optimal blood pressure control is important for maximum benefit in treating C3G. When someone with end-stage renal disease (ESRD) caused by C3G chooses to have a kidney transplant, it is important to know that C3G is likely to return in almost all cases and is the leading cause of transplant failure in 50%-90% of recipients.
 

Prognosis

The prognosis of C3G varies and is affected by various clinical and histological factors. While some patients may have consistently low levels of protein in their urine and maintain stable kidney function over time, others may experience severe nephrotic syndrome or rapidly progressive glomerulonephritis, which often leads to a poor prognosis.

Progression to ESRD is a major complication of C3G, with approximately 70% of affected children and 30%-50% of adults reaching this stage. In addition, disease recurrence is common after kidney transplantation, with about 50% of patients experiencing allograft loss within 10 years. Predictive factors for disease progression, although not robustly established, include initial eGFR at diagnosis, percentage of tubular atrophy, and extent of interstitial fibrosis in the cortical area as observed on kidney biopsies.
 

Clinical Takeaways

For patients exhibiting symptoms like proteinuria and hematuria indicative of glomerulonephritis, a comprehensive evaluation including laboratory tests and a kidney biopsy is essential to confirm a C3G diagnosis through characteristic findings on immunofluorescence microscopy or electron microscopy.

Additional tests to rule out associated conditions like monoclonal gammopathy and comprehensive complement evaluation are also recommended to understand the underlying etiology and guide therapy.

Though there are no treatments specifically targeting the underlying complement dysregulation unique to C3G, nonspecific therapies like ACE inhibitors, immunosuppressants (eg, MMF), and plasmapheresis are commonly used.

Some anticomplement therapies are available or under investigation, which might offer more targeted intervention options.

The prognosis for patients with C3G can vary widely and factors such as initial eGFR, the extent of tubular atrophy, and interstitial fibrosis are important predictors of disease progression.

Dr. Alper is an associate professor, Nephrology, Tulane University School of Medicine, New Orleans, Louisiana. He has disclosed no relevant financial relationships.

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

TOPLINE:

Physical performance significantly correlates with increased survival rates in individuals aged over 80 years.

METHODOLOGY:

• Researchers analyzed data from 195 participants in the ilSIRENTE study, a prospective cohort study in L’Aquila, Italy, that included men and women born before 1924. The analysis focused on participants aged < 85 years at the time of enrollment (mean age, 82 years).
• Physical performance was assessed via the Short Physical Performance Battery (SPPB), which tests balance, gait speed, and leg strength based on the ability to stand from a seated position in a chair.
• Based on SPPB scores, participants were classified as having severe, moderate, mild, or no functional impairment.

TAKEAWAY:

• About 21% of the participants lived to 95 years of age.
• Higher scores on the SPPB and faster gait speed were linked to a lower risk for mortality before that age.
• The average gait speed was 0.88 m/s among participants who lived to 95 years of age and 0.78 m/s for those who died at younger ages.

IN PRACTICE:

“Physical performance is ... a reliable metric for assessing mortality risk in octogenarians,” the authors of the study wrote. “Our findings, together with available evidence, support the view that physical performance is a primary target for interventions to enhance longevity and extend health span.”

SOURCE:

Stefano Cacciatore, MD, with Universita Cattolica del Sacro Cuore, in Rome, was the corresponding author on the paper. The study was published online on May 2, 2024, in Journal of the American Geriatrics Society.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Physical performance significantly correlates with increased survival rates in individuals aged over 80 years.

METHODOLOGY:

• Researchers analyzed data from 195 participants in the ilSIRENTE study, a prospective cohort study in L’Aquila, Italy, that included men and women born before 1924. The analysis focused on participants aged < 85 years at the time of enrollment (mean age, 82 years).
• Physical performance was assessed via the Short Physical Performance Battery (SPPB), which tests balance, gait speed, and leg strength based on the ability to stand from a seated position in a chair.
• Based on SPPB scores, participants were classified as having severe, moderate, mild, or no functional impairment.

TAKEAWAY:

• About 21% of the participants lived to 95 years of age.
• Higher scores on the SPPB and faster gait speed were linked to a lower risk for mortality before that age.
• The average gait speed was 0.88 m/s among participants who lived to 95 years of age and 0.78 m/s for those who died at younger ages.

IN PRACTICE:

“Physical performance is ... a reliable metric for assessing mortality risk in octogenarians,” the authors of the study wrote. “Our findings, together with available evidence, support the view that physical performance is a primary target for interventions to enhance longevity and extend health span.”

SOURCE:

Stefano Cacciatore, MD, with Universita Cattolica del Sacro Cuore, in Rome, was the corresponding author on the paper. The study was published online on May 2, 2024, in Journal of the American Geriatrics Society.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Physical performance significantly correlates with increased survival rates in individuals aged over 80 years.

METHODOLOGY:

• Researchers analyzed data from 195 participants in the ilSIRENTE study, a prospective cohort study in L’Aquila, Italy, that included men and women born before 1924. The analysis focused on participants aged < 85 years at the time of enrollment (mean age, 82 years).
• Physical performance was assessed via the Short Physical Performance Battery (SPPB), which tests balance, gait speed, and leg strength based on the ability to stand from a seated position in a chair.
• Based on SPPB scores, participants were classified as having severe, moderate, mild, or no functional impairment.

TAKEAWAY:

• About 21% of the participants lived to 95 years of age.
• Higher scores on the SPPB and faster gait speed were linked to a lower risk for mortality before that age.
• The average gait speed was 0.88 m/s among participants who lived to 95 years of age and 0.78 m/s for those who died at younger ages.

IN PRACTICE:

“Physical performance is ... a reliable metric for assessing mortality risk in octogenarians,” the authors of the study wrote. “Our findings, together with available evidence, support the view that physical performance is a primary target for interventions to enhance longevity and extend health span.”

SOURCE:

Stefano Cacciatore, MD, with Universita Cattolica del Sacro Cuore, in Rome, was the corresponding author on the paper. The study was published online on May 2, 2024, in Journal of the American Geriatrics Society.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

SAN FRANCISCO — Patients with a low-lying placenta who underwent cesarean deliveries were at higher risk for multiple complications even if they did not have placenta previa, according to data presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Rates of preterm delivery, postpartum hemorrhage, placenta accreta, and need for hysterectomy and transfusion were all significantly higher in patients with low-lying placenta than in patients without, Jacob Thomas, MD, of Advocate Aurora Health in Chicago, Illinois, and Ascension Illinois St. Alexius Medical Center in Hoffman Estates, reported at the meeting.

A low-lying placenta is defined as a placental edge less than 20 mm from the internal os but not covering it. Most studies looking at low-lying placentas, however, group them with placenta previa, making it difficult to know if there are differences in risk of adverse outcomes for those who don’t have placenta previa.

“These are not necessarily shocking findings, but it shows that even low-lying placentas have significant morbidity in and of themselves, not just when they’re lumped with placenta previas,” Dr. Thomas said in an interview. “This means, if you’re doing a C-section for a low-lying placenta, you probably want to treat it a lot like you would treat a placenta previa. You may have blood ready, whether or not you’re going to give it, and you’re going to be more prepared for those complications.”

Noting that approximately 30% of patients with low-lying placenta had preterm deliveries, Dr. Thomas added that these patients might need to be counseled differently as well. The researchers did not have data on how preterm the deliveries were — many could have been 35-37 weeks, for example — but “how you prepare those patients is different,” he said.

Breanna Bolivar, MD, MPH, an obgyn hospitalist at MAHEC Ob/Gyn Specialists in Asheville, North Carolina, said the findings confirm her experience in practice.

“Low-lying placentas are treated very similarly to placenta previas and the results seem similar to patients that have placenta previas,” Dr. Bolivar said in an interview. “In my practice, I treat patients with low-lying placenta the same as I do with placenta previa. I have the same risk factors in mind, and I prepare in the same way.”

The researchers conducted a retrospective analysis of all patients who underwent a cesarean delivery in the National Inpatient Sample from 2017 to 2019 through the Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality. After excluding patients with placenta previa, the researchers compared outcomes among patients with ICD-10 codes for low-lying placenta to those of patients without low-lying placenta. The researchers specifically looked at preterm delivery, hemorrhage, hysterectomy, placenta accreta spectrum (PAS), sepsis, shock, disseminated intravascular coagulation, and blood transfusion.

Among 700,635 patients with cesarean deliveries in the database, 0.4% had low-lying placenta. These patients were more likely to be older, to be anemic, and to deliver at a large or urban teaching hospital. They were less likely to have public insurance or a previous cesarean.

After controlling for confounders that differed between the two populations, the researchers found a higher likelihood of all adverse maternal outcomes studied in patients with low-lying placenta (P < .05). These patients had three times greater risk for preterm delivery (adjusted odds ratio [aOR], 3.07; 95% CI, 2.81-3.35) and nearly three times greater risk for shock (aOR 2.55; 95% CI, 1.44-4.52), and transfusion (aOR, 2.56; 95% CI, 2.14-3.06).

Compared to those without low-lying placenta, risk for patients with low-lying placenta was even higher for hemorrhage (aOR, 8.87; 95% CI, 8.10-9.73), hysterectomy (aOR, 9.42; 95% CI, 7.11-12.47), and PAS (aOR, 13.41; 95% CI, 10.34-17.39).

Within the group with low-lying placenta, older patients were modestly, but significantly, more likely to have hemorrhage, hysterectomy, and PAS (aOR, 1.06 for all). The risk was more elevated and significant in patients with tobacco use for hemorrhage (aOR, 1.43), hysterectomy (aOR, 1.40), and PAS (aOR, 1.40). Patients with anemia were also significantly more likely to experience PAS (aOR, 1.34).

“Interestingly, in this population, prior cesarean was not associated with increased rates of hemorrhage or hysterectomy,” the researchers reported. The findings can also “help guide research in terms of questions for the future,” Dr. Thomas said, such as looking at complication rates for vaginal deliveries in people with low-lying placenta.

No external funding was noted, and the authors all had no disclosures. Dr. Bolivar had no disclosures.

SAN FRANCISCO — Patients with a low-lying placenta who underwent cesarean deliveries were at higher risk for multiple complications even if they did not have placenta previa, according to data presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Rates of preterm delivery, postpartum hemorrhage, placenta accreta, and need for hysterectomy and transfusion were all significantly higher in patients with low-lying placenta than in patients without, Jacob Thomas, MD, of Advocate Aurora Health in Chicago, Illinois, and Ascension Illinois St. Alexius Medical Center in Hoffman Estates, reported at the meeting.

A low-lying placenta is defined as a placental edge less than 20 mm from the internal os but not covering it. Most studies looking at low-lying placentas, however, group them with placenta previa, making it difficult to know if there are differences in risk of adverse outcomes for those who don’t have placenta previa.

“These are not necessarily shocking findings, but it shows that even low-lying placentas have significant morbidity in and of themselves, not just when they’re lumped with placenta previas,” Dr. Thomas said in an interview. “This means, if you’re doing a C-section for a low-lying placenta, you probably want to treat it a lot like you would treat a placenta previa. You may have blood ready, whether or not you’re going to give it, and you’re going to be more prepared for those complications.”

Noting that approximately 30% of patients with low-lying placenta had preterm deliveries, Dr. Thomas added that these patients might need to be counseled differently as well. The researchers did not have data on how preterm the deliveries were — many could have been 35-37 weeks, for example — but “how you prepare those patients is different,” he said.

Breanna Bolivar, MD, MPH, an obgyn hospitalist at MAHEC Ob/Gyn Specialists in Asheville, North Carolina, said the findings confirm her experience in practice.

“Low-lying placentas are treated very similarly to placenta previas and the results seem similar to patients that have placenta previas,” Dr. Bolivar said in an interview. “In my practice, I treat patients with low-lying placenta the same as I do with placenta previa. I have the same risk factors in mind, and I prepare in the same way.”

The researchers conducted a retrospective analysis of all patients who underwent a cesarean delivery in the National Inpatient Sample from 2017 to 2019 through the Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality. After excluding patients with placenta previa, the researchers compared outcomes among patients with ICD-10 codes for low-lying placenta to those of patients without low-lying placenta. The researchers specifically looked at preterm delivery, hemorrhage, hysterectomy, placenta accreta spectrum (PAS), sepsis, shock, disseminated intravascular coagulation, and blood transfusion.

Among 700,635 patients with cesarean deliveries in the database, 0.4% had low-lying placenta. These patients were more likely to be older, to be anemic, and to deliver at a large or urban teaching hospital. They were less likely to have public insurance or a previous cesarean.

After controlling for confounders that differed between the two populations, the researchers found a higher likelihood of all adverse maternal outcomes studied in patients with low-lying placenta (P < .05). These patients had three times greater risk for preterm delivery (adjusted odds ratio [aOR], 3.07; 95% CI, 2.81-3.35) and nearly three times greater risk for shock (aOR 2.55; 95% CI, 1.44-4.52), and transfusion (aOR, 2.56; 95% CI, 2.14-3.06).

Compared to those without low-lying placenta, risk for patients with low-lying placenta was even higher for hemorrhage (aOR, 8.87; 95% CI, 8.10-9.73), hysterectomy (aOR, 9.42; 95% CI, 7.11-12.47), and PAS (aOR, 13.41; 95% CI, 10.34-17.39).

Within the group with low-lying placenta, older patients were modestly, but significantly, more likely to have hemorrhage, hysterectomy, and PAS (aOR, 1.06 for all). The risk was more elevated and significant in patients with tobacco use for hemorrhage (aOR, 1.43), hysterectomy (aOR, 1.40), and PAS (aOR, 1.40). Patients with anemia were also significantly more likely to experience PAS (aOR, 1.34).

“Interestingly, in this population, prior cesarean was not associated with increased rates of hemorrhage or hysterectomy,” the researchers reported. The findings can also “help guide research in terms of questions for the future,” Dr. Thomas said, such as looking at complication rates for vaginal deliveries in people with low-lying placenta.

No external funding was noted, and the authors all had no disclosures. Dr. Bolivar had no disclosures.

SAN FRANCISCO — Patients with a low-lying placenta who underwent cesarean deliveries were at higher risk for multiple complications even if they did not have placenta previa, according to data presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Rates of preterm delivery, postpartum hemorrhage, placenta accreta, and need for hysterectomy and transfusion were all significantly higher in patients with low-lying placenta than in patients without, Jacob Thomas, MD, of Advocate Aurora Health in Chicago, Illinois, and Ascension Illinois St. Alexius Medical Center in Hoffman Estates, reported at the meeting.

A low-lying placenta is defined as a placental edge less than 20 mm from the internal os but not covering it. Most studies looking at low-lying placentas, however, group them with placenta previa, making it difficult to know if there are differences in risk of adverse outcomes for those who don’t have placenta previa.

“These are not necessarily shocking findings, but it shows that even low-lying placentas have significant morbidity in and of themselves, not just when they’re lumped with placenta previas,” Dr. Thomas said in an interview. “This means, if you’re doing a C-section for a low-lying placenta, you probably want to treat it a lot like you would treat a placenta previa. You may have blood ready, whether or not you’re going to give it, and you’re going to be more prepared for those complications.”

Noting that approximately 30% of patients with low-lying placenta had preterm deliveries, Dr. Thomas added that these patients might need to be counseled differently as well. The researchers did not have data on how preterm the deliveries were — many could have been 35-37 weeks, for example — but “how you prepare those patients is different,” he said.

Breanna Bolivar, MD, MPH, an obgyn hospitalist at MAHEC Ob/Gyn Specialists in Asheville, North Carolina, said the findings confirm her experience in practice.

“Low-lying placentas are treated very similarly to placenta previas and the results seem similar to patients that have placenta previas,” Dr. Bolivar said in an interview. “In my practice, I treat patients with low-lying placenta the same as I do with placenta previa. I have the same risk factors in mind, and I prepare in the same way.”

The researchers conducted a retrospective analysis of all patients who underwent a cesarean delivery in the National Inpatient Sample from 2017 to 2019 through the Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality. After excluding patients with placenta previa, the researchers compared outcomes among patients with ICD-10 codes for low-lying placenta to those of patients without low-lying placenta. The researchers specifically looked at preterm delivery, hemorrhage, hysterectomy, placenta accreta spectrum (PAS), sepsis, shock, disseminated intravascular coagulation, and blood transfusion.

Among 700,635 patients with cesarean deliveries in the database, 0.4% had low-lying placenta. These patients were more likely to be older, to be anemic, and to deliver at a large or urban teaching hospital. They were less likely to have public insurance or a previous cesarean.

After controlling for confounders that differed between the two populations, the researchers found a higher likelihood of all adverse maternal outcomes studied in patients with low-lying placenta (P < .05). These patients had three times greater risk for preterm delivery (adjusted odds ratio [aOR], 3.07; 95% CI, 2.81-3.35) and nearly three times greater risk for shock (aOR 2.55; 95% CI, 1.44-4.52), and transfusion (aOR, 2.56; 95% CI, 2.14-3.06).

Compared to those without low-lying placenta, risk for patients with low-lying placenta was even higher for hemorrhage (aOR, 8.87; 95% CI, 8.10-9.73), hysterectomy (aOR, 9.42; 95% CI, 7.11-12.47), and PAS (aOR, 13.41; 95% CI, 10.34-17.39).

Within the group with low-lying placenta, older patients were modestly, but significantly, more likely to have hemorrhage, hysterectomy, and PAS (aOR, 1.06 for all). The risk was more elevated and significant in patients with tobacco use for hemorrhage (aOR, 1.43), hysterectomy (aOR, 1.40), and PAS (aOR, 1.40). Patients with anemia were also significantly more likely to experience PAS (aOR, 1.34).

“Interestingly, in this population, prior cesarean was not associated with increased rates of hemorrhage or hysterectomy,” the researchers reported. The findings can also “help guide research in terms of questions for the future,” Dr. Thomas said, such as looking at complication rates for vaginal deliveries in people with low-lying placenta.

No external funding was noted, and the authors all had no disclosures. Dr. Bolivar had no disclosures.